Maternal analgesic use and cardiovascular malformations

Abstract

Certain drugs used during pregnancy have been associated with an increased risk of congenital malformations in offspring. Whether maternal use of analgesics increases the risk of cardiovascular malformations (CVM) is unclear. We used data from the Baltimore-Washington Infant Study, a population-based case-control investigation of environmental factors and CVM, to examine CVM and maternal analgesic use during the periconceptional period (3 months before and 3 months after conception). During the period 1981–1989, 2,842 infants with CVM (case infants) and 3,516 nonmalformed infants (control infants) were ascertained with information on maternal drug use elicited from home interviews. We compared case and control infants on frequency of maternal use of analgesics during the periconceptional period using odds ratios (ORs) and 95% confidence intervals (CIs) for ORs. Fisher's Exact CIs for ORs were estimated when one or more cell counts fell below 5. Periconconceptional use of any analgesic among control mothers was 20.0%, with the more commonly used analgesics being medications containing aspirin (10.2%), nonsteroidal anti-inflammatory drugs (NSAIDs) (5.9%), and opioids (5.4%). Analyses type of analgesic and CVM diagnosis identified associations of: ibuprofen with transposition of the great arteries (TGA) (OR = 2.1, CI = 1.3, 3.4); atrioventricular septal defects (OR = 1.8, CI = 1.1, 2.8); and membranous ventricular septal defects (OR = 1.5, CI = 1.1, 2.1). Medications containing codeine were also associated with TGA (OR = 1.9, CI = 1.1, 3.2). Maternal use of ibuprofen or codeine containing analgesics during the periconceptional period might be associated with an increased risk of certain cardiovascular malformations in infants. Further investigation into these findings is needed to examine potential confounding by indication.