Evidence for the Association Between STIs and Preterm Birth

Abstract

Source: Gao R, Liu B, Yang W, et al. Association of maternal sexually transmitted infections with risk of preterm birth in the United States. JAMA Netw Open. 2021;4(11):e2133413. doi:10.1001/jamanetworkopen.2021.33413Investigators from multiple institutions conducted a retrospective study to assess the association between maternal sexually transmitted infections (STI) during pregnancy and premature birth. For the study, they reviewed data on birth certificates of children born by singleton birth between 2016 and 2019 in all 50 states and the District of Columbia. Data abstracted from birth certificates included demographic information, maternal pregnancy history, and estimated gestational age at birth. Also included on the birth certificates was a history of maternal infection with chlamydia, gonorrhea, and/or syphilis at the time of the diagnosis of pregnancy or during pregnancy. The primary study outcome was premature birth, defined as gestational age <37 weeks. Secondary outcomes included extremely premature birth (<28 weeks), very preterm birth (28-31 weeks), and moderately preterm birth (32-36 weeks). The association between maternal STI and these outcomes were assessed with logistic and multinomial regression, after adjustment for multiple confounders. Models that included any of the assessed STIs, and specific STIs were conducted. In addition, analyses stratified by maternal age or race/ethnicity were performed.Data on 14,373,023 singleton births were included in the analyses. The mean age of the mothers of these infants was 29 ± 5.8 years. A total 267,260 (1.9%) mothers had chlamydia, 43,147 (0.3%) had gonorrhea, and 16,321 (0.1%) had syphilis. Among the study newborns, 1,146,800 (8.0%) were born prematurely. In the multivariate model, any maternal STI was associated with an increased risk of premature birth (OR, 1.06; 95% CI, 1.05, 1.07); infection with chlamydia (OR, 1.03; 95% CI, 1.02, 1.04), gonorrhea (OR, 1.11; 95% CI, 1.08, 1.15), and syphilis (OR, 1.17; 95% CI, 1.11, 1.22) were each individually associated with an increased risk of premature birth. Maternal STI was associated with an increased risk of very premature birth (OR, 1.07; 95% CI, 1.03, 1.12), and moderately preterm birth (OR, 1.06; 95% CI, 1.05, 1.08), but not extremely premature birth (OR, 1.00; 95% CI, 0.95, 1.05). There was a small but statistically significant (P <0.001) increase in the risk of premature birth associated with maternal STI among women ≥35 years old (OR, 1.09), and those 25-34 years old (OR, 1.08), compared to those <25 years old (OR, 1.06). There was a statistically significant increased risk of premature birth associated with maternal STI among women who were white (OR, 1.10; 95% CI, 1.08, 1.13), Black (1.04; 95% CI, 1.02, 1.06) and Hispanic (OR, 1.06; 95% CI, 1.03, 1.09), but not Asian (OR, 1.01; 95% CI, 0.90, 1.13).The authors conclude that maternal infection with chlamydia, gonorrhea, or syphilis is associated with an increased risk of premature birth.Dr Von Kohorn has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The holy grail of neonatal-perinatal medicine is the prevention of adverse newborn outcomes, and, ultimately, the prevention of preterm birth. Intrauterine infection is thought to be a leading cause of preterm birth, although the precise contribution of specific STIs to preterm birth is unclear.1 The current study, a high-quality observational analysis of more than 14 million women with singleton pregnancies in the US, provides some of the best evidence to date that STIs—specifically chlamydia, gonorrhea, and syphilis—are associated with preterm birth. Still, the nature of the study leaves key questions unanswered.The authors of the accompanying editorial comments that some epidemiologists caution against considering interpreting near-even odds, such as those in the current study, as valid when the sample size is extremely large.2 Furthermore, observational studies, no matter how large, are subject to bias and cannot determine causation.3 Thus, it remains possible that pregnant women with STIs in this study, or in general, are systematically prone to preterm birth for reasons other than the STIs themselves. Perhaps most importantly, the current researchers did not seek to elucidate whether prevention or treatment of STIs is effective in preventing preterm birth. Recent observational data suggest that treatment of STIs in pregnancy is not effective in preventing preterm birth.4 The editorial authors state that they know of no randomized controlled trials that answer this question.2 A randomized trial of STI prevention to decrease preterm birth is intriguing. It is unclear how a randomized trial could be designed for treatment of STIs, since treatment is the standard of care in pregnancy.The best evidence to date indicates that STIs are associated with preterm birth. It remains unclear whether treatment of STIs is an effective intervention to prevent preterm birth.