Case Studies

Case 10: Pre-eclampsia

A healthy 29-year-old G₂P₀₁₀₁ is admitted to labor and delivery at 28 weeks’ gestation complaining of a severe headache and blurred vision. Her BP is 200/110 mmHg with 2+ proteinuria on urinalysis. Repeat BP a few hours later is 160/110 mmHg. Laboratory studies showed a normal hematocrit, platelet count, and liver transaminase levels.

• 1. How is pre-eclampsia defined?

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  Correct answer: Pre-eclampsia (gestational proteinuric hypertension) is defined as new-onset significant hypertension and proteinuria after 20 weeks’ gestation. The correct technique to measure blood pressure (BP) in pregnancy is in the sitting position at rest for at least 5 minutes using an appropriate size BP cuff placed on the upper arm at the level of the heart and using the fifth Korotkoff sound (disappearance) to designate the diastolic BP. Significant hypertension refers to a sustained elevation in BP of ≥140 mmHg systolic and/or ≥90 mmHg diastolic in a previously normotensive parturient. Of note, an increase over the pregnancy in systolic BP of ≥30 mmHg and/or diastolic BP of ≥30 mmHg and ≥15 mmHg, respectively, is no longer sufficient to make the diagnosis. Significant proteinuria refers to a new finding of ≥1+ protein on urine dipstick or, more objectively, ≥300 mg protein in a 24-hour urine collection.

  The original definition of pre-eclampsia included non-dependent edema (ie, swelling of the hands and face), but this is no longer a prerequisite for the diagnosis.

  The diagnosis of pre-eclampsia should be made only after 20 weeks’ gestation. Evidence of gestational proteinuric hypertension before 20 weeks’ gestation should raise the possibility of an underlying molar pregnancy, drug withdrawal, antiphospholipid antibody syndrome, or (rarely) a chromosomal abnormality in the fetus.

• 2. Her 24-hour urinalysis reveals 1.2 g protein. This patient meets criteria for the diagnosis of pre-eclampsia. What type of pre-eclampsia does she have?

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  Correct answer: Once a diagnosis of pre-eclampsia has been made, the patient should be allocated to one of two categories: “mild” or “severe” pre-eclampsia. There is no category of “moderate” pre-eclampsia. Mild pre-eclampsia includes all women with a diagnosis of pre-eclampsia, but without features of severe disease. Severe pre-eclampsia refers to women who meet the diagnostic criteria for pre-eclampsia and have one or more of the criteria listed below. Note that only one of the listed criteria is required for the patient to be assigned to the severe category.

  Features of “severe” pre-eclampsia

  Symptoms

  • Symptoms of central nervous system dysfunction (blurred vision, scotomas, altered mental status, and/or severe headache)
  • Symptoms of liver capsule distention (right upper quadrant and/or epigastric pain)
  • Signs
  • Severe BP elevation (defined as BP ≥160/110 mmHg on two occasions at least 6 hours apart)
  • Pulmonary edema
  • Eclampsia (generalized seizures and/or unexplained coma)
  • Cerebrovascular accident (stroke)
  • Fetal intrauterine growth restriction (IUGR)

  Laboratory findings

  • Proteinuria (>5 g/24 h)
  • Renal failure or oliguria (<500 mL/24 h)
  • Hepatocellular injury (serum transaminase levels two or more times normal)
  • Thrombocytopenia (<100,000 platelets/mm³)
  • Coagulopathy
  • HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome

• 3. What causes pre-eclampsia?

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  Correct answer: Pre-eclampsia is a multisystem disorder specific to human pregnancy and the puerperium. It does not occur naturally in any other animal species. More precisely, it is a disease of the placenta because it has also been described in pregnancies where there is trophoblast but no fetal tissue (complete molar pregnancies). It complicates 5–7% of all pregnancies.

  The pathophysiology of pre-eclampsia remains unclear. At least six hypotheses have been proposed, including:

  
  (1) genetic imprinting;
  (2) immune maladaptation;
  (3) placental ischemia;
  (4) generalized endothelial dysfunction;
  (5) defective free fatty acid, lipoprotein, and/or lipid peroxidase metabolism;
  (6) an imbalance in pro- and antiangiogenic factor expression.
  
  

  The primary defect appears to be a complete or partial failure of the second wave of trophoblast invasion, which is responsible for remodeling of the maternal spiral arterioles and establishment of the definitive uteroplacental circulation. This process is typically complete by 16–18 weeks’ gestation. If this process is deficient (so-called “shallow endovascular invasion” of the placenta), the spiral arterioles are unable to dilate adequately to meet the demands of the growing fetoplacental unit. This leads, in turn, to placental ischemia with the release of a “toxemic factor” that damages the vasculature throughout the maternal circulation, resulting in widespread vasospasm and endothelial injury, which manifests clinically as pre-eclampsia. The blueprint for the development of pre-eclampsia is therefore laid down early in gestation, although the clinical manifestations appear only in the latter half of pregnancy.

• 4. Are there risk factors for the development of pre-eclampsia? Can we accurately predict and prevent pre-eclampsia?

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  Correct answer: A number of risk factors for pre-eclampsia have been described (listed below). That said, it is not possible to accurately predict whether or not an individual will develop pre-eclampsia in a given pregnancy. Moreover, pre-eclampsia cannot be effectively prevented. Despite promising early studies, low-dose aspirin, dietary supplementation with elemental calcium, bed rest, sodium restriction, and/or vitamin C and E supplementation does not appear to prevent pre-eclampsia in either high- or low-risk populations.

  Risk factors for pre-eclampsia

  Risk factor	Relative risk
  Nulliparity	3
  African–American origin	15
  Extremes of age (<18 or >40 years)	3
  Multiple gestation	4
  Family history of pre-eclampsia (first-degree relative on the maternal or paternal side)	5
  Prior history of pre-eclampsia	10–14
  Chronic hypertension	10
  Chronic renal disease	20
  Antiphospholipid antibody syndrome	10
  Diabetes mellitus	2
  Collagen vascular disease (such as systemic lupus erythematosus)	2–3
  Obesity	2
  Angiotensinogen gene T235
  – homozygous	20
  – heterozygous	4

• 5. This patient has severe pre-eclampsia by symptoms and BP criteria. She is only 28 weeks’ gestation. Should she be delivered or can she be managed expectantly?

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  Correct answer: Delivery is the only effective treatment for pre-eclampsia. It should be considered in all women with mild pre-eclampsia once a favorable gestational age has been reached (usually regarded as 36–37 weeks). Delivery is also recommended for all women with severe pre-eclampsia regardless of gestational age, with three possible exceptions:

  • Severe pre-eclampsia by proteinuria alone (because the amount of protein in the urine does not correlate with maternal or perinatal outcome)
  • Severe pre-eclampsia by IUGR alone remote from term with good fetal testing (although such women should be kept in hospital with daily fetal testing)
  • Severe pre-eclampsia by BP criteria alone <32 weeks’ gestation (a number of studies have suggested that it may be both reasonable and safe to continue the pregnancy in this setting with careful BP control and delivery at 34 weeks).

  The magnitude of BP elevation is not predictive of eclampsia (defined as the occurrence of one or more generalized convulsions and/or coma in the setting of pre-eclampsia and in the absence of other neurologic conditions). Although routine use of antihypertensive medications does not change the course of pre-eclampsia for either the mother or the fetus, BP control is important to prevent maternal cerebrovascular accident (stroke), which is usually associated with a BP ≥170/120 mmHg. For this reason, antihypertensive medications can be used while affecting delivery to maintain BP <160/110 mmHg.

  Once the decision has been made to proceed with delivery, the patient should be given magnesium sulfate seizure prophylaxis during labor and for 24–48 hours postpartum. If circumstances permit, antenatal corticosteroids should be administered and delivery delayed for 24–48 hours to allow them to exert their protective effect on the fetus.

• 6. The decision has been made to proceed with delivery. Bimanual examination shows her cervix to be long and closed. Does this mean that the patient has to have a cesarean section delivery?

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  Correct answer: Once the decision has been made to proceed with delivery, there is generally no proven benefit to a cesarean section, and attempted vaginal delivery is a reasonable option. That said, however, the chance of affecting a successful vaginal delivery in a woman with severe pre-eclampsia, remote from term with an unfavorable cervical examination, is only 14–20%. Every effort should be made to avoid prolonged induction of labor. If there is no response to cervical ripening after 12 hours, cesarean section delivery should be considered.

  Pre-eclampsia and its complications typically resolve within a few days of delivery (with the noted exception of stroke). Diuresis (>4 L/day) is the most accurate clinical indicator of resolution. Fetal prognosis depends largely on gestational age at delivery and the presence or absence of complications of prematurity (such as respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and chronic lung disease).