From NBDPS results, first-trimester nitrofurantoin exposure is linked to a twofold risk for cleft lip (Ailes, 2016; Crider, 2009). Considering that the birth prevalence of clefts approximates 1 case per 1000, the likelihood that a nitrofurantoin-exposed fetus would not have a cleft would thus be 998 per 1000. For other birth defects, initial associations with this antibiotic did not persist in the inal NBDPS cohort (Ailes, 2016).
In one systematic review of nitrofurantoin exposure in pregnancy, results of cohort and case-control studies difered (Goldberg, 2015). Five cohort studies included 9275 exposed pregnancies and nearly 1.5 million unexposed pregnancies, and the review found no higher risk for any malformation. However, among three case-control studies that had nearly 40,000 cases matched with 130,000 controls, the rate of hypoplastic left heart syndrome was threefold greater (Goldberg, 2015). For context, this increase in risk would result in a birth prevalence of fewer than 1 case per 1000 exposed infants. The American College of Obstetricians and Gynecologists (2017 e) has concluded that irst-trimester nitrofurantoin use is appropriate if no suitable alternatives are available.
These drugs are often combined with trimethoprim and used to treat infections during pregnancy. One indication is treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The NBDPS, which included 107 pregnancies with periconceptional trimethoprim-sulfamethoxazole exposure and birth defects, identiied a fivefold greater risk to have ofspring with esophageal atresia or diaphragmatic hernia (Ailes, 2016). Similar to findings with nitrofurantoin exposure, this degree of increase would confer a risk of approximately 1 case per 1000 exposed infants for these selected birth defects. However, these findings have not been corroborated by other reports. One review from the Medication Exposure in Pregnancy Risk Evaluation Program included more than 7500 infants with irst-trimester exposure to trimethoprim-sulfamethoxazole (Hansen, 2016). Compared with either unexposed infants or those exposed to penicillins or cephalosporins, no greater risk for any congenital abnormality was identified. The American College of Obstetricians and Gynecologists (2017 e) considers sulfonamides appropriate for irst-trimester use if suitable alternatives are lacking.
Sulfonamides displace bilirubin from protein-binding sites.
Thus, if given near the time of preterm delivery, these agents theoretically might worsen neonatal hyperbilirubinemia. However, a population-based review of more than 800,000 births from Denmark found no association between exposure to sulfamethoxazole in late pregnancy and neonatal jaundice (Klarskov, 2013).
These drugs are no longer commonly used in pregnant women. They are associated with yellowish-brown discoloration of deciduous teeth when used after 25 weeks' gestation. The risk for subsequent dental caries does not appear greater (Billings, 2004; Kutscher, 1966). In contrast, a recent systematic review of doxycycline in pregnancy identified no higher rates of either birth defects or staining of deciduous teeth (Cross, 2016).