Botswana Trial to Test Whether Screening for Chlamydia Can Prevent Preterm Birth

Researchers are preparing to launch a large randomized controlled trial in Botswana to determine whether routinely screening pregnant women for Chlamydia trachomatis, a common and curable sexually transmitted infection, can reduce the risk of preterm birth. The study, known as the Healthy Expectancy through Routine Antenatal STI Screening (HERA) Trial, is described in a newly published protocol in BMC Pregnancy and Childbirth. As a protocol paper, it lays out the planned design and methods of the trial rather than reporting any results on effectiveness.

The motivation is significant. According to the trial team, preterm birth is a leading cause of under-five mortality globally, and rates have remained stubbornly difficult to reduce, making the identification of modifiable risk factors a global priority. Chlamydia trachomatis infection has been consistently associated with an increased risk of preterm birth, yet in most low- and middle-income countries antenatal care relies on syndromic management, an approach that treats only women with recognizable symptoms. Because most chlamydial infections are asymptomatic, the majority of infections are missed under this standard approach.

HERA is designed as a prospective, individually randomized controlled trial that will enrol 2,000 pregnant women attending antenatal clinics in Gaborone, Botswana, and surrounding towns and villages.

To be eligible, women must be at least 15 years of age, no more than 20 weeks pregnant, attending their first antenatal care visit, and asymptomatic for chlamydial infection according to standard-of-care screening at the first antenatal exam. This focus on women without symptoms is deliberate: these are precisely the patients that syndromic management overlooks, and the investigators argue the trial is therefore well positioned to fill a critical evidence gap.

Participants will be randomized in a one-to-one ratio to either the standard-of-care group, which receives syndromic management, or the intervention group, which receives standard of care plus screening for both Chlamydia trachomatis and Neisseria gonorrhoeae, the bacterium that causes gonorrhoea. Women in the intervention arm who test positive will be treated, with screening and treatment offered at the first antenatal visit and again in the third trimester.

The primary outcome the trial will measure is preterm birth, defined as delivery before 37 weeks and 0 days of gestation. Gestational age will be determined using menstrual dating when it is confirmed by ultrasound, or ultrasound alone when menstrual dating and ultrasound estimates are not consistent. Secondary outcomes include low birth weight, very preterm birth, spontaneous preterm birth, and hypertensive disorders of pregnancy, allowing the investigators to capture a broader picture of how screening might affect maternal and neonatal health.

On the analysis side, the trial team plans to use Generalized Estimating Equations regression models to estimate the effect of the intervention. An integrated economic evaluation will also assess costs, cost-effectiveness expressed as cost per disability-adjusted life year averted, and budget impact.

The trial has been registered with ClinicalTrials.gov under identifier NCT07458802, with registration dated March 4, 2026. The published protocol emphasizes that individually randomized evidence evaluating the impact of antenatal chlamydia screening and treatment on preterm birth is limited, which is the gap HERA aims to address.

If the trial demonstrates benefit, the findings could inform national policy in Botswana and contribute to global guidelines on antenatal sexually transmitted infection screening, particularly as affordable diagnostic technologies become more accessible. The investigators note that the work has the potential to improve maternal and neonatal outcomes through more effective detection and management of STIs during pregnancy. For now, however, those benefits remain a hypothesis to be tested: the trial’s value lies in generating rigorous evidence on whether screening asymptomatic pregnant women actually prevents preterm birth, and at what cost.

Subject of Research: A randomized controlled trial protocol testing antenatal chlamydia screening and treatment to prevent preterm birth in Botswana

Article Title: Chlamydia trachomatis infection screening to prevent preterm birth in Botswana: protocol for the HERA individually randomized controlled trial

Article References: Mussa, A., Baradwaj, A., Bame, B., Phinius, B., Setshwaelo, T., Nguyen, K., He, F., Jain, S., Ramagola-Masire, D., Hanson, S. J., Klausner, J. D., Zash, R., Zivin, J. G., Averbach, S., Morroni, C., & Wynn, A. (2026). Chlamydia trachomatis infection screening to prevent preterm birth in Botswana: protocol for the HERA individually randomized controlled trial. BMC Pregnancy and Childbirth. https://doi.org/10.1186/s12884-026-10095-3

Image Credits: AI Generated

DOI: 10.1186/s12884-026-10095-3

Keywords: Chlamydia trachomatis, preterm birth, Botswana, antenatal screening, sexually transmitted infections, randomized controlled trial, pregnancy, syndromic management, maternal health, neonatal outcomes, trial protocol, cost-effectiveness