(115) Associations between Antibiotics and Non-Cardiac Birth Defects, National Birth Defects Prevention Study and Birth Defects Study to Evaluate Pregnancy Exposures

Publication Number: 1110

Background: Untreated bacterial infections during pregnancy can have serious consequences for both mother and infant, but some antibiotics have been associated with birth defects.

Objectives: We analyzed National Birth Defects Prevention Study (NBDPS; 1997-2011) and Birth Defects Study to Evaluate Pregnancy Exposures (BD-STEPS; 2014-2018) data to assess associations between specific antibiotics and non-cardiac birth defects.

Methods: Cases included infants, stillbirths, or terminations with a birth defect and controls included live born infants without a birth defect. Mothers of cases and controls were interviewed about periconceptional medication use during the period from one month before conception through the third month of pregnancy. Mutually exclusive exposure categories included seven specific antibiotics (cephalosporins, macrolides, nitrofurantoin, penicillin, quinolones, tetracyclines, trimethoprim-sulfamethoxazole) and other, multiple, or unknown antibiotics. We excluded non-singleton births and women reporting type 1 or type 2 diabetes; insufficient medication information or exposure dates; or other, multiple, or unknown antibiotic types. We used logistic regression to assess associations between antibiotics and individual non-cardiac birth defects for combinations with at least four exposed cases, with penicillin exposure as the comparator, adjusting for maternal age, race/ethnicity, body mass index, education, year of delivery, and study site.

Results: Exposure to any of the seven specific antibiotics was reported by 8.1% (n=1561) of mothers of cases and 7.7% (n=935) of mothers of controls. Compared to penicillin use, periconceptional tetracycline use was significantly associated with three of the seven defects that met inclusion criteria: anencephaly (adjusted odds ratio: 6.81; 95% confidence interval: 1.65, 28.07), anorectal atresia (5.58; 1.62, 19.25), and cleft palate (3.84; 1.52, 9.67); trimethoprim-sulfamethoxazole with one of 16 defects: duodenal atresia (4.67; 1.23, 17.75); and quinolones with one of six defects: cleft lip (2.01; 1.09, 3.72). Cephalosporins, macrolides, and nitrofurantoin were not significantly associated with any of the non-cardiac defects examined.

Conclusions: Despite some associations (five of 71 examined) between specific antibiotics and individual birth defects, estimates were imprecise. In general, most antibiotics had a similar safety profile to penicillin regarding teratogenicity, which is generally considered safe for use during pregnancy. Further research will consider the potential impact of fever and confounding by indication on these findings.