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Xử trí tiền sản giật (không chỉ vế vấn đề gây mê hồi sức)
Preeclampsia: Management and prognosis
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/contributorsErrol R Norwitz, MD, PhD, MBA
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/contributorsJohn T Repke, MD
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/contributorsCharles J Lockwood, MD, MHCM
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/contributorsVanessa A Barss, MD, FACOG
All topics are updated as new evidence becomes available and our
https://www.uptodate.com/home/editorial-policypeer review process is complete.
Literature review current through: Jun 2017. | This topic last updated: Mar 21, 2017.
INTRODUCTION — Preeclampsia is a multi-system, progressive disorder characterized by the new onset of hypertension and proteinuria or hypertension and end-organ dysfunction with or without proteinuria in the last half of pregnancy (
https://www.uptodate.com/contents/image?imageKey=OBGYN%2F79977&topicKey=OBGYN%2F6825&source=see_linktable 1). Progression from mild to severe on the disease spectrum (
https://www.uptodate.com/contents/image?imageKey=OBGYN%2F76975&topicKey=OBGYN%2F6825&source=see_linktable 2) may be gradual or rapid.
A key focus of routine prenatal care is monitoring pregnancies for signs and symptoms of preeclampsia. If the diagnosis is made, the definitive treatment is delivery to prevent development of maternal or fetal complications from disease progression: Delivery results in resolution of the disease. Timing of delivery is based upon a combination of factors, including disease severity, maternal and fetal condition, and gestational age.
This topic will discuss the management of pregnancies complicated by preeclampsia and maternal prognosis. Other important issues related to this disease are reviewed separately.
https://www.uptodate.com/contents/preeclampsia-clinical-features-and-diagnosis?source=see_link"Preeclampsia: Clinical features and diagnosis".)
https://www.uptodate.com/contents/early-pregnancy-prediction-of-preeclampsia?source=see_link"Early pregnancy prediction of preeclampsia".)
PREECLAMPSIA WITH FEATURES OF SEVERE DISEASE
General approach: Delivery — Preeclampsia with features of severe disease (formerly called severe preeclampsia) (
https://www.uptodate.com/contents/image?imageKey=OBGYN%2F76975&topicKey=OBGYN%2F6825&source=see_linktable 2) is generally regarded as an indication for delivery. Delivery minimizes the risk of development of serious maternal and fetal complications, such as cerebral hemorrhage, hepatic rupture, renal failure, pulmonary edema, seizure, bleeding related to thrombocytopenia, abruptio placenta, or fetal growth restriction [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/1-41-4]. With the exception of fetal growth restriction, any of these life-threatening complications can occur suddenly. (See
https://www.uptodate.com/contents/preeclampsia-clinical-features-and-diagnosis?source=see_link§ionName=SPECTRUM+OF+DISEASE&anchor=H3583231095"Preeclampsia: Clinical features and diagnosis", section on 'Spectrum of disease' and
https://www.uptodate.com/contents/preeclampsia-clinical-features-and-diagnosis?source=see_link§ionName=NATURAL+HISTORY%2FCOURSE+OF+DISEASE&anchor=H1933316941"Preeclampsia: Clinical features and diagnosis", section on 'Natural history/course of disease'.)
Management of delivery is reviewed below. (See
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Intrapartum management' below.)
Conservative management of selected cases — Conservative management rather than delivery is reasonable for selected preterm pregnancies with preeclampsia with features of severe disease to reduce neonatal morbidity from preterm birth, even though the mother and fetus are at risk from disease progression. For consideration of this approach, both the mother and fetus should be stable and hospitalized in a hospital with an appropriate level of newborn care, closely monitored, and cared for by, or in consultation with, a maternal-fetal medicine specialist. We favor limiting conservative management to pregnancies ≥24 weeks and <34 weeks of gestation. Selection of appropriate candidates for this approach and management of these pregnancies are discussed separately. (See
https://www.uptodate.com/contents/expectant-management-of-preeclampsia-with-severe-features?source=see_link"Expectant management of preeclampsia with severe features".)
Pregnancies in which the fetus has not attained a viable gestational age, pregnancies ≥34 weeks of gestation, and pregnancies in which the maternal and/or fetal condition is unstable are not candidates for conservative management. Attempting to prolong pregnancy in these settings subjects the mother and fetus to significant risks with relatively small potential benefits; therefore, delivery is preferable.
PREECLAMPSIA WITHOUT FEATURES OF SEVERE DISEASE
Term pregnancies: Delivery — Experts consistently recommend delivery of women with preeclampsia at ≥37 weeks of gestation, even in the absence of features of severe disease (previously called "mild preeclampsia") [
The benefits of labor induction at ≥37 weeks of gestation were illustrated in a multicenter trial (HYPITAT) that randomly assigned 756 women with mild preeclampsia or gestational hypertension >360/7 weeks to induction of labor or conservative management withmaternal/fetal monitoring [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/88]. This trial showed that preeclamptic women benefited from early intervention, without incurring an increased risk of operative delivery or neonatal morbidity. Routine induction was associated with a 30 percent reduction in a composite of adverse maternal outcomes (31 versus 44 percent; relative risk [RR] 0.71, 95% CI 0.59-0.86), which was primarily driven by a reduction in patients who developed severe hypertension and was not significant for women at 360/7 to 366/7 weeks. The induced group delivered, on average, 1.2 weeks earlier than the control group and had a significantly lower rate of cesarean delivery (14 versus 19 percent). There were no significant differences between groups in neonatal outcome. The composite included maternal mortality, maternal morbidity (eclampsia, HELLP syndrome [Hemolysis, Elevated Liver enzymes, Low Platelet count], pulmonary edema, thromboembolic disease, placental abruption), progression to severe hypertension or proteinuria, and major postpartum hemorrhage. The trial was not large enough to determine whether small differences in newborn outcomes or induction between 36 and 37 weeks might be statistically significant.
Follow-up analyses showed that an unfavorable cervix was not a reason to avoid induction [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/9,109,10]. In a secondary analysis of data from this trial and DIGITAT (pregnancies complicated by fetal growth restriction), induction of labor at term in women with a median Bishop score of 3 (range 1 to 6) was not associated with a higher rate of cesarean delivery than conservative management, and approximately 85 percent of women in both groups achieved a vaginal delivery [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/1010]. Prostaglandins or a balloon catheter was used for cervical ripening.
In addition, an economic analysis of the HYPITAT trial (conducted in from the Netherlands) concluded induction was 11 percent less costly overall than expectant management with monitoring [
Preterm pregnancies: Conservative management — Before term, the risks of serious sequelae from disease progression need to be balanced with the risks of preterm birth. When mother and fetus are stable and without findings of serious end-organ dysfunction, a conservative approach with close monitoring for evidence of progression to the severe end of the disease spectrum is reasonable to achieve further fetal growth and maturity. However, at any gestational age, evidence of severe hypertension, serious maternal end-organ dysfunction (
https://www.uptodate.com/contents/image?imageKey=OBGYN%2F76975&topicKey=OBGYN%2F6825&source=see_linktable 2), or nonreassuring tests of fetal well-being are generally an indication for prompt delivery.
●<34 weeks of gestation – Prior to 340/7 weeks, guidelines from major medical organizations generally recommend conservative management of preeclampsia without features of severe disease, based on expert opinion, given the high risk of complications of prematurity [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/3,4,73,4,7]. We concur with this approach.
●34 to 36 weeks of gestation – The optimum management for women with preeclampsia without features of severe disease and stable maternal and fetal condition at 340/7 to 366/7 weeks is uncertain. Although there are serious maternal risks with conservative management, we believe conservative management is reasonable in fully informed patients because the absolute maternal risk of an adverse outcome is low and the neonatal benefits of delivery at term are substantial.
Data from the randomized HYPITAT-II trial and observational studies indicate that most patients with late-onset preterm disease will reach term without developing an adverse maternal outcome (thromboembolic disease, pulmonary edema, eclampsia, HELLP syndrome, placental abruption, maternal death). In HYPITAT-II, which included women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation, at least one of the above adverse outcomes occurred in 1.2 percent (2/165)of the immediate delivery group versus 2.5 percent (4/159) of the expectant management group, with no maternal deaths or cases of pulmonary edema [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/1212]. Newborns benefited from the extra time in utero: neonates in the immediate delivery group had a higher frequency of respiratory distress (5.7 versus 1.7 percent in the conservative monitoring group, relative risk [RR] 3.3, 95% CI 1.4-8.2).
Components of conservative management
Inpatient versus outpatient care — Close maternal monitoring upon diagnosis of preeclampsia is important to establish disease severity and the rate of progression. Hospitalization is useful for making these assessments and facilitates rapid intervention in the event of rapid progression. After the initial diagnostic evaluation, outpatient care is a cost-effective option for women with stable preeclampsia without severe features [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/13-1713-17]. Patients offered outpatient monitoring should be able to comply with frequent maternal and fetal evaluations (every one to three days) and should have ready access to medical care.
Outpatient care can be provided in the patient’s home or, where available, at an antenatal day care unit, which is a common approach in the United Kingdom [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/1818]. If signs or symptoms of disease progression are noted, hospitalization for more intensive monitoring and possible delivery is indicated.
There are limited data on outcome of outpatient management of preeclamptic women. An observational study and a randomized trial reported good outcomes, but these studies had too few subjects to detect clinically significant differences in outcome between inpatient and outpatient management [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/14,1514,15]. A systematic review of three trials with a total of 504 women with various complications of pregnancy observed no major differences in clinical outcomes for mothers or infants between antenatal day units or hospital admission [
Patient education — All women with preeclampsia should be aware of the signs and symptoms at the severe end of the disease spectrum and should monitor fetal movements daily [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/44]. If a woman develops severe or persistent headache, visual changes, shortness of breath, or right upper quadrant or epigastric pain, she should call her health care provider immediately. As with any pregnancy, decreased fetal movement, vaginal bleeding, abdominal pain, rupture of membranes, or uterine contractions should be reported immediately, as well.
Activity — Strict bedrest is unnecessary as there is no evidence that bedrest improves pregnancy outcome or delays progression of the disease [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/1919]. Furthermore, bedrest in hospitalized pregnant women has been associated with an increased risk of venous thromboembolism [
Restricted activity is often recommended since blood pressure is lower in rested patients. Resting in the left lateral decubitus position can augment uteroplacental flow, which may benefit pregnancies in which this is a concern. In all pregnant women, avoiding the supine sleep position can have favorable fetal effects and appears prudent [
Laboratory follow-up — The minimum laboratory evaluation should include platelet count, serum creatinine, and liver enzymes. These tests should be repeated at least weekly in women with preeclampsia without severe features to assess for disease progression, and more often if clinical signs and symptoms suggest worsening disease [
Although other laboratory abnormalities may occur (see
https://www.uptodate.com/contents/preeclampsia-clinical-features-and-diagnosis?source=see_link§ionName=Laboratory+findings&anchor=H2379046844"Preeclampsia: Clinical features and diagnosis", section on 'Laboratory findings'), the value of monitoring additional laboratory tests is less clear. A rising hematocrit can be useful to look for hemoconcentration, which suggests contraction of intravascular volume and progression to more severe disease, while a falling hematocrit may be a sign of hemolysis. An elevated serum indirect bilirubin and/or LDH concentration is a better marker for hemolysis. Hemolysis can be confirmed by observation of schistocytes and helmet cells on a blood smear (
https://www.uptodate.com/contents/image?imageKey=HEME%2F70851%7EHEME%2F50715&topicKey=OBGYN%2F6825&source=see_linkpicture 1A-B). (See
Since several clinical studies have shown that neither the rate of increase nor the amount of proteinuria affects maternal or perinatal outcome in the setting of preeclampsia [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/22-2522-25], repeated urinary protein estimations are not useful once the threshold of 300 mg/24 hours or random urine protein/creatinine ratio ≥0.3 mg/dL for the diagnosis of preeclampsia has been exceeded. At that point, serum creatinine alone can be used to monitor renal function. It is the practice of some providers, including the authors, to confirm a low positive protein creatinine ratio (0.3 to 0.6) with a 24-hour collection. (See
https://www.uptodate.com/contents/proteinuria-in-pregnancy-evaluation-and-management?source=see_link"Proteinuria in pregnancy: Evaluation and management" and
Treatment of hypertension — Blood pressure should be measured at least twice weekly in outpatients. The use of antihypertensive drugs to control mild hypertension (systolic blood pressure <160 mmHg and diastolic blood pressure <110 mmHg) in the setting of preeclampsia does not alter the course of the disease or diminish perinatal morbidity or mortality, and should be avoided in most patients. It does, however, reduce the occurrence of progression to severe hypertension. The indications for starting antihypertensive therapy, the choice of drug, and blood pressure goals are discussed in detail separately. (See
https://www.uptodate.com/contents/management-of-hypertension-in-pregnant-and-postpartum-women?source=see_link§ionName=Preeclampsia&anchor=H3"Management of hypertension in pregnant and postpartum women", section on 'Preeclampsia'.)
Sodium restriction below the recommended daily intake and diuretics have no role in routine therapy [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/26-2826-28]. Although intravascular vascular volume is reduced, a randomized trial showed that plasma volume expansion did not improve maternal or fetal outcome [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/2929]. Diuretics are only indicated for treatment of pulmonary edema.
Assessment of fetal growth — Early fetal growth restriction may be the first manifestation of preeclampsia and is a sign of severe uteroplacental insufficiency. We perform sonographic estimation of fetal weight to evaluate for growth restriction and oligohydramnios at the time of diagnosis of preeclampsia. If the initial examination is normal, we repeat the ultrasound examination every three weeks. Management of the growth restricted fetus is reviewed separately. (See
https://www.uptodate.com/contents/fetal-growth-restriction-evaluation-and-management?source=see_link"Fetal growth restriction: Evaluation and management".)
Assessment of fetal well-being — There are no data from randomized trials on which to base recommendations for the optimal type and frequency of antepartum fetal monitoring. We suggest daily fetal movement counts and twice weekly nonstress testing with assessment of amniotic fluid volume, or twice weekly biophysical profiles, beginning at the time of diagnosis of preeclampsia. Fetal testing is repeated promptly if there is an abrupt change in maternal condition. (See
https://www.uptodate.com/contents/nonstress-test-and-contraction-stress-test?source=see_link"Nonstress test and contraction stress test" and
https://www.uptodate.com/contents/the-fetal-biophysical-profile?source=see_link"The fetal biophysical profile".)
Evaluation of umbilical artery Doppler indices is useful if fetal growth restriction is suspected, as the results help in optimal timing of delivery. In a meta-analysis of 16 randomized trials in high-risk pregnancies (n = 10,225 infants), knowledge of umbilical artery Doppler velocimetry results resulted in a 29 percent reduction in perinatal death (RR 0.71, 95% CI 0.52-0.98; 1.2 versus 1.7 percent; number needed to treat 203, 95% CI 103-4352), primarily in pregnancies complicated by preeclampsia and/or growth restriction [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/3030]. The frequency of assessment depends on the findings; weekly assessment is reasonable when Doppler indices are normal. (See
https://www.uptodate.com/contents/doppler-ultrasound-of-the-umbilical-artery-for-fetal-surveillance?source=see_link"Doppler ultrasound of the umbilical artery for fetal surveillance".)
Antenatal corticosteroids — Although preeclampsia may accelerate fetal lung maturation, neonatal respiratory distress remains common in premature neonates of preeclamptic pregnancies [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/31,3231,32]. Antenatal corticosteroids (
https://www.uptodate.com/contents/betamethasone-drug-information?source=see_linkbetamethasone) to promote fetal lung maturity should be administered to women <34 weeks of gestation since they are at increased risk of progression to severe disease and preterm delivery. A course of steroids is administered when the clinician believes delivery within the next seven days is likely and neonatal resuscitation is planned. Use of steroids after 34 weeks is more complicated and discussed separately. (See
https://www.uptodate.com/contents/antenatal-corticosteroid-therapy-for-reduction-of-neonatal-respiratory-morbidity-and-mortality-from-preterm-delivery?source=see_link§ionName=GESTATIONAL+AGE+AT+ADMINISTRATION&anchor=H2439085065"Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Gestational age at administration'.)
Timing of delivery — For patients managed conservatively, delivery is indicated at 37 weeks of gestation or as soon as they develop preeclampsia with severe features (
https://www.uptodate.com/contents/image?imageKey=OBGYN%2F76975&topicKey=OBGYN%2F6825&source=see_linktable 2) or eclampsia, whether or not the cervix is favorable.
Route of delivery — The route of delivery is based on standard obstetrical indications. Observational data suggest that the decision to expedite delivery in the setting of preeclampsia with features of severe disease does not mandate immediate cesarean birth [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/4,33,344,33,34]. Cervical ripening agents can be used prior to induction if the cervix is not favorable [
https://www.uptodate.com/contents/techniques-for-ripening-the-unfavorable-cervix-prior-to-induction?source=see_link"Techniques for ripening the unfavorable cervix prior to induction".)
However, we believe that a prolonged induction and inductions with a low likelihood of success are best avoided. For example, cesarean delivery is reasonable for women with preeclampsia with severe features who are less than about 32 weeks of gestation and have a low Bishop score, given the high frequency of abnormal fetal heart rate tracings and failure of the cervix to dilate in this setting [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/35-3735-37]. Less than one-third of preterm inductions in this setting result in vaginal birth.
Intrapartum monitoring — Continuous maternal-fetal monitoring is indicated intrapartum to identify worsening hypertension; deteriorating maternal hepatic, renal, cardiopulmonary, neurologic, or hematologic function; abruptio placenta; or an abnormal fetal heart rate tracing. There are no evidence-based standards for the optimal approach.
Routine invasive maternal hemodynamic monitoring (arterial catheterization, central venous catheter placement) is not recommended, even in the setting of severe preeclampsia [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/44]. Most women can be managed without these invasive tools and should not be exposed to the risks associated with them.
However, information from an arterial or central venous catheter can be useful in selected complicated patients, such as those with severe cardiac disease, severe renal disease, severe oliguria, refractory hypertension, or pulmonary edema. Randomized trials have not been performed [
https://www.uptodate.com/contents/anesthesia-for-the-patient-with-preeclampsia?source=see_link§ionName=HEMODYNAMIC+MONITORING&anchor=H818074266"Anesthesia for the patient with preeclampsia", section on 'Hemodynamic monitoring'.)
Fluids — Fluid balance should be monitored closely to avoid excessive administration, since women with preeclampsia are at risk of pulmonary edema and significant third-spacing, especially at the severe end of the disease spectrum. A maintenance infusion of a balanced salt or isotonic saline solution at about 80 mL/hour is often adequate for a patient who is nil by mouth and has no ongoing abnormal fluid losses, such as bleeding [
Oliguria that does not respond to a modest trial of increased fluids (eg, a 300 mL fluid challenge) suggests renal insufficiency and should be tolerated to reduce the potential for iatrogenic pulmonary edema [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/3939]. In patients with renal insufficiency, it is important to revise the maintenance infusion rate to account for the volume of fluid used to infuse intravenous medications.
Management of hypertension — Severe hypertension in labor should be treated with intravenous
https://www.uptodate.com/contents/hydralazine-drug-information?source=see_linkhydralazine or oral
https://www.uptodate.com/contents/nifedipine-drug-information?source=see_linknifedipine to prevent stroke (
https://www.uptodate.com/contents/image?imageKey=OBGYN%2F110261&topicKey=OBGYN%2F6825&source=see_linktable 3). Antihypertensive medications do not prevent eclampsia. Drugs and doses are reviewed in detail separately. (See
https://www.uptodate.com/contents/management-of-hypertension-in-pregnant-and-postpartum-women?source=see_link§ionName=Acute+therapy&anchor=H8"Management of hypertension in pregnant and postpartum women", section on 'Acute therapy'.)
Candidates for seizure prophylaxis — We administer intrapartum and postpartum seizure prophylaxis to all women with preeclampsia, based on data from randomized trials that demonstrated that
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate treatment reduced the risk of eclampsia (see
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Drug of choice: Magnesium sulfate' below). Although seizure is an infrequent outcome in women without severe features of preeclampsia who do not receive seizure prophylaxis, we feel the benefit of treatment is justifiable given the low cost and toxicity of the treatment of choice: magnesium sulfate, and the relatively small number of patients that need to be treated to prevent one seizure. In the MAGPIE trial (magnesium sulfate for prevention of eclampsia trial), which included 10,000 patients and is the largest randomized placebo-controlled trial that evaluated outcomes by severity of disease, the frequency of eclampsia in women with preeclampsia without severe features was 1.6 percent without prophylaxis versus 0.7 percent with prophylaxis; about 100 women with preeclampsia without severe features and about 60 women with preeclampsia with severe features would need to be treated to prevent one seizure [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/4040]. Although not statistically significant, prophylaxis also reduced the risk of maternal death in women without severe features of preeclampsia (RR 0.54, 95% CI 0.20-1.45; 6/3758 [0.16 percent] versus 11/3710 [0.30 percent] without treatment).
Our recommendation is in contrast to the 2013 American College of Obstetricians and Gynecologists' recommendations, which state that "for women with preeclampsia with systolic blood pressure of less than 160 mmHg and a diastolic blood pressure less than 110 mmHg and no maternal symptoms, it is suggested that
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate not be administered universally for the prevention of eclampsia" [
It is important to emphasize that seizure prophylaxis does not prevent progression of disease unrelated to convulsions. Approximately 10 to 15 percent of women in labor with preeclampsia without severe features will develop signs\symptoms of preeclampsia with severe features (eg, severe hypertension, severe headache, visual disturbance, epigastric pain, laboratory abnormalities) or abruptio placenta, whether or not they receive magnesium therapy [
We do not administer seizure prophylaxis to women with only gestational hypertension (pregnancy-related hypertension without proteinuria or end-organ dysfunction), as the seizure risk in the latter group is less than 0.1 percent [
Drug of choice: Magnesium sulfate — Major medical organizations worldwide consistently recommend
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate as the drug of choice for the prevention of eclampsia [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/4,7,444,7,44]. In a meta-analysis of randomized trials of women with preeclampsia (any severity), magnesium sulfate was more effective for prevention of a first seizure thanplacebo/no treatment (RR 0.41, 95% CI 0.29-0.58; six trials, 11,444 women),
https://www.uptodate.com/contents/phenytoin-drug-information?source=see_linkphenytoin(RR 0.08, 95% CI 0.01-0.60; three trials, 2291 women), or an antihypertensive drug alone (
https://www.uptodate.com/contents/nimodipine-drug-information?source=see_linknimodipine, RR 0.33, 95% CI 0.14-0.77; one trial, 1650 women) [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/4545]. Compared withplacebo/no treatment, magnesium sulfate resulted in a non-statistical but potential clinically important reduction in maternal death (RR 0.54, 95% CI 0.26-1.10) and a slight increase in cesarean deliveries (RR 1.05, 95% CI 1.01-1.10), with no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15) or serious maternal morbidity (RR 1.08, 95% CI 0.89-1.32).
In meta-analyses of randomized trials involving eclamptic women,
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate was safer and more effective for prevention of recurrent seizures than
https://www.uptodate.com/contents/diazepam-drug-information?source=see_linkdiazepam, or lytic cocktail (ie,
https://www.uptodate.com/contents/promethazine-drug-information?source=see_linkpromethazine, and pethidine). These data provide additional indirect evidence of its effectiveness in preeclampsia [
https://www.uptodate.com/contents/eclampsia?source=see_link§ionName=Prevention+of+recurrent+seizures&anchor=H13"Eclampsia", section on 'Prevention of recurrent seizures'.)
The mechanism for the anticonvulsant effects of
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate has not been clearly defined. The primary effect is thought to be central. Hypotheses include raising the seizure threshold by its action at the n-methyl d-aspartate (NMDA) receptor, membrane stabilization in the central nervous system secondary to its actions as a non-specific calcium channel blocker, as well as decreasing acetylcholine in motor nerve terminals [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/49,5049,50]. Another theory is that it promotes vasodilatation of constricted cerebral vessels by opposing calcium-dependent arterial vasospasm, thereby reducing cerebral barotrauma [
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkMagnesium sulfate is contraindicated in women with myasthenia gravis since it can precipitate a severe myasthenic crisis. Alternative anticonvulsant drugs should be used. (See
https://www.uptodate.com/contents/management-of-myasthenia-gravis-in-pregnancy?source=see_link§ionName=Treatment+issues&anchor=H8"Management of myasthenia gravis in pregnancy", section on 'Treatment issues'.)
Although at least one guideline considers pulmonary edema a contraindication to use of
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/5252], the authors administer the drug cautiously to affected patients, with attention to fluid restriction, diuresis, and oxygen supplementation. (See
https://www.uptodate.com/contents/acute-respiratory-failure-during-pregnancy-and-the-peripartum-period?source=see_link§ionName=Pulmonary+edema&anchor=H6"Acute respiratory failure during pregnancy and the peripartum period", section on 'Pulmonary edema'.)
Regimen — There is no consensus on the optimal magnesium regimen, when it should be started and terminated, or route of administration [
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkMagnesium sulfate for seizure prophylaxis is usually initiated at the onset of labor or induction, or prior to a cesarean delivery [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/4,54,554,54,55]. It is usually not administered to stable antepartum patients off the labor unit, but is sometimes given to women with preeclampsia with severe features while they are being considered for conservative management. Prolonged antepartum therapy (more than five to seven days) should be avoided as it has been associated with adverse effects on fetal bones when it was administered for tocolysis [
Dosing — The most common
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate regimen, and the one that we use, is a loading dose of 6 g of a 10 percent solution intravenously over 15 to 20 minutes followed by 2 g/hour as a continuous infusion [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/4,42,55,574,42,55,57]. An alternative regimen is 5 g of a 50 percent solution intramuscularly into each buttock (total of 10 g) followed by 5 g intramuscularly every four hours. These regimens generally result in similar magnesium levels; however, intramuscular administration results in more fluctuation and is associated with more side effects, particularly pain at the injection site [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/5858]. Published dosage regimens for magnesium sulfate vary widely, with loading doses of 4 to 6 g intravenously and maintenance doses of 1 to 3 g/hour.
It is not necessary to check for a therapeutic drug level as there does not appear to be a clear threshold concentration for ensuring the prevention of convulsions. A therapeutic range of 4.8 to 8.4 mg/dL (2.0 to 3.5 mmol/L) has been recommended based on retrospective data [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/5959]. Loading doses less than 6 g are more likely to result in subtherapeutic magnesium levels (less than 4.5 mg/dL) [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/57,6057,60]. Higher maternal weight increases the time required to reach steady state levels [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/6161], which should be considered if the patient has a seizure shortly after receiving the loading dose.
Clinical assessment for magnesium toxicity should be performed every one to two hours. The maintenance dose is only given when a patellar reflex is present (loss of reflexes is the first manifestation of symptomatic hypermagnesemia), respirations exceed 12breaths/minute, and urine output exceeds 100 mL over four hours.
If magnesium toxicity is suspected, the maintenance dose should be decreased or eliminated and the magnesium level should be checked. (See
Renal insufficiency —
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkMagnesium sulfate is excreted by the kidneys. Women with renal insufficiency should receive a standard loading dose since their volume of distribution is not altered, but a reduced maintenance dose. We suggest 1 g/hour if the serum creatinine is >1.2 and <2.5 mg/dL (106 to 221 micromol/L) and no maintenance dose if the serum creatinine is ≥2.5 mg/dL (221 micromol/L) or magnesium toxicity is suspected.
Clinical assessment for magnesium toxicity should be performed every one to two hours, and the maintenance dose is only administered when there are no signs suggestive of toxicity, as described above (see
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Dosing' above). We also obtain serum magnesium levels every six hours as an adjunct to clinical assessment in women with compromised renal function. (See
Side effects — Rapid infusion of
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate causes diaphoresis, flushing, and warmth, probably related to peripheral vasodilation and a drop in blood pressure. Nausea, vomiting, headache, muscle weakness, visual disturbances, and palpitations can also occur. Dyspnea or chest pain may be symptoms of pulmonary edema, which is a rare side effect. (See
https://www.uptodate.com/contents/symptoms-of-hypermagnesemia?source=see_link"Symptoms of hypermagnesemia".)
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate is a weak tocolytic, labor duration does not appear to be affected by its administration [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/6262]. The risk of postpartum hemorrhage, possibly related to uterine atony from magnesium's tocolytic effects, was slightly increased in one trial [
Magnesium therapy results in a transient reduction of total and ionized serum calcium concentration due to rapid suppression of parathyroid hormone release [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/6464]. Rarely, hypocalcemia becomes symptomatic (myoclonus, delirium, electrocardiogram abnormalities). Cessation of magnesium therapy will restore normal serum calcium levels. However,
https://www.uptodate.com/contents/calcium-gluconate-drug-information?source=see_linkcalcium gluconate administration may be required for patients with significant symptoms (calcium gluconate 10 to 20 mL of a 10 percent solution). (See
https://www.uptodate.com/contents/symptoms-of-hypermagnesemia?source=see_link§ionName=HYPOCALCEMIA&anchor=H4"Symptoms of hypermagnesemia", section on 'Hypocalcemia' and
https://www.uptodate.com/contents/causes-and-treatment-of-hypermagnesemia?source=see_link"Causes and treatment of hypermagnesemia".)
Toxicity — Magnesium toxicity is uncommon in women with good renal function [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/6565]. Toxicity correlates with the serum magnesium concentration: loss of deep tendon reflexes occurs at 7 to 10 mEq/L (8.5 to 12 mg/dL or 3.5 to 5.0 mmol/L), respiratory paralysis at 10 to 13 mEq/L (12 to 16 mg/dL or 5.0 to 6.5 mmol/L), cardiac conduction is altered at >15mEq/L (>18 mg/dL or >7.5 mmol/L), and cardiac arrest occurs at >25 mEq/L (>30 mg/dL or >12.5 mmol/L) [
When to check magnesium levels — We obtain serum magnesium levels every six hours as an adjunct to clinical assessment in patients who have:
●A seizure while receiving
●Clinical signs/symptoms suggestive of magnesium toxicity (eg, absent patellar reflex, respiratory rate ≤12 breaths/minute)
●Renal insufficiency (creatinine >1.2 mg/dL [106 micromol/L)
Following serum magnesium levels is not required if the woman's clinical status is closely monitored every one to two hours for signs and symptoms of potential magnesium toxicity and no abnormalities are noted.
https://www.uptodate.com/contents/calcium-gluconate-drug-information?source=see_linkCalcium gluconate 15 to 30 mL of a 10 percent solution (1500 to 3000 mg) intravenously over 2 to 5 minutes is administered to patients in cardiac arrest or with severe cardiac toxicity related to hypermagnesemia [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/6767]. A starting dose of 10 mL of a 10 percent solution (1000 mg) is used for patients with less severe, but life-threatening cardiorespiratory compromise.
https://www.uptodate.com/contents/calcium-chloride-drug-information?source=see_linkCalcium chloride 5 to 10 mL of a 10 percent solution (500 to 1000 mg) intravenously over two to five minutes is an acceptable alternative but is more irritating and more likely to cause tissue necrosis with extravasation.
Fetal effects — Magnesium freely crosses the placenta; as a result, the cord blood concentration approximates the maternal serum concentration. Maternal therapy causes a decrease in baseline fetal heart rate, which generally remains within the normal range, and a decrease in fetal heart rate variability, which may be absent or minimal [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/6868]. Antenatal fetal assessment test results (eg, biophysical profile score and nonstress test reactivity) are not significantly altered [
Drug interactions — Neuromuscular blockade and hypotension due to concurrent use of
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate and calcium channel blockers have been described in case reports, but the risk appears to be minimal [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/7070]. Postpartum patients receiving both magnesium sulfate and opioids are at a higher risk for cardiopulmonary depression. (See
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'General postpartum care' below.)
Duration of therapy —
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkMagnesium sulfate is usually continued for 24 hours postpartum [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/5555]. Timing of drug discontinuation has been arbitrary; there are no high-quality data to guide therapy. In most women who have preeclampsia without severe features, therapy can be safely discontinued after 12 hours [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/7171]. In women with preeclampsia with severe features or eclampsia, seizure prophylaxis is generally continued for 24 to 48 hours postpartum, after which the risk of recurrent seizures is low.
It is probably reasonable to extend the duration of
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate therapy in women whose disease has not begun to improve postpartum and shorten the duration of therapy in women who are clearly improving clinically (eg, diuresis of ≥100 mL/hour for two consecutive hours, absence of symptoms [headache, visual changes, epigastric pain], and absence of severe hypertension) [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/72-7572-75]. Diuresis (greater than 4 L/day) is believed to be the most accurate clinical indicator of resolution of preeclampsia/eclampsia, but is not a guarantee against the development of seizures [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/7676]. In women with persistent renal impairment postpartum, it is important to be cautious when prolonging the magnesium sulfate infusion since these patients are at increased risk for magnesium toxicity.
Management of thrombocytopenia — The risk of bleeding due to thrombocytopenia is generally considered to increase only when the platelet count is below 100,000/microL,and the risk increases substantially only with platelet counts below 50,000/microL. Platelet transfusion should not be used to normalize the platelet count in nonbleeding patients, as long as the platelet count is above 10,000 to 20,000/microL. However, platelets should not be withheld from a patient with potentially life-threatening bleeding or one who requires a higher platelet count to prevent bleeding in a high-risk setting, such as surgery. (See
https://www.uptodate.com/contents/thrombocytopenia-in-pregnancy?source=see_link"Thrombocytopenia in pregnancy".)
Although a platelet count >50,000/microL is generally considered safe for delivery (vaginal or cesarean) [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/77,7877,78], achievement of a specific platelet threshold does not substitute for clinical judgment in preparation for and management of delivery. For severely thrombocytopenic patients (platelet count <20,000/microL), both authors notify the blood bank and have platelets readily available in the delivery room for transfusion in case excessive bleeding develops at vaginal delivery or excessive oozing is observed at the time of the skin incision at cesarean. Excessively bleeding patients are transfused.
The decision for prophylactic platelet transfusion in women with severe preeclampsia-related thrombocytopenia but no excessive bleeding depends on patient-specific factors; consultation with the hematology service may be helpful. Patient-specific factors that may influence the authors' decision to initiate prophylactic platelet transfusion include a rapidly falling platelet count, recent use of low-dose
https://www.uptodate.com/contents/aspirin-drug-information?source=see_linkaspirin, coexistent abruption, and severe hypertension, because all of these factors may impact the risk of clinical bleeding or cerebrovascular accident.
The American College of Obstetricians and Gynecologists has not made a specific recommendation [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/7979] but cites an AABB guideline that recommends platelet transfusion to increase the maternal platelet count to >50,000/microL before major elective non-neuraxial surgery (weak recommendation based on very low-quality evidence) [
The minimum platelet count before placement of neuraxial anesthesia is controversial, depends on factors in addition to platelet concentration, and is institution-dependent. (See
https://www.uptodate.com/contents/adverse-effects-of-neuraxial-analgesia-and-anesthesia-for-obstetrics?source=see_link§ionName=Neuraxial+analgesia+and+low+platelets&anchor=H12561208"Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Neuraxial analgesia and low platelets'.)
Glucocorticoid therapy does not appear to be effective for significantly raising the platelet count in women with preeclampsia [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/8181], but available data in women with preeclampsia or HELLP syndrome [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/8282] are limited by the small number of subjects in the trials. We do not administer steroids to raise the platelet count in patients with these disorders. (See
https://www.uptodate.com/contents/hellp-syndrome?source=see_link§ionName=Role+of+dexamethasone+for+treatment+of+HELLP&anchor=H16"HELLP syndrome", section on 'Role of dexamethasone for treatment of HELLP'.)
Analgesia and anesthesia — Neuraxial techniques are generally safe and effective in preeclamptic women [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/4,834,83]. In preeclampsia, the two major anesthesia-related concerns with use of neuraxial techniques are (1) the potential for a large drop in blood pressure due to the combination of depleted intravascular volume and sympathetic blockade and (2) peridural hematoma in women with severe thrombocytopenia. The former can be minimized by appropriate adjustments in pre-hydration, drug choice, drug dosing, and drug delivery by the anesthesiologist; however, as discussed above, a low platelet count may preclude neuraxial anesthesia. The platelet count necessary to safely perform neuraxial anesthesia is unknown [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/8484], and practice varies. (See
https://www.uptodate.com/contents/anesthesia-for-the-patient-with-preeclampsia?source=see_link"Anesthesia for the patient with preeclampsia".)
The major concerns associated with general anesthesia (for cesarean delivery) are difficult or failed intubation because of oropharyngeal edema, a transient spike in blood pressure during intubation as a response to noxious stimuli, and hypotension from anesthetic-induced reduction in cardiac output and systemic vascular resistance. Given these issues, early patient assessment by the anesthesia team is desirable. (See
Cranial imaging — Most patients with symptoms associated with the severe spectrum of the disease respond to treatment with antihypertensive and analgesic medications. For those with either unremitting headache or neurologic signs/symptoms, we consult the neurology service and leave decisions for further evaluation, such as cranial imaging, to them.
General postpartum care — There are no evidence-based standards for the optimal approach to postpartum maternal monitoring and follow-up. We monitor vital signs every two hours while the patient remains on
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate, and we repeat laboratory tests (eg, platelet count, creatinine, liver function tests) until two consecutive sets of data are normal.
Postpartum patients receiving both magnesium and opioids are at a higher risk for cardiopulmonary depression. Pain should be controlled with the minimally effective dose of opioid while recognizing the possible synergy between the two drugs with respect to respiratory depression. Vital signs are closely monitored, ideally in association with pulse oximetry. It may be necessary to reduce the dose of one or both drugs, and patients with serious toxicity may require an antidote (
https://www.uptodate.com/contents/pain-control-in-the-critically-ill-adult-patient?source=see_link§ionName=Type+and+management+of+side+effects&anchor=H108948142"Pain control in the critically ill adult patient", section on 'Type and management of side effects'.)
Nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control should be avoided in women with poorly controlled hypertension, oliguria, or renal insufficiency, since NSAIDs can have an adverse effect on these conditions. (See
https://www.uptodate.com/contents/nonselective-nsaids-overview-of-adverse-effects?source=see_link"Nonselective NSAIDs: Overview of adverse effects".)
Severe hypertension should be treated; some patients will have to be discharged on antihypertensive medications, which are discontinued when blood pressure returns to normal. (See
https://www.uptodate.com/contents/management-of-hypertension-in-pregnant-and-postpartum-women?source=see_link§ionName=POSTPARTUM+HYPERTENSION&anchor=H523716270"Management of hypertension in pregnant and postpartum women", section on 'Postpartum hypertension'.)
The American College of Obstetricians and Gynecologists suggests monitoring blood pressure in hospital or at home for the first 72 hours postpartum and again 7 to 10 days postdelivery [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/44]. Some patients will require longer monitoring; continued follow-up is needed until all of the signs and symptoms of preeclampsia have resolved. Alternative diagnoses should be sought in those with persistent abnormal findings after three to six months [
https://www.uptodate.com/contents/overview-of-hypertension-in-adults?source=see_link"Overview of hypertension in adults".)
Women with postpartum onset of preeclampsia — Some women are initially diagnosed with preeclampsia after delivery. The American College of Obstetricians and Gynecologists suggests administration of
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate to those with (1) new-onset hypertension and headache or blurred vision, or (2) severe hypertension [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/44]. Antihypertensive therapy should be administered to women with systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg on two occasions four to six hours apart, but within one hour if systolic blood pressure is ≥160 mmHg or diastolic blood pressure is ≥110 mmHg. (See
PROGNOSIS — Prognostic issues include the risk of recurrent preeclampsia and related complications in subsequent pregnancies and long-term maternal health risks.
Recurrence — A 2015 meta-analysis of individual patient data from over 75,000 women with preeclampsia who became pregnant again found that 16 percent developed recurrent preeclampsia and 20 percent developed hypertension alone in a subsequent pregnancy [
The recurrence risk varies with the severity and time of onset of the initial episode [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/8787]. Women with early-onset, severe preeclampsia are at greatest risk of recurrence (as high as 25 to 65 percent) [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/88-9088-90]. The risk of preeclampsia in a second pregnancy is much lower (5 to 7 percent) for women who had preeclampsia without severe features in their first pregnancy and less than 1 percent in women who had a normotensive first pregnancy (does not apply to abortions) [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/88,91-9688,91-96]. These relationships were illustrated by a series of 125 women with severe second-trimester preeclampsia followed for five years: 65 percent developed recurrent preeclampsia and 35 percent were normotensive in their subsequent pregnancy [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/8888]. Of the preeclamptic group, approximately one-third developed the disease at ≤27 weeks, one-third at 28 to 36 weeks, and one-third at ≥37 weeks. Thus, 21 percent of subsequent pregnancies were complicated by severe preeclampsia in the second trimester.
Recurrent preeclampsia is more likely following a preeclamptic singleton pregnancy than a preeclamptic twin pregnancy [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/9797]. The recurrence risk in women with HELLP syndrome (who may develop either HELLP or preeclampsia in a subsequent pregnancy) is discussed separately. (See
https://www.uptodate.com/contents/hellp-syndrome?source=see_link§ionName=Recurrence+in+subsequent+pregnancies&anchor=H632892225"HELLP syndrome", section on 'Recurrence in subsequent pregnancies'.)
Prevention of recurrence — Low-dose
https://www.uptodate.com/contents/aspirin-drug-information?source=see_linkaspirin therapy during pregnancy modestly reduces the risk of preeclampsia in women at high risk for developing the disease. Selection of candidates for prophylaxis, drug dosing, and evidence of efficacy are reviewed in detail separately. Anticoagulation does not prevent recurrence [
Risk of related obstetrical complications — Preeclampsia, growth restriction, preterm delivery, abruptio placenta, and stillbirth can all be sequelae of ischemic placental disease. Women with pregnancies complicated by one of these disorders are at increased risk of developing one of the other disorders in future pregnancies [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/99,10099,100]. Early-onset preeclampsia is more likely to be associated with one of these adverse events in a subsequent pregnancy, even if normotensive, than late-onset preeclampsia [
Long-term maternal risks of pregnancy-associated hypertension
Cardiovascular disease — The American Heart Association considers a history of preeclampsia or pregnancy-induced hypertension a major risk factor for development of cardiovascular disease [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/103103]. This conclusion is based on consistent findings from case-control and cohort studies. The future risk of cardiovascular morbidity and mortality appears to be related to the severity of preeclampsia, the gestational age when delivery was required, and the number of disease recurrences [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/104104]. Women with early-onset/severe preeclampsia with preterm delivery are at highest risk of cardiovascular disease later in life, including during the premenopausal period (
The relationship between preeclampsia and cardiovascular disease has been illustrated in multiple systematic reviews of controlled studies that evaluated the risk of late cardiovascular events in women with and without a history of preeclampsia [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/105-107105-107]. For example:
●A 2017 systematic review of 22 studies including >6.4 million women, of whom >258,000 had preeclampsia, reported the following: Compared with women with no history of the disease, women with preeclampsia were at increased risk for future:
•Heart failure (RR 4.19, 95% CI 2.09-8.38)
•Coronary heart disease (RR 2.50, 95% CI 1.43-4.37)
•Death from cardiovascular disease (RR 2.21, 95% CI, 1.83-2.66)
•Stroke (RR 1.81, 95% CI 1.29-2.55)
These relationships persisted after adjustment for age, body mass index, and diabetes mellitus. The difference in relative risk compared with unaffected women was attenuated 10 years after the affected pregnancy, which the authors attributed to an increasing frequency of these disorders as the control group became older and the low number of events. The authors also noted that prepregnancy cardiovascular risk factor profiles were not available in the majority of the included studies, but where available, pregestational hypertension appeared to account for the increased risk of future coronary heart disease.
●Another systematic review illustrated the graded relationship between severity of preeclampsia and risk of future cardiac disease [
•Mild preeclampsia (RR 2.00, 95% CI 1.83-2.19)
•Moderate preeclampsia (RR 2.99, 95% CI 2.51-3.58)
•Severe preeclampsia (RR 5.36, 95% CI 3.96-7.27)
In this review, preeclampsia was defined as "mild" if the pregnancy had an uncomplicated course, "moderate" if preeclampsia was complicated by fetal growth restriction or maternal seizures, and "severe" if preeclampsia was complicated by preterm delivery or fetal demise.
In addition, preeclampsia is a known risk factor for cardiomyopathy, both peripartum (see
https://www.uptodate.com/contents/peripartum-cardiomyopathy-etiology-clinical-manifestations-and-diagnosis?source=see_link"Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis") and years after delivery. In a retrospective population-based cohort study, women with a history of preeclampsia or gestational hypertension were at increased risk of cardiomyopathy for >5 years after delivery compared with women without such a history [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/108108]. Eleven percent of all cardiomyopathy events in the cohort occurred among women with a history of preeclampsia or gestational hypertension and about 50 percent of the association was related to postpregnancy chronic hypertension. However, the absolute risk of cardiomyopathy was small: 14.6 to 17.3 cases/100,000 person-years.
Some epidemiologic data suggest that the increased risk of late cardiovascularmorbidity/mortality in a previously preeclamptic woman can be attributed to underlying genetic factors and risk factors that are common to both disorders [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/109-112109-112]. It is also possible that preeclampsia-induced physiologic and metabolic changes associated with cardiovascular disease, such as endothelial dysfunction [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/113-116113-116], insulin resistance, sympathetic overactivity, proinflammatory activity, and abnormal lipid profile [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/117117], remain after delivery, leading to late cardiovascular disease [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/118-122118-122] and other disorders associated with these abnormalities. In one study, 20 percent of women with both preeclampsia and a growth-restricted newborn met criteria for metabolic syndrome when evaluated several months postpartum [
It is estimated that lifestyle interventions after preeclampsia would decrease a woman's cardiovascular disease risk by 4 to 13 percent [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/124124]. Assessment of cardiovascular risk factors, type and frequency of patient monitoring, and risk reduction strategies are reviewed separately. (See
https://www.uptodate.com/contents/overview-of-primary-prevention-of-coronary-heart-disease-and-stroke?source=see_link"Overview of primary prevention of coronary heart disease and stroke".)
Diabetes mellitus — Women with a history of preeclampsia or gestational hypertension may be at increased risk of developing diabetes [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/125-128125-128]; however, the available evidence does not support a change in standard screening guidelines. (See
https://www.uptodate.com/contents/screening-for-type-2-diabetes-mellitus?source=see_link§ionName=SCREENING+RECOMMENDATIONS+BY+EXPERT+GROUPS&anchor=H10"Screening for type 2 diabetes mellitus", section on 'Screening recommendations by expert groups'.)
In a population-based retrospective cohort study including over one million women, preeclampsia or gestational hypertension in the absence of gestational diabetes mellitus (GDM) was associated with a twofold increase in the incidence of diabetes during 16.5 years of postdelivery follow-up, after controlling for several confounding variables (but the authors did not control for obesity) [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/125125]. In women who had preeclampsia or gestational hypertension and GDM, the risk of future diabetes was increased 16- to 18-fold, which was above the already elevated 13-fold increase in risk associated with GDM alone. Previous studies have reported similar findings [
End-stage renal disease — Women with preeclampsia may be at increased risk of developing end-stage renal disease (ESRD) later in life, but the absolute risk is small, and evaluation of asymptomatic women is not warranted. A study that linked four decades of data from the Norwegian national birth and ESRD registries found that women with preeclampsia in their first pregnancy had a fourfold increase in risk of ESRD compared with women without preeclampsia (RR 4.7, 95% CI 3.6-6.1) after adjusting for known confounders, but the absolute risk of ESRD was less than 1 percent within 20 years [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/129129]. Similarly, a study using claims data from the Taiwan National Health Insurance Program noted that women with preeclampsia/eclampsia were at significantly higher risk of developing ESRD over time than women without hypertensive disorders during pregnancy (incidence 5.33 versus 0.34 per 10,000 person-years) [
Although women who went on to develop ESRD may have had subclinical renal disease during pregnancy, it is also possible that as yet undefined risk factors predisposed these women to both preeclampsia and ESRD. It is less likely that preeclampsia damages the kidney, thereby initiating a process of chronic deterioration.
Subclinical hypothyroidism — In a nested case-control study, nulliparous women who developed preeclampsia were twice as likely to develop subclinical hypothyroidism during pregnancy and long after delivery compared with matched normotensive controls [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/131131]. The risk was highest in women with recurrent preeclampsia and without thyroid peroxidase antibodies, suggesting an autoimmune mediated mechanism of hypothyroidism was not involved. In a study including 25,000 pregnant women, women with subclinical hypothyroidism identified during pregnancy were at increased risk of developing severe preeclampsia compared with euthyroid women (odds ratio 1.6, 95% CI 1.1-2.4), after adjustment for risk factors for preeclampsia [
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis/abstract/132132]. Abnormal levels of thyroid hormones appear to damage endothelial cells, potentially leading to preeclampsia and long-term cardiovascular sequelae.
All patients with symptoms of hypothyroidism (
https://www.uptodate.com/contents/image?imageKey=ENDO%2F62676&topicKey=OBGYN%2F6825&source=see_linktable 5) should be evaluated for hypothyroidism. Screening of asymptomatic individuals is controversial. (See
https://www.uptodate.com/contents/diagnosis-of-and-screening-for-hypothyroidism-in-nonpregnant-adults?source=see_link§ionName=Candidates+for+screening&anchor=H10"Diagnosis of and screening for hypothyroidism in nonpregnant adults", section on 'Candidates for screening'.)
Cancer — Antiangiogenesis is a key characteristic of preeclampsia. Because antiangiogenesis is also important for restricting tumor growth, it has been hypothesized that women with preeclampsia may be at reduced risk of future development of solid cancers. However, a systematic review of prospective and retrospective cohort studies found no significant association between preeclampsia and later development of cancer [
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See
https://www.uptodate.com/contents/society-guideline-links-hypertensive-disorders-of-pregnancy?source=see_link"Society guideline links: Hypertensive disorders of pregnancy".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see
https://www.uptodate.com/contents/preeclampsia-the-basics?source=see_link"Patient education: Preeclampsia (The Basics)" and
https://www.uptodate.com/contents/high-blood-pressure-and-pregnancy-the-basics?source=see_link"Patient education: High blood pressure and pregnancy (The Basics)" and
https://www.uptodate.com/contents/hellp-syndrome-the-basics?source=see_link"Patient education: HELLP syndrome (The Basics)")
●Beyond the Basics topics (see
https://www.uptodate.com/contents/preeclampsia-beyond-the-basics?source=see_link"Patient education: Preeclampsia (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The definitive treatment of preeclampsia is delivery to prevent development of maternal or fetal complications from disease progression. Timing of delivery is based upon gestational age, the severity of preeclampsia, and maternal and fetal condition. (See
●Preeclampsia with features of severe disease (
https://www.uptodate.com/contents/image?imageKey=OBGYN%2F76975&topicKey=OBGYN%2F6825&source=see_linktable 2) is generally regarded as an indication for delivery, regardless of gestational age, given the high risk of serious maternal morbidity. However, prolonged antepartum management in a tertiary care setting or in consultation with a maternal-fetal medicine specialist is an option for selected women remote from term (<34 weeks of gestation). (See
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Preeclampsia with features of severe disease' above.)
●Antihypertensive therapy is indicated for treatment of severe hypertension (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥110 mmHg) to prevent stroke (
https://www.uptodate.com/contents/image?imageKey=OBGYN%2F110261&topicKey=OBGYN%2F6825&source=see_linktable 3); it does not prevent eclampsia. Antihypertensive therapy to control mild hypertension does not alter the course of preeclampsia or diminish perinatal morbidity or mortality, and should be avoided in most patients. (See
●For women with preeclampsia without features of severe disease, we suggest conservative management with delivery when the pregnancy has reached 37 weeks of gestation (
https://www.uptodate.com/contents/grade/5?title=Grade%202B&topicKey=OBGYN/6825Grade 2B). (See
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Preeclampsia without features of severe disease' above.)
●Expectant management of women with preeclampsia without features of severe disease consists of frequent laboratory monitoring (platelet count, liver and renal function tests), assessment of maternal blood pressure and symptoms, and evaluation of fetal growth and well-being. In most patients, antihypertensive therapy is not indicated for systolic blood pressure <160 mmHg or diastolic blood pressure <110 mmHg. (See
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Components of conservative management' above.)
●For women with a viable fetus and preeclampsia <34 weeks of gestation, we recommend a course of antenatal glucocorticoids (
https://www.uptodate.com/contents/grade/1?title=Grade%201A&topicKey=OBGYN/6825Grade 1A). Use of steroids at 34 to 36 weeks is controversial. (See
https://www.uptodate.com/contents/antenatal-corticosteroid-therapy-for-reduction-of-neonatal-respiratory-morbidity-and-mortality-from-preterm-delivery?source=see_link§ionName=23%2B0+to+33%2B6+weeks&anchor=H2439085631"Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on '23+0 to 33+6 weeks' and
https://www.uptodate.com/contents/antenatal-corticosteroid-therapy-for-reduction-of-neonatal-respiratory-morbidity-and-mortality-from-preterm-delivery?source=see_link§ionName=34%2B0+or+more+weeks&anchor=H2439085123"Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on '34+0 or more weeks'.)
●For women with preeclampsia and features of severe disease, we recommend intrapartum and postpartum seizure prophylaxis (
https://www.uptodate.com/contents/grade/1?title=Grade%201A&topicKey=OBGYN/6825Grade 1A). The benefit of seizure prophylaxis is less clear in women without severe hypertension or preeclampsia symptoms; however, we also suggest intrapartum and postpartum prophylaxis for these women (
https://www.uptodate.com/contents/grade/5?title=Grade%202B&topicKey=OBGYN/6825Grade 2B). We recommend the use of
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate as a first-line agent for seizure prophylaxis in preeclampsia (
https://www.uptodate.com/contents/grade/1?title=Grade%201A&topicKey=OBGYN/6825Grade 1A). (See
●We give a loading dose of 6 g
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate intravenously over 15 to 20 minutes followed by 2 g/hour as a continuous infusion. The maintenance dose is only given when a patellar reflex is present (loss of reflexes is the first manifestation of symptomatic hypermagnesemia), respirations exceed 12 breaths/minute, and urine output exceeds 100 mL over four hours. (See
●The maintenance dose (but not the loading dose) should be adjusted in women with renal insufficiency. We use 1 g/hour if the serum creatinine is >1.2 and <2.5 mg/dL(106 to 221 micromol/L) and no maintenance dose if the serum creatinine is ≥2.5mg/dL (221 micromol/L). (See
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Renal insufficiency' above.)
●Magnesium toxicity is uncommon in women with good renal function. Toxicity is related to serum magnesium concentration: loss of deep tendon reflexes occurs at 7 to 10mEq/L (8.5 to 12 mg/dL or 3.5 to 5.0 mmol/L), respiratory paralysis at 10 to 13 mEq/L(12 to 16 mg/dL or 5.0 to 6.5 mmol/L), cardiac conduction is altered at >15 mEq/L(>18 mg/dL or >7.5 mmol/L), and cardiac arrest occurs at >25 mEq/L (>30 mg/dL or >12.5 mmol/L). (See
●Clinical assessment for magnesium toxicity should be performed every one to two hours. We obtain serum magnesium levels every six hours as an adjunct to clinical assessment in patients who have a seizure while receiving
https://www.uptodate.com/contents/magnesium-sulfate-drug-information?source=see_linkmagnesium sulfate, clinicalsigns/symptoms suggestive of magnesium toxicity, or renal insufficiency. (See
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'When to check magnesium levels' above.)
https://www.uptodate.com/contents/calcium-gluconate-drug-information?source=see_linkCalcium gluconate 15 to 30 mL of a 10 percent solution intravenously over 2 to 5 minutes is administered to women with cardiac arrest or severe cardiac toxicity related to hypermagnesemia. A starting dose of 10 mL of a 10 percent solution is used for patients with less severe but life-threatening cardiorespiratory compromise. (See
●For severely thrombocytopenic patients, we notify the blood bank and have platelets readily available for transfusion in case excessive bleeding develops at vaginal delivery or excessive oozing is observed at the time of skin incision at cesarean. The decision for prophylactic platelet transfusion in women with severe preeclampsia-related thrombocytopenia but no excessive bleeding depends on patient-specific factors; consultation with the hematology service may be helpful. (See
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Management of thrombocytopenia' above.)
●Fluid balance should be monitored closely to avoid excessive administration, which can lead to pulmonary edema. A maintenance infusion of a balanced salt or isotonic saline solution at about 80 mL/hour is often adequate. Oliguria that does not respond to a modest trial of increased fluids (eg, a 300 mL fluid challenge) suggests renal insufficiency and should be tolerated to reduce the potential for iatrogenic pulmonary edema. (See
●There is an increased risk of preeclampsia recurrence in subsequent pregnancies. Early-onset preeclampsia with severe features has a higher risk of recurrence than milder disease with onset at term. (See
●The American Heart Association considers a history of preeclampsia or pregnancy-induced hypertension a major risk factor for development of cardiovascular disease (see
https://www.uptodate.com/contents/preeclampsia-management-and-prognosis?source=related_link'Cardiovascular disease' above). Routine well-woman care should include assessment of cardiovascular risk factors, with appropriate patient monitoring and risk reduction interventions, when indicated. (See
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Topic 6825 Version 80.0th restriction: insights into future vascular risk. Circulation 2010; 122:1846.
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