Browse
Topics & Collections
Search for a specific
disease or term
—  or  —
Learn more about ACP Smart Medicine

Dynamed

X
This content was provided by DynaMed (dynamed.ebscohost.com). For more information click here.
Last Updated: 9/10/2014  

Preeclampsia

Prevention
  • Use low-dose aspirin to prevent preeclampsia in pregnant women with moderate or high risk for preeclampsia, including those with chronic hypertension or chronic medical conditions, such as diabetes or chronic kidney disease, or those with a history of preeclampsia.

Screening
  • Monitor all pregnant patients for preeclampsia by checking blood pressure and evaluating for proteinuria.

Diagnosis
  • Use blood pressure as a key criterion for diagnosing preeclampsia.

  • Quantitate proteinuria and determine renal function in patients with suspected preeclampsia. Define significant proteinuria as urinary protein excretion of ≥300 mg/24 h or >165 mg/12 h or urine protein-to-creatinine ratio ≥0.3 mg/dL or 30 mg/mmol.

  • Diagnose preeclampsia in pregnant patients after 20 weeks' gestation with new hypertension (blood pressure consistently ≥140/90 mm Hg) and proteinuria.

  • Obtain liver function tests and a CBC to determine the severity of preeclampsia.

  • Classify the severity of preeclampsia based on level of blood pressure and the presence of complications; define severe disease in patients with blood pressure ≥160/110 mm Hg or complications.

  • Assess fetal well-being in women with preeclampsia.

Therapy
  • Administer antihypertensive therapy to patients with blood pressure ≥160/110 mm Hg, using labetolol as the first-line agent in most patients.

  • Restrict the activity of women with severe preeclampsia.

  • Administer magnesium sulfate in patients with eclampsia or severe preeclampsia.

  • Give antenatal corticosteroids to women with preterm pregnancies of 24 to 34 weeks' gestation complicated by preeclampsia.

  • Base timing of delivery on severity of disease and gestational age.

Use low-dose aspirin in women with moderate or high risk for preeclampsia for prevention of preeclampsia. 
  • Prescribe low-dose aspirin only in women with high risk for preeclampsia, such as those with

    • Preexisting essential hypertension

    • History of preeclampsia, especially if it was accompanied by preterm delivery

    • Chronic medical conditions, such as kidney disease or diabetes

  • In women who are candidates for aspirin therapy,

    • Treat with 75 or 81 mg daily

    • Begin therapy at the end of the first trimester

  • Do not recommend aspirin in women with low risk for preeclampsia.

Evidence
  • A 2014 USPSTF guideline on low-dose aspirin for the prevention of preeclampsia in high-risk women recommended that pregnant women at high risk for preeclampsia be treated with low-dose (81 mg) aspirin after 12 weeks gestation. The guideline noted that high-risk women include women with history of preeclampsia during a prior pregnancy and those with hypertension, diabetes, kidney disease, autoimmune diseases, and multifetal pregnancy (1).

  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended acetylsalicylic acid, 75 to 162 mg daily, and calcium for women with low calcium intake, to prevent preeclampsia in women at high risk.

  • A 2010 NICE guideline recommended that pregnant women at high risk for preeclampsia take low-dose aspirin (75 mg) daily beginning during week 12 of pregnancy. Women at high risk were defined as those with chronic kidney disease, hypertension during a previous pregnancy, autoimmune disease, diabetes, or chronic hypertension.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended that women with a history of preeclampsia and preterm delivery or of preeclampsia in multiple previous pregnancies be treated with daily low-dose aspirin (60 to 80 mg) beginning late in the first trimester.

  • A 2014 systematic review for the U.S. Preventive Services Task Force of low-dose aspirin for the prevention of preeclampsia included 15 randomized trials (of which 2 were large) of high-risk women and 6 randomized trials and 2 cohort studies of average-risk women. Overall, aspirin reduced the risk of preeclampsia (RR, 0.76 [CI, 0.62 to 0.95]; absolute risk difference, 2% to 5%), intrauterine growth restriction (RR, 0.80 [CI, 0.65 to 0.99]; absolute risk difference, 1% to 5%), and preterm delivery (RR, 0.86 [CI, 0.76 to 0.98]; absolute risk difference, 2% to 4%). No major fetal or maternal harms were identified (2).

  • A 2007 individual patient meta-analysis of antiplatelet agents for the primary prevention of preeclampsia included 32,217 patients from 31 randomized trials. Treatment with antiplatelet agents compared with control treatment resulted in a lower risk for preeclampsia (RR, 0.90 [CI, 0.84 to 0.97]), for birth before 34 weeks' gestation (RR, 0.90 [CI, 0.83 to 0.98]), and for having a pregnancy with a serious adverse outcome (RR, 0.90 [CI, 0.85 to 0.96]). Antiplatelet agents had no significant effect on the risk for death of the fetus or baby, having a small-for-gestational-age infant, or bleeding events for either the women or their babies. No particular subgroup of women was substantially more or less likely to benefit from antiplatelet agents than any other (3).

  • A 2007 Cochrane review of antiplatelet agents to prevent preeclampsia included 59 trials involving 37,560 women. Women receiving antiplatelet agents had a lower risk for preeclampsia (RR, 0.83 [CI, 0.77 to 0.89]) compared with control treatment, which was equivalent to a number-needed-to-treat of 72. Women receiving antiplatelet agents had lower risks for preterm birth (RR, 0.92 [CI, 0.88 to 0.97]), fetal or neonatal deaths (RR, 0.86 [CI, 0.76 to 0.98]), and small-for-gestational-age (RR, 0.90 [CI, 0.83 to 0.98]). No difference was seen for placenta abruption, eclampsia, or maternal death (4).

  • A 2013 randomized trial compared aspirin with placebo in 121 pregnant women with reduced uterine artery blood flow. Rates of preeclampsia were similar in the two groups (RR with aspirin of 0.7 [CI, 0.3 to 1.7]). A systematic review and updated meta-analysis including the new data found that aspirin reduced the risk for preeclampsia with an RR of 0.6 (CI, 0.4 to 0.8) (5).

Rationale
  • The use of aspirin in women with moderate or high risk for preeclampsia results in a small but significant decrease in the risk for preeclampsia, preterm birth, and other serious outcomes.

  • Treatment with aspirin initiated early in pregnancy is an efficient method of reducing the incidence of preeclampsia and its consequences.

Recommend routine prenatal vitamins but not routine calcium supplementation or antioxidants for the prevention of preeclampsia. Consider vitamin D supplementation in women with vitamin D insufficiency.  
  • Recommend prenatal multivitamins for all pregnant patients.

  • Recommend calcium supplementation only in women with low calcium dietary intake for the prevention of preeclampsia.

  • Consider supplementation with L-arginine plus antioxidant vitamins in pregnant women at high risk for preeclampsia.

  • Do not use antioxidants, including vitamins C and E for the prevention of preeclampsia.

  • Consider vitamin D supplementation in pregnant women who are deficient.

Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended acetylsalicylic acid, 75 to 162 mg daily, and calcium for women with low calcium intake, to prevent preeclampsia in women at high risk.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended against antioxidant supplementation, dietary salt restriction, and modification of physical activity to prevent preeclampsia.

  • A 2010 Cochrane review of calcium supplementation in pregnancy to prevent hypertensive disorders included 13 randomized trials with 15,730 participants. Calcium supplementation was associated with a reduced risk for preeclampsia (RR, 0.45 [CI, 0.31 to 0.65]). The greatest reduction in risk was for women at high risk (RR, 0.22 [CI, 0.12 to 0.42]) and those with low baseline dietary calcium intake (RR, 0.36 [CI, 0.20 to 0.65]) (6).

  • A 2008 Cochrane review of antioxidants to prevent preeclampsia included 10 trials involving 6533 women. Included studies compared one or more antioxidants with either placebo or no antioxidants during pregnancy. There was no significant difference in rates of preeclampsia between antioxidant and control groups (RR, 0.73 [CI, 0.51 to 1.06]) (7).

  • A 2007 meta-analysis of vitamin C or E for the prevention of preeclampsia included four randomized trials (4680 women). No difference in the diagnosis of preeclampsia was found (vitamin group, 11%, vs. placebo group, 11.4%; RR, 0.97 [CI, 0.82 to 1.13]) (8).

  • A 2013 systematic review of the association between maternal levels of 25-hydroxy vitamin D and pregnancy outcomes included 31 observational studies. Insufficient serum levels of 25-hydroxy vitamin D were associated with preeclampsia (pooled OR, 1.79 [CI, 1.25 to 2.58]) (9).

  • A 2012 Cochrane review of vitamin D supplementation during pregnancy included 6 trials with 1023 participants, only one of which reported rates of preeclampsia. Women taking calcium plus vitamin D had similar rates of preeclampsia to those taking placebo (RR, 0.67 [CI, 0.33 to 1.35]). However, women receiving vitamin D had lower rates of low birthweight (<2500 grams) than women receiving no treatment or placebo (RR, 0.48 [CI, 0.23 to 1.01]) (10).

  • A randomized trial compared supplementation with medical food bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo in 450 pregnant women at high risk for preeclampsia. The incidence of preeclampsia was lower in the L-arginine plus antioxidant vitamins group compared with placebo (absolute risk reduction, 0.17 [CI, 0.12 to 0.21]; P<0.001) and compared with antioxidant vitamins alone (absolute risk reduction, 0.09 [CI, 0.05 to 0.14]; P=0.004). Antioxidant vitamins alone did not reduce preeclampsia compared with placebo (11).

  • A prospective cohort study evaluated the impact of daily multivitamin use in 1835 pregnant patients at less then 16 weeks' gestation. Patients were divided into two groups: those regularly using (n=860) and those not regularly using multivitamins daily in the past 6 months. When adjusted for multiple demographic factors, there was a significant difference in the risk for preeclampsia between regular users and nonusers of multivitamins (4.4% in nonusers and 3.8% in users; OR, 0.55 [CI, 0.32 to 0.95]) (12).

  • A randomized trial compared 1000 mg of vitamin C plus 400 IU of vitamin E (alpha-tocopherol) to matched placebo daily until delivery in 762 pregnant women with type 1 diabetes. The incidence of preeclampsia was similar in the vitamin (15%; n=57) and placebo (19%; n=70) groups (RR, 0.81 [CI, 0.59 to 1.12]) (13).

  • In a multicenter, randomized, double-blind trial, 10,154 nulliparous women who were at low risk for preeclampsia were randomly assigned to begin daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo between the ninth and sixteenth weeks of pregnancy. Rates of the primary outcome (severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver-enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or perinatal death) did not differ in the vitamin and placebo groups (6.1% and 5.7%, respectively; RR, 1.07 [CI, 0.91 to 1.25]) or in the rates of preeclampsia (7.2% and 6.7%, respectively; RR, 1.07 [CI, 0.93 to 1.24]) (14).

  • In a multinational, multicenter, randomized, controlled, double-blind trial organized by the World Health Organization, 1365 pregnant women with low nutritional status who were between 14 and 22 weeks' gestation were randomly assigned to receive 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily until delivery. Supplementation was not associated with a reduction in preeclampsia (RR, 1.0 [CI, 0.9 to 1.3]), eclampsia (RR, 1.5 [CI, 0.3 to 8.9]), or gestational hypertension (RR, 1.2 [CI, 0.9 to 1.7]). Low birthweight (RR, 0.9 [CI, 0.8 to 1.1]), small size for gestational age (RR, 0.9 [CI, 0.8 to 1.1]), and perinatal deaths (RR, 0.8 [CI, 0.6 to 1.2]) were also unaffected (15).

  • A randomized trial compared daily vitamins C and E with placebo in 739 patients at increased risk for preeclampsia. Rates of preeclampsia were similar in the vitamin (13.8%) and placebo (15.6%) groups (RR, 0.87 [CI, 0.61 to 1.25]) (16).

  • A planned analysis for secondary outcome of the same trial showed an increased risk for premature rupture of the membranes (RR, 1.89 [CI, 1.11 to 3.23]; P=0.015) in the vitamin group (17).

  • A randomized, controlled trial of 1877 nulliparous women assigned to daily supplementation (n=935) with vitamin C, 1000 mg/d, and vitamin E, 400 IU/d, or placebo (n=942) from 14 to 22 weeks' gestation until delivery showed no significant difference in the risk for preeclampsia (6% in the multivitamin group and 5% in the placebo group; RR, 1.20 [CI, 0.82 to 1.75]) (18).

  • A randomized, controlled trial of 2410 pregnant women at increased risk for eclampsia assigned to supplementation (n=1199) with vitamin C, 100 mg/d, and vitamin E, 400 IU/d, or placebo (n=1205) from the second trimester of pregnancy until delivery showed no significant difference in the risk for preeclampsia (15% in the supplementation group and 16% in the placebo group; RR, 0.97 [CI, 0.80 to 1.17]) (19).

  • In a randomized, controlled trial in a population with endemic vitamin D deficiency, supplementation of 2000 and 4000 IU/day of vitamin D appeared safe in pregnancy, and a dose of 4000 IU/day appeared to be the most effective in optimizing serum 25-hydroxy vitamin D concentrations in mothers and their infants (20).

  • In a double-blind, randomized, controlled trial including 350 women, vitamin D supplementation of 4000 IU/day during pregnancy was safe and most effective in achieving sufficiency in all women and their neonates regardless of race (21).

Rationale
  • Prenatal multivitamins may reduce the risk for preeclampsia.

  • Calcium supplementation may prevent preeclampsia only in women with lower dietary intake of calcium.

  • Antioxidants do not reduce the risk for preeclampsia.

  • L-arginine plus antioxidants may reduce the risk for preeclampsia in high-risk women.

  • Observational data suggest an association between Vitamin D insufficiency and preeclampsia.

Treat patients with mild gestational diabetes to prevent preeclampsia. 
  • In patients with mild gestational diabetes (an abnormal result on an oral glucose-tolerance test but a fasting glucose level <95 mg/dL [5.3 mmol/L]), recommend

    • Dietary intervention

    • Self-monitoring of blood glucose

    • Insulin therapy, if necessary

  • See module Diabetes in Pregnancy.

Evidence
  • A randomized trial compared a treatment group (self-monitoring of blood glucose and insulin therapy, if necessary) with a control group in 958 women with mild gestational diabetes mellitus in the 24th to 31st week of gestation. Patients in the treatment group had lower rates of preeclampsia compared with those in the control group (12 [2.5%] vs. 25 [5.5%]; RR, 0.46 [CI, 0.22 to 0.97]; P=0.02) (22).

Rationale
  • Treatment of mild gestational diabetes reduces the risk for hypertensive disorders of pregnancy.

Do not recommend lifestyle or dietary interventions to prevent preeclampsia. 
  • Do not recommend bed rest or exercise during pregnancy for the prevention of preeclampsia.

  • Avoid recommending salt restriction, marine oil, or garlic for the prevention of preeclampsia.

Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended against lifestyle interventions to prevent preeclampsia.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended against antioxidant supplementation, dietary salt restriction, and modification of physical activity to prevent preeclampsia.

  • A 2012 meta-analysis of lifestyle interventions in pregnancy included 44 randomized trials with 7278 participants, addressing diet, exercise, or both. Overall, dietary interventions reduced the incidence of preeclampsia (RR, 0.67 [CI, 0.53 to 0.85]) (six trials were included in the analysis), but exercise interventions did not (RR, 1.16 [CI, 0.70 to 1.90] (four trials were included in the analysis). However, trials with patients with gestational diabetes were included in the meta-analysis (23).

  • A 2006 Cochrane review of exercise to prevent preeclampsia included two good-quality trials with 45 participants, comparing moderate regular aerobic exercise with normal physical activity during pregnancy. Rates of preeclampsia were similar in the groups (RR, 0.31 [CI, 0.01 to 7.09]) (24).

  • A 2006 Cochrane review of rest during pregnancy to prevent preeclampsia in women with normal blood pressure included two trials of uncertain quality with 106 participants. Four to 6 hours rest per day prevented preeclampsia (one trial, 32 women; RR, 0.05 [CI, 0.00 to 0.83]) but not gestational hypertension (RR, 0.25 [CI, 0.03 to 2.00]) (25).

  • A 2006 Cochrane review of marine oil or other prostaglandin precursors included six trials with 2783 participants, of which 4 trials with 1683 women reported data for preeclampsia. Rates of preeclampsia did not differ between the groups (RR, 0.86 [CI, 0.59 to 1.27]) (26).

  • A 2005 Cochrane review of the effect of salt avoidance on preeclampsia included two trials with 603 participants. Salt restriction did not prevent preeclampsia (RR, 1.11 [CI, 0.46 to 2.66]) (27).

  • A randomized trial compared garlic tablets with placebo in 100 pregnant women in the third trimester who were at high risk for preeclampsia. Rates of preeclampsia did not differ between the groups (14% vs. 18%; P=0.799) (28).

Rationale
  • There is insufficient evidence for reliable conclusions about the effects of exercise or bed rest on prevention of preeclampsia and its complications.

  • There is insufficient evidence for reliable conclusions about the effects of marine oil or salt restriction on prevention of preeclampsia and its complications.

  • Garlic does not reduce the incidence of preeclampsia.

Avoid the use of diuretics to prevent preeclampsia. 
  • Do not use diuretics for the prevention of preeclampsia.

Evidence
  • A 2007 meta-analysis of diuretics to prevent preeclampsia included four randomized trials (1391 women) comparing thiazide diuretics with either placebo or no intervention. Overall, thiazide diuretics did not reduce the rate of preeclampsia (RR, 0.69 [CI, 0.40 to 1.27]) but did increase nausea and vomiting (two trials, 1217 women; RR, 5.81 [CI, 1.04 to 32.46]). Women allocated to diuretics were more likely than those allocated to placebo to stop treatment because of side effects (two trials, 1217 women; RR, 1.85 [CI, 0.81 to 4.22]) (29).

Rationale
  • Thiazide diuretics do not reduce the risk for preeclampsia.

Screen pregnant patients for preeclampsia by monitoring for risk factors, elevated blood pressure, proteinuria, and signs or symptoms of the disease.  
  • Screen for preeclampsia at each prenatal visit after 20 weeks' gestation by

    • Checking blood pressure

    • Checking a urinalysis to look for proteinuria

  • Note that specific risk factors include

    • Nulliparity

    • Advanced maternal age (older than 40 years)

    • History of previous preeclampsia

    • Multiple pregnancy

    • In-vitro fertilization

    • Preexisting medical conditions:

      • Type-1 diabetes

      • Chronic hypertension

      • Chronic kidney disease

      • Chronic autoimmune disease

      • Antiphospholipid syndrome

      • Asthma

    • Obesity (increased prepregnancy BMI >35 kg/m2)

    • Polycystic ovary syndrome

    • Black race

  • Consider that urinary tract infection and periodontal disease during pregnancy may be associated with preeclampsia.

Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended assessing all pregnant women for proteinuria.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy noted the risk factors for preeclampsia and recommended using only the patient's history to assess the risk for preeclampsia.

  • A 2005 systematic review of risk factors for preeclampsia included 52 cohort and case-control studies. The risk for preeclampsia was increased in women with a previous history of preeclampsia (RR, 7.19 [CI, 5.85 to 8.83]), antiphospholipid antibodies (RR, 9.72 [CI, 4.34 to 21.75]), preexisting diabetes (RR, 3.56 [CI, 2.54 to 4.99]), multiple (twin) pregnancy (RR, 2.93 [CI, 2.04 to 4.21]), nulliparity (RR, 2.91 [CI, 1.28 to 6.61]), family history (RR, 2.90 [CI, 1.70 to 4.93]), raised blood pressure (diastolic ≥ 80 mm Hg) at booking (RR, 1.38 [CI, 1.01 to 1.87]), raised BMI before pregnancy (RR, 2.47 [CI, 1.66 to 3.67]) or at booking (RR, 1.55 [CI, 1.28 to 1.88]), or maternal age 40 years or older (RR, 1.96 [CI, 1.34 to 2.87], for multiparous women). Individual studies showed that risk was also increased with an interval of 10 years or more since a previous pregnancy, autoimmune disease, renal disease, and chronic hypertension (30).

  • A 2008 systematic review of the accuracy of blood pressure measurements for predicting preeclampsia included 34 studies with 60,599 participants. Second-trimester mean arterial pressure of ≥90 mm Hg showed a positive LR of 3.5 (CI, 2.0 to 5.0) and a negative LR of 0.46 (CI, 0.16 to 0.75). In women deemed to be at high risk, a diastolic blood pressure of ≥75 mm Hg at 13 to 20 weeks' gestation best predicted preeclampsia: positive LR, 2.8 (CI, 1.8 to 3.6); negative LR, 0.39 (CI, 0.18 to 0.71). When blood pressure was measured in the first or second trimester of pregnancy, the mean arterial pressure was a better predictor for preeclampsia than systolic blood pressure, diastolic blood pressure, or an increase of blood pressure (31).

  • A 2008 systematic review of the relationship between maternal infection and preeclampsia included 49 observational studies. The risk for preeclampsia was increased in pregnant women with urinary tract infection (pooled OR, 1.57 [CI, 1.45 to 1.70]) and periodontal disease (pooled OR, 1.76 [CI, 1.43 to 2.18]) (32).

  • A 2011 systematic review of adverse pregnancy outcomes in women with asthma included 40 cohort studies. Maternal asthma was associated with an increased risk for preeclampsia (RR, 1.54 [CI, 1.32 to 1.81]) (33).

  • A prospective multicenter cohort study evaluated risk factors for preeclampsia in 3572 “healthy” nulliparous women with a singleton pregnancy. Independent risk factors at 14 to 16 weeks' gestation included increased mean arterial blood pressure (adjusted OR, 1.4 [CI, 1.2 to 1.5], for a 5 mm Hg increase), increased BMI (adjusted OR, 1.3 [CI, 1.1 to 1.5] for a 5-point increase), family history of preeclampsia (adjusted OR, 1.9 [CI, 1.3 to 2.9]), family history of coronary heart disease (adjusted OR, 1.8 [CI, 1.2 to 2.8]), and maternal birthweight. Protective factors included a previous single miscarriage with the same partner (adjusted OR, 0.44 [CI, 0.21 to 0.92]), taking at least 12 months to conceive (adjusted OR, 0.41 [CI, 0.22 to 0.76]), and a high intake of fruit (adjusted OR, 0.65 [CI, 0.45 to 0.92]) (34).

  • A population-based cohort study evaluated outcomes associated with polycystic ovary syndrome. Polycystic ovarian syndrome was strongly associated with preeclampsia (adjusted OR, 1.45 [CI, 1.24 to 1.69]) (35).

  • A retrospective case-control study used data from a multicenter cohort trial involving 53,337 pregnant women to compare the results of testing for thrombophilia in 113 women who developed preeclampsia and 443 who did not. Thrombophilia was present in 14% of patients with preeclampsia and 21% of control subjects (adjusted logistic regression OR, 0.6 [CI, 0.3 to 1.3]) (36).

Rationale
  • Preeclampsia is a disease occurring primarily after 20 weeks' gestation and is characterized chiefly by hypertension and proteinuria.

  • Predictive models that incorporate risk factors according to clinical phenotypes have a modest predictive accuracy.

  • There is no reliable method to screen for preeclampsia or eclampsia, and current serial blood pressure measurements and proteinuria dipstick screens are based mostly on expert opinion without strong evidence for their predictive ability or potential to improve reproductive outcome.

Comments
  • In a population-based cohort study, women with intrahepatic cholestasis had a higher risk for preeclampsia (adjusted OR, 2.62 [CI, 2.32 to 2.78]) (37).

  • In a population-based cohort study, hyperemesis gravidarum in the first trimester only slightly increased the risk for preeclampsia. Women with hyperemesis gravidarum and first admission in the second trimester had a more than doubled risk for preterm (<37 weeks) preeclampsia (adjusted OR, 2.09 [CI, 1.38 to 3.16]) (38).

  • In a prospective observational study including 175 women, obstructive sleep apnea increased the risk for preeclampsia compared with controls (42.3% compared with 16.9%; P=0.005) (39).

  • In a secondary analysis of a prospective prenatal population-based study, there was a significant association between subclinical hypothyroidism and severe preeclampsia (adjusted OR, 1.6 [CI, 1.1 to 2.4]; P=0.03) (40).

Do not do additional testing to screen for preeclampsia.  
  • Do not use uterine artery Doppler ultrasonography to screen for preeclampsia.

  • Do not use biomarkers to screen for preeclampsia.

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended using only the patient's history to assess the risk for preeclampsia and recommended against any additional testing, including uterine artery Doppler ultrasonography and testing for biomarkers, such as angiogenesis markers and placental protein-13.

  • A 2013 individual patient data meta-analysis of the impact of the addition of Doppler characteristics in the identification of nulliparous women at risk for preeclampsia included 6708 nulliparous women from 8 data sets. Combinations of mean pulsatility index or resistance index and bilateral notching were the best predictors, with areas under the receiver-operating characteristics curve of 0.75 (CI, 0.56 to 0.95) and 0.70 (CI, 0.66 to 0.74), respectively. The addition of Doppler to blood pressure and BMI improved diagnostic discrimination (41).

  • A 2008 systematic review of the accuracy of uterine artery Doppler to predict preeclampsia and intrauterine growth restriction included 74 studies of preeclampsia (total 79,547 patients). Doppler was more accurate in the second trimester than in the first. In low-risk patients, the best index was an increased pulsatility index with diastolic notching (positive LR, 7.5; negative LR, 0.59; sensitivity, 23%; specificity, 99%), whereas for high-risk patients it was unilateral notching (positive LR, 20.2; negative LR, 0.17; sensitivity, 83%; specificity, 96%), and an increased pulsatility index with notching (positive LR, 21; negative LR, 0.82; sensitivity, 19%; specificity, 99%). Severe preeclampsia in low-risk patients was best predicted by an increased pulsatility index (positive LR, 15.6 [CI, 13.3 to 17.3]; negative LR, 0.23 [CI, 0.15 to 0.35]; sensitivity, 42%; specificity, 91%) and bilateral notching (positive LR, 13.4 [CI, 8.5 to 17.4]; negative LR, 0.4 [CI, 0.2 to 0.6]; sensitivity, 43%; specificity, 93%), whereas for high-risk patients, Doppler resistance index showed low diagnostic characteristics (positive LR, 3.7) (42).

  • A 2004 systematic review of screening tests for preeclampsia by the World Health Organization included 43 studies involving 42,261 patients. In low-risk patients, Doppler showed a moderate predictive accuracy (any diastolic notch, positive LR, 3.5; negative LR, 0.8; and bilateral diastolic notch, positive LR, 6.6; negative LR, 0.8). In high-risk patients, Doppler ultrasonography had low predictive value (any diastolic notch, positive LR, 2.4; negative LR, 0.6; and bilateral diastolic notch, positive LR, 2.8; negative LR, 0.6). Fetal and placental peptides had generally low accuracy. Great statistical heterogeneity among included studies was seen (43).

  • A 2007 systematic review evaluating whether elevated soluble fms-like tyrosine kinase-1 receptor (sFlt-1) and decreased placental growth factor predict preeclampsia included 10 studies analyzing sFlt-1 and 14 analyzing placental growth factor. After week 25, levels of placental growth factor and sFlt-1 were lower in women who developed preeclampsia in all studies, although in 2 studies the difference was only statistically significant among women who developed severe preeclampsia. The review was limited by substantial heterogeneity (44).

  • A cohort study assessed the diagnostic accuracy of Doppler ultrasound for the prediction of preeclampsia in 2188 low-risk nulliparous women enrolled in a randomized trial of antioxidant supplemention. Overall, Doppler ultrasound had a sensitivity of 43% and a specificity of 67% (45).

Rationale
  • Uterine artery Doppler ultrasonography has moderate accuracy for the prediction of preeclampsia.

  • Screening with uterine artery Doppler ultrasonography has not been shown to improve clinical outcomes.

Comments
  • Uterine artery Doppler ultrasonography has a prognostic role for neonatal complications in women who are admitted because of preeclampsia.

  • In a cohort study, uterine artery Doppler ultrasonographic examination was performed at admission for patients with severe early-onset (<34 weeks' gestation) preeclampsia. The maternal and neonatal outcomes of women with abnormal uterine artery Doppler results were compared with those of women with normal Doppler results. One hundred twenty patients were included. In 53% of patients, uterine artery Doppler results were abnormal. This group had a lower gestational age at delivery (30.2 vs. 32.7 weeks; P<0.001) and a higher proportion of small-for-gestational-age infants (87.5% vs. 67.9%; P=0.009). Neonatal (40.6% vs. 14.3%; P=0.01) and maternal (28.1% vs. 5.4%; P=0.001) complications were more common in the abnormal uterine artery Doppler group (46).

  • In a study of 99 patients, those with late-onset preeclampsia underwent Doppler interrogation of the uterine arteries. Patients with abnormal findings on uterine artery Doppler studies were compared with those who had normal Doppler findings. The group with abnormal Doppler results presented with significantly lower gestational age at admission (36.1 ± 2.1 weeks vs. 37.2 ± 1.9 weeks; P<0.005), lower gestational age at delivery (36.5 ± 1.9 weeks vs. 37.7 ± 1.7 weeks; P<0.005), lower birthweight (2429 ± 590 g vs. 3013 ± 597 g; P<0.0001), and a higher rate of admission to the neonatal intensive care unit (17 of 51 vs. 6 of 48; OR, 3.5 [CI, 1.2 to 9.5]) (47).

Ask patients about risk factors for preeclampsia and potential signs of severe disease. 
  • Ask about historical risk factors for preeclampsia, including

    • Nulliparity

    • Advanced maternal age (older than 40 years)

    • History of previous preeclampsia

    • Multiple pregnancy

    • Preexisting medical conditions:

      • Type-1 diabetes

      • Chronic hypertension

      • Chronic kidney disease

      • Chronic autoimmune disease

      • Antiphospholipid syndrome

    • Obesity (increased prepregnancy BMI >35 kg/m2)

    • Polycystic ovary syndrome

    • Black race

  • Ask about symptoms of preeclampsia, focusing on symptoms with more ominous implications:

    • Neurologic symptoms, such as

      • Scotomata

      • Blurred vision

      • Headache

    • Epigastric or right-upper-quadrant pain, nausea, or vomiting

    • Dyspnea

    • Decreased fetal movement or vaginal bleeding

  • Note that occurrence of seizures after 20 weeks' gestation in patients with no history of seizures defines eclampsia (preeclampsia with seizures) unless there is firm evidence for an alternative diagnosis.

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy noted the risk factors for preeclampsia and recommended using only the patient's history to assess the risk for preeclampsia.

  • A 2005 systematic review of risk factors for preeclampsia included 52 cohort and case-control studies. The risk for preeclampsia was increased in women with a previous history of preeclampsia (RR, 7.19 [CI, 5.85 to 8.83]), antiphospholipid antibodies (RR, 9.72 [CI, 4.34 to 21.75]), preexisting diabetes (RR, 3.56 [CI, 2.54 to 4.99]), multiple (twin) pregnancy (RR, 2.93 [CI, 2.04 to 4.21]), nulliparity (RR, 2.91 [CI, 1.28 to 6.61]), family history (RR, 2.90 [CI, 1.70 to 4.93]), raised blood pressure (diastolic ≥ 80 mm Hg) at booking (RR, 1.38 [CI, 1.01 to 1.87]), raised BMI before pregnancy (RR, 2.47 [CI, 1.66 to 3.67]) or at booking (RR, 1.55 [CI, 1.28 to 1.88]), or maternal age 40 years or older (RR, 1.96 [CI, 1.34 to 2.87], for multiparous women). Individual studies showed that risk was also increased with an interval of 10 years or more since a previous pregnancy, autoimmune disease, renal disease, and chronic hypertension (30).

  • A 2008 systematic review of the accuracy of blood pressure measurements for predicting preeclampsia included 34 studies with 60,599 participants. Second-trimester mean arterial pressure of ≥90 mm Hg showed a positive LR of 3.5 (CI, 2.0 to 5.0) and a negative LR of 0.46 (CI, 0.16 to 0.75). In women deemed to be at high risk, a diastolic blood pressure of ≥75 mm Hg at 13 to 20 weeks' gestation best predicted preeclampsia: positive LR, 2.8 (CI, 1.8 to 3.6); negative LR, 0.39 (CI, 0.18 to 0.71). When blood pressure was measured in the first or second trimester of pregnancy, the mean arterial pressure was a better predictor for preeclampsia than systolic blood pressure, diastolic blood pressure, or an increase of blood pressure (31).

  • A 2008 systematic review of the relationship between maternal infection and preeclampsia included 49 observational studies. The risk for preeclampsia was increased in pregnant women with urinary tract infection (pooled OR, 1.57 [CI, 1.45 to 1.70]) and periodontal disease (pooled OR, 1.76 [CI, 1.43 to 2.18]) (32).

  • A 2011 systematic review of adverse pregnancy outcomes in women with asthma included 40 cohort studies. Maternal asthma was associated with an increased risk for preeclampsia (RR, 1.54 [CI, 1.32 to 1.81]) (33).

  • A prospective multicenter cohort study evaluated risk factors for preeclampsia in 3572 “healthy” nulliparous women with a singleton pregnancy. Independent risk factors at 14 to 16 weeks' gestation included increased mean arterial blood pressure (adjusted OR, 1.4 [CI, 1.2 to 1.5] for a 5 mm Hg increase), increased BMI (adjusted OR, 1.3 [CI, 1.1 to 1.5] for a 5-point increase), family history of preeclampsia (adjusted OR, 1.9 [CI, 1.3 to 2.9]), family history of coronary heart disease (adjusted OR, 1.8 [CI, 1.2 to 2.8]), and maternal birthweight. Protective factors included a previous single miscarriage with the same partner (adjusted OR, 0.44 [CI, 0.21 to 0.92]), taking at least 12 months to conceive (adjusted OR, 0.41 [CI, 0.22 to 0.76]), and a high intake of fruit (adjusted OR, 0.65 [CI, 0.45 to 0.92]) (34).

  • A population-based cohort study evaluated outcomes associated with polycystic ovary syndrome. Polycystic ovarian syndrome was strongly associated with preeclampsia (adjusted OR, 1.45 [CI, 1.24 to 1.69]) (35).

  • A retrospective case-control study used data from a multicenter cohort trial involving 53,337 pregnant women to compare the results of testing for thrombophilia in 113 women who developed preeclampsia and 443 who did not. Thrombophilia was present in 14% of patients with preeclampsia and 21% of control subjects (adjusted logistic regression OR, 0.6 [CI, 0.3 to 1.3]) (36).

Rationale
  • These risk factors and symptoms comprise the major historical identifying features of preeclampsia.

  • Patients with eclampsia or complications of preeclampsia require immediate care.

Use blood pressure as a key criterion for diagnosing preeclampsia and look for other signs of the disease on physical examination. 
  • Diagnose hypertension by documenting

    • Two blood pressure readings 4 hours apart, with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg in a patient with no known history of chronic hypertension

    • Systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥110 mm Hg

  • If preeclampsia is present and becomes more severe, look for

    • Oliguria (<30 mL/h)

    • Peripheral cyanosis

    • Pulmonary crackles

    • Right-upper-quadrant abdominal tenderness

    • Hyperreflexia and clonus

    • Vaginal bleeding consistent with placental abruption

    • Seizure activity (indicating eclampsia)

    • Visual symptoms

  • See module Hypertension in Pregnancy.

Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada defined preeclampsia as new or worsening hypertension with one or more adverse conditions (e.g., proteinuria) or one or more severe complications.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy defined preeclampsia as hypertension (blood pressure ≥140/90 mm Hg on two occasions 4 hours apart or ≥160/110 mm Hg in a patient with previously normal blood pressure) plus proteinuria (≥300 mg in 24 hours or urinary protein-to-creatinine ratio ≥0.3). The task force recommended diagnosing preeclampsia in patients without proteinuria but with either a platelet count of <100,000/µL, an elevated creatinine level (>1.1 mg/dL or double the baseline value in the absence of another cause), liver enzyme levels twice normal, pulmonary edema, or cerebral or visual symptoms. The report noted that women with preeclampsia and pulmonary edema, renal insufficiency, and visual or CNS disturbance are considered to have severe disease.

  • A 2010 NICE guideline defined preeclampsia as new hypertension after 20 weeks' gestation with significant proteinuria, defined as 24-hour urinary protein >300 mg or spot urine protein-to-creatinine ratio of 30 mg/mmol.

  • A cohort study of 4302 gravidas evaluated normotensive women who developed proteinuria within 7 days of a rise in diastolic blood pressure ≥15 mm Hg (n=82) or who developed proteinuria without a rise in diastolic blood pressure ≥15 mm Hg. The group with the rise in diastolic blood pressure had a greater weight gain (P<0.005) and more frequent abdominal deliveries (P<0.001) with no other evidence of adverse pregnancy outcome (48).

  • In a prospective descriptive study of 383 cases of eclampsia in the U.K., eclampsia presented before any documented hypertension or proteinuria in 38% of cases (49).

Rationale
  • To decrease false-positive diagnoses, an absolute standard of 140/90 mm Hg blood pressure reading is used.

  • Pulmonary congestion and cyanosis suggest decreased oxygenation.

  • Right-upper-quadrant tenderness suggests hepatic involvement, particularly subcapsular swelling.

  • Eclampsia can present as the only sign of the preeclampsia-eclampsia disease.

Comments
  • In a patient with preexisting chronic hypertension, elevation significantly above the values present in the first trimester are considered clinically important for the diagnosis of preeclampsia.

  • Although edema occurs in too many women with normal pregnancies to be a discriminator of preeclampsia and has been abandoned as a marker for preeclampsia, women with nondependent edema or rapid weight gain warrant close observation.

Quantitate proteinuria and determine renal function in patients with suspected preeclampsia. 
  • Look for proteinuria in patients with suspected preeclampsia by measuring

    • A timed (12- to 24-hour) urine collection

    • A spot urinary protein-to-creatinine ratio

    • A urine dipstick only if there are no other available tests

  • Diagnose significant proteinuria in patients with

    • Urinary protein excretion of ≥300 mg/24 hours

    • Urinary protein excretion of >165 mg/12 hours

    • A urine protein-to-creatinine ratio ≥0.3 mg/dL or 30 mg/mmol

  • Obtain a serum creatinine level to calculate creatinine clearance.

  • In patients with preexisting renal disease, look for a significant increase in proteinuria by comparing the degree of proteinuria with a baseline measurement in a first-trimester timed urine collection.

  • Obtain a serum uric acid and 24-hour total urinary calcium measurement.

  • See table Laboratory and Other Studies for Preeclampsia.

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy defined preeclampsia as hypertension (blood pressure ≥140/90 mm Hg on two occasions 4 hours apart or ≥160/110 mm Hg in a patient with previously normal blood pressure) plus proteinuria (≥300 mg in 24 hours or urinary protein-to-creatinine ratio ≥0.3). The task force recommended diagnosing preeclampsia in patients without proteinuria but with either a platelet count of <100,000/µL, an elevated creatinine level (>1.1 mg/dL or double the baseline value in the absence of another cause), liver enzyme levels twice normal, pulmonary edema, or cerebral or visual symptoms. The report noted that women with preeclampsia and pulmonary edema, renal insufficiency, and visual or CNS disturbance are considered to have severe disease.

  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada defined preeclampsia as new or worsening hypertension with one or more adverse conditions (e.g., proteinuria) or one or more severe complications. The guideline recommended that women with suspected preeclampsia be tested with urinalysis, pulse oximetry, CBC, coagulation testing (PT, PTT, and fibrinogen), serum creatinine, uric acid, glucose, AST or ALT, LDH, bilirubin, and albumin.

  • A 2010 NICE guideline defined preeclampsia as new hypertension after 20 weeks' gestation with significant proteinuria, defined as 24-hour urinary protein >300 mg or spot urine protein-to-creatinine ratio of 30 mg/mmol.

  • A 2012 systematic review of the diagnostic accuracy and prognostic value of spot urinary protein-to-creatinine ratio in pregnant women with suspected preeclampsia included 20 studies with 2978 participants. Pooled sensitivity was highest at a threshold of 0.13 to 0.14 (sensitivity, 89%; specificity, 63% to 64%); pooled specificity was highest at a threshold of 0.50 (specificity, 87%; sensitivity, 65%). At a threshold of 0.30, sensitivity and specificity were 81% and 76%, respectively (50).

  • A 2004 systematic review of the diagnostic accuracy of urine dipsticks for the diagnosis of hypertensive disorders in pregnancy included 7 studies. At a threshold of 1+ proteinuria, urinary dipsticks had a pooled sensitivity of 55%, a specificity of 84%, a positive LR of 3.48 (CI, 1.66 to 7.27), and a negative LR of 0.6 (CI, 0.45 to 0.80) (51).

  • A study evaluated the diagnostic accuracy of 12-hour urinary protein and protein-to-creatinine ratio in pregnant women with suspected preeclampsia compared with the reference standard of 24-hour urine protein. A 12-hour urine protein of >165 mg had a sensitivity of 96% and a specificity of 100%; a urine protein-to-creatinine ratio had a sensitivity of 89% and a specificity of 49% (52).

Rationale
  • Nonproteinuric hypertension (gestational hypertension) does not have the same prognosis for the mother and fetus as preeclampsia (proteinuric hypertension).

  • There is a decrease in kidney filtration fraction of about 25% in patients with preeclampsia; however, with the normal physiologic renal changes found in pregnancy (increase in renal function, 35% to 50%), the patient often maintains a normal creatinine level.

Comments
  • Normal creatinine clearance in pregnancy is generally >150 mL/min, measured by 24-hour urine collection.

Diagnose preeclampsia in pregnant patients after 20 weeks' gestation with new hypertension (blood pressure consistently ≥140/90 mm Hg) and proteinuria. 
  • Diagnose preeclampsia in a pregnant woman after 20 weeks' gestation who has

    • Hypertension, defined by a blood pressure ≥140/90 mm Hg on two occasions 4 hours apart or ≥160/110 mm Hg in a patient with previously normal blood pressure

    • Proteinuria, defined by a protein excretion of ≥300 mg in 24 hours, >165 mg in 12 hours, or a urinary protein-to-creatinine ratio ≥0.3

  • In patients with new hypertension who do not have proteinuria, diagnose preeclampsia if they have one of the following:

    • Platelet count <100,000 /µL

    • Elevated creatinine level (>1.1 mg/dL or double the baseline value)

    • Elevated transaminase levels (at least twice normal)

    • Pulmonary edema

    • Cerebral or visual symptoms

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy defined preeclampsia as hypertension (blood pressure ≥140/90 mm Hg on two occasions 4 hours apart or ≥160/110 mm Hg in a patient with previously normal blood pressure) plus proteinuria (≥300 mg in 24 hours or urinary protein-to-creatinine ratio ≥0.3). The task force recommended diagnosing preeclampsia in patients without proteinuria but with either a platelet count of <100,000/µL, an elevated creatinine level (>1.1 mg/dL or double the baseline value in the absence of another cause), liver enzyme levels twice normal, pulmonary edema, or cerebral or visual symptoms. The report noted that women with preeclampsia and pulmonary edema, renal insufficiency, and visual or CNS disturbance are considered to have severe disease.

  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada defined preeclampsia as new or worsening hypertension with one or more adverse conditions (e.g., proteinuria) or one or more severe complications. The guideline recommended that women with suspected preeclampsia be tested with urinalysis, pulse oximetry, CBC, coagulation testing (PT, PTT, and fibrinogen), serum creatinine, uric acid, glucose, AST or ALT, LDH, bilirubin, and albumin.

  • A 2010 NICE guideline defined preeclampsia as new hypertension after 20 weeks' gestation with significant proteinuria, defined as 24-hour urinary protein >300 mg or spot urine protein-to-creatinine ratio of 30 mg/mmol.

Rationale
  • Preeclampsia is a clinical diagnosis.

Obtain liver function tests and a CBC to determine the severity of preeclampsia. 
Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada defined preeclampsia as new or worsening hypertension with one or more adverse conditions (e.g., proteinuria) or one or more severe complications. The guideline recommended that women with suspected preeclampsia be tested with urinalysis, pulse oximetry, CBC, coagulation testing (PT, PTT, and fibrinogen), serum creatinine, uric acid, glucose, AST or ALT, LDH, bilirubin, and albumin.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended that women with preeclampsia have their CBC, liver enzyme levels, and serum creatinine level checked.

Rationale
  • Serum liver transaminase, LDH, and bilirubin levels may be abnormal in HELLP syndrome associated with preeclampsia.

  • Serum albumin can be decreased despite minimal proteinuria, possibly because of incurred vascular permeability, liver involvement, or both.

  • Hematologic abnormalities may be due to hemolysis, a severe manifestation of preeclampsia, or HELLP syndrome.

Comments
  • Liver damage in preeclampsia can range from mild hepatocellular necrosis to HELLP syndrome.

  • Do not routinely order noninvasive or invasive cardiac monitoring in patients with preeclampsia since the heart is rarely affected.

Classify the severity of preeclampsia based on level of blood pressure and the presence of complications. 
  • Classify patients with preeclampsia according to the severity of their disease.

  • Diagnose mild preeclampsia:

    • If systolic blood pressure remains <160 mm Hg and diastolic blood pressure remains <110 mm Hg

    • If there are no hematologic, neurologic, cardiopulmonary, or uteroplacental/fetal complications

  • Diagnose severe preeclampsia if any of the following conditions are satisfied:

    • Systolic blood pressure is ≥160 mm Hg or diastolic blood pressure is ≥110 mm Hg on two separate occasions 4 hours apart while the patient is on bed rest

    • Thrombocytopenia (platelet count <100,000/µL)

    • Liver enzyme levels greater than twice the upper limit of normal or persistent right-upper-quadrant pain

    • Progressive renal insufficiency, with creatinine level >1.1 mg/dL or twice the baseline value

    • Pulmonary edema

    • Cerebral or visual disturbance

  • Diagnose eclampsia in patients who meet criteria for preeclampsia and have generalized seizure activity in the absence of a history of seizure disorder.

  • See table Laboratory and Other Studies for Preeclampsia.

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy defined preeclampsia as hypertension (blood pressure ≥140/90 mm Hg on two occasions 4 hours apart or ≥160/110 mm Hg in a patient with previously normal blood pressure) plus proteinuria (≥300 mg in 24 hours or urinary protein-to-creatinine ratio ≥0.3). The task force defined severe disease in patients with either a blood pressure persistently over 160/110 or with a platelet count of <100,000/µL, an elevated creatinine level (>1.1 mg/dL or double the baseline value in the absence of another cause), liver enzyme levels twice normal, pulmonary edema, or cerebral or visual symptoms.

  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada defined preeclampsia as new or worsening hypertension with one or more adverse conditions (e.g., proteinuria) or one or more severe complications. The guideline defined severe preeclampsia in women with one or more severe complications which include: eclampsia or other neurologic manifestations, uncontrolled severe hypertension, oxygen saturation <90%, myocardial ischemia or need for inotropic support, platelet count <50,000/μL, acute kidney injury, hepatic dysfunction, or placental abruption.

  • A model to predict prognosis in patients with preeclampsia was derived and validated based on data from a prospective cohort study involving women hospitalized with preeclampsia. The final prediction model included gestational age, the presence of chest pain or dyspnea, creatinine level, platelet count, AST level, and oxygen saturation. The presence of chest pain or dyspnea was a strong risk factor for adverse events, with an OR of 6.13 (CI, 3.56 to 10.54) (53).

Rationale
  • Risk to the mother and fetus is related to the severity of preeclampsia.

Assess fetal well-being in women with preeclampsia. 
  • For mild preeclampsia,

    • Refer to an obstetrician with training, experience, and demonstrated competence in the management of preeclampsia

    • Urge all women with any degree of preeclampsia to do a daily fetal movement assessment

    • Consult with an experienced obstetrician to

      • Obtain ultrasonographic estimation of fetal weight and amniotic fluid volume at initial evaluation and, if normal, every 3 weeks until delivery

      • Do a nonstress test, a biophysical profile, or both at initial evaluation and, if reassuring, every week; repeat immediately if there is an abrupt change in maternal condition and twice weekly if there is fetal growth restriction or oligohydramnios

  • For severe preeclampsia,

    • If pregnancy is less than 32 weeks' gestation and conservative management is considered without immediate delivery, be sure that the patient is transferred to a tertiary care center for daily evaluation and fetal surveillance by a maternal-fetal medicine specialist with special expertise treating women with severe preterm preeclampsia

    • Consider laboratory evaluation and fetal surveillance on a daily basis, depending on the severity and progression of the disease

  • See table Laboratory and Other Studies for Preeclampsia.

Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended the following fetal tests in women with suspected preeclampsia: uterine, ductus venosis, middle cerebral, and umbilical artery Doppler velocimetry, fetal monitoring, assessment of amniotic fluid, and assessment of fetal growth.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended that women with mild preeclampsia undergo ultrasound to assess fetal growth and antenatal monitoring including nonstress testing.

Rationale
  • Preeclampsia can decrease uteroplacental function by decreased perfusion, infarction, and abruption.

  • Delivery is always appropriate for the mother but may not be so for the fetus, such as in cases of preterm immature pulmonary function.

Comments
  • Severe fetal growth restriction, nonreassuring fetal testing results, or oligohydramnios can be indications for delivery in severe preeclampsia. The gestational age should be taken into account when making determinations about delivery timing, according to expert guidelines (54).

Differentiate preeclampsia from other hypertensive or proteinuric diseases in pregnant women. 
Evidence
  • Consensus.

Rationale
  • Preeclampsia is managed differently from gestational hypertension and chronic hypertensive/renal diseases of pregnancy.

Comments
  • It is difficult to make the correct diagnosis in patients with prenatal care commencing at more than 20 weeks' gestation because baseline blood pressure and proteinuria are not available in many cases. The physiologic nadir of blood pressure in pregnancy at around 20 weeks' gestation with the resultant rise in blood pressure in all gravidas entering the third trimester makes the physiologic changes of pregnancy difficult to distinguish from the pathophysiology of preeclampsia.

  • Acute and chronic cocaine use can be associated with mental status changes, cardiovascular instability, hypertension, thrombocytopenia, and placental abruption.

Consult an obstetrician for help in making an accurate diagnosis in pregnant patients with hypertension, proteinuria, or both. 
  • Obtain consultation with

    • An obstetrician in patients with elevated blood pressure, proteinuria, or both to differentiate when the diagnosis is unclear

    • An obstetric expert for patients at a tertiary care center when complex testing is required

Evidence
  • Consensus.

Rationale
  • Hypertensive diseases of pregnancy are a significant cause of maternal and fetal/neonatal morbidity and mortality.

Ensure that an obstetric expert and an anesthesiologist manage patients with preeclampsia. 
  • Obtain consultation with

    • An obstetrician as soon as the diagnosis of preeclampsia is suspected to

      • Confirm diagnosis

      • Evaluate and balance maternal and fetal risks individually

      • Determine when delivery should be recommended and how delivery should be performed

    • An anesthesiologist to

      • Evaluate patient airway characteristics in the event general anesthesia is needed and for administration during labor

      • Help plan the delivery

    • A maternal-fetal medicine subspecialist at a tertiary care center to

      • Manage severe preterm preeclampsia

      • Evaluate the risks to the mother and fetus of continuing pregnancy vs. the known risk for prematurity to the neonate

      • Manage atypical eclampsia with neurologic sequelae

Evidence
  • A randomized, controlled trial of 80 women with severe preeclampsia who required cesarean delivery to general endotracheal (n=26), epidural (n=27), or combined spinal-epidural (n=27) anesthesia found that there were no serious maternal or fetal complications attributable to any of the three anesthetic methods (55).

  • A retrospective series of 138 nonlaboring women with severe preeclampsia receiving regional anesthesia for cesarean section found that changes in lowest mean blood pressure, incidence of intraoperative ephedrine use, incidence of postoperative pulmonary edema, and neonatal Apgar scores were similar in women receiving epidural (n=35) vs. spinal (n=103) anesthesia (56).

  • Mainly consensus.

Rationale
  • Preeclampsia is a leading cause of maternal and fetal/neonatal morbidity and mortality.

  • Uteroplacental insufficiency increases the risk for cesarean section, and preeclamptic patients are at increased risk for morbidity from both regional and general anesthesia techniques.

  • Intensive maternal and neonatal care may be needed in cases of severe preterm preeclampsia.

Comments
  • Hypertensive disorders of pregnancy are a leading cause of maternal mortality and can cause significant morbidity, such as placental abruption, disseminated intravascular coagulopathy, cerebral hemorrhage, hepatic failure, and acute renal failure.

Evaluate the risk for fatal or life-threatening complications in women with preeclampsia within 48 hours of hospital admission for the disorder by using predictors of adverse maternal outcome. 
  • Consider gestational age, chest pain or dyspnea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations among women with preeclampsia within 48 hours of hospital admission in order to identify women at increased risk for adverse outcomes up to 7 days before complications arise.

Evidence
  • A model to predict prognosis in patients with preeclampsia was derived and validated based on data from a prospective cohort study involving women hospitalized with preeclampsia. The final prediction model included gestational age, the presence of chest pain or dyspnea, creatinine level, platelet count, AST level, and oxygen saturation. The presence of chest pain or dyspnea was a strong risk factor for adverse events, with an OR of 6.13 (CI, 3.56 to 10.54) (53).

Rationale
  • Awareness of the risk for adverse maternal outcome can help direct patient care.

Hospitalize patients with new-onset preeclampsia. 
  • Hospitalize women with preeclampsia and

    • Blood pressure >160/110 mm Hg

    • Signs of liver, kidney, hematologic, or CNS dysfunction

    • Signs of fetal distress, oligohydramnios, placental abruption, or rupture of membranes

  • For patients with mild new-onset preeclampsia,

    • Consider hospitalization

    • Consider outpatient management with frequent clinical and fetal evaluation and restricted activity

  • Consult with an appropriate obstetric specialist or subspecialist on using these data to decide on continued antepartum management or delivery.

Evidence
  • A 2010 NICE guideline on the management of hypertensive disorders of pregnancy recommended that patients with gestational hypertension and blood pressure >160/110 mm Hg be admitted to the hospital.

  • Among 395 patients with three different pregnancy complications, 85 women with proteinuric hypertension were randomly assigned to day care vs. standard care on an antenatal ward. There were no statistically or clinically significant differences in maternal or perinatal outcomes. The day-care group reported greater satisfaction, with no evidence of unintended psychosocial sequelae. There was no significant difference in either average cost per patient or average cost per day of care (57).

Rationale
  • Maternal and fetal conditions require serial assessment to determine severity of disease.

Comments
  • Severe preeclampsia is associated with an increased risk for maternal and fetal/neonatal morbidity and mortality. Delivery is the only definitive treatment for preeclampsia and is instituted when the maternal/fetal risk and benefit assessment warrants this intervention. Conservative management without delivery can be appropriate under certain situations with extremely preterm severe preeclampsia, but this specialized situation requires management by an experienced maternal-fetal medicine subspecialist. Hospitalization for the duration of the pregnancy is indicated for women with severe preeclampsia.

  • Eclampsia is always an indication for hospitalization and delivery as soon as the mother is medically stabilized.

Base timing of delivery on severity of disease and gestational age. 
  • For patients with preeclampsia and its variations, time delivery as follows:

    • Mild preeclampsia

      • Term (>37 weeks): delivery (induce labor even in women with unfavorable cervix)

      • Preterm (34 to 37 weeks): conservative management

      • Very preterm (24 to 31 weeks): conservative management

      • Previable (20 to 23 weeks): conservative management

    • Severe preeclampsia

      • Term (>37 weeks): delivery

      • Preterm (34 to 37 weeks): delivery

      • Very preterm (24 to 33 weeks): delivery or conservative management (directly managed by maternal-fetal medicine specialist)

      • Previable (20 to 23 weeks): delivery

    • HELLP syndrome

      • Delivery regardless of gestational age

    • Eclampsia

      • Delivery regardless of gestational age

  • Use fetal assessment, including ultrasound estimation of fetal weight and amniotic fluid volume as well as nonstress testing, biophysical profile, or both, to help decide on appropriate delivery (see information on fetal assessment).

Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended immediate delivery of women with severe preeclampsia and consideration of delivery of any woman with preeclampsia at >37 weeks' gestation.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended delivery for women with preeclampsia and ≥37 weeks' gestation and those at ≥34 weeks' gestation with rupture of membranes or labor, abnormal fetal testing, fetal weight estimated to be below the fifth percentile on ultrasound, or suspected placental abruption. In addition, the task force recommended delivery for patients at <34 weeks' gestation and unstable maternal-fetal conditions once the patient is stabilized.

  • A 2010 NICE guideline on the management of hypertensive disorders of pregnancy recommended delivery in patients with preeclampsia after 37 weeks' gestation, between 34 and 37 weeks depending on the fetal and maternal condition, and before 34 weeks' gestation (after corticosteroids have been given) if they have severe refractory hypertension or maternal complications.

  • A multicenter, randomized trial, the Hypertension and Pre-eclampsia Intervention Trial at Term, compared induction of labor (n=377 patients) to expectant monitoring (n=379) in patients with a singleton pregnancy at 36 to 41 weeks' gestation and gestational hypertension or mild preeclampsia. Fewer patients in the induction-of-labor group developed poor maternal outcome (31% vs. 44%; P<0.0001). No cases of maternal or neonatal death or eclampsia were recorded (58).

  • A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial at Term found that in women who were managed expectantly, the longer the cervix, the higher the risk for developing maternal high-risk situations, whereas in patients with labor induction, cervical length was not associated with an increased risk for maternal high-risk situations. This difference in association between cervical length and maternal outcome between the two treatment options was statistically significant (P-value of interaction=0.03) (59).

  • An economic analysis estimated the cost associated with labor induction, using data from the Hypertension and Pre-eclampsia Intervention Trial at Term study. The strategy of induction of labor was less costly than expectant monitoring, with an average difference of –€831 (CI, -€1561 to –€144) (60).

  • A randomized trial allocated 96 patients with severe preeclampsia at 28 to 32 weeks' gestation to either aggressive (n=46) or expectant (n=49) management. There was no eclampsia or perinatal death in either group. The two groups had similar incidences of abruptio placentae (4.1% vs. 4.3%) and similar days of postpartum hospital stay. The expectant-management group had a significantly higher gestational age at delivery (32.9±1.5 vs. 30.8±1.7 weeks, P<0.0001) higher birth weight, lower incidence of admission to the neonatal intensive care unit (76% vs. 100%, P=0.002), lower mean days of hospitalization in the intensive care unit (20.2±14 vs. 36.6±17.4, P<0.0001), and lower incidence of neonatal complications (61).

  • A randomized trial allocated 58 women with severe preeclampsia between 28 and 34 weeks' gestation to either aggressive or expectant management. Expectant management was not associated with an increase in maternal complications, but it significantly prolonged the gestational age (mean, 7.1 days; P<0.05), reduced the number of neonates requiring ventilation (P<0.05), and reduced the number of neonatal complications (P<0.05) (62).

  • A retrospective study evaluated outcomes in 46 patients (51 fetuses) with severe preeclampsia at less than 27 weeks' gestation. The rate of perinatal survival was 0% for those with gestational age <23 weeks, 20% for those between 23 weeks and 23(6/7) weeks, 71% for those between 24 weeks and 24(6/7) weeks, 76% for those between 25 weeks and 25(6/7) weeks, and 90% for those between 26 and 26(6/7) weeks (63).

  • A retrospective cohort study described outcomes in 51 women with preeclampsia treated with expectant management. Perinatal mortality was 100% in pregnancies managed at <24 weeks (n=12). For those at 24 to 24(6/7) and 25 to 25(6/7) weeks, 50% and 57% of the newborns survived, respectively. However, in the presence of severe fetal growth restriction, survival rates were 0% and 30%, respectively (64).

Rationale
  • The maternal and fetal risks of preeclampsia are balanced based on morbidity from conservative management vs. morbidity of prematurity to the fetus.

Comments
  • For women at <34 weeks' gestation, expectant management of severe preeclampsia may be considered, but only in a select group of women and in perinatal centers capable of caring for very preterm infants.

Restrict the activity of women with severe preeclampsia. 
  • Manage women with severe preeclampsia conservatively on relative bed rest with bathroom privileges allowed.

  • Prescribe strict bed rest with seizure precautions, including padded bedrails, for women with eclampsia.

  • Do not prescribe bed rest for women with nonsevere preeclampsia.

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended against strict bed rest for women with mild preeclampsia.

  • A 2005 Cochrane review of bed rest for hypertension during pregnancy included 4 trials with 449 participants. No differences in maternal or perinatal outcomes were seen between strict bed rest and some rest, in hospital (two trials, 145 patients) in women with proteinuric hypertension, although the studies may have been underpowered to find a difference (65).

Rationale
  • Improvement of placental perfusion and possible slowing of progression of disease have been hypothesized to occur with limited activity in preeclampsia.

  • Limiting activity has not been shown to improve outcomes in women with mild preeclampsia.

Administer antihypertensive therapy to patients with blood pressure ≥160/110 mm Hg. 
  • Begin antihypertensive therapy in

    • Patients with systolic blood pressure ≥160 mm Hg

    • Patients with diastolic blood pressure ≥110 mm Hg

    • Most patients with systolic blood pressure 150 to 159 mm Hg or diastolic blood pressure 100 to 109 mm Hg

    • Patients with acute rise in blood pressure or symptoms of hypertension

  • Choose one of the following drugs as a first-line agent:

    • Labetolol

    • Calcium-channel blockers, particularly nifedipine

    • Hydralazine if other drugs are not tolerated or are not available

  • Target a goal systolic blood pressure <150 mm Hg and diastolic blood pressure of 80 to 99 mm Hg.

  • Reserve sodium nitroprusside administration by intravenous drip in a critical care unit to treat uncontrolled hypertension when initial agents fail.

  • Avoid using diuretics to control hypertension unless the patient has signs or symptoms consistent with intravascular fluid overload.

  • See table Drug Treatment for Preeclampsia.

Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended a goal BP <160/100 mm Hg in pregnant women with severe hypertension, goal systolic BP 130 to 165 mm Hg and goal diastolic BP 80 to 105 mm Hg in women with nonsevere uncomplicated hypertension, and goal BP <140/90 mm Hg for women with nonsevere hypertension with comorbid conditions. The guideline recommended labetolol, other β-blockers, and calcium-channel blockers (nifedipine), and either hydrazaline (severe hypertension) or methyldopa (nonsevere hypertension). The guideline recommended against ACE inhibitors and atenolol during pregnancy.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended antihypertensive therapy for patients with preeclampsia and sustained systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg, but did not recommend specific drugs.

  • A 2010 NICE guideline on the management of hypertensive disorders of pregnancy recommended antihypertensive therapy for patients with preeclampsia and either moderate (systolic blood pressure, 150 to 159 mm Hg; diastolic blood pressure, 100 to 109 mm Hg) or severe (systolic blood pressure, ≥160 mm Hg; diastolic blood pressure, 110 mm Hg), with oral labetolol as the first-line agent. The guideline recommended a goal systolic blood pressure <150 mm Hg and a diastolic blood pressure of 80 to 100 mm Hg.

  • A 2013 Cochrane review of drugs for the treatment of very high blood pressure during pregnancy included 35 trials with 3573 participants. Compared with hydralazine, calcium-channel blockers led to lower rates of persistent hypertension (RR, 0.37 [CI, 0.21 to 0.66]), and ketanserin led to higher rates (RR, 4.79 [CI, 1.95 to 11.73]). Compared with diazoxide, labetolol led to a lower risk for hypotension (RR, 0.06 [CI, 0.00 to 0.99]) and a trend toward a lower rate of cesarean section (RR, 0.43 [CI, 0.18 to 1.02]). Magnesium sulfate and nimodipine led to high rates of persistent hypertension (66).

  • A 2003 systematic review of hydralazine compared with other medications for severe hypertension in pregnancy included 21 randomized trials with 893 participants. Eight studies compared hydralazine with nifedipine; 5 compared hydralazine with labetalol. Hydralazine was associated with a trend toward less persistent severe hypertension compared with labetalol (RR, 0.29 [CI, 0.08 to 1.04) but more severe hypertension compared with nifedipine or isradipine (RR, 1.41 [CI, 0.95 to 2.09]). Hydralazine was associated with more maternal side effects (RR, 1.50 [CI, 1.16 to 1.94]) and with less neonatal bradycardia than labetalol (risk difference, -0.24 [CI, -0.42 to -0.06]) (67).

  • A randomized, double-blind trial compared oral nifedipine, 10 mg, with intravenous labetalol, 20 mg, in 50 peripartum patients with a sustained systolic blood pressure of at least 170 mm Hg or a diastolic blood pressure of at least 105 mm Hg. The time to achieve blood pressure control was significantly shorter with nifedipine (mean ± SD, 25 ± 13.6 min) than with labetalol (43.6 ± 25.4 min; P=0.002), and the urine output was significantly higher with nifedipine (99 ± 99 mL nifedipine vs. 44.8 ± 19.1 mL labetalol; P<0.001) (68).

Rationale
  • Acute severe hypertension is a risk factor for placental abruption and maternal stroke.

  • Precipitous drops in blood pressure can decrease uteroplacental perfusion, producing worrisome fetal monitoring results.

Give antenatal corticosteroids to women with preterm pregnancies of 24 to 34 weeks' gestation complicated by preeclampsia. 
  • If imminent delivery is not indicated and the gestation is between 24 and 34 weeks, administer antenatal corticosteroids:

    • Betamethasone, 12 mg intramuscularly, every 24 hours for two total doses, or

    • Dexamethasone, 6 mg intramuscularly, every 12 hours for four total doses

  • Do not administer multiple courses of antenatal corticosteroids.

  • See table Drug Treatment for Preeclampsia.

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended corticosteroids in women with severe preeclampsia at ≤34 weeks' gestation.

  • A 2010 NICE guideline on the management of hypertensive disorders of pregnancy recommended that women with preeclampsia who are at 24 to 34 weeks' gestation and in whom birth is likely within 7 days be treated with 2 doses of betamethasone, 12 mg intramuscularly, 24 hours apart. The guideline recommended considering betamethasone therapy for women at 35 or 36 weeks' gestation.

  • A 2006 Cochrane review of antenatal corticosteroids for fetal lung maturation in women at risk for preterm delivery included 21 studies with 4269 infants. Treatment with corticosteroids led to less neonatal death (RR, 0.69 [CI, 0.58 to 0.81]), respiratory distress syndrome (RR, 0.66 [CI, 0.59 to 0.73]), and other outcomes. There was no evidence of maternal harm (69).

  • A randomized, controlled trial of 218 women with severe preeclampsia assigned to receive betamethasone for fetal lung maturation (n=110) or placebo (n=108) found a decreased frequency of neonatal respiratory distress syndrome in the corticosteroid group (23% in the corticosteroid group and 43% in the placebo group; RR, 0.35 [CI, 0.35 to 0.82]). The relative risk for intraventricular hemorrhage, patent ductus arteriosus, and perinatal infection was also decreased in the corticosteroid group (0.35 [CI, 0.15 to 0.86], 0.27 [CI, 0.08 to 0.95], and 0.39 [CI, 0.39 to 0.97], respectively). There was no difference in the mean maternal blood pressure between the two groups (70).

  • A randomized trial compared antenatal corticosteroids (n=937) with placebo (n=921) in 1858 women at 25 to 32 weeks' gestation who remained undelivered 14 to 21 days after an initial course of antenatal corticosteroids and continued to be at high risk for preterm birth. Treatment was repeated every 14 days until week 33 or delivery. Rates of morbidity and mortality were similar in infants from the corticosteroid (12.9%) and placebo (12.5%) groups. Infants from the corticosteroid group had lower birthweight (2216 g vs. 2330 g, P=0.0026), shorter length (44.5 cm vs. 45.4 cm, P<0.001), and smaller head circumference (31.1 cm vs. 31.7 cm; P<0.001) than those from the placebo group (71).

Rationale
  • Antenatal corticosteroids improve outcomes in premature infants.

Attempt induction of labor and vaginal delivery in most women with preeclampsia who require delivery. 
  • Consult an obstetrician with experience in managing preeclampsia to decide on route of delivery, noting that vaginal delivery is preferred in most patients with preeclampsia.

  • Note that preeclampsia alone is not an indication for cesarean section, although some experts favor cesarean section in patients with severe early-onset preeclampsia with fetal growth restriction or an unripe cervix.

  • Once the decision for delivery has been made, ensure that labor is induced expeditiously.

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy stated that women with preeclampsia do not need to have cesarean delivery and recommended that mode of delivery be determined based on maternal and fetal factors.

  • A retrospective study evaluated the impact of delivery method in 278 very-low-birthweight singletons (with weight 750 to 1500 g) born to mothers with pregnancy complicated by severe preeclampsia. Fifty-two percent had labor induction, among whom vaginal delivery was obtained in 34%. The induced labor group was more likely to have 5-minute Apgar scores ≤3 (6% vs. 2%; P=0.04); the difference remained significant in the multivariable analysis. There were no other differences between the groups in infant outcomes (72).

  • A cross-sectional study evaluated prognostic factors in women with severe preeclampsia who required delivery between 24 and 34 weeks of gestation. Among 491 women, 57.4% underwent induction of labor. Rates of successful vaginal delivery varied with gestational age and occurred in 6.7% of women between 24 and 28 weeks' gestation, 47.5% of women between 28 and 32 weeks' gestation, and 68.8% of women between 32 and 34 weeks' gestation. In the multivariate analysis, labor induction was not associated with neonatal morbidity or mortality (73).

  • In a retrospective chart review of pregnancies of 24 to 34 weeks' gestation in 306 patients with severe preeclampsia, 161 had cesarean section delivery, and 145 had labor induction. Of the patients with labor induction, 48.6% had a vaginal delivery, with 31.6% obtaining vaginal delivery at less than 28 weeks' gestation and 62% at more than 32 weeks' gestation (74).

  • A 2003 narrative review discussed decisions regarding delivery or expectant management (75).

Rationale
  • Vaginal delivery is preferred to cesarean section in women with preeclampsia because it avoids the added maternal stress of surgery.

Comments
  • At the initiation of the delivery process, cervical ripening during induction increases the success rate of a vaginal delivery if the cervix is initially unfavorable for induction.

  • A randomized trial compared the delivery of prostaglandin E2 as a 0.5-mg intracervical gel (n=34) with delivery as a 10-mg controlled-release vaginal insert (n=36), with both regimens followed by oxytocin administration in 70 women with preeclampsia undergoing cervical ripening for labor induction. The mean time from beginning of therapy to delivery was decreased in the intracervical-gel group (intracervical-gel group, 11.5 ± 2.3 hours; vaginal-insert group, 25.8 ± 6.9 hours; P<0.001) (76).

Administer magnesium sulfate in patients with eclampsia or severe preeclampsia.  
  • Administer magnesium sulfate to prevent seizures

    • In patients with severe preeclampsia during vaginal delivery or cesarean section

    • In patients with severe preeclampsia during the immediate postpartum period

    • In patients with eclampsia

  • Do not administer magnesium sulfate to patients with mild preeclampsia.

  • Monitor deep-tendon reflexes closely for signs of magnesium sulfate overdose, which are lost at serum levels of about 8 mg/dL.

  • See table Drug Treatment for Preeclampsia.

Evidence
  • A 2014 guideline on hypertensive disorders of pregnancy from the Society of Obstetricians and Gynaecologists of Canada recommended magnesium as first-line therapy for eclampsia or to prevent eclampsia in women with severe preeclampsia.

  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended magnesium sulfate for patients with eclampsia and for those with severe preeclampsia during vaginal delivery or cesarean section and in the immediate postpartum period. The task force recommended against magnesium sulfate for patients with mild preeclampsia.

  • A 2010 NICE guideline on the management of hypertensive disorders of pregnancy recommended magnesium sulfate for patients with eclampsia and for those with severe preeclampsia in critical care settings in whom delivery is planned within 24 hours.

  • A 2010 Cochrane review of magnesium sulfate for patients with preeclampsia included randomized trials with 11,444 participants. Compared with placebo or no anticonvulsant, magnesium sulfate significantly reduced the risk for eclampsia (RR, 0.41 [CI, 0.29 to 0.58]); number needed to treat, 100), with a trend toward reduction in maternal death (RR, 0.54 [CI, 0.26 to 1.10]). Magnesium sulfate also reduced the risk for placental abruption (RR, 0.64 [CI, 0.50 to 0.83]) (77).

  • A 2009 Cochrane review of magnesium sulfate in women at risk for preterm (<37 weeks) birth included 5 randomized trials involving 6145 babies. Antenatal magnesium sulfate reduced the risk for cerebral palsy (RR, 0.68 [CI, 0.54 to 0.87]) and gross motor dysfunction (RR, 0.61 [CI, 0.44 to 0.85]) in infants but did not affect pediatric mortality (RR, 1.04 [CI, 0.92 to 1.17]) (78).

  • A randomized, controlled trial compared 60 mg of oral nimodipine every 4 hours (n=819) with intravenous magnesium sulfate by protocol (n=831) in gravidas with severe preeclampsia. The rate of eclampsia was higher in the nimodipine group (2.6% in the nimodipine group and 0.8% in the magnesium group; RR, 3.2 [CI, 1.1 to 9.1]) (79).

  • A cohort study assessed outcomes after 2 to 3 years in women who had participated in a randomized trial that compared magnesium sulfate with placebo for preeclampsia. Long-term follow-up data were obtained for 3375 women, representing 71% of eligible patients. Rates of death or serious morbidity were similar in the magnesium sulfate (3.5%) and placebo (4.2%) groups (RR, 0.84 [CI, 0.60 to 1.18]) (80).

  • A cohort study assessed outcomes after 18 months in the children of women who had participated in a randomized trial comparing magnesium sulfate with placebo for preeclampsia. The study included 3283 children, representing 73% of eligible children. Rates of death or neurosensory disability were similar in the magnesium sulfate (15.0%) and placebo (14.1%) groups (RR, 1.06 [CI, 0.90 to 1.25]). Among children who survived, rates of neurosensory disability were similar in the magnesium sulfate (1.3%) and placebo (1.9%) groups (81).

Rationale
  • Magnesium sulfate can prevent recurrent seizure in eclampsia.

  • Magnesium sulfate is the most effective medication for seizure prophylaxis in preeclampsia since it halves the risk for eclampsia.

  • Antenatal magnesium sulfate therapy given to women at risk for preterm birth has a clear neuroprotective role for the fetus.

Comments
  • Seizure prophylaxis is indicated in both mild and severe preeclampsia in the peripartum period until larger clinical trials substantiate the safety of withholding therapy.

  • The use of magnesium sulfate for preeclampsia does not appear to reduce long-term maternal and child mortality.

Inform patients about the diagnosis, management, and course of preeclampsia. 
  • Discuss with patients

    • The criteria for diagnosis of mild and severe preeclampsia

    • The unknown etiology of preeclampsia

    • Warning signs and symptoms of preeclampsia, including

      • Visual changes (scotomata, blurred vision)

      • Persistent/severe headache

      • Epigastric pain

      • Decreased fetal movement

      • Severe abdominal pain

      • Vaginal bleeding

    • The rationale for hospitalization

    • How preeclampsia progresses in severity at variable rates of speed

    • Non-drug therapy used in managing preeclampsia, including bed rest and route of delivery

    • Medications used in preeclampsia management

    • That delivery is the only definitive treatment for preeclampsia

    • That patients generally improve within 24 hours after delivery of the fetus and placenta

    • That usually there are no permanent sequelae from preeclampsia unless the disease has been complicated by stroke or renal cortical necrosis

Evidence
  • Consensus.

Rationale
  • Patients need to know what signs and symptoms to report to their physician.

  • Informed patients are more likely to adhere to prescribed regimens and are better able to participate in decision making.

Comments
  • Preeclampsia is a pregnancy-specific syndrome of reduced organ perfusion related to vasospasm, activation of the coagulation cascade, and capillary leakage with subsequent decrease in intravascular volume.

  • The etiology of preeclampsia is unknown.

Discuss the long-term prognosis of preeclampsia. 
  • Inform patients that there is a risk for recurrence of preeclampsia in a future pregnancy based on

    • Gestational age at which the disease manifested (onset earlier than 30 weeks' gestation predisposes to greater recurrence risk than term preeclampsia)

    • The severity of disease (HELLP syndrome increases recurrence risk)

    • Parity (multiparous patients have greater recurrence risk than nulliparous patients)

    • Change in paternity (increases risk in multiparous patients over same paternity)

  • Inform patients with preeclampsia that they may be at risk for developing

    • Chronic hypertension

    • Chronic kidney disease

    • Postpartum metabolic syndrome

    • Cardiovascular disease, especially if they have multiple pregnancies or severe early-onset (preterm) preeclampsia, or develop preeclampsia as multipara

  • Reassure patients with preeclampsia that they do not appear to be at an increased risk for developing any cancer, including breast cancer.

  • Inform patients with early-onset preeclampsia that they do not appear to be at an increased risk for developing any cancer, including breast cancer.

Evidence
  • A 2008 systematic review of cardiovascular disease in patients with preeclampsia included 5 case-control and 10 cohort studies. Compared with women with uncomplicated pregnancies, those with preeclampsia or eclampsia were at increased risk for cardiac disease in both cohort (RR, 2.33 [CI, 1.95 to 2.78]) and case-control (OR, 2.47 [CI, 1.22 to 5.01]) studies. Patients with preeclampsia were also at increased risk for cerebrovascular disease (RR, 2.03 [CI, 1.54 to 2.67]) and cardiovascular mortality (RR, 2.29 [CI, 1.73 to 3.04]) (82).

  • A 2010 systematic review of kidney disease after preeclampsia included 7 cohort studies. After a mean of 7 years of follow-up time, rates of microalbuminuria were higher in patients with preeclampsia (31% vs. 7%) (83).

  • A 2007 systematic review of the risk for later cardiovascular disease on patients with preeclampsia included 25 observational studies. Compared with those with no history of preeclampsia, women with a history of preeclampsia were at an increased relative risk for hypertension of 3.70 (CI, 2.70 to 5.05) after 14.1 years weighted mean follow-up; for ischemic heart disease, 2.16 (CI, 1.86 to 2.52) after 11.7 years; for stroke, 1.81 (CI, 1.45 to 2.27) after 10.4 years; and for venous thromboembolism, 1.79 (CI, 1.37 to 2.33) after 4.7 years. No increase in risk for any cancer was found (RR, 0.96 [CI, 0.73 to 1.27]), including breast cancer (RR, 1.04 [CI, 0.78 to 1.39]), 17 years after preeclampsia. Overall mortality after preeclampsia was increased (RR, 1.49 [CI, 1.05 to 2.14) after 14.5 years (84).

  • A 2005 systematic review of risk factors for preeclampsia included 52 cohort and case-control studies. The risk for preeclampsia was increased in women with a previous history of preeclampsia (RR, 7.19 [CI, 5.85 to 8.83]), antiphospholipid antibodies (RR, 9.72 [CI, 4.34 to 21.75]), preexisting diabetes (RR, 3.56 [CI, 2.54 to 4.99]), multiple (twin) pregnancy (RR, 2.93 [CI, 2.04 to 4.21]), nulliparity (RR, 2.91 [CI, 1.28 to 6.61]), family history (RR, 2.90 [CI, 1.70 to 4.93]), raised blood pressure (diastolic ≥80 mm Hg) at booking (RR, 1.38 [CI, 1.01 to 1.87]), raised BMI before pregnancy (RR, 2.47 [CI, 1.66 to 3.67]) or at booking (RR, 1.55 [CI, 1.28 to 1.88]), or maternal age 40 years or older (RR, 1.96 [CI, 1.34 to 2.87], for multiparous women). Individual studies showed that risk was also increased with an interval of 10 years or more since a previous pregnancy, autoimmune disease, renal disease, and chronic hypertension (30).

  • A matched cohort study compared 406 women with severe preeclampsia/eclampsia in their first pregnancy with 409 women with no hypertension in their first pregnancy. All were followed for at least 2 years (range, 2 to 24 years). Hypertensive women had a higher incidence of preeclampsia in their second pregnancy (46.8% vs. 7.6%; P<0.0001) and of chronic hypertension (14.8% vs. 5.6%; P<0.001) compared with the normotensive group (85).

  • An observational study consisted of 125 women with severe preeclampsia in the second trimester who underwent follow-up for an average of 5.4 years. Of the 108 women with 169 subsequent pregnancies, 35% of the women were normotensive, 65% of the pregnancies were complicated by preeclampsia, and, overall, 21% of the pregnancies were complicated by severe preeclampsia in the second trimester. Patients with recurrent severe preeclampsia in the second trimester had the greatest risk for developing chronic hypertension (67%), with the lowest risk in women with normotensive subsequent pregnancies (4%) (86).

  • A randomized trial compared low-dose aspirin with placebo in 600 women with previous preeclampsia. The risk for recurrent preeclampsia was 17% in the aspirin group and 19% in the placebo group (RR, 0.9 [CI, 0.6 to 1.2]) (87).

  • A case-control study evaluated thromobophilic mutations in 110 patients with and 110 without obstetrical complications; 34 women had severe preeclampsia as their complication. Women with preeclampsia were more likely than those with normal pregnancy to have factor V Leiden homozygote or heterozygote mutation (OR, 5.3 [CI, 1.8 to 15.6]) and methylene tetrahydrofolate reductase homozygote mutation (OR, 2.9 [CI, 1.0 to 8.5]), but not prothrombin G20210A heterozygote mutation (OR, 2.2 [CI, 0.4 to 13.9]) (88).

  • An observational study of patients with severe early-onset preeclampsia tested for coagulation disturbances 10 weeks' postpartum. Of the 85 patients tested for protein S deficiency, 21 (24.7%) were affected. Of the 50 patients tested for activated protein C resistance, 8 (16.0%) were positive. Of the 79 patients tested for hyperhomocysteinemia, 14 (17.7%) had a positive methionine loading test. Of the 95 patients tested for anticardiolipin antibodies, 27 (29.4%) had detectable immunoglobulin G, M, or both anticardiolipin antibodies (89).

  • A study with data from two large national databases assessed the association between preeclampsia in one or more pregnancies and the subsequent development of end-stage renal disease. Among women who had been pregnant, preeclampsia during the first pregnancy was associated with an increased risk for end-stage renal disease (RR, 4.7 [CI, 3.6 to 6.1]). Among women who had two or more pregnancies, preeclampsia during the first pregnancy (RR, 3.2 [CI, 2.2 to 4.9]), preeclampsia during the second pregnancy (RR, 6.7 [CI, 4.3 to 10.6]), and preeclampsia during both pregnancies (RR, 6.4 [CI, 3.0 to 13.5]) were associated with an increased risk for end-stage renal disease. Among women who had been pregnant three or more times, preeclampsia during one pregnancy (RR, 6.3 [CI, 4.1 to 9.9]) and preeclampsia during two or three pregnancies (RR, 15.5 [CI, 7.8 to 30.8]) were associated with an increased risk for end-stage renal disease (90).

  • In a retrospective cohort study, 849 women with a history of pregnancy complicated by vascular disorders (preeclampsia; gestational hypertension; hemolysis, elevated liver enzymes, low platelets syndrome; eclampsia; placental abruption; fetal growth restriction; and stillbirth as a result of placental insufficiency) were divided into early-onset (delivery before 32 weeks of gestation, n=376) and late-onset (delivery at or beyond 32 weeks, n=473). Women with early-onset vascular complications were at increased risk for metabolic syndrome, with an adjusted OR of 2.51 (CI, 1.66 to 3.80) using the World Health Organization definition of metabolic syndrome (91).

Rationale
  • Patient education will help future pregnancy planning and decision making.

Comments
  • There is no evidence that patient education about these risk factors affects outcomes.

Follow patients with preeclampsia closely until delivery, and monitor for complications. 
  • Follow patients with nonsevere preeclampsia closely:

    • Monitor blood pressure at least twice weekly

    • Follow lab tests, including kidney function, blood counts, and liver testing 1 to 3 times per week

  • Follow up on any previously abnormal laboratory tests.

  • Advise patients to follow fetal movement closely and report any decrease in activity.

Evidence
  • A 2013 report of the ACOG Task Force on Hypertension in Pregnancy recommended that patients with preeclampsia closely monitor fetal activity and that blood pressure be checked at least twice weekly.

  • A 2010 NICE guideline on the management of hypertensive disorders of pregnancy recommended measuring blood pressure at least 4 times per day, monitoring blood tests at least 3 times per week (kidney function, electrolytes, liver function tests, CBC), and close clinical follow-up for women with preeclampsia.

Rationale
  • Patients need close follow-up to determine the need for urgent delivery.

Carefully evaluate patients who have had preeclampsia to exclude chronic disease in the first few months after delivery. 
  • Check blood pressure to determine whether it has returned to normal by 12 weeks' postpartum; if it remains elevated, it may represent chronic hypertension.

  • Follow up on any previously abnormal laboratory tests.

  • Screen for thrombophilias if the patient experienced early-onset severe preeclampsia, including testing for

    • Activated protein C resistance (factor V Leiden)

    • Antiphospholipid antibodies

    • Hyperhomocysteinemia

    • Protein S deficiency

  • Reinforce patient education issues in long-term prognosis and likelihood of recurrence.

Evidence
  • A 2008 systematic review of cardiovascular disease in patients with preeclampsia included 5 case-control and 10 cohort studies. Compared with women with uncomplicated pregnancies, those with preeclampsia or eclampsia were at increased risk for cardiac disease in both cohort (RR, 2.33 [CI, 1.95 to 2.78]) and case-control (OR, 2.47 [CI, 1.22 to 5.01]) studies. Patients with preeclampsia were also at increased risk for cerebrovascular disease (RR, 2.03 [CI, 1.54 to 2.67]) and cardiovascular mortality (RR, 2.29 [CI, 1.73 to 3.04]) (82).

  • A 2010 systematic review of kidney disease after preeclampsia included 7 cohort studies. After a mean of 7 years of follow-up time, rates of microalbuminuria were higher in patients with preeclampsia (31% vs. 7%) (83).

  • A 2007 systematic review of the risk for later cardiovascular disease in patients with preeclampsia included 25 observational studies. Compared with those with no history of preeclampsia, women with history of preeclampsia were at an increased risk for hypertension (RR, 3.70 [CI, 2.70 to 5.05]) after 14.1 years weighted mean follow-up; for ischemic heart disease (RR, 2.16 [CI, 1.86 to 2.52]) after 11.7 years; for stroke (RR, 1.81 [CI, 1.45 to 2.27]) after 10.4 years; and for venous thromboembolism (RR, 1.79 [CI, 1.37 to 2.33]) after 4.7 years. No increase in risk for any cancer was found (RR, 0.96 [CI, 0.73 to 1.27]), including breast cancer (RR, 1.04 [CI, 0.78 to 1.39]), 17 years after preeclampsia. Overall mortality after preeclampsia was increased (RR, 1.49 [CI, 1.05 to 2.14) after 14.5 years (84).

  • An observational study evaluated rates of coagulation disorders 10 weeks' postpartum in patients with severe early-onset preeclampsia. Among 101 patients, 39% had chronic hypertension. Among those tested for each disorder, protein S deficiency was found in 25%, activated protein C resistance was found in 16%, hyperhomocysteinemia was found in 18%, and anticardiolipin IgG and/or IgM antibodies were found in 29% (89).

Rationale
  • Postpartum visits are important to exclude chronic disease and provide information that will help in planning future pregnancies.

Table Grahic Jump Location
 Laboratory and Other Studies for Preeclampsia

Swipe to view table

TestNotes
Timed (24-hour) urine collection for proteinReference standard for determining proteinuria. Proteinuria defined as protein excretion ≥300 mg in 24 hours
Urinary dipstick for proteinAccuracy is poor. Only recommended if there are no other available tests methodologic quality (51)
Timed (12-hour) urine collection for proteinTwelve-hour protein >165 mg has a sensitivity of 96% and a specificity of 100%
Urine protein-to-creatinine ratioCutoff of ≥30 mg/mmol or 0.30 mg/dL is generally used, although sensitivity (81%) and specificity (76%) are moderate
Serum creatinineNormal creatinine in pregnancy is <0.8 mg/dL and creatinine clearance is as high as 150 mg/d
HematocritCan see hemoconcentration in preeclampsia
Platelet countThrombocytopenia with platelet count <100,000 can be a sign of severe preeclampsia
Peripheral blood smearSchistocytes and burr cells can be seen in severe preeclampsia, representing microangiopathic hemolytic anemia
Liver transaminases (AST or ALT)Elevated transaminase levels more than twice the upper limit of normal are a sign of severe preeclampsia
Lactate dehydrogenaseIncreased with preeclampsia
AlbuminCan be decreased even with minimal proteinuria
BilirubinElevated in hemolysis
Fetal ultrasoundTo assess fetal growth and amniotic fluid volume. Fetal growth restriction (3rd to 10th percentile for gestational age), oligohydramnios by amniotic fluid index <5 cm, or absence of a 2 cm × 2 cm pocket can be seen in preeclampsia
Fetal nonstress test or biophysical profileTo assess fetal well-being. Due to the risk for uteroplacental insufficiency, fetal compromise can be found in preeclampsia

ALT = alanine aminotransferase; AST = aspartate aminotransferase.

Table Grahic Jump Location
 Differential Diagnosis of Preeclampsia

Swipe to view table

DiseaseCharacteristics
PreeclampsiaHypertension and proteinuria >300 mg/24 h after 20 weeks of gestation in a previously normotensive woman. Hypertension is defined as two blood pressure readings 6 hours apart with a systolic BP of ≥140 mm Hg or a diastolic BP of ≥90 mm Hg
Chronic hypertensionHypertension with BP >140/90 mm Hg diagnosed before pregnancy or before 20 weeks' gestation. Proteinuria can be present from preexisting hypertensive nephropathy
Gestational hypertensionHypertension with BP >140/90 mm Hg in the absence of proteinuria >300 mg/24 h presenting after 20 weeks' gestation.
Can progress to preeclampsia
Chronic kidney disease without hypertensionProteinuric renal dysfunction without associated hypertension present before 20 weeks' gestation.
Consider superimposed preeclampsia if sustained new-onset hypertension is present after 20 weeks' gestation
Chronic kidney disease with hypertensionProteinuric renal dysfunction with associated hypertension present before 20 weeks' gestation.
Superimposed preeclampsia can present with abrupt increase in blood pressure or reduction in renal function.
Often difficult to diagnose superimposed preeclampsia until signs and symptoms of neurologic or HELLP syndrome manifestations are present
Flare of SLECan have any of the manifestations of preeclampsia.
History of lupus, arthralgias, dermatologic manifestations is useful to suspect diagnosis. Other signs and symptoms of lupus or a decrease in complement levels can help differentiate from severe preeclampsia
Cocaine useManifestations can include neurologic changes, hypertension, thrombocytopenia, and placental abruption.
A history and toxicology screen can establish the presence of cocaine
Acute fatty liver of pregnancyNausea, vomiting, hypertension, abdominal pain, encephalopathy, and jaundice late in the third trimester or early in the postpartum period. Hypoglycemia, elevated bilirubin, elevated liver transaminases, coagulopathy, elevated ammonia levels.
Patients with acute fatty liver can develop secondary severe preeclampsia
Thrombotic thrombocytopenic purpuraPredominant neurologic symptoms, with petechiae, fever, microangiopathic hemolytic anemia, severe thrombocytopenia, and azotemia. Often antepartum.
There is elevation of liver transaminase levels, infrequent neurologic symptoms, and no fever with HELLP syndrome. Hypertension is not usually manifested in TTP
Hemolytic uremic syndromeRenal failure often requiring dialysis, neurologic manifestations, fever, microangiopathic hemolytic anemia, thrombocytopenia
HELLP syndrome does not manifest this degree of renal failure and fever
GlomerulonephritisAcute onset of hematuria, proteinuria, renal insufficiency, edema, and hypertension. Onset in second half of pregnancy.
Clinically indistinguishable from severe preeclampsia; may need renal biopsy
AppendicitisAnorexia, nausea, vomiting, right-sided abdominal pain and tenderness on palpation, adynamic ileus, uterine contractions common.
Preeclampsia does not usually present with adynamic ileus, and appendicitis does not usually present with hypertension
NephrolithiasisMost common presenting symptom is flank and abdominal pain. Can have transient hypertension, tachycardia due to pain. Can have mild proteinuria.
Hypertension resolves with pain control, and abdominal or flank pain is colicky in nature. Subcapsular hematoma pain in preeclampsia is constant and located in right upper quadrant

BP = blood pressure; HELLP = hemolysis, elevated liver enzymes, and low platelet (syndrome); SLE = systemic lupus erythematosus; TTP = thrombotic thrombocytopenic purpura.

Table Grahic Jump Location
 Drug Treatment for Preeclampsia

Swipe to view table

Drug or Drug ClassDosingSide EffectsPrecautionsClinical Use
FirstLineIconLabetalolIntermittent IV: 20-80 mg IV over 2 min. Repeat every 10 min prn. Maximum total dose 220 mgOrthostatic hypotension, bradycardia, CNS effects, bronchospasm, AV block, vomiting. Rare hepatotoxicityAvoid with asthma, HF. Caution with CKD, hepatic disease, hyperthyroidismPersistent DBP 100-110 mm Hg
FirstLineIconHydralazine5 mg IV every 20 min. Maximum total dose 20 mgOrthostatic hypotension, tachycardia, headache, palpitations, GI side effects, drowsiness, angina, flushing, edema, lupus-like symptoms, blood dyscrasiasCaution with severe CKDPersistent DBP 100-110 mm Hg
Nifedipine10 mg PO. May repeat in 30 min. 30-90 mg PO daily, may be divided tidHeadache, edema, flushing, CNS side effects, GI side effects, rare allergic hepatitisAvoid concomitant magnesium. Caution with severe bradycardia, HF, hepatic disease, reflux esophagitis, aortic stenosisAcute or chronic treatment of uncontrolled hypertension. Do not use rapidly acting capsule or sublingual administration
blackboxiconNitroprusside (Nitropress)0.25-5 mcg/kg·min IV infusionHeadache, nausea, vomitingblackboxicon Requires dilution. Significant drop in BP. Cyanide toxicity. Avoid with hepatic disease. Decrease dose with CrCl<60Uncontrolled HTN. Use in critical care unit
FirstLineIconMagnesium sulfate4-6 g IV loading dose, then 2 g/h infusionInjection-site reactions, hypermagnesemiaAvoid with AV block, CrCl<20. Monitor for signs of overdoseSeizure prevention
CorticosteroidsIncreased glucose intolerance in diabetesFetal lung maturation in pregnancies of 24-34 weeks with preeclampsia
Betamethasone12 mg IM q24h for 2 doses total
Dexamethasone6 mg IM q12h for 4 doses total

FirstLineIcon = first-line agent; blackboxicon = black box warning; AV = atrioventricular; bid = twice daily; BP = blood pressure; CKD = chronic kidney disease; CNS = central nervous system; CrCl = creatinine clearance; DBP = diastolic blood pressure; GI = gastrointestinal; HF = heart failure; HTN = hypertension; IM = intramuscular; IV = intravenous; PO = oral; prn = as needed; q12h = every 12 hours; qd = once daily; qid = four times daily; SC = subcutaneous; SCr = serum creatinine; tid = three times daily.

ACP Smart Medicine provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

LeFevre ML. Low-Dose Aspirin Use for the Prevention of Morbidity and Mortality From Preeclampsia: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2014 09 09 [Epub ahead of print]. [Full Text] (PMID: 25200125)
 
Henderson JT, Whitlock EP, O’Connor E, Senger CA, Thompson JH, Rowland MG. Low-Dose Aspirin for Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2014;160:695-703. [Full Text] (PMID: 24711050)
 
Askie LM, Duley L, Henderson-Smart DJ, Stewart LA; PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet. 2007;369:1791-8. (PMID: 17512048)
 
Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007;(2):CD004659. (PMID: 17443552)
 
Villa PM, Kajantie E, Räikkönen K, Pesonen AK, Hämäläinen E, Vainio M, et al.; PREDO Study group. Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised placebo-controlled PREDO Trial and a meta-analysis of randomised trials. BJOG. 2013;120:64-74. (PMID: 23126307)
 
Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2010;(8):CD001059. (PMID: 20687064)
 
Rumbold A, Duley L, Crowther CA, Haslam RR. Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev. 2008;(1):CD004227. (PMID: 18254042)
 
Polyzos NP, Mauri D, Tsappi M, Tzioras S, Kamposioras K, Cortinovis I, et al. Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: a systematic review. Obstet Gynecol Surv. 2007;62:202-6. (PMID: 17306042)
 
Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ. 2013;346:f1169. (PMID: 23533188)
 
De-Regil LM, Palacios C, Ansary A, Kulier R, Peña-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2012;:CD008873. (PMID: 22336854)
 
Vadillo-Ortega F, Perichart-Perera O, Espino S, Avila-Vergara MA, Ibarra I, Ahued R, et al. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. BMJ. 2011;342:d2901. (PMID: 21596735)
 
Bodnar LM, Tang G, Ness RB, Harger G, Roberts JM. Periconceptional multivitamin use reduces the risk of preeclampsia. Am J Epidemiol. 2006;164:470-7. (PMID: 16772374)
 
McCance DR, Holmes VA, Maresh MJ, Patterson CC, Walker JD, Pearson DW, et al.; Diabetes and Pre-eclampsia Intervention Trial (DAPIT) Study Group. Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial. Lancet. 2010;376:259-66. (PMID: 20580423)
 
Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, Leveno KJ, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 2010;362:1282-91. (PMID: 20375405)
 
Villar J, Purwar M, Merialdi M, Zavaleta N, Thi Nhu Ngoc N, Anthony J, et al.; WHO Vitamin C and Vitamin E trial group. World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries. BJOG. 2009;116:780-8. (PMID: 19432566)
 
Spinnato JA, Freire S, Pinto E Silva JL, Cunha Rudge MV, Martins-Costa S, Koch MA, et al. Antioxidant therapy to prevent preeclampsia: a randomized controlled trial. Obstet Gynecol. 2007;110:1311-8. (PMID: 18055726)
 
Spinnato JA, Freire S, Pinto e Silva JL, Rudge MV, Martins-Costa S, Koch MA, et al. Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis. Am J Obstet Gynecol. 2008;199:433.e1-8. (PMID: 18928997)
 
Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS; ACTS Study Group. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med. 2006;354:1796-806. (PMID: 16641396)
 
Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH; Vitamins in Pre-eclampsia (VIP) Trial Consortium. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet. 2006;367:1145-54. (PMID: 16616557)
 
Dawodu A, Saadi HF, Bekdache G, Javed Y, Altaye M, Hollis BW. Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. J Clin Endocrinol Metab. 2013;98:2337-46. (PMID: 23559082)
 
Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011;26:2341-57. (PMID: 21706518)
 
Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009;361:1339-48. (PMID: 19797280)
 
Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T, Tomlinson JW, et al. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ. 2012;344:e2088. (PMID: 22596383)
 
Meher S, Duley L. Exercise or other physical activity for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2006;(2):CD005942. (PMID: 16625645)
 
Meher S, Duley L. Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure. Cochrane Database Syst Rev. 2006;(2):CD005939. (PMID: 16625644)
 
Makrides M, Duley L, Olsen SF. Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction. Cochrane Database Syst Rev. 2006;(3):CD003402. (PMID: 16856006)
 
Duley L, Henderson-Smart D, Meher S. Altered dietary salt for preventing pre-eclampsia, and its complications. Cochrane Database Syst Rev. 2005;(4):CD005548. (PMID: 16235411)
 
Ziaei S, Hantoshzadeh S, Rezasoltani P, Lamyian M. The effect of garlic tablet on plasma lipids and platelet aggregation in nulliparous pregnants at high risk of preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2001;99:201-6. (PMID: 11788172)
 
Churchill D, Beevers GD, Meher S, Rhodes C. Diuretics for preventing pre-eclampsia. Cochrane Database Syst Rev. 2007;(1):CD004451. (PMID: 17253507)
 
Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ. 2005;330:565. (PMID: 15743856)
 
Cnossen JS, Vollebregt KC, de Vrieze N, ter Riet G, Mol BW, Franx A, Khan KS, vam der Post JA. Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis. BMJ. 2008;336:1117-20. (PMID: 18480117)
 
Conde-Agudelo A, Villar J, Lindheimer M. Maternal infection and risk of preeclampsia: systematic review and metaanalysis. Am J Obstet Gynecol. 2008;198:7-22. (PMID: 18166297)
 
Murphy VE, Namazy JA, Powell H, Schatz M, Chambers C, Attia J, et al. A meta-analysis of adverse perinatal outcomes in women with asthma. BJOG. 2011;118:1314-23. (PMID: 21749633)
 
North RA, McCowan LM, Dekker GA, Poston L, Chan EH, Stewart AW, et al. Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort. BMJ. 2011;342:d1875. (PMID: 21474517)
 
Roos N, Kieler H, Sahlin L, Ekman-Ordeberg G, Falconer H, Stephansson O. Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study. BMJ. 2011;343:d6309. (PMID: 21998337)
 
Kahn SR, Platt R, McNamara H, Rozen R, Chen MF, Genest J, et al. Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study. Am J Obstet Gynecol. 2009;200:151.e1-9; discussion e1-5. (PMID: 19070828)
 
Wikström Shemer E, Marschall HU, Ludvigsson JF, Stephansson O. Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study. BJOG. 2013;120:717-23. (PMID: 23418899)
 
Bolin M, Åkerud H, Cnattingius S, Stephansson O, Wikström AK. Hyperemesis gravidarum and risks of placental dysfunction disorders: a population-based cohort study. BJOG. 2013;120:541-7. (PMID: 23360164)
 
Louis J, Auckley D, Miladinovic B, Shepherd A, Mencin P, Kumar D, et al. Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women. Obstet Gynecol. 2012;120:1085-92. (PMID: 23090526)
 
Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol. 2012;119:315-20. (PMID: 22270283)
 
Kleinrouweler CE, Bossuyt PM, Thilaganathan B, Vollebregt KC, Arenas Ramírez J, Ohkuchi A, et al. Value of adding second-trimester uterine artery Doppler to patient characteristics in identification of nulliparous women at increased risk for pre-eclampsia: an individual patient data meta-analysis. Ultrasound Obstet Gynecol. 2013;42:257-67. (PMID: 23417857)
 
Cnossen JS, Morris RK, ter Riet G, Mol BW, van der Post JA, Coomarasamy A, et al. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis. CMAJ. 2008;178:701-11. (PMID: 18332385)
 
Conde-Agudelo A, Villar J, Lindheimer M. World Health Organization systematic review of screening tests for preeclampsia. Obstet Gynecol. 2004;104:1367-91. (PMID: 15572504)
 
Widmer M, Villar J, Benigni A, Conde-Agudelo A, Karumanchi SA, Lindheimer M. Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review. Obstet Gynecol. 2007;109:168-80. (PMID: 17197602)
 
Myatt L, Clifton RG, Roberts JM, Spong CY, Hauth JC, Varner MW, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). The utility of uterine artery Doppler velocimetry in prediction of preeclampsia in a low-risk population. Obstet Gynecol. 2012;120:815-22. (PMID: 22996099)
 
Meler E, Figueras F, Bennasar M, Gomez O, Crispi F, Gratacos E. The prognostic role of uterine artery Doppler investigation in patients with severe early-onset preeclampsia. Am J Obstet Gynecol. 2010;202:559.e1-4. (PMID: 20347432)
 
Ghi T, Youssef A, Piva M, Contro E, Segata M, Guasina F, et al. The prognostic role of uterine artery Doppler studies in patients with late-onset preeclampsia. Am J Obstet Gynecol. 2009;201:36.e1-5. (PMID: 19380119)
 
Levine RJ, Ewell MG, Hauth JC, Curet LB, Catalano PM, Morris CD, et al. Should the definition of preeclampsia include a rise in diastolic blood pressure of ≥15 mm Hg to a level <90 mm Hg in association with proteinuria? Am J Obstet Gynecol. 2000;183:787-92. (PMID: 11035314)
 
Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ. 1994;309:1395-400. (PMID: 7819845)
 
Morris RK, Riley RD, Doug M, Deeks JJ, Kilby MD. Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis. BMJ. 2012;345:e4342. (PMID: 22777026)
 
Waugh JJ, Clark TJ, Divakaran TG, Khan KS, Kilby MD. Accuracy of urinalysis dipstick techniques in predicting significant proteinuria in pregnancy. Obstet Gynecol. 2004;103:769-77. (PMID: 15051572)
 
Tun C, Quiñones JN, Kurt A, Smulian JC, Rochon M. Comparison of 12-hour urine protein and protein:creatinine ratio with 24-hour urine protein for the diagnosis of preeclampsia. Am J Obstet Gynecol. 2012;207:233.e1-8. (PMID: 22939731)
 
von Dadelszen P, Payne B, Li J, Ansermino JM, Broughton Pipkin F, Côté AM, et al.; PIERS Study Group. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet. 2011;377:219-27. (PMID: 21185591)
 
Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183:S1-S22. (PMID: 10920346)
 
Wallace DH, Leveno KJ, Cunningham FG, Giesecke AH, Shearer VE, Sidawi JE. Randomized comparison of general and regional anesthesia for cesarean delivery in pregnancies complicated by severe preeclampsia. Obstet Gynecol. 1995;86:193-9. (PMID: 7617349)
 
Hood DD, Curry R. Spinal versus epidural anesthesia for cesarean section in severely preeclamptic patients: a retrospective survey. Anesthesiology. 1999;90:1276-82. (PMID: 10319773)
 
Turnbull DA, Wilkinson C, Gerard K, Shanahan M, Ryan P, Griffith EC, et al. Clinical, psychosocial, and economic effects of antenatal day care for three medical complications of pregnancy: a randomised controlled trial of 395 women. Lancet. 2004;363:1104-9. (PMID: 15064028)
 
Koopmans CM, Bijlenga D, Groen H, Vijgen SM, Aarnoudse JG, Bekedam DJ, et al.; HYPITAT study group. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet. 2009;374:979-88. (PMID: 19656558)
 
Tajik P, van der Tuuk K, Koopmans CM, Groen H, van Pampus MG, van der Berg PP, et al. Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial. BJOG. 2012;119:1123-30. (PMID: 22703475)
 
Vijgen SM, Koopmans CM, Opmeer BC, Groen H, Bijlenga D, Aarnoudse JG, et al.; HYPITAT study group. An economic analysis of induction of labour and expectant monitoring in women with gestational hypertension or pre-eclampsia at term (HYPITAT trial). BJOG. 2010;117:1577-85. (PMID: 20840526)
 
Sibai BM, Mercer BM, Schiff E, Friedman SA. Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial. Am J Obstet Gynecol. 1994;171:818-22. (PMID: 8092235)
 
Odendaal HJ, Pattinson RC, Bam R, Grove D, Kotze TJ. Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial. Obstet Gynecol. 1990;76:1070-5. (PMID: 2234715)
 
Bombrys AE, Barton JR, Nowacki EA, Habli M, Pinder L, How H, et al. Expectant management of severe preeclampsia at less than 27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management. Am J Obstet Gynecol. 2008;199:247.e1-6. (PMID: 18771971)
 
Belghiti J, Kayem G, Tsatsaris V, Goffinet F, Sibai BM, Haddad B. Benefits and risks of expectant management of severe preeclampsia at less than 26 weeks gestation: the impact of gestational age and severe fetal growth restriction. Am J Obstet Gynecol. 2011;205:465.e1-6. (PMID: 21889120)
 
Meher S, Abalos E, Carroli G, Meher S. Bed rest with or without hospitalisation for hypertension during pregnancy. Cochrane Database Syst Rev. 2005:CD003514. (PMID: 16235323)
 
Duley L, Meher S, Jones L. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2013;(7):CD001449. (PMID: 23900968)
 
Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003;327:955-60. (PMID: 14576246)
 
Vermillion ST, Scardo JA, Newman RB, Chauhan SP. A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy. Am J Obstet Gynecol. 1999;181:858-61. (PMID: 10521742)
 
Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;(3):CD004454. (PMID: 16856047)
 
Amorim MM, Santos LC, Faúndes A. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. Am J Obstet Gynecol. 1999;180:1283-8. (PMID: 10329891)
 
Murphy KE, Hannah ME, Willan AR, Hewson SA, Ohlsson A, Kelly EN, et al; MACS Collaborative Group. Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial. Lancet. 2008;372:2143-51. (PMID: 19101390)
 
Alexander JM, Bloom SL, McIntire DD, Leveno KJ. Severe preeclampsia and the very low birth weight infant: is induction of labor harmful? Obstet Gynecol. 1999;93:485-8. (PMID: 10214819)
 
Alanis MC, Robinson CJ, Hulsey TC, Ebeling M, Johnson DD. Early-onset severe preeclampsia: induction of labor vs elective cesarean delivery and neonatal outcomes. Am J Obstet Gynecol. 2008;199:262.e1-6. (PMID: 18771976)
 
Nassar AH, Adra AM, Chakhtoura N, Gómez-Marín O, Beydoun S. Severe preeclampsia remote from term: labor induction or elective cesarean delivery? Am J Obstet Gynecol. 1998;179:1210-3. (PMID: 9822502)
 
Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol. 2003;102:181-92. (PMID: 12850627)
 
Hennessey MH, Rayburn WF, Stewart JD, Liles EC. Pre-eclampsia and induction of labor: a randomized comparison of prostaglandin E2 as an intracervical gel, with oxytocin immediately, or as a sustained-release vaginal insert. Am J Obstet Gynecol. 1998;179:1204-9. (PMID: 9822501)
 
Duley L, Gülmezoglu AM, Henderson-Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010;(11):CD000025. (PMID: 21069663)
 
Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009;(1):CD004661. (PMID: 19160238)
 
Belfort MA, Anthony J, Saade GR, Allen JC Jr. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003;348:304-11. (PMID: 12540643)
 
Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for women at 2 years. BJOG. 2007;114:300-9. (PMID: 17166220)
 
Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BJOG. 2007;114:289-99. (PMID: 17166221)
 
McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J. 2008;156:918-30. (PMID: 19061708)
 
McDonald SD, Han Z, Walsh MW, Gerstein HC, Devereaux PJ. Kidney disease after preeclampsia: a systematic review and meta-analysis. Am J Kidney Dis. 2010;55:1026-39. (PMID: 20346562)
 
Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335:974. (PMID: 17975258)
 
Sibai BM, el-Nazer A, Gonzalez-Ruiz A. Severe preeclampsia-eclampsia in young primigravid women: subsequent pregnancy outcome and remote prognosis. Am J Obstet Gynecol. 1986;155:1011-6. (PMID: 3777042)
 
Sibai BM, Mercer B, Sarinoglu C. Severe preeclampsia in the second trimester: recurrence risk and long-term prognosis. Am J Obstet Gynecol. 1991;165:1408-12. (PMID: 1957870)
 
Caritis S, Sibai B, Hauth J, Lindheimer MD, Klebanoff M, Thom E, et al. Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med. 1998;338:701-5. (PMID: 9494145)
 
Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med. 1999;340:9-13. (PMID: 9878639)
 
Dekker GA, de Vries JI, Doelitzsch PM, Huijgens PC, von Blomberg BM, Jakobs C, et al. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol. 1995;173:1042-8. (PMID: 7485291)
 
Vikse BE, Irgens LM, Leivestad T, Skjaerven R, Iversen BM. Preeclampsia and the risk of end-stage renal disease. N Engl J Med. 2008;359:800-9. (PMID: 18716297)
 
Stekkinger E, Zandstra M, Peeters LL, Spaanderman ME. Early-onset preeclampsia and the prevalence of postpartum metabolic syndrome. Obstet Gynecol. 2009;114:1076-84. (PMID: 20168110)
 
ACOG

American Congress of Obstetricians and Gynecologists

ALT

alanine aminotransferase

AST

aspartate aminotransferase

BMI

body mass index

BP

blood pressure

CBC

complete blood (cell) count

CI

confidence interval

CNS

central nervous system

HELLP

hemolysis, elevated liver enzymes, and low platelet (syndrome)

im

intramuscular

iv

intravenous

LDH

lactate dehydrogenase

LR

likelihood ratio

NICE

National Institute for Health and Care Excellence

NPV

negative predictive value

OR

odds ratio

po

orally

PPV

positive predictive value

PT

prothrombin time

PTT

Partial thromboplastin time

RR

relative risk, or risk ratio

SD

standard deviation

sFlt-1

soluble fms-like tyrosine kinase-1 receptor

SLE

systemic lupus erythematosus

TTP

thrombotic thrombocytopenic purpura


Terms
Biophysical profile

A nonstress test combined with an obstetric ultrasound using a total of five components to gauge fetal well-being (nonstress test result, amniotic fluid volume, fetal breathing movements, fetal gross body movements, and fetal tone)

Eclampsia

Preeclampsia with the presence of seizures. Typically seizures present as generalized tonic-clonic seizures with no unilateral signs or symptoms

HELLP syndrome

Atypical form of severe preeclampsia characterized by hemolysis, elevated liver enzymes, and low platelet count. Schistocytes can be present on peripheral smear

Nonstress test

A fetal heart rate recording obtained by applying an external Doppler monitor to the mother's abdomen, combined with an external tocodynamometer to record any uterine activity. The graphic information obtained can be used to gauge fetal well-being


Guidelines

Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia

Diagnosis. evaluation, and management of hypertensive disorders of pregnancy: executive summary

National Institute for Health and Clinical Excellence: Hypertension in pregnancy

ACOG Task Force on Hypertension in Pregnancy: Hypertension in pregnancy

Systematic Reviews

U.S. Preventive Services Task Force: Low-dose aspiring for prevention of morbidity and mortality from preeclampsia

Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis

Kidney disease after preeclampsia: a systematic review and meta-analysis

Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth (Cochrane review)

Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis

Drugs for treatment of very high blood pressure during pregnanc (Cochrane review)

Bed rest with or without hospitalisation for hypertension during pregnancy (Cochrane review)

Accuracy of urinalysis dipstick techniques in predicting significant proteinuria in pregnancy

Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis

Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review

World Health Organization systematic review of screening tests for preeclampsia

Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis

Value of adding second-trimester uterine artery Doppler to patient characteristics in identification of nulliparous women at increased risk for pre-eclampsia: an individual patient data meta-analysis

A meta-analysis of adverse perinatal outcomes in women with asthma

Maternal infection and risk of preeclampsia: systematic review and metaanalysis

Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis

Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies

Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis

Antiplatelet agents for preventing pre-eclampsia and its complications (Cochrane review)

Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data

Diuretics for preventing pre-eclampsia (Cochrane review)

Vitamin D supplementation for women during pregnancy (Cochrane review)

Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies

Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: a systematic review

Antioxidants for preventing pre-eclampsia (Cochrane review)

Altered dietary salt for preventing pre-eclampsia, and its complications (Cochrane review)

Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction (Cochrane review)

Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure (Cochrane review)

Exercise or other physical activity for preventing pre-eclampsia and its complications (Cochrane review)

Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems

Magnesium sulphate and other anticonvulsants for women with pre-eclampsia

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus

DOI: 10.7326/d944
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
Disclosures:
Christy M. Isler, MD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Nikolaos P. Polyzos, MD, PhD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations.
Deborah Korenstein, MD, FACP, Editor in Chief, ACP Smart Medicine, has no relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. Richard B. Lynn, MD, FACP, Editor, ACP Smart Medicine, has no relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients.
Related Content
Annals of Internal Medicine