Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis.
BACKGROUND
Cotrimoxazole is widely prescribed to treat a range of infections, and for HIV-infected individuals it is administered as prophylaxis to protect against opportunistic infections. Some reports suggest that fetuses exposed to cotrimoxazole during early pregnancy may have an increased risk of congenital anomalies. We carried out this systematic review to update the evidence of cotrimoxazole safety in pregnancy.


METHODS
Three databases and 1 conference abstract site were searched in duplicate up to October 31, 2013, for studies reporting adverse maternal and infant outcomes among women receiving cotrimoxazole during pregnancy. This search was updated in MEDLINE via PubMed to April 28, 2014. Studies were included irrespective of HIV infection status or the presence of other coinfections. Our primary outcome was birth defects of any kind. Secondary outcomes included spontaneous abortions, terminations of pregnancy, stillbirths, preterm deliveries, and drug-associated toxicity.


RESULTS
Twenty-four studies were included for review. There were 232 infants with congenital anomalies among 4196 women receiving cotrimoxazole during pregnancy, giving an overall pooled prevalence of 3.5% (95% confidence interval: 1.8% to 5.1%; τ² = 0.03). Three studies reported 31 infants with neural tube defects associated with first trimester exposure to cotrimoxazole, giving a crude prevalence of 0.7% (95% confidence interval: 0.5% to 1.0%) with most data (29 neural tube defects) coming from a single study. The majority of adverse drug reactions were mild. The quality of the evidence was very low.


CONCLUSIONS
The findings of this review support continued recommendations for cotrimoxazole as a priority intervention for HIV-infected pregnant women. It is critical to improve data collection on maternal and infant outcomes.
*Department of HIV/AIDS, World Health Organization, Geneva, Switzerland; †Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College, London, United Kingdom; ‡Department of Medicine, Divisions of Infectious Diseases and General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; §ICAP, Mailman School of Public Health, and College of Physicians and Surgeons, Columbia University, New York, NY; ‖Department of Paediatrics and Child Health, Tygerberg Hospital, University of Stellenbosch, Cape Town South Africa; and ¶Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.
Nathan
N
Ford
Zara
Z
Shubber
Jennifer
J
Jao
Elaine J
EJ
Abrams
Lisa
L
Frigati
Lynne
L
Mofenson
D000014:Abnormalities, Drug-Induced; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections; D006801:Humans; D011247:Pregnancy; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000009:adverse effects*
D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination