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Hypertension. Author manuscript; available in PMC 2023 February 01.
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Published in final edited form as:

Hypertension. 2022 February ; 79(2): e21–e41. doi:10.1161/HYP.0000000000000208.
Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals,

and Pharmacotherapy:
A Scientific Statement from the American Heart Foundation
Vesna D. Garovic, MD, PhD [Chair], Ralf Dechend, MD, S. Ananth Karumanchi, MD,
Suzanne McMurtry Baird, DNP, RN, Thomas Easterling, MD, Laura A. Magee, MD, FRCPC,
Sarosh Rana, MD, MPH, Jane V. Vermunt, MBChB, MSc, Phyllis August, MD, MPH [Vice
Chair] on behalf of the American Heart Association Council on Hypertension, Council on
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the Kidney in Cardiovascular Disease Science Subcommittee, Council on Arteriosclerosis,

Thrombosis and Vascular Biology, Council on Lifestyle and Cardiometabolic Health,
Council on Peripheral Vascular Disease, and Stroke Council
Abstract
Hypertensive disorders of pregnancy (HDP) remain one of the major causes of pregnancy-related
maternal and fetal morbidity and mortality worldwide. Affected women are also at increased risk
for cardiovascular disease (CVD) later in life, independent of traditional CVD risks. Despite
the immediate and long-term CVD risks, recommendations for diagnosis and treatment of
HDP in the United States have changed little, if at all, over past decades, unlike hypertension
guidelines for the general population. The reasons for this approach include the question of benefit
from normalization of blood pressure treatment for pregnant women, coupled with theoretical
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concerns for fetal well-being from reduction in utero-placental perfusion and in utero exposure to
antihypertensive medication.
This report is based on a review of current literature and includes: normal physiological changes
in pregnancy that may affect clinical presentation of HDP; HDP epidemiology and their immediate
and long-term sequelae; the pathophysiology of preeclampsia, a HDP commonly associated
with proteinuria and increasingly recognized as a heterogeneous disease with different clinical
phenotypes and likely distinct pathological mechanisms; a critical overview of current national
and international HDP guidelines; emerging evidence that reducing blood pressure treatment goals
in pregnancy may reduce maternal severe hypertension without increasing the risk of pregnancy
loss, high level neonatal care or overall maternal complications; and the increasingly recognized
morbidity associated with postpartum hypertension/preeclampsia. Finally, we discuss the future of
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research in the field and the pressing need to study socioeconomic and biological factors that may
contribute to racial and ethnic maternal health care disparities.
1.0 Introduction
Hypertensive disorders of pregnancy (HDP) encompass chronic hypertension, gestational
hypertension, preeclampsia/eclampsia, and preeclampsia superimposed on chronic
hypertension.1 The diagnostic criteria for HDP in the U.S. have evolved over the past
5 decades;1 (Table 1) the most current definition of hypertension in pregnancy from the
Garovic et al. Page 2
American College of Obstetricians and Gynecologists (ACOG) was published in 2013,1 with
updates and recommendations made in 2019 and 2020.2, 3
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Most guidelines around the world are aligned in defining hypertension in pregnancy as
BP ≥140/90 mm Hg (Table 6, has all the references). There is variability regarding the
threshold for initiating antihypertensive treatment due to uncertainty about the maternal
benefits of lowering blood pressure (BP) and the potential fetal risks from medication
induced reductions in utero-placental circulation and in utero exposure to antihypertensive
medications.2 In contrast, diagnostic and treatment thresholds for the general population
have evolved over the years;4, 5 the 2017 American College of Cardiology (ACC)/
American Heart Association (AHA) guidelines for the Prevention, Detection, Evaluation,
and Management of High Blood Pressure in Adults threshold for the diagnosis of Stage
1 hypertension was further lowered to 130/80 mm Hg, from 140/90 mm Hg,6 based on
observational studies and clinical trials demonstrating reduced CVD events with treatment to
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lower levels.7, 8
This scientific report presents a synthesis of the scientific evidence (from literature
published until August 31st, 2020) that is relevant to the current controversies regarding
HDP diagnostic and treatment strategies. It is a timely statement given that current
trends indicate the incidence of HDP continues to increase9, 10 due to advanced age
at first pregnancy, and increased prevalence of obesity and other cardio-metabolic risk
factors. Cardiovascular disease, including cerebrovascular accidents and cardiomyopathy,
now account for approximately half of all maternal deaths.11 Pregnancy related stroke
hospitalizations increased more than 60% from 1994 to 2011 and HDP associated stroke
rates increased 2-fold compared to non-HDP related stroke.10 Thus, in the discussion that
follows, we emphasize the need for future research aimed at recognizing and appropriately
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treating HDP.
2.0 Epidemiology
The HDP are the second leading cause of global maternal mortality behind maternal
hemorrhage12 and are a significant cause of short and long-term maternal morbidity.
HDP are also associated with adverse fetal outcomes (Tables 2 and 3). Elevated systolic
BPs throughout pregnancy, even below the diagnostic threshold for hypertension are also
associated with increased risk of pre-term delivery, small for gestational age, and low
birthweight.13, 14
Traditionally, incidence of HDP was reported on a per-pregnancy basis to assist prediction

of pregnancy-related complications (both maternal and fetal) in an obstetric clinical setting
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(Table 2).
However, the HDP population-based incidence expressed per-pregnancy (7.5%)

underestimates the number of women affected by this condition during their reproductive
years (15.3%).23 Per-women rather than per-pregnancy incidence provides better assessment
of the number of women at risk for future CVD based on their reproductive histories,24
including development of diabetes and hypertension23, 25 (Table 3).

It is well accepted that hypertension develops significantly more frequently after HDP,
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but studies indicate that hypertension also develops faster and is diagnosed up to 10
years earlier compared to women with normotensive pregnancies,23, 30, 46–48 though the
precise timing requires further examination. Earlier onset of cardio-metabolic risk factors
and CVD events,26, 34, 46 as well as higher rates of accumulated chronic conditions and
multi-morbidity,23 support the thesis of accelerated aging among women who have a history
of HDP.23, 25, 49
3.0 Pathophysiology of HDP

3.1 Hemodynamic Changes in Normal Pregnancy and Preeclampsia
Systemic vascular resistance decreases while plasma volume and cardiac output increase
during pregnancy. There is a physiological drop in BP, often detectable before the end of
the first trimester,50, 51 due to vasodilation.52 Meta-analyses and high quality longitudinal
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studies found that compared to BP at 10 or 12 weeks, the BP drop during the second
trimester was on average 1–2 mm Hg.53–55 There is wide inter-individual variability and
BP trajectories likely relate to pre-existing maternal health factors,55 such as chronic
hypertension, and require further clarification. Renal blood flow and glomerular filtration
rate increase by 50% in normal pregnancy, but are approximately 30% lower in women
with preeclampsia as a result of both decreases in renal blood flow and the ultrafiltration
coefficient, attributable to endotheliosis in the glomerular capillary bed.56 Plasma volume
increases in normal pregnancy, and earlier studies have suggested that it may be decreased
in women with preeclampsia.57 However, multiple longitudinal and cross-sectional studies
in preeclamptic women demonstrating suppressed plasma renin activity, high blood
pressure, decreased glomerular filtration rate and frequent development of edema are more
consistent with an overfilled, vasoconstricted circulation rather than true hypovolemia and
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underfilling.58 Cardio-metabolic changes in normal pregnancy are more pronounced in

women who develop preeclampsia and include increased insulin resistance, total cholesterol,
triglycerides, HDL-C and LDL-C.59 Hypercoagulability, a feature of normal pregnancy, may
be exaggerated in preeclampsia and is caused by increased thrombin generation, fibrinogen,
and activated protein C resistance, and reduced protein S and fibrinolysis.60
3.2 Abnormal Placentation and the Pathogenesis of the Maternal Preeclampsia Syndrome
The diameter of the uterine spiral arteries increase greatly during normal pregnancy due
to remodeling of the endothelium and vascular smooth muscle, stimulated by release
of proteases from endovascular trophoblast and uterine Natural Killer cells.61 Failure of
spiral artery remodeling (i.e., retention of smooth muscle) is a feature of preeclampsia
(Figure1)62, 63 and leads to decreased utero-placental perfusion, demonstrated by non-
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invasive blood flow and perfusion studies using Doppler ultrasound or magnetic resonance
imaging.63
Placental pathology due to rheological consequences includes villous architectural changes

due to turbulent jets entering the intervillous space at rates of 1–2m/s (10–20 times normal),
causing the rupture of anchoring villi and formation of echogenic cystic lesions that are
visible by ultrasound.66 In addition, retention of vascular smooth muscle preserves the

ability of spontaneous vasoconstriction and ischemia-reperfusion injury, which may result in

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oxidative stress.
Alterations in angiogenic factors are recognized as a likely consequence of abnormal

placentation occurring in early pregnancy. Increased circulating soluble fms-like tyrosine
kinase 1 (sFlt1), an anti-angiogenic factor of placental origin, leads to neutralization and
decrease of pro-angiogenic factors, such as placental growth factor (PlGF) and vascular
endothelial growth factor, which then contribute to the hypertension and glomerulopathy
characteristic of the maternal syndrome.63 Measurements of angiogenic biomarkers have
been incorporated into risk stratification in several innovative therapeutic trials for
preeclampsia prevention,67, 68 but are not routinely used to guide clinical care in most
countries, including the US. An increased sFlt1/PlGF ratio may be particularly pronounced
in women with early, (<34 gestational weeks) severe preeclampsia, which has been
designated by some as placental preeclampsia69 because of the association between
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placental ischemia and adverse fetal outcomes (fetal growth restriction, in particular).
Preeclampsia occurring later in pregnancy, labeled by some as maternal preeclampsia, has
been associated with more pronounced maternal vascular dysfunction prior to pregnancy
(secondary to hypertension, diabetes, or obesity), less pronounced placental pathology, and
fewer fetal complications. In maternal preeclampsia, pregnancy acts as a physiological
stress test that exacerbates preexisting endothelial dysfunction. This underscores the
heterogeneity of HDP, whereby the extremes of clinical subtypes (early versus late,
mild versus severe, and presence or absence of fetal growth restriction) may reflect
distinct underlying mechanisms.69 Sharp discrimination between maternal vs. placental
preeclampsia is overly simplistic and artificial as both processes likely play a role, but
with varying contributions. Regardless of the clinical subtype, diagnosis and treatment of
hypertension remains a mainstay of the prevention of immediate maternal complications and
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permanent cardiovascular injury, together with seizure prevention using magnesium sulfate.
4.0 Prevention of preeclampsia and adverse maternal and fetal outcomes

Preconception health, and its impact on both pregnancy outcomes as well as future health,
has gained attention.70 Lifestyle changes before and during pregnancy may ameliorate
both maternal and fetal risks. A meta-analysis of 44 randomized controlled trials reported
that dietary interventions reduce maternal gestational weight gain and improve pregnancy
outcomes.71 Exercise may reduce gestational hypertension and preeclampsia risk by
approximately 30 and 40%, respectively.72, 73 The first Canadian guideline for physical
activity throughout pregnancy published in 2019 recommends that all women without
contraindication should be physically active during pregnancy.74 Low dose aspirin, starting
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between 12 and 16 weeks of gestation, reduces the risk of preeclampsia and related adverse
outcomes by 10 to 20% in women at increased risk (Table 4).75–78 ACOG recommends daily
low dose aspirin for women with a history of early onset preeclampsia and preterm delivery,
or for women with more than one pregnancy complicated by preeclampsia.77
The optimal dose of aspirin has not been formally tested, with most trials using 81
to 150 mg daily.76 Promising results from experimental studies and a pilot trial of
pravastatin104, 105 need to be critically viewed due to concerns related to fetal safety.

Experimental evidence suggests that metformin may prevent preeclampsia by reducing sFlt1
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and soluble endoglin secretion from primary endothelial tissue and through senomorphic
mechanims.106, 107 65 Clinical studies have indicated that metformin may reduce the odds
of gestational hypertension in women with gestational diabetes, and that it may prevent
preeclampsia.108
5.0 Blood pressure measurement in pregnancy

Accurate BP measurement is crucial for classifying hypertension and initiating treatment,
regardless of pregnancy status. As mercury sphygmomanometers are less available, aneroid
devices are commonly used, although they require calibration and are less accurate. Several
oscillometric automated devices have been validated in pregnant women, including those
with gestational hypertension and preeclampsia.109
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While most current guidelines recommend hypertension management based on office BP in

pregnancy, for the general population, out of office BP measurements are widely endorsed
as more accurate and better predictors of cardiovascular morbidity and mortality.6, 110
Although several studies report BP levels during pregnancy using self-measured BP
(SMBP) or ambulatory BP monitoring (ABPM), current data describing appropriate out
of office cut offs for HDP diagnosis are limited.111 American College of Obstetricians and
Gynecologists and the International Society for the Study of Hypertension in Pregnancy
(ISSHP) recommend the use of SMBP in women with chronic or gestational hypertension,
particularly when uncontrolled.1, 112 Available information does not demonstrate a
systematic difference between self and office BP measurements in pregnancy, which
suggests appropriate treatment and diagnostic thresholds for self-monitoring during
pregnancy may be equivalent to standard clinic thresholds; however, additional information
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regarding appropriate methodology and validation of devices is needed.
5.1 Non-sustained hypertension

White coat hypertension is reported in 25% of the non-pregnant adult population. Its
prevalence in pregnancy is less certain, ranging from 4 to 30%.2 On the basis of 24 hour
BP measurements, 32% of hypertensive women had white-coat hypertension, but just 8%
were diagnosed as such.113 A meta-analysis of studies addressing white coat hypertension
reported increased risks of preeclampsia and adverse fetal outcomes compared to women
with normotension. Risks were lower compared to women with sustained chronic or
gestational hypertension.87 The frequency and clinical significance of masked hypertension
in pregnancy has not been extensively studied. Any category of non-sustained BP elevation
in pregnancy can progress to sustained hypertension and requires follow-up. Self-measured
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BP is important for diagnosing non-sustained BP elevations, including masked hypertension

and white coat hypertension which occur prior to 20 weeks of gestation. For clinical
purposes, the definition of hypertension in pregnancy requires two elevated BP four hours
apart (Table 1).

5.2 Blood pressure variation

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In the non-pregnant population, the association between BP variation, independent of

baseline BP, and CVD risk is mixed, although greater variability is more convincingly
associated with increased stroke risk.114–120 Limited small studies of gestational short-term
and visit-to-visit BP variation suggest that greater variation is associated with adverse
maternal and perinatal outcomes,121, 122 but evidence is currently inconclusive and there
is need for consensus regarding the methodology for the measurement of BP variability in
pregnancy.
Standard gestational age-specific BPs and centiles can assist in clinical interpretation of
BP changes from expected levels.55, 122 Nationally representative, population-specific,
gestational BP references have been reported from China and the United Kingdom.51, 53
Studies addressing the association of BP changes in relation to healthy BP standards with
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maternal and perinatal outcomes are needed.
5.3 Secondary hypertension

Most (~90%) women with chronic hypertension have primary hypertension. Secondary
hypertension may occur in a small proportion of women and is associated with worse
maternal and fetal outcomes; it should be considered if: maternal age is <35 years,
hypertension is severe or resistant, there is no family history of hypertension, or there
are suggestive laboratory features, such as hypokalemia, elevated creatinine, or albuminuria
early in pregnancy (Table 5).123, 124 Finally, the prevalence of obesity in reproductive-aged
women has increased in recent years and obstructive sleep apnea may play an increasing
role in secondary hypertension among pregnant women.125, 126 As there are no pregnancy-
specific guidelines for obstructive sleep apnea treatment, pregnant women with sleep apnea
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should be managed concurrently with a sleep medicine specialist for application of available
diagnostic and therapeutic methods depending on the stage of pregnancy.
5.4 Postpartum hypertension and postpartum preeclampsia

Postpartum hypertension and postpartum preeclampsia are not specifically included in the
classification of HDP, but there is increasing awareness of their significance, as documented
in the 2013 ACOG executive summary that implemented changes in clinical practice
through closer postpartum monitoring and visits.127 These entities are particularly important
for two reasons. First, roughly 80% of all maternal deaths occur within the first week
postpartum, and HDP remain one of the leading causes of maternal mortality.128 Second,
postpartum hypertension offers an opportunity to use medications and achieve BP goals
without limitations related to their potential negative impacts on the fetus. The prevalence of
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postpartum hypertension may be as high as 8% in women without antepartum hypertension

(followed 48 hours after delivery and up to 6 weeks postpartum), and up to 50% in women
with a history of preeclampsia 6–12 weeks post-delivery.129, 130 The distinction between
postpartum aggravation of antepartum HDP and de novo postpartum preeclampsia (also
termed, delayed onset postpartum preeclampsia) is unclear. Further research addressing
underlying mechanisms is needed to clarify appropriate treatment and need for magnesium
sulfate for seizure prevention. The duration ranges from days to 3 months, contributing to
serious short term maternal complications such as stroke, seizures and cardiomyopathy, and

metabolic dysregulation such as insulin resistance and weight gain.129, 130 Patient education
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is an important tool for early recognition of symptoms and signs. Novel approaches such as
remote hypertension monitoring programs have potential to improve compliance and early
diagnosis of postpartum hypertension and preeclampsia.131
The rate of elevation in the antepartum sFlt1/PlGF ratio is an independent predictor of

hypertension that persists postpartum.132 Furthermore, preeclampsia associated endothelial
dysfunction and altered cerebrovascular autoregulation have been shown to persist
postpartum133 and may amplify postpartum hypertension risk. Intravenous fluids,
mobilization of extravascular fluid and use of nonsteroidal anti-inflammatory drugs
(NSAIDs) for postpartum analgesia may contribute to its occurrence. A recent randomized
controlled clinical trial has shown that postpartum use of furosemide in women with
HDP was associated with a 60% reduction in persistent hypertension at day 7 following
delivery (adjusted relative risk 0.40).134 If these findings can be implemented in the
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clinic, there is significant opportunity to reduce maternal morbidity in the postpartum

period and avoid unnecessary hospitalization. In non-pregnant individuals, there is abundant
evidence that NSAIDs are associated with clinically significant increases in BP.135–137 A
recent systematic review and meta-analysis that included 5 randomized controlled trials
and 5 retrospective cohorts concluded that compared to acetaminophen, NSAIDs were
not associated with increased BPs up until discharge (2 to 4 days postpartum).138 The
authors considered the quality of evidence to be very low because of the small sample
sizes, imprecise results and short duration of follow up. Additional investigation is needed
to address the impact of longer duration of postpartum NSAID use in older women with
chronic hypertension and additional renal and cardiovascular risk factors.139, 140
6.0 Treatment of Hypertension in Pregnancy

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6.1 Current blood pressure goals for pregnant patients

The recent ACC/AHA task-force guidelines lowered the threshold for the diagnosis of
hypertension in non-pregnant patients to 130/80 mm Hg for stage 1 hypertension, and
140/90 mm Hg for stage 2 hypertension, resulting in larger numbers of individuals being
diagnosed and treated.6 There is robust evidence in the general population demonstrating
reduced CVD risk with treatment to lower levels,7 and indeed, most cardiovascular
events occur in individuals with BP levels of 140–159/90–109 mm Hg.141 Even younger
individuals with hypertension demonstrate early vascular remodeling and endothelial
dysfunction, particularly in smaller arteries and arterioles, which leads to progressive
stiffening of larger blood vessels and organ damage if hypertension is untreated.142, 143 For
all HDP, hypertension is defined internationally as a BP ≥140/90 mm Hg, though treatment
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thresholds and targets vary (Table 6).
The recommendations of published guidelines addressing diagnosis and treatment of HDP

are summarized in Table 6. Differences among societies further demonstrate confusion in
the field, which likely contributes to a failure to move forward. The ACOG recommends
antihypertensive therapy for women with preeclampsia and a sustained systolic BP ≥160
mm Hg and/or diastolic BP ≥110 mm Hg, and with chronic hypertension at a systolic BP
≥160 mm Hg or diastolic BP ≥110 mm Hg, with a treatment goal of 120–160/80–110

mm Hg.2 Internationally the majority of hypertension societies endorse a more aggressive

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approach for antihypertensive treatment, recommending therapy when BP is ≥140/90 mm

Hg.112, 144–146, 152, 154 Therapeutic targets similar to the ACC/AHA target of 130/80 mm
Hg6 are recommended by the ISSHP,112 Hypertension Canada Guidelines,148, 152 NICE,146
and the WHO.145 The question arises: why are the diagnostic and treatment BP thresholds
higher in the U.S. compared to those recommended for non-pregnant individuals and in
comparison to the majority of international guidelines addressing HDP?
Determining the optimal BP threshold in pregnancy for antihypertensive treatment and

therapeutic targets requires a balance between prevention of maternal hypertensive
complications and avoidance of fetal risks. The US (ACOG) guidelines are influenced by
at least three debated issues. First, is the prevailing perspective, based on small studies,
that there are no measurable immediate or long-term health benefits of more strict BP
treatment for the relatively short duration of pregnancy (4 to 9 months, depending on
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type of HDP) in young women without other CVD risks. Second, there are concerns that
lowering maternal BP may compromise utero-placental circulation and negatively affect
fetal well-being and growth. Third, therapeutic options are limited due to concerns regarding
potential adverse fetal effects, particularly malformations from intrauterine exposure to
antihypertensive medications. Furthermore, discrepancies among international guidelines are
a reflection of the country specific context within which they were developed. Such debate
and subsequent inconsistencies in recommendations hinder progression towards consensus
for optimal management of HDP internationally. For example, differences in BP thresholds
for initiating antihypertensive therapy make combining results from observational studies of
antihypertensive therapy for meta-analysis more challenging.
6.2 Blood pressure goals for pregnant patients: emerging data, limitations and current
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controversies
There are several compelling reasons to consider lower BP thresholds. First, more aggressive
treatment of hypertension in pregnancy prevents the development of severe hypertension,
as demonstrated by both a systematic review of randomized trials155 and the Control of
Hypertension In Pregnancy Study trial (CHIPS), in which the average BP achieved by
tight control was 133/85 mmHg.16 While comparison of less tight versus tight control
showed no effect on rates of preeclampsia, the former group demonstrated a higher risk
of thrombocytopenia and elevated liver-enzyme levels, markers of disease severity. Also,
in this trial and elsewhere, ‘tight’ control may have decreased the risk of preterm birth.156
The importance of severe hypertension as an outcome has been questioned,22 although
exploratory analyses of the CHIPS data (adjusted for allocated group and prognostic factors)
showed that severe hypertension is a surrogate marker for adverse maternal and perinatal
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outcomes, independent of and similar in magnitude to preeclampsia.16, 22 This is especially

relevant in high risk populations, such as Black women, for whom the risk of hypertension
related adverse outcomes is high.157 A study of Black women with chronic hypertension
showed that use of antihypertensives prior to 20 weeks of gestation and achieving a BP
<140/90 mm Hg was associated with lower incidences of superimposed preeclampsia and
preterm delivery <35 weeks compared to women with BP ≥140/90 mm Hg.158 Furthermore,
lower (<140/90 mm Hg) versus higher (≥140/90 mm Hg) BP levels during pregnancy

have been associated with lower rates of preeclampsia, including preeclampsia with severe
features, and lower rates of pre-term delivery.156 Lower rates of preeclampsia with treatment
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of hypertension reported by these most recent studies are in sharp contrast with the
majority of previous studies indicating that treatment of hypertension does not prevent
preeclampsia. Whether there is a difference between women with chronic (who were
preferentially recruited in these 2 studies indicating benefit) versus gestational hypertension,
remains unknown; the answer will require prospective, adequately powered studies. Based
on results of retrospective studies, including one showing benefit of tighter BP control,159
and the other indicating that malignant/uncontrolled hypertension in the non-pregnant state
has similar changes in the brain as eclampsia,160 a large randomized controlled trial The
Chronic Hypertension and Pregnancy (CHAP) Project is nearing completion in the United
States (ClinicalTrials.gov Identifier: NCT02299414) comparing outcomes between pregnant,
chronically hypertensive women who are given antihypertensive treatment to maintain BP
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<140/90 mm Hg, to women given no treatment, unless BP is ≥160/105 mm Hg.
Second, there is evidence that the pathophysiology of the neurologic manifestations

(headaches, visual disturbances, seizures) of preeclampsia is similar to that of the posterior
reversible leukoencephalopathy syndrome.161 Women with preeclampsia may be more
susceptible to severe neurologic outcomes, such as intracerebral hemorrhage, at lower
systolic BPs (e.g. 150–170 mmHg)162 compared to non-pregnant subjects, thus raising the
possibility that lowering BP below current targets (e.g., <150/90 mm Hg) may prevent these
rare but devastating outcomes.162
Third, treatment of non-severe hypertension in pregnancy (e.g. BPs 140–155/90–109 mm

Hg) may permit prolongation of pregnancy in women without other severe features of
preeclampsia that would require delivery.
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Fourth, ACOG guidelines recommend withholding antihypertensive therapy for patients

with preeclampsia unless BP approaches 160/110 mm Hg. They also recommend urgent
delivery for women with severe features of preeclampsia, which include uncontrollable
HTN with BP ≥160/ 110 mm Hg, even for pregnancies < 34 gestational weeks, unless
high level care is available in facilities with adequate maternal and neonatal intensive care
resources.3, 112, 163 Lowering thresholds for treatment may allow for timely BP control and
avoidance of rushed deliveries that commonly lead to prematurity and related complications.
Fifth, the classical view that young, hypertensive women without other CVD risk factors are
at low short term CVD risk from untreated hypertension during the duration of pregnancy,
is challenged by current epidemiological and demographic trends towards advanced age
at first pregnancy and higher CVD risk (subclinical or diagnosed).164–167 This could also
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be relevant among women with multiple pregnancies, who may spend several years of
their lives either pregnant or breastfeeding with uncontrolled hypertension. In addition,
modern fertility techniques facilitate pregnancy in women with pre-existing conditions
associated with elevated CVD risk (e.g., diabetes, chronic kidney disease, and polycystic
ovary syndrome). Pre-existing chronic kidney disease and heart disease are present in 3%
and 1–4% of pregnancies in high income countries, respectively.168 Several guidelines
consequently endorse more aggressive treatment in these women.150, 151

Finally, there is abundant evidence that HDP are associated with increased risk of both
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immediate and postpartum complications (such as acute cardiovascular and cerebrovascular

disease)169 and future maternal vascular disease (Table 3). Whether better management
of BP during pregnancy will lead to lower rates of morbidity related to hypertension in
the immediate postpartum period is not known. Traditional CVD risk factors (e.g. obesity,
hypertension, diabetes, hyperlipidemia) are associated with increased risk of HDP,79 but
the associations between HDP and future CVD, renal disease and vascular dementia,
persist, even after adjustment for such factors.34, 39 37 It is estimated that approximately
two thirds of HDP-associated CVD risk is mediated via established risk factors, and
the remainder likely explained by a HDP-specific etiology.25, 33 Whether treatment of
non-severe hypertension is beneficial for preventing long term morbidity beyond pregnancy
and the puerperium, remains to be demonstrated. Further, evidence is needed to clarify
concerns over the observed, albeit non-statistically significant, trend towards increased small
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for gestational age risk and decreased preterm birth in women with tight vs. less tight BP
control in CHIPS.170 Limited, though reassuring information regarding possible risk of drug
associated fetal malformations, long-term neurodevelopmental effects on offspring,171 and
the suggested differential effects on these outcomes by antihypertensive class155, 172 are all
areas that require further investigation.
Given new developments in the field of hypertension outside of pregnancy that support
lower BP treatment targets, together with emerging data from larger clinical trials in
pregnancy, this working group supports continued investigation to determine whether BP
levels similar to those recommended outside of pregnancy for initiation of therapy and
as therapeutic targets are beneficial for the mother, and safe and beneficial for the fetus.
While awaiting more conclusive data and trials nearing completion, we endorse informed
decision making in partnership with the patient as to whether or not to treat non-severe
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hypertension during pregnancy to targets similar to those recommended in non-pregnant

individuals. Personalization of therapy, by giving special attention to other risk factors
related to hypertension-related adverse outcomes (such as pre-existing heart or kidney
disease; obesity and Black race) is a rational approach.
6.3 Antihypertensive medications

Initial antihypertensive therapy is widely established to be monotherapy with an accepted
first-line drug; labetalol, or methyldopa. Some,1, 112, 144–146, 150, 152 but not all,151 societies
support the use of nifedipine as an initial therapy. For countries where labetalol is
unavailable (e.g., Germany), alternative beta-blockers such as metoprolol or oxprenolol
can be considered. These therapeutic options are based on small individual trials and
are advocated by national and international clinical practice guidelines. There is no
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clear evidence that one drug is preferable to another based on systematic review of
randomized trials for all types of pregnancy hypertension considered together, for all
antihypertensives considered together, or for beta-blockers (including labetalol) considered
separately.155 However, in a separate network meta-analysis, specifically for treatment of
chronic hypertension, atenolol was associated with fetal growth restriction,173 especially
when given for a longer duration.174 These data conflict with some observational studies
that have associated beta-blocker treatment (including labetalol) with an excess of small for

gestational age infants, although authors did not necessarily adjust for treatment indication
and severity of maternal disease.175 These conflicting data underscore a need for more fetal
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and newborn data on the safety of currently used antihypertensive agents in pregnancy.
Numerous clinical trials have compared various short acting antihypertensives in the setting
of acute, severe hypertension in pregnancy. The drugs most commonly examined are
parenteral hydralazine, parenteral labetalol, and oral nifedipine (short, intermediate or long
acting). A Cochrane review concluded that these drugs were comparable with respect to
safety and efficacy, and recommended that providers choose on the basis of experience and
familiarity with a particular drug.176 Most cases of severe hypertension can be successfully
controlled with these drugs using doses and protocols recommended by professional
societies.177 In resource-poor countries, a report documented successful treatment of acute
severe hypertension with oral preparations of labetalol, intermediate acting nifedipine,
and methyldopa.178 Additional agents that may be considered for resistant hypertension,
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although not extensively studied, include nicardipine, clonidine, and furosemide.179–181

Notably, diuretics, the mainstay of hypertension treatment in non-pregnant individuals, are
not used often in pregnant women. This position is mainly informed by earlier studies
suggesting that women with preeclampsia have lower plasma volume suggesting that
diuretics may further aggravate volume depletion and promote reactive vasoconstriction.
However, older studies demonstrated their favorable safety profile in pregnancy182 and more
recent guidelines have acknowledged that in women with salt sensitive chronic hypertension,
or chronic kidney disease and reduced GFR, diuretics may be used safely although perhaps
at lower doses.2 Recent studies demonstrate that they may be particularly effective in
postpartum hypertension.134
The limitations of existing data regarding the safety of antihypertensives in pregnancy

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are highlighted by a systematic review of studies addressing in utero exposure to

antihypertensive medications and adverse fetal outcomes. Only 5 of 47 studies were
considered high quality, few studies reported increased odds of adverse effects in treated
compared to normotensive untreated women, including congenital malformations, and
effects were not uniformly observed across different studies using the same medications.171
Further, similar adverse events have been reported in untreated hypertensive women, leading
to the conclusion that the evidence for teratogenicity of most antihypertensive agents is
weak.183, 184
While it is first trimester exposure to medication that raises concern about structural
malformations (other than those due to physical or vascular disruption), the fetal central
nervous system develops throughout gestation and may be affected by exposures at any time
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point. However, no firm conclusions can be drawn regarding long-term child outcomes given
the paucity of relevant high-quality studies.171 No adverse neurodevelopmental effects have
been observed for methyldopa,185 nifedipine,186 or atenolol,187 although atenolol should
be used with caution (see above). Registry data adjusted for important covariates were
reassuring about the effects of preeclampsia itself; only a minimal effect was seen on
standardized mathematics test scores in children from affected pregnancies at ages 9, 12, and
15 years.188 Also, when untreated or treated hypertension controls have been used, children
from labetalol and methyldopa-treated women had similar IQ scores.2, 16, 161, 189, 190 Small

clinical trials and observational studies suggest that amlodipine, clonidine and thiazide
diuretics are probably safe in pregnancy as well.191–193 It is also widely accepted that
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all renin angiotensin system blockers should be avoided during pregnancy,194 especially
during the second and third trimesters when blockade of the fetal renin angiotensin system
clearly interferes with kidney development and function. Given suboptimal, and, frequently,
contradicting data regarding fetal safety after exposure to antihypertensive medications in
utero, well-designed, carefully controlled trials are needed, with attention given to short and
long-term fetal as well as maternal outcomes. Finally, the providers in the field should be
familiar with services offered by The Organization of Teratology Information Specialists.195
The organization was founded in 1987 as a way of connecting experts in the field of birth
defects research to the general public. It provides up-to-date information about the risks of
medications during pregnancy and breastfeeding to patients, health care professionals, and
researchers in the field of teratology.
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7.0 Postpartum screening

International guidelines, including the ACOG, ISSHP, ESC and AHA, emphasize the need
for appropriate postpartum screening and control of cardiovascular risk factors for women
with a history of preeclampsia. However, the lack of studies demonstrating efficacy and
effectiveness of counseling and interventions in formerly preeclamptic women impedes
the development of evidence-based guidelines. The recommendations given by different
guidelines are vague and imprecise (Table 6). Randomized trials are needed to evaluate
potential long-term cardiovascular benefits of early initiation of statins, aspirin, or renin
angiotensin system blockers in women with only a history of HDP as a risk factor. Lifestyle
interventions addressing obesity, hypertension, and dyslipidemia are good clinical practices.
Studies demonstrating the efficacy of these interventions in women of reproductive age are
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also needed.
8.0 Multidisciplinary team approach

Management of hypertension in pregnancy requires multidisciplinary collaborations
among obstetricians, maternal fetal medicine specialists, neonatologists, nephrologists and
hypertension specialists, cardiologists, anesthesiologists, pharmacists, nurses and midwives
– all of whom contribute to providing cohesive and safe preconception, ante-, peri- and
postpartum care. In particular, nurses and midwives in case management roles coordinate
care and facilitate access to resources and services that improve health outcomes, such
as group prenatal care,196 economic vulnerability and chronic stress risk assessments,
medication adjustments, lifestyle advice and patient education. During hospital admission,
nursing recognition of maternal compromise using early warning scores,197 hypertension
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bundles and toolkits ensures timely communication with a physician or advanced practice
nurse and has been shown to reduce maternal mortality from hypertensive disorders.198
9.0 Hypertension in pregnancy and racial disparities

Maternal mortality within the U.S. is among the highest of high income countries, with
a maternal mortality ratio (MMR) of 18 per 100,000 live births.199 Within the U.S.,

racial maternal health disparities are unacceptably large. The estimated MMR in 2016 for
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Caucasian women was 13 per 100,000 live births; 30 for American Indian and Alaskan
Native women and 41 for Black American women, similar to that of an upper-middle
income country.200 In addition to having poorer social determinants of health, implicit
racial bias is present within the U.S. health care system, and management of severe
maternal morbidity is consistently worse for Black and American Indian and Alaskan
Native women.201 Hypertensive disorders of pregnancy disproportionally affect Black and
American Indian and Alaskan Native women,200, 202, 203 predominantly due to the overall
higher prevalence of CVD risk factors,204 but there is also evidence to suggest biological
factors (e.g., specific genetic variants) may increase the risk of preeclampsia for Black
women.205, 206 Furthermore, preeclampsia-related severe morbidity and mortality are higher
for Black women, while for Hispanic women, pregnancy outcomes tend to be better than
those of Black or Caucasian women of similar risk.207, 208
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Studies must include sufficient numbers of participants from all racial groups, especially
Black women, to address maternal health disparities and inform policy and clinical practice.
We endorse studies addressing prevention of shared risk factors for HDP and CVD, and
those aiming to improve antenatal and postnatal outcomes.
10.0 Conclusion and future directives

Evidence suggests that antihypertensive therapy for pregnancy hypertension of any type
halves the incidence of severe hypertension. To some, if not many, this is sufficiently
compelling to dictate a change in practice towards more aggressive treatment. This may
be of particular importance in under-resourced communities with less experience and low
capacity to respond to hypertensive urgencies/emergencies. Of high income countries the
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USA has one of the highest hypertensive related maternal mortality,12 and increasing
maternal morbidity and mortality from cardiovascular conditions and cerebrovascular
accidents.10, 11 A lower treatment threshold than currently proposed by ACOG, has the
potential to decrease serious hypertensive end-organ complications. The view that mild to
moderate hypertension of short duration during pregnancy is not harmful to the mother,
may be partly addressed by the Chronic Hypertension and Pregnancy study, a trial that
will extend observations made in earlier trials of women with chronic hypertension which
demonstrated normalization of BP with antihypertensive treatment did not adversely affect
fetal growth or neurodevelopmental outcomes. Based on existing data, physicians are
encouraged to individualize treatment decisions, taking other risk factors into account.
Future clinical trials should address questions regarding the optimal BP treatment thresholds
and should be adequately powered to assess the effects of different BP targets on
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maternal and fetal/neonatal outcomes. Of note, when HDP was reclassified using the lower
ACC/AHA diagnostic threshold (SBP≥130 mm Hg or DBP ≥80 mm Hg), results indicated
that using the lower diagnostic threshold for hypertension in pregnancy may better identify
women at risk for developing preeclampsia and pregnancies at risk for adverse fetal/neonatal
outcomes.209
Studies are also needed to determine adequate levels of BP control in the postpartum period
given that first, there are no longer reservations about the impact of BP treatment on the

fetus, second, significant maternal morbidity and mortality occurs during this time period,
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and third, prolonged postpartum in-hospital stay and readmissions, have a significant impact
on health care resources and birth experiences.
Treatment of hypertension, prevention of seizures, and timed birth with close fetal
monitoring are currently the main therapeutic options for women with preeclampsia. The
superiority of any of the widely used antihypertensive(s) has not been demonstrated, and
combination therapies have not been tested. While a ‘same drug for all’ approach is
practical in many settings, a more personalized approach, based on patient preferences,
age, race, heart rate, BP variations measured at home or in clinic, or more detailed
hemodynamic assessments, may be more effective in protecting women from complications
of hypertensive pregnancies and possible post-pregnancy CVD consequences. Ongoing
research addressing causative pathways has the potential to identify new biomarkers and
novel therapeutics that target fundamental mechanisms of preeclampsia.
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Finally, on a global level, evidence-based consensus on diagnostic and treatment thresholds

(such as ≥ 140/90 mm Hg), targets (keeping it below 140/90 mm Hg), long-term CVD
risk assessment and HDP terminology are needed to facilitate progression in the field
and importantly ensure all women worldwide receive optimal care, before, during and
after pregnancy. Future guidelines should avoid integration of historical, unsubstantiated
perspectives which impede improvements in women’s health during pregnancy and
throughout women’s reproductive lives.
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Figure 1: Pathogenesis of hypertensive disorders of pregnancy

Pre-existing maternal co-morbidities, non-modifiable patient characteristics, reproductive
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history, genetic and immune factors increase the risk of developing a HDP (hypertensive
disorder of pregnancy). The molecular and pathophysiological mechanisms of preeclampsia
are largely unknown, but the etiology is likely a combination of, and interaction between,
factors from both maternal and placental pathways.63 Variable contributions of the
underlying maternal and placental pathophysiological pathways result in the heterogeneous
phenotypes of HDP. The associated widespread endovascular damage and dysfunction may
be long-lasting with a possible intergenerational effect.

TPR, total peripheral resistance; CO, cardiac output; GFR, glomerular filtration rate;
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ROS, reactive oxygen species; uNK, uterine natural killer cell; sFlt1, soluble fms-like
tyrosine kinase 1; sENG, soluble endoglin; VEGF, vascular endothelial growth factor;
PlGF, placental growth factor; IL-10, Interleukin 10; Th-1, Type 1 T helper cell; AT1-
AA, angiotensin II receptor 1 autoantibodies; ET-1,endothelin-1; TNF-α, tumor necrosis
factor alpha; SASP, senescence-associated secretory phenotype; RAS, renin angiotensin
system; Ang I, Angiotensin I; Ang II, Angiotensin II; ACE, Angiotensin converting
enzyme; ATR1, Angiotensin II type 1 receptor; DIC, disseminated intravascular coagulation;
VTE, venous thromboembolism; PRES, posterior reversible encephalopathy syndrome; MI,
myocardial infarction; PCM, peripartum cardiomyopathy; SCAD, spontaneous coronary
artery dissection; CAD, coronary artery disease; HF, heart failure; AKI, acute kidney injury;
CKD, chronic kidney disease; ESKD end stage kidney disease; SGA, small for gestational
age; FGR, fetal growth restriction.
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Podocyturia: the urinary loss of podocytes (glomerular epithelial cells) in preeclamptic

women contributes to the development of proteinuria and has been documented both before
and at the time of preeclampsia diagnosis.64
Senescence: an irreversible cell-cycle arrest mechanism that leads to systematic metabolic
and functional decline and which may play a role in impaired angiogenesis in
preeclampsia.65
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Table 1.
American College of Obstetricians and Gynecologists definitions for Hypertensive Disorders of Pregnancy1, 2
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Hypertensive
Definitions
Disorder
Hypertension in Systolic BP ≥140, or diastolic BP ≥ 90 mm Hg, or both measured on 2 occasions at least 4 hours apart
pregnancy
Severe-range Systolic BP ≥160, or diastolic BP ≥110 mm Hg, or both measured on 2 occasions at least 4 hours apart (unless
hypertension antihypertensive therapy initiated before this time)
Chronic Hypertension diagnosed or present before pregnancy, or before 20 weeks of gestation; or hypertension that is diagnosed
hypertension for the first-time during pregnancy and that does not resolve in the postpartum period
Gestational Hypertension diagnosed after 20 weeks of gestation and a previously normal BP
hypertension
Chronic Preeclampsia in a woman with a history of hypertension before pregnancy, or before 20 weeks of gestation
hypertension with
superimposed
preeclampsia
Preeclampsia Hypertension in pregnancy >20 weeks of gestation and previously normal BP or severe range hypertension, in addition
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to at least 1 of the following:

• Proteinuria (≥300 mg/24-hour urine, or PCR ≥0.3, or dipstick 2+ only if other quantitative methods not
available)
• Renal insufficiency (creatinine > 1.1 mg/dL or doubling of the serum creatinine concentration in the
absence of other renal disease)
• Thrombocytopenia (<100× 109/L)
• Impaired liver function (ALT/AST ≥ 2x upper limit of normal)
• Pulmonary edema
• New-onset headache or visual disturbances (not due to alternative diagnoses)
Preeclampsia with • Severe range hypertension (Systolic BP ≥160, or diastolic BP ≥110 mm Hg, or both)
severe features
• Renal insufficiency (creatinine > 1.1 mg/dL or doubling of the serum creatinine concentration in the
absence of other renal disease)
• Thrombocytopenia (<100× 109/L)
Author Manuscript
• Impaired liver function (ALT/AST ≥ 2x upper limit of normal)

• Severe persistent right upper quadrant or epigastric pain unresponsive to medications
• Pulmonary edema
• New-onset headache or visual disturbances (not due to alternative diagnoses)
BP, blood pressure; PCR, protein creatinine ratio; AST, aspartate aminotransferase; ALT, alanine aminotransferase
Author Manuscript

Table 2.
Immediate maternal and fetal complications of Hypertensive Disorders of Pregnancy

Author Manuscript
Maternal Outcome Effect estimate (95% confidence interval)

Mortality
Chronic hypertension aOR 1.7 (1.2–2.4)15

Preeclampsia OR 2.7 (1.0–7.1) *16
aOR 2.6 (2.1–3.4)17
Preeclampsia superimposed on chronic hypertension aOR 2.3 (1.5–3.6)17
Myocardial infarction

Gestational hypertension aOR 1.0 (0.5–2.2)17
Preeclampsia aOR 3.0 (2.0–4.6)17
Author Manuscript
Stroke

aOR 1.6 (1.1–2.3)18
aOR 7.1 (5.3–9.6)18
Eclampsia aOR 65.9 (43.6–99.6)18
Peripartum cardiomyopathy
Hypertensive disorder of pregnancy aOR 3.2 (2.1–4.9), White women19

aOR 4.0 (2.3–7.1), Black women19
Author Manuscript
aOR 3.0 (1.3–7.0), Hispanic women19

SCAD 7.6% higher prevalence of preeclampsia in women with SCAD vs. U.S. women of
childbearing age20
Fetal/Neonatal outcomes Effect estimate (95% confidence interval)
SGA (birth weight <10th centile)
Hypertensive disorder of pregnancy RR 1.6 (1.5–1.6)21

Severe hypertension OR 1.8 (1.2–2.6)22
Preeclampsia OR 1.5 (1.0–2.2)22
Author Manuscript
Still birth
Hypertensive disorder of pregnancy RR 1.4 (1.1–1.8)21



Preterm delivery (<37 weeks)
Author Manuscript

aOR 3.1 (3.0–3.1)17
Preterm delivery (<34 weeks)

Placental abruption
Author Manuscript

Postpartum hemorrhage

*
The study endpoint was a composite of mortality and other serious complications
Effect estimates are unadjusted unless specified as aHR/aOR. Different studies have adjusted for different variables; for specifics, please refer to the
original references. Comparison groups are women who had normotensive pregnancies.
SCAD, spontaneous coronary artery dissection; SGA, small for gestational age; OR, odds ratio; RR, risk ratio; a, adjusted.
Author Manuscript
Author Manuscript

Table 3.
Long-term maternal and off-spring complications of Hypertensive Disorders of Pregnancy

Author Manuscript
Maternal Outcome Effect estimate (95% confidence interval)

Hypertension (≥140/90 mm Hg)
Hypertensive pregnancy disorder HR 2.3 (1.9–2.8)23

OR 11.6 (10.6–12.7)25
Preeclampsia aHR 4.5 (4.3–4.6)26
aHR 2.2 (2.1–2.3)26
RR 3.1 (2.5–3.9)27
RR 3.7 (2.7–5.1)28
OR 3.4 (3.1–5.0)29
Type 2 Diabetes

HR 2.0 (1.7–2.4)25
HR 1.4 (1.3–1.7)30
aHR 1.8 (1.6–1.9)26
Author Manuscript
Preeclampsia
OR 2.14 (1.5–3.0)29
Hyperlipidemia

HR 1.5 (1.3–1.7)25
Preeclampsia aHR 1.3 (1.3 to 1.4)26
Sub-clinical markers of vascular damage
Augmentation index Weighted mean difference 5.5 % (1.6–9.4)31
Carotid intima-media test Weighted mean difference 0.02 mm (0.00–0.04)31

> 0.77 mm, aOR 3.2 (1.1–9.1)32
Carotid–femoral pulse wave velocity Weighted mean difference 0.6 m/s (0.2–1.1)31
Arterial stiffness index Unadjusted difference 0.32 m/s (0.13–0.51)25
†
Author Manuscript
Cardiovascular disease
Gestational hypertension aHR 1.4 (1.1–1.9) *33

OR 1.7 (1.3–2.2)24
HR 1.7 (1.6–1.8)34
OR 1.7 (2.5–3.0)24
Preeclampsia with severe features OR 2.7 (2.5–3.0)24
Early onset preeclampsia (<34 weeks of gestation) aHR 4.9 (3.0–7.8)35
OR 5.6 (1.5‐21.4)29
Coronary heart disease
Hypertensive pregnancy disorder aHR 1.9 (1.4–2.5)33

HR 1.7 (1.3–2.3)23
HR 1.6 (1.1–2.2)25
Author Manuscript
HR 1.7 (1.5–1.8)34
RR 2.5 (1.4–4.4)36
Heart failure

HR 2.7 (1.6–4.6)23
HR 2.4 (1.3–4.2)25


aHR 2.0 (1.1–3.7)33
RR 4.2 (2.1–8.4)36
Author Manuscript
Atrial Fibrillation

All stroke

HR 1.9 (1.3–2.6)23
aHR 1.5 (1.1–2.1)33
RR 1.8 (1.3–2.6)36
Ischemic hemorrhage aHR 1.7 (1.4–2.1)34
Intracerebral hemorrhage aHR 1.7 (1.2–2.4)34
Subarachnoid hemorrhage aHR 2.0 (1.6–2.5)34

Author Manuscript
Vascular dementia
Gestational hypertension aHR 3.0 (2.1–4.3)37

HR 3.5 (2.0–6.1)38
Chronic kidney disease
Gestational hypertension RR 1.5 (1.1–2.0)39

Preeclampsia RR 2.3 (1.5–3.5)39
End stage kidney disease
Gestational hypertension RR 3.6 (2.3–5.7)39

Preeclampsia RR 6.6 (2.7–14.8)39
Venous thromboembolism

Author Manuscript
Gestational hypertension aHR 1.4 (1.3–1.5)40

Offspring Outcome Effect estimate (95% confidence interval)

‡
Cardiovascular disease
Severe preeclampsia, term delivery aHR 2.3 (1.1–4.7)41
Stroke
Preeclampsia HR 1.9 (1.2–3.0)42

Gestational hypertension HR 1.4 (1.0–1.8)42
BMI
Preeclampsia Mean difference 0.36 kg/m2 (0.04–0.68)43
Author Manuscript
Hypertension (≥140/90 mm Hg)
Preeclampsia SBP 5.2 mm Hg (1.6–8.7)44

DBP 4.1 mm Hg (0.7–7.4)44
Gestational hypertension SBP 2.0 mm Hg (1.4–2.7)45
DBP 1.1 mm Hg (0.6–1.5)45
*
Chronic hypertension was included as a CVD endpoint in this study.

†
Cardiovascular disease includes ischemic / hypertensive heart disease or stroke
‡
Cardiovascular disease included cardiomyopathy, hypertension, pulmonary heart disease, arrhythmia or heart failure.
All effect estimates are unadjusted unless specified as aHR. Different studies have adjusted for different variables; for specifics, please refer to the
Author Manuscript
original references. Comparison groups are women who had normotensive pregnancies.
BMI; body mass index, SBP, systolic blood pressure; DBP diastolic blood pressure, HR; hazard ratio, OR; odds ratio, RR; risk ratio, a; adjusted.
Author Manuscript
Author Manuscript
Author Manuscript

Table 4.
Risk factors for Preeclampsia

Author Manuscript
Risk Factors Effect estimate (95% confidence interval)
High*
Prior preeclampsia RR 8.4 (7.1–9.9)79
Chronic stage 2 hypertension

† RR 5.1 (4.0–6.5)79
(≥140/90 mm Hg)
Pre-gestational diabetes RR 3.7 (3.1–4.3)79
Multi-fetal pregnancy RR 2.9 (2.6–3.1)79
Antiphospholipid syndrome RR 2.8 (1.8–4.3)79
Systemic lupus erythematosus RR 2.5 (1.0–6.3)79
Chronic kidney disease OR 10.4 (6.3–17.1)80
Moderate*
Author Manuscript
Maternal age >35 years RR 1.2 (1.1–1.3)79

Pre-pregnancy BMI >30 aOR 3.7 (3.5–3.9)81
RR 2.8 (2.6–3.1)79
Family history (1st degree relative) RR 2.9 (1.7–4.9)82
Race (Black) aHR 1.6 (1.5–1.6)83
HR 2.2 (1.9–2.6), early onset84
HR 1.3 (1.2–1.4), late onset84
Low socioeconomic status aOR 4.91 (1.9–12.5)85
Nulliparity RR 2.1 (1.9–2.4)79
History of adverse pregnancy outcome:
Stillbirth RR 2.4 (1.7–3.4)79
Placental abruption RR 2.0 (1.4–2.7)79
Author Manuscript
Other
Chronic hypertension (130–134/80–84 mm Hg) aOR 2.2 (1.9–2.5), mild86

aOR 2.7 (2.0–3.5), severe86
Chronic hypertension (135–139/85–90 mm Hg) aOR 2.7 (2.3–3.2), mild86
aOR 3.8 (2.8–5.1), severe86
White coat hypertension RR 2.4 (1.2–4.8)87
Pre-pregnancy BMI >25 RR 2.1 (2.0–2.2)79
Insulin resistance >75th centile, Gestational diabetes aOR 1.9 (1.1–3.2)88
aOR 1.6 (1.4–1.9)89
Recovered acute kidney injury aOR 2.9 (1.9–4.4)90
Hyperthyroidism aOR 1.8 (1.1–2.9)91
Author Manuscript
Hydatidiform mole OR 10.1 (3.4–30.0)92

Trisomy 13 fetus Incidence, Trisomy 13 24–44% vs. without 2–8%93
Genetic susceptibility94, 95
Assisted reproductive technology RR 1.8 (1.6–2.1)79

Risk Factors Effect estimate (95% confidence interval)

Oocyte donation OR 4.3 (3.1–6.1)96
Author Manuscript
New paternity OR 2.3 (1.2–4.4)97

Pregnancy interval >4 years OR 1.1 (1.0–1.2), recurrent preeclampsia98
OR 2.1 (1.3–3.3)97
Migraine OR 2.1 (1.5–2.9)99
*
Classification of risk factors as high or moderate is based on the ACOG recommendations for aspirin therapy to prevent preeclampsia. Therapy is
indicated when ≥ 1 high or ≥ 2 moderate risk factors are present.77, 100
Others are based on an emerging number of factors that may increase risk of preeclampsia.
†
Based on the 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults6
Cohabitation of >12 months101 and smoking102, 103 have an inverse association with preeclampsia risk.
All estimates are unadjusted unless specified as aHR/aOR. Different studies have adjusted for different variables; for specifics, please refer to the
original references. Comparison groups are women without the risk factor of interest.
Author Manuscript
BMI, body mass index; HR; hazard ratio, OR; odds ratio, RR; relative risk.
Author Manuscript
Author Manuscript

Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Table 5.
Secondary causes of hypertension in pregnancy among young women
Diagnosis Clinical Features Laboratory Features Pregnancy Outcomes Treatment/ Management

Garovic et al.
Chronic Kidney Disease Edema Proteinuria Preeclampsia Antihypertensives

Hypertension Hematuria Pre-term birth IUGR Low dose aspirin
Decreased eGFR
Primary Hyperaldosteronism Postpartum HTN exacerbation Hypokalemia Preeclampsia risk increased Calcium channel blockers
Suppressed PRA Labetalol
Thiazide diuretics
Potassium supplementation
Renovascular Hypertension Resistant HTN Elevated PRA Preeclampsia Antihypertensives

Abdominal bruit Pre-term birth Angioplasty in second trimester
Pheochromocytoma Hypertension Elevated plasma + urine Severe hypertension MRI without gadolinium
Tachycardia metanephrines or catecholamines Fetal + maternal mortality Alpha blockade
Calcium channel blockers
Surgery in second trimester
Cushing’s Disease Gestational diabetes Urinary free cortisol Preeclampsia Metyrapone

Abdominal striae Late night salivary cortisol Pre-term birth Surgery
Hypertension High dose dexamethasone suppression test IUGR
Fetal mortality
Obstructive Sleep Apnea Hypertension Deranged polysomnography Preeclampsia CPAP

Apnea Desaturation Pre-term birth Oral mandibular repositioning devices
Fatigue Elevated HbA1c
Headaches Elevated EPO
Depression
eGFR, estimated glomerular filtration rate; IUGR, intrauterine growth restriction; HTN, hypertension; PRA, plasma renin activity; MRI, magnetic resonance imaging; HbA1c, glycated hemoglobin; EPO,
erythropoietin; CPAP, continuous positive airway pressure.

Page 40
Table 6.
Summary of and key discrepancies between published guidelines for the diagnosis and treatment of hypertensive disorders of pregnancy
HYPERTENSION IN
PREGNANCY Continuation of anti-
Guideline Treatment threshold (mm Hg) Treatment target (mm Hg)
hypertensive therapy
Garovic et al.
Diagnosis*
American College of Obstetricians 20131 ≥ 160/105 with diagnosis of chronic hypertension1 120–159/80–1051 Guided by informed
and Gynecologists 20192 ≥ 160/110 if acute3/chronic hypertension2 120–159/80–109 if chronic2 discussion with women
20203 † †
World Health Organisation 2018144 Not defined ‡ Above lower limits of Not specified
Not specified
2020145 normal145
National Institute for Health and 2019146 ≥ 140/90 ≤135/85 Continue treatment unless
Clinical Excellence <110/70 mm Hg or
symptomatic hypotension
Society of Obstetricians and 2018147 ≥ 140/90148, 149 DBP 85148, 149 Not specified
Gynaecologists, Canada 2020148 <140/90 + comorbidities149
International Society for the Study 2018112 + the absence of preeclampsia ≥ 140/90 in office 110–140/85 Not specified
of Hypertension in Pregnancy features ≥ 135/85 at home
European Society of Cardiology 2018150 “Antenatally unclassified” if first ≥ 150/95 Not specified Consider discontinuation if
BP measure > 20 weeks of ≥ 140/90 + end-organ damage / gestational BP 140–159/90–109 mm Hg
gestation hypertension + normal renal function
Society of Obstetric Medicine of 2014151 ≥ 160/100 Based on clinician Consider discontinuation if
Australia and New Zealand ≥ 140/90, optional assessment BP fall <20 weeks of
gestation
SUPERIMPOSED PREECLAMPSIA ON Treatment threshold (mm

Guideline PREECLAMPSIA Diagnosis § Treatment target (mm Hg)
CHRONIC HYPERTENSION Diagnosis § Hg)
American College of Obstetricians 20191 Chronic hypertension + a sudden change in ≥ 160/1101 Not specified
and Gynecologists preeclampsia diagnostic parameters
National Institute for Health and 2019146 Symptoms include utero- Not specified ≥ 140/90 ≤ 135/85
Clinical Excellence

placental dysfunction ∥
Society of Obstetricians and 2014149 Symptoms include ≥1 severe ≥ 20 weeks of gestation + resistant hypertension ≥ 140/90152 DBP 85152
Gynaecologists, Canada 2018152 complication + new or worsening proteinuria or
≥1 adverse conditions or severe complications of
preeclampsia
International Society for the Study 2018112 Symptoms include utero- Chronic essential hypertension + ≥ 1 sign ≥ 140/90 110–140/85
of Hypertension in Pregnancy ‡ of maternal organ dysfunction consistent with
placental dysfunction preeclampsia, or new-onset proteinuria in the
setting of a rise in BP
European Society of Cardiology 2018150 Proteinuria necessary, only Hypertension <20 weeks of gestation + ≥ 140/90 Not specified
high suspicion if hypertension superimposed gestational hypertension +
+ abnormal biochemistry / proteinuria
symptomatic
Page 41
Society of Obstetric Medicine of 2014151 Symptoms include fetal growth Pre-existing hypertension with proteinuria or ≥1 160/100 Individual assessment
Australia and New Zealand restriction systemic feature of preeclampsia 140–160 / 90–100, optional
Guideline Future cardiovascular disease risk management

American College of Obstetricians and Gynecologists 2019153 Postpartum follow-up visit (early postpartum visit) with either the primary care provider or cardiologist is recommended
Garovic et al.
within 7–10 days of delivery for women with hypertensive disorders

National Institute for Health and Clinical Excellence 2019146 Referral to family care doctor for CVD risk prevention
Society of Obstetricians and Gynaecologists, Canada 2014149 All women who have had a hypertensive disorder of pregnancy should pursue a healthy diet and lifestyle
International Society for the Study of Hypertension in 2018112 Regular general practitioner follow-up to monitor BP + periodic measurement of fasting lipids and blood sugar. Adopt healthy
Pregnancy lifestyle with maintenance of ideal weight and regular aerobic exercise
European Society of Cardiology 2018150 Annual primary care physician CVD risk screen
Society of Obstetric Medicine of Australia and New Zealand 2014151 Advise optimization of CVD risk factors
*
SBP ≥140 mm Hg +/ DBP ≥90 mm Hg; Gestational Hypertension, > 20 weeks of gestation + previously normal BP; Chronic/pre-existing Hypertension, < 20 weeks of gestation
†
American College of Obstetricians and Gynecologists guidelines state to consider a lower treatment threshold for chronic hypertension if comorbidities/renal failure are present and to consult with other
subspecialties regarding antihypertensive treatment BP targets, although this is not specified in the recommendations.2
‡
World Health Organisation recommendations state that “women with non-severe hypertension during pregnancy should be offered antihypertensive drug treatment in the context of good quality antenatal
care follow-up,”145 and “women with severe hypertension during pregnancy should receive treatment with antihypertensive drugs.”144
∥
Utero placental dysfunction: fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, stillbirth
§
All guidelines require SBP ≥140 mm Hg +/ DBP ≥90 mm Hg >20 weeks of gestation + previously normal BP + ≥1 proteinuria / abnormal renal or liver function tests or platelet count / symptoms and
signs consistent with end-organ damage of PE
BP, blood pressure; PE, preeclampsia; SBP, systolic blood pressure; DBP diastolic blood pressure

Page 42

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Published in final edited form as:

Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals,

the Kidney in Cardiovascular Disease Science Subcommittee, Council on Arteriosclerosis,

Traditionally, incidence of HDP was reported on a per-pregnancy basis to assist prediction

However, the HDP population-based incidence expressed per-pregnancy (7.5%)

Hypertension. Author manuscript; available in PMC 2023 February 01.

3.0 Pathophysiology of HDP

underfilling.58 Cardio-metabolic changes in normal pregnancy are more pronounced in

Placental pathology due to rheological consequences includes villous architectural changes

Hypertension. Author manuscript; available in PMC 2023 February 01.

ability of spontaneous vasoconstriction and ischemia-reperfusion injury, which may result in

Alterations in angiogenic factors are recognized as a likely consequence of abnormal

4.0 Prevention of preeclampsia and adverse maternal and fetal outcomes

Hypertension. Author manuscript; available in PMC 2023 February 01.

5.0 Blood pressure measurement in pregnancy

While most current guidelines recommend hypertension management based on office BP in

regarding appropriate methodology and validation of devices is needed.

5.1 Non-sustained hypertension

BP is important for diagnosing non-sustained BP elevations, including masked hypertension

Hypertension. Author manuscript; available in PMC 2023 February 01.

5.2 Blood pressure variation

In the non-pregnant population, the association between BP variation, independent of

maternal and perinatal outcomes are needed.

5.3 Secondary hypertension

5.4 Postpartum hypertension and postpartum preeclampsia

postpartum hypertension may be as high as 8% in women without antepartum hypertension

Hypertension. Author manuscript; available in PMC 2023 February 01.

The rate of elevation in the antepartum sFlt1/PlGF ratio is an independent predictor of

clinic, there is significant opportunity to reduce maternal morbidity in the postpartum

6.0 Treatment of Hypertension in Pregnancy

6.1 Current blood pressure goals for pregnant patients

thresholds and targets vary (Table 6).

The recommendations of published guidelines addressing diagnosis and treatment of HDP

Hypertension. Author manuscript; available in PMC 2023 February 01.

mm Hg.2 Internationally the majority of hypertension societies endorse a more aggressive

approach for antihypertensive treatment, recommending therapy when BP is ≥140/90 mm

Determining the optimal BP threshold in pregnancy for antihypertensive treatment and

outcomes, independent of and similar in magnitude to preeclampsia.16, 22 This is especially

Hypertension. Author manuscript; available in PMC 2023 February 01.

<140/90 mm Hg, to women given no treatment, unless BP is ≥160/105 mm Hg.

Second, there is evidence that the pathophysiology of the neurologic manifestations

Third, treatment of non-severe hypertension in pregnancy (e.g. BPs 140–155/90–109 mm

Fourth, ACOG guidelines recommend withholding antihypertensive therapy for patients

Hypertension. Author manuscript; available in PMC 2023 February 01.

immediate and postpartum complications (such as acute cardiovascular and cerebrovascular

hypertension during pregnancy to targets similar to those recommended in non-pregnant

6.3 Antihypertensive medications

Hypertension. Author manuscript; available in PMC 2023 February 01.

although not extensively studied, include nicardipine, clonidine, and furosemide.179–181

The limitations of existing data regarding the safety of antihypertensives in pregnancy

are highlighted by a systematic review of studies addressing in utero exposure to

Hypertension. Author manuscript; available in PMC 2023 February 01.

7.0 Postpartum screening

8.0 Multidisciplinary team approach

9.0 Hypertension in pregnancy and racial disparities

Hypertension. Author manuscript; available in PMC 2023 February 01.

10.0 Conclusion and future directives

Hypertension. Author manuscript; available in PMC 2023 February 01.