Elsevier

Placenta

Volume 110, July 2021, Pages 24-28
Placenta

Maternal circulating SPINT1 is reduced in small-for-gestational age pregnancies at 26 weeks: Growing up in Singapore towards health outcomes (GUSTO) cohort study

https://doi.org/10.1016/j.placenta.2021.05.007Get rights and content

Highlights

  • SPINT1 was reduced at 26 weeks' gestation in those destined to deliver a <10th centile infant.

  • SPINT1 was most reduced in those delivering a <3rd centile baby.

  • SPINT1 at 26 weeks' was not associated with infant body composition at birth.

  • This study validates prior findings that low maternal SPINT1 is associated with poor fetal growth.

Abstract

Fetal growth restriction arising from placental insufficiency is a leading cause of stillbirth. We recently identified low maternal circulating SPINT1 concentrations as a novel biomarker of poor fetal growth. Here we measured SPINT1 in a prospective cohort in Singapore. Circulating SPINT1 concentrations were significantly lower among 141 pregnant women destined to deliver small-for-gestational age infants (birthweight <10th centile), compared to 772 controls (p < 0.01) at as early as 26 weeks’ gestation. There were no correlations between infant body composition and circulating SPINT1 concentrations at 26 weeks. This provides validation that low maternal SPINT1 concentration is associated with poor fetal growth.

Introduction

Fetal growth restriction (FGR) is a serious obstetric complication associated with a 3–4 fold increased risk of stillbirth [[1], [2], [3]]. Current clinical tools perform modestly in identifying pregnancies at risk for FGR [1,4]. Better diagnostic tests or biomarkers to identify placental insufficiency and fetal growth restriction represent a pressing clinical need.

Our research program includes a pipeline to screen placental molecules released into the maternal circulation as potential biomarkers for pregnancy complications [[5], [6], [7]]. We recently identified associations between low circulating serine peptidase inhibitor, Kunitz type-1 (SPINT1, a protein highly expressed in placenta) and low birthweight and infant body composition at birth in an Australian birth cohort [8].

This study aimed to measure maternal plasma SPINT1 at 26 weeks' gestation to determine whether low SPINT1 was associated with the delivery of a small for gestational age (SGA; birthweight <10th centile) infant. Since perturbations in infant body composition occur when there is placental insufficiency in utero, our secondary aim was to determine whether there was an association between circulating maternal SPINT1 at 26 weeks’ gestation and infant body composition at birth.

Section snippets

Growing up in Singapore towards healthy outcomes (GUSTO) birth cohort study

GUSTO [9] included collection of blood samples from pregnant women attending Singapore's two major public maternity units between June 2009 and September 2010. Participants were of Chinese, Malay or Indian ethnicity with homogeneous parental ethnic background. The study was approved by the Centralized Institutional Review Board (IRB) of SingHealth (2018/2767) and IRB of National Healthcare Group (D/2009/021). Written informed consent was obtained from all participants. Infant birthweights were

Results and discussion

In 141 women who delivered an SGA baby at term (<10th centile birthweight), circulating SPINT1 concentrations were significantly (p < 0.01) reduced with median SPINT1 of 85.9 ng/ml (interquartile range (IQR) 68.8–112 ng/ml) compared to a median of 95.5 ng/ml (IQR, 74.1–120 ng/ml) among the 772 controls. Area under the receiver operator curve (AUC) was 0.57 (Fig. 1A). We also performed a sub-analysis, dividing the SGA cohort into 5–10th, 3rd-5th, and <3rd centile groups (Fig. 1B). As expected,

Disclosure statement

TKL, TM, SW and ST hold a provisional patent (PCT/AU2019/050516) relating to the use of SPINT1 and syndecan as diagnostic markers in pregnancy. KMG, PDG and YSC have received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd. and Danone. The remaining authors have no conflicts of interest to declare. Funding

Funding for this

Declaration of competing interest

TKL, TM, SW and ST hold a provisional patent (PCT/AU2019/050,516) relating to the use of SPINT1 and syndecan as diagnostic markers in pregnancy. KMG, PDG and YSC have received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd. and Danone. The remaining authors have no conflicts of interest to declare.

Acknowledgements

KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF–SI-0515-10042), NIHR Southampton 1000DaysPlus Global Nutrition Research Group (17/63/154) and NIHR Southampton Biomedical Research Centre (IS-BRC-1215-20004)), the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP) and the British Heart Foundation (RG/15/17/3174).

References (12)

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    Both disorders arise from aberrant placentation. Proteins highly expressed by the placenta and released into the maternal circulation could act as biomarkers for earlier disease prediction [3–9]. A disintegrin and metalloproteinase-12 (ADAM12) was first identified as a mediator of muscle cell fusion prior to discovery of abundant expression in the placenta [10–12].

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Equal contribution.

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