Abstract
BackgroundLike many species, pregnant swine mobilize and repartition body nutrient stores during extreme malnutrition to support fetal development. ObjectiveThe objective of this study was to model chronic human maternal malnutrition and measure effects of methylating-vitamins (MVs, containing choline, folate, B-6, B-12, and riboflavin) and docosahexaenoic acid (DHA) supplementation on fetal growth and development. MethodsPregnant gilts (n = 24) were either fully nourished (2.0 kg/d) with a corn-plus-isolated-soy-protein basal diet (control) supplemented with MVs and DHA or nourishment was restricted throughout gestation. Basal diet fed to malnourished gilts was reduced progressively from 50% to 70% restriction (1.0 to 0.6 kg/d) and was supplemented following a 2 (±MVs) x 2 (±DHA) factorial design. Full-term c-sections were performed to assess impacts on low and normal birth weight (LBW/NBW) fetuses (n = 238). ResultsBody weight gain of malnourished gilts was 10% of full-fed control dams (P < 0.05), but offspring birth weight, length, girth, and percentage of LBW fetuses were not different between treatments. The number of pigs per litter was reduced by 30% in malnourished control dams. Fetal brain weights were reduced by 7% compared to positive controls (P < 0.05). Micronutrient supplementation to malnourished dams increased fetal brain weights back to full-fed control levels. Dams with DHA produced offspring with higher DHA concentrations in brain and liver (P < 0.05). Plasma choline concentration was 4-fold higher in fetuses from unsupplemented malnourished dams (P < 0.0001). Global DNA methylation status of fetuses from restricted dams was higher than in control fetuses, including brain, liver, heart, muscle, and placenta tissues (P < 0.05). Addition of DHA increased methylation in LBW fetal brains (P < 0.05). ConclusionsDespite the mobilization of maternal stores, malnourished litters displayed reduced brain development that was fully mitigated by micronutrient supplementation. Severe maternal malnutrition increased global DNA methylation in several fetal tissues that was unaltered by choline and B-vitamin supplementation.
Highlights
Micronutrient monitoring and supplementation during pregnancy in first-world countries is standard practice [1, 2], but developing nations struggle with dietary variability for provision of adequate micronutrients [3]
Severe maternal malnutrition increased global DNA methylation in several fetal tissues that was unaltered by choline and B-vitamin supplementation
The diet was further supplemented with a mixture of methylating vitamins (MVs) containing folic acid (1.3 mg/kg feed), pyridoxine (1.0 mg/kg feed), B-12 (0.015 mg/kg feed), riboflavin (3.75 mg/kg feed), choline (1250 mg/kg feed, vitamins donated by DSM, Heerlen, Netherlands), and docosahexaenoic acid (DHA) (2420 mg/kg feed; life’s DHA S35-O200, rosemary free algal vegetable oil, minimum 35% DHA; DSM, Columbia, MD; Table 2)
Summary
Micronutrient monitoring and supplementation during pregnancy in first-world countries is standard practice [1, 2], but developing nations struggle with dietary variability for provision of adequate micronutrients [3]. Chronic undernutrition in the mother influences the availability of nutrients for fetal growth and development. Several review articles offer extensive overviews linking nutritional status in utero to epigenetic changes, metabolic programming, and chronic adult disease [6, 7, 10]. Despite this emerging link between optimal nutritional intake and epigenetic modification, the effect of the simultaneous supplementation of vitamins supporting one-carbon metabolism (choline, folate, B-6, B-12, and riboflavin) during nutrient deprivation on physiology and metabolism of the placenta and the fetus is not well characterized. Pregnant swine mobilize and repartition body nutrient stores during extreme malnutrition to support fetal development
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