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 and Stephen Tong ()
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Tu’uhevaha J. Kaitu’u-Lino: University of Melbourne
Teresa M. MacDonald: University of Melbourne
Ping Cannon: University of Melbourne
Tuong-Vi Nguyen: University of Melbourne
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
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
Alesia Harper: University of Melbourne
Natalie J. Hannan: University of Melbourne
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
Stephen Tong: University of Melbourne

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16346-x

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