Background: Neonates with severe forms of congenital heart disease (CHD) such as hypoplastic left heart syndrome (HLHS) are at increased risk of delayed brain development and brain injury. Disorders of the placenta have been linked to brain abnormalities in this population, but mechanisms by which the placenta increases this risk are unknown. We hypothesize that placental pathologies impact the development of cerebral autoregulation (CAR), leading to higher risk of brain injury and delayed brain development. Placental vascular malperfusion lesions may be most likely to exert deleterious effects on cerebral hemodynamics. The purpose of this study was to compare the percentage of time spent with impaired CAR during the early postnatal period in neonates with HLHS and healthy placenta versus those with histopathologic lesions of the placenta.

Methodology: In this single center observational cohort study, we analyzed time synchronized vital sign data in neonates with HLHS born at ≥35 weeks' gestation. CAR was determined in the early postnatal and pre-operative time period using the temporal relationship between mean arterial blood pressure (MAP) and regional cerebral oxygen saturation (rSO₂). To assess intact versus impaired CAR, we used a rolling calculation of the Cerebral Oximetry Index (COx), a dynamic correlation in which values >0.3 were considered impaired CAR in accordance with prior studies. Placental pathologic diagnoses were made using Amsterdam guidelines. We used a student's t-test to determine differences between mean time spent with impaired CAR in HLHS neonates with normal versus abnormal placentas. In subgroup analyses, we compared those with normal placentas to neonates with vascular malperfusion lesions of the placenta.

Results: In our cohort of 26 neonates with HLHS, we analyzed an average of 86 hours of continuous monitoring (range 18-153). There was a total of 18 (69%) patients with evidence of placental pathology and 8 (31%) with normal placentas. COx showed a wide range in time spent with impaired CAR between subjects (range 0-35%, Fig 1). Mean time spent with impaired CAR in those with normal placentas was significantly less than those with placental histopathology (3.0 ± 1.8% vs. 8.4 ± 9.0%; p=0.02, Fig 2). In exploratory subgroup analyses, those with vascular malperfusion lesions of the placenta had similar time spent with impaired CAR (8.8 ± 6.5%; n=5) to those with normal placentas (p=0.12).

Conclusion: In neonates with severe forms of CHD such as HLHS, placental histopathologies may increase the risk of brain injury through disrupted development of CAR.