Placental MFSD2a transporter is related to decreased DHA in cord blood of women with treated gestational diabetes

Omega-3 fatty acids, particularly docosahexaenoic fatty acid (DHA), are widely recognized to impact fetal and infant neurodevelopment. The impact of DHA on brain development, and its inefficient synthesis from the essential alpha-linolenic acid (ALA), has led to recommended DHA intakes of 250–375 mg eicosapentaenoic acid + DHA/day for pregnant and lactating women by the Dietary Guidelines for Americans. Despite these recommendations, the intake of omega-3s in women of child-bearing age in the US remains very low. The low maternal status of DHA prior to pregnancy could impair fetal neurodevelopment. This review focuses on maternal omega-3 status in conditions of gestational diabetes mellitus (GDM) and preeclampsia, and the subsequent impact on placental transfer and cord blood concentration of omega-3s. Both GDM and preeclampsia are associated with altered maternal omega-3 status, altered placental omega-3 metabolism, reduced cord blood omega-3 levels and have an impact on neurodevelopment in the infant and on brain health later in life. These findings indicate lower DHA exposure of the developing baby may be driven by lower placental transfer in both conditions. Thus, determining approaches which facilitate increased delivery of DHA during pregnancy and early development might positively impact brain development in infants born to mothers with these diseases.

https://www.mdpi.com/2072-6643/11/5/1107/pdf

Maternal Omega-3 Nutrition, Placental Transfer and Fetal Brain Development in Gestational Diabetes and Preeclampsia.

Vegetarian diets have been associated with health benefits, but paradoxically are low in EPA and DHA which are important for development, particularly of the central nervous system, and for health. Humans have limited capacity for synthesis of EPA and DHA from α-linolenic acid, although this is greater in women than men. Oily fish and, to a lesser extent, dairy foods and meat are the primary sources of EPA and DHA in the diet. Exclusion of these foods from the diet by vegetarians is associated consistently with lower EPA and DHA status in vegetarian women compared with omnivores. The purpose of the present review was to assess the impact of low EPA and DHA status in vegetarian pregnancies on the development and health of children. EPA and DHA status was lower in breast milk and in infants of vegetarian mothers than those born to omnivore mothers, which suggests that in the absence of pre-formed dietary EPA and DHA, synthesis from α-linolenic acid is an important process in determining maternal EPA and DHA status in pregnancy. However, there have been no studies that have investigated the effect of low maternal DHA status in vegetarians on cognitive function in children. It is important to address this gap in knowledge in order to be confident that vegetarian and vegan diets during pregnancy are safe in the context of child development.

/pdf/long-chain-n-3-pufa-in-vegetarian-women-a-metabolic-4cp4czwnwl.pdf

Long-chain n-3 PUFA in vegetarian women: a metabolic perspective.

Gestational diabetes mellitus (GDM) results in reduced docosahexaenoic acid (DHA) transfer to the fetus, likely due to placental dysfunction. Sirtuin-1 (SIRT1) is a nutrient sensor and regulator of lipid metabolism. This study investigated whether the high glucose and insulin condition of GDM regulates DHA transfer and expression of fatty acid transporters and if this effect is related to SIRT1 expression and function. Syncytialized primary human trophoblasts were treated with and without glucose (25 mmol/L) and insulin (10−7 mol/L) for 72 h to mimic the insulin-resistance conditions of GDM pregnancies. In control conditions, DHA transfer across trophoblasts increased in a time- and dose-dependent manner. Exposure to GDM conditions significantly decreased DHA transfer, but increased triglyceride accumulation and fatty acid transporter expression (CD36, FABP3, and FABP4). GDM conditions significantly suppressed SIRT1 mRNA and protein expression. The SIRT1 inhibitor decreased DHA transfer across control trophoblasts, and recombinant SIRT1 and SIRT1 activators restored the decreased DHA transport induced by GDM conditions. The results demonstrate a novel role of SIRT1 in the regulation of DHA transfer across trophoblasts. The suppressed SIRT1 expression and the resultant decrease in placental DHA transfer caused by high glucose and insulin levels suggest new insights of molecular mechanisms linking GDM to fetal DHA deficiency.

https://www.mdpi.com/2072-6643/12/5/1271/pdf

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism.

Maternal health during gestational period is undoubtedly critical in shaping optimal fetal development and future health of the offspring. Gestational diabetes mellitus is a metabolic disorder occurring in pregnancy with an alarming increasing incidence worldwide during recent years. Over the years, there is a growing body of evidence that uncontrolled maternal hyperglycaemia during pregnancy can potentially have detrimental effect on the neurodevelopment of the offspring. Both human and animal data have linked maternal diabetes with motor and cognitive impairment, as well as autism spectrum disorders, attention deficit hyperactivity disorder, learning abilities and psychiatric disorders. This review presents the available data from current literature investigating the relationship between maternal diabetes and offspring neurodevelopmental impairment. Moreover, possible mechanisms accounting for the detrimental effects of maternal diabetes on fetal brain like fetal neuroinflammation, iron deficiency, epigenetic alterations, disordered lipid metabolism and structural brain abnormalities are also highlighted. On the basis of the evidence demonstrated in the literature, it is mandatory that hyperglycaemia during pregnancy will be optimally controlled and the impact of maternal diabetes on offspring neurodevelopment will be more thoroughly investigated. Graphical Abstract

/pdf/the-impact-of-maternal-diabetes-on-the-future-health-and-1hmvf763.pdf

The impact of maternal diabetes on the future health and neurodevelopment of the offspring: a review of the evidence

To evaluate the relation between docosahexaenoic acid (DHA) status and neurodevelopment in the offsprings of gestational diabetic mothers (ODMs). A prospective cohort study was performed. The offspring of 63 pregnant women (23 controls, 21 diet-controlled gestational diabetes mellitus (GDM) and 19 insulin-treated GDM) were recruited. Maternal and venous cord plasma DHA percentages were analyzed. Skin temperature and activity in children were recorded for 72 h at 3 and 6 months of life. Neurodevelopment was assessed using the Bayley Scale of Infant Development II (BSID II) at 6 and 12 months of age. Cord plasma DHA percentage was significantly lower in the ODMs compared with that in the controls (Control 6.43 [5.04–7.82]a; GDM+diet 5.65 [4.44–6.86]ab; GDM+insulin 5.53 [4.45–6.61]b). Both mental (Control 102.71 [97.61–107.81]a; GDM+diet 100.39 [91.43–109.35]a; GDM+insulin 93.94 [88.31–99.57]b) and psychomotor (Control 91.52 [81.82–101.22]a; GDM+diet 81.67 [73.95–89.39]b; GDM+insulin 81.89 [71.96–91.85]b) scores evaluated by the BSID II were significantly lower at 6 months in ODMs, even after adjusting for confounding factors such as breastfeeding, maternal educational level and gender. Cord plasma DHA percentage correlated with the psychomotor score from BSID II (r=0.27; P=0.049) and with the intra-daily variability in activity (r=−0.24; P=0.043) at 6 months. Maternal DHA was correlated with several sleep rhythm maturation parameters at 6 months. Lower DHA levels in cord plasma of ODMs could affect their neurodevelopment. Maternal DHA status was also associated with higher values in the sleep rhythm maturation parameters of children.

Is low docosahexaenoic acid associated with disturbed rhythms and neurodevelopment in offsprings of diabetic mothers

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Is low docosahexaenoic acid associated with disturbed rhythms and neurodevelopment in offsprings of diabetic mothers