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CLINICAL PRACTICE GUIDELINES
on
HYPERTENSIVE COMPLICATIONS
OF PREGNANCY
!
April 2010
April 2010
REGTA L. PITHAY, MD
President
Philippine Obstetrical and Gynecological Society (Foundation), Inc. (POGS), 2010
In line with the thrust of this years 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!
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 originating from the day-to-day academic
interactions from the faculty of the different Residency-Accredited Hospitals in
Obstetrics and Gynecology in the country.
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.
OFFICERS
Regta L. Pichay, MD
President
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
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 EDITOR
Ana Victoria V. Dy Echo, MD
Ernesto S. Uichanco, MD
Chair
Members
Walfrido W. Sumpaico, MD Sol M. Pangan, MD Pilar Lagman-Dy, MD
Virgilio B. Castro, MD Milagros T. Jocson, MD Mario A. Bernardino, MD
Ann Marie C. Trinidad, MD Ramon M. Gonzales, MD Ma. Luisa S. Acu, MD
Raul M Quillamor, MD Ronaldo R. Santos, MD Ma. Antonia E. Habana,
MDCarmencita B. Tiongco, MD Diosdado M. Mariano, MD Ma. Cristina P. Crisologo, MD
Joseph U. Olivar, MD Sherri Ann L. Suplido, MD
Regional Directors
Betha Fe M. Castillo, MD (Region 1) Noel C. de Leon, MD (Region 2)
Concepcion P. Argonza, MD (Region 3) Ernesto S. Naval, MD (Region 4)
Diosdado V. Mariano, MD (Region 4A NCR) Cecilia Valdes-Neptuno, MD (Region 5)
Evelyn R. Lacson, MD (Region 6) Belinda N. Paares, MD (Region 7)
Fe G. Merin, MD (Region 8) Cynthia A. Dionio, MD (Region 9)
Jana Joy R. Tusalem, MD (Region 10) Ameila A. Vega, MD (Region 11)
DISCLAIMER, RELEASE AND WAIVER OF RESPONSIBILITY
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4. Prevention of Pre-eclampsia .
Walfrido W. Sumpaico, M.D. and Milagros T. Jocson, 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.
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Epidemiology of Hypertension in Pregnancy
Ramon M. Gonzalez MD, Ronaldo Santos MD and, Carelle Roux-Ong MD
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Preeclampsia is a life threatening complication of pregnancy characterized by
hypertension and proteinuria that contribute greatly to maternal morbidity and
mortality. This is primarily due to an abnormal implantation of trophoblasts in the
placenta as well as poor 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.
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Primiparity
!
The only well accepted risk factor for preeclampsia is primiparity. Pregnancy-
induced hypertensive disorders, especially preeclampsia have been documented to
occur primarily in first pregnancies. The concept, therefore of primiparity is the
epidemiological cornerstone of this disease.1 In a population based study in Norway
covering all births since 1967 (about 1.5 million women), the risk of preeclampsia in
first pregnancies was 3%. It decreased to 1.7% in the second pregnancy.4
Immunologic Factors
The relationship between maternal weight and the risk of preeclampsia is progressive.
It increases from 4.3% for women with a body mass index (BMI) less than 19.8 kg/m2
to 13.3% in those with a BMI greater than 35 kg/m2. 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
normal BMI which was 11.2%.8
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,
Sibai and co-workers demonstrated a 20% occurrence of preeclampsia.7 More so, the
frequency of preeclampsia rose with increasing severity of diabetes.
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
rate was 14.1% whereas the recurrence rate for twins was only 6.8%.5
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
woman, her risk of developing preeclampsia is 1.8 (95% CI 1.2-2.6).4 Paternal genes
in the fetus may therefore contribute substantially to a womans 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
months the risk is 40% compared to 3-5% over 12 months.1 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
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%
for 33-36 weeks and 12.9% for >37 weeks age of gestation.8 A previous preterm
delivery and small for gestational age newborn increases the risk of preeclampsia in
subsequent pregnancies.9
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
References
!
!
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.
Definition of Terms
1. Hypertension
2. Proteinuria
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.
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
postpartum1 (ACOG, Level III).
5. Pre-eclampsia
7. Mild pre-eclampsia
8. Eclampsia
9. Chronic Hypertension
2. The patient should be seated (or supine) or in the left lateral recumbent position
with arms bared, supported, and at heart level7 (RCOG, Level II-1, Grade A)2.
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.
4. Systolic pressure should be recorded at the appearance of the 1st clear tapping
sound (Korokoff phase 1). Diastolic blood pressure should be recorded at the
disappearance of these sounds (Korotkoff phase V)2 (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 patients blood pressure. If the first 2 regarded differ by 5 mmHg
or more, a 3rd 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).
A summary and comparison of the above classifications and definitions are presented
in Tables 2.2 and 2.3.
1. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in
Pregnancy. Am J Obstet Gynecol 2000;183(1):S1-S22.
2. Diagnosis, evaluation and management of the hypertensive disorders of pregnancy. National Guideline
Clearinghouse. http://www.guideline.gov/about/inclusion.aspx.
3. American College of Obstetricians and Gynecologists. ACOG Committee 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.
4. 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.
5. Barton JR, Sibai BM. Diagnosis and management of hemolysis, elevated liver enzymes, and low platelets
syndrome. Clin Perinatol 2004;31(4):807-833.
6. Magann EF, Martin JN Jr. Twelve steps to optimal management of HELLP syndrome. Clin Obstet Gynecol
1999;42(3):532-550.
7. Royal College of Obstetricians and Gynaecologists. The Management of Severe Pre-eclampsia/ Eclampsia:
Evidence-based Clinical Guideline Number 10 A, 2006, March.
8. American College of Obstetricians 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.
9. 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
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 Chesleys 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
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 review looking at MAP and BP measurements in predicting preeclampsia,
second trimester MAP 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)
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
pressure in women and fluctuations between activity and the rest during different
trimesters. This allows diagnosis before blood pressure becomes elevated.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
When evaluating new screening strategies, not only sensitivity, specificity and predictive
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%. In contrast, women without a notch constitute a very low risk group with < 1%
having delivery before 34 weeks.25 When used to predict hypertension 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 are derived principally from the liver and endothelial cells, and its
release into plasma is a marker of vascular disruption and endothelial cell 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
been said to denote poor prognosis, however, a systematic review concluded that even
increasing levels of protenuria are not predictive of poor maternal nor fetal outcomes.13
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 81-
98% 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
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 between insulin resistance and hypertension arising de novo in pregnancy is
unclear. In a retrospective case-control study, women who developed hypertension in
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
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)
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. Brown MA, Mackenzie C, Dunsmuir W, Roberts L, Ikin K, Matthews J, Mangos G, Davis G. Can we
predict recurrence of pre-eclampsia or gestational hypertension? BJOG 2007;114(8):984-93.
2. Grill S, Rusterholz C, Zanetti-Dllenbach R, Tercanli S, Holzgreve W, Hahn S, Lapaire O. Potential
markers of preeclampsia a review. Reprod Biol Endocrinol 2009;7:70.
3. 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.
4. Vainio M, Kujansuu E, Koivisto AM, Menp J. Bilateral notching of uterine arteries at 12--14 weeks of
gestation for prediction of hypertensive disorders of pregnancy. Acta obstetr et gynecol Scan 2005;84:11,
1062-7.
5. 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.
6. Odegrd RA, Vatten LJ, Nilsen ST, Salvesen KA, Austgulen R. Risk factors and clinical manifestations of
pre-eclampsia. BJOG 2000 Nov;107(11):1410-6.
7. Llurba E, Carreras E, Gratacs E, Juan M, Astor J, Vives A, Hermosilla E, Calero I, Milln P, Garca-
Valdecasas 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.
8. 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.
9. 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.
10. 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.
11. 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 Obstet Gynecol Scand 2009;88(7):758-65.
12. Aydin T, Varol FG, Sayin NC. Third trimester maternal plasma total fibronectin levels in pregnancy-
induced hypertension: results of a tertiary center. Clin Appl Thromb Hemost. 2006;12(1):33-9.
13. 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.
14. Papanna R, Mann LK, Kouides RW, Glantz JC. Protein/creatinine ratio in preeclampsia: a systematic
review. Obstet Gynecol. 2008;112(1):135-44.
15. 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.
16. Solomon CG, Graves SW, Greene MF and Seely EW. Glucose intolerance as a predictor of hypertension in
pregnancy. Hypertension. 1994;23:717-721
17. ACOG Technical Bulletin, Jan 1996
18. Page and Christianson, 1976
19. Chesley and Sibai, 1974
20. Chesley and Sibai, 1988
21. Chesley and Sibai, 1987
22. Sumpaico and Santillan, 1982
23. Kyle and Clark, 1993
24. Vollebregt, 2010
25. Pangan, 1997
26. 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.
The meta-analysis by Hofmeyr, et. al.,1 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 pre-
eclampsia 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
appear to be safer.2
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,
reduced salt intake8, marine oil or other prostaglandin precursor9 and garlic10 in the
prevention of pre-eclampsia. (Level I-II, Grade A-B).
References
1. Hofmeyr GJ, Atallah AN, Duley L. Calcium supplementation during pregnancy for preventing
hypertensive disorders and related problems. Cochrane Database Syst Rev 2006, Issue 3.
2. Duley I, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its
complications. Cochrane Database Syst Rev 2007, Issue 2.
3. Rumbold A, Duley I, Crowther CA, Haslam RR. Antioxidants for preventing pre-eclampsia. Cochrane
Database Syst Rev 2008, Issue 1.
4. Meher S, Duley I. Nitric oxide for preventing pre-eclampsia and its complications. Cochrane Database Syst
Rev 2007, Issue 2.
5. 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.
6. Meher S, Duley L. Exercise or other physical activity for preventing pre-eclampsia and its complications.
Cochrane Database Syst Reviews 2006, Issue 2.
7. 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 complications. Cochrane Database Syst Rev
2006, Issue 3.
!
Gestational Hypertension and Mild Pre-eclampsia
Pilar Lagman-Dy, M.D. and Carmencita B. Tongco, M.D.
Gestational Hypertension
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.
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. Systolic pressure ! 140 mm Hg
4. Proteinuria < 1,000 mg 24 hr or < 2+ on dipstick
5. Platelet count > 120,000/mm
6. Normal fetal growth and testing
7. No indications for delivery
Summary of Evidence
2. Timing of Delivery
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 anti-
hypertension 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
1. ACOG Practice Bulletin No. 33. American College of Obstetricians and Gynecologists. Diagnosis and
management of preeclampsia and eclampsia. Obstet Gynecol 2002;99:159-167 (Level III)
<http://www.acog.com/publications/educational_bulletins/pb033.htm>
2. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in
Pregnancy. Am J Obstet 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
3. Gabbe SG, Neibyl JR, Simpson JL (Eds). Obstetrics: Normal and Problem Pregnancies. 4th Ed.
Hypertension, Chapter 28. Churchill Livingstone, New York, 2002. 945-1004. (Level III)
4. Cunningham GF, et. al. (Eds) Williams Obstetrics, 21st Edition. Hypertensive Disorders in Pregnancy,
Section 7. McGraw-Hill, 2001. 24:567-618. (Level III)
5. 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.ama-
assn.org/cgi/content/full/289/19/2560
!"## Hofmeyr GJ, Atallah AN, Duley L. Calcium supplementation during pregnancy for preventing
hypertensive disorders and related problems. Cochraine Library Syst Revs.
http://www.ihs.gov/generalweb/webapps/sitelink/ site.asp?link=http://www.cochranelibrary.com/enter/#
7. Frangieh AY, Sibai BM. Outpatient management of gestational hypertension and mild preeclampsia.
Contemporary OB-Gyn 1996:67.
8. 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.
9. 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.
10. Barton JR, Stanzino GJ, Sibai BM. Monitored outpatient management of mild gestational hypertension
remote from term. Am J Obstet Gynecol 1994;170:765.
11. Matthews DD, Patel IR, Sengupta SM. Outpatient management of toxemia. Br J Obstet Gynecol
1971;78:610.
12. Feeney JE. Hypertension in pregnancy managed by community midwives. BMJ 1984;288:1046.
13. 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 Obstet Gynecol 1992;167:879.
Severe Pre-eclampsia
Mario A. Bernardino, M.D. and Joseph U. Olivar, M.D.
Background
Incidence
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
mothers 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 non-
preeclamptic 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
itself, an indication for delivery.5 The second is severe preeclampsia on the basis of IUGR alone
with good fetal testing. Although not candidates for immediate delivery, such patients should be
treated as in-patients5 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 of pregnancy (mean 15.4 vs 2.6 days), less time in neonatal
intensive care unit (NICU) (20.2 vs 36.6 days), and a reduce incidence of 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.
!"#$%&%'&()*'+&),"&"-($.-+/&01$%-&
!,/&'2&%3-&2'(('4$,5&6+-0-,%7&
Eclampsia
Pulmonary edema
Magnesium sulfate
Acute renal failure
and delivery
Disseminated intravascular coagulation Yes
Suspected abruptio placenta
Non-reassuring fetal status
Labor or rupture of membranes >34 weeks
gestation
No
HELLP syndrome (Hemolysis, Elevated Liver
enzymes, and Low Platelets) Steroids
Persistent symptoms Yes
No
Steroids Steroids
Terminate Antihypertensives if needed Delivery after 48
pregnancy Daily evaluation of maternal- hours
fetal condition
Delivery if: with indications
(see Table 2)
Delivery at 32-34 weeks
DD
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Table 2. Indications for Delivery During Expectant
45
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'
'
Perinatal Complications
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
management, maternal complications in reported studies include: HELLP syndrome (4.1-27.1%),
pulmonary edema (0-8.5%), eclampsia and acute renal failure (<1%).8,16,20
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
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
NICU.4,23,24,25,28 On the other hand, attempts to prolong pregnancy may result in fetal death and
may expose the mother to severe morbidity.14,16,24,25,27 Overall, in these studies, the 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.
The clinical course of women with HELLP syndrome is characterized by progressive and
sudden deterioration in the maternal condition.29 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
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
Automated methods can systematically underestimate particularly the systolic
blood pressure. 38 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
While it has to be acknowledged that there is poor predictive value from urine
dipstick testing,40 approximate equivalence is +1 = 0.3 g/L, +2 = 1g/L and +3 = 3g/L.
False negative as well as false positive results are possible with the use 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
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
may be an associated coagulation abnormality.46 Clotting studies are not required if the
platelet count is over 100 x 106/L.
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
syndrome or sepsis.34
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)
MgSO4 is the therapy of choice to control seizures. 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 MgSO4,
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
appropriate in these circumstances.34
Patients with 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.
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
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)
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 meta-
analysis 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
effects.54
F6. Nifedipine (10mg or 30 mg XR) should be given orally not sublingually and should
be used with caution if concomitantly used with magnesium sulfate. (Level III, Grade
C)
Calcium antagonists given sublingually are now not recommended for the
treatment of hypertension in nonpregnant patients because of 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 Chronic Hypertension 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.
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)
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)
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 rises again at around 24 hours postpartum. A
reduction in anti-hypertensive therapy should 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. ACOG. Diagnosis and Management of Preeclampsia and Eclampsia: ACOG Practice Bulletin No. 33.
Obstet Gynecol 2002; 99: 159-67.
2. Robson SC. Hypertension and Renal Disease in Pregnancy. In: Edmond DIC, ed. Dewhurets Texbook of
Obs and Gyn for Postgraduates. 6th ed.Oxford: Blackwell Science Ltd.1999:166-85.
3. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in
Pregnancy. Am J Obstet Gynecol 2000;183:S1-22.
4. Phillipine Obstetrical and Gynecological Society Committee on Nationwide Statistics 2005-2008.
5. Norwitz ER. Expectant management of severe preeclampsia remote from term: Hope for the best, but
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28. Withagen MIJ, Walenburg HCS, Steegers EAP, Hop WCJ, Visser W. Morbidity and development in
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29. Bombrys AE, et. al. Expectant management of severe preeclampsia at less than 27 weeks gestation:
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30. Sibai BM. Diagnosis, controversies and management of the syndrome of hemolysis, elevated liver
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31. Visser W, Wallenburg HCS. Temporising management of severe preeclampsia with and without HELLP
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32. van Pampus MG, Wolf H, Westenberg SM, der Post V, Bonsel GJ, Treffers PE. Maternal and perinatal
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33. van Runnard Heimel PJ, Huisjes AJM, Fraux A, Koopman C, Bots ML, Bruinse HW. A randomized
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34. Royal College of Obstetricians & Gynecologists. The management of Severe Preeclapmsia. Evidence
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38. Lewis G, editor. Why Mothers Die 2000-2002. The Sixth Report of the Confidential Inquiries into
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39. Golara M, et al; Inflationary oscillometry provides accurate measurement of blood pressure in preeclampsia
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40. Waugh J, et. al. Optimal bedside urinalysis for the detection of proteinuria in hypertensive proteinuria: a
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41. Crithchley H, et. al. Preeclampsia. London: RCOG Press; 2003.
42. Magpie Triad Collaborative Group: Do women with preeclampsia, and their babies, benefit from
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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.
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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
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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
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50. RCOG. The Use of Electronic Fetal Monitoring. Evidence Based Clinical Guideline No. 8. London: RCOG
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51. Galan HL, et. al. Intrauterine Growth Restriction (IUGR): biometric and doppler assessment. Prenat Diagn
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52. Alfirevic Z, et. al. Doppler ultrasonography in high risk pregnancies: systematic review with meta-analysis.
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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. methyldopa in the treatment of pregnancy induced hypertension. Int
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59. Brown MA, et. al. Efficacy and safety of nifedipine tablets for the acute treatment of severe hypertension in
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blockade. Br J Obstet Gynaecol 1994;101:262-263.
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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
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64. Ascarelli MH, et. al. Postpartum preeclampsia management with Furosemide: A randomized clinical trial.
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Syndrome matter? Am J Obstet Gynecol 1999;180:221-5.
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Pregnancy 2000;19:221-31.
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treatment, and delivery Indications. Am J Obstet Gynecol 2007;514:E1-E9.
Eclampsia
Raul M. Quillamor, MD and Diosdado V. Mariano, MD
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. Urine output of at least 30 ml for the past hour or 100 ml for the past 4 hours
2. Presence of patellar reflex
3. Respiratory rate of not less than 12/min.
4. 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 the level of consciousness, with the aim of overcoming restlessness and keeping
the patient sedated but rousable. During the next 24 hours, an infusion of 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 patients 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 hypertension should be started on IV therapy. The drugs that may be
used are hydralazine (drug of choice); clonidine and nifedipine (Level II-2, Grade B); 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
References
1. Creasy RK, Resnik R. Creasy & Resniks Maternal-Fetal Medicine Principles and Practice, Sixth Edition.
2009, Saunders Elsevier.
2. Cunningham FG, Leveno K, et. al. Williams Obstetrics 23rd Edition 2010, The McGraw-Hill Companies,
Inc.
3. Duley L, Henderson-Smart D. Magnesium Sulfate versus diazepam for eclampsia. Cochrane Database Syst
Rev (4):CD000127, 2003.
4. Greer I, Walker J, et. al. Second line therapy with nifedipine in severe pregnancy induced hypertension.
Clin Exp Hypertens B8:277,1989.
5. RCOG Guideline Number 10, March 2006: The Management of Severe Preeclampsia/Eclampsia.
6. Sibai BM. Diagnosis, Prevention, and Management of Eclampsia. Obstetr Gynecol 2005; 105:402-10.
7. ACOG 2002.
8. National High Blood Pressure Education Program 2000
!
!
Chronic Hypertension
Virgilio B. Castro, MD and Ann Marie C. Trinidad, MD
Definition
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.
3. The beta blocker atenolol may be associated with growth restriction and is not recommended
for use in pregnancy. (Grade B)
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 restriction or superimposed preeclampsia, Antenatal fetal surveillance should
include umbilial artery Doppler velocimetry. (Grade A)
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 placenta-
derived 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
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
use in HELLP syndrome decreases major maternal and perinatal morbidity.24
The results of two recent studies, Fonseca25 and Katz26, both randomized, double-blind,
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)
Most of the patients could be discharged after 4-8 days hospitalization, if the platelet
count is greater than 100,000/mm3 and no evidence of end-organ damage.25
References
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consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982;142:159-67.
2. 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 Obstet Gynecol 1986;155:501-9.
3. Martin JN Jr, Rinehart K, May WL, Magann EF, Terrone DA, Blake PG. The spectrum of severe
preeclampsia: comparative analysis by HELLP sybdrome classification. Am J Obstet Gynecol
1999;180:1373-84.
4. 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.
5. 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.
6. 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 Obstet Gynecol 1991;164:1500-13.
7. 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.
8. Makkonen N, Harju M, Kirkinen P. Postpartum recovery after severe preeclampsia and HELLP
sybdrome. J Perinat Med 1996;24:641-9.
9. Faridi A, Rath W. Differential HELLP syndrome diagnosis. Z Gerburstschilfe 1996;200:88-95.
10. Isler CM, Rinehart BK, Terrone DA, Martin RW, Magann EF, Martin JN Jr. Maternal mortality
associated with HELLP syndrome. Am J Obstet Gynecol 1998;181:924-8.
11. 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.
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nothing? Am J Obstet Gynecol 1990;162:311-6.
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22. Vigil-DeGracia P, Garcia-Caceres E. Dexamethasone in the postpartum treatment of HELLP syndrome.
Int J Gynaecol Obstet 1997;59:217-21.
23. 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.
24. Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in pregnancy. (Cochrane Review) In: The
Cochrane Library, Issue 4, 2004:CD002076 Oxford: Updates Software.
25. 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.
26. 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, placebo-
controlled, randomized clinical trial. Am J Obstet Gynecol 2008;198:283.e1-283.e8.
27. Obrien 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 Obstet Gynecol 2002;186:457-9.
28. 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
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
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
Classification
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 abruption depends on the presentation, the gestational age,
and the degree of maternal and fetal compromise. Because the presentation is widely variable, it
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. Maternal or fetal compromise necessitates delivery. A
decision to delivery interval of </= 20 minutes is associated with a substantial reduction in
neonatal morbidity and mortality in cases of fetal bradycardia. When there is partial placental
abruption and the maternal and fetal status are reassuring, the patient may be managed
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 most cases, for mild abruption (grade I), no evidence of maternal or fetal compromise,
vaginal delivery 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 are no rhythmic superimposed contractions noted. There is no
evidence that oxytocin might predispose to DIC by enhancing entry of thromboplastin into the
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 patients 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 closely. The uterus may be hypotonic, and occasionally hysterectomy may be
necessary. Blood should be drawn for complete blood count and coagulation studies at 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
Couvelaires uterus, seldom interferes with myometrial contractions to cause atony. It is not an
indication for hysterectomy
Tocolysis
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
renal function should be monitored.4
References
LEVEL DEFINITION
I Evidence obtained from at least one properly randomized controlled trial
Evidence obtained from well-designed controlled trials without
II-1
randomization
Evidence obtained from well-designed cohort or case-control analytic
II-2
studies, preferably from more than one center or research group
Evidence obtained from multiple time series with or without the
II-3
intervention.
Opinions of respected authorities, based on clinical experience; descriptive
III
studies and case reports or reports of expert committees.
!
GRADE DEFINITION
There is good evidence to support the recommendation of the practice in
A
the management of hypertensive complications of pregnancy.
There is fair evidence to support the recommendation of the practice in the
B
management of hypertensive complications of pregnancy.
There is insufficient evidence to recommend for or against the inclusion of
C the practice in the management of hypertensive complications of
pregnancy.
There is fair evidence to support the recommendation that the practice be
D
excluded in the management of hypertensive complications of pregnancy.
There is good evidence to support the recommendation that the practice be
E
excluded in the management of hypertensive complications of pregnancy.
A good practice point (GPP) is a recommendation for best practice based
GPP
on the experience of the Task Force.
!