Prenatal exposure to intra-amniotic infection with Ureaplasma species increases the prevalence of bronchopulmonary dysplasia

Abstract

Objectives

The present study investigated the relationship between bronchopulmonary dysplasia (BPD) and intra-amniotic infection with Ureaplasma species.

Methods

This was a single-center, retrospective cohort study. Patients with singleton pregnancies who underwent inpatient management at our department for preterm premature rupture of membranes (PPROM), preterm labor, cervical insufficiency, and asymptomatic cervical shortening at 22–33 gestational weeks were included. Amniocentesis was indicated for patients with PPROM or an elevated maternal C-reactive protein level (≥0.58 mg/dL). Patients with an amniotic fluid IL-6 concentration ≥3.0 ng/mL were diagnosed with intra-amniotic inflammation, while those with positive aerobic, anaerobic, M. hominis, and Ureaplasma spp. cultures were diagnosed with microbial invasion of the amniotic cavity (MIAC). Patients who tested positive for both intra-amniotic inflammation and MIAC were considered to have intra-amniotic infection. An umbilical vein blood IL-6 concentration >11.0 pg/mL indicated fetal inflammatory response syndrome (FIRS). The maternal inflammatory response (MIR) and fetal inflammatory response (FIR) were staged using the Amsterdam Placental Workshop Group Consensus Statement.

Results

Intra-amniotic infection with Ureaplasma spp. was diagnosed in 37 patients, intra-amniotic infection without Ureaplasma spp. in 28, intra-amniotic inflammation without MIAC in 58, and preterm birth without MIR/FIR and FIRS in 86 as controls. Following an adjustment for gestational age at birth, the risk of BPD was increased in patients with intra-amniotic infection with Ureaplasma spp. (adjusted odds ratio: 10.5; 95% confidence interval: 1.55–71.2), but not in those with intra-amniotic infection without Ureaplasma spp. or intra-amniotic inflammation without MIAC.

Conclusion

BPD was only associated with intra-amniotic infection with Ureaplasma species.

Keywords:

• Chorioamnionitis
• interleukin-6
• intra-amniotic inflammation
• microbial invasion of the amniotic cavity
• preterm birth
• preterm premature rupture of membranes

Acknowledgments

We would like to thank Dr. Eiji Sadashima (Saga Medical Centre Koseikan) for his support with data analyses.

Authors’ contributions

All authors accept responsibility for the contents of this manuscript and approved its submission.

Research ethics

Research involving human subjects complied with all relevant national regulations and institutional policies, was performed according to the tenets of the Helsinki Declaration (as revised in 2013), and received approval from the Institutional Review Boards of National Hospital Organization Saga National Hospital (approval number: R4-8).

Informed consent

All patients provided informed consent for the present study.

Disclosure statement

The authors declare no conflicts of interest.

Data availability statement

Raw data are available upon reasonable request from the corresponding author.

Additional information

Funding

This work was supported by JSPS KAKENHI (grant JP20H03564; for IY) and AMED, Japan (grant JP23fk0108677; for MN and IY).