Supplementary Material for: Fetal and Postnatal Head Circumference Growth: Synergetic Factors for Neurodevelopmental Outcome at 2 Years of Age for Preterm Infants

Abstract: Preterm infants present higher risk of non-optimal neurodevelopmental outcome. Fetal and postnatal growth, in particular head circumference (HC), is associated with neurodevelopmental outcome. Objectives: We aimed to calculate the relationship between HC at birth, HC delta Z-score (between birth and hospital discharge), and non-optimal neurodevelopmental outcome at 2 years of corrected age in preterm infants. Methods: Surviving infants born ≤34 weeks of gestation were included in the analysis. The relationship between the risk of being non-optimal at 2 years and both HC at birth and HC growth was assessed. The 2 Z-scores were considered first independently and then simultaneously to investigate their effect on the risk of non-optimality using a generalized additive model. Results: A total of 4,046 infants with both HC measures at birth and hospital discharge were included. Infants with small HC at birth (Z-score <-2 SD), or presenting suboptimal HC growth (dZ-score <-2 SD), are at higher risk of non-optimal neurodevelopmental outcome at 2 years (respectively OR 1.7 [95% CI 1.4-2] and OR 1.4 [95% CI 1.2-1.8]). Interestingly, patients cumulating small HC Z-score at birth (-2 SD) and presenting catch-down growth (HC dZ-score [-2 SD]) have a significantly increased risk for neurocognitive impairment (OR >2) while adjusting for gestational age, twin status, sex, and socioeconomic information. Conclusions: HC at birth and HC dZ-score between birth and hospital discharge are synergistically associated to neurodevelopmental outcome at 2 years of corrected age, in a population-based prospective cohort of preterm infants born ≤34 weeks of gestation.