Placental Findings in Infants with Hypoxic-Ischemic Encephalopathy: The Importance of the Comparison Group.

OBJECTIVE: To determine the effect of 3 distinct comparison groups on associations between placental abnormalities and neonatal hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: This single-center, prospective case-control study of singletons of gestational age ≥36 weeks with predefined criteria for HIE (n = 30) and 3 control groups was conducted from June 2015 to January 2018. The control groups were infants born by repeat cesarean delivery (n = 60), infants born small for gestational age (SGA; n = 80), and infants receiving positive-pressure ventilation (PPV) at birth (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 ORs with 95% CIs provided effect sizes. RESULTS: The odds of maternal vascular malperfusion were increased among HIE group placentas compared with placentas of the repeat cesarean delivery (OR, 4.50; 95% CI, 1.45-14.00) and PPV (3.88; 1.35-11.16) groups, but not those of the SGA group. The odds of fetal vascular malperfusion were increased in the HIE group compared with the SGA group (OR, 9.75; 95% CI, 1.85-51.51). The odds of acute chorioamnionitis were higher in the HIE group compared only with the repeat cesarean delivery group, reflecting a similar incidence of chorioamnionitis in SGA group and PPV group placentas. The absence of placental findings was lowest in the HIE group (6.7%), followed by the SGA (18.8%), PPV (31.4%), and repeat cesarean delivery (75%) groups. CONCLUSIONS: Associations with 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.

Placental findings among newborns with hypoxic ischemic encephalopathy.

OBJECTIVE: To determine if pre-specified placental abnormalities among newborns with hypoxic-ischemic encephalopathy (HIE) differ compared to newborns admitted to a NICU without encephalopathy. STUDY DESIGN: Retrospective case-control study of newborns with HIE (2006-2014) and controls matched for birth year, gestational age, weight, and gender. One pathologist reviewed archived placental sections using pre-specified criteria. RESULTS: Sixty-seven newborns had HIE, 46 had available placentas and were matched with 92 controls. HIE had more maternal vascular malperfusion (46% vs 25%, p = 0.02), fetal vascular malperfusion (13% vs 0%, p < 0.001), and clinical abruption (22% vs 4%, p = 0.001). Controls had more normal placentas (29% vs 7%, p = 0.002), and chorioamnionitis (30% vs 9%, p = 0.005). Pre-specified placental lesions occurred in 87% of HIE and 65% of controls (p = 0.008) and identified >90% of primary diagnoses. CONCLUSIONS: Pre-specified placental lesions identified nearly all abnormalities in HIE and represented both acute and chronic processes.

Occult Massive Visceral Fat Necrosis Following Therapeutic Hypothermia for Neonatal Encephalopathy.

Therapeutic hypothermia (head or whole-body cooling) improves survival and neurodevelopmental outcome in term newborns with moderate-to-severe encephalopathy. Hypothermia treatment is well tolerated; the most common side effect is thrombocytopenia. In about 1% of infants, focal subcutaneous fat necrosis has been reported. We describe a case of clinically unsuspected massive visceral fat necrosis in a term infant with Apgar score 0 at 1 min ("resuscitated apparently stillborn" infant) who was treated with therapeutic hypothermia for 72 h and expired on the 25th day of life following a neonatal course complicated by severe encephalopathy, pulmonary artery hypertension, persistent thrombocytopenia, hypoglycemia, and severe basal ganglia-thalamic abnormalities on magnetic resonance imaging. Postmortem examination revealed extensive visceral (brown) fat necrosis, involving thoracic, abdominal, and retroperitoneal adipose tissue, with distinctive sparing of the subcutaneous (white) fat. The fulminant-yet clinically occult-visceral fat necrosis seen in this case suggests that (lesser degrees of) fat necrosis may go unrecognized in hypoxic-ischemic newborns, especially in those treated with hypothermia, and underscores the importance of close monitoring of encephalopathic newborns both in the short and long terms for complications of fat necrosis (hypercalcemia and nephrocalcinosis).