Preeclampsia – Causes, Symptoms, Diagnosis, treatment

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Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, most often the liver and kidneys. Preeclampsia usually begins after 20 weeks of pregnancy in women whose blood pressure had been normal.

Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine.[rx][rx] When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease, there may be red blood cell breakdown, a low blood platelet count, impaired liver function, kidney dysfunction, swelling, shortness of breath due to fluid in the lungs, or visual disturbances.[rx][rx] Pre-eclampsia increases the risk of poor outcomes for both the mother and the baby.[rx] If left untreated, it may result in seizures at which point it is known as eclampsia.[rx]

Preeclampsia is a disorder of new-onset high blood pressure occurring after 20 weeks of gestation. The diagnosis of preeclampsia is characterized by high blood pressure and either excess protein in the urine or, in the absence of proteinuria, other signs or symptoms, such as thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual symptoms.

Causes of Preeclampsia

There is no definitive known cause of pre-eclampsia, though it is likely related to a number of factors. Some of these factors include:[rx][rx]

  • Abnormal placentation (formation and development of the placenta)
  • Immunologic factors
  • Prior or existing maternal pathology—pre-eclampsia is seen more at a higher incidence in individuals with pre-existing hypertension, obesity, or antiphospholipid antibody syndrome or those with a history of pre-eclampsia
  • Dietary factors, e.g. calcium supplementation in areas where dietary calcium intake is low has been shown to reduce the risk of pre-eclampsia[rx]
  • Environmental factors, e.g. air pollution[rx]
  • Insufficient blood flow to the uterus
  • Damage to the blood vessels
  • A problem with the immune system
  • Certain genes

Those with long term high blood pressure have a risk 7 to 8 times higher than those without.[rx]

Physiologically, research has linked preeclampsia to the following physiologic changes: alterations in the interaction between the maternal immune response and the placenta, placental injury, endothelial cell injury, altered vascular reactivity, oxidative stress, imbalance among vasoactive substances, decreased intravascular volume, and disseminated intravascular coagulation.[rx][rx]

Known risk factors for pre-eclampsia include

  • Having never previously given birth
  • Diabetes mellitus
  • Kidney disease
  • Chronic hypertension
  • Prior history of pre-eclampsia
  • Family history of pre-eclampsia
  • Advanced maternal age (>35 years)
  • Obesity[rx]
  • Antiphospholipid antibody syndrome[rx]
  • Multiple gestations [rx]
  • Having donated a kidney[rx]
  • Having sub-clinical hypothyroidism or thyroid antibodies
  • Placental abnormalities such as placental ischemia
Chronic (long-lasting) high blood pressure
  • Obesity
  • Diabetes
  • Kidney disease
  • Being under 15 years old or over 35 years old
  • It being the woman’s first pregnancy
  • Having had preeclampsia in a previous pregnancy
  • Multiple gestations: twins, triplets, or a greater number of multiples (These pregnancies have more placental tissue. This suggests that the placenta or things it produces may play a role.)
  • Certain autoimmune conditions, including antiphospholipid antibody syndrome and some autoimmune arthritis conditions
  • African-American or Hispanic ethnicity
  • Having a sister, mother, or daughter who had preeclampsia or high blood pressure during pregnancy
  • Having a male partner whose previous partner had preeclampsia (this suggests that the father’s genetic material, passed to the fetus and its placenta, may play a role)
  • Having a male partner with whom you were sexually active for only a short length of time prior to becoming pregnant (this may be due to a change in the way a woman’s immune system reacts to genes from the father after repeated exposure to his semen)

Symptoms of Preeclampsia

Preeclampsia sometimes develops without any symptoms. High blood pressure may develop slowly, or it may have a sudden onset. Monitoring your blood pressure is an important part of prenatal care because the first sign of preeclampsia is commonly a rise in blood pressure. Blood pressure that exceeds 140/90 millimeters of mercury (mm Hg) or greater — documented on two occasions, at least four hours apart — is abnormal.

Other signs and symptoms of preeclampsia may include:

  • Excess protein in your urine (proteinuria) or additional signs of kidney problems
  • Severe headaches
  • Changes in vision, including temporary loss of vision, blurred vision or light sensitivity
  • Upper abdominal pain, usually under your ribs on the right side
  • Nausea or vomiting
  • Decreased urine output
  • Decreased levels of platelets in your blood (thrombocytopenia)
  • Impaired liver function
  • Shortness of breath, caused by fluid in your lungs
  • Weight gain over 1 or 2 days because of a large increase in bodily fluid
  • Belly pain, especially in the upper right side
  • Change in reflexes
  • Peeing less or not at all
  • Dizziness
  • Severe vomiting and nausea
  • Vision changes like flashing lights, floaters, or blurry vision
Some women with preeclampsia don’t have any symptoms, so it’s important to see your doctor for regular blood pressure checks and urine tests.

Sudden weight gain and swelling (oedema) — particularly in your face and hands — may occur with preeclampsia. But these also occur in many normal pregnancies, so they’re not considered reliable 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 GP or midwife 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

If you notice any symptoms of pre-eclampsia, get medical advice immediately by calling your GP surgery or NHS 111.

Without immediate treatment, pre-eclampsia may lead to a number of 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 fetal growth restriction.

If your baby is growing more slowly than usual, this will normally be picked up during your antenatal appointments, when the midwife or doctor measures you.

Diagnosis of Preeclampsia

Testing for pre-eclampsia is recommended throughout pregnancy by measuring a woman’s blood pressure.[rx]

Pre-eclampsia is diagnosed when a pregnant woman develops[rx]

  • Blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic on two separate readings taken at least four to six hours apart after 20 weeks’ gestation in an individual with previously normal blood pressure.
  • In a woman with essential hypertension beginning before 20 weeks’ gestational age, the diagnostic criteria are an increase in systolic blood pressure (SBP) of ≥30 mmHg or an increase in diastolic blood pressure (DBP) of ≥15 mmHg.
  • Proteinuria ≥ 0.3 grams (300 mg) or more of protein in a 24-hour urine sample or a SPOT urinary protein to creatinine ratio ≥0.3 or a urine dipstick reading of 1+ or greater (dipstick reading should only be used if other quantitative methods are not available).[rx]

Suspicion for preeclampsia should be maintained in any pregnancy complicated by elevated blood pressure, even in the absence of proteinuria. Ten percent of individuals with other signs and symptoms of pre-eclampsia and 20% of individuals diagnosed with eclampsia show no evidence of proteinuria.[rx] In the absence of proteinuria, the presence of new-onset hypertension (elevated blood pressure) and the new onset of one or more of the following is suggestive of the diagnosis of pre-eclampsia

  • Evidence of kidney dysfunction (oliguria, elevated creatinine levels)
  • Impaired liver function (noted by liver function tests)
  • Thrombocytopenia (platelet count <100,000/microliter)
  • Pulmonary edema
  • Ankle oedema (pitting type)
  • Cerebral or visual disturbances

Pre-eclampsia is a progressive disorder and these signs of organ dysfunction are indicative of severe pre-eclampsia. A systolic blood pressure ≥160 or diastolic blood pressure ≥110 and/or proteinuria >5g in a 24-hour period is also indicative of severe pre-eclampsia.[rx] Clinically, individuals with severe preeclampsia may also present epigastric/right upper quadrant abdominal pain, headaches, and vomiting.[rx] Severe pre-eclampsia is a significant risk factor for intrauterine fetal death.

A rise in baseline blood pressure (BP) of 30 mmHg systolic or 15 mmHg diastolic, while not meeting the absolute criteria of 140/90, is important to note but is not considered diagnostic.

Predictive tests

There have been many assessments of tests aimed at predicting preeclampsia, though no single biomarker is likely to be sufficiently predictive of the disorder.[rx] Predictive tests that have been assessed include those related to placental perfusion, vascular resistance, kidney dysfunction, endothelial dysfunction, and oxidative stress. Examples of notable tests include:

  • Blood tests – Your doctor will order liver function tests, kidney function tests, and also measure your platelets — the cells that help blood clot.
  • Urine analysis – Your doctor will ask you to collect your urine for 24 hours, for measurement of the amount of protein in your urine. A single urine sample that measures the ratio of protein to creatinine — a chemical that’s always present in the urine — also may be used to make the diagnosis.
  • Fetal ultrasound – Your doctor may also recommend close monitoring of your baby’s growth, typically through ultrasound. The images of your baby created during the ultrasound exam allow your doctor to estimate fetal weight and the amount of fluid in the uterus (amniotic fluid).
  • Nonstress test or biophysical profile – A nonstress test is a simple procedure that checks how your baby’s heart rate reacts when your baby moves. A biophysical profile uses ultrasound to measure your baby’s breathing, muscle tone, movement, and the volume of amniotic fluid in your uterus.
  • Doppler ultrasonography – of the uterine arteries to investigate for signs of inadequate placental perfusion. This test has a high negative predictive value among those individuals with a history of prior preeclampsia.[rx]
  • Elevations in serum uric acid –  (hyperuricemia) is used by some to “define” pre-eclampsia,[rx] though it has been found to be a poor predictor of the disorder.[rx] Elevated levels in the blood (hyperuricemia) are likely due to reduced uric acid clearance secondary to impaired kidney function.
  • Angiogenic proteins – such as vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) and anti-angiogenic proteins such as soluble FMS-like tyrosine kinase-1 (sFlt-1) have shown promise for potential clinical use in diagnosing preeclampsia, though the evidence is sufficient to recommend a clinical use for these markers.[rx]
  • Recent studies – have shown that looking for podocytes (specialized cells of the kidney) in the urine has the potential to aid in the prediction of pre-eclampsia. Studies have demonstrated that finding podocytes in the urine may serve as an early marker of and diagnostic test for pre-eclampsia.[rx][rx][rx]
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Preeclampsia is Defined as Gestational Hypertension Associated with New-Onset Maternal or Uteroplacental Dysfunction at or after 20 Weeks’ Gestation
Gestational hypertension
Systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90
Blood pressure should be repeated to confirm true hypertension
A liquid crystal sphygmomanometer should be used with appropriate size cuff.
Or, if unavailable an appropriately calibrated automated device.
Accompanied by at ≥1 of the following new-onset conditions:
ProteinuriaAn initial assessment with automated dipstick urinalysis. If unavailable, visual analysis can be used.
If dipstick is positive (≥1+), confirmed with spot urine. Abnormal if P:Cr ≥ 30 mg/mmol or A:Cr ≥ 8 mg/mmol
Renal complicationsAcute Kidney Injury (creatinine ≥ 90 mol/L)
Liver complicationsElevated transaminases, with or without right upper quadrant of epigastric abdominal pain
Neurological complicationsEclampsia, altered mental status, blindness, stroke, clonus, severe and persistent visual scotomata
Hematological complicationsThrombocytopenia (platelet count < 150000/µL, disseminated intravascular coagulation, hemolysis)
Uteroplacental dysfunctionFoetal growth restriction, abnormal umbilical artery Doppler waveform analysis, stillbirth

 

Treatment of Preeclampsia

  • Medications to lower blood pressure – These medications, called antihypertensives, are used to lower your blood pressure if it’s dangerously high. Blood pressure in the 140/90 millimeters of mercury (mm Hg) range generally isn’t treated. Although there are many different types of antihypertensive medications, a number of them aren’t safe to use during pregnancy. Discuss with your doctor whether you need to use antihypertensive medicine in your situation to control your blood pressure.
  • Corticosteroids – If you have severe preeclampsia or HELLP syndrome, corticosteroid medications can temporarily improve liver and platelet function to help prolong your pregnancy. Corticosteroids can also help your baby’s lungs become more mature in as little as 48 hours — an important step in preparing a premature baby for life outside the womb.
  • Anticonvulsant medications. If your preeclampsia is severe, your doctor may prescribe an anticonvulsant medication, such as magnesium sulfate, to prevent a first seizure.

The optimal therapy for preeclampsia and eclampsia is to deliver the baby. (Actually, it’s the delivery of the placenta, but one can’t deliver the placenta without delivering the baby.) But complications can still arise after delivery, so close monitoring needs to continue, such as keeping blood pressure well controlled.

How you proceed depends on the severity of your preeclampsia.

  • Preeclampsia without severe features – The goal of treating mild preeclampsia is to delay delivery until the fetus is mature enough to live outside the womb. Your doctor or midwife will monitor your blood pressure, weight, urine protein, liver enzymes, kidney function, and the clotting factors in your blood. Your provider also will monitor the well-being and growth of your fetus. Some women need to be hospitalized for adequate treatment and monitoring, while others can remain at home. If you are not hospitalized, you will need to be seen by your health care professional frequently.
  • Preeclampsia with severe features – The overall goal is to prevent serious consequences to the mother’s and fetus’ health, including eclampsia, stroke, stillbirth, and liver and kidney failure. Women with severe preeclampsia are carefully monitored, and high blood pressure is treated with medication. If the condition of the mother or baby gets worse, the baby may need to be delivered early. If the pregnancy reaches a gestational age at which the consequences of premature delivery are outweighed by the risks of continuing the pregnancy (generally about 32 to 34 weeks of gestation), an obstetrician will usually recommend delivery. Your physical health and well-being will usually begin to improve after the baby is delivered. However, you will need to be closely monitored as complications can still arise after delivery.
  • Eclampsia – Magnesium sulfate is used to prevent eclamptic seizures in women with preeclampsia at highest risk for them. When eclamptic seizures occur, magnesium sulfate will be started (for those not on it already) or given again (for those in whom seizures have occurred in spite of initial treatment) in an effort to prevent recurrent seizures. Other medications, such as lorazepam (Ativan), may be used to stop (“break”) a seizure in progress. The goal of treating mild preeclampsia is to delay delivery until the fetus is mature enough to live outside the womb. Your doctor or midwife will monitor your blood pressure, weight, urine protein, liver enzymes, kidney function, and the clotting factors in your blood. Your provider also will monitor the well-being and growth of your fetus. Some women need to be hospitalized for adequate treatment and monitoring, while others can remain at home. If you are not hospitalized, you will need to be seen by your health care professional frequently.
  • Preeclampsia with severe features – The overall goal is to prevent serious consequences to the mothers and fetus’ health, including eclampsia, stroke, stillbirth, and liver and kidney failure. Women with severe preeclampsia are carefully monitored, and high blood pressure is treated with medication. If the condition of the mother or baby gets worse, the baby may need to be delivered early. If the pregnancy reaches a gestational age at which the consequences of premature delivery are outweighed by the risks of continuing the pregnancy (generally about 32 to 34 weeks of gestation), an obstetrician will usually recommend delivery. Your physical health and well-being will usually begin to improve after the baby is delivered. However, you will need to be closely monitored as complications can still arise after delivery.
    Eclampsia. Magnesium sulfate is used to prevent eclamptic seizures in women with preeclampsia at the highest risk for them. When eclamptic seizures occur, magnesium sulfate will be started (for those not on it already) or given again (for those in whom seizures have occurred in spite of initial treatment) in an effort to prevent recurrent seizures. Other medications, such as lorazepam (Ativan), may be used to stop (“break”) a seizure in progress.
Immediate emergency management

Delivery is the only curative treatment for pre-eclampsia. Management is multidisciplinary, involving an obstetrician, an anesthetist, and a pediatrician. In some cases, consultation of maternal-fetal medicine and hypertension or nephrology subspecialists may be required. Management decisions must balance the maternal risks of continued pregnancy against the fetal risks associated with induced preterm delivery. The criteria for delivery are based on two often interrelated factors, ie, gestational age at diagnosis (estimated fetal weight) and severity of pre-eclampsia.

Severe pre-eclampsia requires treatment with a dual aim, ie, preventing the harmful effects of elevated maternal blood pressure and preventing eclampsia. Management of severe pre-eclampsia begins with the transfer of the mother in a fully equipped ambulance or helicopter to a maternity ward providing an appropriate level of care for both mother and child. At admission and daily thereafter, clinical, cardiotocographic, laboratory, and ultrasound testing are required to detect the severity of pre-eclampsia and tailor management accordingly.

Regardless of the severity of pre-eclampsia, there is no advantage in continuing the pregnancy when pre-eclampsia is discovered after 36–37 weeks. Nor is expectant management justified for severe pre-eclampsia before 24 weeks, because of the high risk of maternal complications and the poor neonatal prognosis. The obstetric team must then discuss with the parents the possibility of a medical interruption of pregnancy. Prolongation of pregnancy in the event of mild pre-eclampsia can be discussed and re-evaluated on a regular basis. At 34 –37 weeks, management depends on the severity of pre-eclampsia. Expectant management is possible for mild pre-eclampsia to limit the risk of induced preterm delivery, but for severe pre-eclampsia, delivery remains the rule due to the increased risk of maternal and fetal complications.,

Similarly, at 24–34 weeks, management depends on the severity of pre-eclampsia. The presence of one or more of the following signs indicates the need for immediate delivery: uncontrolled severe hypertension (not responsive to dual therapy), eclampsia, acute pulmonary edema, abruptio placentae, subcapsular hepatic hematoma, or thrombocytopenia <50,000/mm. Delivery after corticosteroid therapy for pulmonary maturation is necessary if any of the following criteria is present: persistent epigastric pain, signs of imminent eclampsia (headaches or persistent visual disorders), de novo creatinine >120 μmol/L, oliguria below 20 mL/hour, progressive HELLP syndrome, prolonged or severe variable decelerations with short-term variability less than 3 milliseconds. When emergency delivery is not required, labor can be induced by cervical ripening.

Antihypertensive treatment is useful only in severe pre-eclampsia because the sole proven benefit of such management is to diminish the risk of maternal complications (cerebral hemorrhage, eclampsia, or acute pulmonary edema). There is no international consensus concerning the antihypertensive treatment in pre-eclampsia. The four drugs authorized for the treatment of hypertension in severe pre-eclampsia in France are nicardipine, labetalol, clonidine, and dihydralazine. There is no ideal target blood pressure value, and too aggressive a reduction in blood pressure is harmful to the fetus. Therapy with a single agent is advised as first-line treatment, followed by combination treatment when appropriate.

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Long Term Treatment

Interventions for the management and prevention of fetal complications of preeclampsia are limited. As preeclampsia is responsible for around 20%–30% of all preterm births [rx], the management options available to optimize the condition of the fetus, such as the administration of antenatal corticosteroids and magnesium sulfate infusions, are primarily aimed at preventing adverse outcomes associated with prematurity. Additionally, the prevention of adverse fetal outcomes involves optimizing the timing of delivery. However, choosing the timing of delivery is not purely an intervention to reduce fetal complications, and requires a careful balance of the condition and gestation of the fetus and the condition of the mother. Managing preeclampsia also involves optimization of the maternal condition with antihypertensives, and magnesium sulfate if required [rx], which may also provide benefits to the fetus.

Antenatal corticosteroids are recommended if a woman with preeclampsia is suspected to deliver prematurely (between 26 and 36 weeks’ gestation) within the next seven days [rx]. A single course of corticosteroids (betamethasone or dexamethasone) is supported by robust evidence to reduce the risk of perinatal death and neonatal complications including respiratory distress syndrome (RDS), necrotizing enterocolitis, and intensive care admissions in pregnancies at risk of preterm birth [rx]. While studies include women at risk of preterm birth regardless of the cause, subgroup analysis indicates there is no evidence to suggest any difference of effect in preterm birth as a result of hypertensive disease [rx]. The optimal corticosteroid to use, mode of administration at which gestations steroids are effective, and whether repeat dosing is beneficial is less clear. A Cochrane review reported that it remains uncertain whether the use of dexamethasone or betamethasone is preferred; one trial showed dexamethasone may reduce neonatal intraventricular hemorrhage rates more than betamethasone, though they were equivalent for other neonatal outcomes measured [rx]. One small trial suggested intramuscular injection may be a more beneficial mode of delivery than oral, however, more evidence is needed to support this [rx]. Though it is known that two doses of the corticosteroid are required, it is unclear whether an interval of 12 or 24 h between these doses is more effective [rx]. In terms of gestation, most evidence for the administration of antenatal corticosteroids to minimize fetal and neonatal complications supports its use between 26 and 34 weeks’ gestation [rx]. After 34 weeks’ gestation, the evidence is less robust, with some trials showing no benefit [rx]. Nevertheless, a subgroup analysis by gestation in a Cochrane review suggested that despite less evidence, there remains a clear clinical benefit of corticosteroids to reduce RDS after 34 weeks, suggesting any risks are outweighed by potential benefits [rx]. Additionally, a meta-analysis has shown that if an elective cesarean is planned, antenatal corticosteroids may still reduce rates of RDS after 37 weeks’ gestation [rx]. In spite of this, corticosteroids have been shown to cause long-term changes in the vasculature and glucose metabolism of the offspring [rx], which needs to be considered on balance with the benefits at later gestations.

Several RCTs have assessed whether multiple courses of antenatal corticosteroids are beneficial if after the initial dose, a woman does not deliver within seven days and is still at risk of preterm birth. Results of three large RCTs are conflicting [rx,rx,rx]. One trial of 982 women at less than 32 weeks of pregnancy who were at high risk of preterm birth saw them randomized seven or more days after initial corticosteroid treatment to weekly repeat dosing of betamethasone or placebo injections [rx]. They reported a reduction in RDS and severe lung disease, but lower offspring weight and head circumferences at birth. These findings are consistent with another RCT of 1348 women between 28 and 35 weeks of pregnancy [rx]. In contrast, another large RCT of 1858 women did not find any improvement in birth outcomes with repeat dosing of betamethasone but also reported a detrimental effect on birth size [rx]. All studies used intramuscular betamethasone of a similar dose, but the most noticeable difference in methodology was the frequency of repeat dosing, which was weekly, every ten days, and fortnightly in the three studies respectively. Two of the trials reported follow-up at two years, and one at five years [rx,rx,rx]. In all of these long-term follow-up studies no differences were noticed in mortality, body weight, or neurodevelopmental disability [rx,rx,rx]. Due to the lack of certainty in benefits and risks, at present guidelines do not recommend repeat courses of corticosteroids as routine care [rx].

Magnesium sulfate is given as primary and secondary prophylaxis of seizures in women with preeclampsia regardless of gestation and is also recommended in planned or expected preterm delivery for its neuroprotective effects in the offspring.

NICE recommends infusion within 24 h in women with preeclampsia between 24 and 30 weeks’ gestation and should be considered in women up to 34 weeks’ gestation [rx]. Magnesium sulfate appears safe for the fetus and meta-analysis has shown that administration antenatally can reduce the risk of cerebral palsy in the offspring [rx]. However, the majority of large trials conducted have excluded women delivering preterm as a consequence of preeclampsia. Data from the largest trial that did include women with preeclampsia did not find any significant difference in neonatal morbidity [rx], childhood death, or disability at 18 months in those whose mothers were given magnesium sulfate or placebo [rx]. Although there was a tendency to reduction in death and cerebral palsy with magnesium sulfate, this did not reach statistical significance [rx]. Therefore, while magnesium sulfate is recommended for fetal neuroprotection in women with preeclampsia at risk of imminent delivery at less than 34 weeks’ gestation, the evidence supporting this recommendation largely comes from trials in which preeclampsia was excluded as a cause of preterm birth.

The only definitive treatment for preeclampsia is delivery. Optimal timing of delivery requires a careful balance of maternal and fetal risks, including the gestation of the fetus. Overall, indications for planned early delivery are usually maternal, however fetal complications such as abnormalities in fetal ultrasound or CTG monitoring may also result in the decision for early birth [rx]. Adverse outcomes in the offspring, including perinatal mortality, are strongly linked to the gestational age at delivery. In general, from a fetal perspective, at early gestation continuation of the pregnancy is desirable in order to improve prognosis [rx] unless there is severe placental dysfunction. Therefore, in the absence of other indications, recommendations regarding expectant or immediate management and the optimal timing of delivery differ depending on the gestational age at which preeclampsia is diagnosed. If the onset of preeclampsia is before 24 weeks’ gestation (pre-viable), continuing with the pregnancy may not be advisable, due to high maternal morbidity and mortality rates and a low chance of offspring survival [rx]. From 24 to 34 weeks of pregnancy, delivery within 24–48 h is associated with increased risks of adverse events for the fetus and neonate. These include intraventricular hemorrhage, low birth weight, longer stays in intensive care, and increased requirement for respiratory support [rx]. Therefore, in women with preeclampsia before 34 weeks’ gestation, delaying delivery if possible is likely to be beneficial for the offspring. Between 34 and 37 weeks’ gestation, immediate delivery appears beneficial for the mother, however, it can increase adverse neonatal outcomes such as RDS, especially if at less than 36 weeks’ gestation [rx]. The decision to deliver the fetus immediately or to continue expectant management at these gestations can be difficult. In general, it is advised to continue expectant management unless there are indications that immediate delivery is required [rx,rx]. The largest trial to date assessing optimal time for delivery in preeclamptic pregnancies between 34 and 37 weeks’ gestation is currently underway and should provide further evidence [rx]. After 37 weeks’ gestation, expectant management or interventional management does not appear to affect neonatal outcomes, however, interventional management is beneficial for the mother and is therefore advised [rx].

These recommendations according to gestation may not be applicable in the presence of maternal or fetal complications that require more immediate delivery. Fetal indications for delivery may include severe IUGR or evidence of worsening fetal compromise on surveillance modalities, indicating fetal hypoxia [rx,rx,rx]. More specifically, this may include persistent reversed end-diastolic flow in umbilical artery Doppler velocimetry or a nonreassuring CTG, though no consensus exists regarding the most appropriate trigger for delivery [rx,rx]. If a fetal compromise is present, delaying delivery may damage brain development due to prolonged fetal hypoxia, yet early delivery carries the risks associated with prematurity. One study designed to assess this randomized 548 pregnant women to early or delayed delivery. Women were between 24 and 36 weeks of pregnancy with signs of fetal compromise and uncertainty about the most appropriate time to deliver. No difference was seen in infant mortality prior to hospital discharge, or in death or disability at two years of age [rx,rx], leaving the optimal management unclear. In this study, 43% of the pregnancies were hypertensive, but further evidence is lacking regarding when to deliver in the setting of fetal compromise specifically in preeclamptic pregnancies.

Assessment of the ductus venous flow may provide a promising method to predict perinatal outcome and appropriately time delivery in preeclamptic pregnancies complicated by IUGR. A prospective cohort study identified that in pregnancies complicated by early-onset IUGR, an abnormally high ductus venous pulsatility index can predict adverse fetal outcomes more accurately and earlier than changes in fetal heart rate or by umbilical artery Doppler [rx]. It may therefore be a more useful parameter for timing delivery. This has been further assessed in a recent multicentre randomized trial of pregnancies complicated by early-onset IUGR, in which ∽50% were preeclamptic [rx]. This study compared neonatal outcomes when three different antenatal monitoring strategies were used in order to time delivery: reduced fetal heart rate on CTG, early ductus venosus changes (as measured by high pulsatility index), or late ductus venosus changes (measured by the absence of an A wave). They found that by two years of age, neonates assigned to the cohort in which prediction of delivery was based on late ductus venosus changes had a significant reduction in neurodevelopmental impairment when corrected for prematurity. This suggests that a more conservative approach in timing delivery, by waiting for late ductus venosus changes, may improve perinatal outcomes.

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Novel management options studied to reduce adverse fetal outcomes of preeclampsia include antithrombin, sildenafil, pravastatin, metformin, and plasma exchange. Antithrombin has been shown in a small trial to preserve fetal biophysical profile and weight gain in early-onset preeclampsia (<32 weeks) [rx]. Most evidence regarding sildenafil comes from studies on preeclamptic rat models in which fetal blood flow and outcomes have been improved with its use [rx]. There has also been a small preliminary trial of sildenafil in women with severe IUGR, which has shown an improved fetal growth velocity and a trend towards improved perinatal survival. In animal models, pravastatin has been demonstrated to reduce IUGR, lower blood pressure, and improve the balance of angiogenic factors by promoting the release of PlGF and suppressing salt-1 and soluble endoglin production [rx]. Similarly, pravastatin administration in human umbilical vein endothelial cells (HUVECs), cytotrophoblasts, and placental tissue result in reduced markers of endothelial dysfunction [rx]. Despite concerns of teratogenicity, pravastatin use in small studies has not been associated with adverse pregnancy outcomes including birth defects [rx,rx] and further studies are currently underway to validate use as a potential treatment. (StAmP trial: Statins to Ameliorate Early Onset Preeclampsia. Metformin has also emerged as a potential treatment option for preeclampsia. In preclinical studies using primary human tissue, metformin reduced sflt-1 and endoglin secretion improved features of endothelial dysfunction and angiogenesis and enhanced vasodilation [rx]. Due to use in diabetes, metformin is known to be safe in pregnancy, though RCTs evaluating potential use as a treatment for preeclampsia are lacking. Plasma apheresis to facilitate the removal of antiangiogenic protein sFlt-1 has also been evaluated as a treatment method. Small pilot studies of apheresis in women with very preterm preeclampsia have shown a reduction in circulating salt-1 without apparent adverse maternal or fetal events, and a potential prolongation of pregnancy, warranting larger trials to confirm its utility [rx,rx]. These options do not have sufficient evidence for their use in clinical practice. As such, clinicians rely on monitoring and timely delivery, with the consideration of antenatal corticosteroids and/or magnesium sulfate depending on gestation, as options for improving fetal and neonatal outcomes in preeclampsia.

How can preeclampsia affect you and your baby?

Without treatment, preeclampsia can cause serious health problems for you and your baby, even death. You may have preeclampsia and not know it, so be sure to go to all your prenatal care checkups, even if you’re feeling fine. If you have any signs or symptoms of preeclampsia, tell your provider.

Health problems for women who have preeclampsia include
  • Kidney, liver, and brain damage
  • Problems with how your blood clots – A blood clot is a mass or clump of blood that forms when blood changes from a liquid to a solid. Your body normally makes blood clots to stop bleeding after a scrape or cut. Problems with blood clots can cause serious bleeding problems.
  • Eclampsia – This is a rare and life-threatening condition. It’s when a pregnant woman has seizures or a coma after preeclampsia. A coma is when you’re unconscious for a long period of time and can’t respond to voices, sounds, or activity.
  • Stroke – This is when the blood supply to the brain is interrupted or reduced. Stroke can happen when a blood clot blocks a blood vessel that brings blood to the brain, or when a blood vessel in the brain bursts opens.
Pregnancy complications from preeclampsia include
  • Premature birth – Even with treatment, you may need to give birth early to help prevent serious health problems for you and your baby.
  • Placental abruption – This is when the placenta separates from the wall of the uterus (womb) before birth. It can separate partially or completely. If you have placental abruption, your baby may not get enough oxygen and nutrients. Vaginal bleeding is the most common symptom of placental abruption after 20 weeks of pregnancy. If you have vaginal bleeding during pregnancy, tell your health care provider right away.
  • Intrauterine growth restriction (also called IUGR) – This is when a baby has poor growth in the womb. It can happen when mom has high blood pressure that narrows the blood vessels in the uterus and placenta. The placenta grows in the uterus and supplies your baby with food and oxygen through the umbilical cord. If your baby doesn’t get enough oxygen and nutrients in the womb, he may have IUGR.
  • Low birthweight

Having preeclampsia increases your risk for postpartum hemorrhage (also called PPH). PPH is heavy bleeding after giving birth. It’s a rare condition, but if not treated, it can lead to shock and death. Shock is when your body’s organs don’t get enough blood flow.

Complications

Although they’re rare, a number of complications can develop if pre-eclampsia isn’t diagnosed and monitored. These problems can affect both the mother and her baby.

Problems affecting the mother

Fits (eclampsia)

Eclampsia describes a type of convulsion or fit (involuntary contraction of the muscles) that pregnant women can experience, usually from week 20 of the pregnancy or immediately after birth. Eclampsia is quite rare in the UK, with an estimated 1 case for every 4,000 pregnancies. During an eclamptic fit, the mother’s arms, legs, neck or jaw will twitch involuntarily in repetitive, jerky movements. She may lose consciousness and may wet herself. The fits usually last less than a minute. While most women make a full recovery after having eclampsia, there’s a small risk of permanent disability or brain damage if the fits are severe.

Of those who have eclampsia, around 1 in 50 will die from the condition. Unborn babies can suffocate during a seizure and 1 in 14 may die.  Research has found that a medication called magnesium sulfate can halve the risk of eclampsia and reduce the risk of the mother dying.

It’s now widely used to treat eclampsia after it’s occurred and treat women who may be at risk of developing it.

HELLP syndrome

HELLP syndrome is a rare liver and blood clotting disorder that can affect pregnant women. It’s most likely to occur immediately after the baby is delivered, but can appear any time after 20 weeks of pregnancy, and in rare cases before 20 weeks.

The letters in the name HELLP stand for each part of the condition:

  • “H” is for hemolysis – this is where the red blood cells in the blood break down
  • “EL” is for elevated liver enzymes (proteins) – a high number of enzymes in the liver is a sign of liver damage
  • “LP” is for low platelet count – platelets are substances in the blood that help it clot

HELLP syndrome is potentially as dangerous as eclampsia and is slightly more common. The only way to treat the condition is to deliver the baby as soon as possible. Once the mother is in hospital and receiving treatment, it’s possible for her to make a full recovery.

Stroke

The blood supply to the brain can be disturbed as a result of high blood pressure. This is known as a cerebral hemorrhage or stroke. If the brain doesn’t get enough oxygen and nutrients from the blood, brain cells will start to die, causing brain damage and possibly death.

Organ problems

  • pulmonary edema – where fluid builds up in and around the lungs. This stops the lungs from working properly by preventing them from absorbing oxygen.
  • kidney failure – when the kidneys can’t filter waste products from the blood. This causes toxins and fluids to build up in the body.
  • liver failure – disruption to the functions of the liver. The liver has many functions, including digesting proteins and fats, producing bile, and removing toxins. Any damage that disrupts these functions could be fatal.

Blood clotting disorder

The mother’s blood clotting system can break down. This is known medically as disseminated intravascular coagulation. This can either result in too much bleeding because there aren’t enough proteins in the blood to make it clot, or blood clots developing throughout the body because the proteins that control blood clotting become abnormally active.

These blood clots can reduce or block blood flow through the blood vessels and possibly damage the organs.

Problems affecting the baby

Babies of some women with pre-eclampsia may grow more slowly in the womb than normal. This is because the condition reduces the number of nutrients and oxygen passed from the mother to her baby. These babies are often smaller than usual, particularly if the pre-eclampsia occurs before 37 weeks. If pre-eclampsia is severe, a baby may need to be delivered before they’re fully developed. This can lead to serious complications, such as breathing difficulties caused by the lungs not being fully developed (neonatal respiratory distress syndrome). In these cases, a baby usually needs to stay in a neonatal intensive care unit so they can be monitored and treated. Some babies of women with pre-eclampsia can even die in the womb and be stillborn.

It’s estimated around 1,000 babies die each year because of pre-eclampsia. Most of these babies die because of complications related to early delivery.

References

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