Introduction
Preeclampsia is a multisystem progressive disorder characterized by the new onset of hypertension and proteinuria or the new onset of hypertension and significant end-organ dysfunction with or without proteinuria in the last half of pregnancy or postpartum [1]. It is estimated to complicate approximately 4.6% of pregnancies worldwide [2]. Its pathophysiology is complex and not fully understood yet. Both maternal and placental factors are involved. Abnormal placentation and remodeling of spiral arteries may lead to placental hypo-perfusion, hypoxia, ischemia and the release of various antiangiogenic factors into the maternal circulation, causing systemic endothelial dysfunction [3]. In addition, immunological and genetic factors have been proposed.
Preeclampsia can be characterized as early onset (<34 weeks of gestation) and late onset (≥34 weeks of gestation). Early-onset disease is associated with worse prognosis and poorer maternal and fetal outcomes, such as fetal growth restriction and preterm birth [4, 5].
Severe preeclampsia (or preeclampsia with severe features) is diagnosed when there is severe hypertension (systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg) and/or specific signs or symptoms of significant end-organ dysfunction: thrombocytopenia (< 100,000 platelets/microL), impaired liver function that is not accounted for by alternative diagnoses and as indicated by abnormally elevated blood concentrations of liver enzymes (to more than twice the upper limit normal concentrations), or by severe persistent right upper quadrant or epigastric pain unresponsive to medications, renal insufficiency (serum creatinine > 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease), pulmonary edema, new-onset headache unresponsive to medication and not accounted for by alternative diagnoses, visual disturbances [1].
Preeclampsia is associated with an increased risk for life-threatening obstetric or medical complications, intrauterine growth restriction, oligohydramnios and preterm labor. It is estimated that 10-15% of direct maternal deaths are associated with preeclampsia and eclampsia [6]. Therefore, it is essential to estimate the risk of preeclampsia early in pregnancy and identify high risk women that need frequent surveillance and prophylactic administration of low-dose aspirin. Although various laboratory and imaging tests have been proposed for preeclampsia prediction, the optimal screening model to be widely used in clinical practice remains a matter of debate [7].
Lactate dehydrogenase (LDH) is a cytoplasmic enzyme that catalyzes the interconversion of pyruvate and lactate acid and is present in tissues throughout the body. It is released into circulation following cellular death and tissue injury. LDH is a highly sensitive marker for tissue breakdown, but it is nonspecific as it is also elevated in many clinical disorders. It is a marker of hemolysis, liver dysfunction and has been used as a marker of myocardial infarction as well as a biomarker of inflammation [8-10]. Several studies have associated serum LDH levels with severity of preeclampsia, adverse maternal and perinatal outcomes [11-13].
The aim of this systematic review is to assess the usefulness of LDH as a prognostic biomarker in preeclampsia, as well as to provide a summary effect estimate concerning its effectiveness in predicting preeclampsia complications and adverse maternal and neonatal outcomes.