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SMFM clinical opinion| Volume 205, ISSUE 3, P191-198, September 2011

Evaluation and management of severe preeclampsia before 34 weeks' gestation

      Objective

      We sought to review the risks and benefits of expectant management of severe preeclampsia remote from term, and to provide recommendations for expectant management, maternal and fetal evaluation, treatment, and indications for delivery.

      Methods

      Studies were identified through a search of the MEDLINE database for relevant peer-reviewed articles published in the English language from January 1980 through December 2010. Additionally, the Cochrane Library, guidelines by organizations, and studies identified through review of the above documents and review articles were utilized to identify relevant articles. Where reliable data were not available, opinions of respected authorities were used.

      Results and Recommendations

      Published randomized trials and observational studies regarding management of severe preeclampsia occurring <34 weeks of gestation suggest that expectant management of selected patients can improve neonatal outcomes but that delivery is often required for worsening maternal or fetal condition. Patients who are not candidates for expectant management include women with eclampsia, pulmonary edema, disseminated intravascular coagulation, renal insufficiency, abruptio placentae, abnormal fetal testing, HELLP syndrome, or persistent symptoms of severe preeclampsia. For women with severe preeclampsia before the limit of viability, expectant management has been associated with frequent maternal morbidity with minimal or no benefits to the newborn. Expectant management of a select group of women with severe preeclampsia occurring <34 weeks' gestation may improve newborn outcomes but requires careful in-hospital maternal and fetal surveillance.

      Key words

      Introduction

      Preeclampsia is a multisystem disorder that can manifest clinically with hypertension and proteinuria with or without accompanying symptoms, abnormal maternal laboratory test results, intrauterine growth restriction, or reduced amniotic fluid volume.
      • Sibai B.
      • Dekker G.
      • Kupfermic M.
      Preeclampsia.
      The incidence of severe preeclampsia ranges from 0.6-1.2% of pregnancies in Western countries.
      • Kuklina E.V.
      • Aya C.
      • Callaghan W.M.
      Hypertensive disorders and severe obstetric morbidity in the United States.
      • Catov J.M.
      • Ness R.B.
      • Kip K.E.
      • Olsen J.
      Risk of early or severe preeclampsia related to preexisting conditions.
      • Zhang J.
      • Meikle S.
      • Trumble A.
      Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States.
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      Preeclampsia <37 weeks' and severe preeclampsia <34 weeks' gestation complicates 0.6-1.5% and 0.3% of pregnancies, respectively.
      • Catov J.M.
      • Ness R.B.
      • Kip K.E.
      • Olsen J.
      Risk of early or severe preeclampsia related to preexisting conditions.
      • Gupta L.M.
      • Gaston L.
      • Chauhan S.P.
      Detection of fetal growth restriction with preterm severe preeclampsia: experience at two tertiary centers.
      The likelihood of severe and preterm preeclampsia is substantially increased in women with a history of preeclampsia, and in those with diabetes mellitus, chronic hypertension, or a multifetal gestation.
      • Sibai B.
      • Dekker G.
      • Kupfermic M.
      Preeclampsia.
      • Catov J.M.
      • Ness R.B.
      • Kip K.E.
      • Olsen J.
      Risk of early or severe preeclampsia related to preexisting conditions.
      • Sibai B.M.
      • Akl S.
      • Fairlie F.
      • Moretti M.
      A protocol for managing severe preeclampsia in the second trimester.
      • Visser W.
      • Wallenburg H.C.S.
      Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe preeclampsia remote from term.
      • Vigil-DeGarcia P.
      • Montufar-Rueda C.
      • Ruiz J.
      Expectant management of severe preeclampsia between 24 and 34 weeks' gestation.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      Published reports use differing criteria for the diagnoses of preeclampsia, severe and superimposed preeclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Commonly used definitions are presented in the Table.
      Report of the National High Blood Pressure Education Program Working group report on high blood pressure in pregnancy.
      American College of Obstetricians and Gynecologists
      Diagnosis and management of preeclampsia and eclampsia: ACOG practice bulletin no. 33.
      • Sibai B.M.
      • Ramadan M.K.
      • Usta I.
      • Salama M.
      • Mercer B.M.
      • Friedman S.A.
      Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome).
      • Martin Jr, J.N.
      • Blake P.G.
      • Perry K.G.
      • McCaul J.F.
      • Hess L.W.
      • Martin R.W.
      The natural history of HELLP syndrome: patterns of disease progression and regression.
      For women with preexisting hypertension or proteinuria, the diagnosis of severe preeclampsia can be more difficult, but new-onset severe hypertension or proteinuria, or development of other clinical or laboratory findings of severe preeclampsia are suggestive of preeclampsia in this setting.
      The quality of evidence for each included article was evaluated according to the categories outlined by the US Preventative Services Task Force:
      • I
        Properly powered and conducted randomized controlled trial; well-conducted systematic review or metaanalysis of homogeneous randomized controlled trials.
      • II-1
        Well-designed controlled trial without randomization.
      • II-2
        Well-designed cohort or case-control analytic study.
      • II-3
        Multiple time series with or without the intervention; dramatic results from uncontrolled experiments.
      • III
        Opinions of respected authorities, based on clinical experience; descriptive studies or case reports; reports of expert committees.
      Recommendations are graded in the following categories:
      Level A
      The recommendation is based on good and consistent scientific evidence.
      Level B
      The recommendation is based on limited or inconsistent scientific evidence.
      Level C
      The recommendation is based on expert opinion or consensus.
      The practice of medicine continues to evolve, and individual circumstances will vary. This opinion reflects information available at the time of its submission for publication and is neither designed nor intended to establish an exclusive standard of perinatal care. This publication is not expected to reflect the opinions of all members of the Society for Maternal-Fetal Medicine.
      TABLEDiagnostic criteria for preeclampsia, severe preeclampsia, and HELLP syndrome
      Report of the National High Blood Pressure Education Program Working group report on high blood pressure in pregnancy.
      American College of Obstetricians and Gynecologists
      Diagnosis and management of preeclampsia and eclampsia: ACOG practice bulletin no. 33.
      • Sibai B.M.
      • Ramadan M.K.
      • Usta I.
      • Salama M.
      • Mercer B.M.
      • Friedman S.A.
      Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome).
      • Martin Jr, J.N.
      • Blake P.G.
      • Perry K.G.
      • McCaul J.F.
      • Hess L.W.
      • Martin R.W.
      The natural history of HELLP syndrome: patterns of disease progression and regression.
      • Preeclampsia
        • Blood pressure ≥140 mm Hg or ≥90 mm Hg diastolic that occurs >20 wk' gestation in woman with previously normal blood pressure plus proteinuria defined as urinary excretion ≥0.3 g protein in 24-h urine specimen
      • Severe preeclampsia (≥1 of following criteria is required)
        • Blood pressure ≥160 mm Hg systolic or ≥110 mm Hg diastolic on 2 occasions at least 6 h apart while patient is on bed rest
        • Proteinuria ≥5 g in 24-h urine specimen ≥3+ on 2 random urine samples collected at least 4 h apart
        • Oliguria <500 mL in 24 h
        • Cerebral or visual symptoms
        • Pulmonary edema or cyanosis
        • Epigastric or right upper quadrant pain
        • Impaired liver function
        • Thrombocytopenia
        • Fetal growth restriction
      • Superimposed preeclampsia (≥1 of following criteria is required)
        • New-onset proteinuria ≥0.3 g protein in woman with hypertension <20 wk' gestation
        • If hypertension and proteinuria present <20 wk' gestation
          • Sudden increase in proteinuria if both hypertension and proteinuria are present <20 wk' gestation
          • Sudden increase in hypertension in woman whose hypertension has previously been well controlled
          • Thrombocytopenia (platelet count <100,000 cells/mm3)
          • Increase in alanine aminotransferase or aspartate aminotransferase to abnormal levels
          Women with chronic hypertension who develop persistent headache, scotoma, or epigastric pain also may have superimposed preeclampsia
      • HELLP syndrome (differing diagnostic criteria have been reported, 2 commonly used criteria follow)
        • Sibai et al
          • Sibai B.M.
          • Ramadan M.K.
          • Usta I.
          • Salama M.
          • Mercer B.M.
          • Friedman S.A.
          Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome).
          (each of following required)
          • (1)
            Hemolysis on peripheral smear, lactate dehydrogenase >600 U/L, or total bilirubin >1.2 mg/dL
          • (2)
            Aspartate aminotransferase >70 U/L
          • (3)
            Platelet count <100,000 cells/mm3
        • Martin et al
          • Martin Jr, J.N.
          • Blake P.G.
          • Perry K.G.
          • McCaul J.F.
          • Hess L.W.
          • Martin R.W.
          The natural history of HELLP syndrome: patterns of disease progression and regression.
          (each of following required)
          • (1)
            Lactate dehydrogenase >600 U/L
          • (2)
            Aspartate aminotransferase or alanine aminotransferase >40 IU/L
          • (3)
            Platelet count <150,000 cells/mm3
      SMFM. Severe preeclampsia. Am J Obstet Gynecol 2011.
      Severe preeclampsia occurring preterm can result in both acute
      • Sibai B.
      • Dekker G.
      • Kupfermic M.
      Preeclampsia.
      • Kuklina E.V.
      • Aya C.
      • Callaghan W.M.
      Hypertensive disorders and severe obstetric morbidity in the United States.
      • Zhang J.
      • Meikle S.
      • Trumble A.
      Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States.
      • Sibai B.M.
      • Akl S.
      • Fairlie F.
      • Moretti M.
      A protocol for managing severe preeclampsia in the second trimester.
      • Visser W.
      • Wallenburg H.C.S.
      Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe preeclampsia remote from term.
      • Vigil-DeGarcia P.
      • Montufar-Rueda C.
      • Ruiz J.
      Expectant management of severe preeclampsia between 24 and 34 weeks' gestation.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      and long-term complications for both the mother and her newborn.
      • Magnussen E.B.
      • Vatlen L.J.
      • Lund-Nilsen T.I.
      • et al.
      Pregnancy cardiovascular risk factors as predictors of preeclampsia: population based cohort study.
      • Lykke A.
      • Langoff-Ross J.
      • Sibai B.M.
      • et al.
      Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother.
      Maternal complications of severe preeclampsia (Table) (as well as myocardial infarction, stroke, acute respiratory distress syndrome, coagulopathy, severe renal failure, retinal injury) occur more commonly in the presence of preexistent medical disorders, and with acute maternal organ dysfunction related to preeclampsia.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      • Schiff E.
      • Friedman S.A.
      • Sibai B.M.
      Conservative management of severe preeclampsia remote from term.
      Maternal morbidities rarely persist after severe preeclampsia, although cardiovascular disease later in life is more common regardless of clinical presentation.
      • Magnussen E.B.
      • Vatlen L.J.
      • Lund-Nilsen T.I.
      • et al.
      Pregnancy cardiovascular risk factors as predictors of preeclampsia: population based cohort study.
      • Lykke A.
      • Langoff-Ross J.
      • Sibai B.M.
      • et al.
      Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother.
      Fetal and newborn complications of severe preeclampsia result from exposure to uteroplacental insufficiency and/or from preterm birth.
      • Sibai B.
      • Dekker G.
      • Kupfermic M.
      Preeclampsia.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      Historically, women with severe preeclampsia have had delivery initiated upon diagnosis in order to limit maternal complications from worsening disease.
      • Sibai B.
      • Dekker G.
      • Kupfermic M.
      Preeclampsia.
      American College of Obstetricians and Gynecologists
      Diagnosis and management of preeclampsia and eclampsia: ACOG practice bulletin no. 33.
      The clinical course of severe preeclampsia is often characterized by progressive deterioration if delivery is not pursued.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      • Schiff E.
      • Friedman S.A.
      • Sibai B.M.
      Conservative management of severe preeclampsia remote from term.
      However, some have challenged the view that all patients with severe preeclampsia must be delivered expeditiously.
      • Sibai B.M.
      • Akl S.
      • Fairlie F.
      • Moretti M.
      A protocol for managing severe preeclampsia in the second trimester.
      The first attempts at expectant management were aimed at providing brief pregnancy prolongation to allow for antenatal corticosteroid administration, but the potential for longer expectant management was entertained because some patients remained stable or improved during initial observation. Further study has shown that median latency with expectant management ranges from 7–14 days.
      • Magee L.A.
      • Yong P.J.
      • Espinosa V.
      • Côté A.M.
      • Chen I.
      • von Dadelszen P.
      Expectant management of severe preeclampsia remote from term: a structured systematic review.
      In this report, the risks and benefits of expectant management of severe preeclampsia remote from term are reviewed, and recommendations regarding expectant management, maternal and fetal evaluation, and indications for delivery are offered. For the purpose of this document, expectant management is defined as any attempt to delay delivery for antenatal corticosteroid administration or longer.

      What are the benefits and risks of expectant management of severe preeclampsia <34 weeks' gestation?

      Randomized trials

      Only 2 randomized trials of delivery vs expectant management of preterm severe preeclampsia have been published.
      • Odendaal H.J.
      • Pattinson R.C.
      • Bam R.
      • Grove D.
      • Kotze T.J.
      Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial.
      • Sibai B.M.
      • Mercer B.M.
      • Schiff E.
      • Friedman S.A.
      Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.
      Odendaal et al
      • Odendaal H.J.
      • Pattinson R.C.
      • Bam R.
      • Grove D.
      • Kotze T.J.
      Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial.
      studied 38 women with severe preeclampsia between 28-34 weeks' gestation age and whose fetal weight was estimated to be between 650-1500 g. Eighteen women received antenatal corticosteroids for fetal maturation and were then treated expectantly, with delivery only for specific maternal or fetal indications. Another 20 patients were assigned to receive antenatal corticosteroids with planned delivery after 48 hours. Latency to delivery (7.1 vs 1.3 days; P < .05) and gestational age at delivery (223 vs 221 days; P < .05) were both greater with expectant management while total neonatal complications were reduced (33% vs 75%; P < .05) compared with planned delivery.
      Sibai et al
      • Sibai B.M.
      • Mercer B.M.
      • Schiff E.
      • Friedman S.A.
      Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.
      studied 95 women with severe preeclampsia and no concurrent medical (eg, renal disease, insulin-dependent diabetes, connective tissue disease) or obstetric (eg, vaginal bleeding, premature rupture of membranes, multifetal gestation, preterm labor) complications at 28-32 weeks' gestation. Those randomized to expectant management delivered at a more advanced gestational age (32.9 vs 30.8 weeks; P < .01), and had newborns with higher birthweights (1622 vs 1233 g; P < .01) who required less frequent neonatal intensive care unit admission (76% vs 100%; P < .01). Newborns from the expectantly managed group had less frequent respiratory distress syndrome (22.4% vs 50%; P = .002) and necrotizing enterocolitis (0% vs 10.9%; P = .02), but were more frequently small for gestational age at birth (30.1 vs 10.9; P = .04). There were no cases of maternal eclampsia or pulmonary edema in either trial. Abruptio placentae was similar in frequency between the randomized groups in both studies, but was more common in both the expectantly and nonexpectantly managed groups from the Odendaal et al
      • Odendaal H.J.
      • Pattinson R.C.
      • Bam R.
      • Grove D.
      • Kotze T.J.
      Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial.
      trial (22% vs 15%) than in the Sibai et al
      • Sibai B.M.
      • Mercer B.M.
      • Schiff E.
      • Friedman S.A.
      Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.
      study (4.1% vs 4.3%). HELLP syndrome complicated only 2 expectantly managed cases and 1 aggressively managed case in the latter study (4.1% vs 2.1%).
      Two additional randomized trials evaluated therapeutic interventions during expectant management. Fenakel et al
      • Fenakel K.
      • Kenakel G.
      • Appleman Z.
      • et al.
      Nifedipine in treatment of severe preeclampsia.
      described 49 women with severe preeclampsia at 26-36 weeks who were randomly assigned to receive either sublingual and oral nifedipine or intravenous and oral hydralazine treatments for severe hypertension during expectant management. Those assigned to nifedipine therapy delivered more frequently at ≥36 weeks, were less frequently diagnosed with acute fetal distress, and their infants had a shorter mean duration of neonatal intensive care unit stay than those assigned to hydralazine therapy (P < .01 for each). However, mean gestational age at delivery (34.6 vs 33.6 weeks; P < .20) and pregnancy prolongation (15.5 vs 9.5 days; P < .07) were not improved, and no differences in the frequencies of “major” or “minor” newborn complications were seen between groups. In multicenter comparison of antihypertensive therapy alone vs antihypertensive therapy plus plasma volume expansion, Ganzevoort et al
      • Ganzevoort W.
      • Rep A.
      • Bousel G.J.
      • et al.
      A randomized controlled trial comparing two temporizing management strategies, one with and one without plasma volume expansion, for severe preeclampsia.
      found that volume expansion gave no additional benefit among women expectantly managed with severe preeclampsia at 24-33 weeks 6 days.

      Observational studies

      Observational studies regarding expectant management of severe preeclampsia have varied in their inclusion criteria and indications for delivery.
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      • Sibai B.M.
      • Akl S.
      • Fairlie F.
      • Moretti M.
      A protocol for managing severe preeclampsia in the second trimester.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      • Magee L.A.
      • Yong P.J.
      • Espinosa V.
      • Côté A.M.
      • Chen I.
      • von Dadelszen P.
      Expectant management of severe preeclampsia remote from term: a structured systematic review.
      • Chua S.
      • Redman C.W.
      Prognosis for pre-eclampsia complicated by 5 g or more of proteinuria in 24 hours.
      • Olah K.S.
      • Redman W.G.
      • Gee H.
      Management of severe, early pre-eclampsia: is conservative management justified?.
      • van Pampus M.G.
      • Wolf H.
      • Westenberg S.M.
      • der Post V.
      • Bonsel G.J.
      • Treffers P.E.
      Maternal and perinatal outcome after expectant management of HELLP syndrome compared with preeclampsia without HELLP syndrome.
      • Chammas M.F.
      • Nguyen T.M.
      • Li M.A.
      • Nuwayhid B.S.
      • Castro L.C.
      Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?.
      • Hall D.R.
      • Odendaal H.J.
      • Steyn D.W.
      • Grove D.
      Expectant management of early onset, severe preeclampsia; maternal outcome.
      • Hall D.R.
      • Odendaal H.J.
      • Kristen G.F.
      • Smith J.
      • Grove D.
      Expectant management of early onset, severe preeclampsia: perinatal outcome.
      • Shear R.M.
      • Rinfret D.
      • Leduc L.
      Should we offer expectant management in cases of severe preterm preeclampsia with fetal growth restriction?.
      • Oettle C.
      • Hall D.
      • Roux A.
      • Grove D.
      Early onset severe preeclampsia: expectant management at a secondary hospital in close association with a tertiary institution.
      • Bombrys A.E.
      • Barton J.R.
      • Nowacki E.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at <27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Bombrys A.E.
      • Barton J.R.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at 270/7-336/7 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Hall D.R.
      • Grove D.
      • Carstens E.
      Early-preeclampsia: what proportion of women qualify for expectant management and if not, why not?.
      • Sarsam D.S.
      • Shamden M.
      • Al Wazan R.
      Expectant versus aggressive management in severe preeclampsia remote from term.
      • Abdel-Hady el.-S.
      • Fawzy M.
      • El-Negeri M.
      • Nezar M.
      • Ragab A.
      • Helal A.S.
      Is expectant management of early-onset severe preeclampsia worthwhile in low-resource settings?.
      Some included only those women who remained stable after 24-48 hours of observation, while others included women expectantly managed from the time of diagnosis. A recent systematic review summarized the frequency of complications related to severe preeclampsia remote from term.
      • Magee L.A.
      • Yong P.J.
      • Espinosa V.
      • Côté A.M.
      • Chen I.
      • von Dadelszen P.
      Expectant management of severe preeclampsia remote from term: a structured systematic review.
      Presented as (median; interquartile range [IQR]), complications of expectant management included: intensive care unit admission (median, 27.6%; IQR, 1.5–52.6), hypotension (median, 17.0%; IQR, 12.0–21.0), HELLP syndrome (median, 11.0%; IQR, 5.3–17.6]), recurrent severe hypertension (median, 8.8%; IQR, 3.3–27.5), abruption placentae (median, 5.1%; IQR, 2.2–8.5), pulmonary edema (median, 2.9%; IQR, 1.5–52.6), eclampsia (median, 1.1%; IQR, 0–2.0), subcapsular liver hematoma (median, 0.5%; IQR, 0.2–0.7), stroke (median, 0.4%; IQR, 0–3.1), stillbirth (median, 2.5%; IQR, 0–11.3), and neonatal death (median, 7.3%; IQR, 5.0–10.7). Small for gestational age infants were common (median, 36.8%; IQR, 20.5–53.8) after expectant management. Delivery for fetal (46%) or maternal (40%) indications was similarly frequent.
      In summary, expectant management of severe preeclampsia occurring <34 weeks' gestation aimed at increasing gestational age at delivery and birth weight, and decreasing neonatal complications is appropriate in selected cases, but careful in-hospital maternal and fetal surveillance are recommended.

      What is the initial evaluation and management of severe preeclampsia <34 completed weeks' gestation?

      Women with suspected severe preeclampsia should be hospitalized to confirm the diagnosis, evaluate maternal and fetal condition, and monitor for rapid progression of the disease. During this initial assessment, intravenous magnesium sulfate seizure prophylaxis has been suggested by some, and may be considered. Continuous fetal heart rate and uterine contraction monitoring are initiated if there is an intention to intervene for fetal benefit. Maternal assessment should include evaluation of vital signs and physical examination with specific attention for signs of preeclampsia and its complications. Laboratory tests should include at least a complete blood cell count with platelet count, serum creatinine, and liver enzymes (aspartate aminotransferase, alanine aminotransferase). Urinary protein or urinary total protein/creatinine ratio, to confirm the presence of significant proteinuria, are often evaluated from a random urine sample. However, because these tests do not reliably exclude significant proteinuria or accurately quantitate the amount of proteinuria, 24-hour urine collection and analysis should generally be performed. Coagulation studies including serum fibrinogen, prothrombin time, and partial thrombin time, and evaluation for hemolysis (peripheral smear, serum bilirubin and/or lactate dehydrogenase) should be considered if the platelet count is <100,000/mm3, if liver enzymes are elevated, or if there are findings suggestive of abruptio placentae. Ultrasound should be performed to evaluate for fetal presentation, evidence of growth restriction, and/or oligohydramnios.
      Women with persistent symptoms of severe preeclampsia, uncontrollable severe hypertension, eclampsia, pulmonary edema, abruptio placentae, disseminated intravascular coagulation, significant and new-onset renal dysfunction (serum creatinine ≥1.5 mg/dL), HELLP syndrome, and those who have abnormal fetal surveillance results should typically be delivered (vaginal or cesarean delivery as appropriate) after initial maternal stabilization (Figure).
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      The remainder may be candidates for short-term pregnancy prolongation to achieve the benefits of antenatal corticosteroid treatment, or for extended pregnancy prolongation to allow fetal growth and maturation. While data specific to expectantly managed severe preeclampsia are limited, randomized controlled trials involving pregnancies complicated by hypertension syndromes have found antenatal corticosteroid treatment to result in less frequent respiratory distress syndrome (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.35–0.72), neonatal death (RR, 0.50; 95% CI, 0.29–0.87), and intraventricular hemorrhage (RR, 0.38; 95% CI, 0.17–0.87).
      • Roberts D.
      • Dalziel S.R.
      Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.
      In a single placebo-controlled study of weekly betamethasone for women with severe preeclampsia between 26-34 weeks' gestation, treatment (mean exposure 1.7 doses) reduced the frequencies of respiratory distress syndrome (RR, 0.53; 95% CI, 0.35–0.82) and intraventricular hemorrhage (RR, 0.35; 95% CI, 0.15–0.86), among other complications.
      • Amorim M.M.
      • Santos L.C.
      • Faundes A.
      Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia.
      In this study, there were 2 maternal deaths among 218 pregnancies.
      Figure thumbnail gr1
      FIGUREClinical algorithm for management of suspected severe preeclampsia <34 weeks' gestation
      BP, blood pressure.
      SMFM. Severe preeclampsia. Am J Obstet Gynecol 2011.
      If not previously given, and if it is anticipated that there will be time for fetal benefit from this intervention, antenatal corticosteroid administration should be considered regardless of a plan for expectant management. Those who develop new-onset contraindications to expectant management before or after completion of antenatal corticosteroid treatment should be delivered (Figure). If the maternal and fetal conditions remain stable during initial inpatient monitoring, continued expectant management of women <34 weeks' gestational age is appropriate. Continuous fetal monitoring, and magnesium sulfate seizure prophylaxis if initiated, can be discontinued. Women with suspected fetal growth restriction and/or oligohydramnios are not typically considered to be candidates for expectant management beyond completion of antenatal corticosteroid therapy due to the increased risk of adverse outcomes including perinatal death.
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      • Schiff E.
      • Friedman S.A.
      • Sibai B.M.
      Conservative management of severe preeclampsia remote from term.
      • Sibai B.M.
      • Mercer B.M.
      • Schiff E.
      • Friedman S.A.
      Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.
      • Ganzevoort W.
      • Rep A.
      • Bousel G.J.
      • et al.
      A randomized controlled trial comparing two temporizing management strategies, one with and one without plasma volume expansion, for severe preeclampsia.
      • Chammas M.F.
      • Nguyen T.M.
      • Li M.A.
      • Nuwayhid B.S.
      • Castro L.C.
      Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?.
      Management in these cases should be individualized and based on the severity of fetal growth restriction, the presence of coexisting oligohydramnios, and results of fetal surveillance. For the remaining women, the potential maternal risks and perinatal benefits of continued expectant management after antenatal corticosteroid treatment should be determined after consideration of clinical factors such as gestational age, maternal status, and likelihood of significant pregnancy prolongation.
      Because of the potential for rapid deterioration of the maternal and/or fetal condition during expectant management of severe preeclampsia, such women are optimally cared for in a hospital with services capable of managing complicated obstetric cases and preterm newborns.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      Maternal evaluation should include monitoring of blood pressure, urine output, and signs or symptoms of concern (persistent headache, visual changes, epigastric pain, abdominal tenderness, or vaginal bleeding). The frequency and nature of fetal monitoring should be based on gestational age and fetal status. During initial expectant management, at least daily assessment of the complete blood cell count with platelet count, as well as liver and renal functions can help identify those in whom the disease is progressing and requires delivery. Evaluation of maternal coagulation parameters is not typically necessary. The frequency of subsequent laboratory testing can be determined based on the severity of illness and disease progression. Uric acid levels and changes in urinary protein concentrations do not reliably predict adverse maternal or perinatal outcomes and therefore serial measurement offers little clinical benefit.
      • Thangaratinam S.
      • Ismail K.M.K.
      • Sharp S.
      • et al.
      Accuracy of serum uric acid in predicting complications of pre-eclampsia: a systematic review.
      • Schiff E.
      • Friedman S.A.
      • Kao L.
      • Sibai B.M.
      The importance of urinary protein excretion during conservative management of severe preeclampsia.
      • Hall D.R.
      • Odendaal H.J.
      • Stein D.W.
      • Grive D.
      Urinary protein excretion and expectant management of early onset, severe preeclampsia.
      • Newman M.G.
      • Robichaux A.G.
      • Stedman C.M.
      • et al.
      Perinatal outcomes in preeclampsia that is complicated by massive proteinuria.
      Depending on the duration of expectant management, follow-up ultrasound examination for fetal growth evaluation and amniotic fluid volume estimation should also be performed. If contraindications to expectant management are not encountered by 34 weeks of gestation, delivery should be initiated at that time because of the ongoing risks to the mother and fetal risks during continued expectant management.

      Should severe proteinuria alter the approach to management of severe preeclampsia?

      The presence of severe proteinuria in women with severe preeclampsia undergoing expectant management is not associated with worse outcomes. In one study of 42 expectantly managed women with severe proteinuria (defined as ≥5 g/24 h), significant pregnancy prolongation occurred, maternal complications were not increased, and resolution of renal dysfunction occurred in all women by 3 months after delivery.
      • Chua S.
      • Redman C.W.
      Prognosis for pre-eclampsia complicated by 5 g or more of proteinuria in 24 hours.
      A second study categorized women with severe preeclampsia according to the severity of proteinuria as mild (<5 g/24 h), severe (5-9.9 g/24 h), or massive (>10 g/24 h).
      • Newman M.G.
      • Robichaux A.G.
      • Stedman C.M.
      • et al.
      Perinatal outcomes in preeclampsia that is complicated by massive proteinuria.
      No differences in the rates of eclampsia, abruptio placentae, pulmonary edema, HELLP syndrome, neonatal death, or neonatal morbidity were identified between these groups. Although the amount of proteinuria increases over time with expectant management, this change is not predictive of pregnancy prolongation or perinatal outcomes.
      • Schiff E.
      • Friedman S.A.
      • Kao L.
      • Sibai B.M.
      The importance of urinary protein excretion during conservative management of severe preeclampsia.
      On the basis of these data, severe proteinuria alone and the degree of change in proteinuria should not be considered criteria to avoid or terminate expectant management.

      Should expectant management be offered when HELLP syndrome is present?

      Women with HELLP syndrome have been excluded from most published studies of expectantly managed preterm severe preeclampsia as these abnormalities are generally considered to be indications for delivery.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      • Odendaal H.J.
      • Pattinson R.C.
      • Bam R.
      • Grove D.
      • Kotze T.J.
      Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial.
      • Sibai B.M.
      • Mercer B.M.
      • Schiff E.
      • Friedman S.A.
      Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.
      Further, the diagnostic criteria used for HELLP syndrome have varied between publications.
      • Sibai B.M.
      Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count.
      In a systematic review of 12 studies, Magee et al
      • Magee L.A.
      • Yong P.J.
      • Espinosa V.
      • Côté A.M.
      • Chen I.
      • von Dadelszen P.
      Expectant management of severe preeclampsia remote from term: a structured systematic review.
      evaluated the frequency of complications that can occur when expectant management is undertaken in the setting of HELLP syndrome <34 weeks' gestation. Median [IQR] latency to delivery was 5.8 days [0.8–10.3] and delivery for fetal indication was common (median, 70.8%; IQR, 53.9–89.0). Complications (median [interquartile range]) included recurrent severe hypertension (median, 46.2%; IQR, 33.6–58.8), abruptio placentae (median, 5.1%; IQR, 3.3–6.4), eclampsia (median, 0.8%; IQR, 0–4.9), subcapsular liver hematoma (median, 3.1%; IQR, 1.6–4.7), stroke (6.3%), stillbirth (median, 10.5%; IQR, 3.4–19.1), and neonatal death (median, 5.5%; IQR, 4.3–8.9). Delivery of a small for gestational age infant was common (56.3%). Maternal death has also occurred during expectant management of HELLP syndrome.
      • van Runnard Heimel P.J.
      • Huisjes A.J.M.
      • Fraux A.
      • Koopman C.
      • Bots M.L.
      • Bruinse H.W.
      A randomized placebo-controlled trial of prolonged prednisolone administration to patients with HELLP syndrome remote from term.
      A recent metaanalysis of 11 trials evaluated the impact of antenatal maternal corticosteroid treatment on perinatal outcomes during expectant management of HELLP.
      • Woudstra D.M.
      • Chandra S.
      • Hofmeyr G.J.
      • Dowswell T.
      Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy.
      This systematic review found improved maternal platelet counts when corticosteroids are given, but there was no evidence of improvements in maternal mortality, severe maternal morbidities, or perinatal/infant deaths.
      Given current evidence of brief latency and maternal risk without demonstrated fetal benefits, women with HELLP syndrome should not typically be managed expectantly, and vaginal or cesarean delivery should be pursued as appropriate. Antenatal corticosteroid administration may be given concurrently, if it is anticipated that there will be adequate time for fetal benefit from treatment, but the risk of surgical complications in the setting of thrombocytopenia should be considered. If delivery is delayed for antenatal corticosteroid administration (eg, for patients with incomplete findings of HELLP syndrome), magnesium sulfate seizure prophylaxis should be continued and continuous fetal monitoring should be performed because of the potential for eclampsia and fetal death. Delivery should be pursued if the maternal or fetal condition worsens, or upon completion of this treatment.
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      • Sibai B.M.
      • Mercer B.M.
      • Schiff E.
      • Friedman S.A.
      Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.
      • Fenakel K.
      • Kenakel G.
      • Appleman Z.
      • et al.
      Nifedipine in treatment of severe preeclampsia.
      • Hall D.R.
      • Odendaal H.J.
      • Steyn D.W.
      • Grove D.
      Expectant management of early onset, severe preeclampsia; maternal outcome.

      Should expectant management be offered when fetal growth restriction is suspected?

      While no prospective trials have evaluated the benefits and risks of expectant management when fetal growth restriction is suspected in the setting of preterm severe preeclampsia, 2 retrospective observational studies have described outcomes for such pregnancies.
      • Ganzevoort W.
      • Rep A.
      • Bousel G.J.
      • et al.
      A randomized controlled trial comparing two temporizing management strategies, one with and one without plasma volume expansion, for severe preeclampsia.
      • Chammas M.F.
      • Nguyen T.M.
      • Li M.A.
      • Nuwayhid B.S.
      • Castro L.C.
      Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?.
      In one study of volume expansion during expectant management of severe preeclampsia, those with suspected fetal growth restriction (defined as ultrasound estimated weight <10th percentile or abdominal circumference <5th percentile) had a median pregnancy prolongation of 7 days, and the frequency of adverse outcome (perinatal death, chronic lung disease, grade ≥3 intraventricular hemorrhage, or grade ≥2 periventricular leukomalacia) for this group was similar to the overall cohort.
      • Ganzevoort W.
      • Rep A.
      • Bousel G.J.
      • et al.
      A randomized controlled trial comparing two temporizing management strategies, one with and one without plasma volume expansion, for severe preeclampsia.
      A second study compared 14 women with severe preeclampsia and estimated fetal weight <10th percentile with 33 women without fetal growth restriction.
      • Chammas M.F.
      • Nguyen T.M.
      • Li M.A.
      • Nuwayhid B.S.
      • Castro L.C.
      Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?.
      Only brief pregnancy prolongation (3.1 days) was seen with expectant management, and the incidences of abruption and neonatal morbidities were similar between those with or without fetal growth restriction. These investigators recommended delivery after antenatal corticosteroid administration in such cases. While published studies fail to demonstrate benefits from expectant management of severe preeclampsia with concurrent suspected fetal growth restriction, the number of subjects studied is small and there is a wide spectrum of severity of fetal growth restriction. The decision regarding expectant management of these patients should be individualized.

      Should severe preeclampsia occurring before the limit of viability be treated expectantly?

      Severe preeclampsia that develops near the limit of fetal viability is associated with a high likelihood of perinatal morbidities and mortality, regardless of expectant management.
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      • Sibai B.M.
      • Akl S.
      • Fairlie F.
      • Moretti M.
      A protocol for managing severe preeclampsia in the second trimester.
      • Visser W.
      • Wallenburg H.C.S.
      Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe preeclampsia remote from term.
      • Bombrys A.E.
      • Barton J.R.
      • Nowacki E.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at <27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Hall D.R.
      • Grove D.
      • Carstens E.
      Early-preeclampsia: what proportion of women qualify for expectant management and if not, why not?.
      • Moodley J.
      • Koranteng S.A.
      • Rout C.
      Expectant management of early onset of severe preeclampsia in Durban.
      • Hall D.R.
      • Odendaal H.J.
      • Steyn D.W.
      Expectant management of severe pre-eclampsia in the mid-trimester.
      • Jenkins S.M.
      • Head B.B.
      • Hauth J.C.
      Severe preeclampsia at <25 weeks of gestation: maternal and neonatal outcomes.
      • Gaugler-Senden I.P.M.
      • Huijssoon A.G.
      • Visser W.
      • Steegers E.A.P.
      • deGroot C.J.M.
      Maternal and perinatal outcome of preeclampsia with onset before 24 weeks' gestation: audit in a tertiary referral center.
      • Budden A.
      • Wilkinson L.
      • Buksh M.J.
      • McCowan L.
      Pregnancy outcome in women presenting with pre-eclampsia at less than 25 weeks' gestation.
      • Sezik M.
      • Ozkaya O.
      • Sezik H.T.
      • Yapar E.G.
      Expectant management of severe preeclampsia presenting before 25 weeks of gestation.
      However, data regarding outcomes with expectant management categorized by gestational week at diagnosis are limited. Survival rates of 0/34 (0%), 4/22 (18.2%), and 15/26 (57.7%) have been reported after expectant management of severe preeclampsia initiated <23 weeks', at 23 weeks', and at 24 weeks' gestation, respectively.
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      • Bombrys A.E.
      • Barton J.R.
      • Nowacki E.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at <27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Budden A.
      • Wilkinson L.
      • Buksh M.J.
      • McCowan L.
      Pregnancy outcome in women presenting with pre-eclampsia at less than 25 weeks' gestation.
      • Sezik M.
      • Ozkaya O.
      • Sezik H.T.
      • Yapar E.G.
      Expectant management of severe preeclampsia presenting before 25 weeks of gestation.
      Other reports have also suggested rare survival with expectant management of severe preeclampsia <23-24 weeks' gestation.
      • Sibai B.M.
      • Akl S.
      • Fairlie F.
      • Moretti M.
      A protocol for managing severe preeclampsia in the second trimester.
      • Gaugler-Senden I.P.M.
      • Huijssoon A.G.
      • Visser W.
      • Steegers E.A.P.
      • deGroot C.J.M.
      Maternal and perinatal outcome of preeclampsia with onset before 24 weeks' gestation: audit in a tertiary referral center.
      Explicit counseling regarding the likelihood of poor perinatal outcomes with expectant management should be provided. Delivery should be considered when severe preeclampsia occurs before the limit of viability (Figure).
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      • Sibai B.M.
      • Akl S.
      • Fairlie F.
      • Moretti M.
      A protocol for managing severe preeclampsia in the second trimester.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      • Bombrys A.E.
      • Barton J.R.
      • Nowacki E.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at <27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Gaugler-Senden I.P.M.
      • Huijssoon A.G.
      • Visser W.
      • Steegers E.A.P.
      • deGroot C.J.M.
      Maternal and perinatal outcome of preeclampsia with onset before 24 weeks' gestation: audit in a tertiary referral center.
      • Budden A.
      • Wilkinson L.
      • Buksh M.J.
      • McCowan L.
      Pregnancy outcome in women presenting with pre-eclampsia at less than 25 weeks' gestation.
      • Sezik M.
      • Ozkaya O.
      • Sezik H.T.
      • Yapar E.G.
      Expectant management of severe preeclampsia presenting before 25 weeks of gestation.

      What is the role of antihypertensive therapy during expectant management?

      In women with severe preeclampsia, control of maternal blood pressure is necessary to decrease the risks of acute hypertension (eg, maternal cerebrovascular accident, myocardial ischemia), but a dramatic decrease may also impair uteroplacental perfusion. Antihypertensive medications should be considered if systolic blood pressure remains persistently >160 mm Hg, or if diastolic blood pressure persists >110 mm Hg.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      Once treated, the target range should be a systolic blood pressure of 140-155 mm Hg and a diastolic blood pressure of 90-105 mm Hg.
      Although parenteral antihypertensive therapy may be needed initially for acute control of blood pressure, oral medications can be utilized as expectant management is continued. Oral labetalol and calcium channel blockers have been commonly used.
      • Sibai B.M.
      • Barton J.R.
      Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.
      One approach is to begin an initial regimen of labetalol at 200 mg orally every 12 hours, and increase the dose up to 800 mg orally every 8-12 hours as needed (maximum total 2400 mg/d). If the maximum dose is inadequate to achieve the desired blood pressure goal, then short-acting oral nifedipine can be added at an initial dose of 10 mg orally every 6 hours and increased as needed up to 20 mg every 4 hours (40-120 mg/d). An alternative regimen is a long-acting preparation of nifedipine (up to 30-60 mg/d). Following initial control ofsevere hypertension, blood pressure should be measured at least every 6-8 hours. If there is recurrent persistent severe hypertension despite adequate oral or intravenous antihypertensive therapy, delivery should be pursued after maternal stabilization.

      What strategies are available for fetal assessment during expectant management?

      No randomized trials have identified an optimal method of fetal assessment during expectant management of severe preeclampsia, however there is agreement that fetal testing is indicated if the pregnancy is considered viable.
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      • Odendaal H.J.
      • Pattinson R.C.
      • Bam R.
      • Grove D.
      • Kotze T.J.
      Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial.
      • Sibai B.M.
      • Mercer B.M.
      • Schiff E.
      • Friedman S.A.
      Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.
      • Fenakel K.
      • Kenakel G.
      • Appleman Z.
      • et al.
      Nifedipine in treatment of severe preeclampsia.
      • Ganzevoort W.
      • Rep A.
      • Bousel G.J.
      • et al.
      A randomized controlled trial comparing two temporizing management strategies, one with and one without plasma volume expansion, for severe preeclampsia.
      • Chua S.
      • Redman C.W.
      Prognosis for pre-eclampsia complicated by 5 g or more of proteinuria in 24 hours.
      • Olah K.S.
      • Redman W.G.
      • Gee H.
      Management of severe, early pre-eclampsia: is conservative management justified?.
      • van Pampus M.G.
      • Wolf H.
      • Westenberg S.M.
      • der Post V.
      • Bonsel G.J.
      • Treffers P.E.
      Maternal and perinatal outcome after expectant management of HELLP syndrome compared with preeclampsia without HELLP syndrome.
      • Chammas M.F.
      • Nguyen T.M.
      • Li M.A.
      • Nuwayhid B.S.
      • Castro L.C.
      Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?.
      • Hall D.R.
      • Odendaal H.J.
      • Steyn D.W.
      • Grove D.
      Expectant management of early onset, severe preeclampsia; maternal outcome.
      • Hall D.R.
      • Odendaal H.J.
      • Kristen G.F.
      • Smith J.
      • Grove D.
      Expectant management of early onset, severe preeclampsia: perinatal outcome.
      • Shear R.M.
      • Rinfret D.
      • Leduc L.
      Should we offer expectant management in cases of severe preterm preeclampsia with fetal growth restriction?.
      • Oettle C.
      • Hall D.
      • Roux A.
      • Grove D.
      Early onset severe preeclampsia: expectant management at a secondary hospital in close association with a tertiary institution.
      • Bombrys A.E.
      • Barton J.R.
      • Nowacki E.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at <27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Bombrys A.E.
      • Barton J.R.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at 270/7-336/7 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Hall D.R.
      • Grove D.
      • Carstens E.
      Early-preeclampsia: what proportion of women qualify for expectant management and if not, why not?.
      Nonstress testing (NST) is recommended, but the optimal frequency of testing and the additional value of biophysical profile testing have not been determined. One approach for fetal surveillance involves at least daily NSTs, with biophysical profile testing performed should a nonreactive NST result be encountered. Follow-up fetal growth evaluation and amniotic fluid volume estimation should also be performed. If fetal growth restriction is suspected, and expectant management is undertaken, then incorporation of Doppler blood flow studies into an individualized management scheme is appropriate.

      What are the indications for delivery after expectant management?

      In the published studies of preterm severe preeclampsia managed expectantly, delivery has typically been pursued at approximately 34 completed weeks' gestation. However, deterioration of maternal and/or fetal conditions prior to this gestational age is the most common reason for delivery.
      • Magee L.A.
      • Yong P.J.
      • Espinosa V.
      • Côté A.M.
      • Chen I.
      • von Dadelszen P.
      Expectant management of severe preeclampsia remote from term: a structured systematic review.
      Maternal indications for delivery are delineated in Figure. Delivery should also be considered for women declining or noncompliant to ongoing inpatient observation; those developing persistent epigastric or right upper quadrant pain, nausea, or vomiting; and for those who develop preterm labor or premature rupture of membranes (Figure).
      • Haddad B.
      • Deis S.
      • Goffinet F.
      • Daniel B.J.
      • Cabrol D.
      • Sibai B.M.
      Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation.
      Report of the National High Blood Pressure Education Program Working group report on high blood pressure in pregnancy.
      American College of Obstetricians and Gynecologists
      Diagnosis and management of preeclampsia and eclampsia: ACOG practice bulletin no. 33.
      • Odendaal H.J.
      • Pattinson R.C.
      • Bam R.
      • Grove D.
      • Kotze T.J.
      Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial.
      • Sibai B.M.
      • Mercer B.M.
      • Schiff E.
      • Friedman S.A.
      Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial.
      • Chammas M.F.
      • Nguyen T.M.
      • Li M.A.
      • Nuwayhid B.S.
      • Castro L.C.
      Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?.
      • Hall D.R.
      • Odendaal H.J.
      • Steyn D.W.
      • Grove D.
      Expectant management of early onset, severe preeclampsia; maternal outcome.
      • Hall D.R.
      • Odendaal H.J.
      • Kristen G.F.
      • Smith J.
      • Grove D.
      Expectant management of early onset, severe preeclampsia: perinatal outcome.
      • Shear R.M.
      • Rinfret D.
      • Leduc L.
      Should we offer expectant management in cases of severe preterm preeclampsia with fetal growth restriction?.
      • Oettle C.
      • Hall D.
      • Roux A.
      • Grove D.
      Early onset severe preeclampsia: expectant management at a secondary hospital in close association with a tertiary institution.
      • Bombrys A.E.
      • Barton J.R.
      • Nowacki E.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at <27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Bombrys A.E.
      • Barton J.R.
      • Habli M.
      • Sibai B.M.
      Expectant management of severe preeclampsia at 270/7-336/7 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management.
      • Hall D.R.
      • Grove D.
      • Carstens E.
      Early-preeclampsia: what proportion of women qualify for expectant management and if not, why not?.
      When delivery is indicated, vaginal delivery can often be accomplished, but this is less likely with decreasing gestational age. With labor induction, the likelihood of cesarean delivery increases with decreasing gestational age in this setting (range, 93–97% <28 weeks', 53–65% at 28-32 weeks', and 31–38% at 32-34 weeks' gestation).
      • Nassar A.H.
      • Adra A.A.
      • Chakhtoura N.
      • Beydoun S.
      Severe preeclampsia remote from term: labor induction or elective cesarean delivery?.
      • Alexander J.M.
      • Bloom S.L.
      • McIntire D.D.
      • Leveno K.J.
      Severe preeclampsia and the very-low birth weight infant: is induction of labor harmful?.
      • Blackwell S.C.
      • Redman M.E.
      • Tomlinson M.
      • et al.
      Labor induction for the preterm severe pre-eclamptic patient: is it worth the effort?.
      • Alanis M.C.
      • Robinson C.J.
      • Hulsey T.C.
      • Ebeling M.
      • Johnson D.J.
      Early-onset severe preeclampsia: induction of labor vs elective cesarean delivery and neonatal outcomes.

      Recommendations

      Levels I and II evidence, level A recommendation

      • 1
        Expectant management of severe preeclampsia remote from term is appropriate in selected cases, and is associated with pregnancy prolongation and improved newborn outcomes.

      Levels II and III evidence, level B recommendation

      • 2
        Women with persistent symptoms of severe preeclampsia, uncontrollable severe hypertension, eclampsia, pulmonary edema, abruptio placentae, disseminated intravascular coagulation, significant and new-onset renal dysfunction, and those who have abnormal fetal surveillance results, should typically be delivered after initial maternal stabilization.

      Level I evidence, level A recommendation

      • 3
        If not previously given, and if it is anticipated that there will be time for fetal benefit from this intervention before delivery, antenatal corticosteroid administration should be considered regardless of a plan for expectant management.

      Level III evidence, level C recommendation

      • 4
        Because of the ongoing risks to the mother and fetal risks during continued expectant management, delivery for severe preeclampsia should be undertaken at 34 weeks' gestation for those who remain pregnant to this gestational age.

      Level II evidence, level A recommendation

      • 5
        Severe proteinuria alone and the degree of change in proteinuria should not be considered criteria to avoid or terminate expectant management.

      Levels I and II evidence, level A recommendation

      • 6
        Women with HELLP syndrome should not typically be managed expectantly. Vaginal or cesarean delivery should be pursued as appropriate.

      Level II and III evidence, level B recommendation

      • 7
        The decision regarding expectant management of severe preeclampsia with concurrent suspected fetal growth restriction should be individualized.

      Levels I and II evidence, level B recommendation

      • 8
        Explicit counseling regarding the potential maternal risks should be provided and delivery should be considered when severe preeclampsia occurs before the limit of viability.
      This opinion was developed by the Publications Committee of the Society for Maternal-Fetal Medicine with the assistance of Baha M. Sibai, MD, and was approved by the executive committee of the society on June 30, 2011. Dr Sibai and each member of the publications committee (Brian Mercer, MD [Chair], Vincenzo Berghella, MD, Sean Blackwell, MD, Joshua Copel, MD, William Grobman, MD, MBA, Cynthia Gyamfi, MD, Donna Johnson, MD, Sarah Kilpatrick, MD, PhD, George Macones, MD, George Saade, MD, Hyagriv Simhan, MD, Lynn Simpson, MD, Joanne Stone, MD, Michael Varner, MD, Ms Deborah Gardner) have submitted a conflict of interest disclosure delineating personal, professional, and/or business interests that might be perceived as a real or potential conflict of interest in relation to this publication.

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