Background: High protein intake during infancy may contribute to obesity later in life in infants who are not exclusively breastfed. Lowering the protein content of infant formula so it is closer to that of mature breast milk may reduce long-term risk of overweight or obesity in formula-fed infants.

Objective: We assessed the effects of whey-predominant formulas with a protein content of 1.8 g/100 kcal (lower than that in most current formulas and closer to breast milk) on infant growth by comparing against WHO growth standards and breastfed infants. Design: A multicenter pooled analysis was conducted with the use of individual participant data (n = 1882) from 11 randomized controlled trials of healthy term infants. Mixed-effects models that used ANCOVA were generated to estimate weight-for-age z score (WAZ), as well as length-for-age, BMI-for-age, and head circumference-for-age z scores at age 4 mo in infants fed a lower-protein infant formula (LPF) or a lower-protein infant formula with additional active ingredients (probiotics, prebiotics, or both) (LPFA) and breastfed infants. Estimates, including 95% CIs, were compared with a ±0.5 SD of WHO growth standards, a benchmark for clinically significant differences.

Results: The 95% CIs for pooled estimates of WAZ were within ±0.5 SD of WHO growth standards for the LPF [0.07 (-0.16, 0.29)] and LPFA [0.22 (0.01, 0.43)] groups. WAZ was higher in the LPF (P < 0.001) and LPFA (P = 0.003) groups than in the breastfed infants, likely because breastfed infants had a relatively low WAZ [-0.23 (-0.51, 0.05)] compared with WHO growth standards. The 95% CIs for all other z scores in the LPF and LPFA groups were within ±0.5 SD of WHO growth standards, except for head circumference, for which the upper limit of the 95% CI slightly exceeded 0.5 SD. No difference was observed in any z scores between the LPF and LPFA groups. Conclusion: Whey-predominant infant formula with a lower protein content that more closely resembles that of breast milk supports healthy growth comparable to the WHO growth standards and close to breastfed infants.