Most commonly used antibacterial drugs were not associated with birth defects in a large surveillance study.
The study was performed because even though some antibiotics have been used relatively safely during pregnancy for decades, until now “there have been no large-scale studies addressing safety or risk [of birth defects] for many classes of antibacterial drugs,” said Krista S. Crider, Ph.D., and her associates in the National Birth Defects Prevention Study.
Their findings lend “support to the established safety profiles for certain classes of antibacterial [drugs] such as penicillins, erythromycins, and cephalosporins.” In addition, the investigators found it “encouraging” that the use of antibacterial drugs suspected of being teratogenic—such as aminoglycosides, chloramphenicol, and tetracyclines—was “extremely low to none at all” among women just before conception and in early pregnancy (Arch. Ped. Adolesc. Med. 2009;163:978-85).
However, the use of other classes of antibacterial drugs, notably sulfonamides and nitrofurantoins, appeared to be associated with a higher risk for several birth defects, “indicating a need for additional scrutiny,” said Dr. Crider of the Centers for Disease Control and Prevention and her colleagues.
The researchers assessed prenatal exposure to antimicrobial drugs in 13,155 mothers of infants with birth defects (cases) born in 1997-2003 and 4,941 mothers of infants without major birth defects (controls) born in the same geographical locations during the same interval.
The case infants had at least 1 of more than 30 categories of major birth defects identified by surveillance systems in 10 states across the country. The cases included live births, stillbirths, and induced abortions.
This self-report was obtained through telephone interviews 6 weeks to 2 years following delivery. Such a lag time means that some women may not have fully or accurately recalled all their antibacterial drug exposures, or the exact timing of each exposure, the investigators noted. Exposure to antibacterial drugs was common among both case (29.4%) and control (29.7%) mothers.
Penicillins were the most frequently used agents. These antibacterial drugs were associated with an increased odds ratio for only one defect (intercalary limb deficiency). That association was not strong, because there were only 24 total cases of this defect.
Erythromycins were the next most frequently used antibacterial drugs. “Only anencephaly and transverse limb deficiency were associated with erythromycin exposure,” they noted. Similarly, cephalosporins showed only one significantly increased odds ratio, and that was for atrial septal defects.
Quinolones were used infrequently, as they are not recommended during pregnancy. They were associated with the conotruncal defect tetralogy of Fallot.
Nitrofurantoins were associated with anophthalmia or microphthalmos, hypoplastic left heart syndrome, atrial septal defects, and cleft lip with cleft palate.
Tetracyclines were associated with a variety of heart defects plus left ventricular outflow obstruction defects, septal heart defects, and oral clefts.
Exposure to sulfonamides was associated with the most defects, including anencephaly, hypoplastic left heart syndrome, coarctation of the aorta, choanal atresia, transverse limb deficiency, and diaphragmatic hernia. Moreover, associations between sulfonamides and tetralogy of Fallot, small intestinal atresia or stenosis, and craniosynostosis fell just short of statistical significance.
Disclosures: None was reported.