Levels of interleukin-6 in second-trimester amniotic fluid are not predictive of adverse neonatal outcome

Objective: Elevation of interleukin (IL)-6 in the amniotic fluid (AF) during the second trimester is associated with increased risk of preterm delivery. AF IL-6 levels of > 2950 pg/ml within 72 h of delivery are predictive of neonatal brain white-matter lesions, such as periventricular leukomalacia (PVL). The objective of this study was to evaluate whether the presence of elevated AF IL-6 during the early second trimester was associated with the occurrence of relevant neonatal morbidity including PVL or perinatal mortality. Methods: We performed a historical cohort study of women who underwent mid-trimester amniocentesis and had known AF IF-6 levels and pregnancy outcome information available. Included were singleton gestations, without fetal structural or chromosomal anomalies. Results: Among the 50 woman-neonate pairs included in the study, six had AF IL-6 levels above 2950 pg/ml. Occurrence of neonatal complications requiring admission to the neonatal intensive care unit (14% vs. 33%, p = 0.1) and perinatal mortality (11% vs. 17%, p = 0.7) were not significantly different between cases with elevated vs. normal AF IL-6 levels, respectively. Only one neonate had evidence of PVL; the mid-trimester AF IL-6 level was 296.9 pg/ml, below the established predictive threshold for PVL. The difference between the rate of PVL observed among cases with elevated AF IL-6 (0/5) and that expected on the basis of the literature (43%) approached statistical significance (p = 0.08). Conclusions: Elevated mid-trimester AF IL-6 levels do not identify fetuses at risk for relevant neonatal morbidity or perinatal mortality. Larger studies are required to establish whether mid-trimester AF IL-6 levels can predict the occurrence of neonatal brain white-matter lesions.