Most Antibacterial Drugs Not Associated With Birth Defects


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. She reported no financial conflicts.

Their findings lend “support to the established safety profiles for certain classes of antibacterial [drugs] such as penicillins, erythromycins, and cephalosporins.” The investigators also 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, 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. Infants with either isolated or multiple defects were included, although those with suspected chromosomal abnormalities or single-gene conditions were excluded. The mothers reported their use of antimicrobial drugs from the month prior to the estimated date of conception through the end of the first trimester via telephone interviews conducted 6 weeks to 2 years following delivery. Exposure to antibacterial drugs was common among both case (29.4%) and control (29.7%) mothers.

Penicillins, the most frequently used agents, were associated with an increased odds ratio for only one defect (intercalary limb deficiency). Erythromycins, the next most frequently used antibacterial drugs, were associated only with anencephaly and transverse limb deficiency. Similarly, cephalosporins showed only one significantly increased odds ratio, and that was for atrial septal defects.

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, and transverse limb deficiency.

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