HYPERTENSION IN PREGNANCY
CPG
MAIN TOPICS
1. EPIDEMIOLOGY OF HPN IN PREGNANCY
2. CLASSIFICATION OF HPN IN PREGNANCY
3. PREDICTIVE TEST FOR PREECLAMPSIA
4. PREVENTION OF PREECLAMPSIA
5. GESTATIONAL HPN AND PREECLAMPSIA
6. PREECLAMPSIA WITH SEVERE FEATURES
7. ECLAMPSIA
8. CHRONIC HYPERTENSION
9. COMPLICATIONS OF PREGNANCY INDUCED
HPN (HELLP, ABRUPTIO PLACENTA)
I. EPIDEMIOLOGY OF HPN IN PREGNANCY
Hypertensive disorders in pregnancy cover a
spectrum of conditions:
1. Gestational Hypertension
2. Preeclampsia
3. Eclampsia
4. Chronic Hypertension
5. Preeclampsia superimposed on chronic HPN
Preeclampsia:
Preeclampsia complicates about 3% of
pregnancies, and all hypertensive disorders
affect about 5-10% of pregnancies.
- etiology is multifactorial
Material Personal Risk Factors
1. Primiparity - based study in Norway covering
all births since 1967 (about 1.5 million women),
the risk of preeclampsia in first pregnancies was
3%, decreased to 1.7% in the second pregnancy.
Primiparity is associated with approximately 2.4-
fold elevated risk of preeclampsia.
2. Primipaternity - 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. Moreover, if
a woman becomes pregnant by a man who has
fathered a preeclamptic pregnancy in a different
woman, her risk of developing is 1.8%.
3. History of Preeclampsia - The risk of
recurrence is about 14%. The recurrence risk
was reported even higher in a study based on
hospital records, with a 20-fold increase in the
preeclampsia risk compared with parous women
with no previous preeclampsia. Moreover,
severe preeclamptic women in an initial
pregnancy have a recurrence rate of as high as
50%.
4. Obesity - The relationship between maternal
weight and the risk of preeclampsia is
progressive. It increases from 4.3% to 13.3% to
BMI >35kg/m2
5. Family History of Preeclampsia - Chesley et.
al. found that the rate of preeclampsia was
higher in sisters (37%), daughters (26%), and
granddaughters (16%) than it was in daughters-
in-law (6%).
6. Ethnicity - Black women have a risk of
preeclampsia that is twice as high as that of
white women. They are also more likely to have
hypertension.
7. Maternal Age – women aged >40 had
approaching twice the risk of developing
preeclampsia, whether they were primiparous
or multiparous (relative risk IRRI I .68, 95% Cl
1.23-2.29, and RR 1.96, Cl 1.34-2.87,
respectively).
8. Smoking - Smoking in pregnancy has
repeatedly been associated with a reduced risk
of mild and severe preeclampsia in primiparous
and multiparous women, singleton and
multifetal pregnancies. Typically, the RR is about
0.5-0.8 compared with nonsmokers.
9. Other unresolved risk factors include:
• Previous miscarriage and induced abortions
• Environmental risk factors
 Interpregnancy intervals 2 years or 10 years
Maternal Medical Risk Factors
1. Underlying medical conditions:
a. Diabetes mellitus - Among 462 women with
pregestational diabetes mellitus, Sibai, et al.
demonstrated a 20% occurrence of
preeclampsia.
b. Antiphospholipid antibody syndrome - Two
meta-analyses and a number of case-control
and cohort studies have found associations
between preeclampsia and lupus anticoagulant,
anticardiolipin, and/or anti-P2 glycoprotein. The
presence of antiphospholipid antibodies
significantly increases the risk of developing
preeclampsia
c. Systemic lupus erythematosus - Maternal
complications included lupus flare (25.6%),
hypertension (16.3%), nephritis (16.1%),
preeclampsia (7.6%) and eclampsia.
d. Renal disease - Davies, et al. found that the
prevalence of renal disease was higher in
women who developed preeclampsia compared
with those that did not (5.3% vs 1.8%)
2. Maternal Infection - The risk of preeclampsia
was increased in patients with urinary tract
infection (OR 1.57, 95% CI 1.45-1.70) and
periodontal disease (OR 1.76, 95% CI 1.43-2.18).
Placental/Fetal Risk Factors
1. Multiple Pregnancies - In women with twin
gestations compared with those with singletons,
the incidence o fgestational hypertension and
preeclampsia are both significantly increased,
13% in singletons and 5-6% in twins. When a
woman is pregnant with twins, her risk triples.
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2.Molar Pregnancy - associated with very early-
onset preeclampsia. Both have dysfunctional
placentas that are integral to each disease
process. More so, both molar pregnancy and
preeclampsia are caused by an excess of
circulating sFlt-1.
II. CLASSIFICATION OF HPN IN PREGNANCY
“This Task Force report changes the paradigm
that we use in diagnosing preeclampsia from
one that is dependent on new onset
hypertension and proteinuria. The problem is
that many patients with preeclampsia don't
have enough proteinuria to meet the former
criteria, so their diagnosis and treatment is
delayed." - This quote, perhaps, underlines the
reason for the changes recommended by the
most recent Task Force Report on Hypertension
in Pregnancy by the American College of
Obstetricians and Gynecologists (ACOG)
submitted last November 2013 and adopted by
many obstetrical bodies worldwide.
Four categories by ACOG Task Force:
I. Preeclampsia-eclampsia
2. Chronic hypertension (of whatever cause)
3. Chronic hypertension with superimposed
preeclampsia
4. Gestational hypertension
Identified issues that warrant attention:
1. The failure of health care workers to
appreciate the multi-systemic nature of
preeclampsia may in part be due to attempts at
rigid diagnosis
2. Preeclampsia has long been recognized as a
dynamic process and a diagnosis such as "mild
preeclampsia" (now being discouraged) applies
only at the moment the diagnosis is established
because the illness, by nature, is progressive.
Blood Pressure Criteria - systolic and diastolic
BP 140 and 90 mmHg, respectively, occurring
after 20 weeks of gestation. Korotkoff phase V is
used to define diastolic pressure.
Incremental changes in BP is no longer a
recommended criterion because women
showing a rise of 30 mmHg systolic or 15 mmHg
diastolic alone are not likely to experience any
worsening of pregnancy outcome. They may just
be observed more closely.
Proteinuria - having urinary protein spillage of
300 mg/24 hours, protein-to-creatinine ratio 0.3
or 1+ urinary protein dipstick reading. Because
of the variability of qualitative determination
(Dipstick test), it is discouraged for diagnostic
use unless other methods are not readily
available. If this must be used, I + is considered
the cut-off for the diagnosis of proteinuria.
1. Preeclampsia-Eclampsia
Elevation of BP characterizes preeclampsia and
eclampsia. Proteinuria remains an important
and objective marker and is taken as an
evidence of a systemic-wide endothelial leak. In
recognition of the systemic nature of
preeclampsia, the dependency of diagnosis on
proteinuria has been eliminated.
Preeclampsia- In its absence, preeclampsia is
diagnosed as hypertension in association with
other multi-organ involvement such as
thrombocytopenia, impaired liver function, new
development of renal insufficiency, pulmonary
edema, or new-onset cerebral or visual
disturbances
Preeclampsia with severe features:
a. Systolic or diastolic BP values >160 or 110
mmHg, respectively, occurring twice, 4 hours
apart at bed rest
b. Thrombocytopenia (platelet counts <100,000)
c. Impaired liver function defined as either
otherwise unexplained right upper quadrant
epigastric pain unresponsive to medications, or
hepatic transaminase levels 2x normal
d. Progressive renal insufficiency defined as
serum creatinine concentrations 1.1 mg/dL or a
doubling of the serum creatinine concentration
in the absence of other renal disease
e. Pulmonary edema
f. New-onset cerebral or visual disturbances
Eclampsia – this is the term used in women
diagnosed to have preeclampsia and have
convulsions that cannot be attributed to
another cause. The convulsions are generalized
and may occur before, during, or after labor.
Although generally occurring within 48 hours of
delivery, of postpartum eclampsia may initially
occur beyond this time frame
2. Chronic Hypertension
It is hypertension of any cause that predates
pregnancy. BP > 140/90 before pregnancy or
before 20 weeks gestation, or both.
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3. Superimposed Preeclampsia
It is chronic hypertension in association with
preeclampsia. Others define it as worsening
baseline hypertension accompanied by new-
onset proteinuria or other findings supportive of
preeclampsia.
4. Gestational Hypertension
It is new onset of threshold BP elevations after
20 weeks gestation in the absence of
proteinuria or the other systemic findings
alternatively used to support the diagnosis of
preeclampsia. It is hypertension in pregnancy
that does not show signs of developing
preeclampsia and the elevated BP resolves by
12 weeks postpartum. These women are then
reclassified by some as transient hypertension.
III. PREDICTORS OF PREECLAMPSIA
1. What is the significance of mean arterial
pressure (MAP) in detecting or predicting
preeclampsia ?
- MAP, a BP measurement that combines
systolic BP and diastolic BP is better than systolic
BP alone or diastolic BP alone in predicting
preeclampsia.
Lai, et al. explained that the mean multiple of
median MAP, systolic BP and diastolic BP were
significantly higher in intermediate
preeclampsia (preeclampsia requiring delivery
at 34-37 weeks) and late preeclampsia
(preeclampsia requiring delivery at or after 38
weeks) than in normal pregnancy.
2. What biochemical markers can be used to
predict preeclampsia?
- The biochemical predictors of preeclampsia
studied so far reflect our knowledge of the
pathophysiology of preeclampsia. Several
potential predictors describe the fetal and
placental endocrine functions and the maternal
endothelial dysfunction.
Kleinrouweler, et al. confirmed that the
concentration of placental growth
factor (PIGF) and vascular endothelial growth
factor (VEGF) were lower in women who
developed preeclampsia. The failure of
trophoblast invasion may contribute to the
alteration of the surface layer of the
syncytiotrophoblasts and result in leakage of
alpha fetoprotein (AFP) into the maternal
circulation resulting in an increased level
of these proteins in women with preeclampsia.
Summary of biomarkers and their accuracy
3. What is the role of uterine artery Doppler
studies in the prediction of preeclampsia?
- Abnormal placentation, as seen in
preeclampsia, is associated with inadequate
uteroplacental blood flow. Doppler
ultrasonography might be used to assess the
velocity of uterine blood flow and thereby
indirectly evaluate the trophoblastic invasion of
the spiral arteries.
Doppler indices used to evaluate the blood flow
and the most commonly used are:
a. Pulsatility Index (PI): peak systolic flow minus
end diastolic flow divided by mean flow
b. Resistance index (RI): peak systolic flow minus
end diastolic flow divided by peak systolic flow
c. Notching: presence of early diastolic notching
indicating decreased early diastolic flow
compared to later diastolic flow in the uterine
artery
Since preeclampsia is characterized by a
complex pathophysiology with heterogeneous
clinical and laboratory findings, it may not be
realistic to search for a single marker to predict
the disorder. A combination of two or more
independent markers, each representing
separate pathophysiological processes should
theoretically improve the possibility for
predicting preeclampsia with high accuracy.
4. What would be the best combined method for
the prediction of preeclampsia?
- A systematic review by Giguere, et. al. showed
that a combination of biochemical and
ultrasonographic markers might improve the
prediction of preeclampsia.16 In low risk
populations, several combinations, including
PPI3, PAPP-A, a disintegrin and
metalloproteinase (ADAM), Activin A or Inhibin
A measured in the or early 2nd trimester,
combined with uterine artery Doppler
investigation, showed a sensitivity of 60-80%
and a specificity of >80%. A combination of PPI 3
and uterine artery Doppler showed a sensitivity
of 90% and a specificity of 90% for severe
preeclampsia in a high risk population.
Another review where trimester predictors
were evaluated, concluded furthermore that the
combination of biomarkers and uterine artery
Doppler ultrasound predicted preeclampsia
better than a single predictor. The sensitivities
varied between 38% & 100%, specificity of 90%.
IV. PREVENTION OF PREECLAMPSIA
Recommendations:
1. Should aspirin be given to all women for
prevention of hypertensive disorders of
pregnancy?
- Aspirin should be given to patients at high risk
for development of hypertensive disorders of
pregnancy. (Level I; HIGH GRADE)
In a study by Duley, et al. which included 22
randomized trials, patients in the low risk
population given aspirin had a significant
decrease in the risk of preeclampsia, preterm
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birth and small for gestational age babies.
However, no significant difference was seen
with gestational hypertension, eclampsia and
neonatal death.
2. When should aspirin be started to prevent of
hypertensive disorders of pregnancy?
- Aspirin should be given starting 16 weeks age
of gestation. (Level I; HIGH GRADE)
The study by Buold, et al. determined the
optimal timing of initiation of aspirin in patients
at high risk for hypertensive disorders of
pregnancy.Gestational hypertension,
preeclampsia, severe preeclampsia, preterm
birth were significantly reduced when aspirin
was started at 16 weeks. However, it did not
affect the Incidence of abruptio placenta.
Aspirin given after 16 weeks age of gestation
decreased gestational hypertension,
preeclampsia, and preterm birth but did not
affect the occurrence of severe preeclampsia,
intrauterine growth restriction (IUGR) and
abruptio placenta.
3. Should high dose calcium be used in the
prevention of hypertensive disorders?
- High dose calcium is recommended for
patients with adequate and inadequate calcium
intake. (Level 1; HIGH GRADE)
In a meta-analysis by Hofmeyr, et al. in 2014,
the use of high dose calcium supplementation of
1500-2000 mg/day in patients with adequate
and calcium deficient diet showed that there
was statistically significant reduction in
hypertension with or without proteinuria in
pregnancy with a RR of 0.90 (95% Cl 0.81-0.99)
and RR of 0.44 (95% Cl 0.28-0.70). Preeclampsia
was also reduced based on the 4 studies with a
RR of 0.62 (95% CI 0.32-1.2) in patients with
adequate calcium intake versus a RR of 0.36
(95% CI 0.20-0.65) in calcium deficient
individuals.
4. Should regular aerobic exercise versus normal
physical activity be used for prevention of
hypertensive disorders of pregnancy?
- Exercise does not decrease the risk for
hypertensive disorders of pregnancy. More
studies are needed to evaluate its effect in
pregnant patients. (Level IA; MODERATE
GRADE)
In nonpregnant women moderate exercise has
been shown to reduce hypertension and
cardiovascular disease. It is currently
recommended that 30 minutes of moderate
exercise be done during normal pregnancy. It
was hypothesized that this will improve
maternal endothelial dysfunction and stimulate
placental angiogenesis.
5. Should bed rest be used for prevention of
hypertensive disorders of pregnancy?
- Bed rest is not recommended to prevent
preeclampsia. More studies are needed to
evaluate its efficacy. (Level 1B; MODERATE
GRADE)
In a study done last 2010, it was shown that bed
rest results in a statistically significant reduction
in the risk of preeclampsia and gestational
hypertension. However, the sample size is
relatively small and there is unclear risk of bias
in the manner of randomization of the patients.
6. Should folic acid be used to prevent
hypertensive disorders of pregnancy?
- The use of folic acid could not be
recommended as this time. More studies are
needed to evaluate its role In the prevention of
hypeflensive disorders of pregnancy. (Level 1B;
LOW GRADE)
In a cohort study done last 2013 where folic acid
supplementation was given to all patients,
various outcomes were noted. In patients who
are at least 70% compliant with the folic acid,
they noted that 9.6% had gestational
hypertension and 2.4% had preeclampsia. In this
study they computed a RR of 1.00 (95% Cl 0.93-
1.08) for preeclampsia and 1.11 (95% Cl 1.08-
1.14) for gestational hypertension, negating the
role of folic acid for the prevention of
hypertensive disorders of pregnancy.
7. Should marine oil supplementation be given
for the prevention of hypertensive disorders of
pregnancy?
- Fish oil or marine oil supplementation is not
recommended for the prevention of
hypertensive disorders of pregnancy. (Level IA;
HIGH GRADE)
In a meta-analysis published last 2006 regarding
the role of marine oil supplementation, it was
noted that fish oil supplementation did not
reduce the incidence of preeclampsia (RR 0.86,
95% CI 0.59-1.27), gestational hypertension (RR
1.09, 95% CI 0.90-1.33), and eclampsia (RR 0.14,
95% Cl 0.01-2.7)
V. GESTATIONAL HPN AND PREECLAMPSIA
Gestational hypertension and preeclampsia
without severe features is blood pressure (BP)
elevation after 20 weeks of gestation in the
absence of proteinuria (gestational
hypertension) or the other various systemic
findings which would qualify as preeclampsia
with severe features.
Antihypertensives
1. Use of antihypertensives in mild to moderate
hypertension in pregnancy decreases the risk of
severe HPN (Level I. MODERATE GRADE)
2. Use of antihypertensives in mild to moderate
hypertension in pregnancy does not
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significantly decrease the development of
preeclampsia (Level 1, MODERATE GRADE)
3. Use of antihypertensives in mild to moderate
hypertension in pregnancy does not show any
significant difference in the development of
fetal or neonatal death, preterm birth, small
for gestational age (SGA) babies. (Level I, LOW
TO MODERATE GRADE)
4. Hydralazine, compared to labetalol, had
lower rates of persistent severe hypertension
(Level II, MODERATE GRADE)
5.Hydralazine, compared to nifedipine, had
higher rates of persistent severe hypertension.
(Level Il, LOW GRADE)
6. Hydralazine, compared to labetalol, was
associated with more maternal hypotension.
(Level II. MODERATE GRADE)
7. Hydralazine, compared to nifedipine, was
associated with more maternal hypotension
(Level 11, LOW GRADE)
8. For women with mild gestational
hypertension or preeclampsia with a persistent
BP 160 mmHg systolic or 110 mmHg diastolic, it
is suggested that antihypertensive medications
not be administered. (Level III. MODERATE
GRADE)
9. Oral nifedipine and intravenous (IV) labetalol
regimens are similarly effective in the acute
control of severe hypertension in pregnancy.
(Level I, MODERATE GRADE)
Magnesium Sulfate
1. For women with preeclampsia with systolic
BP <160 mmHg and a diastolic BP <110 mmHg
and no maternal symptoms, it is suggested that
magnesium sulfate (MgS04) not be
administered universally for the prevention of
eclampsia
2. There was no excess in neuromuscular
weakness or severe maternal hypotension in
patients who received nifedipine with MgS04 as
compared to controls who received placebo or
other antihypertensives with MgSO4.
(Level IV, VERYLOWGRADE)
3. The lower risk of eclampsia following
prophylaxis with MgS04 was not
associated with a clear difference In the risk of
death or disability for children at 18 months
(Level 1, MODERATE GRADE)
Antiplatelet Therapy
- Low dose aspirin has not been shown to
significantly decrease the incidence of
preeclampsia in patients with gestational
hypertension (Level III, LOW GRADE).
Workup
1. The close monitoring of women with
gestational hypertension or preeclampsia
without severe features with serial assessment
of maternal symptoms and fetal movement
(daily by the woman) and serial measurements
of BP (twice weekly), and assessment of
platelet counts and liver enzymes (weekly) is
suggested. (Level III, MODERATE GRADE)
2. Weekly assessment for proteinuria is
recommended. (Level Ill, MODERATE
GRADE)
3. Fetal growth assessment and antenatal
testing is recommended. If evidence of growth
restriction is noted, Doppler studies should be
done. (Level Ill. MODERATE GRADE)
4. Uric acid is weak in predicting eclampsia,
severe hypertension, poor fetal outcome, (Level
III, VERY LOW GRADE)
5. Platelet count 100,000, elevated
transaminases, creatinine 110 mmol/L predicts
adverse maternal but not fetal outcomes.
(Level 111, LOW GRADE)
Proteinuria
1. Measurement of protein-to-creatinine ratio
has potential diagnostic value for significant
proteinuria in cases of suspected preeclampsia.
(Level III, LOW GRADE)
2. Urine protein-to-creatinine ratio had a
sensitivity of 80-94% and specificity of 74-100%.
(Level III, MODERATE GRADE)
3. Proteinuric women with preeclampsia, as
compared to those without proteinuria, were
significantly more likely to:
a. deliver prior to 37 wks (Level III LOW
GRADE)
b. develop severe hypertension (Level Ill, LOW
GRADE)
c. have a higher perinatal mortality (Level Ill,
LOW GRADE)
4. Proteinuric women with preeclampsia, as
compared to those without proteinuria, were
significantly less likely to develop:
a. Thrombocytopenia (< 100,000) (level III,
LOW GRADE)
b. Thrombocytopenia (< 150,000) (Level III,
LOW GRADE)
c. Liver disease (Level III, LOW GRADE)
5. Non-proteinuric women with preeclampsia,
as compared to those with gestational
hypertension, were significantly more likely:
a. Deliver prior to 37 weeks (Level III LOW
GRADE)
b. Develop severe hypertension (Level Ill. LOW
GRADE)
c. To have small for gestational age (SGA)
babies (Level 111, LOW GRADE)
Timing of Delivery
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1. For women With gestational hypertension or Severe preeclampsia - is characterized by

preeclampsia without severe features and no certain findings in women meeting the basic
indication delivery at less than 37 weeks of criteria for diagnosing the disorder.
gestation, expectant management with
maternal and fetal monitoring is suggested.
(Level IV, LOW GRADE)
2. For women with gestational hypertension or
preeclampsia without severe features at or
beyond 37 weeks of gestation, delivery rather
than continued observation is suggested. (Level
III, MODERATE GRADE)
3. Induction of labor vs. expectant management
monitoring for gestational hypertension or mild
preeclampsia between 34-37 weeks:

The distinction between mild and severe

VI. PREECLAMPSIA WITH SEVERE FEATURES
Preeclampsia - is primarily defined by the
occurrence of new-onset hypertension which
usually occurs after 20 weeks of gestation plus
new onset proteinuria. Although these 2 criteria
are considered the classic definition of
preeclampsia, some women present with
hypertension and multi-systemic signs
indicative of severe disease, yet significant
proteinuria is absent.
Objectives for management:
1. To reduce its severity or prevent progression
of the disease process
2. To prevent convulsions
3. To control severe hypertension
4. To deliver the mother of a fetus at the
optimum time and with the least
5. To detect and appropriately treat end-organ
damage
6. To completely restore the health of the
mother
preeclampsia is important because it dictates
management and one must not be complacent
with mild preeclampsia because apparently mild
disease may progress rapidly to severe disease.
It should also be noted that the terms "mild",
"non-severe" or "less severe" can be misleading
because even in the absence of severe disease,
morbidity and mortality are still significantly
increased. Therefore, the terms "preeclampsia
without severe features" to denote mild
disease and "preeclampsia with severe
features" to denote severe disease be used
instead.
Management
The main objective in the management of
severe preeclampsia must always be the safety
of the mother and the fetus. The initial
management of preeclampsia includes
stabilization of the mother's condition,
confirmation of gestational age and assessment
of fetal well-being. Once the diagnosis of severe
preeclampsia is established, traditional
management has focused on maternal safety
with expedited delivery.

Preeclampsia can be diagnosed, even without

significant proteinuria, as long as the
hypertension exists in association with
any of the following:
a. Thrombocytopenia (platelet count
<100,000), b. Renal insufficiency (serum
creatinine 1.1 mg/dL or a doubling of serum
creatinine
in the absence of other renal disease),
c. Impaired liver function (elevated serum
liver transaminases to twice the normal
values), d. New-onset cerebral or visual
disturbances
e. Pulmonary edema.

Mild preeclampsia - refers to disease that

meets the criteria for the diagnosis of
preeclampsia but is not severe disease.

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In addition, prompt delivery is the safest option
for the woman and her fetus when there is
evidence of pulmonary edema, renal failure,
abruptio placenta, disseminated intravascular
coagulopathy (DIC), cerebral symptoms, and/or
eclampsia, nonreassuring fetal testing, or fetal
demise irrespective of gestational age in women
with severe preeclampsia.
Perinatal Complications
During expectant management of patients with
severe preeclampsia at 24-34 weeks of
gestation, the rate of perinatal death ranged
from 0 to 16.6%. Abruptio placenta is also a
reported complication and it ranged from 4.1%
to 22.9%. In addition, delivery for nonreassuring
fetal Status ranged from 26% to 75%
In all the reported studies, intensive fetal
monitoring for early detection of fetal
compromise is recommended. The most
common indication for delivery was
deterioration in fetal status underscoring the
need that these pregnancies managed
expectantly should be observed in centers that
are capable of rapid intervention for fetal
reasons.
Maternal Complications
During expectant management, maternal
complications in reported studies include. HELLP
syndrome (4.1-27.1%), pulmonary edema (0
8.5%) and eclampsia and acute renal failure.
Expectant 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),
Severe Preeclampsia Before the Limit of Fetal
Viability
Severe preeclampsia that develops in the mid-
trimester of pregnancy is associated with high
perinatal mortality and morbidity rates.
Aggressive treatment in the form of immediate
delivery will usually result in high neonatal
mortality If the fetus survives, significant
neonatal complications are expected and these
will require prolonged hospitalization. On the
other hand, attempts to prolong pregnancy may
result in fetal death and may expose the mother
to severe morbidity.
Recommendations
1. For women with severe preeclampsia ≥34
weeks of gestation, and in those with unstable
maternal or fetal conditions irrespective of
gestational age, delivery soon after maternal
stabilization is recommended. (Level Il, Grade
B)
2. For women with severe preeclampsia at <34
weeks of gestation with stable maternal and
fetal conditions, it is recommended that
continued pregnancy be undertaken only at
facilities with adequate maternal and neonatal
intensive care resources. (Level Il, Grade B)
3. For women with severe preeclampsia
receiving expectant management at 34 weeks or
less of gestation, the administration of
corticosteroids for fetal lung maturity benefit is
recommended (Level I, Grade A)
4. It is recommended that corticosteroids be
given if the fetus is viable and 33 weeks or less
of gestation, but that delivery not be delayed
after initial maternal stabilization regardless of
gestational age for women with severe
preeclampsia that is complicated further with
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any of the following: (Uncontrolled severe
hypertension, eclampsia, pulmonary edema
Abruptio placenta, DIC, Nonreassuring fetal
status, and Fetal death) (Level ll. Grade B)
5. It is recommended that corticosteroids be
administered and delivery deferred for 48
hours if maternal and fetal conditions remain
stable for women with severe preeclampsia and
a viable fetus at 33 6/7 weeks or less of
gestation with any of the following: (PPROM,
Labor, thrombocytopenia, IUGR, Severe
oligohydramnios, REDF in Doppler and Renal
Dysfunction)(Level Il, Grade C)
6. For women with severe preeclampsia
(sustained systolic BP of at least 160 mmHg or
diastolic BP of at least 110 mmHg), the use of
anti-hypertensive therapy is recommended.
(Level Il, Grade B)
7. For women with eclampsia, the
administration of parenteral MgS04 is
recommended. Grade A)
8. For women with severe preeclampsia, the
administration of parenteral MgSO4 during
expectant management is recommended.
(Level I, Grade A)
9. For women with severe preeclampsia the
administration of intrapartum postpartum
MgSO4, to prevent eclampsia is recommended
(Level I, Grade)
10. For women with severe preeclampsia
undergoing cesarean delivery, the continued
intraoperative administration of parenteral
MgSO4 to prevent eclampsia is recommended.
(Level Il, Grade B)
Summary of Evidence
MgS04 is the therapy of choice for eclampsia,
and diazepam and phenytoin should no longer
be used as line drugs. The IV route has few side
effects and in the United States, the IM route is
no longer used. 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 mlJhour, the magnesium
infusion should be halted.Because magnesium is
cleared almost exclusively by renal excretion,
plasma magnesium concentration is excessive if
the glomerular filtration rate is decreased
substantively The initial standard dose of MgS04
can be safely administered without knowledge
of renal function. Renal function is thereafter
estimated by measuring serum creatinine, and
whenever it is 1.3 mg/dL or higher, only half of
the maintenance dose is given.MgS04 toxicity
can also be assessed by clinical assessment of
the maternal deep tendon reflexes (DTRs) and
respiratory rate. If there is loss of the DTRs and
the respiratory rate falls below 12
cycles/minute, the MgSO4 infusion should be
halted. Calcium gluconate 1g (10 ml,) over 10
minutes can be given if there is concern of
MgSO4 toxicity.
MgS04 is the drug of choice for the prevention
of convulsions among patients with severe
preeclampsia who are managed expectantly.
These patients should receive MgS04 for 24
hours during expectant management. The dose
of MgSO4 depends on the patient's body
weight. Two grams per hour is given if the
patient weighs >70 kg. Patients weighing < 70 kg
can receive the 1g hour infusion. If BP is
controlled adequately and fetal testing is
reassuring, MgS04 is discontinued after 24
hours. MgSO4 can be given via:
a. Continuous IV infusion
b. Intermittent Intramuscular injection
11. For women with severe preeclampsia, it is
suggested that a delivery decision should not be
based on the amount of proteinuria or change
in the amount of proteinuria. (Level 11, Grade B)
12. For women with severe preeclampsia and
before fetal viability, delivery after maternal
stabilization is recommended. Expectant
management is not recommended. (Level Il,
Grade B)
13. For women with preeclampsia, it is
suggested that the mode of delivery need not
be cesarean delivery. The mode of delivery
should be determined by fetal gestational age,
fetal presentation, cervical status, and maternal
and fetal conditions. (Level 11, Grade C)
14. For women With preeclampsia who require
analgesia for labor or anesthesia for cesarean
delivery and with a clinical situation that permits
sufficient time for establishment of anesthesia.
the administration of neuraxlal anesthesia
(either spinal or epidural anesthesia) is
recommended. (Level Il, Grade B
15. For women with severe preeclampsia, it is
suggested that invasive hemodynamic
monitoring not be used routinely. (Level Ill,
Grade C)
16. For women in whom gestational
hypertension, preeclampsia, or superimposed
preeclampsia is diagnosed, it is suggested that
BP be monitored in the hospital or that
equivalent outpatient surveillance be
performed for at least 72 hours postpartum and
again 7-10 days after delivery or earlier in
women with symptoms. (Level II. Grade C)
17. Nonsteroidal anti-inflammatory drugs
(NSAIDS) tend to increase the BP, therefore, for
women with hypertension that persists for more
than 1 day postpartum, it is suggested that
these commonly used postpartum pain relief
agents be replaced by other analgesics, usually
opioid drugs. (Level Il, Grade C)
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 HYPERTENSION IN PREGNANCY
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18. For all women in the postpartum period (not

just women with preeclampsia), it is suggested
that discharge instructions include Information
about the signs and symptoms of preeclampsia
as well as the importance of prompt reporting
of this information to their health care
providers. (Level Ill, Grade C)
19. For women in the postpartum period who
present with new-onset hypertension
associated with headaches or blurred vision or
preeclampsia with severe hypertension, the
parenteral administration Of MgSO4, is
suggested. (Level III, Grade C)
20. For women with persistent postpartum
hypertension, BP of 150 mmHg systolic or 100
mmHg diastolic or higher, on at least two
occasions that are at least 4-6 hours apart,
antihypertensive therapy is suggested.
Persistent BP of 160 mmHg systolic or 110
mmHg diastolic or higher should be treated
within I hour. (Level 111, Grade C)

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 HYPERTENSION IN PREGNANCY
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VII. ECLAMPSIA
The basic objectives in the management of
eclampsia are:
1. maternal support of vital functions
2. control of convulsions and prevention of
recurrent convulsions
3. correction of maternal hypoxemia and/or
academia
4. control of severe hypertension to a safe range
5. initiate process of delivery
6. postpartum surveillance
Management
A.. Hospitalization- required for all patients with
eclampsia (Level l, Grade A)
B. Control of convulsions and prevention of
recurrent convulsions - Parenteral magnesium
sulfate (MgSO4) is the drug of choice to
control convulsions and prevent recurrent
convulsions in eclampsia.
The administration of MgSO4, requires proper
monitoring and vigilance, with particular focus
on the following precautions:
a. Urine output of at least 30 mL or 100 mL for
the past hour or 4 hours, respectively
b. Presence of patellar reflex
c. Respiratory rate of not less than 12/minute
d. Intravenous (IV) Calcium gluconate (10ml
Of 10% solution) must be available at bedside
for MgSO4 toxicity
e. If available, serum magnesium levels may
be taken at certain intervals to monitor
MgS04 toxicity. (Lewel 111, Grade C)
f. If a patient is to be transferred to another
hospital, the full loading dose must have been
given and the patient should be conducted by
a responsible health personnel, with
provisions for control of seizures and other
complications, if they occur, while on transit.
(Level 11-2, Grade B)
Alternatives to MgSO4
1. Diazepam – may be used with phenytoin in
the absence of MgSO4
2. Phenytoin – no consensual dosage regimen
but dose may be varied according to patient’s
weight.
C. Antihypertensive Therapy - Patients With
severe hypertension should be started on IV
antihypertensive therapy, with the following
recommended:
1. Hydralazine (drug of choice)- IV bolus of 5 or
10mg, not recommended for drip
2. Clonidine -IM injection of 75-150 mcg is the
next recommended drug
3. Nifedipine - if given orally at 10 or 20mg, this
drug takes effect within 15-50 minutes.
4. Labetalol - IV bolus Of 10-20 mg as initial
dose. Not given in CHF and asthma
5. Nicardipine - The antihypertensive effects of
nicardipine are seen within 10 minutes following
IV infusion, with sufficient BP reduction typically
occurring within 20 minutes.
D. Delivery After Control of Convulsions
Continuation of pregnancy in women with
eclampsia imposes a significant threat to the
well-being of both the mother and the fetus,
and necessitates termination of pregnancy.
Therefore, the final aim should be to designate
the time of delivery in such a fashion that both
the mother and fetus are best able to tolerate
delivery while providing the fetus with the
maximum chance of extrauterine survival.
Cesarean section can be decided upon if:
I. Vaginal delivery does not appear to be easy
and imminent
2. There is failure of progress after induction,
3. There is fetal compromise
VIII. CHRONIC HYPERTENSION
1. Chronic hypertension
in pregnancy is the presence of hypertension
before pregnancy or before 20 weeks of
gestation. The diagnosis Of hypertension is
made when either the systolic blood pressure
(BP) is ≥140 mmHg or the diastolic BP is 90
mmHg, or both. Severe case is SBP ≥160 and
DBP ≥110.
Recommendations
1. Referral to an internist - for investigation and
management of possible secondary causes as
well as for possible target organ damage. (GPP)
2. Antihypertensive therapy in severe chronic
hypertension - Pregnant women with chronic
hypertension with persistent systolic BP 160
mmHg or persistent diastolic BP 105 mmHg, or
those with evidence of target organ damage,
should be given antihypertensive therapy.
3. Antihypertensive therapy for mild to
moderate chronic hypertension. - Those with
persistent systolic BP 160 mmHg or persistent
diastolic BP 105 mmHg, and with no evidence of
target organ damage, should not be routinely in
antihypertensive therapy. (Level I, Grade A)
4. Antihypertensive for continuous therapy in
chronic hypertension in pregnancy -
Methyldopa, a centrally acting alpha-2
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 HYPERTENSION IN PREGNANCY
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adrenergic agonist, is the primary oral
medication recommended for chronic
hypertension in pregnancy.
5. Second line antihypertensives for continuous
therapy in chronic hypertension in pregnancy -
Labetalol, a nonselective β-blocker with vascular
alpha receptor-blocking ability, and nifedipine, a
calcium channel blocker, are second line oral
medications that can be used in chronic
hypertension. (Level I, Grade 4)
6. Antihypertensive drugs that should not be
used during pregnancy - Angiotensin converting
enzyme inhibitors (ACE inhibitors) and
angiotensin receptor blockers (ARBS) should not
be given before conception and during the first
trimester of pregnancy because of evidence of
teratogenicity. Likewise, they should not be
used during the second and third trimesters of
pregnancy because of evidence of fetopathy.
7. Antihypertensive drugs for use in urgent
control of severe chronic hypertension in
pregnancy - The parenteral form of labetalol
and hydralazine and the oral form of nifedipine
are medications that can be safely used in the
urgent control of severe chronic hypertension.
The choice should be based on availability,
familiarity and experience with the use of the
above medications. (Level I. Grade A)
8. Fetal surveillance for IUGR in chronic
hypertension - Serial ultrasonography to screen
for IUGR is recommended. (Level II-3, Grade B)
9. Surveillance for fetal well-being in chronic
hypertension in pregnancy with IUGR - As an
adjunct to conventional antenatal testing,
umbilical artery Doppler velocimetry is
recommended for cases where IUGR has been
confirmed. (Level l, Grade A)
10. Timing of delivery complicated by mild to
moderate chronic hypertension- In
uncomplicated chronic hypertension, delivery
before 38 weeks is not recommended. (Level I,
Grade A)
2. Chronic Hypertension with Superimposed
Preeclampsia
- Chronic hypertension with superimposed
preeclampsia is defined as a sudden increase in
BP in a pregnant woman with a previously well-
controlled chronic hypertension associated with
new onset proteinuria. A sudden increase in
proteinuria in a chronic hypertensive woman
who already has preconceptional proteinuria is
also a basis for the diagnosis.
Chronic hypertension with superimposed
preeclampsia plus severe features:
a. Severe hypertension i.e. systolic BP ≥160
mmHg or diastolic BP ≥110 mmHg or both.
b. Thrombocytopenia (platelets 100,000fuL)
c. Elevated liver transaminases (2x upper limit
of normal)
d. New onset renal insufficiency (sudden
increase in serum creatinine)
e. Cerebral or visual disturbances
Recommendations
1. Where do we manage cases of chronic
hypertension complicated by superimposed
preeclampsia? - The antenatal care and delivery
of women with chronic hypertension with
superimposed preeclampsia regardless of
gestational age should be done in facilities with
adequate maternal and neonatal intensive care
specialists and resources. (GPP)
2. Should MgSO4, be given to women with
chronic hypertension with superimposed
preeclampsia with features? – MgSO4, therapy
is given to prevent eclampsia once there is the
need, and is continued to the intrapartum or
even postpartum period. (Level l, Grade A)
3. When do you give antenatal corticosteroids? -
Antenatal steroids to enhance fetal lung
maturity is given to those with 34 weeks
gestational and who are being managed
expectantly (Level I, Grade A)
4. When do you deliver those with chronic
hypertension with superimposed preeclampsia?
- Delivery is recommended when any one of
these conditions is present. (Uncontrolled HPN,
Eclampsia, Abruptio Placenta, DIC, non-
reassuring fetal status, and Pulmonary edema).
The delivery is done once the maternal
condition is stabilized regardless of gestational
age or completion of antenatal steroids. (Level I,
Grade A)
5. When do you deliver patient’s with
superimposed preeclampsia without severe
features? - For women with chronic
hypertension with superimposed preeclampsia
without severe features, expectant
management up to 37 weeks is suggested.
(Level II-1. Grade B).
6. Can you do conservative management in
pregnancies complicated by chronic
hypertension with superimposed preeclampsia
with severe features <34 weeks? - Expectant
management can be offered to women with
chronic hypertension with superimposed
preeclampsia with severe features before 34
weeks provided that both maternal and fetal
conditions are stable and the patient is admitted
in a hospital capable of providing intensive
maternal and neonatal care. (Level l, Grade A)
7. Can the antihypertensives used during
pregnancy be continued during breastfeeding if
needed for continuous BP control? - The
antihypertensives used during pregnancy can be
used and lactation if needed for continuous BP
control. With the exception of diuretics, other
antihypertensives not used for pregnant women
can be used as well. (GPP).
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IX. COMPLICATIONS OF PREGNANCY-INDUCED 25% are generally reported. In skilled hands,

HYPERTENSION high rates of diagnosis have been reported. If
1. Abruptio Placenta there is ultrasound evidence of abruptio
placenta, the positive predictive value (PPV) is
- defined as separation of the normally located high. Retroplacental hematomas are associated
placenta before delivery of the fetus. It may be with the worst prognosis. Ultrasound signs
concealed or overt. It frequently presents as include:
vaginal bleeding associated with abdominal
pain, uterine contractions, and uterine  Retroplacental hematoma (hyperechoic,
tenderness in the second half of pregnancy. isoechoic, hypoechoic)
Abruptio placenta is associated with increased  Pre-placental hematoma (jiggling
perinatal mortality and morbidity. It is also a appearance with a shimmering effect
cause of significant maternal morbidity. When  of the chorionic plate With fetal movement)
placental separation exceeds 50%, acute  Increased placental thickness and
disseminated intravascular coagulopathy (DIC) echogenicity
and fetal death are common.  Subchorionic collection
Risk Factors  Marginal collection
1. Hypertension
2. Smoking
Management
3. Trauma
4. Cocaine use A.Fetal Demise - The approach to management
Diagnosis of abruptio placenta is made clinically. is similar to when the fetus is alive (i.e.
A retroplacental blood clot is the classic expeditious delivery, preferably by the vaginal
ultrasound finding of abruptio placenta, but is route). If the mother is not in active labor, she
not always present. can be induced by amniotomy and oxytocin.
Women who have had an abruption sufficient to
cause fetal demise are highly likely to have DIC.
Diagnosis
If the maternal condition is worsening with
a. History and Physical Examination – Common severe hemorrhage, cesarean delivery may be
symptoms are abdominal pain, uterine indicated (although rarely). It is important that
contractions, and uterine tenderness. Vaginal both blood and blood products are replaced
bleeding is also considered a classic symptom, before and during the surgery.
but it is important to note that it may not be
B. Live Fetus >34 Weeks Gestation –
present in cases of concealed abruption,
particularly when the placenta is located The aim in these circumstances is expeditious
posteriorly within the uterus delivery. If the mother is in a stable condition
and the fetal heart tracing is reassuring, then
b. Fetal monitoring - FHR should be monitored
vaginal delivery can be attempted. Often the
continuously, at least initially. Abnormalities in
mother is having vigorous contractions, but if
the tracing that suggest an abruption include
the mother is not in active labor, amniotomy
late decelerations, loss of variability, variable
and oxytocin induction usually results in
decelerations, a sinusoidal FHR tracing, and fetal
delivery. Blood coagulation products should be
bradycardia, defined as a persistent FEIR below
readily available and replaced aggressively if
110 beats per minute.
needed. If the maternal condition is worsening
c. Laboratory tests - Hemoglobin, hematocrit, with severe hemorrhage, urgent cesarean
and coagulation studies (prothrombin time CPT delivery may be indicated (although rarely).
l, partial thromboplastin time (PTT), fibrinogen, Unnecessary delay should be avoided.
and fibrinogen breakdown products) should be
ordered immediately in all patients with
bleeding in whom abruption is suspected. When
severe blood loss has occurred over a period of
time, the hemoglobin and hematocrit levels may
be low. DIC occurs typically in the presence of
abruptions large enough to cause fetal death
and should be suspected when the patient
bleeds persistently Without clotting. A simple
test to confirm DIC is to take some blood in a
plain tube (Without anticoagulation), and then
invert the tube at I-minute intervals. The blood
should clot within 8 to 10 minutes; failure to do
so may be taken as evidence of DIC. When DIC
occurs, the fibrinogen levels will be Iow.
d. Ultrasound - may or may not be helpful in the
diagnosis of abruptio placenta but is a useful
initial investigation. Detection rates of only 12-

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C. Live Fetus ≤34 Weeks Gestation – 2. HELLP Syndrome

In cases where the fetus and mother are both
stable and there is no evidence of maternal
coagulopathy, hypotension, or severe ongoing
blood loss, conservative management with the
aim of delivering a more mature fetus is the
main goal of therapy. Corticosteroids should be
given to promote fetal lung maturation in
pregnancies between 24 to 34 weeks. Tocolytics
may be used with extreme caution in cases
where there are uterine contractions in
pregnancies 24 weeks. This is controversial, but
small studies have confirmed that careful use of
tocolytics may be safe in these circumstances.
FHR monitoring, and biophysical profiles (BPP)
fetal well-being studies are done at least
weekly. The particular monitoring program must
be individualized on a case-by-case basis.
HELLP syndrome (Hemolysis with a
microangiopathic blood smear, Elevated Liver
enzymes, and Low Platelet count) develops in
1% of all pregnancies but in 10-20% of
pregnancies with severe preeclampsia/
eclampsia. HELLP syndrome has a variable
presentation usually with a rapid onset.
Differential diagnoses for HELLP syndrome
include acute fatty liver of pregnancy,
gastroenteritis, hepatitis, appendicitis,
gallbladder disease, immune thrombocytopenia,
lupus flare, antiphospholipid syndrome,
hemolytic-uremic syndrome, thrombotic
thrombocytopenic purpura, and nonalcoholic
fatty liver disease.

Diagnosis, Laboratory and Criteria

Currently there are two major criteria for
diagnosing HELLP syndrome.
A. Tennessee Classification System -
Intravascular hemolysis is diagnosed by
abnormal peripheral blood smear, increased
serum bilirubin and elevated LDH levels
Prognosis
B. Mississippi -Triple Class System- a further
For the fetus, the prognosis depends primarily
classification of the disorder is based on the
on the gestational age at which the abruption
nadir platelet count any time during the course
occurs, and on the degree Of the abruption.
of the disease. Class 3 HELLP syndrome is
Cases of extremely preterm gestations and
considered as a clinical significant transition
those with more than 50% separation of the
stage or a phase of the HELLP syndrome which
placenta are associated with a high risk of
had the ability of progression.
perinatal death. Abruption is also an important
cause of indicated preterm birth and is
associated with an increased risk of perinatal
asphyxia and long-term neurodevelopmental
handicap. However, the perinatal outcome may
be good in cases where the abruption is
recognized promptly, and where the fetus is
delivered expeditiously.
The maternal prognosis is linked primarily to the
severity of the abruption, particularly to the
amount of blood lost and to the presence or
absence of associated coagulopathy. There is an
increased risk for blood transfusions, surgical
and anesthetic complications, and cesarean
hysterectomy. Maternal outcomes are excellent
in cases in which there is neither massive blood
loss or coagulopathy.

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 HYPERTENSION IN PREGNANCY
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Management
The management of patients with HELLP
requires availability of neonatal and obstetric
ICU thus should receive care at tertiary care
center.
A. Initial steps - Stabilize the mother, assess
fetal condition and decided whether prompt
delivery is indicated.
B. Timing of Delivery – if HELLP develops before
24 weeks, termination of pregnancy is strongly
considered. Consensus of indication for prompt
delivery:
a. ≥34 weeks of gestation
b. Presence of severe maternal disease
c. Non-reassuring fetal status
C. Platelet Transfusion - Platelet count should
be maintained at 20,000 and 40,000 for vaginal
and cesarean delivery, respectively. In patients
with platelet count 40,000, 4-10 units of
platelets are transfused at the time of
intubation. Platelet transfusion is also indicated
in patients with significant bleeding or platelet
count less than 20,000 irrespective of the
intended mode of delivery.
D. Route of Delivery - Vaginal delivery is
recommended for women in labor or with
ruptured membranes and a vertex-presenting
infant, regardless of gestational age. Labor can
be induced in women with favorable cervices or
pregnancies at least 30- 32 weeks of gestation.
Cesarean delivery is performed for the usual
obstetrical indications (e.g. breech,
nonreassuring fetal status).
E. Anesthesia - Epidural anesthesia can be
administered safely in patients without adverse
hemorrhagic and neurologic sequelae if the
maternal platelet count exceeds. Even a platelet
count of 100,000mmol/L or greater must be
carefully assessed before using conduction
anesthesia because of the altered platelet
function that is present in HELLP syndrome
General anesthesia has potential complications
in the HELLP syndrome patient with impaired
liver function and an altered ability to
metabolize anesthetic agents. However, it does
remain the anesthetic of choice in Class I and
Class 2 disease.
F. Postpartum course - Laboratory values may
initially worsen following delivery. The time
course of recovery from HELLP was evaluated in
a series of 158 women with the disease.
Decreasing platelet counts continued until 24-48
hours after delivery, while serum LDH
concentration usually peaked 24-48 hours
postpartum. In all patients who recovered, a
platelet count: 100,000 was achieved
spontaneously by the postpartum day or within
72 hours of the platelet nadir. An upward trend
in platelet count and a downward trend in LDH
concentration should be seen by the
postpartum day in the absence of complications.
12-STEP TREATMENT APPROACH
1. Anticipate and make the diagnosis
2. Assess the maternal condition
3. Assess the fetal condition: deliver sooner or
later?
4. Control BP
5. Prevent seizures with MgSOr
6. Manage fluid and electrolytes.
7. Exercise judicious hemotherapy.
8. Manage labor and delivery.
9. Optimize perinatal care.
10. Intensively treat the postpartum patient.
11. Remain alert to the development of multiple
organ system failure.
12. Counsel about future pregnancies.
14