Maternal STIs Linked With Increased Risk of Preterm Birth

Because maternal sexually transmitted diseases (STIs) are known to have adverse effects on developing fetuses, the CDC and American College of Obstetricians and Gynecologists recommend pregnant women undergo screening and receive treatment if an STI is detected.

However, this measure is not required and few studies have been conducted investigating the impact of STIs on preterm births. These have also yielded inconclusive findings. To address this knowledge gap, researchers assessed nationwide birth certificate data to better understand the potential link between maternal chlamydia, gonorrhea, and syphilis infections with the risk of preterm birth.

Results of the retrospective cohort study revealed maternal gonorrhea, syphilis, and chlamydia infections were all associated with an increased risk of preterm birth, suggesting this population might benefit from targeted prevention strategies.

Findings were published in JAMA Network Open and were relatively consistent across age and racial and ethnicity groups.¹ Syphilis, chlamydia, and gonorrhea are all curable if detected early enough and correctly treated.

Preterm birth is defined as any birth occurring before 37 weeks of gestation and is the leading cause of neonatal morbidity and mortality around the world, the authors wrote. “In the United States, preterm birth affects approximately 10% of live-born deliveries,” while recent data chart an increase in prevalence between 2016 and 2019.

Alongside a rise in preterm births, data show US rates of chlamydia, gonorrhea, and syphilis have also increased among the general population between 2013 and 2018. It is estimated 2022 infants were born with congenital syphilis in 2020 alone, according to The New England Journal of Medicine; this number surpasses the 1870 cases reported in 2019 and represents the highest case count since 1994.

In the current study, the investigators gleaned information from over 14 million mother-infant pairs via the US National Vital Statistics System (NVSS), documented between 2016 and 2019. All included mothers had a live singleton birth and available data on STIs and gestational age at birth. The researchers classified gestational ages as “extremely preterm birth (<28 weeks of gestation), very preterm birth (28-31 weeks of gestation), and moderately preterm birth (32-36 weeks of gestation).”

Among the 14,373,023 mothers included, the mean (SD) age was 29 (5.8) years and 23.9% identified as Hispanic, 6.4% as non-Hispanic Asian, 14.3% as non-Hispanic Black, and 51.4% as non-Hispanic White. Just under 2% of mothers had chlamydia, 0.3% had gonorrhea, and 0.1% had syphilis. Eight percent of all newborns were categorized as premature.

Analyses revealed:

• The rates of preterm birth were 9.9%, 12.2%, and 13.3% among women with chlamydia, gonorrhea, and syphilis infection, respectively
• Higher rates of gonorrhea, syphilis, and chlamydia infection were found among women younger than age 25, non-Hispanic Black women, women with lower education, women who were unmarried, women who smoked during pregnancy, or women who needed Medicaid
• After adjustment for sociodemographic and medical and/or health factors, the odds ratio (OR) of preterm birth was 1.03 (95% CI, 1.02-1.04) for chlamydia, 1.11 (95% CI, 1.08-1.15) for gonorrhea, 1.17 (95% CI, 1.11-1.22) for syphilis, and 1.06 (95% CI, 1.05-1.07) for any of the STIs compared with infection-free mothers
• The adjusted OR of moderately preterm birth was 1.04 (95% CI, 1.02-1.05) for chlamydia, 1.10 (95% CI, 1.06-1.14) for gonorrhea, and 1.17 (95% CI, 1.11-1.23) for syphilis
• The adjusted OR of very preterm birth was 1.27 (95% CI, 1.16-1.38) for gonorrhea and 1.35 (95% CI, 1.19-1.53) for syphilis; no significant association was found between chlamydia and very preterm birth

The authors hypothesized inflammation could serve as a potential shared mechanism for the relationship between preterm birth and STIs. For example, “chlamydia and gonorrhea, like some other lower genital infections, may ascend via the vagina-cervix and contribute to the occurrence of chorioamnionitis by partial activation of the systemic cytokine network,” while “syphilis, which is spread by hematogenous dissemination, may cause systemic infection and placental inflammatory response,” they explained.

Concentration of the pathogen and timing of infection could also influence whether a maternal infection induces preterm birth.

The NVSS does not include data on treatment of the STIs, and the investigators were unable to examine effect modification by treatment, marking limitations to the study. Data on subtype of premature birth were also not included; residual confounding by unmeasured factors could have affected outcomes as well.

“The present study identified maternal STIs as a novel risk factor for preterm birth, suggesting that addressing maternal STIs might be an unrecognized preventive approach to reduce preterm birth,” the researchers concluded.

Writing in an accompanying editorial,² Emily H. Adhikari, MD, and Scott Roberts, MD, highlighted the lack of randomized controlled trials evaluating the effect of treatment or lack of treatment on chlamydia, gonorrhea, or syphilis infections on primary prevention of preterm birth, but offered cautious views on the retrospective nature of the current study.

“In this study, the effect sizes were larger for very preterm compared with moderately or extremely preterm birth. Why the outcome of interest occurred more commonly in a very specific gestational age window is somewhat perplexing,” they wrote. “We must still interpret the conclusions in light of the known limitations of observational studies.”

Adhikari and Roberts noted that unknown variables in the data set such as chronic stress, gestational age at diagnosis, or lack of treatment access could contribute to findings.

“Without a better understanding of which infections were and were not treated, we have little to guide a search for targeted interventions to prevent preterm birth in a cohort with treatable infectious diseases,” they said, adding more research on understanding to what degree STIs cause preterm birth and how effective STI screening can be in reducing preterm birth in the United States is warranted.

References

1. 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. Published online November 29, 2021. doi:10.1001/jamanetworkopen.2021.33413

2. Adhikari EH and Roberts S. Sexually transmitted infections and preterm birth—attempting to pin down targets for intervention from population-level observational data. JAMA Netw Open. Published online November 29, 2021. doi:10.1001/jamanetworkopen.2021.34459