Systematic Search of Height and Weight Changes of Exclusively Breastfed Infants Until 1 Year of age: A Contribution from the ConcePTION Project

Physiologically based pharmacokinetic (PBPK) modelling and simulation allows prediction of drug exposure in specific populations, such as infants during lactation. However, the influence of feeding type (e.g., human milk vs formula) on physiology has not yet been implemented in current PBPK platforms. We conducted a systematic search to compile datasets during the first year of life of infants who were exclusively breastfed for at least 4 months to incorporate in the virtual breastfed infant populations of PBPK platforms. Physiological data in exclusively breastfed infants were extracted from 223 included articles. This article reports the results on sex-specific height and weight data, collected from 35 and 43 articles, respectively, and assesses these data for girls and boys separately. The datasets were converted to pooled means ± standard deviation and subsequently to mathematical equations describing height and weight trajectories for exclusively breastfed infants. For the purpose of external verification, the novel function was compared with Flemish height and weight profiles stratified by maternal origin, revealing the most similarity with breastfed infants from European mothers. Furthermore, to assess the differences in current functions from PBPK software, data from the literature showed that current PBPK height and weight equations often overestimate relative to the novel equations for breastfed infants from 6 months onwards. These overestimations may result in differences in PBPK predictions. Systematic searches to assess maturational processes of other physiological parameters (e.g., body composition) in exclusively breastfed infants is likely warranted. These patterns should be incorporated in PBPK platforms to more adequately represent infant exposure to medicines, specifically for lactation-related medicine systemic exposure.