1. Introduction

2. Sex-Specific Effects of Nutritional Supplements for Infants 

Early macronutrient supplementation did slightly increase growth in infancy, but none of these effects persisted into later life, and there were no significant sex differences.

Early supplements did not alter BMI or fat mass from infancy through to adolescence. Early macronutrient supplements are very unlikely to increase later adiposity or risk of obesity.

Supplementation slightly increased length in infancy despite significant heterogeneity but had no effect on weight, head circumference, or lean mass in infancy.  Supplementation does increase growth in infancy, but effects are small and do not persist after the first year. 

Different growth patterns between girls and boys before birth may potentially determine sex-specific responses to early environmental perturbations, including nutrition [15]. As is well known, preterm boys are at greater risk of adverse health outcomes than preterm girls [32]. Sex-specific effects have also been reported in animal studies. For example, in sheep, prenatal testosterone treatment reduced the body weight and height of newborn sheep from both sexes, but only females exhibited catch-up growth during 2–4 months of postnatal life [33]. Therefore, the effect of early macronutrient supplements might differ between girls and boys. However, we did not find any sex-specific effects of supplements on BMI in childhood. Supplementation did increase height z-scores in toddler boys but not girls, but the interaction terms were not statistically significant. Thus there is no evidence of widespread sex-specific effects of nutritional supplements in preterm and SGA infants, and therefore no evidence that neonatal nutritional supplements should differ for girls and boys.

Supplementation increased height z-scores for toddlers born >1 kg and decreased height in childhood and height z-scores at >3 years for children born ≤1 kg, although the interaction terms were not significant. Infants born preterm usually have low birthweight, and optimal nutrition plays a crucial role in supporting their growth to reduce morbidity in later life [8]. Furthermore, children with birth weight ≤1 kg usually have poorer growth than children with birth weight >1 kg [35,36].

Supplemented children born very preterm had lower BMI and BMI z-scores during toddlerhood and childhood and lower weight-for-length scores in toddlers than unsupplemented children, but these effects were not seen in children born extremely or moderate to late preterm, although the numbers of included children and trials are smallest in the moderate to late preterm group. The reasons for differences between gestational age at birth groups are not clear but might include greater neonatal illness in the smallest infants, thereby restricting growth in this group, and that weight gain in preterm infants is disproportionately fat [37].

Children who had received supplements post-discharge, but not those who received supplements in hospital, had greater weight, length in infancy, and height z-scores in toddlers. Children who had received supplements in hospital with additional protein also had lower BMI and measures of adiposity into adolescence.

Supplements increased height in toddlers only if the primary feed was formula, but not if the primary feed was breastmilk or if supplements were provided as both parenteral and enteral feeds. Supplemented infants whose primary feed was formula also had greater length and BMC in infancy but lower head circumference and head circumference z-scores in toddlers, although none of these interaction terms were significant. We had hypothesised that infants whose primary feed was breastmilk would receive less baseline (unsupplemented) nutritional intake and may therefore show greater effects of supplementation. Consistent with this, estimated protein intake was lower if breastmilk was the primary feed, and supplements provided a much greater increase in protein, carbohydrate, and energy intakes than for infants who received formula as primary feed. Therefore, comparison of nutrition intakes cannot explain the effect of supplements in the formula group. Another possible explanation may be the effect of growth-regulating hormones and growth factors in breastmilk. One study found a positive correlation between insulin-like growth factor (IGF)-I and weight z-scores in healthy infants [38]; infants fed formula milk had higher IGF-I levels than those fed breastmilk [39]. Leptin, adiponectin, and cortisol in breast milk could also play roles in the short-term control of food intake and have long-term effects on energy balance and body weight regulation [40,41].

This entry is adapted from the peer-reviewed paper 10.3390/nu14020392