Nitrofurantoin Safety in First Trimester
Nitrofurantoin can be used in the first trimester when no other suitable alternative antibiotics are available, though it should be reserved as a second-line option when possible. 1, 2, 3
Primary Recommendation
The American College of Obstetricians and Gynecologists (ACOG) states that prescribing nitrofurantoin in the first trimester is appropriate when no other suitable alternative antibiotics are available, acknowledging that untreated infections commonly lead to serious maternal and fetal complications. 1, 2, 3
Evidence Quality and Nuances
The evidence regarding birth defects is mixed and not definitive. 1, 2, 3 While some studies have raised concerns about potential associations with birth defects including anencephaly, heart defects, and orofacial clefts, 4 a retrospective analysis of 91 pregnancies found no evidence that nitrofurantoin was toxic to the fetus, with no abnormal events considered drug-related. 5
Practical Algorithm for First Trimester Use
When treating UTIs in the first trimester:
First-line options: Consider beta-lactam antibiotics (such as cephalexin) or fosfomycin as preferred alternatives when clinically appropriate. 6
Second-line option: Nitrofurantoin may be prescribed when first-line agents are unsuitable due to allergies, resistance patterns, or other clinical contraindications. 1, 2, 3
Dosing: Standard dosing is nitrofurantoin macrocrystals 50-100 mg four times daily or 100 mg twice daily for 5 days. 6
Critical Caveats
Untreated infections pose greater risk than treatment. 1, 2, 3 The potential harm from untreated UTIs during pregnancy—including pyelonephritis, preterm labor, low birth weight, and sepsis—must be weighed against theoretical medication risks. 4
Trimester-specific guidance: During the second and third trimesters, nitrofurantoin may be used as a first-line agent without the same reservations that apply to first-trimester use. 1, 2, 3
Renal function matters: Nitrofurantoin is contraindicated when creatinine clearance is <60 mL/min due to inadequate urinary drug concentrations and increased toxicity risk. 7
Common Pitfall to Avoid
Do not withhold appropriate antibiotic treatment due to pregnancy concerns. 1, 2, 3 The ACOG explicitly states that pregnant women should not be denied appropriate treatment for infections, as the consequences of untreated infection typically outweigh theoretical medication risks.