Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with Schistosoma japonicum in the Philippines.

Ajibola I Abioye,Sangshin Park,Emily A Mcdonald,Jonathan D Kurtis,Hannah Wu,Jennifer F Friedman,Sunthorn Pond-Tor,Remigio M Olveda,Veronica Tallo,Luz P Acosta,Ayush Joshi,Jan Ernerudh,Surendra Sharma,Palmera Baltazar

doi:10.1371/journal.pntd.0007371

Abstract

BackgroundThe objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment.Methods/FindingsThis was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12–16 weeks’ gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks’ gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-γ. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated.ConclusionsOur study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface.Clinical Trial Registry number and websiteClinicalTrials.gov (NCT00486863).

Highlights

Adverse perinatal outcomes account for a substantial proportion of the global burden of disease [1] and lay the foundation for health in later childhood, adolescence, and adulthood [2,3,4,5]
Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth
The randomized controlled trial (RCT) aimed to address the gaps in evidence concerning the safety and efficacy of praziquantel treatment, and thereby provision of praziquantel treatment to pregnant women infected with Schistosomiasis, in line with recommendations from the World Health Organization (WHO)

Summary

Introduction

Adverse perinatal outcomes account for a substantial proportion of the global burden of disease [1] and lay the foundation for health in later childhood, adolescence, and adulthood [2,3,4,5]. Low birthweight (LBW), fetal growth restriction (FGR) and preterm births together account for more than 80% of all neonatal deaths globally [6] These conditions are more common in developing countries and a considerable part of this difference is attributable to poor nutrition and infections [6, 7]. In a recent randomized controlled trial (RCT) Olveda and colleagues found that treatment with praziquantel at 12–16 weeks gestation had no impact on birthweight, or risk for LBW, small-for-gestational age (SGA), or prematurity [11] This raised the concern that treatment during pregnancy may be too late to modify a pro-inflammatory response at the maternal-fetal interface (MFI). The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment

Objectives

Methods

Results

Conclusion