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

Abstract Background Placental pathological lesions suggesting maternal (MVM) or fetal (FVM) vascular malperfusion are common among pregnancies complicated by fetal growth restriction (FGR). Data on the relationship between pathological placental lesions and subsequent infant neurodevelopmental outcomes are limited. Objective The aim of the study was to assess the relationship between placental pathological lesions and infant neurodevelopmental outcomes at two years of age in a cohort of pregnancies complicated by FGR. Study design An observational cohort study including singleton FGR pregnancies delivered at ≤34 weeks of gestational and with a birth-weight ≤1500 g at a single institution in the period between 2007-2016. Maternal and neonatal data were collected at discharge from the hospital. Infant neurodevelopmental assessment was carried out every three months during the first year of life and every six months in the second year. Penalized logistic regression was used to test the association of MVM and FVM with infant outcomes adjusting for confounders. Results Out of the 249 pregnancies enrolled, neonatal mortality was 8.8% (22/249). Severe and overall MVM were 16.1% (40/249) and 31.7% (79/249), respectively. Severe MVM was associated with an increased risk of neonatal mortality (Adj OR= 3.3, 95% CI=1.2-9.5). Among the 198 survivors after a two-year neurodevelopmental follow-up evaluation, the rate of major and minor neurodevelopmental sequeale was 57.1% (4/7) among severe FVM, (Adj.OR= 24.5,95% C=4.1-146), 44.8% (13/29) (Adj. OR = 5.8, 95% CI 5.1-16.2) among overall FVM and 7.1% (12/169) in pregnancies without FVM. Infants born from pregnancies with FVM also had two-year lower general quotient, personal-social, hearing and speech, and performance subscales scores compared to those without FVM. Finally, in the presence of FVM, the likelihood of a two-year infant survival with normal neurodevelopmental outcomes was reduced by more than 70% (Adj.OR= 0.29, 95% CI = 0.14-0.63). Noticeably, 10 of the 20 subjects with a two-year major neurodevelopmental impairment (3 out of 4 with severe FVM), had little or no abnormal neurological findings at discharge from neonatal intensive care unit (NICU). Conclusions In preterm FGR, placental FVM is correlated with an increased risk of abnormal infant neurodevelopmental outcomes at two years of age even in the absence of brain lesions or neurological abnormalities at discharge from NICU. In the case of a diagnosis of FVM, pediatricians and neurologists should be alerted of an increased risk of subsequent infant neurodevelopmental problems.