Materno-fetal transfer of docosahexaenoic acid is impaired by gestational diabetes mellitus

Abstract

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.

The influence of placental metabolism on fatty acid transfer to the fetus

“…The initial syncytiotrophoblast concentration was C S (0) = (c mv (0) + c fv (0))/2, as an estimated value according to the overall gradient expected at time 0. In addition, it was assumed that the endogenous pool was large, with C P (0) >> K m (33) and C P (0) >> C S (0). Thus, equations 10 and 11 can be simplified as:…”

Placental Fatty Acid Transfer: A Key Factor in Fetal Growth

“…However, an abnormal placental function, as occurs in GDM or intrauterine growth retardation, could disturb the materno-fetal LC-PUFA transport, with unknown consequences for the neurodevelopment of the offspring. Because placental lipid pools serve as a relay towards transport to the fetus, we studied in humans the in vivo placental transfer of FA using labeled FA with stable isotopes [26] . Eleven controls and 9 pregnant women with GDM received orally 13 C-palmitic, 13 C-oleic, and 13 Clinoleic acids and 13 C-docosahexaenoic acid ( 13 C-DHA) 12 h before an elective caesarean section.…”

“…That the maternal hyperlipidemia in GDM is mainly a hypertriglyceridemia has been indicated by the higher concentration of labeled non-LC-PUFA in the maternal plasma triglycerides of GDM patients compared to controls [26] . In type 2 diabetes, it has been reported that insulin resistance causes high postprandial levels of triglyceride-rich lipoproteins and a prolonged presence in the circulation [27] .…”

Maternal and fetal benefits of DHA supplementation during pregnancy

“…Another RCT using a supplementation of 600 mg reported increased maternal but not fetal DHA levels in pregnant patients with GDM [33]. This finding could be explained by an impaired DHA transfer across the placenta due to GDM as reported by Pagan et al using stable isotope tracers for dynamic studies in vivo [34]. A prospective study on maternal fatty acids concentrations during the third trimester also showed that they were lower in patients with GDM.…”