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Preeclampsia 2022
Preeclampsia 2022
Review Article
Preeclampsia
Laura A. Magee, M.D., Kypros H. Nicolaides, M.D., and
Peter von Dadelszen, D.Phil.
P
reeclampsia, which complicates 2 to 4% of pregnancies globally, From the Department of Women and
is progressive, unpredictable, and serious. It is associated with approxi- Children’s Health, School of Life Course
Sciences, King’s College London (L.A.M.,
mately 46,000 maternal deaths and approximately 500,000 fetal and new- K.H.N., P.D.), the Institute of Women and
born deaths annually.1,2 The disease burden is borne disproportionately by women Children’s Health, King’s Health Part-
in low- and middle-income countries or who are otherwise disadvantaged. Much ners Academic Health Science Centre
(L.A.M., P.D.), and the Harris Birthright
of the literature focuses on preterm preeclampsia, which accounts for up to one Research Centre for Fetal Medicine,
third of cases and is associated with a much higher risk of maternal and fetal or King’s College Hospital (K.H.N.) — all in
newborn complications than preeclampsia at term. However, a much larger num- London. Dr. Magee can be contacted at
laura.a.magee@kcl.ac.uk or at King’s Col-
ber of women have term disease, which makes a substantial contribution to pre- lege London, 6th Floor, Addison House
eclampsia-related morbidity and mortality. Guy’s Campus, Great Maze Pond, London
Antepartum care is devoted in large part to blood-pressure screening for hyper- SE1 1UL, United Kingdom.
tension and specifically preeclampsia. Maternal biologic and social risk factors for N Engl J Med 2022;386:1817-32.
preeclampsia include certain demographic characteristics (e.g., membership in a DOI: 10.1056/NEJMra2109523
Copyright © 2022 Massachusetts Medical Society.
minority racial or ethnic group), a history of medical or obstetrical disorders (e.g.,
chronic hypertension), certain characteristics of the current pregnancy (e.g., con- CME
ception by means of assisted reproductive technology), physiological abnormalities at NEJM.org
(e.g., increased blood pressure), abnormal results of laboratory tests (e.g., severe
anemia), and ultrasonographic abnormalities (e.g., an abnormal uterine-artery
pulsatility index, measured by Doppler ultrasonography)3 (Fig. 1). These risk fac-
tors align with the pathogenesis of preeclampsia, which involves uteroplacental
mismatch, syncytiotrophoblast factors, and an imbalance of angiogenic factors,
which lead to maternal systemic endothelial dysregulation and inflammation, a
process similar to sepsis (Fig. 1).
Most cases of preeclampsia arise at term and are mild and transient and resolve
soon after the delivery. However, 5 to 20% of women, especially those in whom
preeclampsia arises well before term, have life-altering, life-threatening, or fatal
complications. Systemic endothelial damage causes the generalized edema once
considered to be a diagnostic criterion. Cardiovascular manifestations are related
primarily to increased peripheral vascular resistance, which causes hypertension,
despite decreased intravascular volume. With adjustment for factors affecting risk
(e.g., maternal age and weight), cardiac output is normal, unless preeclampsia is
complicated by peripartum cardiomyopathy. Pulmonary endothelial activation,
neutrophil activation, and decreased plasma oncotic pressure increase the risk of
pulmonary edema and acute respiratory distress syndrome. Severe hypertension,
especially systolic hypertension, increases the risk of hemorrhagic stroke, and the
combination of hypertension and endothelial activation can result in reversible
ischemic encephalopathy in the posterior hemispheres (manifested as headaches,
scotomata, and scintillations) and the seizures of eclampsia. Whether cerebral
edema is a cause or consequence of eclampsia is unclear.
Renal involvement is most commonly manifested as proteinuria because of the
pathognomonic lesion of glomerular endotheliosis and associated loss of podocyte
Inadequate spiral artery modification Crowding of intervillous space Multiple pregnancy, macrosomia,
and poor villous development (e.g., malaria parasites, term mirror syndrome
or post-term pregnancy)
Molar
pregnancy
Other placental syndromes
(may arise concurrently
with preeclampsia):
Fetal growth restriction
Preterm birth
Stillbirth
Uteroplacental Mismatch
Placental abruption
(demand is greater than supply) Factors Conferring Maternal
Predisposition
Acute or chronic inflammation
(related to obesity, diabetes
Syncytiotrophoblast Stress–Derived mellitus, urinary tract infection,
Factors (e.g., microvesicles) poor oral health, Covid-19
and infection)
Angiogenic Imbalance (increased sFlt-1, Vasculitis
decreased placental growth factor) Antiphospholipid syndrome
Chronic kidney disease
Chronic hypertension
Social determinants of health
Vasoconstriction Maternal Systemic Endothelial (e.g., low socioeconomic status,
Acute atherosis Dysregulation and Inflammation minority ethnic background)
integrity. When severe, these lesions can result who could benefit from enhanced surveillance
in nephrotic-range proteinuria, acute tubular and timed birth.
necrosis, and acute kidney injury. Traditional screening for the risk of pre-
Liver damage is characterized by periportal eclampsia is advocated by most clinical practice
inflammation and hepatocellular damage (mani- guidelines.4 This approach involves an assess-
fested as right-upper-quadrant or epigastric pain ment of clinical risk factors early in pregnancy;
and transaminitis), subcapsular hematoma, and the risk factors are treated independently and
in rare cases, hepatic failure or rupture. Jaundice summarized either without an indication of the
and hypoglycemia are rare and late findings, level of risk or as a count of any factor that con-
which distinguish preeclampsia from acute fatty fers a high risk or one or more factors that
liver of pregnancy. confer a moderate risk.5 This approach is simple,
Hematologic manifestations include relative but the detection rate (i.e., the sensitivity) is low
hemoconcentration (unless hemolysis occurs), for both preterm preeclampsia (approximately
relative neutrophilia, microvascular thrombosis 40%) and term preeclampsia (approximately 35%),
and hemolysis (manifested as an increased lac- with a positive screening rate (i.e., the screen-
tate dehydrogenase level), platelet consumption, positive rate) of approximately 10%.3
and especially with placental abruption, dis- Multivariable models have high detection rates
seminated intravascular coagulation. Abruption when used at 11 to 13 weeks’ gestation for pre-
probably results from ischemia–reperfusion in- term preeclampsia and at 35 to 36 weeks’ gesta-
jury in maternal uteroplacental vessels. tion for term preeclampsia, with a positive
Fetal manifestations are not uniform and in- screening rate of approximately 10%. The com-
clude both fetal growth restriction (as a result of peting-risks model of the Fetal Medicine Foun-
inadequate placentation, usually with early-onset dation (FMF), which is supported by the largest
preeclampsia) and macrosomia (as a cause of body of evidence, comprises the components that
uteroplacental mismatch, often with late-onset are most commonly included in other models
preeclampsia). Both early-onset preeclampsia (i.e., maternal ethnic or racial background, body-
and late-onset preeclampsia are associated with mass index, blood pressure, ultrasonographic
increased perinatal risks. assessment of the uterine-artery pulsatility index,
Here we review the current understanding of and angiogenic markers6). The FMF competing-
preeclampsia, particularly findings published risks approach is based on a survival–time
within the past 5 years. We focus on individual- model that incorporates a prior distribution of
ization and integration of concepts concerning gestational age at delivery with preeclampsia,
the prediction, prevention, diagnosis, and man- derived from maternal characteristics, with like-
agement of preeclampsia during pregnancy and lihood functions from biomarkers to estimate
in the long term. Although some of the manage- an individual woman’s risk of delivery with pre-
ment strategies we discuss apply to women with eclampsia before a specified gestational age
chronic or gestational hypertension, our focus is (e.g., at <37 weeks).3
on preeclampsia. The internationally validated FMF model of
maternal risk factors and biomarkers (i.e., blood
pressure, uterine-artery pulsatility index as mea-
Pr edic t ion of Pr eecl a mpsi a
sured by Doppler ultrasonography, and serum
The following two approaches are commonly level of placental growth factor) identifies ap-
used to identify women who are at increased risk proximately 90% of women at 11 to 13 weeks’
for preeclampsia and who could benefit from gestation in whom early preeclampsia (at <34
preventive interventions: a traditional count of weeks’ gestation) will develop and approximate-
clinical risk factors and multivariable modeling ly 75% of those in whom preterm preeclampsia
of clinical, ultrasonographic, and laboratory as- will develop, with a positive screening rate of
sessment of uteroplacental perfusion and func- 10%.3 Uterine-artery Doppler ultrasonography
tion. Although each approach is usually applied and placental growth factor assays are not per-
in early pregnancy to identify women who can formed routinely, even in well-resourced clinical
benefit from prophylaxis with low-dose aspirin, settings. However, a two-step screening proce-
assessment later in pregnancy may identify women dure can be undertaken, in which 70% of
Weeks of Gestation
0 4 8 12 16 20 24 28 32 36 40
≈40% reduction
Moderate exercise: ≥140 min/wk
in preeclampsia
Assess risk: if at high risk for preeclampsia, initiate aspirin ≈60% reduction
(≥100 mg/day) before 16 wk of gestation in preterm
preeclampsia
≈35% reduction
Timed birth in preeclampsia
after 39 wk 0 days
women who have positive screening results on fies almost all women in whom preeclampsia
the basis of maternal risk factors undergo sec- will develop by 32 weeks. At 32 weeks’ gestation,
ond-stage screening (with ultrasound assessment rescreening identifies 90% of women in whom
and serum biomarker measurements), which re- preeclampsia will develop at 32 to 35 weeks.
sults in a similar overall detection rate for pre- However, only at 35 to 36 weeks’ gestation is the
term preeclampsia, at a reduced cost.3 Black prediction of term preeclampsia possible, with
women and women of South Asian descent are soluble fms-like tyrosine kinase 1 (sFlt-1) mak-
more likely than women of other races or ethnic ing an independent contribution7; this screening
groups to require second-stage screening, but approach at 35 to 36 weeks’ gestation identifies
the detection rate for preterm preeclampsia 75% and 85% of women in whom term pre-
among Black and South Asian women is higher eclampsia will develop, with positive screening
(>95%).3 If the first step in two-step screening rates of 10% and 20%, respectively.
includes either uterine-artery Doppler ultraso-
nography or a placental growth factor assay, Pr e v en t ion
then in the second step, measurement of placen-
tal growth factor or assessment of the uterine- Prevention of preeclampsia is a health care pri-
artery pulsatility index can be reserved for only ority, given that only delivery of the placenta has
30 to 40% of women.3 been proved to initiate the resolution of pre-
For the 90% of women identified as being eclampsia once it has developed. Preventive thera-
at low risk for preterm preeclampsia at 11 to 13 pies have been based on the pathogenesis of
weeks’ gestation, rescreening during the second preeclampsia and focused on redressing angio-
and third trimesters can refine the risk stratifi- genic imbalance, endothelial activation, oxida-
cation and identify women who require closer tive stress, inflammation, vasoconstriction, or a
monitoring. At the routine ultrasound scanning combination of these factors (Fig. 1). Evidence
at 19 to 24 weeks’ gestation, rescreening identi- supports the use of exercise, aspirin, calcium,
and labor induction as effective preventive strat- available is affected by geographic variation; 75-mg
egies (Fig. 2). and 81-mg tablets can be used interchangeably,
and an approximation of the recommended doses
Exercise may be required. Further research must clarify
A systematic review of 15 randomized, con- why women with chronic hypertension did not
trolled trials, involving a total of 3322 women, benefit from aspirin.10
showed that exercise reduces the risk of pre- Aspirin prophylaxis against preeclampsia is
eclampsia (odds ratio, 0.59; 95% confidence in- associated with a very small increase in antepar-
terval [CI], 0.37 to 0.90) without adverse fetal tum and postpartum bleeding, as well as neona-
effects.8 To achieve these benefits, women must tal bleeding in rare cases, on the basis of data
undertake at least 140 minutes per week of from a population-based cohort study involving
moderate-intensity exercise, sufficient to raise the a total of 4088 women treated with aspirin14 and
heart rate and allow speaking but not singing. data from 29 randomized, controlled trials in-
volving a total of 30,775 women.9 These risks
Aspirin could be mitigated by discontinuing aspirin by
A meta-analysis of 60 trials involving a total of 36 weeks’ gestation and are far outweighed by
36,716 women at increased risk for preeclampsia the benefits of preventing preterm preeclampsia
primarily on the basis of clinical risk factors in women at increased risk. Nevertheless, the
showed that aspirin (50 to 162 mg per day, usu- risks argue against universal aspirin prophylaxis
ally ≤75 mg per day) reduces the risk of pre- as an alternative to risk screening.
eclampsia in a dose-dependent manner (relative
risk, 0.82; 95% CI, 0.77 to 0.88), in addition to Calcium
lowering the rates of serious maternal complica- A meta-analysis of 30 trials involving a total of
tions, preterm birth, delivery of a small-for-ges- 20,445 women showed that calcium supplemen-
tational age infant, and fetal or newborn death.9 tation during pregnancy reduces the risk of pre-
In the ASPRE (Combined Multimarker Screening eclampsia (relative risk, 0.49; 95% CI, 0.39 to
and Randomized Patient Treatment with Aspirin 0.61) at term or preterm gestational age, regard-
for Evidence-Based Preeclampsia Prevention) trial, less of whether calcium supplementation is initi-
multivariable first-trimester screening was used ated before, at, or after 20 weeks’ gestation,
to identify a high-risk group of women ran- whether it is given with or without vitamin D,
domly assigned to receive aspirin (150 mg per and whether the dose is high (≥1 g per day) or
day) or placebo from 11 to 13 weeks’ gestation low (usually 500 mg per day).15 However, calcium
until 36 weeks’ gestation. In the aspirin group, was effective only in the subgroup of 24 trials
the risk of preterm preeclampsia was reduced by involving a total of 15,050 women with a low
more than 60% (odds ratio, 0.38; 95% CI, 0.20 average calcium intake at baseline (<900 mg per
to 0.74), but no significant reduction in term day; relative risk, 0.45; 95% CI, 0.35 to 0.58).15 In
disease was observed (odds ratio, 0.95; 95% CI, a network meta-analysis of 25 trials involving
0.57 to 1.57).10 This approach was cost-effective 15,038 women, high-dose and low-dose calcium
in Canada11 and Israel.12 were similarly effective (relative risk, 0.79; 95%
A subsequent meta-analysis of 16 trials in- CI, 0.43 to 1.40).
volving a total of 18,907 women showed that
aspirin is beneficial in preventing preterm pre- Other Preventive Measures
eclampsia (relative risk, 0.62; 95% CI, 0.45 to A trial involving 6106 low-risk, nulliparous
0.87) but not term disease (relative risk, 0.92; women showed that labor induction at 39 weeks
95% CI, 0.70 to 1.21), provided treatment is initi- 0 days to 39 weeks 4 days of gestation, as com-
ated by 16 weeks’ gestation and at a dose of at pared with expectant care, reduced the risks of
least 100 mg per day.13 This effect may be related gestational hypertension and preeclampsia.16
to differences in the predominant pathogenesis Pravastatin has received considerable atten-
or a shift in diagnosis to a later gestational age, tion as a potential preventive agent. In a study
so cases of preeclampsia at term that are pre- involving 1120 women identified at 35 to 36
vented are replaced by cases that would have weeks’ gestation as being at high risk for term
involved preterm delivery. The dose of aspirin preeclampsia on the basis of multivariable screen-
ing, pravastatin (20 mg per day) reduced neither onset hypertension and proteinuria at 20 weeks
the incidence of preeclampsia nor circulating or more of gestation. The growing international
levels of angiogenic markers, despite good ad- consensus is that the definition should be broad
herence to the medication regimen.17 A number in order to include other relevant forms of ma-
of trials evaluating the initiation of pravastatin ternal end-organ involvement and uteroplacental
prophylaxis in early pregnancy are ongoing. dysfunction (Fig. 1). A systematic review of 33
Folic acid (4 mg per day) did not prevent pre- observational studies involving a total of 9426
eclampsia in a trial involving 2464 women at women with suspected preeclampsia showed an
high risk.18 The effectiveness of low-molecular- association between angiogenic imbalance and
weight heparin remains uncertain, and its use is adverse pregnancy outcomes,22 including those
not recommended outside a study protocol un- at term.23 On the basis of these findings, angio-
less high-quality data on safety and efficacy be- genic imbalance is part of the 2021 Interna-
come available.19 Newer candidates being evalu- tional Society for the Study of Hypertension in
ated (e.g., metformin20) have been repurposed Pregnancy (ISSHP) definition of preeclampsia.24
from other indications for which safety is ac- Challenges with the use of angiogenic markers
cepted.21 include limited availability and various assays
with different cutoff points, particularly those
that are not adjusted for maternal characteristics
Surv eil l a nce for Women
at Incr e a sed R isk or gestational age.3 In women with preexisting
hypertension, the diagnosis of superimposed
For women identified as having an increased preeclampsia should be based on nonhyperten-
risk of preeclampsia on the basis of multivari- sive manifestations and not solely on worsening
able or clinical risk factor screening in early hypertension.24
pregnancy, no standardized program of mater- Preeclampsia has been subgrouped by gesta-
nal and fetal surveillance has been shown to tional age at onset. Women with early-onset
reduce maternal or perinatal risk. Women should disease (at <34 weeks’ gestation) are more likely
be encouraged to self-monitor for symptoms than women with late-onset disease (at ≥34
that may reflect preeclampsia, whether maternal weeks’ gestation) to have end-organ involvement,
(e.g., headache) or fetal (e.g., reduced fetal move- associated fetal growth restriction, and a hemo-
ment). Self-monitoring of blood pressure has dynamic profile of low cardiac output and high
become common, particularly since the start of peripheral vascular resistance.25 In women with
the coronavirus disease 2019 (Covid-19) pan- late-onset preeclampsia, who account for at least
demic, but it remains uncertain whether this 70% of all women with preeclampsia, birth
will result in earlier detection of preeclampsia. weight is usually normal or even increased, car-
Pragmatic approaches of potential effectiveness diac output may be increased, and peripheral
include an increased frequency of antenatal care vascular resistance is variable (i.e., decreased25
visits, maternal self-monitoring for proteinuria, or increased26).
monthly maternal laboratory testing for end-
organ involvement (thrombocytopenia, elevated M a nagemen t
creatinine or aminotransferase levels, or angio-
genic imbalance), and third-trimester fetal as- Place of Care
sessment (ultrasonographic monitoring of growth It is reasonable to consider a component of out-
or Doppler velocimetry of the pulsatility indexes patient care for women with preeclampsia that is
of the umbilical and middle cerebral arteries). not associated with severe hypertension or seri-
ous maternal or fetal compromise (Table 1). To
be eligible for outpatient care, women must un-
Di agnosis
derstand the symptoms of disease progression,
The purpose of diagnosing preeclampsia is to have the capacity to measure their own blood
identify women at risk for adverse outcomes and pressure, have open lines of communication
determine the best course of management. The with care teams, and live within 30 minutes of a
traditional definition of preeclampsia is new- hospital.
Risks and Management <24 wk 24 wk 0 days to 33 wk 6 days 34 wk 0 days to 36 wk 6 days ≥37 wk 0 days
Risks
Preeclampsia (%) <0.05 0.2 0.4 2.9
Associated short-term risks
Maternal complications ≤70 Approximately 15 Approximately 5 2–4
(%)23,25
Fetal or newborn death (%) 50–82 2–40 <1 <1
Newborn death without 98–55 4–12 4 4
serious health
problems (%)
The
Management
Antepartum care
Place of care Where resources are sufficient to Where resources are sufficient to Where resources are sufficient to Where resources are sufficient to
deal with sick mothers or babies deal with sick mothers or babies deal with sick mothers or babies deal with sick mothers or babies
(especially for expectant care); (especially for expectant care); (especially for expectant care); (especially for expectant care);
after initial assessment, a com- after initial assessment, a com- after initial assessment, a com- after initial assessment, a com-
ponent of outpatient care can be ponent of outpatient care can be ponent of outpatient care can be ponent of outpatient care can be
considered but should be indi- considered but should be indi- considered but should be indi- considered but should be indi-
vidualized vidualized vidualized vidualized
Maternal monitoring Daily BP; blood tests twice/wk (plate- Daily BP; blood tests twice/wk (plate- Daily BP; blood tests twice/wk (plate- Daily BP; blood tests twice/wk (plate-
(at minimum)† let count, creatinine and liver- let count, creatinine and liver- let count, creatinine and liver- let count, creatinine and liver-
enzyme levels); use fullPIERS enzyme levels); use fullPIERS enzyme levels); use fullPIERS enzyme levels); use fullPIERS
n e w e ng l a n d j o u r na l
model to evaluate risk of adverse model to evaluate risk of adverse model to evaluate risk of adverse model to evaluate risk of adverse
Downloaded from nejm.org by YAHAIRA BORQUEZ on May 16, 2022. For personal use only. No other uses without permission.
to be achieved more slowly if BP to be achieved more slowly if BP to be achieved more slowly if BP to be achieved more slowly if BP
severely elevated severely elevated severely elevated severely elevated
Risks and Management <24 wk 24 wk 0 days to 33 wk 6 days 34 wk 0 days to 36 wk 6 days ≥37 wk 0 days
Magnesium sulfate Use for eclampsia treatment and Use for eclampsia treatment and Use for eclampsia treatment and Use for eclampsia treatment and
(4 g IV over 5 min, prevention; use for women with prevention; use for women with prevention; use for women with prevention; use for women with
then 1 g/hr IV; or preeclampsia who have severe preeclampsia who have severe preeclampsia who have severe preeclampsia who have severe
5 g IM into each hypertension and proteinuria or hypertension and proteinuria or hypertension and proteinuria or hypertension and proteinuria or
buttock, then 5 g IM any hypertension and neurologic any hypertension and neurologic any hypertension and neurologic any hypertension and neurologic
every 4 hr) symptoms or signs23 symptoms or signs23; use for fetal symptoms or signs23 symptoms or signs23
neuroprotection
Antenatal glucocorticoids NA Use to accelerate fetal pulmonary Use to accelerate fetal pulmonary Not recommended for HELLP syn-
maturity and reduce risks of fetal maturity and reduce risks of fetal drome
or newborn death, IVH, and de- or newborn death, IVH, and de-
velopmental delay¶ velopmental delay¶
Postpartum care
Maternal monitoring† Watch for peak BP on days 3–6 after Watch for peak BP on days 3–6 after Watch for peak BP on days 3–6 Watch for peak BP on days 3–6
birth; daily BP and twice/wk birth; daily BP and twice/wk after birth; daily BP and twice/ after birth; daily BP and twice/
blood tests (platelet count and blood tests (platelet count and wk blood tests (platelet count wk blood tests (platelet count
creatinine and liver-enzyme lev- creatinine and liver-enzyme lev- and creatinine and liver-enzyme and creatinine and liver-enzyme
els) until discharge els) until discharge levels) until discharge levels) until discharge
Antihypertensive agents‖ Treat hypertension; most agents can Treat hypertension; most agents can Treat hypertension; most agents can Treat hypertension; most agents can
be used during breast-feeding be used during breast-feeding be used during breast-feeding be used during breast-feeding
Counseling about future Discuss preeclampsia recurrence, Discuss preeclampsia recurrence, Discuss preeclampsia recurrence, Discuss preeclampsia recurrence,
risks long-term health risks (particular- long-term health risks (particular- long-term health risks (particu- long-term health risks (particular-
ly CVD**), lifestyle modifications ly CVD**), lifestyle modifications larly CVD**), lifestyle modifica- ly CVD**), lifestyle modifications
Preeclampsia
tions
* BP denotes blood pressure; CVD cardiovascular disease; fullPIERS Preeclampsia Integrated Estimate of Risk; HELLP hemolysis, elevated liver-enzyme levels, and low platelet count;
IM intramuscular; IV intravenous; IVH intraventricular hemorrhage; and NA not applicable.
† Maternal monitoring should continue after delivery, particularly in the first week.
Downloaded from nejm.org by YAHAIRA BORQUEZ on May 16, 2022. For personal use only. No other uses without permission.
1825
The n e w e ng l a n d j o u r na l of m e dic i n e
Severe Hypertension
Manifestation: Systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg
Objective: Systolic BP <160 mm Hg and diastolic BP <110 mm Hg within 180 min
Management: Choose one of the following four classes of drugs and the preferred route and timing of administration
If BP control is not achieved despite maximal doses, move to another class of medication
If BP control is not achieved by 360 min despite 2 medications, consult critical care, consider ICU admission, stabilize and
deliver (if undelivered)
First-Line Drug Route of Administration and Dosage Units 0 Min 30 Min 60 Min 90 Min 120 Min 150 Min
If BP is controlled, continue
with maintenance oral medication If systolic BP ≥160 mm Hg or diastolic
BP ≥110 mm Hg, use medication from
a class other than maintenance
Nonsevere Hypertension
Manifestation: Systolic BP 140–159 mm Hg or diastolic BP 90–109 mm Hg
Objective: Systolic BP 135 mm Hg and diastolic BP 85 mm Hg
Management: Start with one of the three classes of drugs and use a low–medium dose
If BP control is not achieved within a week with a medium dose, consider adding a low–medium dose from another class, rather than a
high dose of the same medication, for a maximum of three medications
Consider expectant care if antenatal
Labetalol 100–200 mg, 3 or 4 times daily 300 mg, 3 or 4 times daily 1200 mg/day
Intermediate-acting (PA/MR) 10–20 mg, 2 or 3 times daily 30 mg, 2 or 3 times daily 120 mg/day
Nifedipine
Long-acting (XL/LA) 30 mg, 1 or 2 times daily or 30 mg every morning and 120 mg/day
60 mg daily 60 mg every evening
teral hydralazine or oral nifedipine,42 but oral fits and risks, and pediatric developmental follow-
nifedipine may be more effective than parenteral up data are reassuring although limited.51
hydralazine, according to a meta-analysis of 17 Labetalol, an alpha- and beta-blocker, or pure
trials involving a total of 1591 women.43 Oral beta-blockers may warrant neonatal monitoring
labetalol is as effective as oral nifedipine, with for hypoglycemia and bradycardia.52 Renin–angio-
fewer babies of low birth weight admitted to tensin–aldosterone inhibitors are fetotoxic and
neonatal intensive care (10%, vs. 18% with nife- therefore contraindicated during pregnancy.53
dipine).44 Oral methyldopa alone achieves the It has been suggested that antihypertensive
target blood pressure in at least 60% of women.44 therapy should be guided by hemodynamic as-
Treatment of nonsevere hypertension in preg- sessment in women with preeclampsia, with a
nancy is recommended by the World Health vasodilator for increased peripheral vascular
Organization, the ISSHP, the International Fed- resistance (along with intravascular fluid) or a
eration of Gynecology and Obstetrics, and six beta-blocker for high cardiac output. No ran-
non-U.S. national guidelines,4,45,46 on the basis of domized trial of hemodynamically guided anti-
the results of the international Control of Hyper- hypertensive treatment (as compared with em-
tension in Pregnancy Study, involving 987 wom- pirical therapy) to achieve a common target
en.47 In women with chronic or gestational hyper- blood pressure has been conducted. However,
tension, antihypertensive therapy (most commonly plasma volume expansion (as compared with
oral labetalol) administered to achieve a target usual care) was associated with a shorter time to
diastolic blood pressure of 85 mm Hg resulted delivery and a higher incidence of pulmonary
in a mean blood pressure of 133/85 mm Hg after edema and cesarean deliveries in the largest
randomization, and the women were less likely published trial, involving 216 women.54 A cau-
than women with minimal medication use to tious approach to fluid administration is recom-
have severe hypertension (as in prior small tri- mended for women with preeclampsia (i.e., ap-
als48), a platelet count of less than 100 × 109 per proximately 80 ml per hour during labor) that is
liter, or elevated liver-enzyme levels with symp- not associated with acute kidney injury.55
toms47; the women with preeclampsia remained
in their assigned group. A nonsignificant increase Magnesium Sulfate
in babies with birth weight below the 10th per- Magnesium sulfate is effective for the prevention
centile was balanced by a nonsignificant de- and treatment of preeclampsia, but implementa-
crease in preterm births, and there was no in- tion has been challenging (Table 1).4,24,56 Evalua-
crease in fetal or newborn deaths or need for tion of alternative regimens (a lower dose or
prolonged neonatal care.49 The recently pub- abbreviated duration), more targeted adminis-
lished Chronic Hypertension and Pregnancy trial tration in women who may benefit the most,
(involving 2408 women) also showed that blood and the complementary strategy of achieving
pressure control (to <140/90 mm Hg and most good blood-pressure control is ongoing.44
commonly with oral labetalol) was associated
with a reduction in a composite adverse outcome Glucocorticoids
(of preeclampsia with severe features, medically Antenatal glucocorticoids should be adminis-
indicated preterm birth at <35 weeks’ gestation, tered according to local gestational age–based
placental abruption, or fetal or neonatal death), guidance for acceleration of fetal pulmonary
with no significant increase in babies with birth maturity and prevention of fetal or newborn
weight below the 10th percentile for gesta- death, intraventricular hemorrhage, and devel-
tional age.50 opmental delay (Table 1). Glucocorticoids are
Oral labetalol, methyldopa, or nifedipine is not recommended for HELLP (hemolysis, elevat-
usually recommended, according to 49 small ed liver-enzyme levels, and low platelet count)
randomized, controlled trials involving a total of syndrome; a meta-analysis of 11 trials involving
4723 women.48 No clear differences have been a total of 550 women with HELLP syndrome
noted between any two of these agents in 22 showed that the transient improvements in labo-
trials involving 1723 women, but 95% confi- ratory values did not result in improved clinical
dence intervals include clinically relevant bene- outcomes.24
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levels of maternal mortality, 1990–2015: venting pre-eclampsia and its complica- for prevention of preeclampsia and other
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