Placental features of fetal vascular malperfusion and infant neurodevelopmental outcomes at 2 years of age in severe fetal growth restriction

Background: Placental pathologic lesions suggesting maternal or fetal vascular malperfusion are common among pregnancies complicated by intrauterine growth restriction. Data on the relationship between pathologic placental lesions and subsequent infant neurodevelopmental outcomes are limited. Objective: This study aimed to assess the relationship between placental pathologic lesions and infant neurodevelopmental outcomes at 2 years of age in a cohort of pregnancies complicated by intrauterine growth restriction. Study Design: An observational cohort study included singleton intrauterine growth restriction pregnancies delivered at ≤34 weeks’ gestation and with a birthweight of ≤1500 g at a single institution in the period between 2007 and 2016. Maternal and neonatal data were collected at discharge from the hospital. Infant neurodevelopmental assessment was performed every 3 months during the first year of life and every 6 months in the second year. Penalized logistic regression was used to test the association of maternal vascular malperfusion and fetal vascular malperfusion with infant outcomes adjusting for confounders. Results: Of the 249 pregnancies enrolled, neonatal mortality was 8.8% (22 of 249). Severe and overall maternal vascular malperfusion were 16.1% (40 of 249) and 31.7% (79 of 249), respectively. Severe maternal vascular malperfusion was associated with an increased risk of neonatal mortality (adjusted odds ratio, 3.3; 95% confidence interval, 1.2–9.5). Among the 198 survivors after a 2-year neurodevelopmental follow-up evaluation, the rate of major and minor neurodevelopmental sequelae was 57.1% (4 of 7) among severe fetal vascular malperfusion (adjusted odds ratio, 24.5; 95% confidence interval, 4.1–146), 44.8% (13 of 29) among overall fetal vascular malperfusion (adjusted odds ratio, 5.8; 95% confidence interval, 5.1–16.2), and 7.1% (12 of 169) in pregnancies without fetal vascular malperfusion. Infants born from pregnancies with fetal vascular malperfusion also had lower 2-year general quotient, personal-social, hearing and speech, and performance subscales scores than those without fetal vascular malperfusion. Finally, in the presence of fetal vascular malperfusion, the likelihood of a 2-year infant survival with normal neurodevelopmental outcomes was reduced by more than 70% (adjusted odds ratio, 0.29; 95% confidence interval, 0.14–0.63). Noticeably, 10 of the 20 subjects with a 2-year major neurodevelopmental impairment (3 of 4 with severe fetal vascular malperfusion) had little or no abnormal neurologic findings at discharge from neonatal intensive care unit. Conclusion: In preterm intrauterine growth restriction, placental fetal vascular malperfusion is correlated with an increased risk of abnormal infant neurodevelopmental outcomes at 2 years of age even in the absence of brain lesions or neurologic abnormalities at discharge from the neonatal intensive care unit. In the case of a diagnosis of fetal vascular malperfusion, pediatricians and neurologists should be alerted to an increased risk of subsequent infant neurodevelopmental problems.