Type of infant formula increases early weight gain and impacts energy balance: a randomized controlled trial

Abstract

Background Millions of infants are fed breast milk substitutes, and the type of infant formula can impact weight gain patterns. Objective We conducted a randomized controlled trial to determine the direct impact of 2 types of infant formula (cow milk formula, CMF; extensively protein hydrolyzed formula, EHF) on growth and energy balance. Design A racially diverse group of formula-fed infants (n = 113) were randomly assigned to either CMF or EHF from the age of 0.75 to 12.5 mo. At each monthly visit, anthropometric measures were obtained to determine growth z scores and weight gain velocity, and to categorize early weight gain patterns as rapid or nonrapid. Also, diet records were collected to determine energy from formula and other sources. Comprehensive assessments of energy balance (intake, expenditure, loss) were made at 0.75, 3.5, and 12.5 mo. Results Beginning 3 wk after randomization, CMF infants had significantly higher weight, but not length, z scores than did EHF infants, and this persisted after solid foods complemented the formula diet. On average, weight gain velocity from 0.75 to 4.5 mo was within the range of typically growing infants for both groups, yet velocity was 3.9 g/d greater for CMF infants (P = 0.002), who were more likely to be classified as an early rapid weight gainer, than EHF infants (46% compared with 18%; P = 0.007). Early differences in energy intake and fecal loss, yielding greater energy available for deposition among CMF infants, contributed to the differential weight gain patterns. There were no significant differences between the formula treatment groups in total energy expenditure or sleeping energy expenditure. Conclusions Among healthy infants, the type of formula impacted on early rapid weight gain patterns owing to energy intake and loss mechanisms. Research is needed to identify the macronutrients and other compositional constituents in EHF and breast milk that promote satiation and healthy weight gain during sensitive periods of development. This trial was registered at clinicaltrials.gov as: NCT01700205.

Early rapid weight gain among formula‐fed infants: Impact of formula type and maternal feeding styles

“…Data were collected during a double‐blind RCT that investigated the effect of infant formula type on primary outcomes of growth and energy balance (ClinicalTrials.gov no. NCT01700205) . The Office of Regulatory Affairs at the University of Pennsylvania approved all procedures, and informed consent was obtained from each mother prior to study entry.…”

“…Healthy term infants (N = 113), whose mothers' decision not to breastfeed were firmly established and who were being fed cow milk formula (CMF) prior to enrollment, were randomized to one of two groups that differed in the type of formula provided for the infants: CMF (Enfamil, Mead Johnson Nutrition, Evansville, Indiana USA) or EHF (Nutramigen, Mead Johnson Nutrition) for the first year of life (see reference for more details on the RCT design and methods). Beginning at 0.75 month, these infant formulas, which were identical in calories (66.7 kcal/100 mL) and contained no added prebiotics or probiotics, were provided to the mothers monthly to exclusively feed their infants.…”

“…Anthropometric measures were normalized to z scores using World Health Organization (WHO) growth standards . From these data, we determined whether the infant was an “early rapid weight gainer.” We defined early as the first 4.5 months, a time period when formula accounted for the vast majority, if not all, of the infants' energy intake . We defined rapid weight gain as an increase in weight‐for‐length z score (WLZ) > 0.67 standard deviation between the ages of 0.5 and 4.5 months .…”

“…Its milk proteins are treated with enzymes to hydrolyze the peptide bonds to reduce allergenicity, resulting in high levels of free amino acids (FAAs) and low‐molecular‐weight peptides, known satiation signalers . In the longer term, a recent RCT revealed that infants who were fed EHF for the first year of life were significantly less likely to gain weight rapidly during the first four months than those randomized to CMF …”

“…Because the dyads in the recent RCT were repeatedly phenotyped for maternal feeding styles and how often the infant was fed formula daily (hereafter referred to as formula feeding pattern), the data provide a unique opportunity to examine the longitudinal impact of early diet (what formula is fed to the infant) and feeding styles (how the mother feeds the formula) on early rapid weight gain among formula‐fed infants in ways that cross‐sectional studies cannot. The repeated measure of maternal feeding styles and feeding patterning allows us to characterize the stability of maternal feeding style traits and patterning of formula feeding and to determine whether either has independent effects or interacts with the type of formula on how rapidly infants gain weight during the sensitive period of early life.…”