SUMMARY:  

The CDC reported (MMWR, 2018) raised concern regarding the ongoing use of sulfonamides and nitrofurantoin in the first trimester due to the possible risk for birth defects.  The authors in this paper state the following  

According to 2011 guidelines from the Infectious Diseases Society of America, nonpregnant women with uncomplicated UTIs should be treated with nitrofurantoin or trimethoprim-sulfamethoxazole. For pregnant women in their first trimester, a 2011 Committee Opinion from the American College of Obstetricians and Gynecologists recommended that sulfonamides and nitrofurantoin may be prescribed only if other antimicrobial therapies are deemed clinically inappropriate. In this analysis, 34.7% of pregnant women with UTIs in 2014 filled a prescription for nitrofurantoin and 7.6% filled a prescription for trimethoprim-sulfamethoxazole during their first trimester of pregnancy.

ACOG has replaced Committee opinion 294 (2011) with Committee Opinion 717 (reaffirmed 2019) that still recommends the cautious use of sulfonamides and nitrofurantoin in the first trimester of pregnancy due to possible risk of birth defects, if no other alternatives are available.

Recommendations  

• Prescribe antibiotics as indicated and for as brief a time as possible  
• Do not treat presumed contaminants found on urine culture  
  • Mixed gram-positive bacteria | lactobacilli |Staphylococcus species (other than S saprophyticus) 
• If treating an infection in the first trimester 
  • Discuss with patient risk/benefits and fetal/maternal adverse reactions  
  • Sulfonamides and nitrofurantoin in the first trimester of pregnancy can be used if no other alternatives are available  
• If treating an infection in the second or third trimester 
  • Sulfonamides and nitrofurantoins may be used as first-line medications  
• Pregnant women should not be denied appropriate therapy due to serious risks to both mother and fetus 

KEY POINTS:  

Evidence for increased risk for birth defects  

• • Concern about sulfonamides and nitrofurantoin in the first trimester of pregnancy and increased risk for birth defects is derived from a population-based case–control study (Pediatr Adolesc Med, 2009) 

• Study limitations include 
  • • Recall bias: Antibiotic use was obtained from women after pregnancy  
  • • Lack of medication confirmation: 35% of patients did not remember the specific antibiotic name  
  • • Study design: Observational studies can determine association but not causation (for example indication may be culprit and not medication)  
  • Conflicting results: ACOG has updated this latest guidance with data from a 2013 population-based cohort study that did not confirm this association 

Other antibiotics that are not associated with increased risk for birth defects  

• Penicillins, cephalosporins erythromycin and quinolones were not associated with increased risk in the 2009 study  
• ACOG lists the following antibiotics that have not been shown to be associated with increased risk for birth defects 
  • Penicillin  
  • Ampicillin  
  • Cephalosporins  
  • Erythromycin  
  • Augmentin  
  • Pivampicillin  
  • Gentamicin  
  • Oxacillin  
  • Metronidazole  
  • Quinolones 

NOTE: G6PD Deficiency Warning  

• • Sulfonamides and nitrofurantoin are contraindicated in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency or pregnant women who are carriers  

• • G6PD is an X-linked recessive disorder and therefore males, not females, are usually affected 

• • Patients are usually asymptomatic, but significant enzyme deficiency can result in hemolytic anemia, brought about by oxidative stress 

• Female carriers can be affected by certain triggers such as medications, illness, infection, acidosis or certain foods (fava beans)  

Learn More – Primary Sources:

ACOG Committee Opinion 717: Sulfonamides, Nitrofurantoin, and Risk of Birth Defects

CDC: Antibiotics Dispensed to Privately Insured Pregnant Women with Urinary Tract Infections — United States, 2014

Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study (Pediatr Adolesc Med, 2009)

Haemolytic anaemia after nitrofurantoin treatment in a pregnant woman with G6PD deficiency

Neonatal outcomes after gestational exposure to nitrofurantoin(Obstet Gynecol, 2013)

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