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

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

Despite hopes that early feeding could improve brain growth in premature babies, a new study finds no significant impact - changing assumptions about feeding strategies in newborn care.

In a study recently published in the journalChildren's researchResearchers evaluated the influence of early nutrition on brain development and cognition in very preterm (VPT) infants.

Neurodevelopment is a key health outcome of early life experience in preterm infants and is largely preprogrammed and experientially independent. Nevertheless, several important modifiable factors influence brain differentiation and growth, such as oxidative stress, nutrition, inflammation, infection, and environmental enrichment. Although neurological development is largely pre-programmed, it can be influenced by environmental factors such as infections, oxidative stress and diet.

Later stages of pregnancy are critical for brain development and growth, and those born prematurely are particularly vulnerable 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.

In addition, extremely preterm (EPT) infants, defined as those with gestational age (GA) 22–27 weeks, are at highest risk of postnatal malnutrition due to poor enteral intake, limited nutrient reserves, and enteral feeding intolerance. While the role of diet in shaping brain structure has been highlighted, the effects of macronutrients on brain volume remain uncertain, and previous studies report conflicting results.

About the study

In the present study, researchers examined the effects of early nutrition on brain development in premature infants. Approximately 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). A total of 72 infants were included in the final cohort after excluding 15 infants due to incomplete nutritional data, 31 infants without parental consent, and 32 infants without MRI scans.

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

Bronchopulmonary dysplasia was defined as supplemental oxygen 36 weeks after menstrual age (PMA). Provided nutrients were retrieved from electronic medical records and nutritional charts and entered into software to determine macronutrient, fluid, and calorie intakes for the first seven and 28 days. The nutritional protocol was based on the recommendations of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

VPT infants received breast milk starting two hours after birth. The fixture was introduced when enteral intake reached 100 mL/kg/day per protocol. MRIs were performed at time point (40 weeks PMA ± 1.7 weeks). Further, infants were evaluated using a standardized follow-up program including cognitive and motor assessments. A child psychologist conducted formal testing using the third edition of the Bayley Scales of Infant and Toddler Development (BSID) at age 2. Neurodevelopmental Impairment (NDI).

Statistical analyzes were performed both for the entire cohort and for two subgroups: VPT (GA 28–31 weeks) and EPT (GA 22–27 weeks). Associations between exposures (hospital morbidities and cumulative diet) and outcomes (MRI measures and neurodevelopment) were examined using Pearson and Spearman correlation and regressions.

Results

Mean GA and birth weight were 28.1 weeks and 1,190 g, respectively. Thirty-three infants were male, 46 were VPT, and 26 were EPT. Forty-six infants, primarily VPT infants, were delivered via cesarean section. On average, infants spent 8.6 days on mechanical ventilation. No child received postnatal insulin or corticosteroids. Average daily fluid intake and 28-day cumulative caloric intake were significantly higher in VPT infants than in EPT infants.

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

Fifty-nine infants had follow-up data at 2 years of age and 49 had BSID scores. Eleven infants, predominantly EPT infants, had NDI, although there were no significant differences between subgroups. Correlation analysis revealed significant positive associations of white matter volume with 28-day cumulative fluid intake, calories, protein, fat, and carbohydrate. In addition, the apparent diffusion coefficient (ADC) white matter was significantly correlated with fat, protein, carbohydrate, 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 neurological development. Likewise, the BSID language index was significantly correlated with mean daily fluid intake and 28-day cumulative carbohydrate and calorie intake, but not after covariate adjustment.

Conclusions

In summary, the study evaluated the effects of early postnatal nutrition on neurodevelopment at term and cognitive outcomes at two years in preterm infants. Results showed no significant correlations between macronutrient intake and brain morphology, volume, growth, or cognition despite initial unadjusted associations, suggesting that within a cohort receiving standardized diets according to clinical guidelines, additional individual variations in intake did not significantly influence brain growth and development.

However, the study authors note that major nutritional deficiencies, 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 postdischarge nutritional data, which may have influenced long-term neurodevelopmental outcomes. The strict nutritional protocol followed in this study ensured adequate intake and minimized potentially observable differences in brain development in infants.

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