High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium - 25/05/24

Doi : 10.1016/j.ajog.2024.04.034

Joshua F. Robinson, PhD ^a, Sayan Das, MSc ^b, Waqasuddin Khan, PhD ^c,^d, Rasheda Khanam, PhD ^e, Joan T. Price, MD, MPH ^f,^g, Anisur Rahman, PhD ^h, Salahuddin Ahmed, MBBS ⁱ, Said Mohammed Ali, MSc ^b, Saikat Deb, PhD ^b,^j, Brian Deveale, PhD ^a,^k,^l, Arup Dutta, MBA ^j, Matthew Gormley, BS ^a,^k,^m, Steven C. Hall, PhD ^a,^k,^m, A.S.M. Tarik Hasan, MSc ^h, Aneeta Hotwani, MSc, MBA ^d, Mohamed Hamid Juma, DPHN ^b, Margaret P. Kasaro, MBChB, MPH ^f,^g,ⁿ, Javairia Khalid, PhD ^c,^d, Pallavi Kshetrapal, PhD ^o, Michael T. McMaster, PhD ^a,^k,^p, Usma Mehmood, MS ^d, Imran Nisar, PhD ^c,^d, Jesmin Pervin, MPH ^h, Sayedur Rahman, MBBS ^h,ⁱ, Rubhana Raqib, PhD ^q, Ali San, BS ^a,^k, Protim Sarker, PhD ^r, Sami T. Tuomivaara, PhD ^a,^k,^m, Ge Zhang, MD, PhD ^s,^t,^u, Yan Zhou, MD, MS ^a,^k, Shaki Aktar, MPH ^h, Abdullah H. Baqui, DrPH ^e, Fyezah Jehan, MD ^c,^d, Sunil Sazawal, PhD ^j, Jeffrey S.A. Stringer, MD ^g, Susan J. Fisher, PhD ^a,^k,^m,^⁎
^a Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA
^b Public Health Laboratory Ivo de Carneri, Wawi, Chake, Pemba, Zanzibar, Tanzania
^c 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
^d Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan
^e Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
^f UNC Global Projects – Zambia, Lusaka, Zambia
^g Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC
^h Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
ⁱ Projahnmo Research Foundation, Dhaka, Bangladesh
^j Center for Public Health Kinetics, Vinoba Puri, Lajpatnagar II, New Delhi, India
^k Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA
^l Department of Urology, University of California, San Francisco, San Francisco, CA
^m Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, CA
ⁿ Department of Gynaecology and Obstetrics, University of Zambia School of Medicine, Lusaka, Zambia
^o Maternal and Child Health, Translational Health Science and Technology Institute, Faridabad, India
^p Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA
^q International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
^r Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
^s Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
^t Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
^u 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

^∗Corresponding author: Susan J. Fisher, PhD.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 25 May 2024

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.

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Key words : chorionic villi, chronic villitis, inflammation, parturition, placenta, pregnancy, prematurity preterm birth, transcriptomics

Plan

Introduction

Materials and Methods

Placental tissue collection

Morphologic analyses

Transcriptomics

Quantitative reverse transcriptase–polymerase chain reaction validation of differentially expressed genes

Results in the context of what is known

Clinical implications

Research implications

Strengths and limitations

Conclusion

	J.F.R., S.D., W.K., R.K., J.T.P., and A.R. are co-first authors.
	S.A., A.H.B., F.J., S.S., J.S.A.S., and S.J.F. are co-last authors.
	The authors report no conflict of interest.
	This study was supported by the Bill and Melinda Gates Foundation, the Alliance for Maternal and Newborn Health Improvement (AMANHI), and the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS).
	Cite this article as: 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 2024;XX:x.ex–x.ex.