Is nitrofurantoin safe for a pregnant woman without known G6PD deficiency, particularly before 36 weeks gestation?

Is Nitrofurantoin Safe for Pregnant Women?

Yes, nitrofurantoin is safe and recommended as first-line therapy for urinary tract infections throughout most of pregnancy, but must be avoided after 37 weeks gestation due to risk of neonatal hemolytic anemia. 1

Safety Profile by Trimester

First and Second Trimesters (Safe and Recommended)

• Nitrofurantoin is explicitly recommended as first-line therapy for UTIs during the first trimester, with the American College of Obstetricians and Gynecologists (ACOG) stating that prescribing nitrofurantoin in the first trimester is appropriate even when concerns exist, as the benefits outweigh theoretical risks. 2, 3
• The standard dosing is nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5-7 days. 1, 4
• Animal studies at doses 2-6 times the human therapeutic dose showed no adverse effects on maternal health, fetal development, or neonatal survival. 5
• A retrospective analysis of 91 pregnancies treated with nitrofurantoin found no drug-related abnormal events, with outcomes comparable to the general U.S. population. 6

Third Trimester (Safe Until 37 Weeks)

• Nitrofurantoin remains safe and effective through 36 weeks gestation. 1
• After 37 weeks gestation, nitrofurantoin must be avoided due to theoretical risk of hemolytic anemia in G6PD-deficient newborns. 1
• This restriction is based on the potential for oxidant stress in neonates with undiagnosed G6PD deficiency, though actual risk appears low (only 42 confirmed cases out of at least 245 million exposures globally). 7

Clinical Context: Why Treatment Cannot Be Delayed

The urgency of treating UTIs in pregnancy cannot be overstated:

• Untreated bacteriuria increases pyelonephritis risk 20-30 fold (from 1-4% with treatment to 20-35% without treatment). 1, 8
• Treatment reduces preterm birth risk from 53 per 1000 to 14 per 1000 pregnancies. 8
• Treatment reduces very low birth weight from 137 per 1000 to 88 per 1000 infants. 8
• Even asymptomatic bacteriuria must be treated in pregnancy—this is the only clinical scenario where asymptomatic bacteriuria requires treatment. 1, 4, 8

Alternative Antibiotics When Nitrofurantoin Is Contraindicated

After 37 Weeks Gestation

• Cephalexin 500 mg four times daily for 7-14 days is the recommended first-line alternative. 1, 4
• Fosfomycin 3g single dose is acceptable, though with more limited data for late pregnancy. 1, 4
• Amoxicillin-clavulanate is appropriate if the pathogen is susceptible. 4

If G6PD Deficiency Is Known

• While nitrofurantoin carries a warning for G6PD deficiency, the actual risk appears minimal—only 13% of reported hemolytic anemia cases occurred in G6PD-deficient individuals. 7
• For short 3-5 day courses at 200 mg total daily dose, nitrofurantoin may still be considered with appropriate counseling, though cephalosporins are safer alternatives. 7

Critical Management Points

Diagnostic Approach

• Always obtain urine culture before initiating treatment to guide therapy, as screening for pyuria alone has only 50% sensitivity. 1, 4
• Optimal screening timing is 12-16 weeks gestation for asymptomatic bacteriuria. 4
• Do not wait for culture results to initiate empiric treatment in symptomatic patients. 4

Treatment Duration

• Standard duration is 7 days for symptomatic UTI, though 4-7 days is acceptable depending on clinical response. 1, 4
• For asymptomatic bacteriuria, 4-7 days is recommended rather than single-dose therapy. 9, 8
• Single-dose regimens show lower clearance rates and are not recommended. 9, 8

Follow-Up

• Obtain follow-up urine culture 1-2 weeks after completing treatment to confirm cure. 1, 4
• Continue periodic screening throughout pregnancy after any treated episode, as recurrence is common. 8

Common Pitfalls to Avoid

• Do not withhold nitrofurantoin in the first trimester based on outdated concerns—ACOG explicitly states it should not be denied when indicated. 2, 3
• Do not use nitrofurantoin for pyelonephritis—it does not achieve therapeutic blood concentrations; use ceftriaxone or cefepime instead. 4
• Do not rely on dipstick testing alone—it has poor sensitivity (50%) in pregnancy and culture is mandatory. 4
• Do not classify pregnant women with UTI as "complicated" unless they have structural abnormalities—this leads to unnecessary broad-spectrum antibiotic use. 4
• Remember the 37-week cutoff—this is a hard stop for nitrofurantoin use. 1