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

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  • Tu’uhevaha J. Kaitu’u-Lino

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Teresa M. MacDonald

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Ping Cannon

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Tuong-Vi Nguyen

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Richard J. Hiscock

    (Mercy Perinatal, Mercy Hospital for Women)

  • Nick Haan

    (Foresight Health)

  • Jenny E. Myers

    (University of Manchester, Manchester Academic Health Science Centre, St Mary’s Hospital)

  • Roxanne Hastie

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Kirsten M. Dane

    (Mercy Perinatal, Mercy Hospital for Women)

  • Anna L. Middleton

    (Mercy Perinatal, Mercy Hospital for Women)

  • Intissar Bittar

    (Pathology Department, Austin Health)

  • Amanda N. Sferruzzi-Perri

    (University of Cambridge)

  • Natasha Pritchard

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Alesia Harper

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Natalie J. Hannan

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Valerie Kyritsis

    (Mercy Perinatal, Mercy Hospital for Women)

  • Nick Crinis

    (Pathology Department, Austin Health)

  • Lisa Hui

    (Mercy Perinatal, Mercy Hospital for Women)

  • Susan P. Walker

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

  • Stephen Tong

    (University of Melbourne
    Mercy Perinatal, Mercy Hospital for Women)

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.

Suggested Citation

  • 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 Bit, 2020. "Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16346-x
    DOI: 10.1038/s41467-020-16346-x
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