NSAID use in first trimester may increase risk of congenital anomalies

Women who take prescribed non-steroidal anti-inflammatory drugs (NSAIDs) in early pregnancy, specifically the first trimester, may increase their risk of giving birth to a child with congenital anomalies, especially cardiac septal anomalies, compared with women who do not take NSAIDs during this period, according to a recent study published in Birth Defects Research (Part B).

This nested case-control study employed 3 databases in Québec, Canada: La Régie de l'Assurance Maladie du Québec (RAMQ), Med-Echo, and Le fichier des événements démographiques du Québec of l'Institut de la Statistique du Québec (ISQ). The 3 databases were connected to build a population-based pregnancy registry that contained records of all pregnancies from January 1, 1997, to June 30, 2003 (N=36,387).

The age range of the women at study entry was 15 to 45 years. Eligible participants were required to have ongoing insurance by the RAMQ drug plan for ≥1 year before and during the pregnancy, must have been prescribed an NSAID or other medications during pregnancy, and must have had a singleton live birth.

The primary end point was cardiac septal closure and related abnormalities, such as bulbus cordis anomalies, transposition of great vessels, and endocardial cushion defects. Congenital irregularities associated with other major organs also were measured (eg, pulmonary artery defects, respiratory system anomalies, central nervous system anomalies, defects of the limbs and musculoskeletal system).

A total of 1,056 women (2.9%) took prescribed NSAIDs in the first trimester. The most commonly filled prescriptions were naproxen (35%), ibuprofen (26%), rofecoxib (15%), diclofenac (9%), and celecoxib (9%), accounting for 95% of prescriptions. Half of the women who used NSAIDs filled prescriptions with an estimated duration of ≤10 days, and 95% had an estimated duration of ≤40 days. Of the 1,056 women who were taking NSAIDs before giving birth, there were 93 (8.8%) live births of children with congenital irregularities, compared with 2,478 (7%) live births of children with congenital anomalies among the 35,331 women not taking prescribed NSAIDs. The proportion of infants with ≥1 congenital defect who were born to women taking NSAIDs in the first trimester was 16.1%, whereas the proportion who were born to women not taking NSAIDs was 14.2%.

The adjusted OR for any congenital abnormalities in the infants of women who were taking NSAIDs in the first trimester was 2.21 (95% CI, 1.72–2.85). The adjusted OR for cardiac septal closure anomalies was 3.34 (95% CI, 1.87–5.98). The authors did not find significant associations between NSAID use and abnormalities of other organs.

The authors stated that their findings mirror prior epidemiologic research on elevated risks linked to certain cardiac abnormalities. They also stated that the possible harm in taking NSAIDs during pregnancy has not been well publicized.

SOURCE Ofori B, Oraichi D, Blais L, Rey E, Bérard A. Risk of congenital anomalies in pregnant users of non-steroidal anti-inflammatory drugs: A nested case-control study. Birth Defects Res B Dev Reprod Toxicol. 2006; 77:268–279.