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. 2020 Feb:91:24-30.
doi: 10.1016/j.placenta.2020.01.003. Epub 2020 Jan 8.

Circulating Delta-like homolog 1 (DLK1) at 36 weeks is correlated with birthweight and is of placental origin

Teresa M MacDonald  1 , Susan P Walker  1 , Richard Hiscock  2 , Ping Cannon  1 , Alesia Harper  1 , Elizabeth Murray  1 , Lisa Hui  1 , Kirsten Dane  3 , Anna Middleton  3 , Valerie Kyritsis  3 , Natasha de Alwis  1 , Natalie J Hannan  1 , Stephen Tong  1 , Tu'uhevaha J Kaitu'u-Lino  4
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Circulating Delta-like homolog 1 (DLK1) at 36 weeks is correlated with birthweight and is of placental origin

Teresa M MacDonald et al. Placenta. 2020 Feb.

Abstract

Introduction: Recently, Delta-like homolog 1 (DLK1) was identified as a potential marker of small-for-gestational-age (SGA; <10th centile) fetuses; mouse studies suggest reduced levels may represent a fetal stress signal. We sought to measure DLK1 in a large independent cohort of maternal blood samples, correlate levels with measures of placental insufficiency and assess whether DLK1 might be placental derived.

Methods: The Fetal Longitudinal Assessment of Growth (FLAG) study was a prospective blood collection from 2000 women. We assessed a case-control cohort at 28 and 36 weeks from the first 1000 FLAG women, before validating changes in the entire second 1000. A subgroup of FLAG participants underwent ultrasound examinations, and 137 neonates, body composition assessment (PEAPOD). DLK1 secretion was assessed from human placentas ex vivo.

Results: Circulating DLK1 was significantly reduced at 28 and 36 weeks' gestation in women destined to deliver a SGA fetus and associated with birthweight centile (n = 999, p < 0.0001), and placental weight (n = 96, p = 0.0064). Ex vivo, DLK1 was abundantly released from human placenta and significantly reduced under hypoxia (n = 7, p < 0.05). We found no relationship between circulating DLK1 and estimated fetal weight, cerebroplacental ratio, uterine artery or umbilical artery pulsatility index. Nor was there a relationship between DLK1 and neonatal fat or lean mass (n = 137).

Conclusion: We confirmed circulating DLK1 is reduced at both 28 and 36 weeks' gestation preceding delivery of a SGA infant, shown that it is not significantly associated with clinical measures of placental insufficiency, and provide new data demonstrating it may be placenta-derived in humans.

Keywords: Biomarkers; FGR; Fetal growth; Small for gestational age.

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Conflict of interest statement

Declaration of competing interest TMM, SPW, ST and TKL are listed as inventors for molecules to identify placental insufficiency unrelated to DLK1.

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