Trimethoprim–sulfamethoxazole not found to increase infant birth weight in HIV cases

Trimethoprim–sulfamethoxazole not found to increase infant birth weight in HIV cases | Image Credit: © annaperevozkina - © annaperevozkina - stock.adobe.com.

Infant birth weight is not significantly increased by the use of trimethoprim–sulfamethoxazole prophylaxis during pregnancy, according to a recent study published in The New England Journal of Medicine.¹

Risks of preterm birth and maternal infections

Preterm birth, small for gestational age, or low birth weight is reported in 1 in 4 newborns worldwide, increasing the risk of neonatal mortality.² Maternal infections and inflammation during pregnancy, especially human immunodeficiency virus (HIV), further increase the risks of these outcomes.¹

“Antibiotics received during pregnancy may therefore plausibly improve birth outcomes, although evidence to date is heterogeneous,” wrote investigators.

Data collection and treatment regimen

The double-blind, randomized trial was conducted to assess the impact of trimethoprim–sulfamethoxazole, a broad-spectrum antimicrobial agent, on birth outcomes in patients with HIV. Patients attending 1 of 3 antenatal clinics in Shurugwi with a positive urine pregnancy test, known HIV status, not receiving trimethoprim–sulfamethoxazole, and no contraindications were included.

The authors obtained demographic, obstetrical, and clinical data at baseline, with trained midwives performing ultrasonography to measure gestation duration. Participants were randomized 1:1 to receive either trimethoprim–sulfamethoxazole or placebo.

The trimethoprim–sulfamethoxazole regimen included 2, 480-mg tablets per day, with a single tablet containing 400 mg of sulfamethoxazole and 80 mg of trimethoprim. Placebo tablets were taken at the same rate and were indistinguishable from the study drug in appearance and taste.

Follow-up and safety assessments

Participants attended follow-up appointments at 20-, 26-, 30-, 34-, 36-, 38-, and 40-weeks’ gestation. A safety visit also occurred 1 week following initiation of the study regimen, Data about adherence, side effects, dietary intake, illness recall, obstetrical complications, and HIV was obtained during these visits, alongside blood pressure measurements.

Ultrasonography was performed at 26- and 34-weeks’ gestation to assess fetal growth. Safety measurements included liver function, kidney function, and complete blood count. Delivery was tracked by weekly telephone calls starting 36-weeks’ gestation.

Birth weight was reported as the primary outcome, while secondary outcomes included low birth weight, gestation duration, preterm birth, small for gestational age, fetal loss, maternal hospitalization or death, and neonatal hospitalization or death. Investigators also obtained z-scores for weight for age, length for age, and head circumference.

Birth outcome results

There were 993 women included in the final analysis, 495 of whom were given trimethoprim–sulfamethoxazole and 498 placebo. A median age of 24.5 years was reported in the overall study population, and a median gestation duration of 20.4 weeks at enrollment. HIV was identified in 13.2% of participants.

Most participants began the regimen at a median 21.7-weeks’ gestation. Seventeen miscarriages, 19 stillbirths, and 928 live births were reported, with 14 sets of twins. No significant differences in birth weight were reported between groups, with a mean of 3040±460 g in the trimethoprim–sulfamethoxazole group vs 3019±526 g in the placebo group.

The mean difference in birth weight of 20 g was not statistically significant. Additionally, similar results were reported for most secondary outcomes. This included low birth weight with a rate of 10% in the trimethoprim–sulfamethoxazole group and 11.6% in the placebo group.

Secondary outcomes and implications

Additional rates included small for gestational age at 20.3% and 17.3%, respectively, and fetal loss at 4.2% and 3.3%, respectively. Mean gestation durations at birth were 39.3 weeks and 38.9 weeks, respectively. Adverse events were also similar between groups.

“In this trial we found that a universal, pragmatic strategy of antenatal trimethoprim–sulfamethoxazole in a district in Zimbabwe with a high prevalence of HIV did not lead to a significant improvement in birth weight,” concluded investigators.

References

1. Chasekwa B, Munhanzi F, Madhuyu L, et al. A trial of trimethoprim–sulfamethoxazole in pregnancy to improve birth outcomes. N Engl J Med. 2025;392(21):2125-2134. doi:10.1056/NEJMoa2408114
2. Blencowe H, Cousens S, Oestergaard MZ, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012;379(9832):2162-72. doi:10.1016/S0140-6736(12)60820-4