Nitrofurantoin

Pregnancy

ACOG Committee Opinion 717 says evidence on the association between nitrofuran and sulfonamide antibiotics and birth defects is mixed. It says antibiotics in pregnancy should be used for appropriate indications and the shortest effective duration; nitrofurantoin may be used in the first trimester when no suitable alternative is available and may remain first-line for susceptible infections in the second and third trimesters. The CDC Yellow Book says nitrofurantoin is typically avoided in the first trimester, without an explanation in that passage. Osmundson et al. (2025) studied 71,604 commercially insured pregnancies treated for UTI and linked to liveborn infants; 42,402 had first-trimester nitrofurantoin exposure. The adjusted risk of any malformation was similar to beta-lactams (RR 1.12, 95% CI 1.00-1.26). The cohort does not cover pregnancies without a linked liveborn infant or provide evidence on miscarriage. Ailes et al. (2016) used a population-based case-control study with maternal-reported exposure from the month before conception through the third month of pregnancy. Compared with penicillin-treated UTIs, nitrofurantoin was associated with oral clefts (aOR 1.97, 95% CI 1.10-3.53). The study had limited defect-specific counts, potential exposure misclassification, possible confounding by infection, and 43 comparisons; it cannot establish cause. Boissiere-O'Neill et al. analyzed 704,082 pregnancies in linked Norwegian registries. Nitrofurantoin was not associated with increased miscarriage risk; the drug-specific analysis included 5,967 exposed pregnancies and 312 miscarriages. The authors' study addressed several timing biases but could not exclude residual confounding. The Macrobid label states: "Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38 to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent. For the same reason, the drug is contraindicated in neonates under one month of age." Nordeng et al. (2013) found no increased risk of major malformations with first-trimester dispensing. In the same Norwegian cohort, dispensing in the last 30 days before delivery was associated with neonatal jaundice in 103/959 (10.8%) versus 10,336/127,507 (8.1%) among unexposed pregnancies (OR 1.31, 95% CI 1.02-1.70). This was an observational association, not proof of cause.

Breastfeeding

LactMed's July 2024 record says nitrofurantoin doses in milk are low and prefers alternate drugs for mothers of infants under 8 days or infants with G6PD deficiency at any age. It also says relevant published infant drug-level information was not found as of that revision. The Macrobid label reports trace amounts in human milk and warns of potential serious adverse reactions in nursing infants under one month. Pons et al. measured nitrofurantoin in milk in six women treated 2 to 5 days after delivery; the study measured drug transfer, not infant health outcomes. The age guidance differs: LactMed prefers an alternative under 8 days for a full-term infant without G6PD deficiency, while the label and MotherToBaby state an under-one-month warning. The sources also identify G6PD deficiency as a reason for extra caution.

What was tested

The pregnancy outcome evidence reviewed includes observational claims and registry cohorts and a population-based case-control study. The newer first-trimester cohort compared nitrofurantoin with beta-lactam antibiotics among people treated for UTI and included linked liveborn infants. The 2016 case-control study relied on mothers' reports and used penicillin-treated UTIs as the comparison group. The miscarriage study linked four nationwide Norwegian registries and accounted for time-varying exposure and several timing biases. Breastfeeding evidence includes small milk-transfer studies, including six postpartum women; these measurements do not establish infant outcomes.