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Review
. 2025 Mar 27:S0143-4004(25)00090-6.
doi: 10.1016/j.placenta.2025.03.019. Online ahead of print.

Gestational diabetes mellitus affects the cross-talk among placental, maternal and umbilical cord vitamin D metabolites but fetal transfer is not compromised

Layla G Ranquine  1 , Deborah Bauer  2 , Nathalia Zuniga  3 , Brenda A Nagagata  4 , Gabriela D A Pinto  5 , Carolina S Ferreira  6 , Vanessa A Goes  7 , Daniela B Mucci  8 , Lívia Belcastro  9 , Fatima Sardinha  10 , Claudio J Struchiner  11 , Alexandre G Torres  12 , Sarah R Meadows  13 , Kerry S Jones  14 , Tatiana El-Bacha  15
Affiliations
Review

Gestational diabetes mellitus affects the cross-talk among placental, maternal and umbilical cord vitamin D metabolites but fetal transfer is not compromised

Layla G Ranquine et al. Placenta. .

Abstract

Introduction: The pathophysiology of gestational diabetes mellitus (GDM) is not completely understood. Poor maternal vitamin D status associates with increased risk of GDM, and placental vitamin D metabolism seems to be compromised. Here we investigated how GDM affects the associations among placental, maternal and fetal metabolism of vitamin D.

Methods: Matched placental, maternal and umbilical cord plasma samples from a clinically well-controlled cohort of pregnant women grouped into normal weight without co-morbidities (n = 8), overweight/obesity (n = 7) as the sole complication and overweight/obesity aggravated by GDM (n = 6) were analysed for vitamin D metabolites using LC-MS/MS.

Results: Maternal and cord plasma 25(OH)D3 and 24,25(OH)2D3, and placental 25(OH)D3 and vitamin D3 were similar among the groups. Placental VDR and CYP27B1 mRNA were lower and placental-to-maternal 25(OH)D3 ratio was higher in GDM pregnancies. In multiple regression analysis, placental 25(OH)D3 was a positive predictor and GDM a negative predictor of maternal 25OHD3. Importantly, GDM and overweight/obesity induced distinct maternal and placental responses in respect to vitamin D metabolism.

Discussion: GDM modified the relationship between vitamin D metabolites in cord and maternal blood, an effect possibly mediated by the placenta. Also, GDM did not affect the fetal supply of vitamin D, consistent with normal birthweight and length. The differences in metabolism possibly reflect changes in placental VDR and CYP27B1 transcripts in response to syncytiotrophoblast stress, including mitochondrial and ER stress, reported in GDM. A major limitation of this study is the small sample size which impacts on the statistical power. Thus, results should be interpreted with caution.

Keywords: 24,25(OH)(2)D(3); 25(OH)D(3); Gestational diabetes mellitus; Obesity; Placenta; Vitamin D metabolism.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflict of interest. The funding sources had no involvement in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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