Is nitrofurantoin safe during pregnancy?

Nitrofurantoin Safety in Pregnancy

Nitrofurantoin is safe and recommended as a first-line antibiotic for urinary tract infections during the first and second trimesters of pregnancy, but should be avoided near delivery due to risk of neonatal hemolytic anemia and hyperbilirubinemia. 1

Trimester-Specific Safety Profile

First Trimester (Weeks 1-12)

• Nitrofurantoin is the preferred first-line agent for UTI treatment during early pregnancy due to its excellent safety profile and minimal teratogenic risk 1
• The European Respiratory Society classifies nitrofurantoin as "possibly safe" during the first trimester 2
• Historical data from multiple randomized controlled trials used nitrofurantoin extensively in pregnant women without evidence of fetal toxicity or increased malformations 3
• A retrospective analysis of 91 pregnancies treated with nitrofurantoin showed no drug-related abnormal events and no significant difference in fetal outcomes compared to the general U.S. population 4
• ACOG states that prescribing nitrofurantoin in the first trimester is appropriate when indicated, and pregnant women should not be denied treatment as untreated infections lead to serious maternal and fetal complications 5, 6

Second Trimester (Weeks 13-27)

• Nitrofurantoin may continue as a first-line agent throughout the second trimester 5, 6
• The recommended dosing is nitrofurantoin 100 mg orally twice daily for 7-14 days 1
• This longer duration (compared to 5 days in non-pregnant women) ensures complete eradication, as untreated UTI increases pyelonephritis risk 20-30 fold 1

Third Trimester and Near Delivery (Week 28 onward)

• Nitrofurantoin should be avoided at delivery due to risk of neonatal hyperbilirubinemia and hemolytic anemia, similar to sulfonamides 2
• During most of the third trimester (before labor), nitrofurantoin may still be used as a first-line agent 5, 6
• The critical period to avoid is the immediate peripartum period when the drug could be present in the neonate's system at birth 2

Clinical Evidence Supporting Safety

Efficacy in Preventing Complications

• Treatment of asymptomatic bacteriuria with nitrofurantoin during pregnancy decreases pyelonephritis risk from 20-35% to 1-4% 3
• Meta-analyses confirm that antimicrobial treatment (including nitrofurantoin) decreases frequency of low birth weight infants and preterm delivery 3
• Women with untreated bacteriuria have a 20-30 fold increased risk of developing pyelonephritis compared to those without bacteriuria 3

Long-term Safety Data

• Nitrofurantoin was among the most common antimicrobials used in early pregnancy studies establishing the standard of care for treating asymptomatic bacteriuria 3
• Multiple prospective controlled trials and cohort studies spanning decades support its safety profile 3
• A comprehensive review classified nitrofurantoin among antibiotics "generally considered safe and effective in pregnancy" 7

Important Clinical Caveats

Rare Maternal Risks

• Acute pulmonary toxicity is an uncommon but potentially serious side effect that can occur during pregnancy, presenting with fever, cough, dyspnea, and pleuritic chest pain 8
• This immune-mediated reaction requires immediate discontinuation and may need corticosteroid therapy for severe cases 8
• Chronic pulmonary fibrosis can occur with long-term use, though this is rare 8

Contraindications

• Nitrofurantoin should not be used in patients with G6PD deficiency due to hemolytic anemia risk 1
• Avoid in patients with significant renal impairment (CrCl <60 mL/min) as inadequate urinary concentrations are achieved 1

Alternative Agents When Nitrofurantoin Cannot Be Used

• Cephalexin 500 mg four times daily for 7-14 days is the preferred alternative throughout pregnancy 1
• Amoxicillin-clavulanate is acceptable only if the pathogen is proven susceptible on culture 1
• Trimethoprim and trimethoprim-sulfamethoxazole are contraindicated in the first trimester due to interference with folic acid metabolism causing neural tube defects 1

Essential Follow-Up Protocol

• Perform follow-up urine culture 1-2 weeks after completing treatment to confirm bacteriologic cure 1
• Continue periodic screening with urine cultures throughout pregnancy, as recurrence is common 1
• Even asymptomatic bacteriuria requires treatment in pregnancy due to the high risk of progression to pyelonephritis 1