Elevated Amniotic Fluid Interleukin-6 as a Predictor of Neonatal Periventricular Leukomalacia and Intraventricular Hemorrhage.

Objective: To investigate the relationship between amniotic fluid interleukin-6 levels and the development of periventricular leukomalacia and intraventricular hemorrhage in the preterm neonate and to compare the value of amniotic fluid interleukin-6 with amniotic fluid culture and histologic chorioamnionitis in the prediction of periventricular leukomalacia and intraventricular hemorrhage. Methods: 119 women, between 20 and 34 weeks gestation, in preterm labor with intact membranes, underwent transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Ureaplasma urealyticum and Mycoplasma hominis. Amniotic fluid interleukin-6 levels were determined by enzyme-linked immunosorbent assay. The placentas were examined for histopathologic evidence of inflammation. Where the birth weight was <2,000 g, transfontanelle cranial sonography was performed on the 3rd and 7th days of life for diagnosis of periventricular leukomalacia and intraventricular hemorrhage. Student's t test, the Mann-Whitney U test, likelihood ratio chi2, logistic regression, and receiver-operator characteristic curve were used for analysis. Results: 33 women were excluded from the analysis because they delivered at other institutions. The neonates of 33 women did not have sonography because they weighed >2,000 g at birth. Two neonates died before sonography was performed; four neonates who weighed <2,000 g at birth did not have sonography. In the definitive study group of 47 women, those with neonates who developed periventricular leukomalacia and intraventricular hemorrhage (n = 14) had higher median amniotic fluid interleukin-6 levels (42,795 pg/ml versus 8,020 pg/ml; P = 0.009), more positive amniotic fluid cultures (64% vesus 21%; P < 0.003), and a shorter median amniocentesis-to-delivery interval (16 h versus 24 h; P = 0.045) than women (n = 33) who delivered neonates without periventricular leukomalacia or intraventricular hemorrhage. The groups did not differ in gestational age at admission (P = 0.15), birth weight (P = 0.09), or histologic chorioamnionitis (P = 0.37). An amniotic fluid interleukin-6 level >/=20,000 pg/ml had a sensitivity of 71% and a specificity of 70% compared with a sensitivity of 69% and specificity of 79% for amniotic fluid culture, and a sensitivity of 71% and specificity of 42% for histologic chorioamnionitis in the prediction of periventricular leukomalacia and intraventricular hemorrhage. Women with amniotic fluid interleukin-6 levels >/=20,000 pg/ml (n = 20) had more neonates with periventricular leukomalacia or intraventricular hemorrhage than women with amniotic fluid interleukin-6 levels <20,000 pg/ml (n = 27) (50% versus 15%; P = 0.009). They also were of lower birth weight (P = 0.02), had more neonatal morbidity (P = 0.01), had more positive amniotic fluid cultures (P = 0.01), and more histologic chorioamnionitis (P = 0.02). Logistic regression analysis demonstrated that amniotic fluid interleukin-6 was an independent risk factor for the development of periventricular leukomalacia and intraventricular hemorrhage (odds ratio, 5.81; 95% confidence interval, 1.02-33.16; P = 0.05) after controlling for gestational age, birth weight, histologic chorioamnionitis, and amniotic fluid culture (odds ratio, 7.94; 95% confidence interval 1.22-51.77; P = 0.03). Conclusions: In women in preterm labor with intact membranes amniotic fluid interleukin-6 is useful in predicting neonatal periventricular leukomalacia and intraventricular hemorrhage.