The SLC25A42 Transcript Is a Biomarker for Fetal Reprogramming in Response to Placental Insufficiency in Preterm Newborns Under 32 Weeks Gestation—A Pilot Study

Fu-Sheng Chou,Pei-Shan Wang

doi:10.3389/fped.2020.00459

Abstract

Introduction: Timing of medical delivery of preterm newborns exposed to placental insufficiency is largely determined by umbilical artery blood flow and maternal clinical manifestations. There is a lack of tools to properly assess fetal body response to placental insufficiency before or upon delivery. Yet, short- and long-term comorbidities associated with placental insufficiency and the consequential intrauterine growth restriction may be a result of fetal response following prolonged stress. This study aims to establish a procedure to investigate fetal/neonatal transcriptional response to placental insufficiency as part of an initiative to identify cost-effective biomarkers for assessing fetal response to placental insufficiency.Methods: A prospective pilot study involving newborns with birth gestation <32 weeks was conducted to compare gene expression profiles in whole blood collected at birth among three clinically distinct groups - preeclampsia without placental insufficiency (PE), placental insufficiency (PI), and non-PE/PI groups.Results: Whole blood from 11, 3, and 6 newborns in the non-PE/PI, PE, and PI groups were obtained. A transcriptome analysis found that the majority of the genes were downregulated in the PI group, suggesting global transcriptional inactivation. Intriguingly, SLC25A42, which encodes a mitochondrial transporter for coenzyme A and adenosine-3′,5′-diphosphate, was significantly upregulated in the PI group.Conclusion: Transcriptional biomarkers for assessing fetal response to placental insufficiency may provide a useful tool to better understand the pathophysiology of fetal reprogramming in response to placental insufficiency. The validity and the role of SLC25A42, as well as its correlation with short- and long-term neonatal outcomes, warrants further investigation.

Highlights

Timing of medical delivery of preterm newborns exposed to placental insufficiency is largely determined by umbilical artery blood flow and maternal clinical manifestations
The median 1 min APGAR score was lower in the preeclampsia insufficiency (PE) and the Placental insufficiency (PI) groups, indicating higher likelihood of needing resuscitation in the delivery room among E/VPNs born to mothers with preeclampsia or placental insufficiency
We found that the majority of genes in the PI group were downregulated when compared to the non-PE/PI group; on the other hand, the numbers of the genes that were upregulated and downregulated were comparable between the non-PE/PI and the PE groups (Figure 1)

Summary

Introduction

Timing of medical delivery of preterm newborns exposed to placental insufficiency is largely determined by umbilical artery blood flow and maternal clinical manifestations. Short- and long-term comorbidities associated with placental insufficiency and the consequential intrauterine growth restriction may be a result of fetal response following prolonged stress. Surviving E/VPNs are at increased risk for neurodevelopmental abnormalities, including cognitive impairment, learning disabilities, and mental health issues [2,3,4]. Those E/VPNs who experienced intrauterine growth restriction (IUGR) are at even greater risk of adverse neurodevelopmental outcomes and cardiometabolic derangement [5, 6]. Placental vasculopathy causes maternal preeclampsia and eclampsia, and is associated with placental insufficiency, a condition where blood supply toward the growing fetus is compromised, resulting in chronic fetal hypoxia and nutrient deprivation. The diagnosis of IUGR by fetal weight estimation using non-invasive sonography is still a challenge, and the presence of IUGR may indicate that irreversible fetal reprogramming has already occurred [9]

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