High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium

Joshua F Robinson; Sayan Das; Waqasuddin Khan; Rasheda Khanam; Joan T Price; Anisur Rahman; Salahuddin Ahmed; Said Mohammed Ali; Saikat Deb; Brian Deveale; Arup Dutta; Matthew Gormley; Steven C Hall; A S M Tarik Hasan; Aneeta Hotwani; Mohamed Hamid Juma; Margaret P Kasaro; Javairia Khalid; Pallavi Kshetrapal; Michael T McMaster; Usma Mehmood; Imran Nisar; Jesmin Pervin; Sayedur Rahman; Rubhana Raqib; Ali San; Protim Sarker; Sami T Tuomivaara; Ge Zhang; Yan Zhou; Shaki Aktar; Abdullah H Baqui; Fyezah Jehan; Sunil Sazawal; Jeffrey S A Stringer; Susan J Fisher

doi:10.1016/j.ajog.2024.04.034

High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium

Am J Obstet Gynecol. 2024 Apr 30:S0002-9378(24)00560-X. doi: 10.1016/j.ajog.2024.04.034. Online ahead of print.

Authors

Joshua F Robinson¹, Sayan Das², Waqasuddin Khan³, Rasheda Khanam⁴, Joan T Price⁵, Anisur Rahman⁶, Salahuddin Ahmed⁷, Said Mohammed Ali², Saikat Deb⁸, Brian Deveale⁹, Arup Dutta¹⁰, Matthew Gormley¹¹, Steven C Hall¹¹, A S M Tarik Hasan⁶, Aneeta Hotwani¹², Mohamed Hamid Juma², Margaret P Kasaro¹³, Javairia Khalid³, Pallavi Kshetrapal¹⁴, Michael T McMaster¹⁵, Usma Mehmood¹², Imran Nisar³, Jesmin Pervin⁶, Sayedur Rahman¹⁶, Rubhana Raqib¹⁷, Ali San¹⁸, Protim Sarker¹⁹, Sami T Tuomivaara¹¹, Ge Zhang²⁰, Yan Zhou¹⁸, Shaki Aktar⁶, Abdullah H Baqui⁴, Fyezah Jehan³, Sunil Sazawal¹⁰, Jeffrey S A Stringer²¹, Susan J Fisher²²

Affiliations

¹ Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA.
² Public Health Laboratory Ivo de Carneri, Wawi, Chake, Pemba, Zanzibar, Tanzania.
³ Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan.
⁴ Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
⁵ UNC Global Projects - Zambia, Lusaka, Zambia; Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC.
⁶ Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.
⁷ Projahnmo Research Foundation, Dhaka, Bangladesh.
⁸ Public Health Laboratory Ivo de Carneri, Wawi, Chake, Pemba, Zanzibar, Tanzania; Center for Public Health Kinetics, Vinoba Puri, Lajpatnagar II, New Delhi, India.
⁹ Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Department of Urology, University of California, San Francisco, San Francisco, CA.
¹⁰ Center for Public Health Kinetics, Vinoba Puri, Lajpatnagar II, New Delhi, India.
¹¹ Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, CA.
¹² Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan.
¹³ UNC Global Projects - Zambia, Lusaka, Zambia; Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC; Department of Gynaecology and Obstetrics, University of Zambia School of Medicine, Lusaka, Zambia.
¹⁴ Maternal and Child Health, Translational Health Science and Technology Institute, Faridabad, India.
¹⁵ Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA.
¹⁶ Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh; Projahnmo Research Foundation, Dhaka, Bangladesh.
¹⁷ International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.
¹⁸ Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA.
¹⁹ Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.
²⁰ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
²¹ Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC.
²² Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, CA. Electronic address: Susan.Fisher@ucsf.edu.

PMID: 38697337
DOI: 10.1016/j.ajog.2024.04.034

Abstract

Background: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality.

Objective: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births.

Study design: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics.

Results: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments.

Conclusion: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Keywords: chorionic villi; chronic villitis; inflammation; parturition; placenta; pregnancy; prematurity preterm birth; transcriptomics.