Reduced DHA transfer in diabetic pregnancies: mechanistic basis and long-term neurodevelopmental implications

Abstract

Infants born to diabetic mothers have a higher frequency of impaired neurodevelopment. The omega-3 or n-3 fatty acid docosahexaenoic acid (DHA) is an important structural component of neural tissue and is critical for fetal brain development. Maternal DHA supplementation during pregnancy is linked to better infant neurodevelopment; however, maternal-fetal transfer of DHA is reduced in women with diabetes. Evidence of mechanisms explaining altered maternal-fetal DHA transfer in this population is limited. This review explores existing evidence underpinning reduced maternal-fetal DHA transfer in maternal fuel metabolism in this population. Further research is necessary to evaluate the role of peroxisome proliferator-activated receptors in modulating placental fatty acid binding and maternal-fetal DHA transfer. Considerations for clinical practice include a diet high in DHA and/or provision of supplemental DHA to obstetric diabetic patients within minimum guidelines.

Keywords: PPAR; altered omega-3 transfer; diabetes; infant developmental outcomes; omega-3 fatty acids; pregestational type 2 diabetes..

Figure 1

Overview of the literature search strategy

Figure 2

Hypothesized model of the interrelationships impacting the offspring of diabetic mothers. The role of epigenetics in observed lipid pathway impairments is currently unknown with regard to DHA transfer, although the expression of key mediators involved in maternal–fetal lipid transfer has been reported. In diabetic pregnancies, alterations in the metabolic processing of free and/or esterified fatty acids are likely to be involved in the reduced availability of DHA to the fetus. Abbreviations: DHA, docosahexaenoic acid; EL, endothelial lipase; FA, fatty acid; GD, gestational diabetes; LPL, lipoprotein lipase; PPAR, peroxisome proliferator-activated receptor; TG, triglyceride.