Placental Findings among Infants with Hypoxic-Ischemic Encephalopathy (HIE): The Importance of the Comparison Group.

Objective To determine the effect of three distinct comparison groups on associations between placental abnormalities and neonatal hypoxic-ischemic encephalopathy (HIE). Study design A single center, prospective case-control study from Jun 2015-Jan 2018 of singletons with gestational ages ≥ 36 weeks with predefined criteria for HIE (n=30) and THREE control groups. Control groups were infants born by repeat cesarean (repeat CS, n=60), infants born small for gestational age (SGA, n=80), and infants receiving positive pressure ventilation at birth (PPV, n=70). One pathologist blinded to infant category reviewed placental sections using the Amsterdam Placental Workshop criteria. Logistic regression with group contrasts relative to HIE was used to analyze primary placental pathologies, and odds ratios (OR) and 95% CI provided effect sizes. Results The odds of maternal vascular malperfusion were increased among HIE group placentas compared with repeat CS (OR, 4.50, 95% CI, 1.45-14.00) and PPV (3.88, 1.35-11.16) but not SGA. The odds of fetal vascular malperfusion were increased among HIE compared with SGA group placentas (9.75, 1.85-51.51). The odds of acute chorioamnionitis were higher among HIE compared only to repeat CS placentas reflecting a similar incidence of chorioamnionitis among SGA and PPV placentas. The absence of placental findings was lowest among HIE (6.7%), followed by SGA (18.8%), PPV (31.4%) and repeat CS (75%). Conclusions Associations between placental abnormalities among infants with HIE varied based on the specific placental abnormality and the control group. Potentially important associations between placental pathology and HIE may be obscured if control groups are not well designed.