Is cotrimoxazole (trimethoprim/sulfamethoxazole) contraindicated in pregnancy?

Cotrimoxazole in Pregnancy: Safety Considerations

Cotrimoxazole (trimethoprim/sulfamethoxazole) is not absolutely contraindicated in pregnancy, but should be used with caution, particularly during the first trimester due to potential risks of neural tube defects. 1

First Trimester Considerations

• Cotrimoxazole exposure during the first trimester has been associated with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular abnormalities, urinary tract defects, oral clefts, and club foot 1
• The risk appears to be related to the trimethoprim component, which is a folate antagonist that may interfere with folic acid metabolism during critical periods of fetal development 1
• Women taking cotrimoxazole during early pregnancy should be advised of these potential risks 1

Second and Third Trimester Considerations

• Cotrimoxazole can be used with more confidence during the second and third trimesters when the risk of neural tube defects is lower 2
• For pregnant women prescribed cotrimoxazole in the third trimester, clinicians should be aware of the risk for neonatal hyperbilirubinemia 2

Specific Clinical Scenarios

• In Q fever infections during pregnancy, long-term cotrimoxazole therapy (320 mg trimethoprim and 1600 mg sulfamethoxazole for 35 days) is actually recommended to decrease the risk of placentitis, obstetric complications, and maternal chronic Q fever infection 2
• Studies have shown that pregnant women with Q fever who received long-term cotrimoxazole were protected against chronic Q fever, placental infection, and obstetric complications, particularly intrauterine fetal death 3
• For urinary tract infections in pregnancy, cotrimoxazole has been used successfully, though shorter courses may be preferred 4

Risk Mitigation Strategies

• All women capable of becoming pregnant should consume at least 400 μg of folic acid daily from supplements, fortified foods, or both, to reduce the risk of neural tube defects, especially if taking cotrimoxazole 2
• The CDC has assessed the risks and benefits of cotrimoxazole in certain infectious diseases and determined that the risk of acquiring serious infections like Q fever outweighs the risk of antimicrobial drug-related adverse effects 2

Alternative Antibiotics During Pregnancy

• When possible, penicillins and cephalosporins are preferred first-line antibiotics during pregnancy due to their established safety profile 5
• For patients with penicillin allergy, macrolides (except erythromycin estolate) may be considered as alternatives 2

Summary of Recommendations

• First trimester: Avoid cotrimoxazole if possible; use alternatives unless the benefit clearly outweighs the risk (as in Q fever) 1, 5
• Second/third trimester: Can be used with more confidence, but still consider alternatives if equally effective 2
• All trimesters: Ensure adequate folic acid supplementation if cotrimoxazole must be used 2
• Specific infections: For Q fever in pregnancy, long-term cotrimoxazole therapy is actually recommended despite the general caution 2, 3

In conclusion, while cotrimoxazole carries some risks during pregnancy, it is not absolutely contraindicated and may be necessary in certain clinical scenarios where the benefits outweigh the potential risks to the fetus.