(2) Sex Differences in Preterm Infant Growth Based on Macronutrients from Donor Human Milk

Background: From as early as the first trimester, male and female infants exhibit distinct growth trajectories, which persist postnatally as reflected in sex-specific growth charts. Among preterm infants, male neonates are more frequently affected by growth failure during their NICU stay. Optimizing nutrition in this population is critical, as early growth is closely linked to long-term neurodevelopmental outcomes.

Objectives: This study aimed to assess sex-specific differences in short-term growth among preterm infants receiving pasteurized donor human milk (DHM), with a focus on macronutrient intake, and to explore the potential need for sex-specific nutritional strategies.

Design/Methods: We conducted a retrospective chart review of preterm infants (≤32 weeks gestational age) admitted to the Riley Hospital for Children NICU between December 2022 and December 2023. Infants received at least 3 consecutive days of the same DHM batch, which was analyzed for macronutrient composition using the Miris Human Milk Analyzer. Daily intake of calories, protein, fat, and carbohydrates (per kg body weight) was calculated from individualized feeding recipes. Growth outcomes were assessed using changes in weight, length, and head circumference (HC) Z-scores. Linear mixed models were used to evaluate the interaction between sex and macronutrient intake on growth outcomes, adjusting for baseline anthropometrics, gestational age at DHM initiation, and maternal milk volume. The model accounted for repeated measures and clustering by DHM lot.

Results: Among 87 infants (61% female), there were no statistically significant sex differences in baseline characteristics, including gestational age and birth anthropometrics (Table 1). There were no significant sex differences for carbohydrate, fat, or total caloric intake on changes in weight, length, and HC z-score. We found a significant interaction between average daily protein intake and sex for weight growth change (p = 0.044) as shown in Figure 1. Specifically, increased protein intake was associated with improved weight z-score changes in females but decreased weight z-score changes in males.

Conclusions: This study highlights a potential sex-specific response to protein intake in preterm infants receiving DHM, with divergent effects on weight gain between males and females. These findings suggest that uniform nutritional strategies may not equally benefit all preterm infants and underscore the need for further research into sex-specific nutritional interventions in the NICU.