We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, OpenGrey, clinical trial registries, and conference proceedings in October 2022.
SELECTION CRITERIA: We included 11 RCTs (1185 infants) conducted in high-income countries. Seven trials (1629 infants) compared high-
protein formula against standard-
protein formula, and four trials (256 infants) compared standard-
protein formula against low-
protein formula. The longest follow-up was 11 years. High-
protein formula versus standard-
protein formula We found very low-certainty evidence that feeding healthy term infants high-
protein formula compared to standard-
protein formula has little or no effect on underweight (MD in weight-for-age z-score 0.05 SDs, 95% CI -0.09 to 0.19; P = 0.51, I2 = 61%; 7 studies, 1629 participants),
stunting (MD in height-for-age z-score 0.15 SDs, 95% CI -0.05 to 0.35; P = 0.14, I2 = 73%; 7 studies, 1629 participants), and wasting (MD in weight-for-height z-score -0.12 SDs, 95% CI -0.31 to 0.07; P = 0.20, I2 = 94%; 7 studies, 1629 participants) in the first year of life. We found very low-certainty evidence that feeding healthy infants high-
protein formula compared to standard-
protein formula has little or no effect on the occurrence of
overweight (RR 1.26, 95% CI 0.63 to 2.51; P = 0.51; 1 study, 1090 participants) or
obesity (RR 1.96, 95% CI 0.59 to 6.48; P = 0.27; 1 study, 1090 participants) at five years of follow-up. No studies reported all-cause mortality. Feeding healthy infants high-
protein formula compared to standard-
protein formula may have little or no effect on the occurrence of adverse events such as
diarrhea,
vomiting, or
milk hypersensitivity (RR 0.93, 95% CI 0.76 to 1.13; P = 0.44, I2 = 0%; 4 studies, 445 participants; low-certainty evidence) in the first year of life. Standard-
protein formula versus low-
protein formula We found very low-certainty evidence that feeding healthy infants standard-
protein formula compared to low-
protein formula has little or no effect on underweight (MD in weight-for-age z-score 0.0, 95% CI -0.43 to 0.43; P = 0.99, I2 = 81%; 4 studies, 256 participants),
stunting (MD in height-for-age z-score -0.01, 95% CI -0.36 to 0.35; P = 0.96, I2 = 73%; 4 studies, 256 participants), and wasting (MD in weight-for-height z-score 0.13, 95% CI -0.29 to 0.56; P = 0.54, I2 = 95%; 4 studies, 256 participants) in the first year of life. No studies reported
overweight,
obesity, or all-cause mortality. Feeding healthy infants standard-
protein formula compared to low-
protein formula may have little or no effect on the occurrence of adverse events such as
diarrhea,
vomiting, or
milk hypersensitivity (Peto OR 1.55, 95% CI 0.70 to 3.40; P = 0.28, I2 = 0%; 2 studies, 206 participants; low-certainty evidence) in the first four months of life.
AUTHORS' CONCLUSIONS: We are unsure if feeding healthy infants high-
protein formula compared to standard-
protein formula has an effect on
undernutrition,
overweight, or
obesity. There may be little or no difference in the risk of adverse effects between infants fed with high-
protein formula versus those fed with standard-
protein formula. We are unsure if feeding healthy infants standard-
protein formula compared to low-
protein formula has any effect on
undernutrition. There may be little or no difference in the risk of adverse effects between infants fed with standard-
protein formula versus those fed with low-
protein formula. The findings of six ongoing studies and two studies awaiting classification studies may change the conclusions of this review.