Amniotic Fluid Neuron-Specific Enolase: A Role in Predicting Neonatal Neurologic Injury? ANDREW ELIMIAN, MD, REINALDO FIGUEROA, MD, UMA VERMA, MD, PAUL VISINTAINER, PhD, PRAVIN B. SEHGAL, MD, PhD, AND NERGESH TEJANI, MD Objective: To determine the relationship between amniotic fluid (AF) neuron-specific enolase and the development of neonatal intraventricular hemorrhage and periventricular leucomalacia. Methods: Thirty-nine AF samples, obtained from women in preterm labor between 24 and 32 weeks’ gestation, were analyzed for neuron-specific enolase. All women delivered preterm neonates who had neurosonograms on the 3rd and 7th days of life. The results of the neurosonograms were used to divide the study population first into normal and abnormal groups, then into normal, minor, and major brain lesion groups. The groups were compared for the median neuron-specific enolase, proportion with values of 6 g/L or more, and other demographic characteristics. Results: There were no differences between the groups’ maternal and neonatal characteristics. However, the ab- normal group had significantly higher median value of neuron-specific enolase than the normal group (9.5 g/L and 2.0 g/L, respectively; P < .001). The median neuron- specific enolase levels for the major, minor, and normal groups were 9.75 g/L, 6.5 g/L and 2.0 g/L, respectively (P < .001). The optimum cutoff point, with a sensitivity of 89% and specificity of 100%, was 6 g/L; 89% of the abnormals had values of 6 g/L or more, compared with none of the normals (P < .001). The risk of developing intraventricular hemorrhage or periventricular leucomala- cia was 11.5 times greater when AF neuron-specific eno- lase levels were 6 g/L or more. Conclusion: Amniotic fluid neuron-specific enolase is a useful marker of neonatal neurologic injury. (Obstet Gy- necol 1998;92:546 –50. © 1998 by The American College of Obstetricians and Gynecologists.) Intraventricular hemorrhage and periventricular leuco- malacia, manifestations of hypoxic-ischemic brain in- jury in low birth weight (LBW) neonates are closely related to long-term developmental delays and neuro- logic compromises. 1–5 The National cerebral palsy rate remains unchanged at one to two per 1000 live births, despite recent advances in obstetric and neonatal care. Low birth weight neonates are especially vulnerable, with a cerebral palsy rate of 60 per 1000 live births. Ten percent of cerebral palsy is related to intrapartum events, whereas more than 60% of neurologic damage in cerebral palsy is associated with antepartum events. 6,7 No current fetal monitoring methods reliably detect ongoing neuronal damage. Specific biochemical markers in amniotic fluid (AF) or fetal serum might identify cases at risk for development of intraventricu- lar hemorrhage and periventricular leucomalacia when neuroprotective agents might help. Such markers would accurately time neuronal injury and avoid con- servative management of continuing injury. Neuron-specific enolase is a dimeric cytoplasmic isoenzyme that catalyses the interconversion of 2 phos- pho-d-glycerate and phosphopyruvate in the glycolytic pathway. 8 It is predominantly found in neuronal and neuroendocrine tissues. 9 –11 Cell injury releases this isoenzyme into the blood and cerebrospinal fluid (CSF). Investigators have reported its use in adults as a marker of neurologic injury in stroke, intracerebral bleed, sub- arachnoid hemorrhage, head trauma, postcardiac arrest states, and seizure disorders. 12–15 Elevated CSF levels of neuron-specific enolase were found in full-term asphyx- iated neonates with stage 3 hypoxic ischemic encepha- lopathy and correlated with extent of damage and outcome. 16 We hypothesized that AF neuron-specific enolase levels are high in women whose neonates develop intraventricular hemorrhage or periventricular leuco- malacia. The purpose of our study was to examine the relationship between AF neuron-specific enolase in From the Departments of Obstetrics and Gynecology; Cell Biology and Anatomy, Westchester Medical Center, Valhalla, New York; and the Graduate School of Health Sciences, New York Medical College, New York. 546 0029-7844/98/$19.00 Obstetrics & Gynecology PII S0029-7844(98)00273-7