This study aimed to investigate the association between prenatal Chlamydia exposure and early neonatal respiratory failure (NRF) in very preterm infants (VPIs).

This population-based cohort study utilized birth data submitted by 50 states and the District of Columbia to the National Vital Statistics System database in the United States. The study included all VPIs with a gestational age of 24 to 31 weeks from January 1, 2021, to December 31, 2022. Infants exposed to Chlamydia were compared with unexposed infants (no Chlamydia exposure) selected through propensity score matching at a 1:2 ratio, adjusting for confounding factors. The primary outcome was NRF, defined as the requirement for assisted ventilation for more than 6 hours, as recorded in the database.

After propensity score matching, 2,757 Chlamydia-exposed infants and 5,507 no Chlamydia-exposure infants were compared. Infants with Chlamydia exposure had a significantly higher relative risk of NRF compared to no Chlamydia-exposure infants (30.5%, 840/2,757 vs. 25.4%, 1,401/5,507; risk ratio [RR] = 1.20 [95% CI, 1.13–1.29]). Additionally, the risk of assisted ventilation required immediately following delivery was higher in the Chlamydia-exposed group (47.2%, 1,300/2,757 vs. 41.5%, 2,283/5,507; RR = 1.15 [95% CI, 1.10–1.20]). Subgroup analyses by gestational age, sex, and other factors demonstrated consistent results for the primary outcome. Sensitivity analyses, including total infants, 1:1 propensity score matching, and 1:3 propensity score matching, yielded similar findings.

Prenatal Chlamydia exposure is significantly associated with an increased risk of NRF in VPIs. Further investigation is warranted to develop intervention strategies aimed at preventing NRF in high-risk infants with prenatal Chlamydia exposure.

NRF remains the leading cause of early neonatal death in VPIs.

There is limited and inconclusive evidence regarding prenatal Chlamydia and NRF.

VPIs with Chlamydia exposure had a significantly higher risk of NRF.

Because the data used are publicly available, ethical review and informed consent requirements were exempted by the institutional review board of Children's Hospital of Fudan University.

Because all data comes from public databases, there is no need to sign informed consent.

The data used in this study were obtained from the Natality Birth Data of the NVSS, maintained by the National Center for Health Statistics, CDC.

‡ These authors contributed equally to this article and share first authorship.

Affiliation addresses are listed at the end of the article.

Received: 16 June 2025

Accepted: 11 August 2025

Accepted Manuscript online:
12 August 2025

Article published online:
27 August 2025

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