Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at Birth

Detecting SGA (small for gestational age) during pregnancy improves the fetal and neonatal prognosis. To date, there is no valid antenatal biomarker of SGA used in clinical practice. Maternal circulating DLK1 (delta-like non-canonical notch ligand 1) levels have been shown to be significantly lower...

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Main Authors: Aurelie Pham, Delphine Mitanchez, Anne Forhan, Laurence Perin, Yves Le Bouc, Frederic Brioude, Marie-Laure Sobrier, Barbara Heude, Irene Netchine
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.836731/full
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author Aurelie Pham
Delphine Mitanchez
Delphine Mitanchez
Anne Forhan
Laurence Perin
Yves Le Bouc
Frederic Brioude
Marie-Laure Sobrier
Barbara Heude
Irene Netchine
author_facet Aurelie Pham
Delphine Mitanchez
Delphine Mitanchez
Anne Forhan
Laurence Perin
Yves Le Bouc
Frederic Brioude
Marie-Laure Sobrier
Barbara Heude
Irene Netchine
author_sort Aurelie Pham
collection DOAJ
description Detecting SGA (small for gestational age) during pregnancy improves the fetal and neonatal prognosis. To date, there is no valid antenatal biomarker of SGA used in clinical practice. Maternal circulating DLK1 (delta-like non-canonical notch ligand 1) levels have been shown to be significantly lower in pregnant women at 36 weeks of gestation (WG) who delivered a SGA newborn than in controls. Data in the literature are contradictory on the association between maternal circulating DLK1 levels and placental vascular dysfunction. The objective was to determine if maternal DLK1 levels in the second trimester of pregnancy are predictive of SGA, and to assess whether the measurement of DLK1 levels in maternal blood could be a means to distinguish SGA with placental vascular dysfunction from that due to other causes. We conducted a nested cased-control study within the EDEN mother-child cohort. 193 SGA (birth weight < 10th percentile) and 370 mother-child control (birth weight between the 25th and 75th percentile) matched pairs were identified in the EDEN cohort. Maternal circulating DLK1 levels at 26 WG were significantly lower for children born SGA than for controls (27.7 ± 8.7 ng/mL vs 30.4 ± 10.6 ng/mL, p = 0.001). Maternal blood DLK1 levels in the first quartile (DLK1 < 22.85 ng/mL) were associated with an odds ratio for SGA of 1.98 [1.15 - 3.37]. DLK1 was less predictive of SGA than ultrasound, with an area under the curve of 0.578. Maternal circulating DLK1 levels were not significantly different in cases of SGA with signs of placental vascular dysfunction (n = 63, 27.1 ± 9.2 ng/mL) than in those without placental dysfunction (n = 129, 28.0 ± 8.5 ng/mL, p = 0.53). The level of circulating DLK1 is reduced in the second trimester of pregnancy in cases of SGA at birth, independently of signs of placental vascular dysfunction. However, DLK1 alone cannot predict the risk of SGA.
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spelling doaj.art-54434e9b12d244b4afc959af61b29a702022-12-22T01:34:58ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-02-011310.3389/fendo.2022.836731836731Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at BirthAurelie Pham0Delphine Mitanchez1Delphine Mitanchez2Anne Forhan3Laurence Perin4Yves Le Bouc5Frederic Brioude6Marie-Laure Sobrier7Barbara Heude8Irene Netchine9Sorbonne Université, INSERM, Centre de Recherche Saint Antoine, APHP, Hôpital Armand Trousseau, Service de Néonatologie, Paris, FranceSorbonne Université, INSERM, Centre de Recherche Saint Antoine, Paris, FranceCentre Hospitalier Régional Universitaire (CHRU) de Tours, Hôpital Bretonneau, Service de Néonatologie, Tours, FranceUniversité de Paris Cité, INSERM, INRAE, Centre of Research in Epidemiology and StatisticS (CRESS), Paris, FranceSorbonne Université, APHP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Endocrinologie Moléculaire et Pathologies d’Empreinte, Paris, FranceSorbonne Université, INSERM, Centre de Recherche Saint Antoine, Paris, FranceSorbonne Université, INSERM, Centre de Recherche Saint Antoine, APHP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Endocrinologie Moléculaire et Pathologies d'Empreinte, Paris, FranceSorbonne Université, INSERM, Centre de Recherche Saint Antoine, Paris, FranceUniversité de Paris Cité, INSERM, INRAE, Centre of Research in Epidemiology and StatisticS (CRESS), Paris, FranceSorbonne Université, INSERM, Centre de Recherche Saint Antoine, APHP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Endocrinologie Moléculaire et Pathologies d'Empreinte, Paris, FranceDetecting SGA (small for gestational age) during pregnancy improves the fetal and neonatal prognosis. To date, there is no valid antenatal biomarker of SGA used in clinical practice. Maternal circulating DLK1 (delta-like non-canonical notch ligand 1) levels have been shown to be significantly lower in pregnant women at 36 weeks of gestation (WG) who delivered a SGA newborn than in controls. Data in the literature are contradictory on the association between maternal circulating DLK1 levels and placental vascular dysfunction. The objective was to determine if maternal DLK1 levels in the second trimester of pregnancy are predictive of SGA, and to assess whether the measurement of DLK1 levels in maternal blood could be a means to distinguish SGA with placental vascular dysfunction from that due to other causes. We conducted a nested cased-control study within the EDEN mother-child cohort. 193 SGA (birth weight < 10th percentile) and 370 mother-child control (birth weight between the 25th and 75th percentile) matched pairs were identified in the EDEN cohort. Maternal circulating DLK1 levels at 26 WG were significantly lower for children born SGA than for controls (27.7 ± 8.7 ng/mL vs 30.4 ± 10.6 ng/mL, p = 0.001). Maternal blood DLK1 levels in the first quartile (DLK1 < 22.85 ng/mL) were associated with an odds ratio for SGA of 1.98 [1.15 - 3.37]. DLK1 was less predictive of SGA than ultrasound, with an area under the curve of 0.578. Maternal circulating DLK1 levels were not significantly different in cases of SGA with signs of placental vascular dysfunction (n = 63, 27.1 ± 9.2 ng/mL) than in those without placental dysfunction (n = 129, 28.0 ± 8.5 ng/mL, p = 0.53). The level of circulating DLK1 is reduced in the second trimester of pregnancy in cases of SGA at birth, independently of signs of placental vascular dysfunction. However, DLK1 alone cannot predict the risk of SGA.https://www.frontiersin.org/articles/10.3389/fendo.2022.836731/fullDLK1small for gestational age (SGA)fetal growth restrictionplacental vascular dysfunctionbiomarker
spellingShingle Aurelie Pham
Delphine Mitanchez
Delphine Mitanchez
Anne Forhan
Laurence Perin
Yves Le Bouc
Frederic Brioude
Marie-Laure Sobrier
Barbara Heude
Irene Netchine
Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at Birth
Frontiers in Endocrinology
DLK1
small for gestational age (SGA)
fetal growth restriction
placental vascular dysfunction
biomarker
title Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at Birth
title_full Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at Birth
title_fullStr Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at Birth
title_full_unstemmed Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at Birth
title_short Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at Birth
title_sort low maternal dlk1 levels at 26 weeks is associated with small for gestational age at birth
topic DLK1
small for gestational age (SGA)
fetal growth restriction
placental vascular dysfunction
biomarker
url https://www.frontiersin.org/articles/10.3389/fendo.2022.836731/full
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