INTRODUCTION — Preeclampsia is a multisystem progressive disorder characterized by the new onset of hypertension and proteinuria or other significant end-organ dysfunction in the last half of pregnancy or postpartum (table 1). Progression from nonsevere (previously referred to as "mild") to severe (table 2) on the disease spectrum may be gradual or rapid.
A key focus of routine prenatal care is monitoring patients for signs and symptoms of preeclampsia. If the diagnosis is made, the only definitive treatment is delivery to prevent development of maternal or fetal complications from disease progression. Delivery leads to eventual resolution of the disease, although end-organ dysfunction may worsen in the first one to three days postpartum. Timing of delivery is based on a combination of factors, including disease severity, maternal and fetal condition, and gestational age.
Low-dose aspirin can reduce the occurrence of preeclampsia in patients at high risk for the disease. Once the diagnosis has been made, antihypertensive therapy does not prevent disease progression but can prevent the occurrence of severe hypertension and its sequalae (such as stroke and placental abruption) and magnesium sulfate can prevent seizures (eclampsia).
Postpartum maternal monitoring is important to identify the minority of patients whose blood pressure does not return to normal after giving birth. Long-term maternal surveillance is also important because patients with a history of preeclampsia are at increased risk for development of cardiovascular disease later in life.
This topic will discuss the antepartum management of pregnancies complicated by preeclampsia and timing of delivery. Other important issues related to this disease are reviewed separately.
●(See "Preeclampsia: Intrapartum and postpartum management and long-term prognosis".)
●(See "Preeclampsia: Pathogenesis".)
●(See "Preeclampsia: Clinical features and diagnosis".)
●(See "Early pregnancy prediction of preeclampsia".)
●(See "Preeclampsia: Prevention".)
●(See "Preeclampsia with severe features: Expectant management remote from term".)
PREECLAMPSIA WITH FEATURES OF SEVERE DISEASE
General approach: Delivery
●Preeclampsia with features of severe disease (formerly called severe preeclampsia) (table 2) is generally regarded as an indication for delivery in pregnancies ≥34+0 weeks of gestation [1]. Delivery minimizes both the risk of serious maternal complications, such as cerebral hemorrhage (stroke), hepatic rupture, renal failure, pulmonary edema, seizure, bleeding related to thrombocytopenia, myocardial infarction, acute respiratory distress syndrome, retinal injury, or abruption, and the risk of fetal complications, such as growth restriction and demise [1-4]. Maternal life-threatening complications can occur suddenly. (See "Preeclampsia: Clinical features and diagnosis", section on 'Spectrum of disease' and "Preeclampsia: Clinical features and diagnosis", section on 'Natural history/course of disease'.)
●Pregnancies in which the fetus has not attained the gestational age at the lower limit of viability (23 to 24 weeks), pregnancies <34+0 weeks of gestation with preterm labor or prelabor rupture of membranes, and pregnancies in which the maternal and/or fetal condition is unstable are also candidates for delivery. Attempting to prolong pregnancy in these settings subjects the mother and fetus to significant risks with relatively small potential benefits; therefore, delivery is preferable.
Management of delivery is reviewed separately. (See "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Intrapartum management'.)
Expectant management of selected cases — Expectant management rather than expeditious delivery is reasonable for selected preterm pregnancies with preeclampsia with features of severe disease to reduce neonatal morbidity from preterm birth, even though the mother and fetus are at risk from disease progression. Expectant management allows administration of a course of antenatal corticosteroids and may provide time for further fetal growth and maturation.
For consideration of this approach, both the mother and fetus must be stable, closely monitored in a hospital setting with an appropriate level of newborn care, and cared for by, or in consultation with, a maternal-fetal medicine specialist. We favor limiting expectant management to pregnancies ≥24 weeks and <34 weeks of gestation. Selection of appropriate candidates for this approach and management of these pregnancies are discussed separately. (See "Preeclampsia with severe features: Expectant management remote from term".)
PREECLAMPSIA WITHOUT FEATURES OF SEVERE DISEASE
General approach
Term pregnancies: Delivery — Experts consistently recommend delivery of patients with preeclampsia at ≥37+0 weeks of gestation, even without features of severe disease (previously called "mild preeclampsia") [1,4,5].
The benefits of this approach are best supported by a multicenter trial (HYPITAT) that randomly assigned 756 patients with mild preeclampsia or gestational hypertension at 36+0 to 41+0 weeks of gestation to induction of labor within 24 hours of randomization or expectant management with maternal/fetal monitoring [6]. Intervention had favorable effects on maternal outcome, without incurring an increase in cesarean birth or neonatal morbidity. Specifically:
●Induction resulted in a 30 percent reduction in a composite of serious maternal outcomes (31 versus 44 percent, relative risk [RR] 0.71, 95% CI 0.59-0.86), which was primarily driven by a reduction in patients who developed severe hypertension.
The composite included (1) maternal mortality, (2) maternal morbidity (eclampsia, HELLP syndrome [hemolysis, elevated liver enzymes, low platelets], pulmonary edema, thromboembolic disease, abruption), (3) progression to severe disease (systolic blood pressure ≥170 mmHg and/or diastolic blood pressure ≥110 mmHg, proteinuria ≥5 g per 24 h), and (4) major postpartum hemorrhage.
●Induction resulted in a lower rate of cesarean birth (14 versus 19 percent).
●Induction did not result in statistical differences between groups in any neonatal outcome measure, even though the induced group gave birth, on average, 1.2 weeks earlier than the expectantly managed group. The possibility of small differences in newborn outcomes could not be definitively excluded because of the small number of adverse outcomes.
Follow-up analyses have shown that an unfavorable cervix is not a reason to avoid induction [7,8]. In a secondary analysis of data from this trial and DIGITAT (pregnancies complicated by fetal growth restriction), induction of labor at term in patients with a median Bishop score of 3 (range 1 to 6) was not associated with a higher risk of cesarean delivery than expectant management, and approximately 85 percent of patients in both groups achieved a vaginal delivery [8]. Prostaglandins or a balloon catheter were used for cervical ripening.
In addition, an economic analysis of the HYPITAT trial conducted in the Netherlands concluded that induction was 11 percent less costly overall than expectant management with monitoring [9].
Management of delivery is reviewed separately. (See "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Intrapartum management'.)
Preterm pregnancies: Expectant management — At preterm gestational ages, the risks for serious sequelae from disease progression need to be balanced with the newborn risks resulting from preterm birth.
Before 34 weeks — When mother and fetus are stable and have no findings of serious end-organ dysfunction before 34+0 weeks, an expectant approach with close monitoring for evidence of progression to the severe end of the disease spectrum is reasonable to achieve further fetal growth and maturity. Guidelines from major medical organizations generally recommend expectant management of preeclampsia without features of severe disease at this gestational age, based on expert opinion, given the high risk of neonatal morbidity from preterm birth [1,4,5]. We concur with this approach. However, development of severe hypertension, serious maternal end-organ dysfunction (table 2), or nonreassuring tests of fetal well-being is generally an indication for prompt delivery.
34+0 to 36+6 weeks — There is less consensus about the optimum management of preeclampsia without features of severe disease and stable maternal and fetal condition at 34+0 to 36+6 weeks. Although there are serious maternal risks with expectant management, we believe expectant management until 37+0 weeks is reasonable in fully informed patients because the absolute maternal risk of a serious adverse outcome is low, and there are modest neonatal benefits from birth at 37+0 weeks rather than earlier. After a discussion of the risks and benefits of planned late preterm birth (34+0 to 36+6 weeks) versus planned early term birth at or shortly after 37+0 weeks, the timing of birth should ultimately be a shared decision.
The PHOENIX trial provided quantitative data for patient counseling [10]. This multicenter randomized trial compared planned early birth within 48 hours versus expectant management (usual care) in 901 singleton or dichorionic diamniotic twin pregnancies at 34+0 to 36+6 weeks with preeclampsia. Compared with expectant management, planned early birth:
●Reduced adverse maternal composite outcome (maternal morbidity or systolic blood pressure ≥160 mmHg: 289 out of 448 [65 percent] versus 338 out of 451 [75 percent]; adjusted RR 0.86, 95% CI 0.79-0.94). Severe systolic hypertension accounted for at least 60 percent of the composite outcome in both groups.
●Increased adverse perinatal composite outcome (perinatal death or neonatal intensive care unit [NICU] admission: 196 out of 471 [42 percent] versus 159 out of 475 [34 percent], RR 1.26, 95% CI 1.08-1.47). However, there were no perinatal deaths. Thus, this difference derived from a greater number of newborns in the planned early delivery group admitted to the NICU, most of whom were admitted because of preterm gestational age alone; respiratory morbidity was not increased compared with expectant management.
The overall number of serious adverse events was similar in both groups. Neither group had a stillbirth or neonatal death. Both groups included four patients with abruption. Although PHOENIX is the largest randomized trial to address this issue, the number of adverse events was still relatively small, and thus, the trial was underpowered to find statistical differences in individual outcomes of clinical importance in shared decision making. For example, expectant management had statistically significant favorable perinatal effects at 34 and 35 weeks of gestation, which were attenuated by including pregnancies at 36 weeks.
In the expectantly managed group, the median additional prolongation of pregnancy was five days (three days after adjustment of confounders), more than one-half of the patients in this group had an indicated delivery before 37 weeks, and 74 percent progressed to preeclampsia with severe features (versus 64 percent in the planned delivery group). The only maternal death occurred in the expectantly managed group in a patient with underlying medical comorbidities who died unexpectedly five days postpartum; this death was not thought to be related to expectant management.
A follow-up of this trial comparing the cardiovascular effects of planned early birth versus expectant management reported that the prevalence of hypertension at six months postpartum was 71 percent, and 10 percent of the patients had left ventricular ejection fraction <55 percent, with no significant differences between the two approaches [11]. This suggests that expectant management does not further worsen maternal cardiovascular health. Infant follow-up at two years showed that average neurodevelopmental assessment was within the normal range in both groups, but follow-up was lower than anticipated [12]. This suggests that the increased frequency of adverse perinatal composite outcome in the planned early delivery group is probably not associated with a high risk of serious long-term consequences for the child and thus may be an acceptable trade-off for the reduction in adverse maternal composite outcome with early delivery.
A strength of the data from the PHOENIX trial is that the trial was restricted to patients with preeclampsia at 34+0 to 36+6 weeks. A 2022 individual participant data meta-analysis of six randomized trials of planned early delivery versus expectant management primarily included patients with preeclampsia, but also some with gestational hypertension and/or fetal growth restriction, and the patients presented over a wider gestational age range (mostly 34+0 to 36+6 weeks, but one trial included pregnancies as early as 24 weeks and two trials included pregnancies up to 41+0 weeks) [13]. Similar to findings from PHOENIX, early delivery reduced the risk of composite maternal morbidity (2.6 versus 4.4 percent; adjusted RR 0.59, 95% CI 0.36-0.98) and an increased the risk of composite perinatal morbidity/mortality (20.9 versus 17.1 percent; adjusted RR 1.22, 95% CI 1.01-1.47), driven by short-term neonatal respiratory morbidity. In addition, newborns in the expectant management group were more likely to be small for gestational age (7.8 versus 10.6 percent; RR 0.74, 95%CI 0.55-0.99).
Components of expectant management
Inpatient versus outpatient care — Close maternal monitoring upon diagnosis of preeclampsia is important to establish disease severity and the rate of progression. Hospitalization is useful for making these assessments and facilitates immediate intervention in the event of rapid deterioration. After the initial in-hospital diagnostic evaluation, outpatient care (at home or at an antenatal day care unit [14]) is a cost-effective option for patients found to be stable over a period of several days and with no severe features of preeclampsia [15-19]. Patients offered outpatient monitoring should be well-informed and understand the importance of contacting the health care provider if they have symptoms/signs of worsening disease. They should be able to comply with modified activity, undergo blood pressure measurements twice daily, and undergo fetal monitoring and blood tests twice a week. In addition, they should live close to a hospital and have someone with them at home at all times to help in the event of an unexpected adverse event. If signs or symptoms of disease progression are noted, hospitalization for more intensive monitoring and possible delivery is indicated.
There are limited data on the outcome of outpatient management of preeclampsia. An observational study and a randomized trial reported good outcomes, but these studies had too few subjects to detect small but clinically significant differences in outcome between inpatient and outpatient management [16,17]. A systematic review of three trials with a total of 504 patients with various complications of pregnancy observed no major differences in clinical outcomes for mothers or infants when care was provided in an antenatal day care unit versus hospital admission [14].
The American College of Obstetricians and Gynecologists considers ambulatory management at home an option for patients with preeclampsia without severe features as long as the patient is well informed and serial, frequent maternal and fetal monitoring are performed, including blood pressure, ultrasonography, and laboratory studies (platelet count, serum creatinine, liver enzymes), as described below [1].
Patient education and counseling — Patients with preeclampsia should be aware of the signs and symptoms at the severe end of the disease spectrum (table 2) and should monitor fetal movements daily. If a patient develops a severe or persistent headache (eg, does not respond to one dose of acetaminophen), visual changes, new shortness of breath, or right upper quadrant or epigastric pain, they should notify their health care provider immediately. Patients who self-monitor blood pressure should be instructed about the correct procedure. (See "Treatment of hypertension in pregnant and postpartum patients", section on 'Technique for accurate measurement of blood pressure'.)
As with any pregnancy, decreased fetal movement, vaginal bleeding, abdominal pain, rupture of membranes, or regular uterine contractions should be reported immediately, as well.
Physical activity — Because blood pressure is lower in rested patients, restricted activity (eg, no heavy lifting, several hours of daytime rest with the feet elevated, relaxation techniques) is often recommended; however, these is a lack of evidence of favorable effects on the course of preeclampsia or its outcome. Resting in the left lateral decubitus position can augment uteroplacental flow, which may benefit pregnancies in which fetal growth is a concern. In all pregnant patients, avoiding the supine sleep position (which can reduce maternal cardiac output) can have favorable fetal effects and appears prudent [20].
Strict bedrest is unnecessary as there is no evidence that bedrest improves pregnancy outcome or delays progression of the disease [21]. Furthermore, strict bedrest in hospitalized pregnant patients has been associated with an increased risk of venous thromboembolism [22].
Laboratory follow-up — The minimum laboratory evaluation should include:
●Platelet count
●Serum creatinine level
●Serum aminotransferases
These tests should be repeated at least twice weekly in patients with preeclampsia without severe features to assess for disease progression, and more often if clinical signs and symptoms suggest worsening disease.
Although other laboratory abnormalities may occur (see "Preeclampsia: Clinical features and diagnosis", section on 'Potential laboratory findings'), the value of monitoring additional laboratory tests is unclear. A rising hematocrit can be informative as a sign of hemoconcentration, which suggests contraction of intravascular volume and progression to more severe disease, while a falling hematocrit can be a sign of hemolysis; however, an elevated serum indirect bilirubin and/or lactate dehydrogenase (LDH) concentration is a better marker for hemolysis. Hemolysis can be confirmed by observation of schistocytes and helmet cells on a blood smear (picture 1A-B). (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".)
Since several clinical studies have shown that neither the rate of increase nor the amount of proteinuria affects maternal or perinatal outcome in patients with preeclampsia [23-26]. Therefore, repeated urinary protein estimations are not useful once the threshold of 300 mg/24 hours or random urine protein/creatinine ratio ≥0.3 mg/mg for the diagnosis of preeclampsia has been met. At that point, serum creatinine alone can be used to monitor renal function. It is the practice of some providers, including the authors, to confirm a low positive protein creatinine ratio (0.3 to 0.6) with a 24-hour collection. (See "Evaluation of proteinuria in pregnancy and management of nephrotic syndrome" and "Preeclampsia with severe features: Expectant management remote from term".)
Monitoring blood pressure and treatment of hypertension — Blood pressure should be measured twice daily at home in patients being managed expectantly with preeclampsia without severe features, and at least twice weekly in the office when the patient comes in for laboratory and fetal evaluation. In a meta-analysis, systolic blood pressure values measured at home were lower than office values by an average of 4 mmHg (95% CI -6 to -3) and diastolic measurements were lower by an average of 3 mmHg (95% CI -4 to -2) [27].
A confirmed elevation of systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg should prompt immediate hospitalization for further evaluation and management. Antihypertensive therapy (table 3) should be initiated as soon as reasonably possible, ideally within 30 to 60 minutes, with the goal of preventing stroke, and possibly abruption.
The use of antihypertensive drugs to control nonsevere hypertension (defined as systolic blood pressure <160 mmHg and diastolic blood pressure <110 mmHg) in the setting of preeclampsia does not alter the course of the disease or diminish perinatal morbidity or mortality, and is best avoided in most patients. It does, however, reduce the occurrence of progression to severe hypertension. The indications for starting antihypertensive therapy, the choice of drug, and blood pressure goals (<140/90 mmHg) are discussed in detail separately. (See "Treatment of hypertension in pregnant and postpartum patients", section on 'Our approach'.)
Sodium restriction below the recommended daily intake and diuretics have no role in routine therapy [28-30]. Although intravascular vascular volume is reduced, a randomized trial showed that plasma volume expansion did not improve maternal or fetal outcome [31]. In patients who have not delivered, diuretic administration is only indicated for treatment of pulmonary edema, but these drugs may be used more liberally postpartum. (See "Treatment of hypertension in pregnant and postpartum patients", section on 'Approach to patients with severe versus nonsevere hypertension'.)
Assessment of fetal growth — Early fetal growth restriction may be the first manifestation of preeclampsia and is typically a sign of severe uteroplacental insufficiency. At the time of diagnosis of preeclampsia, we perform sonography to estimate fetal weight and assess amniotic fluid volume for evaluation of fetal growth restriction and oligohydramnios. If the initial examination is normal, we repeat the ultrasound examination every three to four weeks. Management of the growth restricted fetus is reviewed separately. (See "Fetal growth restriction: Evaluation".)
Assessment of fetal well-being — There are no data from randomized trials on which to base recommendations for the optimal type and frequency of antepartum fetal monitoring. At a minimum, we suggest daily fetal movement counts with either twice weekly nonstress testing plus assessment of amniotic fluid volume or twice weekly biophysical profiles, beginning at the time of diagnosis of preeclampsia. Fetal testing should be performed promptly if there is an abrupt change in maternal condition or decreased fetal activity. (See "Overview of antepartum fetal assessment".)
Evaluation of umbilical artery Doppler velocimetry indices is useful if fetal growth restriction is suspected, as the results help in optimizing timing of delivery. In a meta-analysis of 16 randomized trials in high-risk pregnancies (n = 10,225 infants), knowledge of umbilical artery Doppler velocimetry resulted in a 29 percent reduction in perinatal death (1.2 versus 1.7 percent; RR 0.71, 95% CI 0.52-0.98; number needed to treat 203, 95% CI 103-4352), primarily in pregnancies complicated by preeclampsia and/or growth restriction [32]. The frequency of Doppler assessment depends on the findings; weekly assessment is reasonable when the indices are normal. The significance of abnormal umbilical artery Doppler velocimetry in the setting of a well grown fetus with normal amniotic volume is unclear.
Antenatal corticosteroids — A course of steroids (betamethasone or dexamethasone) is administered when the clinician believes birth within the next seven days is likely and neonatal resuscitation will be performed, if needed. Although preeclampsia may accelerate fetal lung maturation, neonatal respiratory distress remains common in preterm neonates of pregnancies with preeclampsia [33,34].
Antenatal corticosteroids to promote fetal lung maturity should be administered to patients <34+0 weeks of gestation since they are at increased risk of preterm birth because of progression to severe disease. However, delivery should not be delayed solely for administration of a full course of steroids. Use of steroids at ≥34+0 weeks is more controversial and discussed separately. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Candidates for a first ACS course by gestational age'.)
Disease-modifying therapy — No disease-modifying therapy is available. Investigational therapies include, among others, pravastatin, metformin, plasmapheresis to remove antiangiogenic factors, monoclonal antibodies (against tumor necrosis factor alpha or complement), and gene silencing targeting sFlt-1 production or angiotensinogen [35].
Timing of delivery — For patients managed conservatively, delivery is indicated at or shortly after 37+0 weeks of gestation or as soon as they develop preeclampsia with severe features (table 2), whether or not the cervix is favorable. (See 'Term pregnancies: Delivery' above and 'General approach: Delivery' above.)
Earlier delivery is indicated if standard indications arise, such as abnormal antepartum testing, preterm labor, preterm prelabor rupture of membranes, or abruption [1].
SUMMARY AND RECOMMENDATIONS
●General principles
•The key principles in managing patients with preeclampsia are treatment of severe hypertension, seizure prevention, timely delivery, and postpartum surveillance. (See 'Introduction' above and "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Introduction'.)
•The definitive treatment of preeclampsia is delivery to prevent development of maternal or fetal complications from disease progression. Timing of delivery is based upon gestational age, the severity of preeclampsia, and maternal and fetal condition (algorithm 1). (See 'Introduction' above and "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Introduction'.)
•Preeclampsia with features of severe disease (table 2) is generally an indication for delivery, regardless of gestational age, given the high risk of serious maternal morbidity. However, prolonged antepartum management in a tertiary care setting or in consultation with a maternal-fetal medicine specialist is an option for selected patients remote from term (<34 weeks of gestation). (See 'Preeclampsia with features of severe disease' above.)
•Antihypertensive therapy is required for treatment of severe hypertension (defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg) to prevent stroke (table 3); it does not prevent eclampsia. Antihypertensive therapy to control nonsevere hypertension does not alter the course of preeclampsia or diminish perinatal morbidity or mortality, and is avoided in most patients. (See "Treatment of hypertension in pregnant and postpartum patients".)
●Timing of delivery
•Diagnosis at term – For patients at term (≥37+0 weeks) with preeclampsia without features of severe disease, we suggest delivery rather than expectant management (Grade 2B). Delivery reduces the risk of maternal complications and is associated with a low risk of neonatal morbidity at this gestational age. (See 'Term pregnancies: Delivery' above and 'Timing of delivery' above.)
•Diagnosis preterm – For patients with early preterm (<34+0 weeks) and late preterm (34+0 to 36+6 weeks) preeclampsia without features of severe disease, we suggest expectant management with delivery when the pregnancy has reached 37+0 weeks of gestation (Grade 2C). Earlier delivery is indicated for standard obstetric indications (eg, nonreassuring fetal testing, preterm prelabor rupture of membranes). (See 'Preterm pregnancies: Expectant management' above and 'Timing of delivery' above.)
●Expectant management of undelivered patients
•Close monitoring during expectant management of preterm preeclampsia without features of severe disease consists of:
-Laboratory monitoring (platelet count, liver and renal function tests) at least twice weekly
-Blood pressure measurement at least twice daily
-Ongoing assessment and report of symptoms
-Evaluation of fetal growth at diagnosis, repeat ultrasound in three to four weeks if the fetus is appropriate weight for gestational age
-Evaluation of fetal well-being with daily fetal movement counts and twice weekly nonstress testing plus assessment of amniotic fluid volume, or twice weekly biophysical profiles
In most patients with nonsevere hypertension (systolic blood pressure <160 mmHg or diastolic blood pressure <110 mmHg), antihypertensive therapy is not indicated. (See 'Components of expectant management' above.)
•Antenatal corticosteroids – For patients with a viable fetus and preeclampsia <34+0 weeks of gestation, we recommend a course of antenatal corticosteroids (betamethasone) (Grade 1A). Use of steroids at 34 to 36 weeks is controversial. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Candidates for a first ACS course by gestational age'.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges John T Repke, MD, who contributed to an earlier version of this topic review.
