Pre-term supplementation does not raise developmental risks, review finds

However, the assessment of relevant randomised trials also finds little support for the idea that supplementation improved later cognitive function.

“We found no evidence that early macronutrient supplementation for infants born small altered later cognitive function, although there was some evidence that supplementation may decrease motor impairment in toddlers,”​ concludes the study.

“Contrary to the findings from observational studies, evidence from randomised trials suggests that early macronutrient supplementation for infants born small improves some metabolic outcomes in childhood.”​

Infants born preterm or small for gestational age (SGA) have a higher risk of poor growth, developmental delay, and disability with a higher risk of obesity, diabetes, and cardiovascular disease as adults.

Supplementing preterm and SGA infants with higher protein and energy intake during the first few weeks after birth is linked with improved short-term growth and better developmental outcomes from infancy to adolescence.

However, a number of trials suggest there may be trade-offs between early cognitive development and later metabolic diseases in preterm infants.

Study details ​

A University of Auckland team began the systematic review and meta-analysis by looking at twenty-one randomised and one quasirandomised trial, which involved a total of 3,680 infants.

These studies included infants born preterm (less than 37 weeks’ gestation) or small (birth weight less than 2.5 kg or below 10th centile).

Studies that looked at supplemental intervention intended to increase intake of protein, carbohydrate, fat, energy, or protein to energy ratio with the primary aim of improving growth or development were shortlisted.

Results detailed that in toddlers born small, supplementation did not alter cognitive impairment and there were no differences in cognitive scores or motor scores between supplemented and unsupplemented groups.

However, fewer supplemented children had motor impairment. In further analyses, supplementation improved cognitive scores in boys but not girls born small and did not alter cognitive or motor scores in the subgroup of children born SGA.

In childhood, there was no difference in cognitive impairment or cognitive scores between supplemented and unsupplemented groups.

There were also no differences in blood pressure, triglyceride, and low-density lipoprotein (LDL) concentrations

However, supplemented children had lower fasting glucose and higher high-density lipoprotein (HDL) concentrations.

Further subgroup analyses found no evidence of differences in blood pressure between supplemented and unsupplemented groups in boys or girls born small, or in SGA children.

In adolescence, there was no difference between supplemented and unsupplemented groups in blood pressure, triglycerides, LDL and HDL concentrations, fasting blood glucose, insulin resistance, and fasting insulin concentrations.

Limited evidence ​

“We found limited evidence that early macronutrient supplements decreased the risk of motor impairment in toddlers and, contrary to our hypothesis, improved some metabolic outcomes in childhood,”​ says the team led by Jane Harding a physician scientist and professor of neonatology at the University of Auckland-based Liggins Institute.

“Despite the large numbers of trials and infants included, the evidence is limited by the overall low methodological quality, substantial heterogeneity, and few measures of outcomes after 3 years of age.”​

Subgroup findings looking into the different supplement timing, which found improvements to motor development when the intervention was given in hospital was attributed to the critical third trimester of gestation,

“Here there is extensive foetal brain development, and the brain accounts for 60% of total oxygen and caloric consumption,”​ the study points out.

“Adequate nutrients are therefore most likely to be important to support brain development during this critical period. ​

“These findings in one subgroup must be interpreted with caution but may suggest that providing preterm and SGA infants with supplemented nutrition during initial hospitalisation rather than later is more likely to benefit later developmental outcomes.”​

Source: Plos Medicine​

Published online: doi.org/10.1371/journal.pmed.1002952​​

“​Impact of macronutrient supplements for children born preterm or small for gestational age on developmental and metabolic outcomes: A systematic review and meta-analysis.”​

Authors: Luling Lin et al.