Association of Commonly Prescribed Antepartum Medications and Incidence of Orofacial Clefting.

Background: Pharmacologic agents are often used in the antepartum period, however, studies on their effect on fetal development are limited. Thus, this study aims to examine the effect of commonly prescribed antepartum medications on the development of orofacial clefting.

Methods: Utilizing EPIC Cosmos deidentified data from approximately 180 US institutions was queried. Patients born between January 1, 2013, to January 1, 2023, were included. Eight OC cohorts were identified. Gestational medication use was identified by medications prescribed, provider-administered, or reported use by mothers. Medications used in at least 1 in 10,000 pregnancies were included in this analysis.

Results: A total of 12 098 newborns with available maternal pharmacologic data were born with any type of orofacial clefting. Prevalence for all oral clefts, any cleft palate, and any cleft lip were 20.56, 18.10, and 10.60 per 10 000 individuals, respectively. Notable significant exposures include most anticonvulsants, such as lamotrigine (OR1.33, CI 1.10-1.62), and topiramate (OR1.35, CI 1.13-1.62), as well as nearly all SSRIs/SNRIs, including fluoxetine (OR1.34, CI 1.19-1.51), sertraline (OR1.25, CI 1.16-1.34), and citalopram (OR1.28, CI 1.11-1.47). Corticosteroids were also correlated including dexamethasone (OR1.19, CI 1.12-1.27), and betamethasone (OR1.64, CI 1.55-1.73), as were antibiotics, including amoxicillin (OR1.22, CI 1.14-1.30), doxycycline (OR1.29, CI 1.10-1.52), and nitrofuran derivatives (OR1.10, CI 1.03-1.17).

Conclusion: New associations between commonly prescribed antepartum medications and orofacial clefting were found. These findings should be confirmed as causality is not assessed in this report. Practitioners should be aware of the potential increased risk associated with these medications.