Key Practice Point
#1
Recommendation
What limited evidence exists suggests that there are no important differences in growth between human milk-fed and formula-fed infants from ages birth to three months.
From four months to one year, there may be small differences in growth that may even out by two years of age. Formulas with protein content <1.8 g/100 kcal have been associated with growth patterns more similar to infants fed human milk than higher protein formulas, although the size of this effect is of questionable clinical relevance.
The effect of human milk feeding duration on infant growth is not clear.
The presence of confounding factors in this body of largely observational research limits the certainty of these results.
Evidence Summary
Growth Patterns in Infancy
A 2022 systematic review and meta-analysis of 19 clinical trials found similar growth patterns from birth to three months of age between human milk- and formula-fed infants. There was a small but statistically significant higher weight gain in formula-fed infants compared to human milk-fed infants between four to six months of age, although missing evidence limited the conclusiveness of this data. Effects past six months of age were not studied. Evidence was mixed and varied by protein content.
A 2019 umbrella review found one systematic review examining the effect of breastfeeding or formula feeding on infant growth patterns. Results were inconsistent and the review concluded that infant growth rates may differ according to food source, without elaborating in what way.
A 2019 systematic review and meta-analysis of 20 studies (19 prospective observational studies, one RCT) suggested that longer breastfeeding duration was associated with slightly lower overall weight gain, overall length gain and earlier BMI peak. This relationship was only seen in studies from developed countries and the only RCT included in the review found no differences.
Growth Patterns at 2+ Years
A 2020 systematic review of 42 mostly cohort studies (41 cohorts, one RCT) reported that 14 of 21 studies (66%) that compared overweight/obesity risk in infants who have ever consumed human milk to infants who have never consumed human milk found a lower risk of overweight and obesity at two years of age and older in those who had never consumed human milk, especially when human milk consumption ≥6 months. However, the only RCT that followed participants to 16 years of age found no differences. The authors found inconsistent and insufficient evidence to draw conclusions as to the effect of the duration, proportion, intensity or amount of human milk consumption on overweight and obesity at two years, either as an exclusive or supplementary nutrition source.
A 2019 umbrella review including eight systematic reviews and meta-analyses concluded that the effect of breastfeeding on future obesity is unclear due to the presence of bias and confounding factors, including loss to follow up.
Grade of Evidence C
Remarks
The clinical relevance of these differences is questionable and this data is highly susceptible to confounding factors. Additionally, some non-responsive feeding behaviours (such as using a large bottle or encouraging the child to finish the bottle) are associated with excess weight gain and do not apply to breastfed infants, introducing another confounding variable.
Many studies of infant formulas have been found prone to selective reporting bias and are industry funded. Studies comparing feeding methods in infants should be examined with consideration of these factors.
The terms “overweight” and “obesity” were rarely defined in the studies cited.
Preterm or low birth weight infants may regain birth weight more quickly when they are enterally given formula rather than enterally given donor breast milk. Preterm and low birth weight infants also increased weight, length and head circumference more quickly when they were enterally fed formula compared to donor human milk. However, long-term growth was not different between groups.