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

Aurelie Pham; Delphine Mitanchez; Anne Forhan; Laurence Perin; Yves Le Bouc; Frederic Brioude; Marie-Laure Sobrier; Barbara Heude; Irene Netchine

doi:10.3389/fendo.2022.836731

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

Front Endocrinol (Lausanne). 2022 Feb 28:13:836731. doi: 10.3389/fendo.2022.836731. eCollection 2022.

Authors

Aurelie Pham¹, Delphine Mitanchez^{2

3}, Anne Forhan⁴, Laurence Perin⁵, Yves Le Bouc², Frederic Brioude⁶, Marie-Laure Sobrier², Barbara Heude⁴, Irene Netchine⁶

Affiliations

¹ Sorbonne Université, INSERM, Centre de Recherche Saint Antoine, APHP, Hôpital Armand Trousseau, Service de Néonatologie, Paris, France.
² Sorbonne Université, INSERM, Centre de Recherche Saint Antoine, Paris, France.
³ Centre Hospitalier Régional Universitaire (CHRU) de Tours, Hôpital Bretonneau, Service de Néonatologie, Tours, France.
⁴ Université de Paris Cité, INSERM, INRAE, Centre of Research in Epidemiology and StatisticS (CRESS), Paris, France.
⁵ Sorbonne Université, APHP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Endocrinologie Moléculaire et Pathologies d'Empreinte, Paris, France.
⁶ Sorbonne Université, INSERM, Centre de Recherche Saint Antoine, APHP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Endocrinologie Moléculaire et Pathologies d'Empreinte, Paris, France.

Abstract

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 < 10^th percentile) and 370 mother-child control (birth weight between the 25^th and 75^th 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.

Keywords: DLK1; biomarker; fetal growth restriction; placental vascular dysfunction; small for gestational age (SGA).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Birth Weight
Calcium-Binding Proteins
Female
Fetal Growth Retardation
Gestational Age
Humans
Infant, Newborn
Membrane Proteins
Placenta*
Pregnancy
Pregnancy Trimester, Third
Prospective Studies
Ultrasonography, Prenatal*

Substances

Calcium-Binding Proteins
DLK1 protein, human
Membrane Proteins