Quantifying breast milk intake by term and preterm infants for input into paediatric physiologically based pharmacokinetic models

Despite the many benefits of breast milk, mothers taking medication are often uncertain about the risks of drug exposure to their infants and decide not to breastfeed. Physiologically based pharmacokinetic models can contribute to drug‐in‐milk safety assessments by predicting the infant exposure and subsequently, risk for toxic effects that would result from continuous breastfeeding. This review aimed to quantify breast milk intake feeding parameters in term and preterm infants using literature data for input into paediatric physiologically based pharmacokinetic models designed for drug‐in‐milk risk assessment. Ovid MEDLINE and Embase were searched up to July 2, 2019. Key study reference lists and grey literature were reviewed. Title, abstract and full text were screened in nonduplicate. Daily weight‐normalized human milk intake (WHMI) and feeding frequency by age were extracted. The review process retrieved 52 studies. A nonlinear regression equation was constructed to describe the WHMI of exclusively breastfed term infants from birth to 1 year of age. In all cases, preterm infants fed with similar feeding parameters to term infants on a weight‐normalized basis. Maximum WHMI was 152.6 ml/kg/day at 19.7 days, and weighted mean feeding frequency was 7.7 feeds/day. Existing methods for approximating breast milk intake were refined by using a comprehensive set of literature data to describe WHMI and feeding frequency. Milk feeding parameters were quantified for preterm infants, a vulnerable population at risk for high drug exposure and toxic effects. A high‐risk period of exposure at 2–4 weeks of age was identified and can inform future drug‐in‐milk risk assessments.