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Published in final edited form as: Semin Perinatol. 2025 Dec 25;50(3):152210. doi: 10.1016/j.semperi.2025.152210

Preeclampsia Trials that Changed Practice

Eniola R Ibirogba 1, Jennifer Grasch 2, Maged M Costantine 3
PMCID: PMC12818694  NIHMSID: NIHMS2132985  PMID: 41453814

Abstract

Hypertensive disorders of pregnancy are major contributors to adverse maternal, fetal and neonatal outcomes. This review summarizes pivotal clinical and translational studies that have shaped the clinical approach to the prevention and treatment of preeclampsia. Early preclinical trails established the pathophysiological basis and rationale for prevention strategies culminating in the standard use low dose aspirin and the emerging potential of statins. Recent randomized trials have also demonstrated that treatment of mild chronic hypertension reduces the risk preeclampsia and associated complications. Furthermore, clinical studies examining the use of magnesium sulfate for seizure prophylaxis and the optimal delivery timing have defined key aspects of evidence-based preeclampsia management. Further research to identify novel therapeutic targets and refine management strategies to mitigate the persistent burden of preeclampsia is urgently needed.

Introduction

Hypertensive disorders of pregnancy including preeclampsia have been a major driver of maternal and neonatal mortality and morbidity, with over 50 thousand mothers and 700 thousand neonates dying from preeclampsia related causes annually worldwide. Despite this, pregnant individuals have traditionally been excluded from therapeutic research, resulting in a paucity of innovations in therapeutics on pregnancy-specific medical conditions, especially preeclampsia, compared with medical conditions of similar incidence or burden (1). The goal of this paper is to summarize some of the key studies that have shaped the care of individuals with preeclampsia. We will initially discuss prevention trials, including the use of aspirin and statin as well as obstetrical interventions shown to decrease the odds of preeclampsia and then summarize management-related trials, including the use of magnesium sulfate and delivery considerations of individuals with hypertensive disorders of pregnancy.

Prevention Trials

Aspirin Trials

Although the exact mechanisms are not well known, poor placentation —driven by shallow implantation— along with oxidative stress, endothelial dysfunction, aberrant inflammatory or immune responses, and angiogenic imbalance are widely recognized as the unifying pathophysiological mechanism underlying preeclampsia (2, 3). Earlier studies, however, proposed that an imbalance between prostacyclin and thromboxane A2 (TXA2), leading to endothelial dysfunction and clotting, plays a critical role in the development of the disorder. These findings provided the rationale for early clinical trials investigating the use of low-dose aspirin for the prevention of preeclampsia. Aspirin’s mechanism of action involves selective inhibition of cyclooxygenase-1 (COX-1), leading to reduced platelet synthesis of TXA2, a potent vasoconstrictor and promoter of platelet aggregation (4, 5).

The role of aspirin in the prevention of preeclampsia has been further evaluated in several large clinical trials, using different doses, and in various populations, which overall show a beneficial role (6). The Collaborative Low-dose Aspirin Study in Pregnancy (CLASP) was a multicenter, randomized trial involving over 9,000 participants. It assessed the efficacy of low-dose aspirin (60 mg daily, initiated between 12 and 32 weeks) in individuals at risk of developing preeclampsia or fetal growth restriction (FGR) as well as those already diagnosed with preeclampsia or FGR. In this trial, aspirin use was not associated with reduction in rates of preeclampsia or FGR overall (Table 1). However the trial demonstrated a correlation between preeclampsia and gestational age at delivery— the lower the gestational age at delivery, the lower the rate of preeclampsia, suggesting the potential benefit of aspirin specifically for the prevention of early-onset preeclampsia (7). In addition, aspirin significantly reduced the risk of preterm delivery (19.7% vs 22.2%) compared with control group.

Table 1:

Key Preeclampsia Prevention Trials

Intervention Trial Study population Dose Key finding
Aspirin Low-dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy induced hypertension – Italian study of aspirin in pregnancy, 1993 (8) Individuals at elevated risk for preeclampsia—including those with chronic hypertension, a history of fetal growth restriction, or twin gestation (N= 1,106) 50 mg No significant benefit in reducing risk of preeclampsia or FGR
Collaborative Low-dose Aspirin Study in Pregnancy – CLASP collaborative group, 1994 (7) Individuals at risk of developing preeclampsia or fetal growth restriction and those already diagnosed with preeclampsia or FGR (N = 9,000) 60 mg

  • No difference in rate of preeclampsia or FGR

  • Reduction in rate of preterm delivery
Prevention of preeclampsia with low-dose aspirin in healthy nulliparous pregnant women (MFMU – Sibai et al), 1993 (10) Healthy nulliparous women (N=3,135) 60 mg Lower incidence of preeclampsia
Low dose aspiring to prevent preeclampsia in women at high risk (MFMU–Caritis et al), 1998 (9) At-risk pregnant individuals, including those with prior preeclampsia, chronic hypertension, diabetes, or multifetal gestation (n=2,539) 60 mg No reduction in the incidence of preeclampsia among at risk individuals
Aspirin vs Placebo in pregnancies at high risk for preterm preeclampsia – Rolnik et al, 2017 (11) Individuals at high risk for preeclampsia, based on a1st trimester screening algorithm (n=1,776) 150 mg Lower incidence of preterm preeclampsia.
No difference in the rates of any preeclampsia or FGR
Pravastatin Safety and pharmacokinetics of Pravastatin for preeclampsia prevention – Costantine et al, 2016 (19) History of prior preeclampsia that required preterm delivery before 34 weeks (n=20) 10 mg Lower incidence of preeclampsia, preeclampsia with severe features, and indicated preterm delivery before 37 weeks
Pravastatin vs placebo in pregnant patients at risk of preeclampsia – Costantine et al, 2021 (20) History of prior preeclampsia that required preterm delivery before 34 weeks (n=20) 20 mg
INOVASIA – Akbar et al, 2022; Akbar et al, 2024 (21, 22) At risk of developing preeclampsia based on clinical and uterine artery Doppler velocimetry findings, (N=173) 20mg twice daily Lower incidence of preterm preeclampsia and preterm birth
Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia: STATIN trial (Dobert et al, 2021) (23) Singleton pregnancies at high risk of term preeclampsia (based on Fetal Medicine Foundation Risk model) (N=1,120) 20mg No differences in the rates of preeclampsia
Chronic hypertension management Treatment for Mild Chronic Hypertension during Pregnancy: CHAP trial – Tita et al, 2022 (28) Individuals with mild chronic hypertension N/A Active treatment of mild chronic hypertension was associated with lower rate of composite measure of preeclampsia with severe features, medically indicated preterm delivery before 35 weeks of gestation, placental abruption, stillbirth, or neonatal death, and lower rates of preeclampsia. No difference in rates of SGA
A Randomized Trial of Induction Versus Expectant Management: ARRIVE – Grobman et al, 2018 (32) Low-risk nulliparous women between 38 to 38 weeks 6 days gestation (N=6167) N/A No difference in composite adverse perinatal outcome (death or severe neonatal morbidity)
Lower incidence of cesarean delivery and hypertensive disorders of pregnancy
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In contrast, the Italian Study of Aspirin in Pregnancy, which enrolled pregnant individuals at elevated risk for preeclampsia—including those with chronic hypertension, a history of fetal growth restriction, or twin gestation—found no significant benefit of low-dose aspirin (50 mg daily) in reducing the risk of preeclampsia or FGR (8). These finding were corroborated by the Eunice Kennedy Shriver National Institute of Child Health and Human Development – Maternal Fetal Medicine Units Networks’ subsequent double-blind, randomized, placebo-controlled trial, which similarly reported no significant reduction in the incidence of preeclampsia with low-dose aspirin (60 mg daily initiated between 13 and 26 weeks) among at-risk pregnant individuals (Table 1), including those with prior preeclampsia, chronic hypertension, diabetes, or multifetal gestation (9), and also among low-risk nulliparous individuals (10).

A more recent multicenter, double-blind, placebo-controlled trial randomized 1,776 individuals at high risk for preeclampsia, based on a1st trimester screening algorithm, to low-dose aspirin (150 mg daily initiated between 11 and 14 weeks of gestation) and continued until 36 weeks gestation. The trial demonstrated a significantly lower incidence of preterm preeclampsia (preeclampsia with delivery < 37 weeks) with the use of aspirin (1.6% vs. 4.3%; odds ratio, 0.38; 95% CI, 0.20–0.74), but no difference in the rates of any preeclampsia or FGR (Table 1) (11). The efficacy of aspirin in reducing the risk of preeclampsia among high-risk patients has also been supported by multiple meta-analyses(6, 12, 13).

In light of this evidence, both the U.S. Preventive Services Task Force (USPSTF) (14) and the American College of Obstetricians and Gynecologists (ACOG) (3) recommend initiating low-dose aspirin between 12 and 28 weeks of gestation in individuals with one or more high-risk factors, or with more than one moderate-risk factor for preeclampsia.

There is considerable variability in the aspirin dosage (ranging from 60 to 150 mg daily) and gestational age at initiation of aspirin across studies. In the United States, 81 mg daily is the standard recommended dose (3). Ongoing research is evaluating the comparative effectiveness of different dosing strategies, including 81 mg versus 162 mg daily, for the prevention of preeclampsia (ClinicalTrials.gov Identifier: NCT06468202; Pan African Clinical Trial Registry: PACTR202108825067735).

Statin Trials

Despite being unique to pregnancy, preeclampsia shares pathophysiological pathways and common risk factors with adult atherosclerotic cardiovascular (CV) disease (CVD) (15, 16) Endothelial injury and inflammation underlie both preeclampsia and atherosclerosis. Additionally, preeclampsia has been identified as an independent risk factor for cardiovascular disease later in life (17, 18). Biological plausibility and data from preclinical studies ignited interest in the potential use of statin for the prevention or treatment of preeclampsia.

Two pilot double-blind, placebo-controlled preeclampsia prevention trials using pravastatin, were conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Obstetric-Fetal Pharmacology Research Units Network. They randomized individuals with a history of prior preeclampsia that required preterm delivery before 34 weeks to either 10mg of oral pravastatin or placebo (in the first trial) and then 20mg or placebo (in the second trial) from 12 to 16 weeks until delivery (19, 20). Maternal and neonatal outcomes were overall more favorable in women randomized to pravastatin compared with placebo, with reduced rates of preeclampsia (10 vs. 45%, RR 0.22, 95% CI 0.05–0.9), severe features of preeclampsia (0% vs. 40%), and indicated preterm delivery before 37 weeks (20% vs. 55%, RR 0.36, 95% CI 0.14–0.95) (Table 1). Of note, 47.5% of participants also received low dose aspirin with no difference between the two groups.

The INOVASIA study was a multicenter randomized clinical trial of pravastatin to prevent preeclampsia in high-risk patients conducted in Indonesia (21, 22). Pregnant individuals deemed at risk of developing preeclampsia (based on clinical and uterine artery Doppler velocimetry findings) were randomized to low-dose aspirin and calcium (control group, n=86) or low-dose aspirin, calcium, and pravastatin (20mg twice daily, intervention group, n=87). Treatment was initiated between 14–20 weeks until delivery. Receipt of pravastatin (in addition to standard of care) was associated with lower rate of preterm preeclampsia (13.8% vs 26.7%; OR 0.34, 95%CI 0.20–0.91) and preterm birth (16.1 % vs. 36 %; OR= 0.34, 95% CI 0.17–0.7), mostly indicated preterm birth (Table 1).

Lasty, the STATIN study was a multicenter, double-blind, placebo-controlled trial, which randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia (based on Fetal Medicine Foundation Risk model which combines maternal demographic characteristics and medical history, mean arterial pressure, and maternal serum placental growth factor and soluble Fms-like tyrosine kinase-1) to receive pravastatin at a dose of 20mg daily or placebo from 35 to 37 weeks until delivery or 41 weeks (Table 1). There were no differences in the rates of preeclampsia (14.6% vs. 13.6%), maternal or neonatal secondary outcomes between the two groups (23).

In addition to these prevention trials, the Pravastatin for early-onset pre-eclampsia (StAmP) trial randomized women with early-onset preeclampsia (24 to 31 weeks) to pravastatin 40 mg or placebo (24). There was no difference in the primary outcome (sFlt-1 levels 3 days after randomization) between the pravastatin (n = 27) and placebo (n = 29) groups. Subjects who received pravastatin had a similar gestational latency after randomization when compared to placebo (HR 0.84; 95%CI 0.50–1.40; p=0.6) with a median time to delivery of 9 days (IQR 5–14) in the pravastatin group and 7 days (IQR 4–11) in the placebo group (Table 2).

Table 2:

Key Preeclampsia Treatment Trials

Intervention Trial Key finding
Magnesium sulfate for seizure prophylaxis Which anticonvulsant for women with eclampsia – The Eclampsia Trial Collaborative Group, 1995 (43) Lower rates of recurrent seizures with magnesium sulfate compared to diazepam and phenytoin
Effect of magnesium sulfate on labor duration in women with Mild Preeclampsia – Witlin et al, 1997 (46) No effect on labor duration and no difference in the rates of progression to severe preeclampsia
Do women with preeclampsia and their babies, benefit from magnesium sulphate (Magpie) – Altman et al, 2002 (44) Lower rates of eclampsia and maternal mortality with magnesium
Magnesium sulfate vs placebo for mild preeclampsia – Livingston et al, 2003 (47) No difference in the rates of progression to severe preeclampsia
Delivery timing Aggressive vs expectant management for patients with severe preeclampsia between 28 to 34 weeks – Odendaal et al, 1990 (51) Increased latency from diagnosis to delivery and lower rates of composite neonatal morbidity and mortality
Aggressive vs expectant management of severe preeclampsia at 28 to 32 weeks – Sibai et al, 1994 (50) Increased latency from diagnosis to delivery and lower rates of neonatal complications in expectant management group
Induction of labor vs expectant monitoring for gestational hypertension or mild preeclampsia after 36 weeks (HYPITAT) – Koopmans et al, 2009) (48) Lower incidence of maternal morbidity with induction group
No difference in fetal or neonatal adverse outcomes
Immediate delivery vs expectant monitoring for hypertensive disorders of pregnancy between 34- and 37-weeks gestation (HYPITAT-II) – Broekhuijsen et al, 2015 (49) No difference in maternal morbidity. Higher rate of adverse neonatal outcomes in immediate delivery group
Pravastatin Pravastatin for early-onset preeclampsia (StAmp Trial) – Ahmed et al, 2019 (24) No improvement in plasma sFlt-1 or placental growth factor levels with the use of pravastatin 40mg among women with severe preterm preeclampsia
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In addition, the utility of statins in preventing and treating preeclampsia was evaluated in several, but small and some poorly designed cohorts. However, despite the limitations, none of the reported studies identified any maternal or neonatal safety signals, and long-term neuromotor, cognitive, and behavioral assessment of children exposed to pravastatin in utero during the second and third trimesters of pregnancy was reassuring (25). Importantly, these studies demonstrated the potential to repurpose medications to prevent or treat adverse pregnancy outcomes and supported the FDA’s decision to remove their strongest warning against using cholesterol-lowering statins during pregnancy (26).

Chronic Hypertension and Pregnancy (CHAP) Trial

Chronic hypertension in pregnancy is defined as hypertension that is either pre-existing before conception, diagnosed prior to 20 weeks of gestation, or persist >12 weeks after delivery (27). Chronic hypertension is associated with adverse pregnancy outcomes, including placental abruption, preterm birth, small-for-gestational-age (SGA) birth weight, perinatal mortality, and a three- to five-fold increased risk of developing preeclampsia (28). The maternal and fetal risks associated with chronic hypertension correlate with the severity of the disease. For pregnant individuals with severe hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 110 mmHg), antihypertensive therapy is used to reduce the acute risks for stroke, congestive heart failure, and renal failure. In addition, control of severe hypertension can permit pregnancy prolongation and thereby improve perinatal outcome. On the other hand, and until recently, evidence supporting the benefits and safety of antihypertensive therapy for pregnant individuals with mild hypertension (systolic blood pressure between 140 and 160 mmHg or diastolic blood pressure between 90 and 110 mmHg) was lacking (29, 30).

The Chronic Hypertension and Pregnancy (CHAP) trial was an open-label, multicenter, randomized controlled trial designed to address this knowledge gap (28). Pregnant individuals diagnosed with mild chronic hypertension prior to 23 weeks of gestation were randomized to receive either active treatment (antihypertensive medications titrated to maintain blood pressure < 140/90 mm Hg) or standard of care (treatment reserved for severe hypertension, defined as ≥ 160/105 mm Hg). The primary outcome was a composite measure that included superimposed preeclampsia with severe features, medically indicated preterm delivery before 35 weeks of gestation, placental abruption, stillbirth, or neonatal death. The principal safety outcome was the incidence of Small for Gestational Age (SGA, birth weight < 10th percentile).

Findings from the CHAP trial demonstrated that active treatment was associated with lower incidence of preeclampsia (24.4% versus 31.1%, aRR 0.79; 95% CI, 0.69–0.89), primary composite outcome (30.2% versus 37.0%, aRR 0.82, 95% CI, 0.74–0.92) compared with the control group (Table 1). The incidence of SGA was comparable between groups: 11.2% in the treatment group and 10.4% in the control group (aRR 1.04; 95% CI, 0.82–1.31). Rates of severe neonatal and serious maternal complications were similarly comparable between groups (28).

Following the publication of the CHAP trial results, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) now recommend the initiation and titration of antihypertensive medications to maintain blood pressure below 140/90 mm Hg in pregnant patients with chronic hypertension (31) with the goal to reduce the risk of preeclampsia and preterm delivery in this population.

ARRIVE: A Randomized Trial of Induction Versus Expectant Management

The ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management in Low-Risk Nulliparous Women) was designed to evaluate the perinatal and maternal outcomes associated with labor induction at 39 weeks of gestation in low-risk, nulliparous individuals (32). In this study, 6,167 eligible women were randomized to labor induction between 39 weeks 0 days and 39 weeks 4 days or expectant management until as late as 42 weeks 2 days.

The primary composite adverse perinatal outcome (death or severe neonatal morbidity) was similar between the two groups; however, induction of labor was associated with lower rate of cesarean delivery (18.6% vs. 22.2%; RR 0.84; 95% CI, 0.76–0.93) and hypertensive disorders of pregnancy (9.1% vs. 14.1%; RR, 0.64; 95% CI, 0.56–0.74) compared with expectant management (Table 1) (32).

Prevention Approaches Not Supported by Current Evidence

Oxidative stress has been implicated in the pathophysiology of preeclampsia (33), leading to the investigation of antioxidants such as vitamins C and E as potential preventive strategies. However, clinical trials have not demonstrated any significant benefit from these interventions in reducing the incidence or severity of preeclampsia (34–38).

Vasodilators such as sildenafil showed initial promise in in vitro and animal studies, suggesting a potential role in enhancing uteroplacental blood flow. Despite these early findings, clinical trials in humans have failed to demonstrate efficacy in the treatment or prevention of preeclampsia (39) with potential neonatal safety concerns (increased risk of neonatal pulmonary hypertension) (40).

Additionally, genetic polymorphisms in components of the renin–angiotensin system have been associated with an increased risk of preeclampsia (41). However, the clinical utility of genetic screening or targeted intervention based on these findings remains uncertain.

Treatment Trials

Different anticonvulsants, alone and in combinations of “lytic cocktails”, have been trialed for seizure prevention in individuals with preeclampsia and for prevention of recurrent seizures in those with eclampsia. Despite risk of toxicity and labor-intensive administration, magnesium sulfate emerged as the standard of care for individuals with preeclampsia with severe features or eclampsia due to its efficacy (42). Compared to individuals who received diazepam or phenytoin, those allocated to magnesium sulfate in the Collaborative Eclampsia Trial had significantly lower rates of recurrent seizure activity (43). Maternal mortality was also lower but did not reach statistical significance. This trial, however, included only individuals who already had convulsions.

The MAGnesium sulphate for Prevention of Eclampsia (Magpie) Trial included more than 10,000 individuals from 33 countries who were randomized to magnesium sulfate or placebo for the prevention, rather than the treatment, of eclampsia (44). Rates of eclampsia and maternal mortality were significantly lower in the magnesium sulfate group (0.8%) compared to the placebo group (1.9%) (Table 2). Side effects of treatment occurred more frequently in the magnesium sulfate group (24% vs 5% in the placebo group), but most side effects were mild, with flushing being the most common. Treatment was stopped early due to maternal request or side effects in 8% of participants in the magnesium sulfate group, compared with 2% in the placebo group.

The Magpie Trial enrolled individuals with both mild and severe preeclampsia. Although treatments varied by country, in the United States, individuals with preeclampsia, whether mild or severe, routinely received magnesium sulfate infusion until the early 2000s (45, 46). Subsequent studies concluded that the baseline risk of progression to eclampsia from preeclampsia without severe features is low, and the costs and side effects of magnesium sulfate outweigh potential benefits among individuals without severe features.

Livingston et al. randomized 222 individuals with mild preeclampsia to intravenous magnesium sulfate vs placebo (47). No participants in either group progressed to eclampsia. There were no significant differences in the rates of progression to severe preeclampsia (Table 2). Similarly, Witlin et al. conducted a randomized controlled trial (RCT) of 135 individuals with mild preeclampsia at term comparing magnesium sulfate treatment to placebo (46). The primary outcomes focused on length and characteristics of labor, but there were no differences in rates of progression to severe preeclampsia (Table 2). One individual in the magnesium treatment group had a seizure 8 days postpartum, but no other participants had seizures. These trials were overall limited and underpowered for the outcome of eclampsia, but they highlight the low risk of seizures in preeclampsia without severe features. Given its many side effects and risks of toxicity, evidence does not justify routine use of magnesium sulfate for seizure prophylaxis for individuals with preeclampsia without severe features (42, 45).

Magnesium sulfate treatment mitigates risks of seizures, but the definitive cure for preeclampsia is delivery. Current guidelines in the US recommend delivery no later than 34 weeks’ gestation among individuals with preeclampsia with severe features and no later than 37 weeks’ gestation for preeclampsia without severe features, or at diagnosis if it occurs later than these gestational ages. These guidelines are based on trials that examined risks of worsening maternal morbidity with continuation of pregnancy balanced with fetal risks of prematurity.

The HYPITAT trial was a multicenter RCT comparing induction of labor with expectant management at or after 36 weeks’ gestation in individuals with gestational hypertension or mild preeclampsia (48). The primary outcome, a composite of maternal morbidity, occurred less frequently among those randomized to induction (31% vs 44%), with a relative risk reduction of 29% and number needed to treat of 8. Progression to severe preeclampsia also occurred less frequently in the induction group. There were no differences in fetal or neonatal adverse outcomes (Table 2). Although the HYPITAT trial was underpowered for subgroup analyses, beneficial effects of induction were not clear in the small group of participants who were randomized at less than 37 weeks’ gestation.

Ideal management of mild hypertensive disorders before 37 weeks’ therefore remained uncertain. The subsequent HYPITAT-II trial compared immediate delivery to expectant management of individuals with gestational hypertension or mild preeclampsia at 34–37 weeks’ gestation (49). Rates of maternal morbidity were low in both groups and not significantly different (1.1% vs 3.1%, p=0.07). However, rates of neonatal adverse outcomes occurred were significantly higher in the immediate delivery group (5.7 vs. 1.7%, p=0.005), driven largely by higher rates of neonatal respiratory distress (Table 2). Based largely on these trials, expectant management of preeclampsia without severe features is recommended until 37 weeks’ gestation.

Preeclampsia with severe features is associated with higher risks of maternal and fetal morbidity than without severe features. For individuals with severe preeclampsia at 28 to 32 weeks’ gestation, Sibai et al. compared delivery 48 hours after antenatal corticosteroids with expectant management (50). In the expectant management group, latency from diagnosis to delivery was longer, and gestational age at delivery was later (32.9 vs 30.8 weeks, p<0.0001). Rates of neonatal intensive care unit (NICU) admission and neonatal complications were lower in the expectant management group, demonstrating neonatal benefit of expectant management of severe preeclampsia (Table 2).

In a similarly designed study that included participants at 28–34 weeks’ gestation with severe preeclampsia, Odendaal et al. demonstrated increased latency from diagnosis to delivery in those randomized to expectant management (7.1 vs 1.3 days, p<0.05) (Table 2), as well as lower rates of composite neonatal morbidity and mortality (51). Only one patient in the expectant management group reached 34 weeks’ gestation without developing complications necessitating delivery. Subsequent observational studies have confirmed that in resource-rich settings, expectant management of preeclampsia with severe features up to 34 weeks’ gestation with intensive monitoring is associated with prolongation of pregnancy with improved neonatal outcomes and low maternal risk (52–54). Conversely, the benefits of expectant management have not been demonstrated in low resource settings and may be associated with increased risk of SGA (55).

Conclusion

Hypertensive disorders of pregnancy are common and associated with significant maternal and fetal morbidity. Preventive and therapeutic strategies have evolved over the past decade especially with the use of aspirin, statins, magnesium sulfate, management of chronic hypertension, and timely delivery. Despite these the frequency of these disorders and their severity is increasing, and novel therapeutics and management strategies are urgently needed.

Acknowledgment:

Dr Costantine is supported by grants from The Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant number: UG1HD027915, R24 HD113024). This manuscript does not necessarily represent the official views of the NICHD or the National Institute of Health.

Footnotes

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Conflicts of interest: The authors have nothing to disclose.

Disclosure

The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

Declaration of interests

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Maged Costantine, MD reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Contributor Information

Eniola R. Ibirogba, Fellow, Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The Ohio State University.

Jennifer Grasch, Assistant Professor, Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The Ohio State University.

Maged M. Costantine, Professor, Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The Ohio State University.

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