Teresa M MacDonald1, Susan P Walker1, Richard Hiscock2, Ping Cannon1, Alesia Harper1, Elizabeth Murray1, Lisa Hui1, Kirsten Dane3, Anna Middleton3, Valerie Kyritsis3, Natasha de Alwis1, Natalie J Hannan1, Stephen Tong1, Tu'uhevaha J Kaitu'u-Lino4. 1. Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia. 2. Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, 3084, Victoria, Australia. 3. Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia. 4. Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia. Electronic address: t.klino@unimelb.edu.au.
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.
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.
Authors: Clive J Petry; Keith A Burling; Peter Barker; Ieuan A Hughes; Ken K Ong; David B Dunger Journal: J Clin Endocrinol Metab Date: 2021-05-13 Impact factor: 5.958