Early Maturation of Heart Rate Variability in Very Preterm Infants Depends on Neonatal Factors and Is Associated With Neurodevelopmental Risk

AIM: This study investigated central autonomic network maturation deviations using a previously defined machine learning model set to estimate a functional maturation age (FMA) from heart rate variability (HRV) analysis. We investigated whether these deviations were associated with maternal, fetal, perinatal, or postnatal complications and with neurodevelopment at 2 years of age. METHODS: Differences (ΔHRV) between post-menstrual age (PMA) and FMA were measured in a multicenter prospective cohort of 132 preterm infants born < 30 weeks gestational age (GA). The relationship between ΔHRV and clinical factors, occurrence of complications or alterations in neurodevelopment assessed by Ages and Stages Questionnaire (ASQ) at 2 years of age was studied. RESULTS: ΔHRV expressed in weeks delay at 34 weeks of PMA was greater when GA was lower (3 IQR 2.3-3.9) at 24-26 versus 1.3 (IQR 0.8-2.4) at 28-30 weeks GA (p < 0.0001), in cases of bronchopulmonary dysplasia (p < 0.0001) or patent ductus arteriosus (p < 0.0001). ΔHRV was also associated with altered social skills at 2 years of age (OR 2.05, 95% CI 1.02; 4.14 for each week, p < 0.05) but not with ASQ total score (p = 0.06). CONCLUSION: ΔHRV, early and non-invasively estimated, depends on GA, perinatal and postnatal complications. Its assessment could contribute to evaluation of neurodevelopmental risk.