Is nitrofurantoin (antibiotic) safe to use during the first trimester of pregnancy?

Nitrofurantoin Safety in the First Trimester of Pregnancy

Nitrofurantoin can be safely used during the first trimester of pregnancy as there is no significant evidence of increased risk for major congenital malformations. 1, 2

Evidence Assessment

Safety Profile

• Multiple studies have evaluated nitrofurantoin use in early pregnancy:
  • A large population-based retrospective cohort study of 105,492 pregnancies found no association between first trimester nitrofurantoin exposure and increased risk of major congenital malformations (adjusted OR = 0.85,95% CI 0.67-1.08) 1
  • A systematic review and meta-analysis of cohort studies including 9,275 exposed pregnancies showed no increased risk of major malformations (RR = 1.01,95% CI 0.81 to 1.26) 2

Prescribing Considerations

• Nitrofurantoin is commonly prescribed for urinary tract infections (UTIs) during pregnancy, which occur in approximately 8% of pregnant women 3
• UTIs require treatment during pregnancy as untreated infections can lead to serious complications including:
  • Pyelonephritis
  • Preterm labor
  • Low birth weight
  • Sepsis 3

Dosing and Duration

• For uncomplicated UTIs in pregnancy, nitrofurantoin monohydrate/macrocrystals should be dosed at 100 mg twice daily for 5-7 days 4

Important Contraindications and Precautions

• Third trimester contraindication: Nitrofurantoin should be avoided in the last three months of pregnancy due to risk of hemolytic anemia in the newborn 4, 5
• Renal function: Contraindicated in patients with renal impairment (GFR <30 ml/min) 4, 5
• Resistance patterns: Consider local resistance patterns when selecting antibiotics for UTI treatment 4

Algorithm for UTI Treatment in Pregnancy

1. First trimester:

   • Nitrofurantoin 100 mg twice daily for 5-7 days is appropriate first-line therapy
   • Alternative: Cephalexin if nitrofurantoin is contraindicated

2. Second trimester:

   • Same as first trimester options

3. Third trimester:

   • Switch to alternatives such as cephalexin or appropriate beta-lactams
   • Avoid nitrofurantoin due to risk of hemolytic anemia in newborns

4. For all trimesters:

   • Obtain urine culture before treatment to guide therapy
   • Ensure adequate follow-up to confirm resolution
   • Consider antibiotic resistance patterns when selecting therapy

Clinical Perspective

While some older recommendations expressed caution about nitrofurantoin use in the first trimester, more recent and robust evidence supports its safety. The benefits of treating UTIs during pregnancy with effective antibiotics like nitrofurantoin generally outweigh the theoretical risks, particularly given the serious maternal and fetal complications that can result from untreated UTIs.