Writing in the journal Nutrients, researchers in the United States analyzed data from 5,515 infants to evaluate how cow-milk-based infant formula types and breastfeeding affect growth in infants and toddlers under the age of three.
Results showed that non-standard infant formula, such as those marketed as “gentle digestion,” or “hypoallergenic”, may have a differential effect on growth during the first year of life compared to standard infant formula and breastfeeding.
“These findings raise important questions about the metabolic and growth-related consequences of altered formula composition during infancy,” the researchers wrote.
Infant formula composition and obesity risk
Nutrition during the first 1,000 days of life actively shapes metabolic programming, gut microbiome development and long-term health. Although breast milk is recognized as providing the optimal infant nutrition, only around 44% of infants are exclusively breastfed at six months, according to the World Health Organization (WHO).
In powdered formulas, many are often lactose-reduced or lactose-free. These non-standard formulas often contain added carbohydrates such as maltodextrin or sucrose, which can raise blood glucose, disrupt satiety and potentially encourage overfeeding. Hydrolyzed protein formulas may also alter metabolic responses due to faster absorption.
These mechanisms, the researchers on the new study explained, may increase adiposity rather than linear growth, noting that elevated weight-for-age and BMI z-scores could signal a higher risk of overweight and obesity later in childhood.
Non-standard infant formulas and higher early growth and BMI
The researchers conducted a retrospective cohort study in children in the University of Iowa Health Care outpatient pediatric clinics between January 2017 and January 2024
Infants were categorized into three feeding groups at two months: non-standard formula, standard cow-milk formula and exclusively breastfed.
Non-standard formulas were defined as formulas with altered protein or carbohydrate content compared with standard formulas. This includes lactose-reduced or lactose-free formulas, partially or extensively hydrolyzed protein formulas, and formulas marketed for “sensitive stomachs,” “gentle digestion,” or “hypoallergenic”.
In contrast, a standard infant formula is a cow-milk–based formula with intact proteins and lactose as the primary carbohydrate, closely modeled on the macronutrient profile of human milk.
The researchers assessed growth using WHO z-scores at 12 and 24 months: weight-for-age, length-for-age, weight-for-length and BMI.
Results indicated that at two months, 35% of infants were breastfed, 42% received standard formula, and 23% received non-standard formula.
At 12 months, infants on non-standard formula weighed more than those on standard formula, having higher weight-for-age and BMI scores. At 24 months, non-standard formula infants still had higher weight-for-age scores compared to the standard formula group, while BMI, length-for-age and weight-for-length scores did not differ significantly.
Across both time points, both formula-fed infant groups consistently had higher growth scores than breastfed infants for weight-for-age, BMI, length-for-age and weight-for-length, even after adjusting for confounders.
Subgroup analysis also showed that female infants on non-standard formula had significantly higher BMI z-scores at 12 months versus standard formula, an effect that did not appear in males. White and non-Hispanic infants on non-standard formula also showed higher BMI z-scores than those on standard formula.
“Non-standard infant formulas appear to have a differential impact on early growth compared to standard formulas and breastfeeding, particularly in the first year of life,” the researchers concluded. “Our findings highlight the need for clearer clinical guidance regarding their use in infants without medical indications.”
They stated that future research is needed to evaluate the long-term metabolic and developmental consequences of non-standard formulas.
Source: Nutrients 2025, 17(19), 3111. doi: 10.3390/nu17193111; “Effects of Infant Formula Type on Early Childhood Growth Outcomes: A Retrospective Cohort Study.” Authors: Rani, U. et al.
