Abstract
Background: Global health organizations recommend breastfeeding, but maternal pharmacotherapy can disrupt this due to safety concerns. Physiologically based pharmacokinetic (PBPK) models predict medication transfer through breastfeeding, relying on validated milk intake volume data. However, the literature is mainly focused on different measurement methods, or such intake data have been collected without systematic review. This systematic review therefore aims to gather data on human milk intake volume derived using the (dose-to-the-mother) deuterium oxide dilution method, allowing for comparison with the literature. Additionally, it aims to explore the effects of maternal conditions on milk intake volume. Methods: PubMed, Embase, Web of science, Cochrane library, Scopus and CINAHL were searched for studies on the dilution method and breastfeeding in healthy infants. Risk of bias was assessed using the Newcastle-Ottawa scale (NOS) and the Risk of Bias 2 (RoB2) tool. Data on mean human milk intake volume were extracted and synthesized (mL/day and mL/kg/day) throughout infancy. Results: Sixty studies (34 countries) reported on the milk intake volume of 5502 infants. This intake was best described by logarithmic regression y(mL/kg/day) = 149.4002 - 0.2268 × x - 0.1365 × log(x) (x = postnatal age, days). Maternal conditions showed no significant influence on human milk intake, except for maternal smoking (reduction). Conclusions: This function corresponds with previous research, particularly for infants aged between 1.5 and 12 months. The limited availability of early infancy data underscores the need for additional data for future PBPK modeling to enhance informed healthcare decisions and improve outcomes for mothers and infants.