Dietary protein intake in the first year of life might influence later growth. We conducted a systematic review to investigate the growth effects of interventions based on infant formula composition providing different amounts of protein within the first year of life of healthy term infants; in the absence of other comparable information over the investigated period, a meta-analysis further compared weight or length gain at 120 days from high- (>2.0 g/100 kcal) and low-protein (≤2.0 g/100 kcal) content formula groups. Twelve papers (n = 2275) were included and five of them (n = 677) contributed to the meta-analysis. Most studies compared a high-protein formula, a low-protein formula, and breastfeeding. Evidence from the systematic review was inconclusive due to heterogeneity in design and treatments. In the presence of modest heterogeneity but in the absence of publication bias, the weighted mean difference for weight gain at 120 days was -0.02 g/day (95% CI: -1.41, 1.45); with higher heterogeneity, the weighted MD estimate of length gain at 120 days was 0.004 cm/month (95% CI: -0.26, 0.27). Although limited and underpowered, evidence from the meta-analysis does not support the assumption that high- vs. low-protein content formulas during exclusive milk-feeding lead to different growth outcomes in the first months of life. Prospero registration number: CRD42017058535. IMPACT: The optimal amount of dietary protein that should be given to healthy full-term infants early in life is still debated. Despite heterogeneity in study design, treatments, and outcomes, this systematic review showed that there is no clear-cut effect on the growth of different amounts of protein intake from formulas or complementary feeding. Evidence from the meta-analysis based on the five articles enrolling infants <1 month of life does not support the previous assumption that high- vs. low-protein content formulas during exclusive milk-feeding lead to different growth outcomes in the first 4 months of life.
© 2023. The Author(s).