Maternal DHA Intake Research Articles

Maternal DHA intake in mice increased DHA metabolites in the pup brain and ameliorated MeHg-induced behavioral disorder

Although pregnant women’s fish consumption is beneficial for the brain development of the fetus due to the DHA in fish, seafood also contains methylmercury (MeHg), which adversely affects fetal brain development. Epidemiological studies suggest that high DHA levels in pregnant women’s sera may protect the fetal brain from MeHg-induced neurotoxicity, but the underlying mechanism is unknown. Our earlier study revealed that DHA and its metabolite 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) produced by cytochrome P450s (P450s) and soluble epoxide hydrolase (sEH) can suppress MeHg-induced cytotoxicity in mouse primary neuronal cells. In the present study, DHA supplementation to pregnant mice suppressed MeHg-induced impairments of pups’ body weight, grip strength, motor function, and short-term memory. DHA supplementation also suppressed MeHg-induced oxidative stress and the decrease in the number of subplate neurons in the cerebral cortex of the pups. DHA supplementation to dams significantly increased the DHA metabolites 19,20-epoxydocosapentaenoic acid (19,20-EDP) and 19,20-DHDP as well as DHA itself in the fetal and infant brains, although the expression levels of P450s and sEH were low in the fetal brain and liver. DHA metabolites were detected in the mouse breast milk and in human umbilical cord blood, indicating the active transfer of DHA metabolites from dams to pups. These results demonstrate that DHA supplementation increased DHA and its metabolites in the mouse pup brain and alleviated the effects of MeHg on fetal brain development. Pregnant women’s intake of fish containing high levels of DHA (or DHA supplementation) may help prevent MeHg-induced neurotoxicity in the fetus.

The Effects of Maternal Intake of EPA and DHA Enriched Diet During Pregnancy and Lactation on Offspring's Muscle Development and Energy Homeostasis.

EPA and DHA are n-3 long-chain polyunsaturated fatty acids with a diversity of health benefits on offspring. The objective of this study was to test the in vivo effect of maternal ingestion of EPA and DHA on fetal and offspring muscle development and energy balance. Two groups of female C57BL/6 mice were fed EPA and DHA enriched diet (FA) and diet devoid of EPA and DHA (CON) respectively throughout the entire period of gestation and lactation. Embryos at E13 and offspring at age of D1 and D21 were selected for sample collection and processing. No change in birth number and body weight were observed between groups at D1 and D21. Transient increase in the expression levels of myogenesis regulating genes was detected at D1 (p < 0.05) in FA group. Most of the expression of muscle protein synthesis regulating genes were comparable (p > 0.05) between FA and CON groups at D1 and D21. The significant increase in MHC4, and IGF-1 was not linked to increased muscle mass. A persistent increase in ISR expression (p < 0.05) but not in GLUT-4 (p > 0.05) was detected in offspring. Up-regulation of adipogenesis regulating genes was accompanied by increasing intramuscular fat accumulation in the offspring of FA group. Considerable increase in transcripts of genes regulating lipid catabolism and thermogenesis in liver (p < 0.05) was noticed in FA group at D21; whereas, only the levels of carnitine palmitoyl transferase 1A (Cpt1α) and Enoyl-CoA Hydratase And 3-Hydroxyacyl CoA Dehydrogenase (Ehhadh) increased at D1. Similarly, genes regulating lipolysis were highly expressed at D21 in FA group. EPA and DHA treatment promoted BAT development and activity by increasing the expression of BAT signature genes (p < 0.05). Also, maternal intake of EPA and DHA enriched diet enhanced browning of sWAT. Taken together, maternal ingestion of EPA/DHA may be suggested as a therapeutic option to improve body composition and counteract childhood obesity- related metabolic disorders and confer lifelong positive metabolic impact on offspring.

The Physiological and Metabolic Effects of Maternal Intake of EPA and DHA during Pregnancy and Lactation on Offspring's Muscle Development and Energy Homeostasis

EPA and DHA are long-chain fatty acids with health benefits on offspring underpinning the accumulative recommendations for their prenatal ingestion. Recent in vivo studies have emerged indicating a positive correlation of EPA and DHA with fetal BAT development, while other in vitro trials demonstrated their negative implication in promoting fetal myoblast reprogramming into adipoblasts. Therefore, the objective of this study was to test the effect of maternal EPA and DHA on fetal muscle development and energy balance. Two groups of Female C57BL/6 mice were assigned to different diets throughout the entire period of gestation and lactation; the first group was fed EPA and DHA enriched diet (FA); whereas, the other was fed a diet devoid of n-3 PUFA (CON). Embryos at day 13 of gestation and offspring at age of 1 and 21day were selected for sample collection and processing. No change in little number and body weight were observed between groups in newborns at day1, but a tendency to weigh loss in the FA group was detected after weaning. Transient increase in the expression levels of MYOD1, MYOG, MRF4, and MHC4 were observed at day 1 post-parturition (P<0.05). Except of IGF-1 P<0.05, the expression levels of genes regulating muscle protein synthesis and catabolism were comparable (P>0.05) between groups at day 1 and 21. Persistent increase in ISR expression (P<0.05) but not in GLUT-4 (P>0.05) were detected in day 1 and 21 age offspring. An increase in the expression of PPARγ and AP2 but not C/EBPα (P<0.05) at day 1 were observed. The three key regulators of basal adipogenesis were up-regulated in weaned mice (P<0.05). Up-regulation of PPARγ, AP2, and C/EBPα levels were accompanied by increasing intramuscular fat accumulation in day 1 and 21 samples. Considerable increase in the transcripts of genes regulating lipid catabolism and thermogenesis in liver including Cpt1α,Ehhadh, Mcad, Lcad, Acadvl, slc22a5, slc25a20, and Pparα (P<0.05) was noticed in (FA) group after 21 day of treatment; whereas, only the transcripts of Cpt1α andEhhadh increased in day1 neonates’ livers . Similarly, genes regulating lipolysis (ATGL and HSL, MGL and LPL) were up-regulated at day 21 of treatment only in (FO) group (P<0.05) while EPA and DHA maternal intake does not affect the expression of lipogenesis regulating genes (Fasn and Srebp1c) (P>0.05) in day 1 and 21 offspring. EPA and DHA treatment promoted BAT development and activity through increasing the expression of BAT signature genes including (UCP1, Cidea, Prdm16, Pgc1α, Dio2, Zic1, Fgf21, P2rx5, and PPARα(P<0.05). Also, maternal intake of EPA/ DHA enriched diet enhanced browning of sWAT by stimulating the expression of beige markers such as UCP1, Shox2, Tmem26, and PAT2 and thermogenesis regulating genes (PPARα, PGC1α, Cox7α1, and Cox8β) (P<0.05). Taken together, maternal ingestion of EPA and DHA may be suggested as a therapeutic option to encounter many pathophysiological disorders, mainly childhood obesity, and confer long-lasting metabolic benefits on offspring.

Maternal Docosahexaenoic Acid Status during Pregnancy and Its Impact on Infant Neurodevelopment.

Dietary components are essential for the structural and functional development of the brain. Among these, docosahexaenoic acid, 22:6n-3 (DHA), is critically necessary for the structure and development of the growing fetal brain in utero. DHA is the major n-3 long-chain polyunsaturated fatty acid in brain gray matter representing about 15% of all fatty acids in the human frontal cortex. DHA affects neurogenesis, neurotransmitter, synaptic plasticity and transmission, and signal transduction in the brain. Data from human and animal studies suggest that adequate levels of DHA in neural membranes are required for maturation of cortical astrocyte, neurovascular coupling, and glucose uptake and metabolism. Besides, some metabolites of DHA protect from oxidative tissue injury and stress in the brain. A low DHA level in the brain results in behavioral changes and is associated with learning difficulties and dementia. In humans, the third trimester-placental supply of maternal DHA to the growing fetus is critically important as the growing brain obligatory requires DHA during this window period. Besides, DHA is also involved in the early placentation process, essential for placental development. This underscores the importance of maternal intake of DHA for the structural and functional development of the brain. This review describes DHA’s multiple roles during gestation, lactation, and the consequences of its lower intake during pregnancy and postnatally on the 2019 brain development and function.

Fish intake reflects on DHA level in breast milk among lactating women in Latvia

BackgroundDocosahexaenoic acid (DHA) is an essential fatty acid required for proper growth and development. DHA levels in breast milk vary worldwide. Higher levels are observed among coastal populations and are associated with marine food consumption. Latvia is located in Northern Europe, on the eastern shore of the Baltic Sea. Nevertheless, fish consumption among women of reproductive age is low. The aim of this study was to determine DHA levels in breast milk among lactating women in Latvia.MethodsInvitation to participate in the study was posted on a social media member group for breastfeeding mothers. In total, 71 women were enrolled from November 2016 until December 2017. DHA levels (% of total fatty acids) in breast milk were measured by gas chromatography. Information about food consumed during the three consecutive days prior to the milk sampling was obtained and a food frequency questionnaire (FFQ) was completed. Information about maternal and infant characteristics, current breastfeeding pattern and milk expression method was also collected.ResultsThe mean age of participants was 31 ± 4 years and the mean BMI was 22.1 ± 3.2. 27 participants were primiparas. The average age and birth weight for infants (34 males, 33 females) was 6 ± 4 months and 3.46 ± 0.55 kg, respectively. The median DHA level in breast milk (n = 60) was 0.30 ± 0.18% of total fatty acids and it was not influenced by any of the maternal or infant’s characteristics nor current breastfeeding pattern or milk expression manner (p > 0.05). Fish intake was a positive predictor for DHA levels in breast milk (r = 0.318, p = 0.013). Average maternal DHA intake was 136 ± 26, 137 ± 33 and 178 ± 49 (SEM – standard error of the mean) mg, for the third, second and last day prior to sampling day, respectively.ConclusionsDHA levels in breast milk among lactating women in Latvia correspond to the suggested target DHA value in breast milk (0.30%). Fish consumption is a significant positive predictor for DHA levels in breast milk, however, daily DHA intake among the participants was lower than recommended (200 mg).

Fetal DHA inadequacy and the impact on child neurodevelopment: a follow-up of a randomised trial of maternal DHA supplementation in pregnancy.

DHA is an important component of neural lipids accumulating in neural tissue during development. Inadequate DHA in gestation may compromise infant development, but it is unknown whether there are lasting effects. We sought to determine whether the observed effects of fetal DHA inadequacy on infant development persist into early childhood. This follow-up study assessed children (5-6 years) whose mothers received 400 mg/d DHA or a placebo during pregnancy. Child neurodevelopment was assessed with several age-appropriate tests including the Kaufman Assessment Battery for Children. A risk-reduction model was used whereby the odds that a child from the maternal placebo group would fail to achieve a test score in the top quartile was calculated. The association of maternal DHA intake and status in gestation with child test scores, as well as with child DHA intake and status, was also determined. No differences were detected in children (n 98) from the maternal placebo and DHA groups achieving a high neurodevelopment test score (P>0·05). However, maternal DHA status was positively related to child performance on some tests including language and short-term memory. Furthermore, child DHA intake and status were related to the mother's intake and status in gestation. The neurodevelopment effects of fetal DHA inadequacy may have been lost or masked by other variables in the children. Although we provide evidence that maternal DHA status is related to child cognitive performance, the association of maternal and child DHA intake and status limits the interpretation of whether DHA before or after birth is important.

Role of DHA, ARA, & phospholipids in brain development: An Indian perspective

Long-chain polyunsaturated fatty acids such as docosahexaenoic acid and arachidonic acid play vital roles in brain development during infancy. In India, LCPUFA intake during pregnancy is substantially low, mostly attributed to poor dietary intake. Infants are likely to have similar trend considering low intake of DHA in lactating mothers as well as low/absent DHA in bovine milk and standard infant formulae. Studies on maternal intake of DHA during pregnancy and lactation are in favor of routing supplementation. Though studies on benefits of DHA and ARA supplemented infant formulas have shown heterogeneous results, the latest long term studies showing better cognitive skills.

Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: An early neurodevelopmental measure

BackgroundDocosahexaenoic acid (DHA; 22:6n−3) is highly important during pregnancy for optimal development and functioning of fetal neural tissue. Infant ability to organize sleep and wake states following parturition is highly associated with later developmental outcomes. The impact of maternal DHA intake on sleep organization has not been previously investigated. AimsTo examine the effect of a DHA-containing functional food consumed during pregnancy on early neurobehavioral development as assessed by infant sleep patterning in the first 48 postnatal hours. Study designA longitudinal, randomized, double-blinded, placebo-controlled design was used. SubjectsWomen (18–35y) with no pregnancy complications consumed a cereal-based functional food (92kcal) containing 300mg DHA an average of 5d/week or placebo bars (n=27 DHA, n=21 Placebo). The intervention began at 24weeks gestation and continued until delivery (38–40weeks). Outcome measuresInfant sleep/wake states were measured on postnatal days 1 (D1) and 2 (D2) using a pressure sensitive mattress recording respiration and body movements. ResultsUsing ANCOVA and controlling for ethnic variation, there were significant group differences in arousals in quiet sleep on D1 (P=0.006) and D2 (P=0.011) with fewer arousals in the DHA intervention group compared to the placebo group. Similarly, arousals in active sleep on D1 were significantly lower in the DHA-intervention group (P=0.012) compared to the placebo group. ConclusionsWe conclude that increased prenatal supply of dietary DHA has a beneficial impact on infant sleep organization.

Fish consumption during child bearing age: A quantitative risk–benefit analysis on neurodevelopment

The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content.

Is there a dietary requirement for DHA in pregnancy?

The metabolic demand for docosahexaenoic acid (22:6 n-3, DHA) is increased during pregnancy because of the extra needs of the fetus, expanded maternal cell mass and placenta. In Western countries maternal dietary DHA intake in pregnancy is low and it is not clear whether adaptive metabolic mechanisms, such as increased DHA synthesis from precursor fatty acids, are capable of meeting the increased DHA need in pregnancy. Consequently randomized controlled trials are important to determine whether additional dietary DHA in pregnancy modifies maternal or infant health outcomes. The available randomized comparisons of DHA supplements vs placebo have assessed outcomes as diverse as maternal depression, infant visual acuity and development, and infant growth and allergy. The outcomes of these trials have not been conclusive because they have often been limited by small sample size. On the other hand, large-scale trials assessing marine oil supplementation with large doses indicate that DHA supplementation in pregnancy is safe.

Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age

Long-chain polyunsaturated fatty acids (LCPUFA) rapidly accumulate in the central nervous system (CNS) during the perinatal CNS growth spurt. This particularly concerns arachidonic acid (AA: 20:4n-6) and docosahexaenoic acid (DHA: 22:6n-3), which are thought to play important roles in CNS development and function. The aim of this study was to investigate the relation between motor function at 7 years of age and the levels of AA and DHA in umbilical venous plasma phospholipids, representing the prenatal availability of these fatty acids, and in plasma phospholipids sampled at age 7 years. Motor function was assessed both quantitatively (the ability to perform a movement) and qualitatively (how the movement is performed) with the Maastricht Motor Test (MMT) in 306 children, born at term, at 7 years of age as part of a follow-up study. Backward stepwise multiple regression analyses revealed a significant, positive relation between umbilical plasma DHA concentrations (but not plasma DHA levels at 7 years) and the MMT total and quality score, corrected for the covariables gender, cognitive performance, gestational age and age at measurement (partial beta=0.13, P=0.01 and 0.14, P=0.01, respectively). The contributions of DHA and AA (both at birth and at 7 years of age) to quantitative movement scores were not significant. Our results suggest that prenatal DHA availability, which can be influenced by maternal dietary DHA intake during pregnancy, can have an effect on quality of movement in later life.

Plasma fatty acid profiles in 37 pairs of maternal and umbilical cord blood samples

In order to study the fatty acid transfer from the mother to fetus, their fatty acid profiles were compared by 37 pairs of maternal and umbilical cord plasma specimens obtained from healthy Japanese women at delivery. The fetal/maternal fatty acid concentration ratios differed among individual fatty acids. The ratios were low for linoleic acid (LN, 0.12±0.04) and linolenic acid (LnN, 0.07±0.05) but high for arachidonic acid (AA, 0.66±0.17) and docosahexaenoic acid (DHA, 0.44±0.13). Significant correlations were observed between the maternal and fetal EPA (r=0.74) and DHA (r=0.40) concentrations. These results suggest that DHA and AA are preferentially transferred to the fetus. Fetal fatty acid profile reflects the maternal intake of EPA and DHA.