Chronic Hypertension in Pregnancy ACOG

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ACOG PRACTICE BULLETIN

Clinical Management Guidelines for Obstetrician–Gynecologists


NUMBER 203
Committee on Practice Bulletins—Obstetrics. This Practice Bulletin was developed by the American College of Obstetricians and
Gynecologists’ Committee on Practice Bulletins—Obstetrics in collaboration with Alex Vidaeff, MD, MPH; Jimmy Espinoza, MD,
MSc; Hyagriv Simhan, MD; and Christian M. Pettker, MD.

Chronic Hypertension in Pregnancy


Chronic hypertension is present in 0.9–1.5% of pregnant women (1) and may result in significant maternal, fetal, and
neonatal morbidity and mortality. The rate of maternal chronic hypertension increased by 67% from 2000 to 2009,
with the largest increase (87%) among African American women. This increase is largely secondary to the obesity
epidemic and increasing maternal age (1, 2). The trend is expected to continue.
The purpose of this document is to clarify the criteria used to define and diagnose chronic hypertension before or
during pregnancy, to review the effects of chronic hypertension on pregnancy and vice versa, and to appraise the
available evidence for management options. The purpose of these revised best practice recommendations is to provide
a rational approach to chronic hypertension in pregnancy based on new research data and relevant pathophysiologic
and pharmacologic considerations.

(AHA) have changed the criteria for diagnosing hyperten-


Background sion in adults (4). These recommendations include classi-
Chronic Hypertension fying blood pressure into four categories: 1) normal
Definition and Diagnosis of (systolic blood pressure less than 120 mm Hg and diastolic
Chronic Hypertension blood pressure less than 80 mm Hg); 2) elevated (systolic
blood pressure of 120–129 mm Hg and diastolic blood
Chronic hypertension in pregnancy is defined as hyper-
pressure less than 80 mm Hg); 3) stage 1 hypertension
tension diagnosed or present before pregnancy or before
(systolic blood pressure of 130–139 mm Hg or diastolic
20 weeks of gestation. Hypertension that is diagnosed for blood pressure of 80–89 mm Hg); and 4) stage 2 hyper-
the first time during pregnancy and that does not resolve tension (systolic blood pressure of 140 mm Hg or more or
in the typical postpartum period also is classified as diastolic blood pressure of 90 mm Hg or more). These
chronic hypertension (3). Traditionally, the criteria for changes were made to assist in clinical and public health
hypertension in pregnancy under this definition are a sys- decision making and reflect data to suggest modifiable
tolic blood pressure of 140 mm Hg or more, a diastolic long-term cardiovascular risk even in the elevated and
blood pressure of 90 mm Hg or more, or both. In general, stage 1 hypertension ranges (5). Importantly, the recom-
it is recommended that a diagnosis of hypertension re- mendations now suggest beginning treatment in nonpreg-
quires at least two determinations at least 4 hours apart, nant adults with risk factors for current or future
although on occasion, especially when faced with severe cardiovascular disease in patients with stage 1 hyperten-
hypertension, the diagnosis can be confirmed within sion (systolic blood pressure of 130–139 mm Hg or dia-
a shorter interval (even minutes) to facilitate timely stolic blood pressure of 80–89 mm Hg) (6). Thus, obstetric
therapy. care providers may see an increase in patients classified as
Recent recommendations from the American College hypertensive based on these ACC/AHA definitions. For
of Cardiology (ACC) and the American Heart Association these patients, it is reasonable to continue to manage the

e26 VOL. 133, NO. 1, JANUARY 2019 OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
patient in pregnancy as chronically hypertensive as spec- authors of the study concluded that hypertension arising in
ified in this guideline. The effect of the ACC/AHA the first 20 weeks of pregnancy may not necessarily indi-
changes on the diagnosis of hypertension in women of cate chronic hypertension. Indeed, it defies logic to think
reproductive age, on pregnancy outcomes, and on the use that one point in time (eg, 20 weeks of gestation) may
of health care resources for pregnant women is unknown. always and reliably differentiate disease preceding fertiliza-
For instance, it is not clear what should be done with tion from a pregnancy-related condition. The 20-week con-
a patient without a prior diagnosis of chronic hypertension vention should not be used dogmatically, but rather for
who has blood pressures in the stage 1 hypertension range orientation while maintaining clinical judgment.
(systolic blood pressure of 130–139 mm Hg or diastolic To establish a diagnosis of chronic hypertension, it is
blood pressure of 80–89 mm Hg) before 20 weeks of ideal to have knowledge of prepregnancy blood pressure
gestation. Based on the recommendations in this Practice values. However, for many women, prepregnancy blood
Bulletin this range would not require initiation of antihy- pressures are not known. Moreover, the prevalence of
pertensive medication. However, a conservative approach hypertension is underestimated when based on self-
of a higher degree of observation may be warranted. A reporting as opposed to documented measurements or
secondary analysis of a randomized trial of low-dose aspi- physician diagnosis (9). In addition, previously undiag-
rin in the prevention of preeclampsia looked at outcomes nosed chronic hypertension may be masked because of
in the placebo patients who at the time were diagnosed as the pregnancy-related hemodynamic changes in the first
normotensive, but according to this new criterion would and second trimesters. The normal physiologic decrease
have stage 1 chronic hypertension. These patients had
in systemic vascular resistance leads to a decrease in
a higher risk of preeclampsia, gestational diabetes, and
blood pressure, with its nadir at 16–18 weeks of gesta-
indicated preterm birth. However, aspirin, compared with
tion, followed by return to prepregnancy levels by the
placebo, did not appear to lower the risk of preeclampsia
among patients in the stage 1 hypertension group (7). The third trimester. The 30% decrease in systemic vascular
uncertainty of the new approach to hypertension recom- resistance that normally occurs early in pregnancy typi-
mended by the ACA and AHA as applied to the care of cally generates a decrease in blood pressure of 10% as
pregnant women should be an active area of investigation. early as 7 weeks of gestation (and even more by mid-
Using the ACC/AHA definition to determine chronic pregnancy), which results in a potential blood pressure
hypertension for pregnant women presents a lower thresh- normalization in the absence of any treatment. The
old for diagnosis than traditionally used. Some borderline decrease in diastolic blood pressure (by as much as
and possibly inconsequential cases of blood pressure 20 mm Hg) is more marked than the decrease in systolic
elevation, particularly in patients diagnosed with chronic blood pressure. Because blood pressure usually returns to
hypertension during pregnancy before 20 weeks of gesta- prepregnancy levels in the third trimester, diagnostic con-
tion, may mislabel some women as abnormal. In the fusion is possible, and chronic hypertension may be mis-
absence of a preexisting diagnosis, detection of hyperten- labeled as gestational hypertension or preeclampsia in
sion at any time before 20 weeks of gestation is assumed to this setting. Moreover, approximately 11% of women
indicate chronic hypertension antedating the pregnancy or, with chronic hypertension have proteinuria (more than
much more rarely, is associated with fetoplacental abnor- 300 mg/day) at baseline (10) because of hypertension-
malities such as hydatidiform mole. On the other hand, related nephrosclerosis or, less frequently, undiagnosed
hypertension detected after 20 weeks of gestation typically chronic kidney disease. Therefore, the distinction
is indicative of preeclampsia or gestational hypertension if between chronic hypertension and either gestational
the woman was normotensive before 20 weeks of gestation.
hypertension or preeclampsia sometimes can be made
The approach of using more conservative thresholds, like
only in retrospect, especially among women who initiate
those of the ACC/AHA guidelines, with higher sensitivity
prenatal care beyond 20 weeks gestation. It has been
admittedly errs on the side of caution. The assumption that
the 20-week mark always can discriminate chronic hyper- suggested that hypertension persisting longer than 12
tension from pregnancy-related hypertension is not well weeks after delivery may be retrospectively reclassified
substantiated by scientific data. For example, a retrospective as chronic. However, the time required for resolution of
cohort study found that 46 of 119 (39%) women with pregnancy-related hypertension has not been clearly es-
a history of obstetric complications and normal blood tablished. For example, a prospective cohort study of 205
pressure before pregnancy (as indicated on blood pressure preeclamptic women in the Netherlands found that 39%
recordings before and during pregnancy) developed non- still had hypertension 12 weeks after delivery, and in
proteinuric gestational hypertension before 20 weeks of 50% of these women it took up to 2 years for blood
gestation that resolved in the postpartum period (8). The pressure to normalize (11).

VOL. 133, NO. 1, JANUARY 2019 Practice Bulletin Chronic Hypertension in Pregnancy e27

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Types of Chronic Hypertension is seated with legs uncrossed and back supported. No
It is estimated that chronic hypertension antedating caffeine or tobacco should have been used for at least
pregnancy is essential (ie, of unknown cause) in more 30 minutes before measurement, because these can
than 86–89% of cases of hypertension and secondary (ie, temporarily elevate blood pressure. An appropriate-
related to underlying renal, endocrine, or vascular con- sized cuff (eg, one with a length 1.5 times the upper
ditions) in 11–14% of cases of hypertension (1). A thor- arm circumference or a cuff with a bladder that encircles
ough history and physical examination are crucial to at least 80% of the arm and a width of at least 40% of arm
detect the rarer secondary forms of hypertension. To help circumference) positioned at the level of the heart to
in defining either the hypertensive mechanism or the ensure accurate readings should be used. Appropriate
extent of end-organ damage, directed tests, such as serum cuff sizes for specific arm circumferences are the
electrolytes (specifically potassium), blood urea nitrogen, following:
serum creatinine, a complete blood count, liver function c For an arm circumference of 22226 cm, the cuff
tests, a urinalysis, a toxicology screen, or an electrocar- should be small adult size: 12 3 22 cm.
diogram, should be obtained as appropriate. c For an arm circumference of 27234 cm, the cuff
Hypertension in pregnancy also is classified as should be adult size: 16 3 30 cm.
severe if at or above cutoff points of 160 mm Hg for c For an arm circumference of 35244 cm, the cuff
systolic blood pressure or 110 mm Hg for diastolic blood should be large adult size: 16 3 36 cm.
pressure, or both (Table 1). Prior publications have sug- c For an arm circumference of 45252 cm, the cuff
gested a diastolic cutoff of 105 mm Hg based on safety should be adult thigh size: 16 3 42 cm.
concerns but for consistency and based on the best avail-
able evidence the diastolic cutoff of 110 mm Hg is rec- Blood pressure cuffs that are too small will result in
ommended. At least two blood pressure readings at or an overestimation of actual blood pressure, and an
above the cutoffs of 160 mm Hg (systolic) or 110 mm Hg unsupported back, crossed legs, or unsupported arm
(diastolic), measured 4 hours apart, are necessary to con- can cause small overestimations as well. If blood
sider the hypertension diagnosis as severe. However, pressure must be taken in a recumbent position, the
antihypertensive treatment should not be delayed just patient should be placed in a left lateral decubitus
for the sake of confirming the nomenclature for the type position and the cuff should be at the level of the right
of hypertension, and the initiation and effectiveness of atrium (12). These details represent the standard for
antihypertensive therapy should be considered when blood pressure assessment. Abnormal values not taken
classifying the degree of hypertension. In these cases, in this manner are sometimes overestimated and, thus,
the diagnosis may be confirmed within a shorter interval repeat assessment using the best methods is advisable.
(even minutes) to facilitate timely therapy.
Chronic Hypertension With
Measuring Blood Pressure Superimposed Preeclampsia
The blood pressure levels that meet the definition criteria Preeclampsia is considered superimposed when it com-
should be documented on repeat readings only after the plicates preexisting chronic hypertension. Up to 20–50%
patient has rested (preferably for 10 minutes or more) and of women with chronic hypertension may develop

Table 1. American College of Obstetricians and Gynecologists Definitions of Hypertensive


Disorders

Disorder Definition

Hypertension in pregnancy Systolic blood pressure $140 mm Hg or diastolic BP $90 mm Hg, or both,
measured on two occasions at least 4 hours apart
Severe-range hypertension Systolic blood pressure $160 mm Hg or diastolic BP $110 mm Hg, or both,
measured on two occasions at least 4 hours apart
Chronic hypertension Hypertension diagnosed or present before pregnancy or before 20 weeks
of gestation; or hypertension that is diagnosed for the first time during
pregnancy and that does not resolve it the postpartum period
Chronic hypertension with Preeclampsia in a woman with a history of hypertension before pregnancy
superimposed preeclampsia or before 20 weeks of gestation

e28 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
superimposed preeclampsia, an incidence five times or Monitoring Blood Pressure
more than that of pregnant women without hypertension Good clinical practice dictates increased monitoring for
(10, 13, 14). In women with end-organ disease or sec- women with elevated blood pressure especially in the
ondary hypertension, the rate of superimposed pre- second half of pregnancy. Although out-of-office and
eclampsia has been reported to be as high as 75% (15– self-monitoring of blood pressure has not been evaluated
18). In patients with chronic hypertension, preeclampsia in pregnant women with hypertension, the literature
tends to have an earlier onset and to be more severe, and examining nonpregnant women with hypertension sug-
the prognosis for the woman and her fetus is worse than gest that it is safe to use in both populations. Presumed
in either condition alone (10, 15). There are currently no advantages of out-of-office and self-monitoring include
useful tools for predicting superimposed preeclampsia, patient convenience, increased therapeutic adherence,
but the risk of superimposed preeclampsia is higher in confirmation of white coat hypertension, and assistance
women who are African American, obese, smoke, have with adjusting medications when there is uncertainty.
had hypertension for 4 years or more, have a diastolic However, many home blood pressure devices are sold
blood pressure higher than 100 mm Hg at baseline, and without formal validation of accuracy (22). For example,
have a history of preeclampsia (10, 19). several reports have shown that 25–70% of tested blood
Superimposed preeclampsia is not always easy to pressure devices were not accurate to within 5 mm Hg,
diagnose and is often a diagnosis of exclusion. A sudden a degree of blood pressure difference considered to be
increase in baseline hypertension or a sudden increase in clinically important (23, 24). Procedures for the use of
proteinuria (above the threshold for normal or a clear home blood pressure monitoring are available and
change from baseline) should prompt assessment for emphasize patient training, use of appropriately validated
a possible diagnosis of superimposed preeclampsia and devices, and clear instructions (4). It may be useful to
consideration for subspecialty (eg, maternal–fetal medicine) have a patient bring in her home monitor to compare
referral. However, it is often difficult to distinguish between against measurements done in the office. Home monitor-
worsening of chronic hypertension and chronic hyperten- ing may reduce the frequency of office visits in cases
sion with superimposed preeclampsia. New onset of with marginal blood pressure control.
thrombocytopenia may be helpful because—in contrast to
blood pressure elevation and proteinuria—platelet activa- Effects of Chronic Hypertension
tion, aggregation, and consumption are not present with
on Pregnancy
gestational or chronic hypertension. As with thrombocyto-
penia, a sudden increase in liver enzymes to abnormal Maternal Risks
levels or the sudden development of symptoms suggestive A population study of nearly 30,000 pregnant women
of preeclampsia should point to the diagnosis of super- with chronic hypertension demonstrated that maternal
imposed preeclampsia. Elevated uric acid levels may be mortality and the risk of cerebrovascular accidents,
helpful in cases of diagnostic uncertainty as well (20). On pulmonary edema, or renal failure were about fivefold
the other hand, a thorough evaluation may detect specific to sixfold higher than in normotensive pregnant women
circumstances indicative of chronic hypertension aggrava- (16). However, the absolute risk of mortality and major
tion (eg, cocaine or methamphetamine use or nonadherence maternal morbidity is low in developed countries, and
with treatment) rather than superimposed preeclampsia. most women with mild essential hypertension will have
uncomplicated gestations (25). Only in cases of severe,
White Coat Hypertension uncontrolled hypertension does the risk of maternal com-
White coat hypertension, defined as elevated blood pressure plications markedly increase (13).
primarily in the presence of health care providers, may Accelerated hypertension with resultant end-organ
damage (heart, brain, kidneys) is extremely uncommon.
account for up to 15% of individuals with office hyperten-
The diagnosis of superimposed preeclampsia is much
sion, although the exact prevalence in pregnancy is not
more likely when a sudden exacerbation of hypertension,
known. It must be emphasized that even white coat hyper-
typically with end-organ dysfunction, develops after 20
tension should not be considered entirely benign, because weeks of gestation requiring an acute escalation of
8% and 40% of such cases will progress to preeclampsia antihypertensive therapies.
and gestational hypertension, respectively, later in preg- Chronic hypertension is associated with an increased
nancy (21). For women with suspected white coat hyper- risk of gestational diabetes, possibly as a consequence of
tension, the use of ambulatory blood pressure monitoring common risk factors (such as obesity) and shared
may be beneficial to confirm the diagnosis and to assist pathogenic context (such as increased insulin resistance,
with decisions for initiation of antihypertensive therapy. chronic inflammation, and endothelial dysfunction) (17,

VOL. 133, NO. 1, JANUARY 2019 Practice Bulletin Chronic Hypertension in Pregnancy e29

Copyright ª by the American College of Obstetricians


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26, 27). In a prospective cohort study, the incidence of noted to be lower than in pregnancies not complicated by
gestational diabetes was 8.1% in women with chronic chronic hypertension (a median of 28 weeks of gestation
hypertension compared with 2.3% in those without versus 35 weeks of gestation, respectively) (28).
chronic hypertension (adjusted odds ratio [AOR] 1.6; The incidence of these adverse perinatal effects
95% CI, 1.27–2.05) (28). appears to be related to the duration and severity of
In addition, compared with normotensive women, chronic hypertension as possible surrogates for end-organ
those with uncomplicated chronic hypertension have damage. Consequently, the rate of fetal adverse effects
a 1.8-fold increased risk of planned cesarean delivery before may be correlated with factors such as proteinuria at
labor and twice the risk of postpartum hemorrhage (18, 28). baseline or maternal cardiac dysfunction (10, 33). Women
with severe hypertension, end-organ disease, or secondary
Fetal Risks hypertension represent the highest risk category, in which
A large body of evidence indicates that chronic hypertension the risk of fetal growth restriction increases to 25–40%,
in pregnancy is associated with poorer perinatal outcomes. A preterm delivery to 67%, placental abruption to 8–20%,
systematic review of 55 studies demonstrated that the pooled and perinatal death to 11% (10, 13, 34–36).
incidence for low birth weight was approximately 17%, and In the setting of superimposed preeclampsia, higher
the pooled incidence for preterm delivery was 28% (29). rates of adverse maternal and fetal outcomes can be
The increase in preterm delivery appears to be ascribed to expected. The risk of preterm delivery and placental
indicated preterm deliveries, without an increase in sponta- abruption are further increased (16), and the risk of fetal
neous preterm deliveries, according to a prospective cohort growth restriction has been reported to be as high as 50%
study that included 1,417 pregnant women with chronic (15). The relative risk of perinatal mortality is 3.6 in women
hypertension (28). In the same cohort, the incidence of fetal with superimposed preeclampsia compared with those with
growth restriction was twice as high in pregnant women uncomplicated chronic hypertension (34).
with chronic hypertension compared with those without Limited evidence is emerging that patients with
chronic hypertension (30). chronic hypertension may be at higher risk of fetal
The perinatal mortality rate reported with maternal congenital malformations. In a systematic review of 16
chronic hypertension is 2–4 times higher than that of the observational studies, a higher relative risk of congenital
general population (31), and the increased risk of stillbirth heart disease of 1.4 (95% CI, 1.221.7) and 2.0 (95% CI,
or neonatal death appears to be independent of other pos- 1.522.7) was found among the offspring of women with
sible contributors such as superimposed preeclampsia, fetal both untreated and treated chronic hypertension, respec-
growth restriction, or gestational diabetes (32). In a Swedish tively (37). The specific mechanism involved is unclear,
population study, the risk of placental abruption was re- but it does not appear to be simply because of a terato-
ported as 1.1% in women with chronic hypertension genic effect from medication. The authors of a case–
(AOR 2.3; 95% CI, 1.6–3.4) compared with controls with- control study based on registry data confirmed the
out hypertension (17). The gestational age at stillbirth in above findings supporting the hypothesis that physio-
pregnancies complicated by chronic hypertension has been logical changes early in pregnancy among women with

Box 1. Risks of Chronic Hypertension in Pregnancy


Maternal Fetal and Neonatal
 Death  Stillbirth or perinatal death
 Stroke  Growth restriction
 Pulmonary edema  Preterm birth
 Renal insufficiency and failure  Congenital anomalies (eg, heart defects, hypospadias, esophageal atresia)
 Myocardial infarction
 Preeclampsia
 Placental abruption
 Cesarean delivery
 Postpartum hemorrhage
 Gestational diabetes

e30 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians


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chronic hypertension may play a role in the etiology of
cardiac septal defects, hypospadias, and esophageal Box 2. Tests for Baseline Evaluation for
atresia (38). The main risks of chronic hypertension in Chronic Hypertension in Pregnancy
pregnancy are listed in Box 1.
Serum aspartate aminotransferase and alanine
Clinical Considerations aminotransferase

and Recommendations Serum creatinine


Serum electrolytes (specifically potassium)
< What considerations are important for prepregnancy Blood urea nitrogen
counseling in patients with chronic hypertension?
Complete blood count
A woman with chronic hypertension should be Spot urine protein/creatinine ratio or 24-hour urine
evaluated prepregnancy to identify possible end-organ for total protein and creatinine (to calculate creati-
involvement, to consider evaluation for secondary hyper- nine clearance) as appropriate
tension, and for the optimization of maternal comorbidities Electrocardiogram or echocardiogram as appropriate
(eg, obesity, diabetes) before pregnancy. Women with
modifiable risk factors, such as obesity and poor glycemic
control, may benefit from counseling on weight loss, diet,
and lifestyle modifications (39–41). Women with chronic pregnancy. Although uric acid has historically been
hypertension should have their blood pressure optimized among these tests and may be helpful in cases of diag-
before pregnancy and should avoid excessive sodium and nostic uncertainty, it is no longer a recommended routine
caffeine intake as well as smoking. Prepregnancy counsel- baseline test.
ing should include an explanation of the risks associated Because the kidneys are usually the first end-organ
with chronic hypertension in pregnancy (Box 1). to be affected by chronic hypertension, baseline renal
The medication review should place special emphasis function assessment commonly includes serum creati-
on agents to be avoided, in particular angiotensin- nine, a spot urine protein-to-creatinine ratio, and, if
converting enzyme inhibitors and angiotensin receptor needed, a 24-hour urinary collection for total protein
blockers. These drugs, active against renin-dependent and creatinine clearance. The spot urine protein-to-
vasoconstriction, represent the first line of treatment in creatinine ratio can be used effectively as a screening
nonpregnant patients with decompensated heart failure, test to rule out proteinuria and is a sensible first step. For
pulmonary edema, coronary ischemia, proteinuric renal patients with borderline or abnormal urine protein-to-
disease, and diabetes (for renal protection). However, they creatinine ratios or serum creatinine values, a 24-hour
are fetopathic, and exposure in the first trimester should be urine collection is recommended. A spot urine protein-to-
avoided if possible because of the risk of malformations creatinine ratio of less than 0.15 safely indicates a level
(eg, renal dysgenesis, calvarial hypoplasia) and fetal of proteinuria less than 300 mg for a 24-hour sample and,
growth restriction (42). However, there may be cases of in the absence of an abnormality in serum creatinine,
primary or secondary hypertension in pregnancy refractory likely does not warrant further evaluation with a 24-hour
to other antihypertensive medications and, thus, controlled urine collection, unless there is a need to assess creatinine
only by angiotensin-converting enzyme inhibitors. When clearance. One systematic review from 2008 found that
angiotensin-converting enzyme inhibitor therapy is being protein-to-creatinine ratio cutoffs of 0.13–0.15 had sen-
considered in pregnancy, a maternal–fetal medicine sub- sitivities ranging from 90% to 99% to rule out significant
specialty referral is advised. proteinuria of 300 mg or more (44). A more recent meta-
analysis demonstrated sensitivities of 88% (95% CI,
< Which clinical tests are useful in the initial evaluation 86293%) for a protein-to-creatinine ratio cutoff of 0.13
of a pregnant woman with chronic hypertension? and 88% (95% CI, 85292%) for a cutoff of 0.15 to
Specific testing before or at the time of presenting detect 300 mg or more of protein in a 24-hour urine
for pregnancy care is used to detect possible end-organ sample (45).
involvement. This baseline evaluation (Box 2) may be There is a relationship between the degree of renal
influenced by the physiologic changes of pregnancy seen impairment and physiologic adaptation to pregnancy,
as early as the early first trimester and underscores the indicating why assessment of creatinine clearance may be
importance of prepregnancy testing (43). However, if helpful in some cases. With mild renal impairment
testing was not done before pregnancy, it should be per- (serum creatinine between 0.9 mg/dL and 1.4 mg/dL),
formed at entry to prenatal care. Box 2 summarizes the there is normal intravascular volume expansion and an
tests for baseline evaluation for chronic hypertension in incremental increase in creatinine clearance although

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Copyright ª by the American College of Obstetricians


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somewhat less than in normal pregnancy (46). With mod- ger than 30 years) warrants consideration and diagnostic
erate impairment (serum creatinine from 1.4 mg/dL to workup for secondary (and potentially curable) hyperten-
2.4–2.8 mg/dL), only 50% of women will have the ex- sion unless such evaluations were previously performed
pected increase in creatinine clearance despite a normal (4). A strong family history of kidney disease also may
blood volume expansion. With severe impairment (serum indicate a renal etiology for secondary hypertension.
creatinine more than 2.4–2.8 mg/dL), there is a markedly Other signs and symptoms, listed in Box 3, also suggest
attenuated increase in blood volume and no increase in secondary hypertension (4). When evaluation for second-
creatinine clearance (47). Knowledge of impaired creat- ary hypertension is considered, the work-up should be
inine clearance can assist in managing complications performed in consultation with a maternal–fetal medi-
related to changes in normal physiology. Further, patients cine subspecialist and those in the appropriate medical
with impaired creatinine clearance and elevated serum subspecialty (such as cardiology, nephrology, endocri-
creatinine levels are at risk of worsening of their renal nology, or pulmonology). Given the complexity and
disease during pregnancy and, thus, serial assessment is variability in the recommended strategies for diagnosing
indicated. secondary hypertension, referral to a physician with
Assessment of kidney function by serum and urinary expertise in treating hypertension is suggested for the
components can assist counseling and management work-up of women with features suggestive of secondary
through pregnancy. Renal dysfunction, when detected, hypertension.
indicates an increased risk of adverse pregnancy out-
< What treatments should be used for pregnant women
comes. Baseline proteinuria in women with chronic with chronic hypertension, and what are the goals of
hypertension significantly increases the risk of super- treatment?
imposed preeclampsia, preterm delivery, fetal growth
restriction, and neonatal admission to intensive care (10,
33). Furthermore, a normal baseline renal function
Control of Chronic Hypertension
assessment, including the absence of proteinuria, will Controversy exists over the potential benefits and harms
permit subsequent comparisons and will assist in estab- of treatment with antihypertensive drugs during preg-
lishing the diagnosis of superimposed preeclampsia if nancy. Because of the underlying physiology of preg-
suspected later in pregnancy. nancy as well as fetal considerations, the
Women who have had poorly controlled hyperten- antihypertensive protocols used for nonpregnant individ-
sion for more than 4 years or those suspected of having uals cannot be extrapolated to pregnant women. The
long-standing hypertension based on age (older than 30 precise blood pressure level at which antihypertensive
years) are more likely to have cardiac hypertrophic therapy is indicated during pregnancy in women with
changes, cardiomegaly, and ischemic heart disease and chronic hypertension continues to be debated. In non-
are candidates for additional diagnostic testing. Detecting pregnant adults, therapy is universally recommended at
these problems is important for risk mitigation in a blood pressure of 140/90 mm Hg or more based on
pregnancy, childbirth, and the postpartum period. Good therapeutic benefit (eg, decreased incidence of stroke,
clinical practice suggests assessing cardiac status in myocardial infarction, and heart failure) demonstrated in
women with long-standing hypertension, specifically left large clinical trials with long-term blood pressure control
ventricular function, with electrocardiography as an (4). Patients with blood pressures of 130–139/80–89 mm
acceptable first-line test. Patients with extenuating risk Hg and other cardiovascular morbidities and risk factors
factors or abnormal electrocardiography should be eval- may benefit from treatment as well (4). Few clinical trials
uated with echocardiography. on this topic have been conducted in pregnancy and the
evidence is limited. Most of the available studies
< When is evaluation for secondary hypertension included women with chronic hypertension and women
appropriate, and what is that evaluation? with pregnancy-related hypertension, making the inter-
In general, patients with primary (essential) hyper- pretation of the results less specific (48). Moreover, their
tension demonstrate gradual increases in blood pressure design is variable, with antihypertensive drugs being
over time (months to years), lifestyle factors favoring compared to one another, to a placebo, or to no therapy.
higher blood pressures (obesity, poor diet, lack of Demonstrated maternal and perinatal benefits outweigh-
physical exercise, smoking, or excessive alcohol use), ing the theoretical adverse maternal, fetal, and neonatal
or a family history (Box 3). Secondary hypertension de- risks are needed to justify the use of antihypertensive
scribes the 10% of adult patients with hypertension due therapy during pregnancy at the same blood pressure
to a specific and remediable cause (4). Hypertension threshold as in nonpregnant adults. The benefit of blood
resistant to treatment or diagnosed at a young age (youn- pressure treatment for the pregnant woman to achieve

e32 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

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Box 3. Historical Features Favoring Hypertension Cause

Primary Hypertension Secondary Hypertension


 Gradual increase in BP, with slow rate of rise in BP  BP lability, episodic pallor, and dizziness
(pheochromocytoma)
 Lifestyle factors that favor higher BP (eg, weight  Snoring or hypersomnolence (obstructive sleep
gain, high-sodium diet, decreased physical activity, apnea)
job change entailing increased travel, excessive  Muscle cramps or weakness (hypokalemia from
consumption of alcohol) primary aldosteronism or secondary aldosteronism
due to renovascular disease)
 Family history of hypertension  Weight loss, palpitations, heat intolerance
(hyperthyroidism)
 Edema, fatigue, frequent urination (kidney disease
or failure)
 History of coarctation repair (residual hypertension
associated with coarctation)
 Central obesity, facial rounding, easy bruisability
(Cushing syndrome)
 Medication or substance use (eg, alcohol, NSAIDS,
cocaine, amphetamines)
 Absence of family history of hypertension

Abbreviations: BP, blood pressure; NSAIDs, nonsteroidal antiinflammatory drugs.


Reprinted from: Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/
AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of
high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical
Practice Guidelines [published erratum appears in J Am Coll Cardiol 2018;71:2275-9]. J Am Coll Cardiol 2018;71:e127–248.

targets that are recommended for nonpregnant individu- 85 mm Hg) in 987 pregnant women, 75% of whom
als may not be apparent during the short time frame of had chronic hypertension, reached similar conclusions
puerperal treatment (13). (48). Tight control of hypertension conferred no ben-
A 2014 Cochrane systematic review of 49 trials efit to the fetus and had only marginal effects for the
(4,723 women) concluded that treatment of mild-to- woman, namely reduced frequency of progression to
moderate hypertension reduced the risk of developing severe hypertension. A large multicenter, randomized
severe hypertension but had no effect on the incidence study in the United States to evaluate whether a blood
of preeclampsia, preterm birth, fetal death, fetal pressure treatment strategy during pregnancy aiming
growth restriction, or any other measured outcome to achieve targets that are recommended for nonpreg-
(49). Notably, the theoretical concern of fetal harm nant reproductive-aged adults (less than 140/90 mm
(primarily growth restriction) resulting from possible Hg) is safe and effective when compared with no treat-
impairment of the uteroplacental blood flow could not ment (unless hypertension is severe), is currently
be verified in this systematic review. However, in the ongoing. In the absence of clear evidence supporting
absence of any improvement in perinatal outcomes, the use of antihypertensive therapy for lower blood
the authors concluded that it remains unclear whether pressures, initiation of antihypertensive therapy is rec-
antihypertensive drug therapy for mild-to-moderate ommended for persistent chronic hypertension when
hypertension during pregnancy is worthwhile. The systolic pressure is 160 mm Hg or more, diastolic
2015 CHIPS trial, an international randomized con- pressure is 110 mm Hg or more, or both. In the setting
trolled trial comparing less tight control (ie, target of comorbidities or underlying impaired renal func-
diastolic blood pressure below 100 mm Hg) to tight tion, treating at lower blood pressure thresholds may
control (ie, target diastolic blood pressure below be appropriate.

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Severe elevation in blood pressure may be associ- pregnant woman. There is also the practical aspect
ated with acute maternal cerebrovascular and cardiac requiring close monitoring of blood pressure if medica-
events; however, the precise blood pressure level at tion is withdrawn. Reductions or discontinuations of
which the risk of such adverse events increases is not therapy in these cases should be countered with appro-
known and is likely dependent on comorbidities and priate surveillance to ensure the patient does not develop
other factors such as the rate of blood pressure increase. blood pressures that do require treatment. Drugs contra-
A Cochrane systematic review, including 35 trials (3,573 indicated in pregnancy should be promptly replaced with
women), evaluating treatment for severe hypertension other antihypertensive agents and subsequent therapy
during pregnancy provided only limited evidence for adjustments should be made based on clinical findings.
women with chronic hypertension as they were generally There also are limited data to address the ideal target
excluded from the individual studies and, when they blood pressure for a pregnant woman receiving therapy
were included, no subgroup analyses were reported (50). for chronic hypertension in order to improve maternal
Future placebo-controlled trials addressing treatment of and perinatal outcomes. Overly aggressive blood pres-
severe hypertension in pregnancy are unlikely and may sure lowering is discouraged because of concerns that
not be recommended given ethical considerations. There- uteroplacental blood flow may be compromised. It is
fore, recommendations for treating women with chronic recommended to maintain blood pressure levels for
hypertension in the severe range (ie, systolic blood pres- pregnant women with chronic hypertension treated with
sure of 160 mm Hg or more or diastolic blood pressure of antihypertensive medications at or above 120 mm Hg but
110 mm Hg or more) are based on indirect evidence from below 160 mm Hg systolic and at or above 80 mm Hg
treatment of preeclampsia and extrapolation of national but below 110 mm Hg diastolic. For women with
guidelines for nonpregnant adults (51, 52). In women comorbid conditions, such as diabetes or renal disease,
with evidence of end-organ damage (such as left ventric- blood pressure goals should be lower, as noted pre-
ular hypertrophy or renal insufficiency) or severe throm- viously, and optimal management can be achieved in
bocytopenia, antihypertensive treatment is recommended consultation with other subspecialties.
at even lower thresholds (eg, systolic blood pressure of When antihypertensive therapy is used during preg-
150 mm Hg and diastolic blood pressure of 100 mm Hg) nancy, an important consideration is the context of therapy,
to reduce the risks of further end-organ damage or hem- which is either 1) chronic treatment to lower blood pressure
orrhagic stroke (53). to maintenance levels, sometimes slowly during 24–48
There are minimal data to guide decisions regarding hours often in the outpatient setting, or 2) acute lowering
continuing or discontinuing therapy for women with of critical hypertension in the hospital setting.
chronic hypertension with blood pressures of less than For chronic maintenance treatment, the oral agents
160 mm Hg systolic or less than 110 mm Hg diastolic, or listed in Table 2 can be considered alone or in combination.
well-controlled blood pressure, who were receiving The table lists the most commonly used medications in
antihypertensive medication before pregnancy. Because pregnancy and is not meant to be comprehensive. For the
treatment was initiated before the pregnancy with the long-term treatment of pregnant women who require phar-
understanding that it offers long-term health benefits, macologic therapy, labetalol or nifedipine are reasonable
some question whether the lack of short-term benefits options and are recommended above all other antihyperten-
noted with treatment during pregnancy are a reasonable sive drugs. The use of angiotensin-converting-enzyme in-
argument for discontinuation of treatment. Two case– hibitors, angiotensin receptor blockers, renin inhibitors,
control studies of women in whom medication was and mineralocorticoid receptor antagonists is generally not
reduced or stopped early in pregnancy detected no recommended. Methyldopa is generally less favored
increase in preeclampsia, placental abruption, or perinatal because it appears to be less effective compared with other
death (10, 54). However, a prospective observational agents (49) and because of adverse effects. Diuretics, like
study, including 222 women with mild chronic hyper- hydrochlorothiazide, generally are considered second-line
tension, found that although discontinuation of treatment agents for the treatment of hypertension in pregnancy
had no effect on the incidence of preeclampsia, fetal (56). Theoretical concern has been raised regarding the
growth restriction, or perinatal death, there was a signif- potential for diuretics to cause intravascular volume deple-
icantly higher occurrence of severe hypertension, pla- tion and thereby lead to fetal growth restriction or oligohy-
cental abruption, preterm delivery, and neonatal intensive dramnios; however, this concern is not supported based on
care unit admissions in the group that discontinued data from a meta-analysis of nine randomized trials as well
treatment (55). With such mixed and limited information, as a systematic review of diuretics for the prevention of
the decision to continue or discontinue must be individ- preeclampsia (57, 58). Other agents such as clonidine and
ualized and guided by an informed discussion with the prazosin have been used but should only be considered with

e34 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

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Unauthorized reproduction of this article is prohibited.
Table 2. Common Oral Antihypertensive Agents in Pregnancy

Drug Dosage Comments

Labetalol 200–2,400 mg/d orally in two to three Potential bronchoconstrictive effects.


divided doses. Commonly initiated at Avoid in women with asthma, preexisting
1002200 mg twice daily myocardial disease, decompensated cardiac
function, and heart block and bradycardia.
Nifedipine 30–120 mg/d orally of an extended-release Do not use sublingual form.
preparation. Commonly initiated at 30260 Immediate-release formulation should
mg once daily (extended-release) generally be reserved for control of severe,
acutely elevated blood pressures in
hospitalized patients. Should be avoided in
tachycardia.

Methyldopa 500–3,000 mg/d orally in two to four Safety data up to 7 years of age in offspring.
divided doses. Commonly initiated at 250 May not be as effective as other
mg twice or three times daily medications, especially in control of severe
hypertension. Use limited by side effect
profile (sedation, depression, dizziness).

Hydrochlorothiazide 12.5–50 mg daily Second-line or third-line agent

appropriate input from maternal–fetal medicine and cardi- pregnancy excluded women with chronic hypertension or
ology subspecialists. Atenolol, a b-blocker, is not recom- previous antihypertensive therapy, the available evidence
mended in pregnancy because of the risk of growth is inadequate to demonstrate a therapeutic advantage of
restriction and low birth weight (59). any medication over another. Therefore, drug selection
should be individualized depending on potential adverse
Control of Acute-Onset Severe- effects and contraindications. Because of the unique
Range Hypertension physiologic and fetal considerations of pregnancy, the
Because most existing randomized controlled trials of antihypertensive protocols used for nonpregnant individ-
acute treatment of severe-range blood pressure during uals cannot be extrapolated simply to pregnant women.

Table 3. Antihypertensive Agents Used for Urgent Blood Pressure Control in Pregnancy

Drug Dosage Comments Onset of Action

Labetalol 10–20 mg IV, then 20–80 mg every Tachycardia is less common and 1–2 minutes
10–30 minutes to a maximum cumu- fewer adverse effects than other
lative dosage of 300 mg; or constant agents.
infusion 1–2 mg/min IV Avoid in women with asthma,
preexisting myocardial disease,
decompensated cardiac function,
and heart block and bradycardia.
Hydralazine 5 mg IV or IM, then 5–10 mg IV every Higher or frequent dosage associated 10–20 minutes
20–40 minutes to a maximum with maternal hypotension,
cumulative dosage of 20 mg; or headaches, and abnormal fetal heart
constant infusion of 0.5–10 mg/hr rate tracings; may be more common
than other agents.
Nifedipine 10–20 mg orally, repeat in May observe reflex tachycardia and 5–10 minutes
(immediate 20 minutes if needed; then 10–20 mg headaches.
release) every 2–6 hours; maximum daily
dose is 180 mg
Abbreviations: IM, intramuscularly; IV, intravenously.

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Although blood pressure levels in the nonpregnant or worsening chronic hypertension) and the extent of
population are not considered the only criteria for end-organ damage. Serum uric acid may have value in
hypertensive crisis, in obstetric practice blood pressure the management of specific patients where there is
levels are traditionally relied upon for diagnostic and diagnostic uncertainty. Toxicology screen or electrocar-
management decisions. More conservative thresholds diogram, or both may be appropriate in certain clinical
have been established because cerebrovascular accidents situations.
or hypertensive encephalopathy can occur in pregnancy It must be stressed that acute hypertensive epi-
at lower blood pressure levels (60). Women with chronic sodes in pregnancy typically are approached more
hypertension and preeclampsia have an increased risk of seriously than those in nonpregnant patients given the
cerebral complications or stroke during pregnancy even continuum of risk between incremental increases in
without excessive elevations in blood pressure (61). This maternal blood pressure and perinatal morbidity and
may be explained by the fact that cerebral autoregulation mortality (67). In cases of acute-onset, severe hyper-
is impaired in pregnant women with chronic hyperten- tension, a structured and sequential antihypertensive
sion or preeclampsia (62). approach with careful attention to both maternal and
Antihypertensive treatment should be initiated expe- fetal conditions is recommended to ensure the best
ditiously for acute-onset, severe hypertension (systolic overall outcome. Box 4, Box 5, and Box 6 outline
blood pressure of 160 mm Hg or more or diastolic blood uniform sample order sets for the use of immediate-
pressure of 110 mm Hg or more, or both) that is release oral nifedipine, intravenous (IV) hydralazine,
confirmed as persistent (15 minutes or more) (See Boxes and IV labetalol for the initial management of acute-
4, 5, and 6). The available literature suggests that anti- onset, severe hypertension in women who are pregnant
hypertensive agents should be administered within 30– or in the postpartum period. Monitoring of viable fe-
60 minutes. However, it is recommended to administer tuses usually is recommended for evaluating maternal
antihypertensive therapy as soon as reasonably possible hemodynamics and the fetal response to lowering
after the criteria for acute-onset severe hypertension are maternal blood pressures.
met (63–66). It is not known how quickly one should Overzealous correction of blood pressure can be
lower blood pressure in an acute setting. Mindful that harmful and can cause hypoperfusion of critical territo-
blood pressure control should be expeditious and occur ries, such as the maternal brain and heart or the placenta
as safely as possible, evidence suggests that therapy (68). A drop in diastolic blood pressure below 80 mm Hg
should be initiated within 60 minutes and this goal is may cause fetal heart rate abnormalities because the ute-
emerging as an important quality metric in obstetrics roplacental circulation does not autoregulate blood flow.
(65, 66). If blood pressure remains elevated after initiat- The influence of concomitant obstetric management tools
ing antihypertensive therapy or for initial blood pressure should not be overlooked either. As an example, epidural
elevations of 180 mm Hg or more systolic or 120 mm Hg anesthesia can by itself lower blood pressure by approx-
or more diastolic, this represents further and ongoing risk imately 15%, frequently minimizing the need for antihy-
of severe maternal morbidity and mortality and requires pertensive medication when used for typical obstetric
accelerated maternal and obstetric evaluation and deci- indications of pain control (69). However, the effect of
sion making by the obstetric care provider. Evidence of magnesium sulfate IV infusion on hypertension is modest
acute end-organ damage, usually at blood pressure values if it occurs at all.
exceeding 240/140 mm Hg, identifies the patient as hav- A systematic review of 35 randomized trials (3,573
ing a genuine hypertensive emergency, and management women) examining different agents for acute antihyper-
in an intensive care unit with evaluation by a maternal– tensive therapy for severe-range blood pressure (ie,
fetal medicine or critical care subspecialist, or both is a systolic blood pressure of 160 mm Hg or more and
advisable. a diastolic blood pressure of 110 mm Hg or more) during
A thorough history and physical examination are pregnancy showed insufficient evidence to conclude that
essential to detect occult, secondary forms of hyperten- one agent was more effective (50). A randomized trial
sion; however, in a hypertensive crisis, drug therapy is comparing IV hydralazine to oral nifedipine showed
frequently initiated before a final diagnosis is established. equivalence of the two agents in the time to achieve
Laboratory tests, including serum electrolytes, serum blood pressure targets (70). No specific recommenda-
creatinine, complete blood count with platelets, aspartate tions are available regarding the choice of antihyperten-
aminotransferase and alanine aminotransferase, urinaly- sive agent based on the suspected hypertensive
sis, and urine protein-to-creatinine ratio, should be mechanism (eg, superimposed preeclampsia or worsen-
promptly obtained as appropriate to help define both ing chronic hypertension), and the following are the
the hypertensive mechanism (superimposed preeclampsia choices of therapeutic modalities for rapid parenteral

e36 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Box 4. Sample Order Set for Severe Intrapartum or Postpartum Hypertension Initial First-
line Management With Immediate-Release Oral Nifedipine*†

c Notify physician if systolic blood pressure (BP) is greater than or equal to 160 mm Hg or if diastolic BP is greater
than or equal to 110 mm Hg.
c Institute fetal surveillance if undelivered and fetus is viable.
c If severe BP elevations persist for 15 minutes or more, administer immediate-release nifedipine capsules (10 mg
orally).‡
c Repeat BP measurement in 20 minutes and record results.
c If either BP threshold is still exceeded, administer immediate-release nifedipine capsules (20 mg orally). If BP is
below threshold, continue to monitor BP closely.
c Repeat BP measurement in 20 minutes and record results.
c If either BP threshold is still exceeded, administer nifedipine immediate release capsule (20 mg orally). If BP is
below threshold, continue to monitor BP closely.
c Repeat BP measurement in 20 minutes and record results.
c If either BP threshold is still exceeded, administer labetalol (20 mg intravenously for more than 2 minutes) and
obtain emergency consultation from maternal–fetal medicine, internal medicine, anesthesia, or critical care
subspecialists.
c Give additional antihypertensive medication per specific order.
c Once the aforementioned BP thresholds are achieved, repeat BP measurement every 10 minutes for 1 hour,
then every 15 minutes for 1 hour, then every 30 minutes for 1 hour, and then every hour for 4 hours.
c Institute additional BP timing per specific order.

*Please note there may be adverse effects and contraindications.



When used with magnesium sulfate, facilities should monitor maternal vital signs as described above in reference to blood
pressure, with attention to normal heart rate and blood pressure.

Capsules should be administered orally and not punctured or otherwise administered sublingually.
Data from Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Joint National Committee on Pre-
vention, Detection, Evaluation, and Treatment of High Blood Pressure, National Heart, Lung, and Blood Institute, National High
Blood Pressure Education Program Coordinating Committee. Hypertension 2003;42:1206–52; Vermillion ST, Scardo JA,
Newman RB, Chauhan SP. A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive
emergencies of pregnancy. Am J Obstet Gynecol 1999;181:858–61; Raheem IA, Saaid R, Omar SZ, Tan PC. Oral nifedipine
versus intravenous labetalol for acute blood pressure control in hypertensive emergencies of pregnancy: a randomised trial.
BJOG 2012;119:78–85; Shekhar S, Sharma C, Thakur S, Verma S. Oral nifedipine or intravenous labetalol for hypertensive
emergency in pregnancy: a randomized controlled trial. Obstet Gynecol 2013;122:1057–63; and Duley L, Meher S, Jones L.
Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database of Systematic Reviews 2013, Issue 7.
Art. No.: CD001449. Available at https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001449.pub2/media/
CDSR/CD001449/CD001449_standard.pdf.

correction of acute, severe hypertension in pregnancy mg because there is a wide spectrum of individual dose
irrespective of etiology. response that is unpredictable based on clinical charac-
For acute blood pressure treatment, the agents listed teristics (71). If there is no response to the first bolus of
below and in Table 3 can be considered alone or in 10–20 mg, incremental repeat doses (such as 20 mg, 40
sequence (as specified in Box 4, Box 5, and Box 6). If mg, 80 mg, 80 mg, and 80 mg) may be administered
a maximum cumulative dose is achieved with any agent, every 10–30 minutes up to a maximum cumulative
it is recommended to switch to another class of agent. dosage of 300 mg. The onset of action after
IV administration of labetalol occurs rapidly (within
Labetalol 5 minutes) with peak effect at 10–20 minutes and a total
Labetalol is a mixed a-adrenergic and b-adrenergic duration of action up to 6 hours. Labetalol can be
blocker and the most common b-blocker used in preg- administered as a continuous infusion (1 mg/kg), but the
nancy. To avoid the risk of precipitous fall in blood bolus IV administration is more frequently used. La-
pressure, the initial bolus should not be larger than 20 betalol should be avoided in women with preexisting

VOL. 133, NO. 1, JANUARY 2019 Practice Bulletin Chronic Hypertension in Pregnancy e37

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Box 5. Sample Order Set for Severe Intrapartum or Postpartum Hypertension Initial
First-line Management With Hydralazine*

c Notify physician if systolic BP is 160 mm Hg or more or if diastolic BP is 110 mm Hg or more.


c Institute fetal surveillance if undelivered and fetus is viable.
c If severe BP elevations persist for 15 minutes or more, administer hydralazine (5 mg or 10 mg IV for more than
2 minutes).
c Repeat BP measurement in 20 minutes and record results.
c If either BP threshold is still exceeded, administer hydralazine (10 mg IV for more than 2 minutes). If BP is below
threshold, continue to monitor BP closely.
c Repeat BP measurement in 20 minutes and record results.
c If either BP threshold is still exceeded, administer labetalol (20 mg IV for more than 2 minutes). If BP is below
threshold, continue to monitor BP closely.
c Repeat BP measurement in 10 minutes and record results.
c If either BP threshold is still exceeded, administer labetalol (40 mg IV for more than 2 minutes) and obtain
emergency consultation from maternal–fetal medicine, internal medicine, anesthesia, or critical care
subspecialists.
c Give additional antihypertensive medication per specific order.
c Once the aforementioned BP thresholds are achieved, repeat BP measurement every 10 minutes for 1 hour,
then every 15 minutes for 1 hour, then every 30 minutes for 1 hour, and then every hour for 4 hours.
c Institute additional BP timing per specific order.

Abbreviations: BP, blood pressure; IV, intravenously.

*Please note there may be adverse effects and contraindications.

Data from Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure, National Heart, Lung, and Blood Institute, National High Blood
Pressure Education Program Coordinating Committee. Hypertension 2003;42:1206–52.

myocardial disease, decompensated cardiac function, hydralazine use may affect uteroplacental blood flow or
and heart block and bradycardia. Labetalol also should maternal renal blood flow, which may lead to oliguria,
be avoided in individuals with asthma as it can pre- particularly in pregnant women who are volume
cipitate bronchospasm. depleted. Late decelerations that occur after the adminis-
tration of hydralazine often respond to fluid loading and
Hydralazine position changes, but cases with placental abruption or
fetal distress requiring emergency cesarean delivery have
Hydralazine has been used extensively for severe been reported. Whenever a powerful antihypertensive is
hypertension in pregnancy for more than 65 years. The administered, prior correction of hypovolemia may be
onset of action is relatively slow for an IV drug (10– helpful to prevent the hypotensive overshoot.
20 minutes) because it must be metabolized after The hypotensive overshoot with hydralazine is an
attachment to the vessel wall in order to be effective. unpredictable complication that is not always dose
Common limiting adverse effects, which are experienced related. Because hydralazine has a long duration of
by up to 50% of recipients, include reflex tachycardia, action, it can last up to 12 hours (72). Fetal distress
hypotension, headaches, palpitations, flushing, anxiety, secondary to maternal hypotension seems to be more
tremors, vomiting, epigastric pain, and fluid retention by frequent when a continuous infusion of hydralazine is
activation of the renin-angiotensin system. Many of these used instead of repeat bolus administrations (73). Fur-
adverse effects resemble the signs and symptoms of thermore, in a comparative study of hydralazine bolus
severe preeclampsia, confusing the clinical picture. The injection compared with continuous infusion, bolus in-
hypotensive overshoot that may be associated with jections achieved the therapeutic goal significantly

e38 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Box 6. Sample Order Set for Severe Intrapartum or Postpartum Hypertension, Initial First-
line Management With Labetalol*

c Notify physician if systolic BP measurement 160 mm Hg or more or if diastolic BP measurement is 110 mm Hg or


more.
c Institute fetal surveillance if undelivered and fetus is viable.
c If severe BP elevations persist for 15 minutes or more, administer labetalol (20 mg IV for more than 2 minutes).
c Repeat BP measurement in 10 minutes and record results.
c If either BP threshold is still exceeded, administer labetalol (40 mg IV for more than 2 minutes). If BP is below
threshold, continue to monitor BP closely.
c Repeat BP measurement in 10 minutes and record results.
c If either BP threshold is still exceeded, administer labetalol (80 mg IV for more than 2 minutes). If BP is below
threshold, continue to monitor BP closely.
c Repeat BP measurement in 10 minutes and record results.
c If either BP threshold is still exceeded, administer hydralazine (10 mg IV for more than 2 minutes). If BP is below
threshold, continue to monitor BP closely.
c Repeat BP measurement in 20 minutes and record results.
c If either BP threshold is still exceeded, obtain emergency consultation from maternal–fetal medicine, internal
medicine, anesthesia, or critical care subspecialists.
c Give additional antihypertensive medication per specific order.
c Once the aforementioned BP thresholds are achieved, repeat BP measurement every 10 minutes for 1 hour, then
every 15 minutes for 1 hour, then every 30 minutes for 1 hour, and then every hour for 4 hours.
c Institute additional BP timing per specific order.

Abbreviations: BP, blood pressure; IV, intravenously.

*Please note there may be adverse effects and contraindications.

Data from Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure, National Heart, Lung, and Blood Institute, National High Blood
Pressure Education Program Coordinating Committee. Hypertension 2003;42:1206–52.

faster and with smaller total doses (74). Therefore, inter- IV access (50, 76–78). Nifedipine has been associated
mittent bolus is recommended over continuous IV infu- with an increase in maternal heart rate and has less risk
sion. Repeat IV bolus administration is recommended as of overshoot hypotension (76). Immediate-release
5–10 mg injections every 20–40 minutes to a maximum nifedipine should not be given sublingually given the
cumulative dose of 20 mg until blood pressure control is risk of hypotension with this route of administration.
achieved. One study assessing the feasibility of using extended-
In a meta-analysis, hydralazine was more effective release nifedipine tablets instead of immediate-release
than labetalol in lowering severe blood pressure in capsules for the acute lowering of severe hypertension
pregnancy but was associated with more adverse mater- in pregnancy (79) found that absorption for tablets
nal and perinatal events (eg, maternal tachycardia, peaked at 60–70 minutes compared with 30 minutes
prolonged hypotension, oliguria, cesarean delivery, pla-
for capsules; moreover, it took 45–90 minutes to ach-
cental abruption, nonreassuring fetal heart tracing, and
ieve adequate lowering of blood pressure, making the
low Apgar scores) (75).
performance of nifedipine tablets unacceptable in acute
situations.
Nifedipine In the rare circumstance that these first-line agents,
Immediate-release oral nifedipine, a calcium channel used as directed, fail to relieve acute-onset, severe
blocker, is an acceptable first-line alternative to hydral- hypertension, emergent consultation with an anesthesi-
azine or labetalol, especially in cases of patients without ologist, maternal–fetal medicine subspecialist, or critical

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Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
care subspecialist to discuss further interventions is rec- appropriate (84). This may be justified because the risk of
ommended (66). Second-line agents to consider in such fetal growth restriction is higher in women with chronic
emergencies include nicardipine or esmolol by infusion hypertension and the sensitivity of fundal height meas-
pump or IV enalapril. urements to detect fetal growth restriction is inadequate
Once blood pressure control has been achieved with for high-risk women including women with hypertension
the acute therapeutic agent, it is important to anticipate or obesity (85).
the need for further treatment and to initiate oral The performance of electronic fetal monitoring in
maintenance. Failure to do so may expose the patient labor has been tested predominantly in low-risk popula-
to a recurrent acute situation. tions, and these studies have largely excluded patients at
high risk of adverse outcomes. It is recommended that
< What is the role for low-dose aspirin in patients with
chronic hypertension in pregnancy? patients with high-risk conditions be monitored with
continuous fetal heart rate monitoring in labor (86); thus,
Evidence suggesting that an imbalance in prostacy- patients with chronic hypertension at higher risk of
clin and thromboxane A2 metabolism is involved in the adverse outcomes (eg, those who require any blood pres-
development of preeclampsia prompted interest in the sure control or with other short-term or long-term
study of aspirin for preeclampsia prevention because of sequelae), at a minimum, should have continuous fetal
its preferential inhibition of thromboxane at lower doses. monitoring.
Low doses of aspirin also inhibit platelet aggregation
(80). The 2014 U.S. Preventive Services Task Force < Are there intrapartum concerns unique to pregnant
guidelines on low-dose aspirin for the prevention of pre- women with chronic hypertension?
eclampsia concluded with moderate certainty that there Women with chronic hypertension who are admitted
are benefits with this intervention in women at high risk for delivery should continue their medications. Blood
of preeclampsia without evidence of adverse effects (81). pressure should be monitored at regular intervals and
The recent American College of Obstetricians and acute elevations should be addressed accounting for
Gynecologists’ recommendations for women at high risk of transient elevations that may occur in the setting of
preeclampsia are to start treatment with 81 mg daily between labor. Women with severe hypertension complicated by
12 weeks and 28 weeks of gestation and to continue until cardiovascular or renal disease may present with special
delivery (82). Thus, for women with chronic hypertension, it problems peripartum and should be collaboratively
is recommended to initiate daily low-dose aspirin (81 mg) managed with subspecialists (cardiology, nephrology,
between 12 weeks and 28 weeks of gestation (optimally maternal–fetal medicine) as appropriate. Assessment of
before 16 weeks) and to continue this therapy until delivery. urine for proteinuria should be considered, as the diag-
Initiating treatment after 28 weeks of gestation is unlikely to nosis of preeclampsia in a patient with chronic hyper-
be beneficial. Low-dose aspirin should not be used in tension could have important management implications.
women with risk factors for gastrointestinal hemorrhage Urine output monitoring may be appropriate in pop-
(eg, bleeding disorders or peptic ulcer). ulations that are susceptible to fluid overload with
resultant pulmonary edema.
< Is there a role for fetal surveillance in pregnancies Results of a retrospective cohort study using data
complicated by chronic hypertension?
from the Consortium on Safe Labor (which represents 19
Antenatal fetal surveillance may be beneficial in hospitals in the United States) seem to indicate that
reducing perinatal morbidity and mortality in high-risk women with chronic hypertension and superimposed
pregnancies (83). Therefore, antenatal fetal testing is rec- preeclampsia have longer first stages of labor, particu-
ommended for women with chronic hypertension com- larly nulliparous patients (87). Allowing a longer first
plicated by issues such as the need for medication, other stage of labor in these women may avoid unnecessary
underlying medical conditions that affect fetal outcome, cesarean deliveries.
any evidence of fetal growth restriction, or superimposed Issues related to analgesia or anesthesia in pregnant
preeclampsia. However, limited data exist regarding the women with chronic hypertension have not been studied
timing and interval of testing. Furthermore, in the extensively. Although women with hypertension are
absence of randomized trials comparing testing to no more vulnerable to sympathetic blockade, it appears that
testing, it remains unclear whether antenatal fetal testing axial anesthesia is safe even in cases with severe
translates into outcome improvements. hypertension in labor, and that it has no adverse effects
The risks of fetal growth restriction in patients with on neonatal outcomes or maternal condition (88). When-
chronic hypertension warrant third-trimester ultrasound ever possible, unless contraindicated by maternal throm-
assessment of fetal growth, with subsequent evaluation as bocytopenia, neuraxial anesthesia should be employed

e40 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
because general anesthesia may pose a higher risk for increases in blood pressure from transient hypertension.
pregnant women with severe hypertension. Intubation The assessment for superimposed preeclampsia typically
and extubation may be associated with acute elevations takes a few hours but sometimes requires longer, perhaps
in blood pressure. In these situations, administration of up to 48 hours, in challenging cases of patients with
IV antihypertensive agents, such as b-blockers, may be comorbidities or end-organ damage that antedate
necessary. When possible, severe hypertension should be pregnancy.
corrected before intubation to avoid health risks of fur-
< When is delivery of a woman with chronic hyperten-
ther increases in acute blood pressure. sion indicated?
< How is chronic hypertension distinguished from There is a paucity of reliable clinical trial data to
superimposed preeclampsia? guide decisions about the timing of delivery in women
It often is difficult to distinguish chronic hyperten- with chronic hypertension. A small clinical trial has
sion from superimposed preeclampsia when a patient suggested that the risk of adverse perinatal outcomes in
with chronic hypertension presents with elevated blood women with chronic hypertension without any obstetric
pressure later in pregnancy. The clinical work-up should complications is similar to the risk among women without
screen for symptoms associated with preeclampsia, and chronic hypertension (89). Moreover, a cohort study of
a comprehensive laboratory evaluation may be useful in women with chronic hypertension found that delivery at
making a diagnosis. New-onset proteinuria meeting 38 0/7–39 6/7 weeks of gestation was optimal for balanc-
criteria for preeclampsia, for instance, makes the diag- ing fetal and neonatal risks (90). Other publications also
nosis simple. Performing a baseline work-up for patients have endorsed delivery from 38 0/7 weeks to 39 6/7 weeks
with chronic hypertension at the beginning of pregnancy of gestation for women with chronic hypertension who are
is important because it can provide a context for not prescribed medication or from 37 0/7 weeks to 39 6/7
comparison. However, in women with chronic hyperten- weeks of gestation for women whose chronic hypertension
sion and chronic renal end-organ impairment antedating is well-controlled with medication (91).
pregnancy, it may not be possible to distinguish between Based on this, the earlier gestational age in the
the two entities. Acute, severe, and persistent elevations suggested range for timing of delivery for women at term
in blood pressure, in the absence of other explanations, depends on the use of maintenance antihypertensive
such as cocaine intoxication, may suggest superimposed medications. For women with chronic hypertension and
preeclampsia. Less commonly, a woman presenting with with no additional maternal or fetal complications
hypertension late in pregnancy could have systemic lupus supporting earlier delivery, if not prescribed maintenance
erythematosus, primary renal disease, or hyperthyroid- antihypertensive medications, delivery before 38 0/7
ism. Although it is not necessary to screen all women weeks of gestation is not recommended. For women
with hypertension for these conditions, the possibility with chronic hypertension and with no additional mater-
should be considered in the clinical context of unclear nal or fetal complications supporting earlier delivery, if
and severe presentations. prescribed maintenance antihypertensive medications,
In cases of diagnostic uncertainty in discriminating delivery before 37 0/7 weeks of gestation is not
transient blood pressure increases in chronic hyperten- recommended. Patients with hypertension that is difficult
sion from superimposed preeclampsia, particularly with to control, such as those requiring frequent maintenance
severe-range blood pressures, initial surveillance in the medication adjustments or those on maximal doses of
hospital setting is recommended. Work-up should maintenance medications, may require earlier delivery,
include evaluation of hematocrit, platelets, creatinine, such as in the late preterm period.
and liver function tests as well as assessment of new- The data regarding the later gestational age in the
onset proteinuria. Serum uric acid may be a helpful suggested range for timing of delivery is mixed. As
marker. Elevated hematocrit (indicating hemoconcentra- previously described, expectant management up to 39
tion), thrombocytopenia, hyperuricemia, new-onset or 6/7 weeks of gestation may be considered. However,
worsening proteinuria, elevated serum creatinine, and a retrospective cohort study of 683 women found that
elevated liver transaminases are more indicative of planned delivery before 39 0/7 weeks of gestation was
preeclampsia than chronic hypertension, and, from associated with a decreased risk of preeclampsia with
a practical point of view, the practitioner should think severe features. When compared with patients with
preeclampsia first. Fetal well-being should be assessed as a planned delivery at 39 weeks of gestation or more,
appropriate with fetal heart rate monitoring and sonog- those delivered before 39 0/7 weeks of gestation had
raphy. Often, serial blood pressure assessment during 4– a lower rate of preeclampsia with severe features (10%
8 hours can be helpful in discriminating acute and serious versus 1% absolute risk) (AOR for severe preeclampsia

VOL. 133, NO. 1, JANUARY 2019 Practice Bulletin Chronic Hypertension in Pregnancy e41

Copyright ª by the American College of Obstetricians


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Unauthorized reproduction of this article is prohibited.
of 0.07; 95% CI, 0.01–0.5) (92). Additionally, a recent weeks of gestation with close maternal and fetal
retrospective population-based study looked at the surveillance is suggested. Induction at term for
practice of routine induction at 38 weeks or 39 weeks women with mild pregnancy-related hypertensive
of gestation, suggesting that induction of labor at 38 weeks disease has not been associated with an increased risk
or 39 weeks of gestation may prevent severe hypertensive of cesarean delivery (94). Given the lack of clinical
complications (superimposed preeclampsia and eclampsia) trials and prospective studies in women with chronic
without increasing the risk of cesarean delivery when hypertension and superimposed preeclampsia, the
compared with expectant management (93). Therefore, aforementioned recommendations for timing of deliv-
expectant management beyond 39 0/7 weeks of gestation ery are based on indirect evidence from the manage-
should only be done after careful consideration of the risks ment of preeclampsia consistent with published expert
and benefits and with appropriate surveillance. opinions (95).
Delivery timing in preterm pregnancies involves There is a paucity of data to support outpatient
careful consideration of risks and benefits for a woman management of superimposed preeclampsia. Reasonable
and fetus. Expectant management before term helps the and cautious practice would indicate that outpatient
fetus but risks the health of the woman. Women with management be considered for cases without any severe
severe acute hypertension that is not controlled with features (eg, severe-range blood pressures, symptoms,
traditional chronic antihypertensive regimens or laboratory abnormalities).
women who develop superimposed preeclampsia with
severe features should be delivered upon diagnosis at <What are the postpartum considerations and recom-
34 0/7 weeks of gestation or more. Because of the mendations in patients with chronic hypertension?
significant maternal–fetal and maternal–neonatal Blood pressure control usually continues to be an
morbidity, immediate delivery after maternal stabili- issue postpartum, and even women who were not treated
zation is recommended if any of the following are during pregnancy may require treatment with antihyper-
present at any gestational age in women with super- tensive medication in the postpartum period. This
imposed preeclampsia: uncontrollable severe hyper- elevation of blood pressure is considered to be related
tension, eclampsia, pulmonary edema, disseminated to the mobilization of extravascular fluid with rise in
intravascular coagulation, new or increasing renal intravascular volume in addition to factors such as pain
insufficiency, placental abruption, or abnormal fetal or anxiety.
testing. Women who develop superimposed pre- After an initial decline immediately after delivery,
eclampsia with severe features before 34 0/7 weeks of blood pressure tends to rise. Therefore, a rapid decrease
gestation may be candidates for expectant management in blood pressure postpartum is more likely to indicate
under certain circumstances, although expectant man- substantial blood loss than a rapid resolution of the
agement is not recommended beyond 34 0/7 weeks of disease process. Blood pressure in the postpartum period
gestation. In these cases, inpatient management is is often higher compared with antepartum levels, partic-
recommended and should be undertaken only at ularly in the first 1–2 weeks postpartum (96). Severe
facilities with adequate maternal and neonatal inten- hypertension or superimposed preeclampsia also may
sive care resources. Initiation of antenatal steroids is develop for the first time in the postpartum period; there-
recommended according to American College of Ob- fore, women with chronic hypertension should be closely
stetricians and Gynecologists’ guidelines. Even in ca- monitored for blood pressure changes and symptoms of
ses of preterm pregnancies with anticipated imminent severe-range hypertension or superimposed preeclamp-
delivery, neonates may benefit from exposure to a first sia. Early ambulatory visits in the first 1–2 weeks after
dose. A retrospective case series examining a subset of delivery or home blood pressure monitoring may be pru-
29 women with superimposed preeclampsia managed dent surveillance for these postpartum changes (97).
expectantly (36) found latency periods similar to Medication in the weeks postpartum should be adjusted
women with severe preeclampsia in the absence of to maintain a systolic blood pressure not higher than
chronic hypertension (8.4 days compared with 8.5 150 mm Hg and a diastolic blood pressure not higher
days), with no differences in the rates of placental than 100 mm Hg (98–100).
abruption, oliguria, or hemolysis, elevated liver en- Some common medications and substances used in
zymes, and low platelet count (HELLP) syndrome the postpartum period may potentially aggravate hyper-
between the two groups. tension through three major mechanisms: 1) volume
In women with superimposed preeclampsia with- retention, 2) sympathomimetic activation, and 3) direct
out any severe features and with stable maternal and vasoconstriction. Of particular interest are the nonsteroi-
fetal conditions, expectant management until 37 0/7 dal anti-inflammatory drugs (NSAIDs) which are

e42 Practice Bulletin Chronic Hypertension in Pregnancy OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
frequently prescribed as postpartum analgesics. These in breast milk are low, and these drugs may be used
medications decrease prostaglandins leading to a lack of safely during breastfeeding unless high doses are
vasodilation and increased sodium retention. Nonsteroi- required. No adverse effects are known to occur with
dal antiinflammatory medications should continue to be calcium channel blockers during breastfeeding.
used preferentially over opioid analgesics; however, Although the concentration of diuretics in breast milk
women with chronic hypertension theoretically may is low, these agents may reduce the quantity of milk
require intensification of blood pressure monitoring and production.
regimen adjustments when on these medications. Over-
all, data support the safe use of NSAIDs in postpartum
patients with blood pressure issues. In a randomized trial Clinical Considerations
comparing use of ibuprofen to acetaminophen in post-
partum patients with preeclampsia with severe features,
and Recommendations
ibuprofen did not lengthen the duration of severe-range The following recommendation is based on good and
blood pressures (101). In a cohort of 399 patients with consistent scientific evidence (Level A):
preeclampsia with severe features, there was no associa-
tion of NSAID use with postpartum blood pressure ele- < For women with chronic hypertension, it is recom-
vations (102). Further, another cohort study of mended to initiate daily low-dose aspirin (81 mg)
postpartum patients on magnesium for seizure prophy- between 12 weeks and 28 weeks of gestation (opti-
laxis for preeclampsia did not show differences in blood mally before 16 weeks) and to continue this therapy
pressure, antihypertensive requirements, or other adverse until delivery.
events for patients managed with NSAIDs in the post-
The following recommendations are based on limited or
partum period (103).
inconsistent scientific evidence (Level B):
Antihypertensive medications may be used more
liberally in the postpartum period than during pregnancy. < Initiation of antihypertensive therapy is recommended
Blood pressure parameters to guide medication dosage in for persistent chronic hypertension when systolic
the postpartum period should be adjusted given that there pressure is 160 mm Hg or more, diastolic pressure is
are no longer fetal considerations. Therefore, the goal 110 mm Hg or more, or both. In the setting of co-
should be a lower blood pressure range. Methyldopa, morbidities or underlying impaired renal function,
however, should be avoided because it often can be treating at lower blood pressure thresholds may be
associated with depression, and the postpartum period is appropriate.
already characterized by increased vulnerability for < For the long-term treatment of pregnant women
depression (104). A recent, small (n550) randomized who require pharmacologic therapy, labetalol or
controlled trial comparing labetalol to extended-release nifedipine are reasonable options and are recom-
nifedipine in women with persistent postpartum hyper- mended above all other antihypertensive drugs. The
tension not previously on medication found that both use of angiotensin-converting-enzyme inhibitors,
agents were effective; however, labetalol had fewer angiotensin receptor blockers, renin inhibitors,
adverse effects and achieved control more often with and mineralocorticoid receptor antagonists is gen-
the starting dose (105). Patients with chronic hyperten- erally not recommended.
sion also may be returned to their prepregnancy regimen
in collaboration with their primary care provider or inter-
< Antihypertensive treatment should be initiated expe-
ditiously for acute-onset severe hypertension (systolic
nal medicine provider.
blood pressure of 160 mm Hg or more or diastolic
Antihypertensives, in general, can be used in
blood pressure of 110 mm Hg or more, or both) that is
breastfeeding women. Most antihypertensive medica-
confirmed as persistent (15 minutes or more). The
tions are detectable, albeit at low concentrations, in
available literature suggests that antihypertensive
breast milk thus their use during lactation is not
agents should be administered within 30–60 minutes.
contraindicated (106). Some b-blockers (eg, atenolol
and metoprolol) are concentrated in breast milk result- However, it is recommended to administer antihy-
ing in higher levels, whereas propranolol and labetalol pertensive therapy as soon as reasonably possible after
with their higher plasma protein binding are not con- the criteria for acute-onset severe hypertension are
centrated in breast milk and remain at low levels. Thus, met.
propranolol and labetalol are preferred for treatment in < For women with chronic hypertension and with no
breastfeeding women. Angiotensin-converting enzyme additional maternal or fetal complications supporting
inhibitors (eg, enalapril and captopril) concentrations earlier delivery,

VOL. 133, NO. 1, JANUARY 2019 Practice Bulletin Chronic Hypertension in Pregnancy e43

Copyright ª by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
 if not prescribed maintenance antihypertensive med- with severe-range blood pressures, initial surveillance
ications, delivery before 38 0/7 weeks of gestation is in the hospital setting is recommended. Work-up
not recommended. should include evaluation of hematocrit, platelets,
 if prescribed maintenance antihypertensive medica- creatinine, and liver function tests as well as assess-
tions, delivery before 37 0/7 weeks of gestation is not ment of new-onset proteinuria. Serum uric acid may
recommended. be a helpful marker. Elevated hematocrit (indicating
hemoconcentration), thrombocytopenia, hyperurice-
< Women with severe acute hypertension that is not con-
trolled with traditional chronic antihypertensive regimens mia, new-onset or worsening proteinuria, elevated
or women who develop superimposed preeclampsia with serum creatinine, and elevated liver transaminases are
severe features should be delivered upon diagnosis at 34 more indicative of preeclampsia than chronic hyper-
0/7 weeks of gestation or more. Because of the signifi- tension, and, from a practical point of view, the
cant maternal–fetal and maternal–neonatal morbidity, practitioner should think preeclampsia first. Fetal
immediate delivery after maternal stabilization is rec- well-being should be assessed as appropriate with fetal
ommended if any of the following are present at any heart rate monitoring and sonography. Often, serial
gestational age in women with superimposed blood pressure assessment during 4–8 hours can be
preeclampsia: uncontrollable severe hypertension, helpful in discriminating acute and serious increases in
eclampsia, pulmonary edema, disseminated intravascular blood pressure from transient hypertension.
coagulation, new or increasing renal insufficiency, < In women with superimposed preeclampsia without
placental abruption, or abnormal fetal testing. severe features and with stable maternal and fetal
< Women who develop superimposed preeclampsia with conditions, expectant management until 37 0/7 weeks
severe features before 34 0/7 weeks of gestation may be of gestation with close maternal and fetal surveillance
candidates for expectant management under certain is suggested.
circumstances, although expectant management is not
recommended beyond 34 0/7 weeks of gestation. In
these cases, inpatient management is recommended and
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Published online on December 20, 2018.
The MEDLINE database, the Cochrane Library, and the
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Institutes of Health and the American College of
Obstetricians and Gynecologists were reviewed, and Chronic hypertension in pregnancy. ACOG Practice Bulletin
additional studies were located by reviewing No. 203. American College of Obstetricians and Gynecologists.
bibliographies of identified articles. When reliable Obstet Gynecol 2019;133:e26–50.
research was not available, expert opinions from
obstetrician–gynecologists were used.
Studies were reviewed and evaluated for quality
according to the method outlined by the U.S.
Preventive Services Task Force:
I Evidence obtained from at least one properly de-
signed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled
trials without randomization.
II-2 Evidence obtained from well-designed cohort or
case–control analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in
uncontrolled experiments also could be regarded as
this type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to
the following categories:
Level A—Recommendations are based on good and
consistent scientific evidence.
Level B—Recommendations are based on limited or
inconsistent scientific evidence.
Level C—Recommendations are based primarily on
consensus and expert opinion.

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Unauthorized reproduction of this article is prohibited.
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