Inflammation linked to preterm birth in developing regions

Inflammation linked to preterm birth in developing regions | Image Credit: © Alessandro Grandini - © Alessandro Grandini - stock.adobe.com.

Inflammation is linked to preterm birth (PTB) in both developed and developing countries, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

PTB is the leading cause of morbidity and mortality in pediatric patients aged under 5 years and has a worldwide rate of approximately 11%.² Low-income countries experience significantly increased mortality rates from PTB vs higher income countries, with 2 in 3 PTB deaths in 2019 occurring in Western Sub-Saharan Africa and South Asia.¹

A significant association has been reported between ascending infection and PTB, and pathogens have been proven to cross the cervical and placental or fetal membrane barrier. However, according to investigators, “the specific pathophysiology of infection-related preterm labor (PTL) remains poorly understood.”

The study was conducted to determine the link between placental inflammation and PTB in developing countries. Standard operating procedures were used to collect the placental biopsies of participants within 1 hour of delivery.

Samples were obtained from patients residing in Pakistan, Zambia, Tanzania, and Bangladesh. Specimens were washed in sterile phosphate buffered saline and submerged in a 50 mL container of 10% neutral buffered formalin for 48 to 72 hours.

Six endpoints were evaluated in samples. These included basal plate (BP), chorionic villi (CV), and chorionic plate (CP) presence, villus, syncytiotrophoblasts (STB), and cytotrophoblast (CTB) changes, inflammation, blood vessel changes, villous core edema, and avascular fibrotic villi.

A pathologic system was scored with a 1 if present and a 0 if absent. For endpoints with multiple features such as villus, STB, or CBT changes, inflammation, and blood vessel changes, scores were summed and averaged.

Microfluidic electrophoresis was used to evaluate RNA integrity after isolation using a spin column–based nucleic acid purification approach. If concentrations went beyond the dynamic range, the aliquots were diluted to 500 ng/μL. RNA integrity was measured with a score of 0 to 10, with those receiving a score of at least 7 undergoing sequencing.

Placental samples from term delivery vs preterm delivery cases with differentially expressed (DE) genes were identifies using DESeq2 (v. 1.28.0). Investigators also performed functional analysis of DE genes to identify enriched gene ontology (GO) terms. Differential expression was confirmed through quantitative reverse transcriptase–polymerase chain reaction.

Placental biopsies were obtained from all 5 collection sites, all of which determined gestational age using early ultrasound dating. Deliveries at 36 weeks’ gestation or earlier were preterm, while those later were controls. CV was identified in all biopsies, and CP was the most absent compartment. BP presence was more varied in comparison.

In PTB cases, CV was impacted the most compared to other compartments, ranging from 25% at the Pakistan site to 62% at the Zambia site. All 5 collection sites reported significantly higher CV with leukocyte infiltration in PTB vs term samples.

Histologic evidence of inflammation was reported in 42% of CV samples from PTB cases vs 9% of controls. Robust leukocyte infiltration of the decidua was the most frequent finding in births with BP.

When evaluating placental CV, signs of inflammation were more common in the PTB group compared to the control group. Additionally, leukocyte infiltration of the BVs and their walls was often observed.

There were 267 DE genes between PTB pregnancy vs term pregnancy placentas, 123 of which were upregulated and 144 were downregulated. In the GO analysis, 20 biological samples were identified as enriched in PTB samples, with leukocyte activation and inflammatory responses among the highlighted processes.

These results indicated higher than expected incidence of inflammation in preterm samples collected at biorepository sites. Investigators concluded “this finding raises the possibility that pregnancies in certain developing regions around the world may be affected similarly.”

References

1. Robinson JF, Das S, Khan W, et al. High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium. Am J Obstet Gynecol 2025;232:230.e1-19. doi:10.1016/j.ajog.2024.04.034
2. Preterm birth. World Health Organization. Accessed February 19, 2024. https://www.who.int/news-room/fact-sheets/detail/preterm-birth