Disease Pathophysiology Must Be Considered when Associating Medications with Changes in Milk Composition

A recent study by Whaites Heinonen et al. ¹ asserted that “maternal medications were associated with lower levels of protein and fat in milk, which could impose health risks for breastfed infants.” However, underlying disease states, such as depression or inflammatory conditions, may explain the observed changes in milk protein content rather than the medications themselves. At minimum, the conclusions cannot at present separate the association of medication from disease.

In breastfeeding medicine, the understanding of lactation physiology often lags behind pharmacology. Yet, it is well-documented that conditions such as depression or inflammation can affect the integrity of physiological barriers, including the blood–brain barrier.^2,3 If similar mechanisms influence the mammary gland, disease states could plausibly alter milk composition. Analyses should include comparisons between disease-matched and healthy controls to better isolate the impact of the disease from that of the medication.

An examination of the study’s selective serotonin reuptake inhibitor (SSRI) results could support this hypothesis. The significant reduction in milk protein levels for SSRI-exposed milk compared with healthy controls (adjusted p = 0.04) becomes nonsignificant when compared with disease-matched controls (adjusted p = 0.81). If these findings hold true, discontinuing SSRIs during lactation is unlikely to normalize milk protein content, as the underlying disease process—not the treatment—could drive these changes.

A recent study analyzing sertraline in the human milk of 38 women reported protein concentrations notably higher than those observed by Whaites Heinonen et al. ⁴ These discrepancies may stem from the high prevalence of concomitant inflammatory conditions in the SSRI and disease-matched samples analyzed by Whaites Heinonen, as well as differences in analytical methodologies between studies. Moreover, while Whaites Heinonen et al. found statistically significant differences in protein levels among SSRI-exposed mothers, these concentrations likely remain within published reference ranges for mature milk of term infants, ⁵ suggesting the differences may lack clinical significance.

Assertions that such changes in macronutrient content “impose health risks for breastfed infants” require robust evidence and must be carefully balanced against the well-established benefits of breastfeeding and maternal treatment. Maternal medication use is a common source of anxiety, often leading to the cessation of breastfeeding or treatment. However, untreated maternal diseases carry significant risks, ⁶ particularly for mental health treatments, as suicide remains a leading cause of death in peripartum women. ⁷ Researchers and healthcare providers must respect maternal instincts to protect their children while ensuring that maternal health is not compromised by overly cautious interpretations of research findings. ⁸

The interpretation of results such as in the Whaites Heinonen et al. study risks discouraging treatment for maternal depression, which could ultimately undermine maternal and infant health. Discontinuing maternal medication to prevent changes in milk macronutrient composition poses a risk of worsening health conditions while failing to account for the potential effects of the underlying disorder on milk composition. Future research must consider disease physiology to avoid conclusions that could needlessly deter essential maternal medication treatment.