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.

Israel Macedo,Lília Brito,Manuela Cardoso,Luis Pereira-Da-Silva

doi:10.31744/einstein_journal/2019ao4607

Abstract

ABSTRACTObjective: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 r2=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.

Highlights

Male sex has been described as an independent risk factor for adverse neurodevelopmental outcomes in preterm infants.[1,2] Some reasons have been proposed to explain this disadvantage in male preterm infants, such as impaired adaptive response to prenatal stress,(3) a pro-oxidant state in the placentae,(4) and specific morphological characteristics of the brain.[5,6]
Early human milk (HM) intake appears to be independently associated with better neurodevelopment.[7,8]
A study involving preterm infants did not find an interaction between diet and sex on neurodevelopment at 9 months’ corrected age.[9]. In contrast, other authors have suggested that suboptimal in-hospital nutrition in preterm infants can alter brain organization and neurocognitive outcome, with particular sensitivity in males.[10,11] In addition, improved neurodevelopmental outcome in female preterm infants receiving higher intakes of protein[10] and docosahexaenoic acid[12] has been reported

Summary

Introduction

Male sex has been described as an independent risk factor for adverse neurodevelopmental outcomes in preterm infants.[1,2] Some reasons have been proposed to explain this disadvantage in male preterm infants, such as impaired adaptive response to prenatal stress,(3) a pro-oxidant state in the placentae,(4) and specific morphological characteristics of the brain.[5,6]The type of feeding is an important independent factor for neurocognitive development. Early human milk (HM) intake appears to be independently associated with better neurodevelopment.[7,8]. It is controversial whether nutritional requirements in the neonatal period differ between male and female preterm infants, and whether neurodevelopment is affected. Published studies assessing the association between early diet and neurodevelopmental outcome adjusted to sex, in HM-fed preterm infants, have not measured the composition of HM. Nutrient intakes provided by HM have relied on its assumed composition, or on growth as surrogate of nutritional support.[10,11,13,14,15]

Methods

Results

Conclusion