Male sex is an independent risk factor for poor neurodevelopmental outcome at 20 months' corrected age, in human milk-fed very preterm infants: a cohort study

Objective: To determine associations between sex and neurodevelopmental outcomes in human milk-fed very preterm infants, adjusted to early measured nutrient intakes and other neonatal cofactors. Methods: Consecutive inborn human milk-fed infants, with gestational age <33 weeks, were eligible. In-hospital energy and protein intakes have relied on measured human milk composition. The Bayley Scales of Infant Development II mental and psychomotor developmental indexes were used to assess neurodevelopment at 20 months' corrected age. After univariate analysis, some covariables were used for linear multiple regression. Results: Thirty-two infants were included, with a mean (standard deviation) gestational age of 29.8 (1.8) weeks, and a median birth weight of 1168g (interquartile range 990-1419g). Minimum recommended intakes were achieved in 63.6% and 15.2% of infants for protein and energy, respectively. The mental and psychomotor developmental indexes were within normal limits in 93.8% of infants. The mean mental and psychomotor developmental indexes were significantly lower in males. Only male sex negatively and significantly affected the mental and psychomotor developmental indexes (B=-9.44; 95%CI: -17.64- -1.23; adjusted r(2) = 0.17; p = 0.026), adjusted to gestational age and measured energy intake. Conclusion: In human milk-fed very preterm infants, males had a significantly lower mental and psychomotor developmental indexes score at 20 months' corrected age, adjusted for gestational age and measured energy intake.