A randomized controlled trial involving nearly 1,000 women in Zimbabwe found that a daily dose of a broad-spectrum antibiotic during pregnancy did not significantly increase infant birth weight, an international group of researchers reported yesterday in the New England Journal of Medicine.
But women who received prophylactic (preventive) trimethoprim-sulfamethoxazole had fewer preterm births than those who received a placebo, a finding the study authors say needs to be further explored.
The trial, conducted by researchers with Queen Mary University of London and the Zvitambo Institute for Maternal and Child Health Research in Zimbabwe, enrolled pregnant women from a district in Zimbabwe where preterm births are high and at least 15% of the population has HIV. Because prematurity and low birth weight are among the adverse events associated with maternal infection and inflammation, the investigators hypothesized that prophylactic use of trimethoprim-sulfamethoxazole, which is widely used in people with HIV in sub-Saharan Africa, might reduce infection and inflammation and result in improved birth outcomes.
"New approaches to prevent small-for-gestational-age status and prematurity are needed to reduce childhood mortality, prevent stunting, and improve lifelong health," the study authors wrote.
No significant difference in birth weight
The women were randomized 1:1 to receive a 960-milligram daily dose of trimethoprim-sulfamethoxazole or placebo from at least 14 weeks' gestation to delivery. The primary outcome was birth weight. Secondary outcomes included duration of gestation and preterm birth. Investigators also analyzed adverse outcomes.
Of the 993 women enrolled for the study (median age, 24.5 years; 131 with HIV), 495 were assigned to the trimethoprim-sulfamethoxazole group and 498 to the placebo group. The first dose of trimethoprim-sulfamethoxazole was received at a median of 21.7 weeks' gestation. Birth outcomes were assessed for 950 women.
In the intention-to-treat analysis, there was no significant difference in birth weight between the two groups. The mean birth weight in the trimethoprim-sulfamethoxazole group was 3,040 grams (6.7 pounds), compared with 3,019 grams (6.66 pounds) in the placebo group (mean difference, 20 grams; 95% confidence interval [CI], -43 to 83). Analysis of women with HIV found a small increase in birth weight among infants in the trimethoprim-sulfamethoxazole group.
Analysis of secondary outcomes showed the duration of gestation was 39.3 weeks in the trimethoprim-sulfamethoxazole group and 38.9 weeks in the placebo group (mean difference, 0.5 weeks; 95% CI, 0.2 to 0.7). The percentage of women with preterm births was 6.9% in the trimethoprim-sulfamethoxazole group and 11.5% in the placebo group (difference, -4.6 percentage points; 95% CI, -8.3 to -1.0), representing a 40% relative reduction in preterm births (relative risk, 0.60; 95% CI, 0.39 to 0.91).
The reduction in preterm births was even greater among women with HIV. Only 2% of births in the trimethoprim-sulfamethoxazole group were preterm, compared with 14% in the placebo group. But the investigators say that, since the number of women with HIV in the study was small, the results "should be viewed as hypothesis-generating."
The number of serious adverse events was similar between the two groups, with 31 in the women who received trimethoprim-sulfamethoxazole and 33 in those who received placebo, including 2 deaths.
Promising secondary findings
Although the investigators found that prophylactic trimethoprim-sulfamethoxazole had no significant impact on birth weight, they note that it's possible the effect may have been greater if the antibiotic had been started earlier in pregnancy. They also say the secondary outcomes warrant further study.
"Our trial, conducted within routine antenatal care and enrolling women predominantly from rural areas, showed that trimethoprim-sulfamethoxazole did not improve birthweight, which was our main outcome," first author Bernard Chasekwa, MSc, of the Zvitambo Institute for Maternal and Child Health Research in Harare, Zimbabwe, said in a Queen Mary University of London press release. "However, there was an intriguing suggestion that it may have improved the length of pregnancy and reduced the proportion of preterm births."
"If we can confirm in other trials that trimethoprim-sulfamethoxazole reduces the risk of babies being born too soon, it would be a promising new approach to help newborns survive and thrive," added Andrew Prendergast, PhD, a professor of pediatric infection and immunology at Queen Mary.
