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Hypertension in Pregnancy

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DOI: 10.26502/aimr.0018

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Arch Intern Med Res 2020; 3(1): 010-017 DOI: 10.26502/aimr.0018

Mini-Review

Hypertension in Pregnancy

Mohammad Tinawi*

Department of Internal Medicine and Nephrology, Nephrology Specialists, Munster, IN, USA

*
Corresponding author: Mohammad Tinawi, Department of Internal Medicine and Nephrology, Nephrology
Specialists, P.C., 801 MacArthur Blvd., Ste. 400A, Munster, IN 46321, USA, E-mail: [email protected]

Received: 23 December 2019; Accepted: 04 January 2020; Published: 08 January 2020

Citation: Mohammad Tinawi. Hypertension in Pregnancy. Archives of Internal Medicine Research 3 (2020): 010-
017.

Abstract
Hypertension is commonly encountered in the course of 1. Chronic hypertension is diagnosed prior to
pregnancy. It can predate or manifest during pregnancy. pregnancy or before 20 weeks of gestation.
It requires prompt recognition and treatment. If left 2. Gestational hypertension arises after 20 weeks
untreated, hypertension in pregnancy will lead to of gestation.
significant maternal and fetal morbidity and mortality. 3. Preeclampsia is diagnosed after 20 weeks of
This mini-review will discuss the classification of gestation and can be superimposed on chronic
hypertension in pregnancy, identify treatment goals, hypertension. About 25% of women with
discuss preeclampsia in some detail and discuss chronic hypertension develop preeclampsia.
management of these disorders based on recent
guidelines. This review is intended as a quick summary 2. Definition
and a practical guide. Extensive reviews of the subject Hypertension in pregnancy is defined as systolic BP ≥
are widely available. 140 and/or diastolic BP ≥ 90. It affects 10%-15% of
pregnancies [2]. Blood pressure is preferably measured
Keywords: Hypertension; Pregnancy; Preeclampsia using automated devices. If Aneroid devices are used,
they should be regularly calibrated. Abnormal readings
1. Classification should be confirmed by repeat measurements. These
Hypertension in pregnancy is divided into three issues are detailed in American College of
categories [1]: Cardiology/American Heart Association hypertension

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Arch Intern Med Res 2020; 3 (1): 010-017 DOI: 10.26502/aimr.0018

guidelines [3]. Ideally hypertension is confirmed with gestation. Onset can be intrapartum and postpartum as
24 h ambulatory blood pressure monitoring or home well. The diagnosis is established when hypertension
monitoring. The vast majority of pregnant women have (defined as systolic BP ≥ 140 and/or diastolic BP ≥ 90
essential hypertension. Clinicians should always be on two occasions at least 4 hours apart) is associated
vigilant to the presence of secondary hypertension with proteinuria (≥ 300 mg/24 h or random urine
because failure to recognize secondary forms of protein/creatinine ratio ≥ 0.3) [1]. In order to establish a
hypertension may lead to serious complications [2]. timely diagnosis, BP measurement and urine dipstick
for protein are recommended at each prenatal visit.
3. Treatment Goals If the patient does not have proteinuria, a new onset of
The International Society for the Study of Hypertension one of the following severe features is needed [1, 4]:
in Pregnancy (ISSHP) guidelines [1] state that 1. Acute kidney injury (creatinine > 1.1 mg/dl or
antihypertensives are indicated in all of the above- doubling of serum creatinine)
mentioned three categories to maintain BP in the range 2. Elevated liver enzymes to two times the upper
of 110-140/80-85.Treatment is initiated for BP ≥ limit of normal
140/90 while urgent treatment and hospitalization are 3. Epigastric or right upper quadrant pain
indicated for BP ≥ 160/110. In contrast, The American 4. Thrombocytopenia (platelet count < 100,000 x
College of Obstetrician and Gynecologists Practice 109/L)
Bulletin [4] recommends initiating treatment for BP 5. Neurological complications including visual
≥160/110 in the absence of evidence of end organ disturbances and severe headache
damage. 6. Pulmonary edema
Severe preeclampsia is defined as systolic BP ≥ 160

4. Preeclampsia and/or diastolic BP ≥ 110 (severe BP elevation) in

Preeclampsia affects 2%-8% of pregnancies globally addition to one of the aforementioned six

and is the cause of 10% to 15% of maternal death [4]. It manifestations. In severe preeclampsia BP elevation

is also associated with increased maternal morbidity. should be confirmed within minutes (rather than 4

Preeclampsia may result in perinatal morbidity and hours) for prompt initiation of antihypertensive therapy

mortality due to intrauterine growth restriction (IUGR), [1]. A 24 h urine collection for creatinine clearance is

preterm birth and oligohydramnios. Preeclampsia is due required to evaluate kidney function in pregnancy.

to abnormal placental implantation with subsequent Equations for estimation of glomerular filtration rate

increase in anti-angiogenic factors such as soluble fms- (eGFR) such as MDRD and CKD-EPI formulae cannot

like tyrosine kinase-1 (sFlt-1) and decrease in be utilized as they underestimate GFR in pregnant

angiogenic factors such as placental growth factor women [8].

(PIGF) [5, 6]. Risk factors for preeclampsia include [7]:

nulliparity, history of chronic kidney disease, 4.1 Eclampsia

hypertension, previous episodes of preeclampsia, Eclampsia (preeclampsia + seizures) is a severe

obesity, gestational diabetes and multiple gestation complication of preeclampsia. The patient develops a

pregnancy. Preeclampsia is diagnosed after 20 weeks of new-onset tonic-clonic, multifocal or focal seizures. It

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Arch Intern Med Res 2020; 3 (1): 010-017 DOI: 10.26502/aimr.0018

carries significant morbidity and mortality. It was highly sensitive in ruling out the diagnosis
complicates about 0.1% of all pregnancies [9]. [15].

4.2 Differential diagnosis of preeclampsia 4.3 Prevention of preeclampsia

A diagnostic renal biopsy is not recommended to A randomized controlled trial in women with singleton
establish pregnancies and high risk for preeclampsia showed that
1. HELLP syndrome (Hemolysis, Elevated Liver aspirin had resulted in a lower incidence of preterm
enzymes, Low Platelets) is a severe form of preeclampsia compared to placebo. Aspirin dose was
preeclampsia characterized by right upper quadrant 150 mg daily starting at week 11-14 of gestation until
abdominal pain and elevated lactate dehydrogenase week 36 [16]. Calcium carbonate is unlikely to have a
(LDH) > 600 IU/L. It is associated with significant role in prevention of preeclampsia especially in women
morbidity and mortality [10]. Prompt delivery is with adequate calcium intake [17].
indicated.
2. Acute fatty liver of pregnancy (AFLP) is a rare 4.4 Management of preeclampsia
condition. It presents with vomiting, hypoglycemia, BP should be controlled (see below). Bedrest is
lactic acidosis, increased INR and elevated liver recommended. Delivery if feasible is the definitive
enzymes [11]. It can progress to acute kidney injury management. Women with gestational age of 37 weeks
and disseminated intravascular coagulation (DIC). or greater should be delivered. Initial evaluation should
As in HELLP syndrome prompt delivery is include a complete blood count, serum creatinine, LDH,
indicated. AFLP is attributed to abnormal fatty AST, ALT, uric acid, and urinary testing for proteinuria
acids beta-oxidation in fetal mitochondria. (preferably a 24 h urine collection). A detailed fetal and
3. Thrombotic Microangiopathies (TTP/HUS) are maternal evaluation is paramount [1, 4]. Observation
associated with high morbidity and mortality. Acute may be appropriate for women with preterm fetuses
kidney injury, hemolysis and thrombocytopenia are without the severe features mentioned above. In case of
prominent [12]. Pregnancy can trigger TTP in a observation (expectant management), evaluation of fetal
patient with ADAMTS-13 deficiency and can also growth with serial ultrasounds is indicated. Laboratory
be a trigger for acquired HUS by activating the testing is done at least weekly along with close BP
alternative complement pathway [13, 14]. A monitoring. Abnormal fetal testing and persistently
diagnostic renal biopsy is not recommended to uncontrolled severe hypertension defined as systolic BP
establish the diagnosis of preeclampsia, HELLP ≥ 160 and/or diastolic BP ≥ 110 are contraindications to
syndrome, AFLP or TTP/HUS during pregnancy. expectant management [1, 4]. Magnesium sulfate is the
Measurement of sFlt-1 and PIGF in urine or plasma drug of choice for seizure prevention and is more
may help in differentiating preeclampsia from other effective than phenytoin or diazepam. It reduces the
disorders with hypertension and proteinuria. This incidence of seizures by over 50% [18, 19]. There are
testing is not available commercially in the USA. multiple regimens. One such regimen includes a loading
PROGNOSIS study showed that a low sFlt1/PIGF dose of 6 g IV over 15-20 minutes followed by a
ratio (≤ 38) in women with preeclampsia features continuous infusion at 2 g per hour. The therapeutic

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Arch Intern Med Res 2020; 3 (1): 010-017 DOI: 10.26502/aimr.0018

range is not well defined; however, a range of 4.8-8.4 considered. Extended-release nifedipine is the most
mg/dl is reasonable [20]. Magnesium sulfate is widely used calcium channel blocker. Amlodipine has
contraindicated in patients with myasthenia gravis. been used, but the data are limited [25]. If an
Magnesium toxicity is rare except in women with intravenous agent is required labetalol and nicardipine
chronic kidney disease or acute kidney injury. are good choices. Hydralazine is less desirable because
Management includes IV calcium, discontinuation of of increased risk of maternal hypotension and maternal
magnesium sulfate and intravenous normal saline to oliguria. Nitroprusside should be avoided due to the risk
facilitate magnesium excretion. Loop diuretics may be of fetal cyanide toxicity if used for more than 4 hours
utilized as well. Hemodialysis is indicated in severe [26]. Diuretics should not be used in preeclampsia
cases [19]. because extracellular volume contraction is undesirable.
They may be continued in gestational hypertension if
4.5 Outcome of preeclampsia the patient had been taking them prior to pregnancy
Proteinuria and hypertension improve after delivery in [27]. Inhibitors of the renin-angiotensin-aldosterone
80% of women and resolve completely after 12 weeks. system (RAAS) are absolutely contraindicated. This
In 20% of women hypertension persists. In mild includes angiotensin converting enzyme (ACE)
preeclampsia the risk of chronic hypertension increases inhibitors, angiotensin receptor blockers (ARBs) and
by more than threefold, while it increases by more than direct renin inhibitors. The package insert of these
sixfold in severe preeclampsia [21, 22]. agents comes with a black box warning [28] stating that
usage during the second and third trimesters can cause
5. Drug Management of Hypertension in injury and death to the developing fetus; therefore,

Pregnancy discontinuation is indicated as soon as pregnancy is

Aggressive BP lowering in not indicated in pregnancy detected. RAAS inhibitors use in the second and third

as it impairs fetal growth and result in placental trimesters is associated with renal agenesis, pulmonary

ischemia [4]. In patients with preeclampsia BP should hypoplasia and IUGR. The evidence of fetal injury

be monitored every 4-6 hours for the first 3 days during first trimester exposure is unclear. Post-delivery

postpartum. Oral agents (Table 1) should be started first. lactating mothers may use enalapril, captopril or

If adequate control is not achieved, the patient should be quinapril because they have low concentration in breast

hospitalized for administration of intravenous agents milk. Labetalol may be continued in lactating mothers.

(Table 2). Labetalol and extended-release nifedipine are Diuretics may decrease milk production [29].

first line agents as they are safe and effective [1, 4, 23]. Spironolactone use in pregnancy is not recommended. It

Methyldopa and hydralazine may be utilized, but are is a category C medication (animal reproductive studies

associated with more frequent adverse reactions. have shown fetal adverse effects with inadequate human

Atenolol should be avoided because a study in 33 studies). Spironolactone carries a possible risk of

pregnant women showed that atenolol was associated feminization of male fetuses [30]. The Control of

with IUGR [24]. Beta-Blockers other than labetalol are Hypertension in Pregnancy Study (CHIPS) [31]

less well investigated. If labetalol cannot be used examined the effect of tight versus less-tight BP control

metoprolol, propranolol, pindolol and acebutolol may be on pregnancy complications. It enrolled approximately

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Arch Intern Med Res 2020; 3 (1): 010-017 DOI: 10.26502/aimr.0018

1000 pregnant women with office diastolic BP of 90- including maternal complication, preeclampsia, loss of
105 mmHg. Less-tight control target was 100 mmHg pregnancy or high-level neonatal care. Severe maternal
while the control target was 85 mmHg. The study hypertension (≥ 160/110) was more frequent in the less-
concluded that there was no difference between the two tight control group. Tight control was not associated
targets with regard to pregnancy complications with major fetal or neonatal risks.

Antihypertensive Dosage Potential Adverse Reactions

Methyldopa 250-750 mg twice a day Sedation, headache, hepatic impairment,
hemolytic anemia
Labetalol 200-600 mg twice a day Fatigue, bradycardia, do not use in patients
with asthma
Extended-release nifedipine 30-90 mg once daily Peripheral edema, headache, dizziness,
flushing
Hydralazine 10-100 mg two to three times daily Palpitations, tachycardia, diarrhea,
headache

Table 1: Oral Antihypertensives in Pregnancy.

Antihypertensive Dosage Potential Adverse reactions Onset of action

Labetalol 10-20 mg IV bolus followed Avoid in patients with asthma or 1-2 minutes
by infusion at 1-2 mg/min acute congestive heart failure
Nicardipine Infuse at 2.5-5 mg/h, Edema, tachycardia, headache 1-2 minutes
maximum dose: 15 mg/h
Hydralazine 5-10 mg every 2-4 h, switch to Headache, tachycardia, hypotension 10-20 minutes
PO ASAP

Table 2: Intravenous Antihypertensives in Pregnancy.

6. Secondary Causes of Hypertension in 6.1 Pheochromocytoma

Pregnancy Pheochromocytoma is a very rare cause of

Secondary hypertension should be diagnosed and hypertension during pregnancy and is associated with

treated prior to pregnancy. Clues to a secondary high morbidity and mortality [32, 33]. The diagnosis

cause of hypertension include absence of family is usually made during the second and third

history of hypertension, hypokalemia, chest pain, trimesters. Labor should be avoided by performing a

pallor, palpitations, early onset of hypertension (< 30 Cesarean section. If left undiagnosed labor and spinal

years), resistant and severe hypertension [2]. anesthesia can precipitate a severe hypertensive
crisis.

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Arch Intern Med Res 2020; 3 (1): 010-017 DOI: 10.26502/aimr.0018

6.2 Primary hyperaldosteronism  Magnesium sulfate is the preferred agent for

The diagnosis is suspected when hypokalemia seizure prevention in preeclampsia.
complicates hypertension in pregnancy [33]. Most  Secondary hypertension should be
women have adrenal adenomas. Hypokalemia is not considered in the appropriate clinical setting.
expected in pregnancy in absence of hyperemesis.
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