"#$%& '()%
Philippine Obstetrical and Gynecological Society (POGS), Foundation, Inc.
April 2010
Task Force on Clinical Practice Guideline In the Diagnosis and Management of Hypertensive Complications of Pregnancy
Philippine Obstetrical and Gynecological Society (POGS), Foundation, Inc.
CLINICAL PRACTICE GUIDELINES on HYPERTENSIVE COMPLICATIONS OF PREGNANCY
April 2010
Task Force on Clinical Practice Guidelines In the Diagnosis and Management of Hypertensive Complications of Pregnancy
FOREWORD
REGTA L. PITHAY, MD
President Philippine Obstetrical and Gynecological Society (Foundation), Inc. (POGS), 2010
The 2nd Edition of the Clinical Practice Guideline (CPG) on Hypertensive Complications of Pregnancy is a timely addition to our growing number of “must have” reference books. The urgency and dispatch with which this edition came to be, was in response to our resolve in reducing the unacceptably high rate of attendant maternal and fetal morbidity and mortality. In line with the thrust of this year’s centerpiece project, the Millennium Development (MDG) Countdown Program, this CPG is a significant tool in providing health workers & stakeholders with fresh, scientifically validated data in the detection and management of one of the leading challenges of obstetric practice. It is envisioned that with this book more of our colleagues and partners will help the country reach its MDG 4 and 5 before 2015. I commend the teamwork of the 2010 Committee on CPG and the Taskforce on CPG - Hypertensive Complications of Pregnancy. Your unselfish contribution to this body of work is a testimony of your unwavering commitment and support to a major mission of POGS.
REGTA L. PICHAY, MD
INTRODUCTION
EFREN J. DOMINGO, MD, PhD
Chair, AdHoc Committee on the Clinical Practice Guidelines, 2010
The Clinical Practice Guidelines on Hypertensive Complications of Pregnancy is the Second Edition of this Publication, 2010. The Philippine Obstetrical and Gynecological Society, (Foundation), Inc. (POGS), through the Committee on Clinical Practice Guidelines initiated and led to completion the publication of this manual in plenary consultation with the Residency Accredited Training Hospitals’ Chairs and Training Officers, The Regional Board of Directors, The Board of Trustees, The Task Force on the Diagnosis and Management of Hypertensive Complications of Pregnancy and the Committee on Continuing Medical Education. This publication represents the collective effort of the POGS in updating the clinical practice of Obstetrics and Gynecology, specifically on Hypertensive Complications of Pregnancy, and making it responsive to the most current and acceptable standard in this procedure. A greater part of the inputs incorporated in this edition are the contributions srcinating from the day-to-day academic interactions from the faculty of the different Residency-Accredited Hospitals in Obstetrics and Gynecology in the country. This Clinical Practice Guideline on Hypertensive Complications of Pregnancy is envisioned to become the handy companion of the Obstetrician-Gynecologist in his/her day-to-day rendition of quality care and decision making in managing the Obstetric patient. This is also envisioned to provide the academic institutions in the country a nd in S outheast Asia updated information on Hypertensive Complications of Pregnancy treatments being practiced in the Philippines. Profound gratitude is extended to all the members of the POGS, the Chairs and Training Officers of the Residency-Training Accredited Institutions, the Regional Directors, The Task Force Reviewers/Contributors, The CME Committee members, and the 2010 POGS Board of Trustees.
EFREN J. DOMINGO, MD, PhD
BOARD OF TRUSTEES 2010
OFFICERS
Regta L. Pichay, MD President Sylvia delas Alas Carnero, MD Vice President Ditas Cristina D. Decena, MD Secretary Jericho Thaddeus P. Luna, MD Treasurer Gil S. Gonzales, MD
Public Relations Officer
BOARD OF TRUSTEES Efren J. Domingo, MD, PhD Virgilio B. Castro, MD Blanca C. de Guia, MD Raul M. Quillamor, MD Rey H. delos Reyes, MD Ma. Cynthia Fernandez-Tan, MD
COMMITTEE ON CLINICAL PRACTICE GUIDELINES ON HYPERTENSIVE COMPLICATIONS OF PREGNANCY
Efren J. Domingo, MD, PhD Chair
MEMBERS Ann Marie C. Trinidad, MD Ma. Victoria V. Torres, MD Lisa T. Prodigalidad-Jabson, MD Christine D. Dizon, MD Rommel Z. Duenas, MD MANAGING EDITO R Ana Victoria V. Dy Echo, MD TECHNICAL STAFF ASSISTANTS Ms. Emiliana C. Enriquez Ms. Jhasmin G. De Guzman
TASK FORCE ON DIAGNOSIS AND MANAGEMENT OF HYPERTENSIVE COMPLICATIONS OF PREGNANCY
Ernesto S. Uichanco, MD Chair
Walfrido W. Sumpaico, MD Virgilio B. Castro, MD Ann Marie C. Trinidad, MD Raul M Quillamor, MD MDCarmencita B. Tiongco, MD Joseph U. Olivar, MD
Members Sol M. Pangan, MD Milagros T. Jocson, MD Ramon M. Gonzales, MD Ronaldo R. Santos, MD Diosdado M. Mariano, MD Sherri Ann L. Suplido, MD
Pilar Lagman-Dy, MD Mario A. Bernardino, MD Ma. Luisa S. Acu, MD Ma. Antonia E. Habana, Ma. Cristina P. Crisologo, MD
TASK FORCE REVIEWERS AND PLENARY R EVIEWERS
Regta L. Pichay, MD Rogelio P. Mendiola, MD Amaryllis Digna Yazon, MD Zaida N. Gamilla, MD Teresita Cardenas, MD Rommel Z. Duenas, MD Jennifer T. Co, MD Sharon A. Capule, MD Analyn Matignas, MD Ma. Carmen H. Quevedo, MD Marilyn D. Ruaro, MD
Lourdes B. Capito, MD Nelinda Pangilinan, MD Eugenia Mendoza, MD Julieta Cadano, MD Gilbert Reyes, MD Aida San Jose, MD Rainerio S. Abad, MD Belen P. Rajagulgul, MD Genara Manuel-Limson, MD Carmelita Pasay-Recto, MD Annelee B. Lojo, MD
Regional Directors Betha Fe M. Castillo, MD (Region 1) Concepcion P. Argonza, MD (Region 3) Diosdado V. Mariano, MD (Region 4A NCR) Evelyn R. Lacson, MD (Region 6) Fe G. Merin, MD (Region 8) Jana Joy R. Tusalem, MD (Region 10)
Ma. Lorelli P. Parado, MD Janette Tuquero, MD Paz Leticia Anacta, MD Mila Zaragoza-Ibay, MD Lisa T. Prodigalidad-J abson, MD Rodante P. Galiza, MD Grace delos Angeles, MD Blanca C. de Guia, MD Florentina A. Villanueva, MD Rey H. delos Reyes, MD
Noel C. de Leon, MD (Region 2) Ernesto S. Naval, MD (Region 4) Cecilia Valdes-Neptuno, MD (Region 5) Belinda N. Pañares, MD (Region 7) Cynthia A. Dionio, MD (Region 9) Ameila A. Vega, MD (Region 11)
DISCLAIMER, RELEASE AND WAIVER OF RESPONSIBILITY
•
•
• •
•
•
•
•
This is the Clinical Practice Guidelines (CPG) on Hypertensive Complications of Pregnancy, Second Edition, April 2010. This is the publication of the Philippine Obstetrical and Gynecological Society, (Foundation), Inc. (POGS). This is the o wnership of the POGS, its officers, and its entire membership. The obstetrician-gynecologist, the general practitioner, the patient, the student, the allied medical practitioner, or for that matter, any capacity of the person or individual who may read, quote, cite, refer to, or acknowledge, any, or part, or the entirety of any topic, subject matter, diagnostic condition or idea/s willfully release and waive all the liabilities and responsibilities of the POGS, its officers and general membership, as well as the Commiittee on the Clinical Practice Guidelines and its Editorial Staff in any or all clinical or other disputes, disagreements, conference audits/controversies, case discussions/critiquing. The reader is encouraged to deal with each clinical case as a distinct and unique clinical condition which will never fit into an exact location if reference is made into any or all part/s of this CP G. The intention and objective of this CPG is to serve as a guide, to clarify, to make clear the distinction. It is not the intention or objective of this CPG to serve as the exact and precise answer, solution and treatment for clinical conditions and situations. It is always encouraged to refer to the individual clinical case as the one and only answer to the case in question, not this CPG. It is hoped that with the CPG at hand, the clinician will find a handy guide that leads to a clue, to a valauable pathway that leads to the discovery of clinical tests leading to clinical treatments and eventually recovery. In behalf of the POGS, its Board of Trustees, the Committee on The Clinical Practice Guidelines, 2009, this CPG is meant to make each one of us a perfect image of Christ, the Healer.
CPG ON HYPERTENSIVE COMPLICATIONS OF PREGNANCY TABLE OF CONTENTS / AUTHORS
1. Epidemiology of Hypertensive Complic ations of Pregnancy ……………… ………….. .1 Ramon M. Gonzalez, M.D. and Ronaldo R. Santos, M.D. 2. The Classification of Hypertensive Complications of Pregnancy ……………………… Ernesto S. Uichanco, M.D. and Sherri Ann L. Suplido, M.D. 3. Predictive Tests for Hypertensive Complications of Pregnancy ………………………. Ma. Antonia E. Habana, M.D and Ma. Cristina P. Crisologo, M.D. 4. Prevention of Pre-eclampsia ………………………………………… …………………. Walfrido W. Sumpaico, M.D. and Milagros T. Jocson, M.D. 5. Gestational Hypertension an d Mild Pre-eclampsia …………………………………….. Pilar Lagman-Dy, M.D. and Carmencita B. Tongco, M.D. 6. Severe Pre-eclampsia …………………………………………… ……………………… Mario A. Bernardino, M.D. and Joseph Olivar, M.D. 7. Eclampsia …………………………… …………………………………………… ……... Raul M. Quillamor , M.D. and Diosdado V. Mariano, M.D. 8. Chronic Hypertension …………………………………………………………………… Virgilio B. Castro, M.D. and Ann Marie C. Trinidad, M.D. 9. Complications of Pregnancy Induced Hypertension (HELLP, Abruptio Placenta) ……. Ma. Luisa S. Acu, M.D. and Sol M. Pangan, M.D
Epidemiology of Hypertension in Pregnancy Ramon M. Gonzalez MD, Ronaldo Santos MD and, Carelle
Roux-Ong MD
Preeclampsia is a life threatening complication of pregnancy characterized by hypertension and proteinuria that contribute greatly to maternal morbidity and mortality. This as is poor primarily due to an abnormal implantation of trophoblasts in the placenta as well placental perfusion. It occurs in about 3% of all pregnancies. This disease has long been recognized but the exact etiology of preeclampsia is still obscure despite many attempts to identify possible causes. The etiology therefore, is more likely to be multifactorial. Clues regarding the etiology may be derived from the various risk factors that have been identified.
Primiparity
The only well accepted risk factor for preeclampsia is primiparity. Pregnancyinduced hypertensive disorders, especially preeclampsia have been documented to occur primarily in first pregnancies. The concept, therefore of primiparity is the 1 epidemiological cornerstone of this disease. In a population based study in Norway covering all births since 1967 (about 1.5 million women), the risk of preeclampsia in 4 first pregnancies was 3%. It decreased to 1.7% in the second pregnancy.
Immunologic Factors
There is circumstantial evidence to support the theory that preeclampsia is immune mediated. Normal pregnancy is well known to be an immunological stimulation towards the tolerance pathway and not an immunological depression of the mother. In the past the theory was that this immunological tolerance could be due to blocking antibodies, hiding the father’s antigens. More recently, it is now thought that this tolerance rather involves cytokines through the tolerance network called T helper 2 (Th2) reaction. Preeclampsia caused by the failure of the trophoblast invasion can be considered as a kind of rejection reaction by the mother towards the trophoblast antigens through a failure of the tolerance system allowing the invasion. This may arise in situations in which effective immunization by a previous pregnancy is lacking, as in first pregnancies. The immunization concept is supported by 1 that preeclampsia develops less often in multiparas who had a prior term observations pregnancy.
Previous Pregnancy Complicated by Preeclampsia / Eclampsia / HELLP
Women who had previous pregnancies complicated by preeclampsia have an increased risk for recurrence in subsequent pregnancies. Moreover, severe preeclamptic women in an initial pregnancy have a recurrence rate of as high as 50%.
In a study by Campbell and coworkers, the rate of recurrence of preeclampsia was 7.5% and 65% when the previous pregnancy was complicated by severe preeclampsia. Van Rijn and co-workers showed that there was a 25% chance of recurrence in women with a history of early onset preeclampsia resulting in delivery before 34 weeks of gestation. Those with pre-existing chronic hypertension had higher rates of preeclampsia, about 75%. Sibai and Sullivan in separate studies revealed a recurrence rate of preeclampsia with previous pregnancies with HELLP syndrome to be 19% and 43% respectively. In a study by Sibai involving 366 eclamptic women, the rate of recurrence of eclampsia in subsequent pregnancies was 5 2% and the risk for developing preeclampsia was 22%.
Family History of Preeclampsia
The predisposition to hereditary hypertension undoubtedly is linked to preeclampsia and the tendency for preeclampsia–eclampsia is inherited. Women with preeclampsia were 2.3 times more likely to have a sister who had preeclampsia. Those with gestational hypertension on the other hand, were 1.6 times more likely to have a sister with gestational hypertension. If two sisters have the same father but different 4 mothers the risk of preeclampsia is 1.8 (95% CI 1.01-2.9). The pathophysiologic role for genetic and behavioural factors that cluster families is consistent with the likelihood of preeclampsia among sisters of women with previous preeclamptic 10 pregnancies.
Body Mass Index
The relationship between maternal weight and the risk of preeclampsia is progressive. 2 It increases from 4.3% for women with a body mass index (BMI) less than 19.8 kg/m 2 to 13.3% in those with a BMI greater than 35 kg/m . In a population based cohort study in Missouri between 1989-1997 obese and overweight women had higher risks of recurrent preeclampsia 19.3% and 14.2% respectively compared with women with 8 normal BMI which was 11.2%.
Underlying Medical Conditions
Underlying medical conditions with vascular and connective tissue disorders or renal implications are at risk for developing preeclampsia . In a study by Stamilio the odds ratio was 6.9 (95% CI 1.1-42.3). Among 462 women with pregestational diabetes, 7 Sibai and co-workers demonstrated a 20% occurrence of preeclampsia. More so, the frequency of preeclampsia rose with increasing severity of diabetes. Pregnancy Related Conditions
Conditions with an increased trophoblast mass like hydrops fetalis and multifetal gestation are at increased risk for preeclampsia. In women with twin gestations compared with those with singletons, the incidence of gestational hypertension and preeclampsia are both significantly increased, 13% in singletons and 5-6% in twins.
Although multiple gestations are considered at risk for preeclampsia, the risk for recurrence in subsequent pregnancies is not clear. Trogstad and co-workers examined a total of 550,218 women between 1967 and 1998. They found out that for women with a previous singleton pregnancy complicated with preeclampsia, the recurrence 5 rate was 14.1% whereas the recurrence rate for twins was only 6.8%.
Primipaternity
Recently, it has been suggested that primipaternity rather than primiparity is the relevant risk factor. Immunogenetic factors explain the primipaternity phenomenon. The role of the father has long been hypothesized to be central in the primipaternity model which can be interpreted by an immunogenetic hypothesis. This may be interpreted as an immunological habituation to paternal antigens through contact between the sperm and the female genital tract. Having a new sexual partner will expose the mother to new paternal antigens to which she may not be tolerant. Thus, changing the father, for a woman with no history of preeclampsia may increase her risk to the same level that she would have had as a primipara. This disease therefore, may be a problem of primipaternity rather than primigravity. Moreover, if a woman becomes pregnant by a man who has fathered a preeclamptic pregnancy in a different 4 woman, her risk of developing preeclampsia is 1.8 (95% CI 1.2-2.6). Paternal genes in the fetus may therefore contribute substantially to a woman’s risk of preeclampsia. In support of this theory, a higher risk for preeclampsia has also been observed in women who had artificial insemination by an unknown donor.
Sexual Co-habitation
Robillard, et. al. suggested that preeclampsia is a “disease of new couples” and that the longer the duration of co-habitation (without barrier contraceptives), the lower the risk of preeclampsia. There is a linear decrease of the risk of preeclamsia with the timing of conception within the first year of sexual co-habitation. Within the first four 1 months the risk is 40% compared to 3-5% over 12 months. Regardless of parity, the length of sexual co-habitation was noted to be inversely related to the incidence of pregnancy induced hypertension. A longer period of sexual co-habitation with the father before conception reduces the risk of preeclampsia. One explanation is that the mother adapts to the imprinted antigens from the father.
Maternal Infection
Systematic review and meta-analysis of observational studies were done to examine the relationship between maternal infection and preeclampsia. The risk of preeclampsia was increased in patients with urinary tract infection (OR 1.57, 95% CI 1.45-1.70) and periodontal disease (OR 1.76, 95% CI 1.43-2.18). Conclusion was that urinary tract infection and periodontal diseases increased the risk of developing 6 preeclampsia.
Gestational Age at Delivery in the First Pregnancy
The risk of recurrent preeclampsia is inversely related to the gestational age at the first delivery: 38.6% for <28 weeks gestation, 29.1% between 29-32 weeks, 21.9% 8 for 33-36 weeks and 12.9% for >37 weeks age of gestation. A previous preterm delivery and small for gestational age newborn increases the risk of preeclampsia in 9 subsequent pregnancies.
Socioeconomic Status
Women from different socioeconomic status share the similar risk of developing preeclampsia. This disease is the only major perinatal risk factor which is not reported to be evidently associated with poor social status.
Smoking
Although smoking during pregnancy causes a variety of adverse pregnancy outcomes, ironically, smoking has consistently been associated with a reduced risk of hypertension during pregnancy.
References 1. 2. 3. 4. 5. 6. 7.
8. 9.
Robillard P, Dekker G, Hulsey T. Revisiting the epidemiological standard of preeclampsia: primigravidity or primipaternity? Eur J Obstet Gynecol Reprod Bio 1999 ;84(1):37-41. Eskenazi B, Fenster L, Sidney S . Multivariate analysis of risk factors for preeclamps ia. JAMA 1991;266(2):237-241. Lie RT, Rasmussen S, Brunborg H, et. al. Fetal and maternal contributuions to risk of preeclampsia: population b ased study BMJ 1998;316:1343-1347. Dildy G, Belfort M, Smulian J. Preeclampsia recurrence and prevention. Sem Perinat 2007:31(3):135-141. Agudelo AC, Villar J, Lindheimer M. Maternal infection and risk of preeclampsia: systematic review and meta-analysis. Am J Obstet Gynecol 2008:198(1):7-22. Sibai B, Caritis S, Hauth J, et. al. Risks of preeclampsia and adverse neonatal outcome among women with pregestational diabetes mellitus. Am J Obstet G ynecol 2000:364-369. Mostello D, Kallogjeri D, Tungsiripat R, Leet T. Recurrence of preeclamsia: Effects of gestational age at delivery of the first pregnancy, body mass index, paternity, and interval between births . Am J Obstet Gynecol 2008: 55.e1-55.e7. Mostello D, Tegan C, Roman L, Holcomb W, Leet T. Preeclampsia in the parous woman: who is at risk? Am J Obstet Gynecol 2002;187(2):425-429.
Darcy C, Epplein M, Johnson C, et. al. A sister’s risk: family history as a predictor of preeclampsia. Am J Obstet Gynecol 2005:193(3):965-972. 10. Eskanazi B, Harley K. Commentary: revisiting the primipaternity theory of preeclampsia. Int J Obstet Gyneco l 2001;30:1323-1324. 11. Cunningham F, Grant NF, et. al. Williams Obstetrics 22 nd ed. New York NY:McGrawHill;2005.
Classification of Hypertensive Complications of Pregnancy Ernesto S. Uichanco, MD and Sherri Ann L. Suplido, MD
Modern day obstetrics is still wanting of a classification of hypertensive disorders of pregnancy that is simple, encompassing and meaningful in the clinical situation. The various classification systems each have their own defects and deficiencies. The confusions brought about by these numerous classification methods may be one of the reasons why it is difficult to come up with researches on the topic with significant results and conclusions. Local medical centers are using a combination of the various definitions and classification system of hypertensive disorders in pregnancy. Some terms are used interchangeably, adding to the confusion when trying to give a diagnosis and in labeling a patient. The committee is presenting this classification system for uniformity and standardization in practice.
Recommendations of the Consensus Meeting
The committee recommends the following classification of hypertensive complications of pregnancy, based on a review of three commonly-used classification system used presently in the Philippines and several recommendations from different societies and guidelines abroad.
Classification of Hypertensive Disorders in Pregnancy A. Gestational hypertension / non- proteinuric hypertension of pregnancy / transient hypertension B. Pre-eclampsia 1. Mild 2. Severe C. Eclampsia D. Chronic Hypertension E. Chronic Hypertension with Superimposed Pre-eclampsia
Definition of Terms 1. Hypertension
The National High Blood Pressure Education Program (NHBPEP) Working Group defines hypertension in pregnant women as having a systolic blood pressure (BP) of 140 mmHg or higher or a diastolic blood pressure of 90 1 mmHg or higher on more than 1 occasion (American College of Obstetrics and
Gynecology (ACOG), Level III). In the past, it has been recommended that an incremental increase of 30 mmHg systolic or 15 mmHg diastolic pressure be used as a diagnostic criteria, regardless if absolute values were below 140/90 mmHg. These criteria are no longer used because evidence reveals that these women are unlikely to suffer adverse perinatal outcomes and because similar increases are seen in uncomplicated pregnancies. Although this is the case, the Working Group recommends “close observation” of these patients. The diagnosis of hypertension should be based on office or in-hospital BP measurement and is based on the average of at least two measurements, taken 2 using the same arm (National Guideline Clearinghouse (NGC), Level II-2, Grade B). Korotkoff phase V is used to designate diastolic blood pressure 2 (NGC, Level I, Grade A). 2. Proteinuria
Proteinuria is defined as the presence of 0.3 grams or 300 mg or more of protein in a 24- hour urine specimen, which usually correlates with a +1 (30 mg/dl) or greater, but should be confirmed with a random urine dipstick 1 evaluation or and a 24- hour or timed collection (ACOG, Level III). It may also be defined as greater than 30 mg/mmol urinary creatinine in a spot (random) urine 2 sample (NGC, Level II, Grade A-B). 3. Edema
This is defined as swelling of the hands and the face or leg edema after an overnight rest, and is no longer a criterion for the diagnosis of pre-eclampsia. 3. Pregnancy Induced Hypertension
This is defined as hypertension that develops as a consequence of pregnancy and regresses post-partum however The term pregnancy-induced 2 hypertension should be abandoned, as its meaning in clinical practice is unclear (NGC, Level III, Grade D). 4. Gestational Hypertension
The NHBPEP Working Group has recommended that the term “gestational hypertension” replace the term “pregnancy-induced hypertension” to describe cases in which elevated blood pressure without proteinuria develops in a woman after 20 weeks of gestation and blood pressure levels return to normal 12 weeks 1 postpartum (ACOG, Level III). 5. Pre-eclampsia
Preeclampsia is a multiorgan disease process characterized by the presence of hypertension and proteinuria occurring after 20 weeks of gestation in a woman with a previously normal blood pressure.
6. Severe pre-eclampsia
Pre-eclampsia is characterized as severe if the patient manifests any of the following3 (ACOG, Level III): BP > or = 160 mm Hg systolic or > or = 110mm Hg diastolic taken at least 6 hours apart on 2 occasions while the patient is on bed rest Proteinuria > or = 5 g/24 hrs or >/= +3 in 2 random urine samples collected at least 4 hours apart Elevated serum creatinine Pulmonary edema •
•
• • • • • •
• •
Oliguria < 500 ml/24 hrs Microangiopathic hemolysis Thrombocytopenia Hepatocellular dysfunction (elevated alanine transaminotransferase or aspartase aminotransferase) Intrauterine growth restriction or oligohydramnios Symptoms suggesting end-organ involvement: Headache Visual disturbances Epigastric or right upper quadrant abdominal pain
7. Mild pre-eclampsia
Pre-eclampsia is characterized as mild if the patient does not manifest any of the signs and symptoms of severe pre-eclampsia. 8. Eclampsia
Eclampsia is defined as hypertension in pregnancy with proteinuria along with convulsions or the occurrence of grand mal seizures in a patient with pre3 eclampsia. 9. Chronic Hypertension
Chronic hypertension is characterized by elevation of blood pressure that antecedes pregnancy or persists post-partum. It is defined by the NHBPEP Working Group on High Blood Pressure in Pregnancy as hypertension present 1 before the 20th week of pregnancy or hypertension present before pregnancy (ACOG, Level III). The diagnosis is also made in a woman taking antihypertensive medications before conception. It is classified as mild (BP > 140/90 mm Hg) or severe (BP > 180/110 mmHg, and is also present if the hypertension 3
persists longer than 12 weeks post delivery
.
10. Chronic Hypertension with Superimposed Pre-eclampsia
This is characterized by elevation of blood pressure that antecedes pregnancy or persists post-partum with associated signs and symptoms of preeclampsia. Diagnostic criteria include “new-onset proteinura” in a woman with hypertension before 20 weeks gestation, sudden increase in proteinuria if already present in early gestation, a sudden increase in hypertension, or the development
3
of HELLP syndrome . The acronym HELLP describes a variant of severe preeclampsia characterized by hemolysis, elevated liver enzymes, and low platelet count. 11. Unclassified Hypertension – hypertension when essential clinical information is lacking (This classification is put to insure that “pregnancy induced” and “chronic” are not confused by the inclusion of equivocal cases and to enable all patients to be placed in a definite category. Post-partum, patients may be reclassified to amore definitive category.) This is now no longer encountered in any of the recent guidelines and literature except for ICD-9 2101 which included
Unspecified Hypertension. Should any other classification system is to be used, it is recommended that the system of classification be mentioned and proper definitions presented for clarification. The measurement of blood pressure will follow the recommendations presented by the Multi-sectoral Task Force on the Detection and Management of Hypertension convened by the Philippine Society of Hypertension, 1997 (Table 2.1), the NHBPEP Working Group on High Blood Pressure in Pregnancy, the ACOG, the Royal College of Obstetricians and Gynecologists (RCOG) and the NGC.
Table 2.1 Method of Indirect Measurement of Blood Pressure
1. A mercury manometer is ideal for accurate measurement. Aneroid, digital or other 2 automated devices provide reasonable alternatives (NGC, Level II, Grade A), provided that they satisfy technical requirements for accuracy, and are calibrated and tested on a regular basis. Automated methods, however, need to be used with 7 caution, as they may give inaccurate blood pressure readings (RCOG, Level II-2, Grade B). The manometer cuff should cover at least 2/3 of the length of the patient’s arm, or the length 1.5 times upper arm circumference while the bladder should cover at least 80% of the arm circumference. 2. The patient should be seated (or supine) or in the left lateral recumbent position 7 2 with arms bared, supported, and at heart level (RCOG, Level II-1, Grade A) . They should not have rested for at least 5 to 10 minutes, and should not have smoked or ingested caffeine within 30 minutes before measurement.3. The edge of the cuff should be placed 1 inch above the elbow crease, with the bladder directly over brachial artery. 3. The bladder should be inflated to 30 mmHg above the point of radial pulse extinction as determined by a preliminary palpatory determination. It should then be deflated at a rate of 2 mmHg/beat, with the stethoscope bell placed directly over the brachial artery. st
4. Systolic pressure should be recorded at the appearance of the 1 clear tapping sound (Korokoff phase 1). Diastolic blood pressure should be recorded at the 2 disappearance of these sounds (Korotkoff phase V) (NGC, Level I, Grade A), unless these are still present near 0 mmHg in which case, softening of the sounds should be used as diastolic pressure (Korotkoff phase IV).
5. For every visit, the mean of readings, taken at least 2 minutes apart, should be regarded as the patient’s blood pressure. If the first 2 regarded differ by 5 mmHg rd or more, a 3 reading should included in the average. 6. If blood pressure is being taken for the first time, the procedure should be repeated with the outer arm. Subsequent determination should then be performed on the arm with a higher pressure reading. 7. If BP is consistently higher in one arm, the arm with the higher values should be used for all BP measurements2 (NGC, Level III, Grade B). 8. Ambulatory BP monitoring (by 24-hour or home measurement) may be useful to 2 detect isolated office (white coat) hypertension (NGC, Level II, Grade B). 9. Patients should be instructed on proper BP measurement technique if they are to 2 perform home BP monitoring (NGC, Level III, Grade B)
Basis for the Recommendations
The above recommendations were based on a discussion on the classifications used in the Philippines. A review of the classifications and definitions of hypertensive disorders in pregnancy used in local hospitals and medical centers appeared to take their srcins from definitions and classifications used in the following sources, namely: A. William’s Textbook of Obstetrics, 22nd Edition B. International Statistical Classification of Disease and Related Health Problems by the World Health Organization C. XIIth World Congress of Gynecology & Obstetrics in Rio De Janeiro D. ACOG Practice Bulletin No. 33 on Diagnosis and Management of Pre-eclampsia and Eclampsia and ACOG Practice Bulletin No. 29 on Chronic Hypertension in Pregnancy E. RCOG Evidence-based Clinical Guideline Number 10 A on The Management of Severe Pre-eclampsia/ Eclampsia F. NHBPEP Report on Hypertension in Pregnancy 2000 G. National Guideline Clearinghouse Guideline on Diagnosis, evaluation and management of the hypertensive disorders of pregnancy H. International Statistical Classification of Diseases and Related Health Problems (ICD-10) A summary and comparison of the above classifications and definitions are presented in Tables 2.2 and 2.3.
A. Classification of Hypertensive Disorders Complicating Pregnancy from William’s Textbook of Obstetrics
This is perhaps the most popular definition and classification used in the Philippines, our country most strongly influenced by teachings from the United States. In the past editions of Williams’ Obstetrics, the term “pregnancy-induced hypertension” was utilized. The latest edition, which is the 22nd edition, also adapts the current scheme of the Working Group of the NHBPEP in 2000. The diagnosis of chronic underlying hypertension is suggested by the following: 1. Hypertension (140/90 mm Hg or greater) antecedent to pregnancy 2. Hypertension detected before 20 weeks or 3. Persistent hypertension long after delivery Additional factors that support the diagnosis are multiparity, hypertension complicating a previous pregnancy and a strong family history of hypertension. Diagnosis of Pregnancy – aggravated hypertension or superimposed preeclampsia) is given when a pre-existing chronic hypertension worsen and is usually accompanied by proteinuria or pathologic edema.
B. International Statistical Classification of Disease and Related Health Problems by the World Health Organization (ICD-10) In this comprehensive classification of diseases, there is a section on “Oedema, proteinuria and hypertensive disorders in pregnancy, childbirth and the puerperium”. This classification may be easily compared to the ACOG classification and the NHBPEP Working Group presented above and corresponding classes may be matched. Without a corresponding category though is the class Gestational edema and proteinuria without hypertension (ICD 10 code 012.2). Perhaps this may be indicative on broader outlook at the possible complications of pregnancy with regards to this topic – possibly initially starting as to involve other organ systems even prior to the clinical manifestation of overt elevation in blood pressure. Another difference in the classification is ICD 10 code 013, where Gestational Hypertension without significant proteinuria, or Gestational Hypertension not otherwise specified are also known as Mild Preeclampsia. According to the 22nd edition of Williams Obstetrics and the Working Group, to make the diagnosis of gestational hypertension, there should be no proteinuria. The ICD 10 also included the term “Moderate Pre-eclampsia” (ICD 10 code 014). This is the classification system used mainly by the group of the Fetal As A Patient but the term EPH Gestosis (Edema, Proteinuria, Hypertension is used to correspond to the term “pre-eclampsia”.
C. XIIth World Congress of Gynecology & Obstetrics This is a classification based solely on the physical signs of hypertension and proteinuria – with the intention of defining clinical categories without necessarily implying a particular etiology or pathology. Edema is not included because it was noted not to have prognostic significance.
In this classification, Gestational hypertension, proteinuria and proteinuric hypertension are further subdivided into antepartum, intrapartum or postpartum types because of possible differences in clinical, pathologic and prognostic significance. The Unclassified hypertension and/or proteinuria in pregnancy is used for cases when essential clinical information is lacking – which happens quite often. This is important to insure that “chronic or “ gestational categories are not confused by the inclusion of equivocal cases and enable patients to be placed in a definite category. This classification however, is no longer encountered in any of the recent guidelines and latest literature. In this proposal, complications are to be classified separately. For example, severe hypertension and severe proteinuria should be defined separately. Suggested criteria for “severe” hypertension are as follows: A. DBP of 120 mmHg or more on any one occasion, or B. DBP of 110 mmHg or more on two or more consecutive occasions 4 or more hours apart
D. ACOG Practice Bulletin No. 33 on Diagnosis and Management of Preeclampsia, Eclampsia and ACOG Practice Bulletin No. 29 on Chronic Hypertension in Pregnancy and National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy The National High Blood Pressure Education Program’s (NHBPEP) Working Group on High Blood Pressure in Pregnancy recently issued a report identifying four hypertensive disorders of pregnancy namely: chronic hypertension that predates pregnancy; preeclampsia-eclampsia, a serious, systemic syndrome of elevated blood pressure, proteinuria and other findings; chronic hypertension with superimposed preeclampsia; and gestational hypertension, or nonproteinuric hypertension of pregnancy. This scheme and the criteria for each category differ from former diagnostic schemes and the current schemes of other groups. Important features of the preeclampsia elimination of a change in blood pressure as a diagnostic criterion wherein the group recommends using cut-off of 140/90 mm Hg, elimination of edema as a criterion, because this finding is so common in healthy pregnant women and absolute requirement of proteinuria of more than 300 mg per 24 hours for the diagnosis. The gestational hypertension category is used in women with nonproteinuric hypertension of pregnancy, in which the pathophysiologic perturbations of the preeclampsia syndrome do not occur before delivery. The American College of Obstetricians and Gyneocologists adapt the present scheme of the NHBPEP Working Group, as reported in the ACOG Practice Bulletin No. 29 and 33. For a more detailed breakdown of the three classification systems, please see Table 2.2.
Table 2.2: Classification of Hypertensive Disorders in Pregnancy WHO (ICD-10) XIIth World Congress Williams Obstetrics 22nd Ed/NHBPEP Working Group/ACOG Gestational hypertension Gestational hypertension The term “pregnancyw/o sig. proteinuria (w/o proteinuria) induced hypertension” is now replaced by gestational hypertension
Same
5 Types of Hypertensive
Gestational hypertension with sig. Proteinuria
Disease in Pregnancy: A. Gestational Hypertension/ Transient Hypertension B. Pre-eclamsia Mild Severe C. Eclampsia
Eclampsia
Eclampsia
Pre-existing hypertension
Chronic hypertension w/o proteinuria Chronic hypertension w/ superimposed preeclampsia
D. Chronic Hypertension
Unspecified hypertension
Unspecified hypertension w/o proteinuria
Used interchangeably with gestational hypertension
Gestational edema & proteinuria w/o hypertension
Gestational proteinuria (w/o hypertension) Chronic renal dis. (w/ or w/o hypertension) Unclassified proteinuria (wo hypertension)
Pre-existing hypertension w/ superimposed preeclampsia
E. Pre-eclampsia superimposed on Chronic Hypertension
Table 2.3: Definitions Williams Obstetrics 22nd WHO (ICD – 10) Ed/NHBPEP Working Group/ACOG >/=140/90 mm Hg 140/90 Incremental increase in BP is no !30mmHg systolic or longer included. !15 mmHg diastolic Hypertension Korotkoff phase V is used to (6 hours apart)
Proteinuria
Edema
XIIth World Congress
DBP 110 mmHg DBP 90 mmHg (4 hours apart)
define diastolic BP
(Korotkoff Ph.IV)
(Korotkoff Ph.IV)
> 300 mg per 24 hours 30 mg/dl (+1) dipstick in random urine samples
0.3 g/L in 24 hr collection 0.1 g/L or 2+ in 2 random 6 hours apart
300 mg in 24 hours 1 g/L or 2+ in 2 random 4 hours apart 0.3 g/L or 1+ on reagent (SG >1.030 & pH < 8)
Abandoned as diagnostic criterion
Swelling of hands & face Weight gain of 5 lbs (2.27 kg) in a week
References
1. 2. 3.
4. 5. 6. 7. 8.
9.
Report of the National High Blood Press ure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Ob stet Gynecol 2000;183(1):S1-S22. Diagnosis, eval uation and management of the hypertensi ve disorders of pregnancy. National Guideline Clearinghouse. http://www.guideline.gov/about/inclusion.aspx . American College of Obstetric ians and Gynecologists. ACOG Committe e on Practice Bulletins — Obstetrics. ACOG Practice Bulletin No. 33, January 2002. Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol 2002;99(1):159-167. Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 2004;103(5 pt 1):981-991. Barton JR, Sibai BM. Diagnosi s and management of hemolysis, e levated liver enzymes, and low platelets syndrome. Clin Perinatol 2004;31(4):807-833. Magann EF, Martin JN Jr. Twelve steps to optimal management of HELLP syndrome. Clin Obstet Gynecol 1999;42(3):532-550. Royal College of Obstetricians a nd Gynaecologists . The Management of Severe Pre-eclampsia/ Eclampsia: Evidence-based Clinical Guideline Number 10 A, 200 6, March. American College of Obstetricia ns and Gynecologists. ACOG Committee on Practice Bulletins— Obstetrics. ACOG Practice Bulletin No. 29, July 2001. Chronic Hypertension in Pregnancy. Obstet Gynecol 2001; 98: 177-185. Cunningham, et.al, Williams Obstetrics. 22 ed.2005.
Predictive Tests for Hypertensive Complications of Pregnancy Ma. Antonia E. Habana, MD and Ma. Cristina P. Crisologo, MD
Hypertensive Complications of Pregnancy are more likely to develop in a woman who – (1) (2) (3) (4)
is exposed to abnormal chronic villi for the first time is exposed to super abundance of chorionic villi, or with twins or hydatidiform mole has preexisting vascular disease, or is genetically predisposed to hypertension developing during pregnancy
The tendency to develop pre-eclampsia is said to be heritable. Cooper and Siston (1971) examined the possibility that susceptibility to pre-eclampsia is dependent upon a single recessive gene. Chesley and Cooper (1986) reanalyzed Chesley’s extensive data and concluded that the single gene hypothesis fits well, but multifactorial inheritance cannot be excluded. Risk factors for hypertensive complications of pregnancy are found in Table 3.1. 17 Table 3.1. Risk Factors for Hypertension in Pregnancy Factor Diabetes Mellitus Hypertension in previous pregnancy Nulliparity Change of partner for second or subsequent pregnancy Age > 40 years
Risk Ratio 2:1 2-3:1 3:1 3:1
Twin gestation Family History of PIH Chronic Hypertension Chronic renal disease Anti-phospholipid syndrome Angiotensinogen gene Homozygous Heterzygous
4:1 5:1 10:1 20.1 10:1
3:1
20:1 4:1
Regardless of the lack of existing prophylactic and therapeutic means to address preeclampsia, the search for non-invasive markers that could predict the development or assist in the detection of this life-threatening pregnancy disorder is still of utmost importance. The availability of such markers could have decisive impact not only on the medical management of pregnant women and their child, such as referral to a tertiary centre, but also on the health costs associated with this prevalent medical condition. There are many proposed strategies on the detection or prediction of hypertensive complication of pregnancy.
The following are suggested predictive tests for pre-eclampsia: 1. Case Finding as part of General Physical Examination Opportunities for case finding are common in general practice. Health service providers are encouraged to measure the blood pressure at each patient visit and consultation (either on outpatient or on emergency basis) even if the patient complains for unrelated symptoms. Reviewing maternal history for potential risk factors, coupled with uterine artery Doppler assessment showed that these seem to select two different populations - early and late-onset preeclampsia, which might suggest a different pathogenesis for these - hypertensive states7. (Level II, Grade A) 2. Screening Maneuvers a. Mean Arterial Pressure The mean arterial pressure (MAP) is defined as diastolic blood pressure (DBP) + 1/3 the pulse pressure [MAP = DBP + 1/3 (systolic blood pressure (SBP)-DBP)]. A MAP value in the second trimester (MAP -2) > 90 mmHg (sensitivity of 61-71% and specificity of 62-74%) or a MAP value in the third trimester (MAP -3) > 105 mmHg has resulted in an increased incidence of pre-eclampsia.18 The lower critical cut off in the second trimester represents the mid-trimester drop in blood pressure (BP) which strengthens the belief that throphoblastic proliferation at this time has resulted in dilatation of the spiral arterioles. Therefore, the absence of a mid-trimester drop in BP despite MAP -2 values < 90 mmHg may predict future pregnancy induced hypertension (PIH) based on the absence of arteriolar vasodilatation and should alert the physician for closer follow-up. Several authors suggest that the MAP -2 value may be more predictive for chronic hypertension or essential or transient hypertension.19,20 Recent reports suggest the sensitivity of this test may be much lower (22-35%) any may be of little value in predicting preeclampsia. 21 In a systematic at MAP and BP measurements in predicting preeclampsia, second trimesterreview MAPlooking of 90 mm Hg or more showed a positive likelihood ratio of 3.5 (95% CI 2.0-5.0) and a negative likelihood ratio of 0.46 (95% CI 0.16-0.75). In women deemed to be at high risk, a DBP of 75 mm Hg or more at 13 to 20 weeks' gestation best predicted pre-eclampsia: positive likelihood ratio 2.8 (95% CI 1.8-3.6), negative likelihood ratio 0.39 (95% CI 0.18-0.71). Thus, When BP is measured in the first or second trimester of pregnancy, the MAP is a better predictor for pre-eclampsia than SBP, DBP, or an increase of BP.9 (Level I, Grade B) b. Supine Pressure Test or Roll Over Test Originally described by Gant, et. al. in 1974, women were seen between 28-32 weeks of pregnancy when their DBP in the superior arm were first stabilized in the left lateral recumbent position. The women were then rolled over to the supine position and BP readings were taken immediately and after 5 minutes. An increase of at least 20 mmHg in the diastolic pressure constituted a positive roll over test. A positive roll over test is associated with a 3-fold increase of developing pre-eclampsia, similar to the results of the angiotensin sensitivity test. Gant, et. al. (1973) and Oney and Kaulhausen (1982) with infused angiotensin II and demonstrated increased pressor response in primigravidas, 20 mmHg as the positive response. However, the positive predictive value of this test in predicting preeclampsia is only 33 percent. (Level I, Grade B)
c. Combination of the MAP-2 and Roll Over Test Performed singly, the MAP -2 test or the roll over test predicted a 60% risk hypertension or pre-eclampsia later in pregnancy but when a MAP -2 value >90 mmHg and a positive roll over test are combined, the prediction rate increased to 78%.22 (Grade B) d. 48-hour BP Monitoring In the first trimester, the test accurately diagnosed 93% of the 60 women who later developed pregnancy induced hypertension or pre-eclampsia. This rose to 99% by the third trimester. The test does not require monthly monitoring during pregnancy which was done during the study to validate the test. It is additionally examines lower blood 23 pressure women fluctuations activity and the rest during different trimesters.inThis allowsand diagnosis before between blood pressure becomes elevated. (Grade C)
e. 24 hours Ambulatory BP and Heart Rate The sensitivity in predicting pre-eclampsia for MAP of ! 85 mmHg at 20 weeks was 65%, with a positive predictive value for a test combining MAP ! 85 mmHg and a heart rate ! 90 bpm were 53% and 45% respectively. The efficiency of the test is increased by combining the awake ambulatory heart rate and blood pressure measurement together. 23 (Grade C) f. Hyperbaric Index (HBI) – The HBI was calculated as a time-specified BP excess over a pre-set tolerance limit for SBP, DBP and MAP. In a study comparing its predictive efficacy with standard sphygmomanometry and 48-hour ambulatory BP monitoring, the predictive value was low for all three methods, sensitivity between 54 and 77%, specificity between 41 and 78%. 24 (Level II-2) 3. Laboratory Tests new screening strategies, not only sensitivity, specificity and predictive When evaluating values should be taken into account, but also costs, patient's acceptability and quality control a. Doppler Velocimetry Diminished blood flow may be reflected as an increased systolic/diastolic ratio (Stuart Index) or the more ominous absence or reversed end diastolic (ARED) blood flow.24 Bilateral notching of uterine arteries at 12-14 weeks is a useful tool in predicting the development of hypertensive disorders in high-risk pregnancies. The sensitivity of bilateral notching in predicting hypertensive disorders of pregnancy decreased with advancing pregnancy from 91 to 35%, and the specificity and the positive predictive values increased from 41 to 94% and from 7 to 70%, respectively. The negative predictive values ranged from 86 to 97%.4 (Level II-1) Doppler velocimetry of the uterine and uteroplacental arteries at 24 weeks is an effective test to predict PIH. Persistence of the early diastolic notch in both uterine arteries strongly correlates with severe PIH requiring delivery before 34 weeks with a sensitivity of 81% and specificity of 87%. delivery In contrast, women very lowhypertension risk group with 1% having before 34 without weeks.25a notch Whenconstitute used toa predict in < twin pregnancies, the sensitivity of abnormal uterine artery Doppler results defined by twin nomograms vs. singleton nomograms was 36.4% vs. 18.2% for pre-eclampsia. Despite
using specially constructed twin nomograms, uterine artery Doppler studies in twin gestations had an overall low sensitivity in predicting adverse obstetric outcome. Negative predictive values of uterine Doppler studies in twin gestations are lower compared to those reported in unselected singleton pregnancies, i.e. maternal and fetal complications occur more frequently despite normal uterine artery waveforms. This suggests that there is an additional pathomechanism, causing pre-eclampsia and consequent growth restriction in twin gestations, that is unrelated to uteroplacental insufficiency.10 (Level II-2) b. Fibronectin This glycoprotein from the liverand andendothelial endothelialcell cells, and its release into plasmaare is derived a markerprincipally of vascular disruption activation. Increased levels have been found to predict pre-eclampsia but not in chronic hypertension. In a study among 125 pregnant women, the elevated maternal plasma fibronectin level over 40 mg/dL is capable of predicting preeclampsia in the third trimester with a sensitivity of 73% and a specificity of 92%. These results suggest that serial plasma fibronectin measurements before 24 weeks' of gestation may be helpful in the early detection of preeclampsia in normotensive gravid women who are destined to become clinically preeclamptic.12 (Level II-2) c. Hematocrit Pre-eclampsia represents a state of hemoconcentration and increased hematocrit levels. A fall in repeat hematocrit values may denotes clinical improvements.26 c. Proteinuria Amounts greater than 300mg/24 hr urine sample or dipsticks values of +1 or more have 13 been said to denote poor prognosis, a systematic review nor concluded that even increasing levels of protenuria are nothowever, predictive of poor maternal fetal outcomes. Deemed more important than the proteinuria values is the urinary protein/creatinine ratio in its ability to predict hypertensive complications during pregnancy. For protein/creatinine ratio 130-150 mg/g, sensitivity ranged from 90-99%, and specificity ranged from 33-65%; for protein/creatinine ratio 300 mg/g, sensitivity ranged from 8198% and specificity ranged from 52-99%; for protein/creatinine ratio 600-700 mg/g, sensitivity ranged from 85-87%, and specificity ranged from 96-97%. Random protein/creatinine ratio determinations are helpful primarily when they are below 130-150 mg/g, in that 300 mg or more proteinuria is unlikely below this threshold. Midrange protein/creatinine ratio (300 mg/g) has poor sensitivity and specificity, requiring a full 24-hour urine for accurate results.14
d. Serum uric acid Uric acid values correlate with the development of pre-eclampsia, its severity and increased perinatal mortality.26 e. Hemoglobinuria, elevated SGPT and thrombocytopenia comprise the diagnosis of the HELLP syndrome.
f. Maternal serum alpha fetoprotein (MSAFP) levels > 2 multiples of median (MOM) were associated with a higher incidence of pre-eclampsia compared to controls. This elevation also correlated with a higher likelihood of developing adverse perinatal outcomes such as growth restriction, preterm delivery and intrauterine fetal demise.15 g. Hypocalciuria and the calcium/creatinine ratio are tests to predict pre-eclampsia from chronic hypertension.26,27 h. Glucose Intolerance Insulin resistance is associated with and may be causal in essential hypertension, but the relation insulin resistance and hypertension de novo in pregnancy in is unclear. between In a retrospective case-control study, womenarising who developed hypertension pregnancy had significantly higher glucose levels on 50-g oral glucose loading test and a significantly higher frequency of abnormal glucose loading tests (> or = 7.8 mmol/L) than women who remained normotensive. Relative glucose intolerance was particularly common in women who developed nonproteinuric hypertension. Women who developed hypertension also had greater prepregnancy body mass index and baseline systolic and diastolic blood pressures, although all subjects were normotensive at baseline by study design. However, after adjustment for these and other potential confounders, an abnormal glucose loading test remained a significant predictor of development of hypertension and, specifically, nonproteinuric hypertension in pregnancy.17 i.
Inhibin A and circulating angiogenic factors levels obtained at 12 to 19 weeks’ age of gestation have significant associations with onset of preeclampsia at less than 27 weeks, as do levels obtained at 24-28 weeks with onset of preeclampsia at less than 37 weeks. However, because the corresponding sensitivities and/or positive predictive values were 5 low, theseprevious markerspreeclamspia might not beand/or clinically useful to predict preeclampsia in women with previous chronic hypertension.
4. In the recent years, other biochemical markers have been proposed as potential predictors for preeclampsia. To be effective, a screening test need to be sufficiently sensitive and specific and must provide an adequate positive predictive value. Several promising markers have been described, alone or in combination, that might fulfill these criteria. However, these data came often from small case studies with selected populations. Therefore, there is a need for worldwide large scale prospective studies to confirm the sensitivity and specificity of these promising markers and assess their utility in different subtypes of preeclampsia before they could serve in clinically useful screening tests. 2 The following table summarizes the potential predictive biochemical markers for preeclampsia. (Level III, Grade C) Biochemical Marker
sflt-1
sEng
Plasma Concentrations Reported st nd combinations 1 2 Manifest trimester trimester preeclampsia for prediction -! ! sEng, PlGF VEGF Ultrasound -! ! sflt-1, PlGF Ultrasound
Altered levels are also correlated with:
IUGR HELLP
PlGF PP-13
! !
! "
! sEng, sflt-1 " Ultrasound
P-Selectin
"
"
"
"
"
"
Cell free DNA ADAM12
--
--
"
PTX3 PAPP-A Visfatin
" !
Adrenomedullin
Cell-free DNA
fetal
! --
--
--
-- " -- !
--
" ! "!
"
"
-- "
"!--
SGA SGA IUGR Preterm delivery
Activin A sflt-1 Other adhesion molecules Inhibin A IUGR Polyhydramnios Trisomy 21 Preterm labor Trisomy 21 Trisomy 18 SGA IUGR birthweight Type-2 diabetes mellitus Gestational diabetes mellitus Obesity IUGR Vascular disorders
Summary of potential biochemical markers for the prediction (1. trimester, 2. trimester) or the detection (Manifest preeclampsia) of preeclampsia in ma ternal peripheral b lood. sflt-1: soluble fms-like tyrosine kinase 1; sEng : soluble Endoglin; PlGF : placental growth factor; PP-13 : Placental protein 13; ADAM12: A disintegrin and metalloprotease 12; PTX3: Pentraxin 3; PAPP-A : pregnancy-associated plasma protein A; IUGR: Intrauterine growth retardation; SGA: Small for gestational age; HELLP: Hemolysis elevated liver enzymes; low platelets
Because of the abundance of tests evaluating the predictive value of different parameters in predicting preeclampsia, a systematic review of these reviews were conducted. Where multiple studies were available, only a body mass index of > 34, alpha-fetoprotein, fibronectin (cellular and total), and uterine artery Doppler (bilateral notching) measurements reached specificity above 90%. Only Doppler (any/unilateral notching, resistance index, and combinations) measurements were over 60% sensitive. Further research should focus on tests which offer much higher levels of sensitivity than tests currently available. High sensitivity is a more useful attribute in early detection of pre-eclampsia than specificity because consideration of benefits, harms and costs indicates a much greater preference for minimizing false negatives than false positives, although the ideal would be to avoid both.11
References
1. 2.
Brown MA, Mackenzie C, Dunsmuir W, Roberts L, Ikin K, Matthews J, Mangos G, Davis G. Can we predict recurrence of pre-eclampsia or gestationa l hypertension? BJOG 2007;114(8):984-93. Grill S, Rusterholz C, Zanetti -Dällenbach R, Tercanli S, Holzgreve W, Hahn S, La paire O. Potential
3.
4.
5.
6. 7.
8.
9.
10.
11.
12. 13. 14. 15.
16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26.
markers of preeclampsia – a review. Reprod Biol Endocrinol 2009;7:70. Caritis S, Sibai B, Hauth J, Lindheimer M, VanDorsten P, Klebanoff M, Thom E, Landon M, Paul R, Miodovnik M, Meis P, Thurnau G, Dombrowski M, McNellis D, Roberts J. Predictors of pre-eclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. AJOG 1998;179:4,946-51. Vainio M, Kujansuu E, Koivisto AM, Mäenpää J. Bilateral notching of uterine arteries at 12--14 weeks of gestation for prediction of hypertensive disorders of pregnancy. Acta obstetr et gyneco l Scan 2005;84:11, 1062-7. Sibai BM, Koch MA, Freire S, Pinto e Silva JL, Rudge MV, Martins-Costa S, Bartz J, de Barros Santos C, Cecatti JG, Costa R, Ramos JG, Spinnato JA. Serum inhibin A and angiogenic factor levels in pregnancies with previous preeclampsia and/or chronic hypertension: are they useful markers for prediction of subsequent preeclampsia? AJOG 2008;199:3,268.e1-9. Odegård RA, Vatten LJ, Nilsen ST, Salvesen KA, Austgulen R. Risk factors and clinical manifestations of pre-eclampsia. BJOG 2000 Nov;107(11):1410-6. Llurba E, Carreras E, Gratacós E, Juan M, Astor J, Vives A, Hermosilla E, Calero I, Millán P, GarcíaValdecasas B, Cabero L. Maternal history and uterine artery Doppler in the assessment of risk for development of early- and late-onset preeclampsia and intrauterine growth restriction. Obstet Gynecol Int 2009:275613. Epub 2009 May 27. Vollebregt KC, Gisolf J, Guelen I, Boer K, van Montfrans G, Wolf H. Limited accuracy of the hyperbaric index, ambulatory blood pressure and sphygmomanometry measurements in predicting gestational hypertension and preeclampsia J Hypertens 2010;28(1):127-34. Cnossen JS, Vollebregt KC, de Vrieze N, ter Riet G, Mol BW, Franx A, Khan KS, van der Post JA. Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis. BMJ 2000;336(7653):1117-20. Geipel A, Berg C, Germer U, Katalinic A, Krapp M, Smrcek J, Gembruch U. Doppler assessment of the uterine circulation in the second trimester in twin pregnancies: prediction of pre-eclampsia, fetal growth restriction and birth weight discordance. Ultrasound Obstet Gynecol 2002;20(6):541-5. Cnossen JS, ter Riet G, Mol BW, van der Post JA, Leeflang MM, Meads CA, Hyde C, Khan KS. Are tests for predicting pre-eclampsia good enough to make screening viable? A review of reviews and critical appraisal. Acta Obs tet Gynecol Scand 2009;88(7):758-65. Aydin T, Varol FG, Sayin NC. Third trimester maternal plasma total fibronectin levels in pregnancyinduced hypertension: results of a tertiary center. Clin Appl Thromb Hemost. 2006;12(1):33-9. Thangaratinam S, Coomarasamy A, O'Mahony F, Sharp S, Zamora J, Khan KS, Ismail KM. Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review. BMC Med. 2009;24;7-10. Papanna R, Mann LK, Kouides RW, Glantz JC. Protein/creatinine ratio in preeclampsia: a systematic review. Obstet Gynecol. 2008;112(1):135-44. Toal M, Chaddha V, Windrim R, Kingdom J. Ultrasound detection of placental insufficiency in women with elevated second trimester serum alpha-fetoprotein or human chorionic gonadotropin. J Obstet Gynaecol Can . 2008;30(3):198-206. Solomon CG, Graves SW, Greene MF and Seely EW. Glucose intolerance as a predictor of hypertension in pregnancy. Hypertension. 1994;23:717-721 ACOG Technical Bulletin, Jan 1996 Page and Christianson, 1976 Chesley and Sibai, 1974 Chesley and Sibai, 1988 Chesley and Sibai, 1987 Sumpaico and Santillan, 1982 Kyle and Clark, 1993 Vollebregt, 2010 Pangan, 1997 Sumpaico, 1995
27. Lim and Cardenas, 1996
Prevention of Pre-eclampsia Milagros J. Tia-Jocson, MD and Walfrido W. Sumpaico, MD
Strategies to effectively prevent pre-eclampsia have been the subject of investigations for decades. In fact, the latest issue of the Cochrane Database of Systematic Reviews revealed a number of meta-analyses on various interventions aimed at preventing preeclampsia. However, the only strategies found to significantly reduce the risk of this complication are calcium supplementation and use of antiplatelet agents. 1
The meta-analysis by Hofmeyr, et. al., which included 12 randomized controlled trials (RCTs) of good quality, showed that pregnant women who were given calcium supplementation at dose of 1.5 to 2g per day before 32 weeks age of gestation (AOG) until delivery, had significantly reduced incidence of hypertension (RR 0.70, 95% CI 0.57-0.86) and pre-eclampsia (RR 0.48, 95% CI 0.33-0.69) when compared to those taking placebo. There was no overall effect on the risk of preterm birth (RR 0.81, 95% CI 0.64-1.03) nor on stillbirth or neonatal death prior to discharge (RR 0.89, 95% CI 0.73-1.09)1. The meta-analysis by Duley, et. al. on use of antiplatelet agents for preventing pre-eclampsia and its complications,2 which included 59 RCTs comparing antiplatelet agents with either placebo or no antiplatelet agent, also showed a significant reduction (by 17%) in the risk of preeclampsia among those given antiplatelet agents (RR 0.83, 95% CI 0.77-0.89). There was no overall difference in the risk of placental abruption between the comparison groups (RR 1.10, 95% CI 0.89-1.37). Women included in the studies were either at moderate to high risk in developing pre-eclampsia. Interventions varied as to the doses of aspirin (ASA), (ranging from 60 mg to 150 mg/day) and dipyridamole (200 mg to 400 mg/day in combination with ASA except in one study), although conclusion of the authors was that doses of ASA up to 75 mg 2
appear to be safer. Recommendations
1. Calcium supplementation to pregnant women (both low risk and those at risk for developing pre-eclampsia), given at a dose of 1.5 to 2g per day before 32 weeks AOG until delivery, appears to decrease the risk of developing hypertension by around a third and pre-eclampsia by half. (Level I, Grade A) 2. Use of antiplatelet agents, either ASA or dipyridamole, has also been shown to reduce the risk of pre-eclampsia by 17% among moderate to high risk women. This intervention has not been shown to increase the risk of placental abruption. (Level I, Grade A) 3. There are insufficient evidence to support the use of anti-oxidants (vitamin C, vitamin E, lycopene, red palm oil, selenium)3, nitric oxide4, rest during pregnancy5, exercise6, diuretics7, 8
9
reduced salt intake , marine oil or other prostaglandin precursor and prevention of pre-eclampsia. (Level I-II, Grade A-B).
10
garlic
in the
References
1. 2. 3. 4. 5. 6.
Hofmeyr GJ, Atallah AN, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev 2006, Issue 3. Duley I, Henderson-Smart DJ, Meher S, King JF. Antiplatelet a gents for preventing pre-ecla mpsia and its complications. Cochrane Database Syst Rev 2007, Issue 2. Rumbold A, Duley I, Cr owther CA, Haslam RR. Antioxidants for preventing pre -eclampsia. Cochrane Database Syst Rev 2008, Issue 1. Meher S, Duley I. Nitric oxide for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2007, Issue 2. Meher S, Duley I. Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure. Cochrane Database Syst Rev 2006, Issue 2.
Meher S, Duley L. Exercise or other physical activity for preventing pre-eclampsia and its complications. Cochrane Database Syst Reviews 2006, Issue 2. Churchill D, Beevers GCG, Meher S, Rhodes C. Diuretics for preventing pre-eclampsia. Cochrane Database Syst Rev 2007, Issue 1. 8. Duley L, Henderson-Smart D. Reduced salt intake compared to normal dietary salt, or high intake, in pregnancy. Cochrane Database Syst Rev 1999, Issue 3. 9. Makrides M, Duley, Olsen S. Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction. Cochrane Database Syst Rev 2006, Issue 3. 10. Meher S, Duley L. Garlic for preventing pre- eclampsia and its complicati ons. Cochrane Database Syst Rev 2006, Issue 3. 7.
Gestational Hypertension and Mild Pre-eclampsia Pilar Lagman-Dy, M.D. and Carmencita B. Tongco, M.D.
Gestational Hypertension
Definition: Blood pressure elevation of 140/90 unaccompanied by proteinuria after 20 weeks gestational age and usually resolves by six weeks postpartum.
Mild Preeclampsia
Definition: 1. Blood pressure of 140 mmHg systolic or higher, or 90 mmHg diastolic or higher, in an upright sitting blood pressure after a 10-minute rest, that occurs after 20 weeks of gestation in a woman with previously normal blood pressure. 2. Proteinuria, defined as urinary excretion of 300 g protein or higher in a 24-hour urine specimen. Approximately 35% of women with gestational hypertension with onset at < 34 weeks develop preeclampsia, and the associated risks of serious maternal (2%) and perinatal complications (16%) are high. These women should receive heightened maternal and fetal surveillance, the nature and frequency of which has not been established. The following should be part of the management of Gestational Hypertension/Mild Preeclampsia: 1. Home Health Care As long as the criteria for severe pre-eclampsia are excluded, this may be recommended for women with mild hypertension without heavy proteinuria. This may continue as long as the disease does not worsen and if fetal growth restriction is not suspected. Sedentary activity throughout the greater part of the day is essential. Home blood pressure and urine protein monitoring or frequent evaluation visits by a visiting nurse or training midwife are acceptable. These women should be instructed in detail about reporting symptoms. During such home management, they are allowed a regular diet, without salt restriction, and they are allowed to be up and about as desired. She should also be instructed about recording fetal kick counts and about immediate reporting of symptoms.7 (Grade B) Patients having all of the following criteria can be managed at home: (Grade B) 1. Ability to comply with recommendation 2. Diastolic pressure ! 100 mm Hg 3. 4. 5. 6.
Systolic pressure ! 140 mm Hg Proteinuria < 1,000 mg 24 hr or < 2+ on dipstick Platelet count > 120,000/mm Normal fetal growth and testing
7. No indications for delivery
Summary of Evidence
The management of gestational hypertension/mild preeclampsia during pregnancy was based largely on clinical experience rather than the result of randomized controlled trials. In theory, hospital admission for bed rest could delay or prevent progression of hypertension to severe preeclampsia and might reduce the frequency of eclampsia or abruption placentae, with improvement in fetal survival.8 This practice was challenged in 1971 by a British team who showed a reduction in perinatal mortality in policy, patientsthey withreduced nonproteinuric despite ambulatory management. As a result of this hospital hypertension admissions by 72% when only patients with proteinuric hypertension were hospitalized. In a subsequent study, they reported on 135 patients with gestational hypertension entered on a randomized trial. They showed that complete bed rest in hospital appeared to have no advantage over ‘ambulation as desired’ in controlling the severity of maternal disease.9 Hospitalization was not associated with an overall improvement in fetal growth or reduction in the neonatal morbidity. 10 Several other studies supported the idea of out-patient management of gestational hypertension and mild preeclampsia.11-13 Recently, obstetricians were increasingly using outpatient management of gestational hypertension, especially with the increasing pressure to curb medical expenses. Outpatient ambulatory management was endorsed by American College of Obstetricians and Gynecologists (ACOG) provided the patient had a thorough initial evaluation.14 Ambulatory management was also recommended for a select group of patients in the 1993 issue of Williams’ Obstetrics.4 In an attempt to reduce hospitalization, improved patient satisfaction and reduce costs, several programs were introduced during the past decade to 15 patients at home. All such programs involved some form of maternal and fetal manage such evaluation. The success rate of outpatient management depends mostly on maternal status (presence or absence of proteinuria, diastolic blood pressure, and gestational age) at time of enrolment. Pregnancies complicated by mild preeclampsia with proteinuria are associated with a lower gestational age at delivery, shorter pregnancy prolongation, and an increased requirement for antepartum hospitalization as compared with pregnancies with gestational hypertension.8 Women who develop gestational hypertension/preeclampsia at an earlier age tend to have an earlier gestational age at delivery, a worsening of the disease status, and worse fetal outcome when compared with those who develop the disease at term.16
2. Timing of Delivery The delivery of patients with gestational hypertension-mild preeclampsia will depend on fetal gestational age and fetal testing as well as maternal blood pressure, amount of proteinuria, and maternal symptoms.(Grade Patients considered for delivery: A) having any of the following should be hospitalized and Gestational age ! 40 weeks Gestational age ! 37 weeks if there is:
Bishop score > 5 Fetal weight <10th percentile Non-reactive NST Gestational age 34 weeks and above with the presence of: Labor Rupture of Membranes Vaginal bleeding Abnormal biophysical profile Criteria for severe preeclampsia Expectant management should be considered for women remote from term who have mild preeclampsia. (Grade C) 3. Monitoring of Fetal Well-Being The patient should be evaluated by a physician for maternal and fetal well-being at least once weekly. This weekly check-up should include the following: a. Blood pressure at each visit (Grade A) b. Platelet count and liver enzymes at regular intervals (Grade B) c. Non-stress tests at regular intervals (Grade B) d. Fetal growth every 2 to 3 weeks (Grade B) In contrast, patients with gestational age < 37 weeks who do not satisfy the criteria for home management should be immediately hospitalized. Subsequently management should depend on results of maternal and fetal conditions. (Grade A)
4. Medications: Magnesium sulfate and other anti-convulsants are not recommended and should be withheld in cases of gestational hypertension/mild preeclampsia. (Grade B) Patients with mild preeclampsia and gestational hypertension will be given antihypertension medications only if there is an increase in blood pressure readings from baseline. 17 Please refer to the recommendations for medications in the section on severe pre-eclampsia. Low dose aspirin and high dose calcium are not recommended for the prevention of the progression to severe preeclampsia. (Grade B)
Summary
Management of women with gestational hypertension/mild preeclampsia must always consider maternal safety first and then the delivery of a newborn who will not require intensive and prolonged neonatal care. management patients with hypertension/mild preeclampsia has Outpatient been documented to be moreofcosteffective than gestational similar inpatient therapy. Therefore, out-patient management must provide evaluation of maternal and fetal status similar to that of in-patient management.
References
1. ACOG Practice Bulletin No. 33. American College of Obstetricians and Gynecologists. Diagnosis and 2.
3. 4. 5.
!"
7. 8.
9. 10. 11. 12. 13.
management of preeclampsia and eclampsia. Obstet Gynecol 2002;99:159-167 (Level III) Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Ob stet Gynecol 2000;183:S1-S22. (Level III) http://www.ncbi.nlm.nih.gov/entrez/query. fcgi?cmd=Retrieve&db=PubMed&list_uids=10920346&dopt=Abstract th Gabbe SG, Neibyl JR, Simpson JL (Eds). Obstetrics: Normal and Problem Pregnancies. 4 Ed. Hypertension, Chapter 28. Churchill Livingstone, New York, 2002. 945-1004. (Level III) st Cunningham GF, et. al. (Eds) Williams Obstetrics, 21 Edition. Hypertensive Disorders in Pregnancy, Section 7. McGraw-Hill, 2001. 24:567-618. (Level III) Chobanian AV, et. al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. JAMA 2003;289:2560-2571. (Level III) http://jama.amaassn.org/cgi/content/full/289/19/2560 Hofmeyr GJ, Atallah AN, Duley L. Calcium supplementation during pregnancy for preventing Cochraine Library Syst Revs. hypertensive disorders and related problems. http://www.ihs.gov/generalweb/webapps/sitelink/ site.asp?link=http://www.cochranelibrary.com/enter/ Frangieh AY, Sibai BM. Outpatient management of gestational hypertension and mild preeclampsia. Contemporary OB-Gyn 1996:67. Crowther CA, Bouwmeester AM, Ashurst HM. Does admission to hospital for bed rest prevent disease progression or improve fetal outcome in pregnancy complicated by non-proteinuric hypertension? Br J Obstet Gynecol 1992;99:13. Matthews DD, Agarwal V, Shuttleworth TP. The effect of rest and ambulation on plasma urea levels in pregnant women with proteinuric hypertension. Br J Obstet Gynecol 1980;87:1095. Barton JR, Stanzino GJ, Sibai BM. Monitored outpatient management of mild gestational hypertension remote from term. Am J Obstet Gyn ecol 1994;170:765. Matthews DD, Patel IR, Sengupta SM. Outpatient management of toxemia. Br J Obstet Gyneco l 1971;78:610. Feeney JE. Hypertension in pregnancy managed by community midwives. BMJ 1984;288:1046. Tuffnell DJ, Lilford RJ, Buchan PC, et. al. Randomized controlled trial of day care for hypertension in
pregnancy. Lancet 1992;339:224. 14. American College of Obstetricians and Gynecologists. Technical Bulletin: Hypertension in pregnancy. Washington DC, 219, January 1996. 15. Dawson AJ, Middlemiss C, Coles EC. A randomized study of a domiciliary antenatal care scheme: The effect on hospital admissions. Br J Obstet Gynecol 1989;96:1319. 16. Hamlin RHJ. The prevention of eclampsia-preeclampsia. Lancet 1982;1:64. 17. Sibai BM, Barton JR, Aki S. A randomized prospective comparison of nifedipine and bed rest versus bed rest alone in the management of preeclampsia remote from term. Am J Obs tet Gynecol 1992;167:879.
Severe Pre-eclampsia Mario A. Bernardino, M.D. and Joseph U. Olivar, M.D.
The objectives in the management of severe preeclampsia include the following: 1. To reduce its severity or prevent progression of the disease process. 2. To prevent convulsions. 3. To control severe hypertension. 4. To deliver the mother of a fetus at the optimum time and with the least trauma. 5. To detect and appropriately treat end-organ damage. 6. To completely restore the health of the mother.
Background
Incidence As the most common medical disorder of pregnancy, hypertension is reported to complicate 5 – 6% of all pregnancies worldwide, 1 with 5- 10 % being severe. 2 It is the 2 nd most common cause of maternal death in the US.1,3 Locally, the incidence of severe preeclampsia is 25% and is the 2 nd most common cause of maternal death.4 It is also associated with a high perinatal mortality and morbidity rate, which is primarily due to iatrogenic prematurity.5 The development of preeclampsia cannot be accurately predicted nor effectively prevented. Delivery of the fetus and placenta remains the only definitive treatment.6 For all these reasons, the timing of delivery is critical to optimize maternal and perinatal outcome.
Classification of Preeclampsia Preeclampsia is classified as mild and severe. Mild preeclampsia refers to disease that meets the criteria for the diagnosis of preeclampsia but is not severe disease. A diagnosis of severe preeclampsia requires evidence of new-onset proteinuric hypertension occurring at > 20 weeks age of gestation with > 1 of a series of complications (see Table 1). It is emphasized that only 1 of the listed criteria in Table 1 is required for the diagnosis of severe preeclampsia. The distinction between mild and severe preeclampsia is important because it dictates management,5 and one must not be complacent with mild preeclampsia6 because apparently mild disease may progress rapidly to severe disease.6
!"#$%&" ()*+ ,*)-.%/0 12$&3%#4% +#4#5&+&4% *( 6&7&)& $)&&38#+$6.# )&+*%& ()*+ %&)+0 !+ 9 :;6%&% <=4&3*8 >??@ 0
Management The main objective in the management of severe preeclampsia must always be the safety of the mother and the fetus.5 The initial management of preeclampsia includes stabilization of the mother’s condition, confirmation of gestational age and assessment of fetal well-being. Once the diagnosis of severe preeclampsia is established, traditional management has focused on maternal safety with expedited delivery. Because these pregnancies are associated with high rates of maternal morbidity and mortality and with potential risks for the fetus, there is general agreement that such patients should be delivered if the disease develops > 34 weeks of gestation.7,8 Although delivery is always appropriate for the mother, it may not be optimal for the premature fetus (< 34 weeks). 9 Complications of prematurity include respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, sepsis and even death. In the past, it was believed that infants born prematurely to severely preeclamptic women had lower
rates of neonatal morbidity and mortality than infants of similar gestational age born to nonpreeclamptic women. In contrast, several recent case-control studies have demonstrated that premature infants born after severe preeclampsia have neonatal complications and mortality similar to those of other premature infants of similar gestational age and have higher rates of admission to NICU.10 In addition, case-control studies have revealed that fetuses of preeclamptic women do not exhibit accelerated lung or neurological maturation.10 There are 3 circumstances in which expectant management of severe preeclampsia remote from term (< 34 weeks) is clearly acceptable. The first is severe preeclampsia by proteinuria.5 Neither the amount of protein spilled in the urine nor the rate of increase correlates with maternal or perinatal outcome.11,12 As such, proteinuria > 5 grams per 24 hours is not, of 5
itself, an indication for delivery. second is severe preeclampsia on the basis of IUGR alone with good fetal testing. Although The not candidates for immediate delivery, such patients should be 5 treated as in-patients with at least daily fetal well-being studies. Third, there is precedent in the literature to support the expectant management of women with severe preeclampsia by blood pressure criterion. This approach, although potentially dangerous for the mother, has been substantiated in a number of clinical trials.7,8 There are only 2 published randomized trials on the expectant management of severe preeclampsia. In 1990, Odendaal, et. al. studied 38 patients with severe preeclampsia at 28-34 weeks of gestation. 20 patients underwent aggressive treatment (steroid therapy followed by delivery in 48 hours), and 18 patients were treated expectantly (steroid therapy followed by delivery only for maternal and fetal indications). In the conservative group, the authors reported no increase in maternal complications but with statistically significant prolongation of pregnancy (mean, 7.1 days), a reduction in neonates that required ventilation (11% vs 35%), and a reduction in total neonatal complications (33 vs 75%). 7 Sibai, et. al. studied 95 patients with severe preeclampsia at 28-32 weeks of gestation: 46 patients underwent aggressive treatment and 49 were assigned to expectant management. In women who were treated conservatively, there was no increase in maternal complications, but there was a statistically significant prolongation pregnancy (mean 15.4 vsincidence 2.6 days),ofless time in neonatal intensive care unit (NICU) (20.2 vsof 36.6 days), and a reduce respiratory distress syndrome (22.4% vs 50.5%).8 These 2 trails7,8, demonstrated improved perinatal benefit with reasonable maternal safety when expectant management was conducted in a select group of patients with severe preeclampsia at 28-34 weeks of gestation.13 Recently, the results of several retrospective and observational studies that described expectant management of severe preeclampsia at 24-34 weeks of gestation have suggested that such management improves perinatal outcome without increasing maternal morbidity.14-23
In 2005, Sibai published an algorithm in the expectant management of preeclampsia < 34 weeks. !"#$% %' ()*'+ )," "-($.-+/ 01$%• • •
Maternal-fetal evaluation for 24 hours Magnesium sulfate for 24 hours Antihypertensives if systolic blood pressure >160 mmHg, diastolic blood pressure > 110 mmHg, or mean arterial pressure >125 mmHg
!,/ '2 %3- 2'(('4$,5 6+-0-,%7 • • • • • • •
Eclampsia Pulmonary edema Acute renal failure Disseminated intravascular coagulation Suspected abruptio placenta Non-reassuring fetal status Labor or rupture of membranes >34 weeks’ gestation
Magnesium sulfate and delivery
Yes
No •
•
HELLP syndrome enzymes, and Low(Hemolysis, Platelets) Elevated Liver Persistent symptoms
Steroids
Yes
No
< 23 weeks
Terminate pregnancy
23–32 weeks
• • •
•
•
33 – 34 weeks
Steroids Antihypertensives if needed Daily evaluation of maternalfetal condition
• •
Delivery if: 2) with indications (see Table Delivery at 32-34 weeks
8$51+- 9: ;),)5-#-,% '2 0-.-+- 6+--<()#60$) = >? 4--@0: A!")6%-" 2+'# B$*)$:C
DD
Steroids Delivery after 48 hours
Table 2. Indications for Delivery During Expectant
45
!"#$%&" ()*+ ,-.#- #/" 0#)%*/1 2334 6*%&7 89$&)%&/:-*/ -: ;/<*/%)*==&" >?&/ %?& 0@ )&+#-/: -/ %?& :&A&)& )#/B& "&:$-%& +#C-+;+ "*:&: *( #/%-?9$&)%&/:-A& #B&/%:D !<<*)"-/B %* +*:% )&$*)%:1 %?& +#C-+;+ "*:& *( ?9")#=#E-/& -: 23 +B FGH 6-(&"-$-/& I3 +B @J #/" 6-<#)"-$-/& ")-$ K3 +BL?*;)D
Perinatal Complications Though the main aim of expectant management is to improve perinatal outcome by prolonging gestation and reducing neonatal morbidities (acute and long term)13 due to prematurity, expectant treatment has potential complications. During expectant management of patients with severe preeclampsia at 24-34 weeks of gestation, the rate of perinatal death ranged from 0 to 16.6 %. 7,8 Abruptio placenta is also a reported complication and it ranged from 4.1% to 22.9%. 8,22 In addition, delivery for nonreassuring fetal status ranged from 26-75%.18,20 In all the reported studies, intensive fetal monitoring for early detection of fetal compromise is recommended. The most common indication for delivery was deterioration in fetal status underscoring the need that these
pregnancies managed expectantly should be observed in centers that are capable of rapid intervention for fetal reasons.
Maternal Complications The main aim of the expectant management of severe preeclampsia remote from term is prolonging gestation without jeopardizing maternal safety. Progressive deterioration in maternal condition during the clinical course of severe preeclampsia may occur. Thus, any protocol for management of severe preeclampsia has potential for maternal complications.5 During expectant 8,16,20syndrome (4.1-27.1%), management, maternal complications reported studies include: HELLP pulmonary edema (0-8.5%), eclampsiainand acute renal failure (<1%). Expectant management must provide heightened surveillance to ensure adequate maternal oxygenation, provide prompt intervention for symptoms of hepatic dysfunction (HELLP syndrome or subcapsular hematoma of the liver), and particularly provide evaluation of the fetal status and maternal presentation given the risks of placental abruption.5
Severe Preeclampsia < 25 weeks Only few literatures are published regarding maternal and perinatal outcomes during expectant treatment of patients with severe preeclampsia at <25 weeks of gestation. Severe preeclampsia that develops in the mid-trimester of pregnancy is associated with high perinatal mortality and morbidity rates. 14-16,23 Aggressive treatment in the form of immediate delivery will usually result in high neonatal mortality rate. 14,26 If the fetus survives, significant neonatal complications are expected and these will require prolonged hospitalization in the 4,23,24,25,28
NICU. the other hand, morbidity. attempts to14,16,24,25,27 prolong pregnancy result in fetal and may expose the On mother to severe Overall, inmay these studies, thedeath perinatal death rate ranged from 71% to 100%, with few newborn infant surviving without handicap. 14,27,28 There was one reported maternal death in a patient who had eclampsia and HELLP syndrome who underwent expectant treatment at 23 weeks age of gestation.27 Furthermore, maternal morbidities were very high.5 Bombrys and colleagues29 found small studies that focused on expectant management of severe preeclampsia before 28 weeks. In pregnancies before 23 weeks, maternal complications were common and there were no infant survivors. Thus, the authors recommended pregnancy termination for these women. For those at 23 weeks, the perinatal survival rate was 18%, but long term perinatal morbidity is yet unknown. For women with pregnancies at 24 to 26 weeks, perinatal survival approached 60%, and it averaged 90% for those at 26 weeks.
Preeclampsia with HELLP 29 syndrome is characterized by progressive and clinical course women with HELLP sudden The deterioration in theof maternal condition. Because this syndrome is associated with increased rates of maternal morbidity and mortality, some authors consider its presence an
indication for immediate delivery, except for the benefit of steroid for fetal lung maturity in gestation at 24-34 weeks.5 There are 3 studies30-32 published regarding expectant management in patients with HELLP syndrome at < 34 weeks of gestation. Their results suggest that expectant treatment is possible in a select group of women with alleged HELLP syndrome at < 34 weeks of gestation. However, despite pregnancy prolongation in some of these cases, the overall perinatal outcome was not improved, compared with cases of similar gestational age who were delivered within 48 hours after steroid therapy. Since the sample size in these studies is inadequate, such approach is currently experimental.5
Clinical Considerations and Recommendations A. What are the clinical features of severe preeclampsia? A diagnosis of severe preeclampsia requires evidence of new onset proteinuric hypertension along with ! of a series of complications (summarized in Table 1). (Level
III, Grade C) Although the classification of severity of preeclampsia is primarily based on the level of blood pressure and the degree of proteinuria, other organ may be potentially involved and clinicians should be vigilant when assessing the maternal risk.34 It is emphasized that only 1 of the listed clinical features in addition to hypertension ( ! 140/90 mmHg) and proteinuria (!300 mg/24 hours) is required for the diagnosis of severe disease. 5 Ultimately as many clinical criteria are subjective, women should be managed according to a careful clinical assessment rather than relying overly on precise criteria.34
B. Assessment of the Woman B1. What is the initial management in a woman with severe preeclampsia? In a woman with severe preeclampsia, immediate admission preferably in risk unit is mandatory. (Level I, Grade A)
a high
Hospitalization is considered in women with severe preeclampsia.6 Hospitalization is indicated in cases in which the woman is unreliable, ! 2 systolic blood pressure (SBP) >150 mmHg or diastolic blood pressure (DBP) > 100 mmHg, heavy proteinuria or persistent maternal symptoms.35,36
B2. How should the BP be taken? When taking the blood pressure, the woman should be rested sitting at 45-degree angle. The cuff should be of the appropriate size and should be placed at the level of the heart. Multiple readings should be used to confirm the diagnosis. Korotkoff phase 5 is the appropriate measurement of diastolic blood pressure. (Level I, Grade A) Automated methods should be used with caution.(Level II-2, Grade B)
The blood pressure should be checked every 15 minutes until the woman is stabilized and then every 30 minutes in the initial phase of the assessment. The blood pressure should be checked every 4 hours except between midnight and morning if a conservative management plan is in place and the woman is stable and asymptomatic. (Level III, Grade C)
When taking the blood pressure the woman should be appropriately positioned and the cuff should be of an appropriate size placed at the level of the heart. Multiple readings are required to accurately assess the blood pressure because of natural variations. Korotkoff phase 5 is the appropriate method for diastolic blood pressure.37 38 methods can systematically underestimate particularly the systolic Automated blood pressure. It has been suggested that mercury sphygmomanometers should be used to establish baseline blood pressure as a reference.39 However, many units no longer have mercury sphygmomanometers and a baseline check with another validated device would be an alternative. Initial assessment of the woman with severe preeclampsia requires more frequent monitoring of the blood pressure until the woman is stabilized.13
B3. How should proteinuria be measured? The usual screening test is visual dipstick assessment. A (+)1 dipstick measurement can be taken as evidence of proteinuria but a negative (-) dipstick may not be accurate. Ideally, a more accurate test (24 hour urine protein collection) is required to confirm this. (Level III, Grade C)
While it has to be acknowledged that there is poor predictive value from urine 40
dipstick testing,as approximate is +1 are = 0.3 g/L, +2with = 1g/L = 3g/L. False negative well as falseequivalence positive results possible the and use +3 of dipstick assessment 40 because the degree of proteinuria may fluctuate widely over the 24 hour period, even in severe cases.6 In view of this, laboratory testing usually by a 24 hour urine collection is recommended to confirm significant proteinuria unless the clinical urgency dictates immediate delivery.41
B4. What other laboratory exams should be requested? The following laboratory exams should be requested in cases of severe preeclampsia: CBC with platelet count, peripheral blood smear, liver enzymes (AST, ALT), creatinine, uric acid, LDH, and total bilirubin.(Level III, Grade C)
A falling platelet count is associated with worsening disease and is itself a risk to the mother.45 A platelet count persistently less than 100 x 106/L should be a consideration for delivery. On the other hand, it is not until the count is less than 100 x 106/L that there 46
may be count an associated coagulation platelet is over 100 x 106/L. abnormality. Clotting studies are not required if the A diagnosis of HELLP syndrome needs confirmation of hemolysis, either by LDH levels (! 600U/L), blood film to look for fragmented red cells or total bilirubin >1.2
mg/dL; elevated liver enzymes (AST or ALT >70 U/L) and low platelet (< 100 x 106/L).5 If only 1 or 2 of the 3 criteria are met, the diagnosis is partial HELLP syndrome.6 In preeclampsia, there can be a rise in uric acid that correlates with poorer outcome for both mother and the fetus.47 This rise confirms the diagnosis of preeclampsia but the levels should not be used for clinical decision-making. Renal function is generally maintained in preeclampsia until the late stage unless HELLP syndrome develops.48 If creatinine is found to be elevated early in the disease process, underlying renal disease should be suspected. In severe disease, serum creatinine can be seen to rise and is associated with a worsening outcome 48 but renal failure is not uncommon in preeclampsia and when it does occur, it is usually associated with hemorrhage, HELLP 34
syndrome or sepsis. C. Anti-Seizure Prophylaxis C1. How should seizure be prevented? Magnesium sulfate (MgSO4) is the drug of choice for the prevention of convulsions. This drug should be considered for women with preeclampsia for whom there is concern about the risk of eclampsia. This is usually in the context of moderate to severe preeclampsia (at least 150-160/100-110 mmHg), once a delivery decision is made and in the immediate postpartum period. In women with mild disease, the decision is less clear and will depend on individual case assessment.(Level I, Grade
A) The MagPie Trial (Magnesium sulfate for Prevention of Preeclampsia) has demonstrated that administration of MgSO4 to women with preeclampsia reduces the risk of an eclamptic seizure.42 Women allocated MgSO4 had a 58% lower risk of an eclamptic seizure (95% CI 40-71%).More Thewomen relativeneed risk to reduction waswhen similar regardless of the severity of preeclampsia. be treated preeclampsia is not severe (109) to prevent one seizure when compared with severe preeclampsia (63). When MgSO4 is given, regular assessment of the urine output, maternal reflexes, respiratory rate and oxygen saturation is important.34 MgSO4 can be given in 2 ways: continuous intravenous infusion and intermittent intramuscular injections (see Table 3).
C2. How should seizure be controlled? The principles of management should follow the basic principles of airway, breathing, and circulation. (Level III, Grade C)
MgSO4 is the therapy of choice to control eizures. s A loading dose of 4 grams should be given over 5-10 minutes, followed by a further infusion of 1 gram / hour maintained for 24 hours after the last seizure.(Level I, Grade A)
Recurrent seizures should be treated with either a further bolus of 2 grams MgSO 4, or an increase in the infusion rate to 1.5 grams or 2 grams/hour.(Level I, Grade A)
Do not leave the woman alone but call for help. Ensure that it is safe to approach the woman and do effort to prevent maternal injury during the convulsion. Place the woman in left lateral recumbent position and administer oxygen. Assess the airway and breathing and check the pulse and blood pressure. The use of the pulse oximeter is helpful.43 Once stabilized, plans should be made to deliver the woman but there is no particular hurry and a delay of several hours to make sure the correct care is in hand is acceptable, assuming that there is no acute fetal concern such as fetal bradycardia.34 MgSO4 is the therapy of choice and diazepam and phenytoin should no longer be used as first-line drugs.44 The intravenous route is has few side effects. Magnesium toxicity is unlikely with the recommended regimens and the levels do not need to be routinely measured. MgSO4 is mostly excreted in the urine. Urine output should be closely observed and if it becomes reduced below 20 ml/hour, the magnesium infusion should be halted.34 Because magnesium is cleared almost exclusively by renal excretion, plasma magnesium concentration is excessive if glomerular filtration is decreased substantively. The initial standard dose of MgSO4 can be safely administered without knowledge of renal function. Renal function is thereafter estimated by measuring plasma creatinine, and whenever it is 1.3 mg/dL or higher, only half of the maintenance MgSO4 dose is given.6 Magnesium toxicity can also be assessed by clinical assessment of the maternal deep tendon reflexes and respiratory rate. If there is loss of the deep
tendon reflexes (DTRs) and the respiratory rate falls below 12 cpm, the MgSO4 infusion should be halted. Calcium gluconate 1 gram (10 ml) over 10 minutes can be given if there is concern of MgSO4 toxicity.34 In the collaborative eclampsia trial,44 a further bolus of 2 gram MgSO4 was administered for recurrent seizures. An alternative is to increase the infusion rate to 1.5 grams or 2 grams/hour. If there are repeated seizures, then alternative agents such as diazepam or thiopentone may be used, but only as a single dose, since prolonged use of diazepam is associated with an increase in maternal death.44 If convulsions persist, intubation is likely to be necessary to protect the airway and maintain oxygenation. Transfer to intensive care facilities with intermittent positive pressure ventilation is 34
appropriate in these Patients withcircumstances. severe preeclampsia who are expectantly managed should receive MgS04 for 24 hours. If blood pressure is controlled adequately and fetal testing is reassuring, MgS04 is discontinued. MgS04 is cleared by the kidneys 4 hours after the last dose. After this time, the risk of convulsion is again present. MgS04 should be given once the blood pressure rises again and remains in the severe range, or when delivery is planned. This should be continued up to 24 hours postpartum.
D. How should fluid balance be managed? Fluid restriction is advisable to reduce the risk of fluid overload in the intrapartum and postpartum periods. In usual circumstances, total fluids should be limited to80 ml/hour or 1 ml/kg/hour. (Level III, Grade C) Close fluid balance with charting of input and output is essential. A catheter is advisable in the acute situation, especially in the immediate postpartum period.
(Level III, Grade C) Pulmonary edema is a significant cause of maternal death.38 This has often been associated with inappropriate fluid management. There is no evidence of the benefit of fluid expansion49 and a fluid restriction regimen is associated with good maternal outcome.43 There is no evidence that maintenance of a specific urine output is important to prevent renal failure, which is rare.34 Fluid restriction should be maintained until there is postpartum diuresis, as oliguria is common with severe preeclampsia. If there is associated hemorrhage, fluid balance is more difficult and fluid restriction is inappropriate.34
E. How should the fetus be assessed? A baseline cardiotocography (CTG) shouldbe undertaken. This gives information about fetal well-being at that time but does not give any predictive information.
(Level II-2, Grade B) Women in labor with severe preeclampsia should have continuous electronic fetal monitoring (EFM). (Level II-2, Grade B)
If conservative management is planned, then further assessment of the fetus with ultrasound measurements of fetal size every 2 weeks, biophysical screening (BPS) and amniotic fluid index (AFI) measurement at least twice weekly, umbilical artery Doppler once a week and daily nonstress test (NST) should be undertaken. Serial assessment will allow timing of delivery to be optimized.(Level I, Grade A)
CTG is the mainstay of fetal monitoring. It gives information concerning fetal well-being at that time but has little predictive value. If the woman is in labor, then continuous EFM is appropriate.50 The main pathology affecting the restriction fetus, apart(IUGR). from prematurity placental insufficiency leading to intrauterine growth Ultrasoundisassessment of fetal size, at the time of the initial presentation with hypertension, is a valuable measurement to assess fetal growth. Measurement of the abdominal circumference is the best method of assessment since IUGR in this case is usually asymmetrical. Reduced amniotic fluid volume is also associated with placental insufficiency and fetal growth restriction. Serial estimations of amniotic fluid volume can detect fetal compromise. Randomized trials have shown that investigation with umbilical artery Doppler using absent or reversed-end diastolic flow, improves neonatal outcome52 and serial investigations of this and other fetal vessels can be used to follow pregnancies under treatment and optimize delivery.51
F. How should we control the blood pressure? F1. Antihypertensive treatment should be started in woman with BP! 160/110 mmHg. In woman with other markers of potentially severe disease, treatment can be considered at lower degrees of hypertension.(Level III, Grade C)
There is consensus that severe hypertension in pregnancy, defined as ! 160/110 mmHg requires treatment because these women are at increased risk of intracerebral hemorrhage, and that treatment decreases the risk of maternal death. 53 There is also a consensus that, if the blood pressure is below 160/110 mmHg, there is no immediate need for antihypertensive therapy. An exception may be if there are markers of potentially more severe disease, such as heavy proteinuria or disordered or haematological test results. Since, in this situation, alarming rise in blood pressure may be anticipated, anti-hypertensive treatment at lower blood pressure levels may be justified.38
F2. What blood pressure is the aim of anti-hypertensive therapy? The aim of anti-hypertensive therapy is tokeep systolic blood pressure between 140 and 155 mmHg and diastolic blood pressure between 90 and 105 mmHg.(Level III,
Grade C) In treating severe hypertension, it is important to avoid hypotension, because the degree to which placental blood flow is autoregulated is not established, and aggressive
lowering may cause fetal distress. Consideration should be given to initiating agents for treatment of acute severe hypertension at lower doses, because these patients may be intravascularly volume depleted and may be at increased risk for hypotension.53
F3. Labetalol given orally or intravenously, intravenous hydralazine, or oral nifedipine can be used for the acute management of severe hypertension.(Level I, Grade A)
The preferred therapeutic agents are labetalol, nifedipine or hydralazine. Labetalol has the advantage that it can be given initially by mouth in severe hypertension and then, ifalthough needed, the intravenously. A review suggested that hydralazine preferable, evidence is not strong has enough to preclude its use.54 may be less The National High Blood Pressure Education Program (NHBEP) Working Group Report on High Blood Pressure in Pregnancy published in the journal of American Heart Association the recommended drugs for urgent control of severe hypertension in pregnancy. Drugs for Urgent Control of Severe Hypertension in Pregnancy Drug (FDA Risk*) Labetalol ( C )
Dose and Route 10 to 20 mg IV, then 20 to 80 mg every 20 to 30 minutes, maximum of 300 mg; for infusion: 1 to 2 mg/min
Precaution & Adverse Effect Because of a lower incidence of maternal hypotension and other adverse effects, its use now supplants that of hydralazine; avoid in women with asthma or congestive heart failure. Not available locally .
Hydralazine ( C )
5 mg, IV or IM, then 5 to 10 mg every 20 to 40 minutes; once BP controlled repeat every 3 hours; for infusion: 0.5 to 10.0 mg/hr; If no success with 20 mg IV or 30 mg IM, consider another drug
A drug of choice according to NHBEP; long experience of safety and efficacy
Nifedipine ( C )
Tablets recommended only: 10 to 30 mg PO, repeat in 45 minutes if needed
Should be used with caution if concomitantly used with MgSO4
IV Nicardipine
D5W 90 mL + Nicardipine 10 mg in soluset Concentration = 0.1 mg/ mL Start drip at 10 ugtts/min (equivalent to 1 mg/hr) Titrate every hour (increments of 1 mg/hr). Maximum dose 10 mg/hr Note: The IV infusion site must be changed every 12 hours
Should be used with caution if concomitantly used with MgSO4
Note: Since Labetalol is not locally available, hydralazine is the first line drug in the urgent control of severe hypertension in pregnancy. If no success with 20 mg IV, another drug should be considered, and this is usually a calcium channel blocker (oral nifedipine or IV nicardipine). The maximum dose of oral nifedipine is 50 mg PO and 10mg/hour for IV nicardipine. Maternal adverse effects include tachycardia, palpitation, peripheral edema, headache and facial flushing. Patients with resistant severe hypertension after maximum doses of these drugs should be delivered.
F4.Treatment
of
moderate
hypertension
may
assist
in
the
prolongation
of
pregnancy. (Level III, Grade C)
There is continuing debate concerning women with blood pressure between 150 – 160 systolic and 100 – 110 diastolic. Maternal treatment is associated with a reduction of severe hypertensive crises and a reduction in the need for further antihypertensive therapy. With treatment, a prolongation of pregnancy of an average of 15 days is possible as long as there is no other reason to deliver.55 Methyldopa and labetalol were the most commonly used therapies. Methyldopa has been proven safe in long term follow-up of the delivered babies.56 The NHBEP Working Group Report on High Blood Pressure in Pregnancy published in the journal of American Heart Association the recommended drugs for the treatment of gestational hypertension and chronic hypertension (Table 4). Doctors should use the drugs with which they are familiar. A recent metaanalysis of 24 trials concluded that there is insufficient data to favour one agent over another.57 Although others have concluded that agents other than parenteral hydralazine (eg labetalol or nifedipine) are preferable because of reduced maternal and fetal adverse 54
effects. F5. Atenolol, angiotensin converting-enzyme (ACE) inhibitors, angiotensin receptor blocking drugs (ARB) and diuretics should be avoided during pregnancy. (Level II-
2, Grade B) Atenolol is associated with an increase in fetal growth restriction. ACE inhibitors and ARBs would appear contraindicated because of unacceptable fetal adverse effects. Diuretics are relatively contraindicated for hypertension and should be reserved for pulmonary edema. 34
F6. Nifedipine (10mg or 30 mg XR) should be given orally not sublingually and should (Level III, Grade be used with caution if concomitantly used with magnesium sulfate.
C) Calcium antagonistsingiven sublingually arebecause now not for the treatment of hypertension nonpregnant patients of recommended reports of myocardial infarction and death in hypertensive patients with coronary artery disease.58 One study has shown efficacy and safety of long-acting oral nifedipine in pregnant patients with
Table 4. Drugs for Gestational or ChronicHypertension in Pregnancy
severe hypertension in pregnancy.59 A concern with the use of calcium antagonists for BP control in preeclampsia has been the concomitant use of magnesium sulfate to prevent seizures; drug interactions between nifedipine and magnesium sulfate were reported to cause neuromuscular blockade, myocardial depression, or circulatory collapse in some cases.60 In a recent evaluation,61 these medications are commonly use together without increased risk.
F7. How is postpartum hypertension managed? Anti-hypertensive drugs should be given if the BP exceed 150 mmHg systolic or 100 mmHg diastolic during the postpartum. (Level III, Grade C) Agents commonly used in the antepartum period may be used or continued postpartum. (Level III, Grade C) Diuretics can be used during the postpartum period.(Level I, Grade A)
It is prudent to avoid non-steroidal anti-inflammatories in postpartum women who are hypertensive. (Level III, Grade C)
Postpartum, no guidelines currently exist with regard to antihypertensive medications but Tan and de Swiet62 have suggested that antihypertensive drugs should be given if the BP exceeds 150 mmHg systolic or 100 mmHg diastolic in the first 4 days of the puerperium. Choice of antihypertensive agent in the postpartum period is often influenced by breast feeding, 63 but in general, the agents commonly used in the antepartum period may be continued postpartum. 53 The medication may when in thethis blood pressure normalizes. Home blood pressure monitoring bybe thediscontinued patient is helpful regard. In select cases of women with severe preeclampsia, there seems to be some benefit to a brief course of furosemide diuresis in the days postpartum.64 A few case reports have suggested that nonsteroidal anti-inflammatories may contribute to blood pressure elevation postpartum,65 and the effects on blood pressure in non-pregnant individuals are well documented. Thus, in postpartum patients who are already hypertensive, these drugs should be used cautiously or should perhaps be avoided.
G. Use of Corticosteroids G1. Is corticosteroid therapy indicated for fetal lung maturity? Between 24-34 weeks, corticosteroids should be given to enhance fetal lung maturity. The recommended regimens are the following: Betamethasone 12 mg IM every 24 hours for 2 doses Dexamethasone 6mg IM every 12 hours for 4 doses(Level I, Grade A)
In pregnancies less than 34 weeks and the pregnancy can be prolonged in excess of 24 hours, steroids help to reduce fetal respiratory mortality.66-67 There is probable benefit from steroid therapy even if delivery is less than 24 hours after administration.68-69
G2. Does steroid therapy have a role in the treatment of HELLP syndrome? The use of dexamethasone or other steroids for therapy specific for HELLP syndrome is not recommended and this approach should be considered experimental. (Level I, Grade A)
Two trials70-71 compared treatment with dexamethasone vs. placebo in women with HELLP syndrome. Both studies revealed outcomes that were not significantly different between 2 groups. One study72 suggests that corticosteroids use lead to a more rapid resolution of the biochemical and hematological abnormalities but there is no evidence that they reduce morbidity.
H. Delivery H1. When is the woman with severe preeclampsia delivered? Pregnancies ! 34 weeks of gestation complicated by severe preeclampsia is best managed by delivery after maternal stabilization.(Level I, Grade A) If the fetus is less than 34 weeks of gestation and delivery can be deferred, corticosteroids should be given, although after 24 hours, the benefits of conservative management should be reassessed. (Level I, Grade A)
If the gestation is greater than 34 weeks and complicated by severe preeclampsia, 34
delivery afterand stabilization recommended. gestational approaches 34 weeks, short long termisneonatal outcomes As are the excellent, fetal age survival is already similar to that of term gestations, and the potential benefits of expectant management becomes less compelling. Prolonging the pregnancy at very early gestation may improve the outcome for the premature infant but can only be considered if the mother remains stable. 68,69 Two small randomized controlled trials73,74 have reported a reduction in neonatal complications with an expectant approach to management of severe early-onset preeclampsia with no increase in maternal complications. Several case series have also reported similar outcomes in different settings with gestations as early as 24 weeks .7,8,68,69
H2. What is the mode of delivery? The mode of delivery should be determined after considering the presentation of the fetus and the fetal condition, together with the likelihood of success of induction of labor after assessment of the cervix. (Grade C)
In all situations, a carefully planned delivery is appropriate. Vaginal delivery is generally preferable but, if gestation is below 32 weeks, caesarean section is more likely as the success of induction is reduced. After 34 weeks with cephalic presentation, vaginal delivery should be considered. 5,34 The obstetrician should discuss the mode of delivery with the mother. Vaginal prostaglandins will increase the chance of success. Anti-hypertensive treatment should be continued throughout assessment and labor.34
I. How should the woman be managed following delivery? I1. Clinicians should be aware of the risk of late seizures and ensure that women have a careful review before discharge form the hospital.(Level III, Grade C) I2. Anti-hypertensive medication should be continued after delivery as dictated by the blood pressure. It may be necessary to maintain treatment for up to 3 months.
(Level III, Grade C) I3. Women with persisting hypertension and proteinuria at 6 weeks may have renal disease and should be considered for further investigation. (Level III, Grade C)
Severe preeclampsia can occur postpartum. Women who develop hypertension or symptoms of preeclampsia postnatally (headaches, visual disturbances, nausea and vomiting or epigastric pain) should be assessed.75 As eclampsia has been reported up to 4 weeks postnatally, the optimum length of inpatient postnatal stay is unclear but the incidence of eclampsia and severe preeclampsia falls after the 4th postpartum day.76 The decision about discharge from hospital needs to consider the risk of late seizures. Most women with severe preeclampsia or eclampsia will need inpatient care for 4 days or more following delivery. Careful assessment of the woman to ensure improving clinical signs is needed before disacharge.34 Antihypertensive therapy should be continued after delivery. Although, initially, blood pressure may fall, it usually at around 24 hours postpartum. A reduction in anti-hypertensive therapy rises shouldagain be made in a stepwise fashion. There is no reason why the woman cannot go home on treatment, to be weaned off therapy as an outpatient. After preeclampsia, blood pressure can take up to 3 months to return to normal. During this time, blood pressure should not be allowed to exceed 160/100 mmHg. There is insufficient evidence to recommend any particular drug, however, it is good practice to avoid the use of methydopa in the postnatal period because of its adverse effect profile, particularly depression. Atenolol and metoprolol are also found to be concentrated in the breastmilk.34,53
References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
ACOG. Diagnosis and Management of Preeclampsia and Eclampsia: ACOG Practice Bulletin No. 33. Obstet Gynecol 2002; 99: 159-67. Robson SC. Hypertension and Renal Disease in Pregnancy. In: Edmond DIC, ed. Dewhuret’s Texbook of th Obs and Gyn for Postgraduates. 6 ed.Oxford: Blackwell Science Ltd.1999:166-85. Report of theAm National High Blood2000;183:S1-22. Pressure Education Program Working Group on High Blood Pressure in Pregnancy. J Ob stet Gynecol Phillipine Obstetrical and Gynecological Society Committee on Nationwide S tatistics 2005-2008. Norwitz ER. Expectant managem ent of severe preeclampsia remote from term: Hope for the best, but expect the worst. Am J Obstet Gynecol 2008:209-212. Cunningham, F6, Cox K, Gant NF, Leveno KJ. Pregnancy Hypertension. In: Williams Obstetrics, 23 rd ed. New York: Mc-Gr aw-Hill 20 10:706-756. Odendaal HJ, et. al. Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks gestation: A randomized controlled trial. Obstet Gynecol 1990;76:1070-5. Sibai BM, et. al. Aggressive versus expectant management of severe preclampsia at 28-32 weeks gestation: A Randomized controlled trial. Am J Obstet Gyn ecol 1994;171:818-22. Sarsam DS. Expectant versus aggressive management in severe preeclampsia remote from term. Singapore Med J 2008;49(9):698. Friedman SA, Schiff E, Lobarsky SL, Sibai BM. Expectant management of severe preeclampsia remote from term. Clin Obstet Gynecol 1999;42:470-8. Schiff E, Friedman SA, Kao L, Sibai BM. The importance of urinary protein excretion during conservative management of severe preeclampsia. Am J Obstet Gynecol 1996; 175: 1313-6. Hall DR, Odendaal HJ, Steyn DW, Grive D. Urinary protein excretion and expectant management of early onset severe preeclampsia. Int J Gynaecol Ob stet 2002;77:1-6. Sibai BM, Barton JR. Expectant management of severe preeclampsia remote from term: Patient selection, treatment and delivery indication. Am J Ob stet Gynecol 2007;514:E1-9. Sibai BM, Akl S, Fairlie F, Morette M. A protocol for managing severe preeclampsia in the second trimester. Am J Obstet Gyn ecol 1990;163:733-8.
15. Olah KS, Redman WG, Gee H. Management of severe, early preeclampsia: Is conservative management justified? Eur J Obs tet Gynecol Reprod Biol 1993;51:175-80. 16. Visser W, Wallenburg HCS. Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe preeclampsia remote from term. Eur J Obstet Gynecol Reprod Biol 1995;63:147-54. 17. Chammas MF, Nguyen TM, Li MA, Nuwayhid BS, Castro LC. Expectant management of severe preterm preeclampsia: Is in trauterine growth restriction an indication for immediate delivery? Am J Obstet Gynecol 2000;183:853-8. 18. Hall DR, Odendaal HJ, Kristen GF, Smith J, Grove D. Expectant management of early onset, severe preeclampsia: perinatal outcome. BJOG 2000;107:1258-64. 19. Vigil-DeGarcia P, Montufar-Rueda C, Ruiz J. Expectant management of severe preeclampsia between 24 and 34 weeks’ gestation. Eur J Obs tet Gynecol Reprod Biol 2003;107:24-7. 20. Haddad B, Deis S, Goffinet F, Daniel BJ, Cabrol D, Sibai BM. Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks’ gestation. Am J Obstet Gynecol 2004;190:1590-5. 21. Shear RM, Rinfret D, Leduc L. Should we offer expectant management in cases of severe preterm preeclampsia with fetal growth restriction? Am J Obs tet Gynecol 2005;192: 1119-25. 22. Oettle C, Hall D, Roux A, Grove D. Early onset severe preeclampsia: expectant management at a secondary hospital in close association with a tertiary institution. BJOG 2005;112:84-8. 23. Ganzevoort W, Rep A, Bousel GJ, et al. A randomized controlled trial comparing two temporizing management strategies, one with and one without plasma volume expansion, for severe preeclampsia. BJOG 2005;112:1358-68. 24. Withagen M, et. al. Neonatal outcome of temporizing treatment in early onset preeclampsia. Eur J Obstet Gynecol Reprod Biol 2001;94:211-5. 25. Hall DR, Odendaal HJ, Steyn DW. Expectant management of severe preeclampsia in the mid-trimester. Eur J Obstet Gynecol 2001;96:168-72. 26. Jenkins SM, Head BB, Hauth JC. Severe preeclampsia at <25 weeks of gestation: maternal and neonatal outcomes. Am J Obs tet Gynecol 2002;186:790-5. 27. Budden A, Wilkinson L, Buksh MJ, McCowan L. Pregnancy outcome in women presenting with preeclampsia at less than 25 weeks’ gestation. Aust N Z J Obstet G ynaecol 2006;46:407-12. 28. Withagen MIJ, Walenburg HCS, Steegers EAP, Hop WCJ, Visser W. Morbidity and development in childhood of infants born after temporisisng treatment of early onset preeclampsia. BJOG 2004;112:910-4. 29. Bombrys AE, et. al. Expectant management of severe preeclampsia at less than 27 weeks gestation: maternal and perinatal outcome according to gestational age by weeks at onset of expectant management: Am J Obs tet Gyneco l 199:247.El, 2008. 30. Sibai BM. Diagnosis, controversies and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 2004;103:981-91. 31. Visser W, Wallenburg HCS. Temporising management of severe preeclampsia with and without HELLP syndrome. BJOG 1995;102:111-7.. 32. van Pampus MG, Wolf H, Westenberg SM, der Post V, Bonsel GJ, Treffers PE. Maternal and perinatal outcome after expectant management of HELLP syndrome compared with preeclampsia without HELLP syndrome. Eur J Obs tet Gynecol Reprod Biol 1998;76:31-6. 33. van Runnard Heimel PJ, Huisjes AJM, Fraux A, Koopman C, Bots ML, Bruinse HW. A randomized placebo-controlled trial of prolonged prednisolone administration to patients with HELLP syndrome remote from term. Eur J Ob stet Gynecol Reprod Biol 2006;128:187-93. 34. Royal College of Obstetricians & Gynecologists. The management of Severe Preeclapmsia. Evidence Based Clinical Guideline No 10 (A). London: RCOG Press; 2006. 35. Boxter Jk. Hypertensive Disorders. Maternal - Fetal Medicine. Evidence Based Guidelines 2007; 1: 3-22. 36. Pottecler T, et. al. Multidisciplinary Management of Severe Preeclampsia. January 27 2009. 37. Brown MA, et. al. Randomized trial of management of hypertensive pregnancies by korotkoff phase IV or phase V. Lancet 1998;352:777-81. 38. Lewis G, editor. Why Mothers Die 2000-2002. The Sixth Report of the Confidential Inquiries into Maternal Deaths in the United Kingdom. London: RCOG Press; 2004. 39. Golara M, et al; Inflationary oscillometry provides accurate measurement of blood pressure in preeclampsia BJOG 2002;109:1143-7.
40. Waugh J, et. al. Optimal bedside urinalysis for the detection of proteinuria in hypertensive proteinuria: a study of diagnostic accuracy? BJOG 2005: 112: 412-17. 41. Crithchley H, et. al. Preeclampsia. London: R COG Press; 2003. 42. Magpie Triad Collaborative Group: Do women with preeclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomized placebo-control led trial. Lancet 359:1877-2002. 43. Trufnell DJ, et. al. Outcome of severe preeclampsia/ eclampsia in Yorkshire 1999/2003. BJOG 2005;112:875-80. 44. Which anticonvulsant for women with preeclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995;345(8963):1455-63. 45. Redman CW, et. al. Early platelet consumption in preeclampsia. Br Med J 1978;(6111):467-9. 46. Sharma SK, et. al. Assessment of changes in coagulation in parturient with preeclampsia using thromboelastography. Anesthesiology 1999;90:385-90. 47. Martin JN, et. al. Early risk assessment of severe preeclampsia: admission battery of symptoms and laboratory tests to predict likelihood of subsequent significant maternal morbidity. Am J Obstet Gynecol 1999;180:1407-14. 48. Martin JN, et. al. The spectrum of severe preeclampsia: comparative analysis of HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome classification. Am J Obstet Gynecol 1999;180:1373-84. 49. Duley L, et. al. Plasma volume expansion for treatment of women with preeclampsia. Cochrane Database Syst Rev 2000(2):CD001805. 50. RCOG. The Use of Electronic Fetal Monitoring. Evidence Based Clinical Guideline No. 8. London: RCOG Press; 2001. 51. Galan HL, et. a l. Intrauterine Growth Restriction (IUGR): biometric and doppler assessment. Prenat Diagn 2002;22:331-7. 52. Alfirevic Z, et. al. Doppler ultrasonography in high risk pregnancies: systematic review with meta-analysis. Am J Obs tet Gyneco l 1995;172:1379-87. 53. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Ob stet Gynecol 2000;183:S1-S22. 54. Magee LA, et. al. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ 2003;327:955-60. 55. Magee LA, et. al. Fortnightly Review: management of hypertension in pregnancy. BMJ 1999;318:1322-6. 56. El-Qarmalawi AM, et. al. Labetalol vs. me thyldopa in the treatment of pregnancy induced hypertension. Int J Gynaeco l Obstet 1995;49:125-30. 57. Duley L, et. al. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev 2006; 3:CD001449. 58. Furberg CD, et. al. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation 1995;92:1326-1331. 59. Brown MA, et. al. Efficacy and safety of nifedipine tablets for the acute treatment of severe hypertension in pregnancy. Am J Obs tet Gyne col 2002:187:1046-1050. 60. Ben-Ami M, et. al. The combination of magnesium sulfate and nifedipine: a cause of neuromauscular blockade. Br J Obstet Gynaecol 1994;101:262-263. 61. Magee LA, et. al. Therapy with both m agnesium sulfate and nifedipine does not increase the risk of serious magnesium related maternal side effects in wo men with preeclampsia. Am J Obstet Gynecol 2005:193:153163. 62. Tan LK, de Swiet M. The management of postpartum hypertension. BJOG 2002.109:733-736. 63. Beardmore KS, et, al. Excretion of anti-hypertensive medication into human breastmilk: a systematic review. Hypertens Pregnancy 2002;21:85-95. 64. Ascarelli MH, et. al. Postpartum preeclampsia management with Furosemide: A randomized clinical trial. Obstet Gynecol 2005;105:29-33. 65. Makris A, et. al. Postpartum hypertension and non-steriodal analgesia. Am J Obstet G ynecol 2004;190:577578. 66. Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2000 (2): CD000065. 67. Leveno KJ, Cunningham FG, Lindheimer MD, Roberts JM, Cunningham FG (eds): Chesley’s Hypertensive Disorder of Pregnancy 3 rd ed. New York, In Pr ess, 2009, p.395.
68. Magan EF, et. al. Neonatal salvage by weeks’ gestation in pregnancies complicated by HELLP syndrome. J Soc Gynecol Investig 1994;1:206-9. 69. Bramovici D, et. al. Neonatal outcome in severe preeclampsia at 24-36 weeks gestation: Does the HELLP Syndrome matter? Am J Obstet Gynecol 1999;180:221-5. 70. Fonseca JE, et. al. Dexamethasone treatment does not improve the outcome of women with HELLP syndrome. A Double blind placebo-controlled, randomized clinical trial. Am J Obstet Gynecol 193:1591,2005. 71. Katz L, et. al. Postpartum dexamethasone for women with. HELLP Syndrome. A double blind, placebocontrolled, randomized clinical trial. Am J Obstet Gyn ecol 198.283. el, 2008. 72. Clenny TL, Viera AJ. Corticosteroid for HELLP syndrome. BMJ 2004;329;270-2. 73. Murphy DJ, Stirrat GM. Mortality and morbidity associated with early onset preeclampsia. Hypertens Pregnancy 2000;19:221-31. 74. Haddad B, Deis S. Goffinet F, Paniel BJ, Cabral D, Sabai BM. Maternal and perinatal outcome during expectant management of 239 severe preeclampsia women between 24-33 weeks gestation . Am J Obstet Gynecol 2004;190-1590-7. 75. Atterburry JL, et. al. Clinical presentation of women readmitted with postpartum severe preeclampsia or eclampsia. J Obstet Gynecol Neonatal Nurs 1998;27:134-41. 76. Lubarsky SL, Sibai BM. Late postpartum eclampsia revisited. Obstet Gynecol 1994;83:502-5. 77. Sibai BM. Expectant management of preeclampsia. OBG Management 2005;3:18-36. 78. Sibai BM, Bartom JR. Expectant management of severe preeclampsia remote from term: patient selection treatment, and delivery Indications. Am J Ob stet Gynecol 2 007;514:E1-E9.
Eclampsia Raul M. Quillamor, MD and Diosdado V. Mariano, MD
The aims in the treatment of eclampsia are: control of seizure correction of hypoxia and acidosis control of blood pressure delivery after control of seizure • • • •
The protocol of active management of eclampsia consists of: A. Hospitalization - required for all patients with eclampsia. (Level I, Grade A) B. Control of seizures and prevention of recurrence
Magnesium sulfate (MgSO4) is currently considered the drug of choice in the prevention of eclamptic seizures as well as the reduction of recurrent seizures. The Eclampsia Collaborative Trial Group in 1995 has established the superiority of magnesium sulfate over diazepam and phenytoin in the treatment of convulsions. Significantly fewer recurrences of seizures were noted among patients given magnesium sulfate than those given diazepam or phenytoin, although no significant reduction in maternal and perinatal mortalities was noted among the three groups. The recommended MgSO4 dosage schedules for severe preeclampsia and eclampsia have been previously mentioned in the chapter on management of severe pre-eclampsia (Section Six) but they are restated here for emphasis: 1. Loading doses of 4 g IV slowly over 5-10 minutes and 10 g deep IM (5 g to each buttock), then 5 g IM every 4 hours until 24 hours after delivery. (Pritchard 1984). 2. Loading dose of 4 g IV followed immediately by IV infusion of 2 g per hour. Incorporate 20 g MgSO4 (four 10-ml ampules of 50% MgSO4) to 1000 ml D5W or Normosol-M, and infuse IV at a rate of 100 ml/hour (2 g/hr), via infusion pump or soluset (Anderson 1986). One may reduce the drip to 1 g/hr after 24 hours. The following precautions must be observed prior to administration of succeeding doses: 1. 2. 3. 4.
Urine output of at least 30 ml for the past hour or 100 ml for the past 4 hours Presence of patellar reflex Respiratory rate of not less than 12/min. IV Calcium gluconate (10 ml of 10% solution) available at bedside for MgSO4 overdose. 5. Serum magnesium levels may be taken at certain intervals to monitor for magnesium toxicity (Level III, Grade C). Maintenance of plasma magnesium levels at 4-7 meq/L almost always prevents eclamptic convulsions.2 Patellar reflexes disappear with plasma levels of 8-10 meq/L. This sign warns of impending magnesium toxicity since respiratory depression develops at 12 meq/L, followed by respiratory and cardiac paralysis and arrest.
6. If a patient is to be transferred to another hospital, the full loading dose must have been given and the patient should be accompanied by a responsible health personnel, with provisions for control of seizures and other complications, if they occur. (Level II-2, Grade B) If MgSO4 is not available, other anti-seizure options that may be used are: Diazepam A loading dose of 10 mg IV over 2 minutes, repeated if convulsions recurred, followed by an intravenous infusion of 40 mg in 500ml normal saline for 24 hours. The rate of infusion is titrated based on thebut level of consciousness, with 24 thehours, aim ofan overcoming and keeping the patient sedated rousable. During the next infusion ofrestlessness 20 mg diazepam in 500 ml normal saline is given and slowly reduced. It may be used with Phenytoin in the management of convulsions in the absence of magnesium sulfate. (Level II-2, Grade B) Phenytoin There is no consensus about an ideal phenytoin regimen, although the dose may be varied according to the patient’s weight. Since phenytoin is only recommended for the prevention of seizures, 10mg diazepam IV should be given to control the seizures. Thereafter, an initial phenytoin loading dose of 1 gm slow IV (over 20 min) is given with continuous cardiac monitoring, and followed by succeeding doses of 100 mg every 6 hours for the next 24 hours. (Level II-2, Grade B)
C. Anti-hypertensive therapy
Patients with severe should be and started on IV therapy. drugs thatBmay be used are hydralazine (drug hypertension of choice); clonidine nifedipine ( LevelThe II-2, Grade ); and labetalol7 (Level I, Grade A) Give Hydralazine by IV boluses of 5 or 10 mg at 20 to 30 min intervals until the desired BP is attained. Administering hydralazine via an IV drip is not recommended because of the instability of the preparation. (Level II-1, Grade B) a. Clonidine IM 75-150 mcg is the next recommended drug. b. Nifedipine 5 or 10 mg can be given orally and takes effect within 15-50 minutes. The sublingual route is not recommended for pregnant patients because of the acute fluctuations in blood pressure levels and the absence of good studies on fetal effects of calcium antagonists. (Level II-2, Grade C) c. Labetalol can be given with an initial dose of 20 mg IV bolus. If the desired BP is not attained within 10 minutes, give 40 mg, then 80 mg every 10 minutes but not to exceed a total of 220 mg per episode treated.7,8 This drug should be avoided in women with asthma or congestive heart failure.
D. Delivery after control of seizures
It is generally accepted that continuation of pregnancy in eclamptic patients constitutes a significant threat to maternal and fetal well being such that pregnancy should be terminated. It is recommended to induce labor or to perform a cesarean section as soon as the patient becomes conscious and oriented, since temporization to gain fetal maturity in the presence of eclampsia is always risky. (Level II-3, Grade B) It has been observed that the uterus is sensitive to oxytocin so that labor can be induced even with an “unfavorable” cervix and assisted vaginal delivery can be performed if labor progresses. Cesarean section is reserved if: 1. vaginal delivery does not appear easy and imminent 2. there is failure of progress after induction, or 3. there is fetal compromise. Anticonvulsant therapy should be continued for at least 24 hours after delivery. In comatose patients, a neurologic evaluation with possibly a CT scan should be performed.
References
1. Creasy RK, Resnik R. Creasy & Resnik’s Maternal-Fetal Medicine Principles and Practice, Sixth Edition. 2. 3. 4. 5. 6. 7. 8.
2009, Saunders Elsevier. rd Cunningham FG, Leveno K, et. al. Williams Obste trics 23 Edition 2010, The McGraw-Hill Companies, Inc. Duley L, Henderson-Smart D. Magnesium Sulfate versus diazepam for eclampsia. Cochrane Database Syst
Rev (4):CD000127, 2003. Greer I, Walker J, et. al. Second line therapy with nifedipine in sever e pregnancy induced hypertension. Clin Exp Hypertens B8:277,1989. RCOG Guideline Number 10, March 2006: The Management of Severe Preeclampsia/Eclampsia . Sibai BM. Diagnosis, Prevention, and Management of Eclampsia . Obstetr Gynecol 2005; 105:402-10. ACOG 2002. National High Blood Pressure Education Program 2000
Chronic Hypertension Virgilio B. Castro, MD and Ann Marie C. Trinidad, MD
Definition
Chronic hypertension, defined as BP 140/90 mm Hg either predating pregnancy or developing before 20 weeks’ gestation and hypertension that persists 12 weeks postpartum. This complication may result in significant maternal, fetal and neonatal mortality and morbidity. Hypertensive disorders during pregnancy occurwho in develop women new-onset with pre-existing primary or secondary chronic hypertension, and in women hypertension in the second half of pregnancy. Antihypertensive agents are mainly used to prevent and treat severe hypertension; to prolong pregnancy for as long as safely possible, thereby maximizing the gestational age of the infant and to minimize fetal exposure to medications that may have adverse effects. The goal of treatment is to maintain BP at a level that minimizes maternal cardiovascular and cerebrovascular risk. Prevention of preeclampsia is desirable; however, current evidence has not shown that either specific BP targets in pregnancy or specific antihypertensive agents modify the risk of superimposed preeclampsia in women with pre-existing hypertension. The challenge is in deciding when to use antihypertensive medications and what level of BP to target. The choice of antihypertensive agents is less complex, because only a small proportion of currently available drugs have been adequately evaluated in pregnant women, and many others are contraindicated.
Recommendations
1. Low dose Aspirin (65-85 mg PO) at bedtime everyday from 12 weeks until birth should be considered in women with historical risk factors to decrease superimposed preeclampsia (e.g. hypertensive disease during a previous pregnancy, chronic renal disease, autoimmune disease such as systemic lupus erythematosis or antiphospholipid syndrome, type 1 or type 2 diabetes, chronic hypertension) (Grade A) Some women are more resistant than others to the effects of aspirin, a dose of at least 75 mg/d may be necessary to inhibit both platelet and placental thromboxane. However, a dose of 100 mg/d may affect fetal prostacyclin synthesis. 2. Angiotensin converting enzyme (ACE inhibitors) and Angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy. (Level II-2, Grade A) 3. The beta blocker atenolol may be associated with growth restriction and is not recommended for use in pregnancy. (Grade B) 4. Antihypertensive therapy should be reinstituted if BP exceeds 150-160 systolic or 100-110 diastolic. Initial antihypertensive therapy include the following: a. Methyldopa 250–500mg PO BID-QID (max 2g/day) b. Labetalol 100–400mg PO BID-TID (max 1200 mg/day)
c. Nifedipine PA (intermediate release) tablets (10–20 mg PO BID-TID, max 180 mg/day) or XL (slow release) preparation (20–60 mg PO OD, max 120 mg/day) Methyldopa and labetalol are the first line antihypertensive therapies. (Level I, Grade A)
Obstetric Management
1. Baseline ultrasound at 18-20 weeks and repeat scan at 28-32 weeks to monitor fetal growth and to check amniotic fluid volume. 2. If with growth or superimposed include umbilialrestriction artery Doppler velocimetry.preeclampsia, (Grade A) Antenatal fetal surveillance should 3. For women with pre-existing hypertension laboratory exams at initial visit include complete blood count (CBC), serum creatinine, serum potassium and urinalysis. (Grade B) 4. If with suspicion of preeclampsia, creatinine clearance and 24 hour urine protein are encouraged. (Grade A) 5. Vaginal delivery should be considered unless a cesarean section is required for the usual obstetric indication. (Grade B) 6. If vaginal delivery is planned and the cervix is unfavourable, then cervical ripening should be used to increase the chance a successful vaginal delivery. (Grade A) 7. Women with long standing hypertension should be evaluated for end-organ disease including cardiomegaly, renal insufficiency and retinopathy. (Grade C)
Complications of Pregnancy Induced Hypertension (HELLP, Abruptio Placnta) Ma. Luisa S. Acu, MD and Sol M. Pangan, MD
HELLP Syndrome
Definition •
•
•
•
The acronym HELLP was created by Louis Weinstein in 1982 to describe a subset of severe preeclampsia/eclampsia with microangiopathic hemolytic anemia, moderate to severe thrombocytopenia, disrupted or destroyed erythrocytes on peripheral smear, and abnormal liver function tests presenting with right upper quadrant/epigastric pain, nausea and vomiting. (H = hemolysis, EL = elevated liver enzymes, and LP = low platelets)1 Two classification systems have been created to stratify patients’ risks for significant maternal morbidity, to guide therapeutic intervention and assess outcomes. The Tennessee Classification (Sibai 1986)2 defines “complete” HELLP syndrome if all the following criteria are met: (1) moderate to severe thrombocytopenia with platelets 100,000/ml or less; (2) hepatic dysfunction with AST 70 IU/L or greater; (3) evidence of hemolysis with an abnormal peripheral smear in addition to either total serum LDH 600 IU/L or greater, or bilirubin 1.2 mg/dL or greater. When some but not all these parameters are present, the term “partial” or “incomplete” HELLP is used. The Mississippi Triple Class System (Martin 1999)3 divides patients into 3 classes based on their platelet counts: class 1 requires severe thrombocytopenia (platelets < 50,000/ml, evidence of hepatic dysfunction (AST and/or ALT > 70 IU/L), and evidence of hemolysis (total serum LDH > 600 IU/L); class 2 requires similar criteria except thrombocytopenia is moderate ( >50,000 to < 100,000/ml ); and class 3 includes patients with mild thrombocytopenia (platelets >100,000 but < 150,000/ml), mild hepatic dysfunction (AST and/or ALT > 40 IU/L), and hemolysis (total serum LDH > 600 IU/L).
Pathophysiology •
The pathophysiology of HELLP remains unclear. Strand et al4 postulated that placentaderived proteins are shed into the maternal circulation which damage hepatic cells, suggesting that HELLP syndrome is a placenta-instigated, liver-targetted acute inflammatory condition and disordered immunologic process.5
Clinical Presentation •
•
•
•
•
• •
Usually develops suddenly in the third trimester or immediate postpartum. Progression is usually rapid with 35-50 % decrease in platelets per day and rise in AST and ALT until 24 – 48 hours postpartum when levels begin to recover.6,7,8 Onset of disease occurs antepartum in 70 %, and postpartum in 30 % of cases. 15 Hypertension and proteinuria may be mild and may not directly correlate with laboratory parameters. Patients are usually seen complaining of malaise (90%), epigastric or right upper quadrant pain (90%), or nausea or vomiting (50%), and some with non-specific viral-like symptoms.13 The most important symptom is severe epigastric/right upper quadrant pain, found in 100% of Weinstein’s srcinal series of 29 advanced cases, often heralds rapidly progressive disease.1,3,9 A patient with severe preeclampsia who suddenly develops severe writhing epigastric/upper abdominal pain, may have hepatic hematoma or rupture, and constitutes an obstetric emergency. Rupture of a subcapsular liver hematoma is one of the most dreaded, life-threatening complication of the HELLP syndrome. If suspected, hepatic imaging with transabdominal ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI), can be performed.14 Significant maternal morbidity occurs with worsening thrombocytopenia, very high LDH, AST and/or uric acid levels.3,11 HELLP usually resolves within a week postpartum.5,6,25 60 % of maternal mortalities occur with class 1 disease and the most common cause is cerebral hemorrhage/stroke. Other causes of death are cardiac arrest, DIC, ARDS, renal failure, sepsis, hepatic rupture and hypoxic encephalopathy.10
Management •
•
•
•
•
Liver function tests and platelet counts should be done in all preeclamptic women, especially with suspected HELLP. (Level II, Grade B) Best managed in a center with intensive care facilities for hepatologic, hematologic and obstetric emergencies. (Grade B) There is a consensus of opinion that prompt delivery is indicated if the syndrome develops beyond 34 weeks gestation, or earlier if there is multiorgan dysfunction, disseminated intravascular coagulopathy, liver infarction or hermorrhage, renal failure, suspected abruption placentae, or nonreassuring fetal status. In these situations, treatment consists of prophylaxis against convulsions with magnesium sulfate, control of hypertension, stabilization of maternal condition, and then delivery.16 (Level III, Grade B) There is no general agreement, however, on the management of women with HELLP syndrome before 34 weeks gestation when the maternal condition is stable except for mild to moderate abnormalities in blood tests with a reassuring fetal condition. 29,16 (Grade C) Aggressive high dose corticosteroid therapy has been advocated to improve maternal and neonatal outcome in HELLP. Intravenous dexamethasone 10-12 mg every 12 hours, or
intramuscular betamethasone 10-12 mg every 12 hours, until delivery, and additional 3 more doses after delivery, were given with reported improvement in laboratory values, improvement in blood pressure, shorter hospital stay and an increased use of regional anesthesia.16-23,27 Most of these studies are retrospective and have critical design flaws, mainly in inclusion criteria, choice of historical controls and/or clinical outcome reported.29 The 4 randomized trials were not placebo controlled. Although improved laboratory values and urine output were obtained in the patients given dexamethasone, no differences in serious maternal morbidity such as need for transfusion, pulmonary edema, renal failure, or serous hepatic complications were shown. 29 Hence a Cochrane review (2004) concluded that there is insufficient evidence to determine whether corticosteroid 24 •
•
•
•
25 use HELLP major maternal and26perinatal morbidity. double-blind, The in results of syndrome two recentdecreases studies, Fonseca and Katz , both randomized, placebo-controlled clinical trials, with the largest sample sizes to date, on the use of high dose dexamethasone to improve maternal outcome in patients with HELLP syndrome, do not support routine use of this regimen for all HELLP cases. However, a subgroup analysis according to severity of disease, of the Fonseca cases, showed that among the patients with Class 1 HELLP (platelet counts less than 50,000/mm3 ), there was a shorter average platelet count recovery and less duration of hospitalization in those who received dexamethasone (4.6 versus 10.4 days). Replacement of clotting factors with frozen plasma and factor concentrates, and platelet transfusion for counts below 50,000/mm3 should be given as needed. (Level III, Grade B) Epidural or spinal anesthesia is the preferred anesthesia for patients with preeclampsia. Aggressive high dose corticosteroids can increase the platelet count to 75,000/mm3 , the threshold deemed adequate to undertake regional anesthesia (from 0% to 42%), and to enable cervical ripening, induction of labor, and possible vaginal delivery.27,28 (Level II,
Grade B)the patients could be discharged after 4-8 days hospitalization, if the platelet Most of count is greater than 100,000/mm3 and no evidence of end-organ damage.25
References
1. 2.
3.
4. 5.
6.
Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Ob stet Gynecol 1982;142:159-67. Sibai BM, Taslimi MM, el-Nazer A, Amon E, Mabie BC, Ryan GM. Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia. Am J Obs tet Gyneco l 1986;155:501-9. Martin JN Jr, Rinehart K, May WL, Magann EF, Terrone DA, Blake PG. The spectrum of severe Am J Obstet Gyneco l preeclampsia: comparative analysis by HELLP sybdrome classification. 1999;180:1373-84. Strand S, Strand D, Seufert R, Mann A, Lotz J, Blessing M, et. al. Placenta-derived CD95 ligand causes liver damage in HELLP syndrome. Gastroenterology 2004;126:849-58. Martin JN Jr, Magann EF, Isler CM. HELLP sybdrome: the scope of disease and treatment. In: Belfort MA, Thornton S, Saade GR, editors. Hypertension in pregnancy. Chap 7. Oxford: Marcel Dekker; 2003.p.141-88. Martin JN Jr, Blake PG, Perry KG, McCaul JF, Hess LW, Martin RW. The natural history of HELLP syndrome: patterns of disease progression and regression. Am J Ob stet Gynecol 1991;164:1500-13.
7. 8. 9. 10. 11.
12. 13. 14.
15.
16. 17. 18. 19. 20.
21.
22. 23. 24. 25.
26.
27.
28.
Katz VL, Thorp JM, Rozas L, Bowes WA Jr. The natural history of thrombocytopenia associated with preeclampsia. Am J Obstet Gynecol 1990;163:1142-3. Makkonen N, Harju M, Kirkinen P. Postpartum recovery after severe preeclampsia and HELLP sybdrome. J Perinat Med 1996;24:641-9. Faridi A, Rath W. Differential HELLP syndrome diagnosis. Z Gerburstschilfe 1996;200:88-95. Isler CM, Rinehart BK, Terrone DA, Martin RW, Magann EF, Martin JN Jr. Maternal mortality associated with HELLP syndrome. Am J Obstet Gyn ecol 1998;181:924-8. Catanzarite VA, Steinberg SM, Mosley CA, Lauders CF, Cousins LM, Sneider JM. Severe preeclampsia with fulminant and extreme elevationof aspartate aminotransferase and lactate dehydrogenase levels: high risk for maternal death. Am J Perinatol 1995;12:310-3. Martin JN Jr, Rose CH, Briery CM. Understanding and managing HELLP syndrome: the integral role of aggressive glucocorticoids for mother and child. Am J Obstet Gynecol 2006;195:914-34. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gyn ecol 1990;162:311-6. Wicke C, Pereira PL, Neeser E, Flesch I, Rodegerdts EA, Becker HD. Subcapsular liver hematoma in HELLP syndrome: evaluation of diagnostic and therapeutic options – A unicenter study. Am J Obstet Gynecol 2004;190:106-112. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obs tet Gynecol 1993;169:1000-6. Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes and low platelet count. Obstet Gynecol 2004;103:981-91. Martin JN Jr, Magann EF. High-dose dexamethasone:a promising therapeutic option for HELLP. Contemp Ob Gyn 1999;44:55-65. Magann EF, Bass D, Chouhan SP, Sullivan DL, Martin RW, Martin JN Jr. Antepartum corticosteroids: disease stabilization in patients with HELLP syndrome. Am J Obstet Gynecol 1994;171:1148-53. Magann EF, Perry KG Jr, Meydrech EF, Harris RL, Chouhan SP, Martin JN Jr. Postpartum corticosteroids: accelerated recovery fom HELLP syndrome. Am J Obstet Gyn ecol 1994;171:1154-8. van Runnard Heimel PH, Juisjes AJM, Franx A, Koopman C, Bots ML, Bruinse HW. A randomized placebo controlled trial of prolonged prednisolone administration to patients with HELLP syndrome remote from term: maternal and neonatal complications. Am J Obstet Gynecol 2004;191:S41. Isler CM, Barrilleaux PS, Magann EF, Bass JD, Martin JN Jr. A prospective randomized trial comparing the efficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP syndrome. Am J Ob stet Gynecol 2001;184:1332-7. Vigil-DeGracia P, Garcia-Caceres E. Dexamethasone in the postpartum treatment of HELLP syndrome. Int J Gynaecol Obstet 1997;59:217-21. Yalcin OT, Sener T, Hass H, Ozalp S, Okur A. Effects of postpartum corticosteroids in patients with HELLP syndrome. Int J Gynaecol Obstet 1997;61:141-8. Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in pregnancy. (Cochrane Review) In: The Cochrane Library, Issue 4, 2004:CD002076 Oxford: Updates Software. Fonseca JE, Mendez F, Catano C, Arias F. Dexamethasone treatment does not improve the outcome of women with HELLP syndrome: a double blind, placebo-controlled, randomized clinical trial. Am J Obstet Gynecol 2005;193:1591-8. Katz L, de Amorin MMR, Figueroa JN, Pinto eSilva JL. Postpartum dexamethasone for women with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: a double-blind, placebocontrolled, randomized clinical trial. Am J Obs tet Gynecol 2008;198:283.e1-283.e8. O’brien JM, Shumate SA, Satchwell SL, Milligan DA, Barton JR. Maternal benefit of corticosteroid therapy in patients with HELLP (hemolysis, levated liver enzymes, and low platelet count) syndrome: impact on the rate of regional anesthesia. Am J Obs tet Gynecol 2002;186:457-9. Rose CH, Thigpen BD, Bofill JA, Cushman J, May WL, Martin JN Jr. Obstet implications of antepartum corticosteroid therapy for HELLP syndrome. Obstet Gynecol 2004;104:1011-4.
29. Sibai BM, Barton JR. Dexamethasone to improve maternal outcome in women with hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Obstet Gynecol 2005;193:1587-90.
Abruptio Placenta
Definition
Placental abruption is defined as premature separation of a normally implanted placenta. Approximately 0.5 – 1% of all pregnancies are complicated by placental abruption. Abruption may be “revealed,” in which case blood tracks between the membranes and the decidua, and escapes through the cervix into the vagina. The less common “concealed” abruption occurs when blood accumulates behind the placenta, with no obvious external bleeding. Total abruption involves the entire placenta, in which case it typically leads to fetal death, while in partial abruption, only a portion of the placenta is detached from the uterine wall. There are no randomized controlled studies that have specifically studied abruption, Majority of the studies published in English are observational (i.e. cohort, case-control, or case series). Most large studies with abruption have examined the risk factors for this condition. Studies dealing on management strategies for abruptio are usually limited by small sample size. The levels of available evidence for the diagnosis and management of abruptio placenta are mostly II-1, II-2, and III. There are no trials to assess any intervention for prevention of abruption or its complications.
Clinical Importance
Placental abruption has a wide spectrum of clinical significance, varying from cases with minor bleeding and little or no consequences, to massive abruption leading to fetal death and severe maternal morbidity. The maternal effect of abruption depends primarily on its severity, whereas its effect on the fetus is determined both by its severity and the gestational age at which it occurs. Maternal complications include antepartum and postpartum hemorrhage, disseminated intravascular coagulation (DIC) and acute renal failure, need for blood transfusions, hysterectomy, and less commonly, maternal death. Fetal complications include a high perinatal mortality, preterm delivery, fetal hypoxia and/or exsanguination, and growth restriction. This high perinatal mortality is largely due to preterm delivery, because approximately one half of the excess perinatal deaths are associated with early delivery. Abruption may be implicated in up to 10% of preterm births. Although placental abruption is an important cause of spontaneous preterm birth, it is also often an indication for iatrogenic preterm delivery. Premature separation of the placenta before delivery may deprive the fetus of oxygen and nutrition, leading to long-term handicap among survivors. Hypertensive diseases in pregnancy are strongly associated with placental abruption. However, the severity of hypertension does not necessarily correlate with the incidence of abruption.
Table 1. Evidence and Strength of Association Linking Major Risk Factors with Placental Abruption Based on Published Studies
Risk Factors
Strength of Evidence
RR or OR
Chronic hypertension
++
1.8 – 5.1
Mild and Severe Preeclampsia
++
0.4 -4.5
Chronic hypertension with Preeclampsia
+++
7.8
RR, relative risk; OR, odds ratio. These estimat es are the ranges of RR or OR found in independent studies. Reprinted from Yeo L, Ananth CV, Vintzileos AM. Placental abruption . In: Sciarra J, editor. Gynecology and obstetrics. Vol 2. Hagerstown (MD). Lippincott, Williams & Wilkins; 2003. © 2003 Lippincott Williams & Wilkins .
Clinical Presentation
The clinical presentation of abruption varies widely from totally asymptomatic cases to those where there is fetal death with severe maternal morbidity. The classically described symptoms of placental abruption are vaginal bleeding and abdominal pain. Abruptio placenta must be considered whenever bleeding occurs in the second half of pregnancy . It is also possible to have severe abruption without neither or just of one of these signs. The amount of vaginal bleeding correlates poorly with the degree of abruption. The severity of symptoms depends on the location of the abruption, whether it is revealed or concealed, and the degree of abruption. There is a correlation between the extent of placental separation and the risk of stillbirth, with stillbirth occurring in most cases in which there is greater than 50% placental separation. Typically, there is uterine hypertonus with associated high-frequency, low- amplitude uterine contractions. The uterus is frequently tender and may feel hard on palpation. Backache may be the only symptom, especially when the placental location is posterior. There may be acute fetal distress, and in cases where more than 50% of the placenta has separated, fetal demise. Rarely fetal death due to abruption may occur with no other symptoms or signs. In some cases, evidence of abruption may be found on ultrasonographic examination of asymptomatic patients. Finally, abruption may present as idiopathic preterm labor. A variety of fetal heart rate patterns have been described in association with abruption. There may be recurrent late or variable decelerations, reduced variability, bradycardia, or a sinusoidal fetal heart rate pattern. More infrequently, in cases of concealed abruption associated with fetal death, the first clinical sign may be of evidence of abnormal bleeding, the result of disseminated intravascular coagulopathy. In addition, there may be maternal hypovolemic shock. Labor typically proceeds fairly rapidly in cases of abruption. Placental abruption may be associated with acute tubular necrosis and acute cortical necrosis, leading to oliguria and renal failure.
Diagnosis
The diagnosis of placental abruption is made primarily on clinical presentation. Symptoms may vary, depending on how much of the placenta has separated and the age of
gestation it occurs. The classic presentation of abruption is the presence of painful cramps or contractions with dark red or bright red vaginal bleeding after the 20th week of pregnancy. Frequency of the clinical findings in women with placental abruption are the following: vaginal bleeding (76%), fetal non-reassuring testing (60%), uterine-abdominal tenderness/back pain (66%), uterine contractions >5 / 10 minutes (17%), uterine hypertonus (17%). About 10 % of abruption present with only concealed bleeding. Occasionally the presenting sign is fetal death. Severity of abruption often depends on how quickly the woman is seen following symptom onset. With delay, the likelihood of extensive separation causing fetal death is increased remarkably. Maintaining a high index of suspicion even in the absence of the “classic” signs of shock is warranted. Do not perform a digitalofexamination on aBefore pregnant patientexamination with vaginalcan bleeding without first ascertaining the location the placenta. a pelvic be performed safely, an ultrasonographic examination should be performed to exclude placenta previa. Ultrasound is primarily useful in ruling out other causes of third trimester bleeding. However, when the ultrasonogram seems to show an abruption, the likelihood that there is indeed an abruption is extremely high. Importantly, a negative ultrasonogram does not rule out an abruption. If clinical circumstances of ultrasound findings are confusing, magnetic resonance imaging (MRI) may help better define the location of the placenta and the presence pf abrutpion. Ultrasonography may also predict prognosis in abruption; Nyberg and colleagues in a retrospective review of 69 cases of abruption, found that fetal mortality correlated with the ultrasonographically estimated percentage of abruption and with the location, with the worst prognosis occurring in retroplacental abruptions. The differential diagnosis includes all causes of abdominal pain and bleeding. These include placenta previa, appendicitis, urinary tract infections, preterm labor, fibroid degeneration, ovarian pathology, and muscular pain. The Kleihauer-Betke test has limited usefulness in the diagnosis of abruption. A negative test shouldHowever, not be used to rule out abruption, does a positive test necessarily confirm abruption. a Kleihauer-Betke test allowsnor quantification of feto-maternal transfusion to guide dosing of Rh-immune globulin in Rh-negative women.
Classification
Class 1 – mildest type, 48% 1. No vaginal bleeding to mild bleeding 2. Slightly tender uterus 3. Normal maternal BP and HR 4. No coagulopathy 5. No fetal distress Class 2 – moderate, 27% 1. No vaginal bleeding to mild bleeding 2. Maternal Moderate tachycardia to severe uterine tenderness changes with possible 3. with orthostatic in BPtetanic and HRcontractions 4. Fetal distress 5. Low fibrinogen levels present
Class 3 – severe, 24% 1. No vaginal bleeding to heavy bleeding 2. Very painful tetanic uterus 3. Maternal shock 4. Coagulopathy 5. Fetal death
Management
The goals in the management of abruption are to assess, control and restore the amount of blood lost and to deliver a viable infant to prevent coagulation disorders. History, physical examination, laboratory and ultrasonographic studies guide management. Admission is required if abruptio placenta is considered. The following should be performed once it is diagnosed: 1. Obtain intravenous access using 2 large-bore IV lines. 2. Institute crystalloid resuscitation. 3. Begin external fetal monitoring for both fetal heart rate and contractions. 4. Type and cross-match blood. 5. Foley catheter should be placed and the hourly urine output should be monitored closely. 6. Begin blood transfusion if patient is hemodynamically unstable after fluid resuscitation. 7. Correct coagulopathy. 8. Administer Rh immune globulin is patient is Rh-negative. The management of placental depends on the gestational age,it and the degree of maternal and fetal abruption compromise. Because the presentation, presentation isthe widely variable, is important to individualize management on a case-by-case basis. More aggressive management, desirable in cases of severe abruption, may not be appropriate in milder cases of abruption. Prompt delivery is indicated if the pregnancy is at or near term. The main question is whether vaginal delivery can be achieved without fetal or maternal death or severe morbidity. In cases in which there is evidence of fetal compromise and delivery is not imminent, cesarean delivery should be performed promptly, because total placental detachment could occur without warning. When both maternal and fetal status are reassuring, conservative management, with the goal of vaginal delivery, is reasonable. Labor, if established, should be allowed to progress, otherwise induction of labor should be considered. Both mother and fetus should be monitored closely during labor. Should the fetal heart rate tracing become non-reassuring, with bradycardia, loss of variability, or persistent late decelerations, prompt cesarean delivery is indicated. Similarly, should maternal compromise occur, the fetus should be delivered promptly. However, if <34 weeks, expectant management for mild (grade 1) abruption may allow time for glucocorticoid administration. or associated fetal compromise delivery. in A decision to delivery interval of
conservatively. Preterm birth is the leading cause of perinatal death in women with abruption, and to optimize perinatal outcomes, it is desirable, if possible, to prolong gestation. However, it cannot be overemphasized that these patients require extremely close monitoring, because there is a significant risk of fetal death. In cases where the gestational age is between 24 and 34 weeks, steroids should be administered to promote fetal lung maturation. Patients should be delivered in a center with adequate neonatal facilities and the parents should be counseled by a neonatologist regarding potential treatments and out- comes for the neonate. Prolonged hospitalization and monitoring may be necessary. It may be possible to discharge these patients to outpatient management if the fetal status is reassuring once they have remained stable for several days. The mode of delivery is dependent primarily on the condition of the mother and the fetus: 1. In mostdelivery cases, for mild abruption (grade I), no evidence of maternal or fetal compromise, vaginal is indicated. 2. Moderate abruption (grade 2, evidence of fetal non-reassuring testing, - rapid delivery typically by cesarean is indicated. 3. Severe abruption (grade 3), fetal demise, often with DIC – vaginal delivery is indicated if patient is stable. In cases of severe abruption with fetal death, regardless of gestational age, as long as the mother is stable, it is reasonable, in the absence of other con- traindications, to allow the patient to have a vaginal delivery. Typically, the uterus is contracting vigorously, and labor rapidly progresses. Amniotomy is frequently sufficient to speed up delivery. Amniotomy is not proven to decrease bleeding from spiral arteries and reduce the entry of thromboplastin into the maternal circulation. If the fetus is reasonably mature, rupture of the membranes may hasten delivery. If the fetus is immature, the intact sac may facilitate cervical dilatation. Oxytocin is given in standard doses to effect vaginal delivery if there has been no previous uterine surgery and there arepredispose no rhythmic superimposed contractions noted. There is the no evidence that oxytocin might to DIC by enhancing entry of thromboplastin into maternal circulation. There is a significant risk of coagulopathy and hypovolemic shock. Intravenous access should be established and blood and coagulation factors should be replaced aggressively. Meticulous attention should be paid the amount of blood loss; clinicians frequently underestimate this. It is prudent to involve an anesthesiologist in the patient’s care early. When labor does not progress rapidly, and in cases in which there is feto-pelvic disproportion, fetal malpresentation, or a prior classical cesarean delivery, cesarean delivery may be necessary to avoid worsening of the coagulopathy. Bleeding from surgical incisions in the presence of DIC may be difficult to control, and it is important to stabilize the patient and to correct any coagulation derangement during surgery. After delivery, the patient should be monitored closely, with particular attention paid to vital signs, amount of blood loss, and urine output. In addition, the uterus should be observed closely to ensure that it remains contracted and is not increasing in size, and blood loss should be monitored Blood closely. The be uterus may hypotonic, occasionally hysterectomy be necessary. should drawn for be complete bloodand count and coagulation studies atmay regular intervals until the patient is stable. Finally, some cases of abruption may be associated with severe preeclampsia, which may be masked because the patient may be normotensive due to
hypovolemia. Thus, there should be a high index of suspicion for severe preeclampsia in patients with abruption not resulting from an obvious cause such as trauma or cocaine use. In such cases, the patients may benefit from close volume status monitoring, early recognition of hypovolemia, and adequate blood replacement. The extensive extravasation of blood into the uterine musculature, a condition known as Couvelaire’s uterus, seldom interferes with myometrial contractions to cause atony. It is not an indication for hysterectomy
Tocolysis
It is generally taught that tocolytics, especially sympathomimetics such as terbutaline, are contraindicated in the presence of vaginal bleeding, because side effects such as tachycardia could mask the clinical signs of blood loss. However, a few retrospective cohort and case– control studies have evaluated the use of tocolytics (including sympathomimetics) in the presence of bleeding in the second half of pregnancy, including patients with suspected stable placental abruption before 35 weeks gestation. Based on these reports tocolytics may be used in caution in stable women remote from term who Most cases of placental abruption cannot be predicted or prevented. However, in some cases, maternal and infant outcomes can be optimized through attention to the risks and benefits of conservative management, ongoing evaluation of fetal and maternal well-being, and through expeditious delivery where appropriate. Algorithm for the management of placental abruption in term or near term (A) and preterm births (B). In all cases, complete blood count and coagulation indices should be checked; blood or blood volume should be replaced; coagulopathy should be corrected; and intake, output, and 4
renal function should be monitored.
References
1. 2. 3. 4. 5. 6. 7. 8.
Obstetric evidence based guidelines by Vincenzo B erghella, 2007; p 193-200. Cunningham L, et. al. Williams Obstetrics, 23 rd edition, 2010; p 761-769. Neilson JP . Interven tions for treating p lacental abruption. Cochrane Database Syst Rev 2009. Oyelese Y, Ananth CV. P lacental abruption. Obstet Gynecol 2006;108:1005-1016. Bernischke K, Kaufmann P. Pathology of the human placenta. 4th ed. N ew York (NY): Springer; 2000. Saller DN Jr, Nagey DA, Pupkin MJ, Crenshaw MC Jr. Tocolysis in the management of third trimester bleeding. J Perinatol 1990;10:125–8. Towers CV, Pircon RA, Heppard M. Is tocolysis safe in the management of third-trimester blee ding? Am J Obstet Gynecol 1999;180:1572–8. Ananth CV, Berkowitz GS, Savitz DA, Lapinski RH. Placental abruption and adverse perinatal outcomes .
JAMA 1999;282: 1646–51. Nyberg DA, Cyr DR, Mack LA, Wilson DA, Shuman WP. Sonographic spectrum of placental abruption. AJR Am J Roentgenol 1987;148:161–4. 10. Glantz C, Purnell L. Clinical utility of sonography in the diagnosis and treatment of placental abruption. J Ultrasound Med 2002;21:837–40. 9.
APPENDIX
LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION
LEVEL I II-1 II-2 II-3 III
GRADE A B C D E GPP
DEFINITION Evidence obtained from at least one properly randomized controlled trial Evidence obtained from well-designed controlled trials without randomization Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group Evidence obtained from multiple time series with or without the intervention. Opinions of respected authorities, based on clinical experience; descriptive studies and case reports or reports of expert committees.
DEFINITION There is good evidence to support the recommendation of the practice in the management of hypertensive complications of pregnancy. There is fair evidence to support the recommendation of the practice in the management of hypertensive complications of pregnancy. There is insufficient evidence to recommend for or against the inclusion of the practice in the management of hypertensive complications of pregnancy. There is fair evidence to support the recommendation that the practice be excluded in the management of hypertensive complications of pregnancy. There is good evidence to support the recommendation that the practice be excluded in the management of hypertensive complications of pregnancy. A good practice point (GPP) is a recommendation for best practice based on the experience of the Task Force.
