Background: To what extent does the circulating 25-hydroxyvitamin D (25[OH]D) concentration help to meet the physiological needs of humans is an ongoing subject of debate. Remaining unexposed to the sun to reduce melanoma cancer risk, current lifestyle with less out door activities, and increasing obesity rates, which in turn increases the storage of vitamin D in the adipose tissue, are presumably factors that contribute to the substantial upsurge in the prevalence of vitamin D deficiency in humans. Since evidence is lacking regarding the appropriate cut-off points to define vitamin D status during pregnancy, references used to establish the intake recommendations and vitamin D content of prenatal vitamin supplements are quite conservative. Summary: The foetus depends fully on maternal 25(OH)D supply. 25(OH)D readily crosses the placenta and it is activated into 1,25(OH)₂D by foetal kidneys. Moreover, 1,25(OH)₂D can also be synthesized within the placenta to regulate placental metabolism. The importance of vitamin D during pregnancy for maintaining maternal calcium homeostasis and therefore for foetal bone development is well recognized; major discussions are in progress regarding the potential maternal detrimental effects on pregnancy outcomes, foetal development, and the long-term health of children. Interventional studies have also evaluated the effect of vitamin D for reduction on preterm birth and asthma programming. Key Messages: Clinically, by understanding the effects of vitamin D on perinatal outcomes, we could individualize antenatal counselling regarding vitamin D supplementation to ensure vitamin D repletion without increasing the risk of foetal hypercalcemia.

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Better knowledge on the disturbed mechanisms implicated in materno-fetal long-chain polyunsaturated fatty acid (LC-PUFA) transfer in pregnancies with gestational diabetes mellitus (GDM) may have potentially high implications for later on in effective LC-PUFA supplementation. We studied in vivo placental transfer of fatty acids (FA) using stable isotope tracers administrated to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally [(13)C]palmitic, [(13)C]oleic and [(13)C]linoleic acids, and [(13)C]docosahexaenoic acid ((13)C-DHA) 12 h before elective caesarean section. Maternal blood samples were collected at -12, -3, -2, and -1 h, delivery, and +1 h. Placental tissue and venous cord blood were also collected. FA were quantified by gas chromatography (GC) and (13)C enrichments by GC-isotope ratio mass spectrometry. [(13)C]FA concentration was higher in total lipids of maternal plasma in GDM vs. controls, except for [(13)C]DHA. Moreover, [(13)C]DHA showed lower placenta/maternal plasma ratio in GDM vs. controls and significantly lower cord/maternal plasma ratio. For the other studied FA, ratios were not different between GDM and controls. Disturbed [(13)C]DHA placental uptake occurs in both GDM treated with diet or insulin, whereas the last ones also have lower [(13)C]DHA in venous cord. The tracer study pointed toward impaired placental DHA uptake as critical step, whereas the transfer of the rest of [(13)C]FA was less affected. GDM under insulin treatment could also have higher fetal fat storage, contributing to reduce [(13)C]DHA in venous cord. DHA transfer to the fetus was reduced in GDM pregnancies compared with controls, which might affect the programming of neurodevelopment in their neonates.

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Key points Placental structure and function can be modified as a result of maternal obesity affecting materno‐fetal fatty acids (FA) transport. We report for the first time, in humans and in vivo, the kinetics of placental FA transfer in normo‐weight and in normolipemic obese pregnant women using stable isotopes. The administration of different tracer FA with similar behaviour to the mother at different time points allows the collection of kinetic information on materno‐fetal transfer of FA despite only one sample of placenta and cord can be collected per subject. Computational modelling showed a good fit to the data when considering all maternal plasma lipid classes but not when based only on non‐esterified FA. The novel approach using multiple tracer FA administration combined with computational modelling shows a consistent time course of placental tracer FA and predicted total FA accumulation. Abstract We analyse for the first time the in vivo materno‐fetal kinetic transfer of fatty acids (FA) labelled with stable isotopes in control and obese (OB) pregnant women. Labelled FA with a similar metabolism (stearic acid: 13C‐SA; palmitic acid: 13C‐PA; oleic acid: 13C‐OA) were orally administered at −4 h, −8 h and −12 h, respectively prior to elective caesarean section to 10 pregnant women with a body mass index >30 (OB) and 10 with a body mass index in the range 20–25 (NW). Placenta, venous and arterial cord blood were collected obtaining a wide range of FA enrichments. A combined experimental and computational modelling analysis was applied. FA fractional synthesis rate (FSR) in placenta was 11–12% h–1. No differences were observed between NW and normo‐lipidemic OB. It was not possible to estimate FA FSR in cord blood with this oral bolus dose approach. Computational modelling demonstrated a good fit to the data when all maternal plasma lipid classes were included but not with modelling based only on the non‐esterified FA fraction. The estimated materno‐fetal 13C‐FA transfer was ∼1%. In conclusion, our approach using multiple 13C‐FA tracers allowed us to estimated FSR in placental/maternal plasma but not in fetal/maternal compartments. Computational modelling showed a consistent time course of placental 13C‐FA transfer and predicted total fetal FA accumulation during the experiment. We conclude that, in addition to non‐esterified FA fraction in the maternal circulation, maternal plasma very low‐density lipoprotein and other lipoproteins are important contributors to placental FA transfer to the fetus.

There is little information available on the effect of Gestational diabetes mellitus (GDM) treatment (diet or insulin) on placental lipid carriers, which may influence fetal fat accretion. Insulin may activate placental insulin receptors protein kinase (AKT) and extracellular signal regulated kinase ERK mediators, which might affect lipid metabolism. Placenta was collected from 25 control women, 23 GDM-Diet and 20 GDM-Insulin. Western blotting of insulin signaling mediators and lipid carriers was performed. The human choricarcinoma-derived cell line BeWo was preincubated with insulin inhibitors protein kinase (AKT) and extracellular signal regulated kinase (ERK) and ERK inhibitors to evaluate insulin regulation of lipid carriers. Maternal serum insulin at recruitment correlated to ultrasound fetal abdominal circumference in offspring of GDM and placental endothelial lipase (EL). Lipoprotein lipase in placenta was significantly reduced in both GDM, while most of the other lipid carriers tended to higher values, although not significantly. There was a significant increase in both phosphorylated-Akt and ERK in placentas from GDM-Insulin patients; both were associated to placental fatty acid translocase (FAT), fatty acid binding protein (A-FABP), and EL. BeWo cells treated with insulin pathway inhibitors significantly reduced A-FABP, fatty acid transport protein (FATP-1), and EL levels, confirming the role of insulin on these carriers. We conclude that insulin promotes the phosphorylation of placental insulin mediators contributing to higher levels of some specific fatty acid carriers in the placenta and fetal adiposity in GDM.

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