Systematic Search of Height and Weight Changes of Exclusively Breastfed Infants Until 1 Year of age: A Contribution
Martje Van Neste1,2, Julia Macente3, Nina Nauwelaerts3,4
1Clinical pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Insights
Physiologically based pharmacokinetic (PBPK) models need updated infant data. This study provides new sex-specific height and weight equations for breastfed infants, improving drug exposure predictions during lactation.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Pediatric Pharmacology
- Computational Biology
Background:
- Physiologically based pharmacokinetic (PBPK) modeling predicts drug exposure in specific populations like infants.
- Current PBPK platforms lack physiological data influenced by infant feeding types (human milk vs. formula).
- Accurate infant PBPK models are crucial for assessing drug safety during lactation.
Purpose of the Study:
- To develop novel, sex-specific height and weight equations for exclusively breastfed infants.
- To incorporate these equations into PBPK platforms for improved infant modeling.
- To compare new equations with existing PBPK software data and validate against external datasets.
Main Methods:
- Systematic literature search to compile physiological data from 223 articles on exclusively breastfed infants.
- Extracted and analyzed sex-specific height and weight data from 35 and 43 articles, respectively.
- Developed mathematical equations for height and weight trajectories and compared them with existing PBPK models and Flemish data.
Main Results:
- Compiled and analyzed sex-specific height and weight data for exclusively breastfed infants.
- Generated novel mathematical equations describing infant height and weight trajectories.
- Found that current PBPK software equations often overestimate height and weight for breastfed infants from 6 months onwards compared to the new equations.
Conclusions:
- The developed equations provide a more accurate representation of exclusively breastfed infants' growth.
- Incorporating these novel equations into PBPK platforms can enhance the accuracy of drug exposure predictions.
- Further research into other physiological parameters (e.g., body composition) in breastfed infants is warranted for comprehensive PBPK modeling.
Abstract:
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.
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