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HYPERTENSION IN PREGNANCY

CPG

MAIN TOPICS 5. Family History of Preeclampsia - Chesley et.


1. EPIDEMIOLOGY OF HPN IN PREGNANCY al. found that the rate of preeclampsia was
higher in sisters (37%), daughters (26%), and
2. CLASSIFICATION OF HPN IN PREGNANCY granddaughters (16%) than it was in daughters-
3. PREDICTIVE TEST FOR PREECLAMPSIA in-law (6%).
4. PREVENTION OF PREECLAMPSIA 6. Ethnicity - Black women have a risk of
5. GESTATIONAL HPN AND PREECLAMPSIA preeclampsia that is twice as high as that of
white women. They are also more likely to have
6. PREECLAMPSIA WITH SEVERE FEATURES hypertension.
7. ECLAMPSIA 7. Maternal Age – women aged >40 had
8. CHRONIC HYPERTENSION approaching twice the risk of developing
9. COMPLICATIONS OF PREGNANCY INDUCED preeclampsia, whether they were primiparous
HPN (HELLP, ABRUPTIO PLACENTA) or multiparous (relative risk IRRI I .68, 95% Cl
1.23-2.29, and RR 1.96, Cl 1.34-2.87,
respectively).
I. EPIDEMIOLOGY OF HPN IN PREGNANCY 8. Smoking - Smoking in pregnancy has
Hypertensive disorders in pregnancy cover a repeatedly been associated with a reduced risk
spectrum of conditions: of mild and severe preeclampsia in primiparous
1. Gestational Hypertension and multiparous women, singleton and
multifetal pregnancies. Typically, the RR is about
2. Preeclampsia 0.5-0.8 compared with nonsmokers.
3. Eclampsia 9. Other unresolved risk factors include:
4. Chronic Hypertension • Previous miscarriage and induced abortions
5. Preeclampsia superimposed on chronic HPN • Environmental risk factors
 Interpregnancy intervals 2 years or 10 years

Preeclampsia:
Maternal Medical Risk Factors
Preeclampsia complicates about 3% of
pregnancies, and all hypertensive disorders 1. Underlying medical conditions:
affect about 5-10% of pregnancies. a. Diabetes mellitus - Among 462 women with
- etiology is multifactorial pregestational diabetes mellitus, Sibai, et al.
demonstrated a 20% occurrence of
Material Personal Risk Factors preeclampsia.
1. Primiparity - based study in Norway covering b. Antiphospholipid antibody syndrome - Two
all births since 1967 (about 1.5 million women), meta-analyses and a number of case-control
the risk of preeclampsia in first pregnancies was and cohort studies have found associations
3%, decreased to 1.7% in the second pregnancy. between preeclampsia and lupus anticoagulant,
Primiparity is associated with approximately 2.4- anticardiolipin, and/or anti-P2 glycoprotein. The
fold elevated risk of preeclampsia. presence of antiphospholipid antibodies
significantly increases the risk of developing
2. Primipaternity - The role of the father has
preeclampsia
long been hypothesized to be central in the
primipaternity model which can be interpreted c. Systemic lupus erythematosus - Maternal
by an immunogenetic hypothesis. This may be complications included lupus flare (25.6%),
interpreted as an immunological habituation to hypertension (16.3%), nephritis (16.1%),
paternal antigens through contact between the preeclampsia (7.6%) and eclampsia.
sperm and the female genital tract. Moreover, if d. Renal disease - Davies, et al. found that the
a woman becomes pregnant by a man who has prevalence of renal disease was higher in
fathered a preeclamptic pregnancy in a different women who developed preeclampsia compared
woman, her risk of developing is 1.8%. with those that did not (5.3% vs 1.8%)
3. History of Preeclampsia - The risk of 2. Maternal Infection - The risk of preeclampsia
recurrence is about 14%. The recurrence risk was increased in patients with urinary tract
was reported even higher in a study based on infection (OR 1.57, 95% CI 1.45-1.70) and
hospital records, with a 20-fold increase in the periodontal disease (OR 1.76, 95% CI 1.43-2.18).
preeclampsia risk compared with parous women
with no previous preeclampsia. Moreover,
severe preeclamptic women in an initial Placental/Fetal Risk Factors
pregnancy have a recurrence rate of as high as 1. Multiple Pregnancies - In women with twin
50%. gestations compared with those with singletons,
4. Obesity - The relationship between maternal the incidence o fgestational hypertension and
weight and the risk of preeclampsia is preeclampsia are both significantly increased,
progressive. It increases from 4.3% to 13.3% to 13% in singletons and 5-6% in twins. When a
BMI >35kg/m2 woman is pregnant with twins, her risk triples.

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2.Molar Pregnancy - associated with very early- 1. Preeclampsia-Eclampsia


onset preeclampsia. Both have dysfunctional Elevation of BP characterizes preeclampsia and
placentas that are integral to each disease eclampsia. Proteinuria remains an important
process. More so, both molar pregnancy and and objective marker and is taken as an
preeclampsia are caused by an excess of evidence of a systemic-wide endothelial leak. In
circulating sFlt-1. recognition of the systemic nature of
preeclampsia, the dependency of diagnosis on
II. CLASSIFICATION OF HPN IN PREGNANCY proteinuria has been eliminated.

“This Task Force report changes the paradigm Preeclampsia- In its absence, preeclampsia is
that we use in diagnosing preeclampsia from diagnosed as hypertension in association with
one that is dependent on new onset other multi-organ involvement such as
hypertension and proteinuria. The problem is thrombocytopenia, impaired liver function, new
that many patients with preeclampsia don't development of renal insufficiency, pulmonary
have enough proteinuria to meet the former edema, or new-onset cerebral or visual
criteria, so their diagnosis and treatment is disturbances
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: Preeclampsia with severe features:


1. The failure of health care workers to a. Systolic or diastolic BP values >160 or 110
appreciate the multi-systemic nature of mmHg, respectively, occurring twice, 4 hours
preeclampsia may in part be due to attempts at apart at bed rest
rigid diagnosis b. Thrombocytopenia (platelet counts <100,000)
2. Preeclampsia has long been recognized as a c. Impaired liver function defined as either
dynamic process and a diagnosis such as "mild otherwise unexplained right upper quadrant
preeclampsia" (now being discouraged) applies epigastric pain unresponsive to medications, or
only at the moment the diagnosis is established hepatic transaminase levels 2x normal
because the illness, by nature, is progressive.
d. Progressive renal insufficiency defined as
serum creatinine concentrations 1.1 mg/dL or a
Blood Pressure Criteria - systolic and diastolic doubling of the serum creatinine concentration
BP 140 and 90 mmHg, respectively, occurring in the absence of other renal disease
after 20 weeks of gestation. Korotkoff phase V is e. Pulmonary edema
used to define diastolic pressure.
f. New-onset cerebral or visual disturbances
Incremental changes in BP is no longer a
recommended criterion because women
showing a rise of 30 mmHg systolic or 15 mmHg Eclampsia – this is the term used in women
diastolic alone are not likely to experience any diagnosed to have preeclampsia and have
worsening of pregnancy outcome. They may just convulsions that cannot be attributed to
be observed more closely. another cause. The convulsions are generalized
and may occur before, during, or after labor.
Although generally occurring within 48 hours of
Proteinuria - having urinary protein spillage of delivery, of postpartum eclampsia may initially
300 mg/24 hours, protein-to-creatinine ratio 0.3 occur beyond this time frame
or 1+ urinary protein dipstick reading. Because
of the variability of qualitative determination
(Dipstick test), it is discouraged for diagnostic 2. Chronic Hypertension
use unless other methods are not readily It is hypertension of any cause that predates
available. If this must be used, I + is considered pregnancy. BP > 140/90 before pregnancy or
the cut-off for the diagnosis of proteinuria. before 20 weeks gestation, or both.

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3. Superimposed Preeclampsia 3. What is the role of uterine artery Doppler


It is chronic hypertension in association with studies in the prediction of preeclampsia?
preeclampsia. Others define it as worsening - Abnormal placentation, as seen in
baseline hypertension accompanied by new- preeclampsia, is associated with inadequate
onset proteinuria or other findings supportive of uteroplacental blood flow. Doppler
preeclampsia. ultrasonography might be used to assess the
velocity of uterine blood flow and thereby
4. Gestational Hypertension indirectly evaluate the trophoblastic invasion of
It is new onset of threshold BP elevations after the spiral arteries.
20 weeks gestation in the absence of Doppler indices used to evaluate the blood flow
proteinuria or the other systemic findings and the most commonly used are:
alternatively used to support the diagnosis of a. Pulsatility Index (PI): peak systolic flow minus
preeclampsia. It is hypertension in pregnancy end diastolic flow divided by mean flow
that does not show signs of developing b. Resistance index (RI): peak systolic flow minus
preeclampsia and the elevated BP resolves by end diastolic flow divided by peak systolic flow
12 weeks postpartum. These women are then c. Notching: presence of early diastolic notching
reclassified by some as transient hypertension. indicating decreased early diastolic flow
compared to later diastolic flow in the uterine
artery
III. PREDICTORS OF PREECLAMPSIA Since preeclampsia is characterized by a
1. What is the significance of mean arterial complex pathophysiology with heterogeneous
pressure (MAP) in detecting or predicting clinical and laboratory findings, it may not be
preeclampsia ? realistic to search for a single marker to predict
- MAP, a BP measurement that combines the disorder. A combination of two or more
systolic BP and diastolic BP is better than systolic independent markers, each representing
BP alone or diastolic BP alone in predicting separate pathophysiological processes should
preeclampsia. theoretically improve the possibility for
Lai, et al. explained that the mean multiple of predicting preeclampsia with high accuracy.
median MAP, systolic BP and diastolic BP were 4. What would be the best combined method for
significantly higher in intermediate the prediction of preeclampsia?
preeclampsia (preeclampsia requiring delivery - A systematic review by Giguere, et. al. showed
at 34-37 weeks) and late preeclampsia that a combination of biochemical and
(preeclampsia requiring delivery at or after 38 ultrasonographic markers might improve the
weeks) than in normal pregnancy. prediction of preeclampsia.16 In low risk
2. What biochemical markers can be used to populations, several combinations, including
predict preeclampsia? PPI3, PAPP-A, a disintegrin and
- The biochemical predictors of preeclampsia metalloproteinase (ADAM), Activin A or Inhibin
studied so far reflect our knowledge of the A measured in the or early 2nd trimester,
pathophysiology of preeclampsia. Several combined with uterine artery Doppler
potential predictors describe the fetal and investigation, showed a sensitivity of 60-80%
placental endocrine functions and the maternal and a specificity of >80%. A combination of PPI 3
endothelial dysfunction. and uterine artery Doppler showed a sensitivity
Kleinrouweler, et al. confirmed that the of 90% and a specificity of 90% for severe
concentration of placental growth preeclampsia in a high risk population.
factor (PIGF) and vascular endothelial growth Another review where trimester predictors
factor (VEGF) were lower in women who were evaluated, concluded furthermore that the
developed preeclampsia. The failure of combination of biomarkers and uterine artery
trophoblast invasion may contribute to the Doppler ultrasound predicted preeclampsia
alteration of the surface layer of the better than a single predictor. The sensitivities
syncytiotrophoblasts and result in leakage of varied between 38% & 100%, specificity of 90%.
alpha fetoprotein (AFP) into the maternal
circulation resulting in an increased level IV. PREVENTION OF PREECLAMPSIA
of these proteins in women with preeclampsia. Recommendations:

Summary of biomarkers and their accuracy 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. evaluate its efficacy. (Level 1B; MODERATE
However, no significant difference was seen GRADE)
with gestational hypertension, eclampsia and In a study done last 2010, it was shown that bed
neonatal death. rest results in a statistically significant reduction
2. When should aspirin be started to prevent of in the risk of preeclampsia and gestational
hypertensive disorders of pregnancy? hypertension. However, the sample size is
- Aspirin should be given starting 16 weeks age relatively small and there is unclear risk of bias
of gestation. (Level I; HIGH GRADE) in the manner of randomization of the patients.

The study by Buold, et al. determined the 6. Should folic acid be used to prevent
optimal timing of initiation of aspirin in patients hypertensive disorders of pregnancy?
at high risk for hypertensive disorders of - The use of folic acid could not be
pregnancy.Gestational hypertension, recommended as this time. More studies are
preeclampsia, severe preeclampsia, preterm needed to evaluate its role In the prevention of
birth were significantly reduced when aspirin hypeflensive disorders of pregnancy. (Level 1B;
was started at 16 weeks. However, it did not LOW GRADE)
affect the Incidence of abruptio placenta. In a cohort study done last 2013 where folic acid
Aspirin given after 16 weeks age of gestation supplementation was given to all patients,
decreased gestational hypertension, various outcomes were noted. In patients who
preeclampsia, and preterm birth but did not are at least 70% compliant with the folic acid,
affect the occurrence of severe preeclampsia, they noted that 9.6% had gestational
intrauterine growth restriction (IUGR) and hypertension and 2.4% had preeclampsia. In this
abruptio placenta. study they computed a RR of 1.00 (95% Cl 0.93-
3. Should high dose calcium be used in the 1.08) for preeclampsia and 1.11 (95% Cl 1.08-
prevention of hypertensive disorders? 1.14) for gestational hypertension, negating the
- High dose calcium is recommended for role of folic acid for the prevention of
patients with adequate and inadequate calcium hypertensive disorders of pregnancy.
intake. (Level 1; HIGH GRADE) 7. Should marine oil supplementation be given
In a meta-analysis by Hofmeyr, et al. in 2014, for the prevention of hypertensive disorders of
the use of high dose calcium supplementation of pregnancy?
1500-2000 mg/day in patients with adequate - Fish oil or marine oil supplementation is not
and calcium deficient diet showed that there recommended for the prevention of
was statistically significant reduction in hypertensive disorders of pregnancy. (Level IA;
hypertension with or without proteinuria in HIGH GRADE)
pregnancy with a RR of 0.90 (95% Cl 0.81-0.99) In a meta-analysis published last 2006 regarding
and RR of 0.44 (95% Cl 0.28-0.70). Preeclampsia the role of marine oil supplementation, it was
was also reduced based on the 4 studies with a noted that fish oil supplementation did not
RR of 0.62 (95% CI 0.32-1.2) in patients with reduce the incidence of preeclampsia (RR 0.86,
adequate calcium intake versus a RR of 0.36 95% CI 0.59-1.27), gestational hypertension (RR
(95% CI 0.20-0.65) in calcium deficient 1.09, 95% CI 0.90-1.33), and eclampsia (RR 0.14,
individuals. 95% Cl 0.01-2.7)
4. Should regular aerobic exercise versus normal
physical activity be used for prevention of
hypertensive disorders of pregnancy? V. GESTATIONAL HPN AND PREECLAMPSIA

- Exercise does not decrease the risk for Gestational hypertension and preeclampsia
hypertensive disorders of pregnancy. More without severe features is blood pressure (BP)
studies are needed to evaluate its effect in elevation after 20 weeks of gestation in the
pregnant patients. (Level IA; MODERATE absence of proteinuria (gestational
GRADE) hypertension) or the other various systemic
findings which would qualify as preeclampsia
In nonpregnant women moderate exercise has with severe features.
been shown to reduce hypertension and
cardiovascular disease. It is currently Antihypertensives
recommended that 30 minutes of moderate 1. Use of antihypertensives in mild to moderate
exercise be done during normal pregnancy. It hypertension in pregnancy decreases the risk of
was hypothesized that this will improve severe HPN (Level I. MODERATE GRADE)
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 2. Use of antihypertensives in mild to moderate
preeclampsia. More studies are needed to hypertension in pregnancy does not

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significantly decrease the development of without severe features with serial assessment
preeclampsia (Level 1, MODERATE GRADE) of maternal symptoms and fetal movement
(daily by the woman) and serial measurements
of BP (twice weekly), and assessment of
3. Use of antihypertensives in mild to moderate platelet counts and liver enzymes (weekly) is
hypertension in pregnancy does not show any suggested. (Level III, MODERATE GRADE)
significant difference in the development of
fetal or neonatal death, preterm birth, small 2. Weekly assessment for proteinuria is
for gestational age (SGA) babies. (Level I, LOW recommended. (Level Ill, MODERATE
TO MODERATE GRADE) GRADE)
4. Hydralazine, compared to labetalol, had 3. Fetal growth assessment and antenatal
lower rates of persistent severe hypertension testing is recommended. If evidence of growth
(Level II, MODERATE GRADE) restriction is noted, Doppler studies should be
5.Hydralazine, compared to nifedipine, had done. (Level Ill. MODERATE GRADE)
higher rates of persistent severe hypertension. 4. Uric acid is weak in predicting eclampsia,
(Level Il, LOW GRADE) severe hypertension, poor fetal outcome, (Level
6. Hydralazine, compared to labetalol, was III, VERY LOW GRADE)
associated with more maternal hypotension. 5. Platelet count 100,000, elevated
(Level II. MODERATE GRADE) transaminases, creatinine 110 mmol/L predicts
7. Hydralazine, compared to nifedipine, was adverse maternal but not fetal outcomes.
associated with more maternal hypotension (Level 111, LOW GRADE)
(Level 11, LOW GRADE)
8. For women with mild gestational Proteinuria
hypertension or preeclampsia with a persistent 1. Measurement of protein-to-creatinine ratio
BP 160 mmHg systolic or 110 mmHg diastolic, it has potential diagnostic value for significant
is suggested that antihypertensive medications proteinuria in cases of suspected preeclampsia.
not be administered. (Level III. MODERATE (Level III, LOW GRADE)
GRADE) 2. Urine protein-to-creatinine ratio had a
9. Oral nifedipine and intravenous (IV) labetalol sensitivity of 80-94% and specificity of 74-100%.
regimens are similarly effective in the acute (Level III, MODERATE GRADE)
control of severe hypertension in pregnancy. 3. Proteinuric women with preeclampsia, as
(Level I, MODERATE GRADE) compared to those without proteinuria, were
significantly more likely to:
Magnesium Sulfate a. deliver prior to 37 wks (Level III LOW
1. For women with preeclampsia with systolic GRADE)
BP <160 mmHg and a diastolic BP <110 mmHg b. develop severe hypertension (Level Ill, LOW
and no maternal symptoms, it is suggested that GRADE)
magnesium sulfate (MgS04) not be
administered universally for the prevention of c. have a higher perinatal mortality (Level Ill,
eclampsia LOW GRADE)
2. There was no excess in neuromuscular 4. Proteinuric women with preeclampsia, as
weakness or severe maternal hypotension in compared to those without proteinuria, were
patients who received nifedipine with MgS04 as significantly less likely to develop:
compared to controls who received placebo or a. Thrombocytopenia (< 100,000) (level III,
other antihypertensives with MgSO4. LOW GRADE)
(Level IV, VERYLOWGRADE)
3. The lower risk of eclampsia following b. Thrombocytopenia (< 150,000) (Level III,
prophylaxis with MgS04 was not LOW GRADE)
associated with a clear difference In the risk of c. Liver disease (Level III, LOW GRADE)
death or disability for children at 18 months 5. Non-proteinuric women with preeclampsia,
(Level 1, MODERATE GRADE) as compared to those with gestational
hypertension, were significantly more likely:
Antiplatelet Therapy
- Low dose aspirin has not been shown to a. Deliver prior to 37 weeks (Level III LOW
significantly decrease the incidence of GRADE)
preeclampsia in patients with gestational b. Develop severe hypertension (Level Ill. LOW
hypertension (Level III, LOW GRADE). GRADE)
c. To have small for gestational age (SGA)
Workup babies (Level 111, LOW GRADE)

1. The close monitoring of women with


gestational hypertension or preeclampsia 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


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",
VI. PREECLAMPSIA WITH SEVERE FEATURES "non-severe" or "less severe" can be misleading
Preeclampsia - is primarily defined by the because even in the absence of severe disease,
occurrence of new-onset hypertension which morbidity and mortality are still significantly
usually occurs after 20 weeks of gestation plus increased. Therefore, the terms "preeclampsia
new onset proteinuria. Although these 2 criteria without severe features" to denote mild
are considered the classic definition of disease and "preeclampsia with severe
preeclampsia, some women present with features" to denote severe disease be used
hypertension and multi-systemic signs instead.
indicative of severe disease, yet significant
proteinuria is absent. Management
The main objective in the management of
Objectives for management: severe preeclampsia must always be the safety
1. To reduce its severity or prevent progression of the mother and the fetus. The initial
of the disease process management of preeclampsia includes
2. To prevent convulsions stabilization of the mother's condition,
3. To control severe hypertension confirmation of gestational age and assessment
4. To deliver the mother of a fetus at the of fetal well-being. Once the diagnosis of severe
optimum time and with the least preeclampsia is established, traditional
5. To detect and appropriately treat end-organ management has focused on maternal safety
damage with expedited delivery.
6. To completely restore the health of the
mother

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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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),

In addition, prompt delivery is the safest option


for the woman and her fetus when there is Severe Preeclampsia Before the Limit of Fetal
evidence of pulmonary edema, renal failure, Viability
abruptio placenta, disseminated intravascular Severe preeclampsia that develops in the mid-
coagulopathy (DIC), cerebral symptoms, and/or trimester of pregnancy is associated with high
eclampsia, nonreassuring fetal testing, or fetal perinatal mortality and morbidity rates.
demise irrespective of gestational age in women Aggressive treatment in the form of immediate
with severe preeclampsia. 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
Perinatal Complications recommended (Level I, Grade A)
During expectant management of patients with 4. It is recommended that corticosteroids be
severe preeclampsia at 24-34 weeks of given if the fetus is viable and 33 weeks or less
gestation, the rate of perinatal death ranged of gestation, but that delivery not be delayed
from 0 to 16.6%. Abruptio placenta is also a after initial maternal stabilization regardless of
reported complication and it ranged from 4.1% gestational age for women with severe
preeclampsia that is complicated further with

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any of the following: (Uncontrolled severe halted. Calcium gluconate 1g (10 ml,) over 10
hypertension, eclampsia, pulmonary edema minutes can be given if there is concern of
Abruptio placenta, DIC, Nonreassuring fetal MgSO4 toxicity.
status, and Fetal death) (Level ll. Grade B) MgS04 is the drug of choice for the prevention
5. It is recommended that corticosteroids be of convulsions among patients with severe
administered and delivery deferred for 48 preeclampsia who are managed expectantly.
hours if maternal and fetal conditions remain These patients should receive MgS04 for 24
stable for women with severe preeclampsia and hours during expectant management. The dose
a viable fetus at 33 6/7 weeks or less of of MgSO4 depends on the patient's body
gestation with any of the following: (PPROM, weight. Two grams per hour is given if the
Labor, thrombocytopenia, IUGR, Severe patient weighs >70 kg. Patients weighing < 70 kg
oligohydramnios, REDF in Doppler and Renal can receive the 1g hour infusion. If BP is
Dysfunction)(Level Il, Grade C) controlled adequately and fetal testing is
6. For women with severe preeclampsia reassuring, MgS04 is discontinued after 24
(sustained systolic BP of at least 160 mmHg or hours. MgSO4 can be given via:
diastolic BP of at least 110 mmHg), the use of a. Continuous IV infusion
anti-hypertensive therapy is recommended. b. Intermittent Intramuscular injection
(Level Il, Grade B)
7. For women with eclampsia, the 11. For women with severe preeclampsia, it is
administration of parenteral MgS04 is suggested that a delivery decision should not be
recommended. Grade A) based on the amount of proteinuria or change
in the amount of proteinuria. (Level 11, Grade B)

8. For women with severe preeclampsia, the


administration of parenteral MgSO4 during 12. For women with severe preeclampsia and
expectant management is recommended. before fetal viability, delivery after maternal
(Level I, Grade A) stabilization is recommended. Expectant
management is not recommended. (Level Il,
9. For women with severe preeclampsia the Grade B)
administration of intrapartum postpartum
MgSO4, to prevent eclampsia is recommended 13. For women with preeclampsia, it is
(Level I, Grade) suggested that the mode of delivery need not
be cesarean delivery. The mode of delivery
10. For women with severe preeclampsia should be determined by fetal gestational age,
undergoing cesarean delivery, the continued fetal presentation, cervical status, and maternal
intraoperative administration of parenteral and fetal conditions. (Level 11, Grade C)
MgSO4 to prevent eclampsia is recommended.
(Level Il, Grade B) 14. For women With preeclampsia who require
analgesia for labor or anesthesia for cesarean
Summary of Evidence delivery and with a clinical situation that permits
MgS04 is the therapy of choice for eclampsia, sufficient time for establishment of anesthesia.
and diazepam and phenytoin should no longer the administration of neuraxlal anesthesia
be used as line drugs. The IV route has few side (either spinal or epidural anesthesia) is
effects and in the United States, the IM route is recommended. (Level Il, Grade B
no longer used. Magnesium toxicity is unlikely 15. For women with severe preeclampsia, it is
with the recommended regimens and the levels suggested that invasive hemodynamic
do not need to be routinely measured. MgSO4, monitoring not be used routinely. (Level Ill,
is mostly excreted in the urine, Urine output Grade C)
should be closely observed and if it becomes
reduced below 20 mlJhour, the magnesium 16. For women in whom gestational
infusion should be halted.Because magnesium is hypertension, preeclampsia, or superimposed
cleared almost exclusively by renal excretion, preeclampsia is diagnosed, it is suggested that
plasma magnesium concentration is excessive if BP be monitored in the hospital or that
the glomerular filtration rate is decreased equivalent outpatient surveillance be
substantively The initial standard dose of MgS04 performed for at least 72 hours postpartum and
can be safely administered without knowledge again 7-10 days after delivery or earlier in
of renal function. Renal function is thereafter women with symptoms. (Level II. Grade C)
estimated by measuring serum creatinine, and 17. Nonsteroidal anti-inflammatory drugs
whenever it is 1.3 mg/dL or higher, only half of (NSAIDS) tend to increase the BP, therefore, for
the maintenance dose is given.MgS04 toxicity women with hypertension that persists for more
can also be assessed by clinical assessment of than 1 day postpartum, it is suggested that
the maternal deep tendon reflexes (DTRs) and these commonly used postpartum pain relief
respiratory rate. If there is loss of the DTRs and agents be replaced by other analgesics, usually
the respiratory rate falls below 12 opioid drugs. (Level Il, Grade C)
cycles/minute, the MgSO4 infusion should be

8
HYPERTENSION IN PREGNANCY
CPG

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)

9
HYPERTENSION IN PREGNANCY
CPG

VII. ECLAMPSIA 5. Nicardipine - The antihypertensive effects of


The basic objectives in the management of nicardipine are seen within 10 minutes following
eclampsia are: IV infusion, with sufficient BP reduction typically
1. maternal support of vital functions occurring within 20 minutes.
2. control of convulsions and prevention of
recurrent convulsions D. Delivery After Control of Convulsions
3. correction of maternal hypoxemia and/or
academia Continuation of pregnancy in women with
4. control of severe hypertension to a safe range eclampsia imposes a significant threat to the
5. initiate process of delivery well-being of both the mother and the fetus,
6. postpartum surveillance and necessitates termination of pregnancy.
Therefore, the final aim should be to designate
Management the time of delivery in such a fashion that both
A.. Hospitalization- required for all patients with the mother and fetus are best able to tolerate
eclampsia (Level l, Grade A) delivery while providing the fetus with the
maximum chance of extrauterine survival.
B. Control of convulsions and prevention of Cesarean section can be decided upon if:
recurrent convulsions - Parenteral magnesium I. Vaginal delivery does not appear to be easy
sulfate (MgSO4) is the drug of choice to and imminent
control convulsions and prevent recurrent 2. There is failure of progress after induction,
convulsions in eclampsia. 3. There is fetal compromise
The administration of MgSO4, requires proper
monitoring and vigilance, with particular focus VIII. CHRONIC HYPERTENSION
on the following precautions: 1. Chronic hypertension
a. Urine output of at least 30 mL or 100 mL for in pregnancy is the presence of hypertension
the past hour or 4 hours, respectively before pregnancy or before 20 weeks of
b. Presence of patellar reflex gestation. The diagnosis Of hypertension is
c. Respiratory rate of not less than 12/minute made when either the systolic blood pressure
d. Intravenous (IV) Calcium gluconate (10ml (BP) is ≥140 mmHg or the diastolic BP is 90
Of 10% solution) must be available at bedside mmHg, or both. Severe case is SBP ≥160 and
for MgSO4 toxicity DBP ≥110.
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 Recommendations
the absence of MgSO4
2. Phenytoin – no consensual dosage regimen 1. Referral to an internist - for investigation and
but dose may be varied according to patient’s management of possible secondary causes as
weight. well as for possible target organ damage. (GPP)
2. Antihypertensive therapy in severe chronic
C. Antihypertensive Therapy - Patients With hypertension - Pregnant women with chronic
severe hypertension should be started on IV hypertension with persistent systolic BP 160
antihypertensive therapy, with the following mmHg or persistent diastolic BP 105 mmHg, or
recommended: those with evidence of target organ damage,
should be given antihypertensive therapy.
1. Hydralazine (drug of choice)- IV bolus of 5 or
10mg, not recommended for drip 3. Antihypertensive therapy for mild to
moderate chronic hypertension. - Those with
2. Clonidine -IM injection of 75-150 mcg is the persistent systolic BP 160 mmHg or persistent
next recommended drug diastolic BP 105 mmHg, and with no evidence of
3. Nifedipine - if given orally at 10 or 20mg, this target organ damage, should not be routinely in
drug takes effect within 15-50 minutes. antihypertensive therapy. (Level I, Grade A)
4. Labetalol - IV bolus Of 10-20 mg as initial 4. Antihypertensive for continuous therapy in
dose. Not given in CHF and asthma chronic hypertension in pregnancy -
Methyldopa, a centrally acting alpha-2

10
HYPERTENSION IN PREGNANCY
CPG

adrenergic agonist, is the primary oral d. New onset renal insufficiency (sudden
medication recommended for chronic increase in serum creatinine)
hypertension in pregnancy. e. Cerebral or visual disturbances
5. Second line antihypertensives for continuous
therapy in chronic hypertension in pregnancy - Recommendations
Labetalol, a nonselective β-blocker with vascular 1. Where do we manage cases of chronic
alpha receptor-blocking ability, and nifedipine, a hypertension complicated by superimposed
calcium channel blocker, are second line oral preeclampsia? - The antenatal care and delivery
medications that can be used in chronic of women with chronic hypertension with
hypertension. (Level I, Grade 4) superimposed preeclampsia regardless of
gestational age should be done in facilities with
6. Antihypertensive drugs that should not be adequate maternal and neonatal intensive care
used during pregnancy - Angiotensin converting specialists and resources. (GPP)
enzyme inhibitors (ACE inhibitors) and
angiotensin receptor blockers (ARBS) should not 2. Should MgSO4, be given to women with
be given before conception and during the first chronic hypertension with superimposed
trimester of pregnancy because of evidence of preeclampsia with features? – MgSO4, therapy
teratogenicity. Likewise, they should not be is given to prevent eclampsia once there is the
used during the second and third trimesters of need, and is continued to the intrapartum or
pregnancy because of evidence of fetopathy. even postpartum period. (Level l, Grade A)

7. Antihypertensive drugs for use in urgent 3. When do you give antenatal corticosteroids? -
control of severe chronic hypertension in Antenatal steroids to enhance fetal lung
pregnancy - The parenteral form of labetalol maturity is given to those with 34 weeks
and hydralazine and the oral form of nifedipine gestational and who are being managed
are medications that can be safely used in the expectantly (Level I, Grade A)
urgent control of severe chronic hypertension. 4. When do you deliver those with chronic
The choice should be based on availability, hypertension with superimposed preeclampsia?
familiarity and experience with the use of the - Delivery is recommended when any one of
above medications. (Level I. Grade A) these conditions is present. (Uncontrolled HPN,
8. Fetal surveillance for IUGR in chronic Eclampsia, Abruptio Placenta, DIC, non-
hypertension - Serial ultrasonography to screen reassuring fetal status, and Pulmonary edema).
for IUGR is recommended. (Level II-3, Grade B) The delivery is done once the maternal
condition is stabilized regardless of gestational
9. Surveillance for fetal well-being in chronic age or completion of antenatal steroids. (Level I,
hypertension in pregnancy with IUGR - As an Grade A)
adjunct to conventional antenatal testing,
umbilical artery Doppler velocimetry is 5. When do you deliver patient’s with
recommended for cases where IUGR has been superimposed preeclampsia without severe
confirmed. (Level l, Grade A) features? - For women with chronic
hypertension with superimposed preeclampsia
10. Timing of delivery complicated by mild to without severe features, expectant
moderate chronic hypertension- In management up to 37 weeks is suggested.
uncomplicated chronic hypertension, delivery (Level II-1. Grade B).
before 38 weeks is not recommended. (Level I,
Grade A) 6. Can you do conservative management in
pregnancies complicated by chronic
hypertension with superimposed preeclampsia
2. Chronic Hypertension with Superimposed with severe features <34 weeks? - Expectant
Preeclampsia management can be offered to women with
- Chronic hypertension with superimposed chronic hypertension with superimposed
preeclampsia is defined as a sudden increase in preeclampsia with severe features before 34
BP in a pregnant woman with a previously well- weeks provided that both maternal and fetal
controlled chronic hypertension associated with conditions are stable and the patient is admitted
new onset proteinuria. A sudden increase in in a hospital capable of providing intensive
proteinuria in a chronic hypertensive woman maternal and neonatal care. (Level l, Grade A)
who already has preconceptional proteinuria is 7. Can the antihypertensives used during
also a basis for the diagnosis. pregnancy be continued during breastfeeding if
Chronic hypertension with superimposed needed for continuous BP control? - The
preeclampsia plus severe features: antihypertensives used during pregnancy can be
used and lactation if needed for continuous BP
a. Severe hypertension i.e. systolic BP ≥160 control. With the exception of diuretics, other
mmHg or diastolic BP ≥110 mmHg or both. antihypertensives not used for pregnant women
b. Thrombocytopenia (platelets 100,000fuL) can be used as well. (GPP).
c. Elevated liver transaminases (2x upper limit
of normal)

11
HYPERTENSION IN PREGNANCY
CPG

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-

12
HYPERTENSION IN PREGNANCY
CPG

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


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

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.

13
HYPERTENSION IN PREGNANCY
CPG

Management in the HELLP syndrome patient with impaired


The management of patients with HELLP liver function and an altered ability to
requires availability of neonatal and obstetric metabolize anesthetic agents. However, it does
ICU thus should receive care at tertiary care remain the anesthetic of choice in Class I and
center. Class 2 disease.

A. Initial steps - Stabilize the mother, assess F. Postpartum course - Laboratory values may
fetal condition and decided whether prompt initially worsen following delivery. The time
delivery is indicated. course of recovery from HELLP was evaluated in
a series of 158 women with the disease.
B. Timing of Delivery – if HELLP develops before Decreasing platelet counts continued until 24-48
24 weeks, termination of pregnancy is strongly hours after delivery, while serum LDH
considered. Consensus of indication for prompt concentration usually peaked 24-48 hours
delivery: postpartum. In all patients who recovered, a
a. ≥34 weeks of gestation platelet count: 100,000 was achieved
b. Presence of severe maternal disease spontaneously by the postpartum day or within
72 hours of the platelet nadir. An upward trend
c. Non-reassuring fetal status in platelet count and a downward trend in LDH
C. Platelet Transfusion - Platelet count should concentration should be seen by the
be maintained at 20,000 and 40,000 for vaginal postpartum day in the absence of complications.
and cesarean delivery, respectively. In patients
with platelet count 40,000, 4-10 units of
platelets are transfused at the time of 12-STEP TREATMENT APPROACH
intubation. Platelet transfusion is also indicated 1. Anticipate and make the diagnosis
in patients with significant bleeding or platelet 2. Assess the maternal condition
count less than 20,000 irrespective of the 3. Assess the fetal condition: deliver sooner or
intended mode of delivery. 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.

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

14

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