Background:  Infants of HIV-infected mothers, particularly mothers with advanced disease, are at high risk of adverse birth outcomes, including preterm delivery, low birth weight, and neonatal mortality. We investigated whether introduction of cotrimoxazole prophylaxis among HIV-infected women with low CD4 counts reduces adverse birth outcomes.

Methods:  In a trial of prevention of mother-to-child HIV transmission in Lusaka, Zambia, birth outcome data from 1075 HIV-positive pregnant women who delivered singleton live-born infants between May 2001 and April 2005 were analyzed. Cotrimoxazole prophylaxis was introduced as part of routine HIV care in November 2003 for all HIV-infected women with CD4 cell counts <200 cells/μL. We compared the risks of adverse birth outcomes occurring in this cohort before and after the introduction of cotrimoxazole prophylaxis. Women who received ART before delivery were excluded. Logistic regression was used to adjust for possible changes in other risk factors over this time period.

Results:  Among 255 women with CD4 cell counts <200, delivery after November 2003 was associated with significant improvements in several pregnancy outcomes. The percentage of births substantially earlier than expected (≤34 weeks estimated gestation) declined from 31% to 18% (p = 0.04); the detection of clinical chorioamnionitis declined from 6% to 0 (p = 0.04); the mean birth weight was on average 100 g greater (p = 0.15) and neonatal mortality (infant death ≤28 days) improved from 9% to 0 (p = 0.01). After adjustment for other risk factors that might have changed over the period, including poverty, maternal education, hemoglobin, low weight, and when enrolled during pregnancy, delivery after the introduction of the cotrimoxazole program was associated with about half the risk of preterm birth (OR=0.5 95% CI: 0.2, 0.9).  In contrast, birth outcomes in the cohort of 820 women with CD4 counts ≤ 200 who were not eligible for cotrimoxazole prophylaxis displayed no consistent patterns of improvement over the same time interval.

Conclusions:  We observed reductions in chorioamnionits, prematurity, and neonatal mortality after the introduction of routine cotrimoxazole prophylaxis for HIV-infected women with CD4 cell counts <200. These data suggest that this intervention may have indirect benefits for neonatal and infant health in addition to its direct benefits for maternal health.