Treating chlamydial infections in pregnancy and preventing adverse birth outcomes

Chlamydia trachomatis is one of the most common sexually transmitted infections globally; WHO estimates that there are more than 130 million new cases of chlamydia annually. Because chlamydial infections are often asymptomatic, screening programmes are imperative to control infection and to prevent adverse sequelae. Chlamydial infections are important causes of pelvic inflammatory disease and tubal infertility and can lead to ectopic pregnancies.¹ Additionally, chlamydial infections increase the risk of acquiring HIV infection.² Most, but not all, observational studies^1,3,4 and meta-analyses have shown that chlamydial infection is associated with adverse obstetric outcomes in pregnancy and increased morbidity and mortality of neonates.

In their Article⁵ in The Lancet Infectious Diseases, Joanne Reekie and colleagues report on a large study of chlamydial infection and adverse birth outcomes among reproductive-aged women in the Australian state of Western Australia. They conducted a population-based retrospective cohort study, linking a government registry of women in Western Australia to datasets of laboratory test results, notifiable disease reporting, hospital morbidity, and birth outcomes. The report included birth outcome data on 101 588 women who had singleton births in Western Australia from 2001 to 2012. Of those births, 3921 (3·9%) were spontaneous preterm births, 9726 (9·6%; of 101 371 births with available data) were small for gestational age, and 682 (0·7%) were stillbirths.

One strength of the study was that the authors could differentiate between women who were tested for chlamydia before pregnancy and those tested during pregnancy. Within the cohort, 21 267 (20·9%) were tested for chlamydia during their pregnancy, of whom 1365 (6·4%) tested positive. Of the 19 157 (18·9%) women who were tested before pregnancy, 1595 (8·3%) tested positive. The authors report that women who were tested before pregnancy, but not during pregnancy, had an increased risk of preterm birth or stillbirth but a reduced risk of having a baby who was small for gestational age. Women who were only tested before pregnancy might represent a higher risk group, which prompted testing (eg, because of symptoms of infection, several sexual partners, or diagnosis of other sexually transmitted infections); this explanation would account for the findings of an increased risk of preterm births and stillbirths. In that case, testing is a marker of risk and might not apply to the general population of women in Western Australia, since only about 40% of the population had ever been screened in their dataset.

Among women who tested positive for chlamydia during pregnancy, 232 (17·1%) had an infant who was small for gestational age and 81 (6·2%) had a spontaneous preterm birth; among women who tested negative for chlamydia during pregnancy, 2418 (12·2%) women had an infant who was small for gestational age and 864 (4·5%) women had a spontaneous preterm birth. Although a univariate analysis suggested that women with chlamydia have a higher risk for adverse birth outcomes, there was no association in multivariable analyses when controlling for potential confounders. One important limitation of the study was that the authors did not have access to treatment data, which would have strengthened the interpretation of their main findings. Based on a previous clinical audit among the same population, the authors assumed that most cases were treated. With that caveat in mind, the findings suggest that women with chlamydial infections who are screened and treated during pregnancy have the same risk of adverse birth outcomes as women without an infection.

The benefits of antenatal screening and treatment of chlamydial infections have been evaluated in a few prospective studies.^6–9 Most of those studies support screening and treatment as an effective means to improve pregnancy outcomes. As noted by the authors, there are other observational studies that have not shown an increase in adverse obstetric outcomes associated with chlamydia, although these studies are not without substantial limitations. Cost-effectiveness studies^10,11 from high-income settings have supported chlamydia screening and treatment programmes for pregnant women. The report by Reekie and colleagues contributes to the evidence that supports the benefits of screening and treatment of chlamydia among pregnant women; however, the effect size and, therefore, cost-effectiveness is not known.

There is an urgent need to further elucidate the necessity of screening and treatment of chlamydia during pregnancy, especially in regions of the world with both a high prevalence of adverse birth outcomes and a high prevalence of chlamydial infections. It is estimated that 99% of stillbirths occur in resource-limited settings and, as a 2016 review¹ noted, there is a high prevalence of chlamydial infections among pregnant women from low-resource settings in sub-Saharan Africa and Asia. Chlamydial screening and treatment programmes during pregnancy will require substantial investments by governments, which can be difficult to prioritise in resource-limited settings, especially given the absence of data on the effect size and cost-effectiveness of these programmes. It is time for large, randomised clinical trials to investigate the effects of chlamydial screening and treatment programmes in pregnant women on adverse birth outcomes and the potential cost-effectiveness of different screening approaches. Findings from those studies will provide crucial evidence to guide policy makers on how to address chlamydial infection in pregnancy and to improve the lives of pregnant women and their children.