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

ABSTRACT 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 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.摘要 研究目的：明确人乳喂养极早产儿的性别与神经发育结局之间的关联，并校正早期测得的营养素摄入情况及其他新生儿混杂因素。研究方法：纳入连续收治的院内分娩、人乳喂养且胎龄<33周的早产儿作为研究对象。住院期间的能量与蛋白质摄入基于实测母乳成分进行计算。采用贝利婴儿发育量表第二版（Bayley Scales of Infant Development II）的精神发育指数与精神运动发育指数，在矫正胎龄20个月时评估受试者的神经发育状况。经单变量分析后，选取部分协变量开展线性多重回归分析。研究结果：本研究共纳入32例早产儿，平均胎龄为29.8（标准差1.8）周，出生体重中位数为1168g（四分位间距990~1419g）。分别有63.6%和15.2%的婴儿达到蛋白质与能量的最低推荐摄入量。93.8%的婴儿精神发育指数与精神运动发育指数处于正常范围。男性婴儿的精神发育指数与精神运动发育指数均值显著更低。在校正胎龄与实测能量摄入后，仅男性性别对精神发育指数与精神运动发育指数存在显著负向影响（B=-9.44；95%置信区间：-17.64~-1.23；校正后决定系数r²=0.17；P=0.026）。研究结论：在人乳喂养的极早产儿中，在校正胎龄与实测能量摄入后，男性婴儿在矫正胎龄20个月时的精神发育指数与精神运动发育指数得分显著更低。