Feeding strategies in preterm infants do not alter brain growth or cognition

Despite hopes that early nutrition could enhance brain growth in preterm infants, a new study finds no significant impact—challenging assumptions about feeding strategies in neonatal care.

Study: Impact of early nutrition on brain development and neurocognitive outcomes in very preterm infants. Image Credit: Mircea Moira / Shutterstock

In a recent study published in the journal Pediatric Research, researchers assessed the impact of early nutrition on brain development and cognition in very preterm (VPT) infants.

Neurodevelopment is an essential health outcome of early life experience in preterm infants, and it is largely preprogrammed and experience-independent. Nevertheless, several important modifiable factors influence brain differentiation and growth, such as oxidative stress, nutrition, inflammation, infection, and environmental enrichment. While largely preprogrammed, neurodevelopment can be influenced by environmental factors such as infection, oxidative stress, and nutrition.

Later gestational stages are critical for brain development and growth, and those born preterm are particularly susceptible to disruptions in this process because much of their maturation and neurogenesis occurs outside the womb. Preterm infants have smaller brain volumes and impaired neurocognitive development compared to infants born at term.

Further, extremely preterm (EPT) infants, defined as those with gestational age (GA) 22–27 weeks, have the highest postnatal malnutrition risk due to deficient enteral uptake, limited nutrient reserves, and enteral feeding intolerance. While the role of nutrition has been emphasized in shaping brain structure, the effects of macronutrients on brain volume remain uncertain, with previous studies reporting conflicting results.

About the study

In the present study, researchers examined the impact of early nutrition on the development of the brain in preterm infants. About 170 VPT infants with GA < 32 weeks cared for at a children’s hospital between July 2011 and December 2014 were screened for inclusion. Of these, 150 infants survived, and 118 underwent brain magnetic resonance imaging (MRI). Overall, 72 infants were included in the final cohort after excluding 15 outborn infants due to incomplete nutritional data, 31 infants without parental consent, and 32 infants lacking MRI scans.

The team collected the following data: GA, antenatal steroid exposure, delivery mode, sex, birth weight, and Apgar scores. The number of days on mechanical ventilation served as a surrogate for illness severity. Necrotizing enterocolitis was defined as a histopathological diagnosis following laparotomy. Sepsis was the presence of clinical symptoms and either higher C-reactive protein levels or a positive blood culture.

Bronchopulmonary dysplasia was defined as receiving supplemental oxygen at 36 weeks post-menstrual age (PMA). Nutrients provided were retrieved from electronic medical records and nutrition charts and entered into software to determine the intake of macronutrients, fluid, and calories for the first seven and 28 days. The nutritional protocol was based on the recommendations of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).

VPT infants received human milk starting two hours after birth. Fortification was introduced when enteral intake reached 100 mL/kg/day, per protocol. MRIs were performed at term (40 weeks PMA ± 1.7 weeks). Further, infants were assessed based on a standardized follow-up program, including cognitive and motor assessments. A child psychologist performed formal testing using the third edition of the Bayley Scales of Infant and Toddler Development (BSID) at age 2. Neurodevelopmental impairment (NDI) was defined as a cerebral palsy diagnosis or a score below 85 in any BSID domain.

Statistical analyses were performed for the entire cohort as well as two subgroups: VPT (GA 28–31 weeks) and EPT (GA 22–27 weeks). The associations between exposures (hospital morbidities and cumulative nutrition) and outcomes (MRI measures and neurodevelopment) were investigated using Pearson and Spearman correlation and regressions.

Findings

The mean GA and birth weight were 28.1 weeks and 1,190 g, respectively. Thirty-three infants were males, 46 were VPT, and 26 were EPT. Forty-six infants, mainly VPT infants, were delivered via Cesarean section. On average, infants spent 8.6 days on mechanical ventilation. No infant received postnatal insulin or corticosteroids. The mean daily fluid intake and the 28-day cumulative calorie intake were significantly higher in VPT infants than in EPT infants.

MRI assessments revealed no significant differences in Kidokoro scores or total brain volumes between VPT and EPT infants. While white matter volume was lower in EPT infants numerically, this difference was not statistically significant after adjusting for covariates.

Fifty-nine infants had follow-up data at age 2, and 49 had BSID scores. Eleven infants, predominantly EPT infants, had NDI, albeit there were no significant differences between the subgroups. The correlation analysis revealed significant positive associations of white matter volume with 28-day cumulative fluid intake, calories, protein, fat, and carbohydrates. Further, the white matter apparent diffusion coefficient (ADC) was significantly correlated with fat, protein, carbohydrates, calories, and enteral fluid intake.

Nevertheless, these correlations were no longer significant after adjusting for covariates. This suggests that individual variations in macronutrient intake did not directly influence brain growth or neurodevelopment. Likewise, the BSID language index significantly correlated with the mean daily fluid intake and the 28-day cumulative intake of carbohydrates and calories, but not after covariate adjustment.

Conclusions

In sum, the study evaluated the impact of early, postnatal nutrition on neurodevelopment at term and cognitive outcomes at two years in preterm infants. The findings showed no significant correlations between the intake of macronutrients and brain morphology, volumes, growth, or cognition, despite initial unadjusted associations, suggesting that within a cohort receiving standardized nutrition according to clinical guidelines, additional individual variations in intake did not significantly impact brain growth and neurodevelopment.

However, the study authors note that larger nutritional deficits, which were not observed in this cohort, may still pose risks to brain development. Additionally, the study had limitations, including its small sample size, retrospective design, and lack of post-discharge nutritional data, which may have influenced long-term neurodevelopmental outcomes. The strict nutritional protocol followed in this study ensured adequate intake, potentially minimizing any observable differences in brain development among infants.