Antenatal cotrimoxazole prophylaxis leads to cost-effective reduction in preterm delivery and neonatal mortality, Zambian study reveals

Results from a retrospective cohort study of 1,397 HIV-positive pregnant women recruited at antenatal clinics in Lusaka between April 2001 and September 2004 suggest that cotrimoxazole (trimethoprim-sulfamethoxazole) prophylaxis can significantly reduce preterm deliveries, neonatal mortality and clinical chorionamnionitis in women with CD4 counts lower than 100cells/mm³, as reported in the 1st December 2006 issue of The Journal of Infectious Diseases.

The study supports previous findings that a relatively inexpensive intervention such as cotrimoxazole prophylaxis can improve maternal health for HIV-infected women.

Due to its wide spectrum activity on various parasitic, fungal and bacterial pathogens, including the causative agent of pneumonia Pneumocistis Jiroveci, cotrimoxazole is an effective prophylactic agent against many infections. Prophylaxis with cotrimoxazole was one of the first interventions to play a key role in the care of HIV positive individuals with low CD4 cell counts, and clinical trials have demonstrated significant reductions in illness and death in a variety of settings.

The World Health Organization (WHO) recommends the use of cotrimoxazole for HIV-infected individuals with CD4 cell counts below 350 cells/mm³, including pregnant women at any stage of pregnancy, since benefits to women’s health outweigh the risks of birth defects. Concerns have however been raised due to the possibility of development of bacterial resistance to the drug, resistance to sulfadoxine-pirimethamine in Plasmodium falciparum in malaria-endemic areas, teratogenicity, and low birth weight (due to the antagonistic effect of cotrimoxazole on folate metabolism).

Historical records on 1,397 HIV-positive pregnant women were analysed to compare rates of adverse pregnancy and birth outcomes with and without cotrimoxazole prophylaxis prior to the availability of antiretroviral treatment.

Data on body mass index, CD4 cell counts, viral load and haemoglobin level at enrolment were analysed. Women were classified according to WHO guidelines for the staging of HIV disease by means of self-reporting of symptoms. All study participants received general antenatal care such as malaria prophylaxis, multivitamin supplementation and screening for syphilis. Treatment for sexually transmitted infections (STIs) was offered to women with positive results and to their partners. Gestational age was calculated based on reported last menstrual period (LMP) dates and on fundal height at enrolment.

All women (n = 1,397) were asked to attend regularly scheduled appointments at the antenatal clinics and to bring their babies to hospital as soon as possible in the case of home deliveries, with weekly monitoring of mother and child continuing up to five weeks after birth. Hospital admissions, maternal and infant deaths were investigated by means of hospital records or interviews with caregivers.

In order to avoid potential teratogenic effects, prophylaxis with daily doses of two single-strength tablets (400mg sulfamethoxazole and 80mg trimethoprim) was started at 14 weeks gestational age for women who enrolled in the first trimester of pregnancy, or at enrolment for those at a more advanced stage of gestation. In the group of 330 women with CD4 cell counts 3, a total of 275 live births were recorded (n=97 women on cotrimoxazole prophylaxis), whereas 883 live births occurred in the group of 1,067 women with CD4 cell counts >200 cells/mm³ (n=308 women on cotrimoxazole prophylaxis).

Univariate and multivariate analysis of the data was performed to investigate the effects of cotrimoxazole prophylaxis and to assess the role of potential confounding factors like changes in malaria prophylaxis, severe poverty, maternal education, haemoglobin level and gestational age at enrolment.

Results indicate that cotrimoxazole prophylaxis did not have a significant impact on outcomes in women with CD4 cell counts above 200 cells/mm³ (n=883) and their babies.

However, in women with CD4 cell counts below 200 cells/mm³ (n=330) the intervention led to a significant reduction in preterm births from 31 to 18% (p = 0.04; adjusted OR 0.46 (95% CI 0.22 – 0.97)), neonatal mortality (9% to 0% p = 0.01) and chorionamnionistis (p = 0.04), with a trend toward a 114g increase in mean birth weight (95% CI -42 – 271g).

Birth weight improvement was more pronounced in the subgroup with CD4 cell counts below 100cells/mm³ subgroup (mean 319g; 95%CI -21 –.659g; p = 0.07), suggesting that cotrimoxazole prophylaxis may provide greater benefits for mothers with very low immunity levels and their babies. A non-significant trend towards reduced maternal mortality (p = 0.19) was also observed, but researchers think sample size was inadequate for significant results to be achieved for this and possibly other variables.

According to Heather Watts and Lynne Mofenson in an editorial review of the article in The Journal of Infectious Diseases: “These results are exciting because an intervention known to be of benefit for maternal health appears to benefit infant outcomes as well…”, and even more so when viewed in a wider perspective: firstly, because the reduction in preterm births due to cotrimoxazole prophylaxis is likely to reduce perinatal transmission of HIV (which is associated with preterm birth), and secondly because there is evidence that by reducing maternal mortality the longer term chances of infant survival may be increased by two to five times.