Preeclampsia

Under pressure
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Diagnosis and reasoning

This lady has a moderately elevated blood pressure (BP), even though she was not hypertensive prior to pregnancy. In addition, the urinary protein:microalbumin ratio demonstrates that significant proteinuria is present - thus establishing the the diagnosis to be preeclampsia. Preeclampsia is a serious disorder with numerous complications. She should be assessed for target organ damage via estimation of renal and liver functions, while an ultrasound scan with doppler flowmetry is necessary to assess the condition of the fetus. She needs admission with careful fetal and maternal surveillance. Oral labetalol is suitable for BP control, while corticosteroids should be commenced to promote fetal lung maturation. Induction of labor should be considered after 37 weeks of amenorrhea (at which point the fetus is mature). Further delay will merely increase the risk of maternal and fetal complications, without significant added benefit. Note that new dietary salt restriction is not recommended in these patients.


Discussion

Early in pregnancy, the BP falls because of vasodilation induced by local mediators such as prostaglandins and nitric oxide. The maximum reduction occurs by 22 to 24 weeks of amenorrhea, following which the BP slowly rises, reaching pre-pregnancy levels at term. Hypertension in pregnancy is defined when a diastolic BP of >= 90 mmHg is present, regardless of the systolic BP. Up to 15% of all pregnancies are complicated by hypertension. Severe hypertension is defined as a systolic BP >= 160 mmHg or a diastolic BP of >= 110 mmHg. This is based on the fact that a BP in excess of these values is associated with a higher risk of stroke. Hypertension in pregnancy can be broadly classified into 4 categories : chronic hypertension, gestational hypertension, preeclampsia-eclampsia, and preeclampsia superimposed on chronic hypertension. Chronic hypertension is diagnosed when there is a known history of hypertension prior to pregnancy, or when an elevated BP is noted before 20 weeks of amenorrhea. Note however that hypertension may be masked in certain patients due to the initial reduction in BP, leading to misdiagnosis. Gestational hypertension is defined as new hypertension presenting after 20 weeks of amenorrhea, in the absence of significant proteinuria. The importance of proteinuria lies as a marker of end organ damage - when significant urinary protein excretion is present, these patients are said to have preeclampsia, a much more serious disorder. Alternatively, if patients show other manifestations of target organ damage such as headaches or visual disturbances, or fetal abnomalities such as oligohydramnios or intrauterine growth restriction, or abnormal investigation results such as elevated transaminases, thrombocytopenia and evidence of hemolysis (HELLP syndrome), the diagnosis of preeclampsia may be made. When patients with chronic hypertension manifest significant proteinuria or one of the above described co-morbid conditions, they are defined as having preeclampsia superimposed on chronic hypertension. In general, chronic hypertension approximately doubles the risk of developing preeclampsia. Note that significant proteinuria is defined as either urinary excretion of > 300 mg of protein over 24 hours, or the presence of a urinary protein:creatinine ratio > 30 mg/mmol. It should also be kept in mind that normal pregnancy is associated with an increase in both the glomerular flow and the permeability of the glomerular basement membranes. Thus certain healthy women may manifest mild proteinuria, which however, is non-significant. In the first trimester of a healthy pregnancy, the trophoblast invades the uterine decidua and reaches the inner layer of the myometrium. This migration transforms the spiral arteries into large sinusoidal vessels, resulting in a high capacitance, low resistance blood supply to the intervillous space. In preeclampsia, the initial pathology is failure of these vascular alterations to occur. In addition, the spiral arteries maintain their response to vasomotor influences, which further impairs perfusion to the intervillous space. This utero-placental maladaption leads to maternal systemic manifestations : hypertension, reduction in plasma volume, and impaired perfusion to almost every maternal organ. In addition, there is vasospasm and activation of platelets and the coagulation system, resulting in microthrombi formation. Mild preeclampsia may be asymptomatic, while severe preeclampsia may show clinical manifestations of target organ dysfunction : right upper quadrant pain due to hepatic edema or hemorrhage; headaches, visual disturbances and blindness secondary to cerebral edema; and hyperreflexia and clonus. Eclampsia is defined as the occurrence of a grand mal seizure in association with preeclampsia, and is an obstetric emergency. In general, patients with preeclampsia require in-patient care, with close maternal and fetal surveillance. Note however, that certain units may have the policy of managing patients with mild preeclampsia (and good maternal and fetal health) on an outpatient basis. Patients who present prior to 34 weeks of amenorrhea should receive corticosteroids (for acceleration of fetal pulmonary maturity), if delivery is anticipated within one week following administration. Severe hypertension may require initial control with IV labetalol or hydralazine, followed by maintenance with oral labetalol or nifedipine. Mild to moderate hypertension may be controlled with oral labetalol, nifedipine or methyldopa. Note that ACE inhibitors and ARBs are fetotoxic and should be avoided. In addition, prazocin is not recommended for control. The ultimate treatment is delivery - although the timing varies based on the maternal and fetal condition. Maternal indications for urgent delivery include eclampsia, progressive deterioration of renal or hepatic function, persistent severe headaches, visual disturbances, upper abdominal pain, nausea or vomiting and severe thrombocytopenia. Fetal indications include severe intrauterine growth restriction, oligohydramnios, or fetal deterioration or distress. During labor, the goals are to prevent seizures and control hypertension. Magnesium sulfate is the medication of choice for prevention and treatment of seizures (note that magnesium sulfate is not recommended as an antihypertensive). Ergometrine is absolutely contraindicated in these patients, as it may precipitate severe hypertension. In the postpartum period, these patients required continued monitoring of their BP, while if end-organ dysfunction was present in pregnancy, recovery should be confirmed. In addition, patients with preeclampsia are at a higher risk for venous thromboembolism, and thus thromboprophylaxis may be considered. Note that hypertension and proteinuria may persist for up three to six months postpartum. In addition, these patients should be further screened for pre-existing hypertension, underlying renal disease, and the presence of thrombophilia.


Take home messages

  1. Preeclampsia is defined as hypertension in pregnancy associated with the presence of proteinuria or certain comorbid conditions.
  2. Features of severe preeclampsia include right upper quadrant pain, headaches, visual disturbances, blindness, hyperreflexia and clonus.
  3. Eclampsia is defined as the occurrence of a grand mal seizure in association with preeclampsia and is an obstetric emergency.
  4. Patients with preeclampsia require in-patient care, with close maternal and fetal surveillance.
  5. Delivery is the ultimate treatment. Other key elements of management include control of hypertension, fetal pulmonary maturation and prevention/control of seizures.
  6. Magnesium sulphate is the drug of choice for control and prevention of seizures. It is not recommended as an antihypertensive.
  7. Monitoring should be continued through the post-partum period, while patients should be screened for underlying disease including hypertension, renal disorders and thrombophilias.

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  1. AFP : Diagnosis and Management of Preeclampsia (2004)
  2. AFP : Hypertensive Disorders of Pregnancy (2008)
  3. BMJ : Management of hypertensive disorders during pregnancy: summary of NICE guidance (2010)
  4. Heart: Management of hypertension before, during and after pregnancy (2004)
  5. Journal of Obstetrics and Gynecology Canada : Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy (2008)
  6. Journal of the American Society of Hypertension : Hypertension in pregnancy (2008)
  7. Obstetrics and Gynecology : Diagnosis and management of gestational hypertension and preeclampsia (2003)