Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction

Tu’uhevaha J. Kaitu’u-Lino, Teresa M. MacDonald, Ping Cannon, Tuong-Vi Nguyen, Richard J. Hiscock, Nick Haan, Jenny E. Myers, Roxanne Hastie, Kirsten M. Dane, Anna L. Middleton, Intissar Bittar, Amanda N. Sferruzzi-Perri, Natasha Pritchard, Alesia Harper, Natalie J. Hannan, Valerie Kyritsis, Nick Crinis, Lisa Hui, Susan P. Walker, Stephen Tong

Research output: Contribution to journalArticlepeer-review

Abstract

Placental insufficiency can cause fetal growth restriction and stillbirth. There are no reliable screening tests for placental insufficiency, especially near-term gestation when the risk of stillbirth rises. Here we show a strong association between low circulating plasma serine peptidase inhibitor Kunitz type-1 (SPINT1) concentrations at 36 weeks’ gestation and low birthweight, an indicator of placental insufficiency. We generate a 4-tier risk model based on SPINT1 concentrations, where the highest risk tier has approximately a 2-5 fold risk of birthing neonates with birthweights under the 3rd, 5th, 10th and 20th centiles, whereas the lowest risk tier has a 0-0.3 fold risk. Low SPINT1 is associated with antenatal ultrasound and neonatal anthropomorphic indicators of placental insufficiency. We validate the association between low circulating SPINT1 and placental insufficiency in two other cohorts. Low circulating SPINT1 is a marker of placental insufficiency and may identify pregnancies with an elevated risk of stillbirth.
Original languageEnglish
Article number2411
JournalNature Communications
Volume11
DOIs
Publication statusPublished - 15 May 2020

Keywords

  • Animals
  • Anthropometry
  • Biomarkers/blood
  • Female
  • Fetal Growth Retardation/diagnosis
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Mice
  • Placenta/physiopathology
  • Placental Insufficiency
  • Plethysmography
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy Trimester, Third
  • Proteinase Inhibitory Proteins, Secretory/blood
  • Sensitivity and Specificity
  • Ultrasonography, Prenatal
  • Umbilical Arteries/physiology
  • Uterine Artery/physiology

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