The association between breastfeeding, drug exposure, and infant outcomes: more research is needed

In a recent study published in the PLOS ONE Journal, researchers explored the data linking breastfeeding, infant outcomes, and drug exposure.

The study aimed to identify databases and cohorts holding information on medicines’ impact on breastfeeding and pinpoint information and research gaps.

​​​​​​​Study: Where are the data linking infant outcomes, breastfeeding and medicine exposure? A systematic scoping review. Image Credit: Nastyaofly/Shutterstock.com

Background

It is difficult to separate the immunological, nutritional, and psychosocial elements of breastfeeding. It has a significant impact on women and infants.

The safety of a drug during lactation is complicated because it entails the effects of the drug on the infant as well as the mother, along with their interactions and bonding. Their vastly distinct pharmacokinetics and the demand to compute them for the mother, newborn, and preterm neonate further complicate safety evaluation.

About the study

The team performed a scoping review utilizing systematic searches to identify and map the databases containing quantitative proof of drug exposure, infant outcomes, and breastfeeding and to summarize the evidence.

Combining controlled vocabulary and free text terms, a total of 12 electronic databases, including Scopus, PubMed/Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, British Nursing Database, Web of Science, Drugs and Lactation Database (LactMed), Proquest, ZETOC, Turning Research Into Practice (TRIP), The Maternity & Infant Care Database from the Midwives Information and Resource Service (MIDIRS), and Wiley Online Library were searched till May 2022.

The text terms included ‘breastfeeding,’ ‘lactation,’ ‘infant nutrition,’ ‘pharmacovigilance,’ ‘drug monitoring,’ and drug surveillance.

Reports from databases or groups contained empirical information on breastfeeding, maternal exposure to medications, infant outcomes, and adverse drug reactions (ADRs) or pharmacovigilance.

After the search, duplicates were eliminated, and publication titles were evaluated to detect those more likely to satisfy the study’s inclusion criteria. Then, papers were selected for a thorough evaluation. All selected articles’ full texts were retrieved, read, and a consensus was reached regarding their inclusion.

Other potentially relevant studies were identified by examining the reference lists of the studies that had been included. The team distinguished between studies that reported established databases and those that reported recruited cohorts.

Results

The results of the search revealed 858 titles. Revision of the reference lists of eligible studies led to the identification of four additional studies, for a total of 862. Taking out duplicates reduced the total to 752 items. For 52 of these, the team was unable to locate an abstract, so the articles were reviewed as per title, date, and origin.

Prescription medications, marijuana, and pesticides negatively impacted breastfeeding rates in databases and cohorts. The duration of breastfeeding was curtailed for a variety of reasons, including patients’ concerns regarding prescription medications, weak suckling, or adverse impacts on the infant.

Due to reduced lactation after exposure to estrogen and progesterone, breastfeeding was terminated prematurely. Additionally, mental health medications, such as olanzapine, selective serotonin reuptake inhibitors (SSRIs), and antiepileptics, were associated with early weaning.

Some but not all neonates were impacted by drug exposure via breast milk. One cohort and two databases showed that some breastfed infants experienced severe adverse drug reactions (ADRs), primarily the well-known side effects of medications.

For instance, there have been cases of infant apnoea after breastmilk exposure to benzodiazepines or analgesics, infant hemorrhage or renal insufficiency after ketoprofen, and infant neutropenia after carbimazole. There was one case report of hypotension related to a beta blocker and one case of poor suckling and vomiting associated with carbamazepine.

Some infants whose mothers consumed opioids or benzodiazepines, olanzapine, or other mental health medications were sedated, tired, or constipated, which may have contributed to insufficient feeding and failure to acquire weight.

Minor and well-known ADRs were prevalent, affecting 94 of 838 infants. These ADRs included infant diarrhea in response to maternal antibiotics or antipsychotics and infant oral candidiasis in response to metronidazole. Two studies from a single database found no negative effects in neonates exposed to marijuana.

Developmental delay was observed in one of six infants, three of 22 olanzapine-exposed infants, five of 28 olanzapine-, quetiapine-, and risperidone-exposed infants, and one of 10 antidepressant-exposed infants.

After in-utero exposure to antiepileptic drugs, breastfed infants showed lower chances of manifesting autistic traits than formula-fed infants. Four out of 10 neonates exposed to lithium exhibited abnormal thyroid and renal function in venous blood specimens, while no other ADRs were observed.

Conclusion

The study findings showed that the available data from databases and cohorts are insufficient to support any definitive conclusions, except for the requirement for more information.

The researchers believe that due to the lack of data from databases, intergenerational ADRs from breastmilk exposure are unquantifiable but appear to be uncommon; however, concerns persist, especially for the central nervous system (CNS)-acting drugs.

There is sufficient evidence to necessitate frequent, in-depth surveillance of infants exposed through breastmilk, in addition to routine “well-baby” examinations. For some medications, there is insufficient information to determine whether breastfeeding benefits surpass the risks of exposure to breast milk.

The pervasive harm of decreased breastfeeding rates after drug exposure in late pregnancy, labor, and peripartum will be unquantifiable unless a whole-population database along with hospital-prescribing pharmaco-epidemiological research is conducted.