Abstract

BackgroundFetal growth restriction, pre-eclampsia, and pre-term birth are major adverse pregnancy outcomes. These complications are considerable contributors to fetal/maternal morbidity and mortality worldwide. A significant proportion of these cases are thought to be due to dysfunction of the placenta. However, the underlying mechanisms of placental dysfunction are unclear. The aim of the present study was to investigate whether adverse pregnancy outcomes are associated with evidence of placental eukaryotic infection.ResultsWe modified the 18S Illumina Amplicon Protocol of the Earth Microbiome Project and made it capable of detecting just a single spiked-in genome copy of Plasmodium falciparum, Saccharomyces cerevisiae, or Toxoplasma gondii among more than 70,000 human cells. Using this method, we were unable to detect eukaryotic pathogens in placental biopsies in instances of adverse pregnancy outcome (n = 199) or in healthy controls (n = 99).ConclusionsEukaryotic infection of the placenta is not an underlying cause of the aforementioned pregnancy complications. Possible clinical applications for this non-targeted, yet extremely sensitive, eukaryotic screening method are manifest.

Highlights

  • Fetal growth restriction, pre-eclampsia, and pre-term birth are major adverse pregnancy outcomes

  • To study associations between placental eukaryotic infection and pregnancy complications, cases of Fetal growth restriction (FGR) (less than third percentile based on customized birth weight accounting for gestational age, fetal sex, maternal weight/height, ethnicity, parity, and smoking [12] (n = 50) or pre-eclampsia according to the 2013 ACOG Guidelines (The American Congress of Obstetricians and Gynecologists [13]; n = 49)) were selected (Additional file 1: Table S2)

  • Single-index 18S rRNA sequencing we studied three groups: (1) 44 placental samples obtained from four placentas delivered following a normal pregnancy (11 biopsies per placenta), (2) positive controls, and (3) negative controls

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Summary

Introduction

Pre-eclampsia, and pre-term birth are major adverse pregnancy outcomes. These complications are considerable contributors to fetal/maternal morbidity and mortality worldwide. A significant proportion of these cases are thought to be due to dysfunction of the placenta. The underlying mechanisms of placental dysfunction are unclear. The aim of the present study was to investigate whether adverse pregnancy outcomes are associated with evidence of placental eukaryotic infection. Fetal growth restriction (FGR), pre-eclampsia, and pre-term birth are major adverse pregnancy outcomes, and a significant proportion of cases are thought to be due to placental dysfunction. Pregnancy is associated with increased susceptibility to certain infections, including candidiasis and Plasmodium falciparum [1,2,3]. Plasmodium falciparum infection has been associated with maternal death, reduced

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