Preeclampsia and Eclampsia in Pregnancy

Preeclampsia and eclampsia are part of the spectrum of high blood pressure, or hypertensive, disorders that can occur during pregnancy.

At the mild end of the spectrum is gestational hypertension, which occurs when a woman who previously had normal blood pressure develops high blood pressure when she is more than 20 weeks pregnant and her blood pressure returns to normal within 12 weeks after delivery.

This problem usually occurs without other symptoms. In many cases, gestational hypertension does not harm the mother or fetus. Severe gestational hypertension, however, may be associated with preterm birth and infants who are small for their age at birth. Some women who have gestational hypertension later develop preeclampsia.

Preeclampsia is similar to gestational hypertension because it also involves high blood pressure at or after 20 weeks of pregnancy in a woman whose blood pressure was normal before pregnancy. But preeclampsia can also include blood pressure at or greater than 140/90 mmHg, increased swelling, and protein in the urine. 

The condition can be serious and is a leading cause of preterm birth (before 37 weeks of pregnancy). If it is severe enough to affect brain function, causing seizures or coma, it is called eclampsia.

A serious complication of hypertensive disorders in pregnancy is HELLP syndrome, a situation in which a pregnant woman with preeclampsia or eclampsia suffers damage to the liver and blood cells. The letters in the name HELLP stand for the following problems:

• H – Hemolysis, in which oxygen-carrying red blood cells break down
• EL – Elevated Liver enzymes, showing damage to the liver
• LP – Low Platelet count, meaning that the cells responsible for stopping bleeding are low

Postpartum preeclampsia describes preeclampsia that develops after the baby is delivered, usually between 48 hours and 6 weeks after delivery. Symptoms can include high blood pressure, severe headache, visual changes, upper abdominal pain, and nausea or vomiting. Postpartum preeclampsia can occur regardless of whether a woman had high blood pressure or preeclampsia during pregnancy.

Postpartum eclampsia refers to seizures that occur between 48 and 72 hours after delivery. Symptoms also include high blood pressure and difficulty breathing. About one-third of eclampsia cases occur after delivery, and nearly half of those are more than 48 hours after the birth.

Postpartum preeclampsia and eclampsia can be serious and, if not treated quickly, may result in death.

How common is Preeclampsia

According to research referenced in the AHA Journals, with the greatest morbidity and mortality, preeclampsia affects 5% to 7% of all pregnant women but is responsible for over 70 000 maternal deaths and 500 000 fetal deaths worldwide every year. In the United States, it is a leading cause of maternal death, severe maternal morbidity, maternal intensive care admissions, cesarean section, and prematurity.

Risk factors for the development of preeclampsia have been studied extensively and major risk factors include;

• a history of preeclampsia,
• chronic hypertension,
• pregestational diabetes mellitus,
• antiphospholipid syndrome, and
• obesity, among others. 

Other risk factors include advanced maternal age, nulliparity, history of chronic kidney disease, and use of assisted reproductive technologies. Relatively rare risk factors are a family history of preeclampsia and mothers carrying a trisomy 13 fetus.

Does Preeclampsia target ethnic groups

According to an article published in the US National Library of Medicine entitled Racial/ethnic differences in pregnancy-related hypertensive disease in nulliparous women, researchers found the following.

“In general, our results are consistent with findings from prior studies, which likewise showed that non-Hispanic blacks have a higher risk of pregnancy-induced hypertension and Asians/Pacific Islanders a lower risk of preeclampsia compared with non-Hispanic white women”

Warning Signs of Preeclampsia

Early signs and symptoms

Initially, pre-eclampsia causes:

• high blood pressure (hypertension)
• protein in urine (proteinuria)

You probably won’t notice any symptoms of either of these, but your doctor should pick them up during your routine antenatal appointments.

High blood pressure affects 10 to 15% of all pregnant women, so this alone doesn’t suggest pre-eclampsia, but if protein in the urine is found at the same time as high blood pressure, it’s a good indicator of the condition.

Further symptoms

As pre-eclampsia progresses, it may cause:

• severe headaches
• vision problems, such as blurring or seeing flashing lights
• severe heartburn
• pain just below the ribs
• nausea or vomiting
• excessive weight gain caused by fluid retention
• feeling very unwell
• sudden increase in oedema – swelling of the feet, ankles, face and hands

Without immediate treatment, pre-eclampsia may lead to a number of rare, but serious complications, including:

• convulsions (eclampsia)
• HELLP syndrome (a combined liver and blood clotting disorder)
• stroke

Signs in the unborn baby

The main sign of pre-eclampsia in the unborn baby is slow growth. This is caused by poor blood supply through the placenta to the baby. The growing baby receives less oxygen and fewer nutrients than it should, which can affect development. This is called intra-uterine or foetal growth restriction.

If your baby is growing more slowly than usual, this will normally be picked up by your healthcare provider during your antenatal appointments.

Treating Preclampsia

Pre-eclampsia can only be cured by delivering your baby. If you have pre-eclampsia, you’ll be closely monitored until it’s possible to deliver the baby.

Once diagnosed, you’ll be referred to a hospital specialist for further assessment and any necessary treatment. If you only have high blood pressure without any signs of pre-eclampsia, you can usually return home afterwards and attend regular (possibly daily) follow-up appointments.

If pre-eclampsia is confirmed, you’ll usually need to stay in hospital until your baby can be delivered.

Monitoring in hospital

While you’re in hospital, you and your baby will be monitored by:

• having regular blood pressure checks to identify any abnormal increases
• having regular urine samples taken to measure protein levels
• having various blood tests – for example, to check your kidney and liver health
• having ultrasound scans to check blood flow through the placenta, measure the growth of the baby, and observe the baby’s breathing and movements
• electronically monitoring the baby’s heart rate using a process called cardiotocography, which can detect any stress or distress in the baby

Medication for high blood pressure

Medication is recommended to help lower your blood pressure. These medications reduce the likelihood of serious complications, such as stroke and have proven track records of safety. This means the medications have undergone clinical trials that have found them to be safe and effective for this purpose. An extensive list of these can be found below in the section labeled “For Healthcare Professionals”.

Other drugs may be considered by your doctor that have known benefits and can be used “off-label” (outside their licence) if it’s felt the benefits of treatment are likely to outweigh the risks of harm to you or your baby.

If your doctors recommend treatment with one of these medications, you should be made aware that the medication is unlicensed in pregnancy and any risks should be explained before you agree to treatment, unless immediate treatment is needed in an emergency.

Other medications

In clinical practice, therapies involving antiplatelet agents such as low aspirin doses (ACOG, 2018) and calcium supplementation in women with low calcium diets (Hofmeyr et al., 2014) have proven to bring small to moderate benefit to women with high risk pregnancies.

Anticonvulsant medication may be prescribed to prevent fits if you have severe pre-eclampsia and your baby is due within 24 hours, or if you have had convulsions (fits).

They can also be used to treat fits if they occur.

Delivering your baby

In most cases of pre-eclampsia, having your baby at about the 37th to 38th week of pregnancy is recommended. This may mean that labor needs to be started artificially (known as induced labor) or you may need to have a caesarean section.

This is recommended because research suggests there’s no benefit in waiting for labour to start by itself after this point. Delivering the baby early can also reduce the risk of complications from pre-eclampsia.

If your condition becomes more severe before 37 weeks and there are serious concerns about the health of you or your baby, earlier delivery may be necessary. Deliveries before 37 weeks are known as premature births and babies born before this point may not be fully developed.

You should be given information about the risks of both premature birth and pre-eclampsia so the best decision can be made about your treatment.

After the delivery

Although pre-eclampsia usually improves soon after your baby is born, complications can sometimes develop a few days later.You may need to stay in hospital after the delivery so you can be monitored.

Your baby may also need to be monitored and stay in a hospital neonatal intensive care unit if they’re born prematurely. These units have facilities that can replicate the functions of the womb and allow your baby to develop fully.

Once it’s safe to do so, you’ll be able to take your baby home.

You’ll usually need to have your blood pressure checked regularly after leaving hospital, and you may need to continue taking medication to lower your blood pressure for several weeks.

You should be offered a postnatal appointment 6 to 8 weeks after your baby is born to check your progress and decide if any treatment needs to continue. This appointment will usually be with your doctor.

For Healthcare Professionals

Treatment of hypertension in pregnant and postpartum women
Author:Phyllis August, MD, MPH
Section Editors:Charles J Lockwood, MD, MHCMGeorge L Bakris, MD
Deputy Editor:Vanessa A Barss, MD, FACOG

Please refer to the Full Article above for references and further reading

OVERVIEW OF ANTIHYPERTENSIVE DRUG OPTIONS

Overall safety — All antihypertensive drugs cross the placenta. There are no data from large well-designed randomized trials on which to base a strong recommendation for use of one drug over another. Data regarding both comparative efficacy in improving pregnancy outcome and fetal safety are inadequate for almost all antihypertensive drugs. Although adverse fetal and neonatal outcomes have been reported in women exposed to antihypertensive medications during pregnancy, clear conclusions about the impact of these drugs on pregnancy and the fetus are not possible given the significant methodologic weaknesses and lack of statistical power of available studies.

Adding to the confusion in this area are data suggesting that offspring of women with chronic hypertension, either treated or untreated, are at increased risk for congenital malformations, particularly cardiac malformations, compared with offspring of normotensive women. Although it is possible that hypertension increases the risk for congenital heart disease (CHD) and that antihypertensive drugs further increase this risk, it is also possible that hypertension and CHD share similar risk factors.

●In a meta-analysis that evaluated the risk of CHD in offspring of women with hypertension during pregnancy compared with offspring of women without hypertension, the risk of CHD was approximately 80 percent higher in women with hypertension (relative risk [RR] 1.8, 95% CI 1.5-2.2).

When the effect of treatment was analyzed, the risk of CHD was 100 percent higher in treated hypertensive women (RR 2.0, 95% CI 1.5-2.7) and 40 percent higher in untreated hypertensive women (RR 1.4, 95% CI 1.2-1.7).

The magnitude of effect was generally similar across subtypes of CHD and across the range of antihypertensive therapies; however, data were insufficient to exclude modest differences. Although a positive association was noted in 14 of 15 studies, these results should be interpreted with caution as neither a dose-response relationship between maternal antihypertensive medication and CHD nor some potentially important characteristics of the population (eg, severity of hypertension) could be ascertained.

Drug options — The following drugs are effective antihypertensive agents with an acceptable safety profile in pregnancy. The choice of drug depends on the acuity and severity of hypertension and whether parenteral or oral therapy is appropriate; these factors are discussed below. Response to antihypertensive medication is variable, and generalizations about comparative efficacy in overall or specific hypertensive populations are difficult to make. The most widely used medications (labetalol, methyldopa, hydralazine, nifedipine) have not been examined in comparative effectiveness trials.

Methyldopa — Methyldopa has been widely used in pregnant women and its long-term safety for the fetus has been demonstrated, but it is only a mild antihypertensive agent and has a slow onset of action (three to six hours). Many women will not achieve blood pressure goals on this oral agent or are bothered by its sedative effect at high doses.

Although methyldopa is not widely used outside of pregnancy, it remains useful in this setting, particularly in women who develop adverse effects or are intolerant of other, more widely used medications.

Methyldopa has been used for several decades, and its safety has been more extensively documented than other antihypertensive agents. Clinical trials (eg, Control of Hypertension in Pregnancy Study [CHIPS] ) utilized this agent and demonstrated that women treated with methyldopa may have had better outcomes compared with those treated with labetalol, although these data may be biased by residual confounding.

Beta blockers — Beta blockers are widely used in pregnancy. Asthma is a common contraindication as bronchospasm may occur.

●Choice of beta blocker

•Labetalol has both alpha- and beta-adrenergic blocking activity. It is the preferred drug in this class because early studies in experimental models suggested that it may preserve uteroplacental blood flow to a greater extent than traditional beta blockers. Labetalol has been associated with maternal hepatotoxicity, which, although rare, is important to recognize as it may be confused with the elevated liver chemistries of HELLP syndrome. Most cases are reversible, but fatalities have been reported.

•Although less well studied in pregnant women, metoprolol and pindolol are acceptable alternative agents.

Beta-adrenergic blockers that lack alpha blocking properties (eg, atenolol) have been associated with slightly lower placental and fetal weight at delivery when used early in pregnancy and are generally avoided if an effective drug with a better safety profile is available. In addition, myometrial relaxation of the gravid uterus is a beta-2-receptor-mediated process, and nonselective beta-adrenergic blockers (such as propranolol) may counteract the effect of beta-2 stimulation.

●Evidence of the safety of beta blockers –Despite the widespread use of labetalol in pregnancy, the safety of beta blockers remains somewhat controversial due to inconsistent reports of preterm birth, fetal growth restriction/small for gestational age infant, perinatal mortality, and neonatal apnea, bradycardia, and hypoglycemia, as well as inconsistent reports of an increased risk for congenital malformations. Further research is required given the limitations of available data, including inability to analyze data by type of beta blocker; variability in timing of exposure within the first trimester; and the fact that most studies did not address differences in indications for beta blocker therapy (eg, hypertension versus control of heart rate) or recall, recording, publication, and survivor biases.

•In a meta-analysis of 13 population-based case-control or cohort studies examining the risk of congenital malformations associated with first-trimester oral beta blocker exposure compared with no exposure, there was no overall increase in major congenital malformations (odds ratio [OR] 0.90, 95% CI 0.91-1.10). Associations with some organ-specific malformations were observed: cardiovascular defects (OR 2.01, 95% CI 1.18-3.42, four studies), cleft lip/palate (OR 3.11, 95% CI 1.79-5.43, two studies), and neural tube defects (OR 3.56, 95% CI 1.19-10.67, two studies).

•In a systematic review specifically examining the risk for congenital heart defects associated with treated and untreated maternal hypertension, beta blocker therapy was associated with an increased risk compared with no treatment (RR 2.1, 95% CI 1.6-2.7).

•Subsequent studies have reported conflicting results but overall have generally been reassuring that there is no large relative or absolute increase in the risk for overall malformations or cardiac malformations that is independent of measured confounders (eg, hypertension, obesity, diabetes). Most recently, the InPreSS consortium pooled data from large cohorts drawn from six countries and reported that beta blocker use was not associated with large increases in the relative and absolute risks for major malformations overall (RR 1.07, 95% CI 0.89-1.30; risk difference per 1000 persons exposed 3.0, 95% CI -6.6 to 12.6) or cardiac malformations (RR 1.12, 95% CI 0.83-1.51; risk difference per 1000 persons exposed 2.1, 95% CI -4.3 to 8.4), the most common class of birth defects. Strengths of this study were that medication use was defined on the basis of exposure during the first trimester, the major period of organogenesis; exposure was based on filled prescriptions, which avoided recall bias but did confirm actual intake of the medication; and the analysis was restricted to women with hypertension, addressing the issue of confounding by this common indication for beta blockers.

Calcium channel blockers

●Choice of calcium channel blocker

•Nifedipine is the most widely used drug in this class in pregnancy. It is available in immediate-release rapid-acting, intermediate-acting, and extended-release formulations. We generally prefer to use an intermediate- or extended-release formula. (See ‘Nifedipine’ below.)

•Although amlodipine is widely used in nonpregnant individuals with hypertension, there are sparse data on its use in pregnancy. The largest report of documented birth outcomes was among 231 Japanese women, of whom 48 had first-trimester exposure to amlodipine, 54 were exposed to other antihypertensives, and 129 had hypertension but were not exposed to any drug. The rate of fetal morphologic abnormalities was similar in the three groups (range 4.2 to 5.6 percent), suggesting that amlodipine may not be associated with an increased risk of malformations.

•Nondihydropyridine calcium antagonists, such as verapamil and diltiazem, have been used as well, although most reports in the literature included only a small number of women.

●Evidence of safety of calcium channel blockers – Calcium channel blockers have been widely used for tocolysis and acute blood pressure reduction in the second half of pregnancy, but minimal information is available on fetal effects in early pregnancy.

Although a meta-analysis of in utero exposure to antihypertensive medication found evidence of increased risks of stillbirth (OR 3.0, 95% CI 1.0-8.7), preterm birth (OR 4.6, 95% CI 2.9-7.3), and CHD (OR 1.4, 95% CI 1.2-1.7) in pregnancies exposed to calcium channel blockers, the ORs were based on single studies, and the studies did not evaluate the effect of treated versus untreated hypertension and did not specify the type of hypertensive disorder being treated.

Hydralazine — Intravenous hydralazine has been widely used for many years for treatment of acute severe hypertension in pregnancy and is an acceptable antihypertensive drug in this setting. However, the hypotensive response to intravenous hydralazine is less predictable than that seen with labetalol. Although hydralazine can be taken orally, it causes reflex tachycardia and fluid retention, which limit its usefulness in pregnancy.

A meta-analysis demonstrated a slightly increased rate of adverse events with hydralazine compared with labetalol, but the evidence was not sufficient to make a definitive recommendation for one drug over the other.

Thiazide diuretics — Diuretics are generally not used in pregnancy except for treatment of pulmonary edema. The role of thiazide diuretics has been a source of controversy for decades, although some guidelines suggest that these agents can be continued in women with chronic hypertension who were taking them prior to pregnancy. Significant volume depletion is not likely in this setting since most of the fluid loss occurs within the first two weeks of use, assuming that drug dose and dietary sodium intake are relatively constant.

Clonidine — Clonidine has a similar mechanism of action as methyldopa and can be an effective drug for treatment of nonsevere hypertension in pregnancy. However, it has bothersome side effects and the possibility of rebound hypertension if it is stopped suddenly, so other agents are preferred.

The author has prescribed clonidine for rare patients in whom methyldopa, labetalol, and nifedipine could not be used. Because clonidine is available as a transdermal patch, it is particularly useful for patients who cannot take an oral antihypertensive drug.