Maternal Docosahexaenoic Acid Research Articles

Maternal supplementation with docosahexaenoic acid does not cause constriction of fetal ductus arteriosus: randomized controlled trial.

Docosahexaenoic acid (DHA) is recommended routinely in pregnancy to promote fetal development. DHA has anti-inflammatory activity, but its effects on the fetal heart and circulation are unknown. This study aimed to investigate whether maternal DHA supplementation in the third trimester affects maternal prostaglandin levels and fetal ductus arteriosus flow dynamics. This was a double-blind randomized controlled trial with parallel groups conducted between 2018 and 2021. Pregnant women aged over 18 years with a normal fetus at 27-28 weeks' gestation showing no cardiac/extracardiac anomalies or ductal constriction were eligible for the trial. Women consuming substances with a known inhibitory effect on prostaglandin metabolism, such as non-steroidal anti-inflammatory drugs and polyphenol-rich foods, were excluded. The intervention group received oral supplementation of omega-3 with 450 mg/day of DHA for 8 weeks and the placebo group received capsules of soy lecithin for 8 weeks. Anthropometric measurements, assessment of polyphenol and omega-3 consumption, fetal morphological ultrasound examination, fetal Doppler echocardiographic examination and blood sample collection were performed at the start of the study and the latter two were repeated at follow-up. Prostaglandin E2 (PGE2) level and echocardiographic parameters were compared between the intervention and placebo groups and between baseline and follow-up. A total of 24 participants were included in each group. After 8 weeks, there were no significant differences between the intervention and placebo groups in maternal serum PGE2 level or Doppler echocardiographic parameters of ductal flow. No case of ductus arteriosus constriction was observed. The expected intragroup changes in cardiac morphology, as a result of advancing gestation, were present. Maternal DHA supplementation in the third trimester at a clinically recommended dose did not result in inhibition of PGE2 or constriction of the ductus arteriosus. These findings should be confirmed in postmarket surveillance studies with larger patient numbers in order to test the full safety profile of DHA and provide robust clinical reassurance. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Astaxanthin and DHA Supplementation Modulates the Maternal Undernutrition-induced Impairment of Cognitive Behavior and Synaptic Plasticity in Adult Life of Offspring's -Exploring the Molecular Mechanism.

Maternal nutrition was recognized as a significant part of brain growth and maturation in most mammalian species. Timely intervention with suitable nutraceuticals would provide long-term health benefits. We aim to unravel the molecular mechanisms of perinatal undernutrition-induced impairments in cognition and synaptic plasticity, employing animal model based on dietary nutraceutical supplementation. We treated undernourished dams at their gestational, lactational, and at both the time point with Astaxanthin (AsX) and Docosahexaenoic acid (DHA), and their pups were used as experimental animals. We evaluated the cognitive function by subjecting the pups to behavioral tests in their adult life. In addition, we assessed the expression of genes in the hippocampus related to cognitive function and synaptic plasticity. Our results showed downregulation of Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), cAMP response-element-binding protein (CREB), and uncoupling protein-2 (UCP2) gene expression in pups born to undernourished dams in their adult life, which AsX and DHA modulated. Maternal AsX and DHA supplementation ameliorated the undernutrition-induced learning impairment in novel object recognition (NOR) tests and partially baited radial arm maze (RAM) tasks in offspring's. The expressions of Synapsin-1 and PSD-95 decreased in perinatally undernourished groups compared to control and AsX-DHA treated groups at CA1, CA2, CA3, and DG. AsX and DHA supplementation upregulated BDNF, NT-3, CREB, and UCP2 gene expressions in perinatally undernourished rats, which are involved in intracellular signaling cascades like Ras, PI3K, and PLC. The results of our study give new insights into neuronal differentiation, survival, and plasticity, indicating that the perinatal period is the critical time for reversing maternal undernutrition-induced cognitive impairment in offspring's.

Differential DHA and EPA Levels in Women with Preterm and Term Births: A Tertiary Hospital Study in Indonesia.

BACKGROUND Preterm birth is one of the main causes of neonatal death worldwide. One strategy focused on preventing preterm birth is the administration of long chain polyunsaturated fatty acids (LCPUFAs) during pregnancy. Omega-3 LCPUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential in metabolic and physiological processes during embryonic and fetal development. This study aimed to compare DHA and EPA levels in 44 women with preterm births and 44 women with term births at a tertiary hospital in West Java Province, Indonesia, between November 2022 and March 2023. MATERIAL AND METHODS A total of 88 patients in this study consisted of 44 patients with term births (≥37 gestational weeks) and 44 patients with preterm births (<37 gestational weeks) at a tertiary hospital in West Java Province, Indonesia. This observational, cross-sectional study was conducted from November 2022 to March 2023. Using the enzyme-linked immunosorbent assay test, maternal DHA and EPA levels were investigated. IBM SPSS 24.0 was used to statistically measure outcomes. RESULTS Average maternal DHA and EPA levels in patients with preterm births were significantly lower than those in term births. Preterm labor risk was further increased by DHA levels of ≤5.70 µg/mL (OR=441.00, P=0.000) and EPA levels ≤3971.54 µg/mL (OR=441.00, P=0.000). CONCLUSIONS Since the average maternal DHA and EPA levels were significantly lower in patients with preterm births, adequate intake of omega-3 LCPUFA in early pregnancy and consistency with existing nutritional guidelines was associated with a lower risk of preterm delivery for pregnant women.

Maternal docosahexaenoic acid supplementation during lactation improves exercise performance, enhances intestinal glucose absorption and modulates gut microbiota in weaning offspring mice.

Intestinal dysfunction induced by weaning stress is common during breastfeeding period. Docosahexaenoic acid (DHA) is well known for promoting visual and brain development, but its effects on early intestinal development remain unknown. This study investigated the impact of maternal DHA supplementation during lactation on intestinal glucose absorption and gut microbiota in weaning offspring mice. Dams were supplemented with vehicle (control), 150 mg/(kg body weight · day) DHA (L-DHA), or 450 mg/(kg body weight · day) DHA (H-DHA) throughout lactation by oral administration. After weaning, pups were randomly divided into three groups for athletic analysis, microbial and proteomic analysis, biochemical analysis, 4-deoxy-4-fluoro-D-glucose (4-FDG) absorption test, and gene expression quantitation of glucose transport-associated proteins and mTOR signaling components. The H-DHA group exhibited enhanced grip strength and prolonged swimming duration compared to the control group. Additionally, there were significant increases in jejunal and ileal villus height, and expanded surface area of jejunal villi in the H-DHA group. Microbial analyses revealed that maternal DHA intake increased the abundance of beneficial gut bacteria and promoted metabolic pathways linked to carbohydrate and energy metabolism. Proteomic studies indicated an increased abundance of nutrient transport proteins and enrichment of pathways involved in absorption and digestion in the H-DHA group. This group also showed higher concentrations of glucose in the jejunum and ileum, as well as elevated glycogen levels in the liver and muscles, in contrast to lower glucose levels in the intestinal contents and feces compared to the control group. The 4-FDG absorption test showed more efficient absorption after oral 4-FDG gavage in the H-DHA group. Moreover, the expressions of glucose transport-associated proteins, GLUT2 and SGLT1, and the activation of mTOR pathway were enhanced in the H-DHA group compared to the control group. The L-DHA group also showed similar but less pronounced improvements in these aspects relative to the H-DHA group. Our findings suggested that maternal DHA supplementation during lactation improves the exercise performance, enhances the intestinal glucose absorption by increasing the expressions of glucose transporters, and beneficially alters the structure of gut microbiome in weaning offspring mice.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice

BackgroundPolyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal–fetal fatty acid metabolism. ObjectiveThis study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. MethodsInsulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/β-catenin/MFSD2a) of the placenta and fetal brain using western blotting. ResultsGDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n–3 PUFA and n–6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n–3 PUFA in the fetal brain. GDM downregulated the Wnt3/β-catenin/MFSD2a signaling pathway, which transfers n–3 PUFA in the placenta and fetal brain. The HF diet increased n–6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n–6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental β-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). ConclusionsMaternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/β-catenin/MFSD2a pathway of the placental–fetal barrier and by affecting maternal fatty acid metabolism.

Analysis of factors related to postpartum depression in pregnancy-induced hypertension syndrome patients and construction and evaluation of nomograms.

It is positive to integrate and evaluate the risk factors for postpartum depression in patients with pregnancy-induced hypertension syndrome and to detect high-risk patients as early as possible, which has application value for the clinical development of personalized prevention programs and prognosis of patients. To analyze factors related to postpartum depression in patients with pregnancy-induced hypertension and construct and evaluate a nomogram model. The clinical data of 276 patients with pregnancy-induced hypertension admitted to Huzhou Maternity and Child Health Care Hospital between January 2017 and April 2022 were retrospectively analyzed. We evaluated the depression incidence at 6 wk postpartum. The depression group included patients with postpartum depression, and the remainder were in the non-depression group. Multivariate logistic regression analysis and the LASSO regression model were applied to analyze the factors related to postpartum depression in patients with pregnancy-induced hypertension. After that, a risk prediction model nomogram was constructed and evaluated. Multivariate logistic regression analysis showed that vitamin A deficiency (VAD) during pregnancy and puerperium, family history of hypertension, maternal intestinal flora imbalance, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were independent risk factors for postpartum depression in patients with pregnancy-induced hypertension (P < 0.05). We constructed the nomogram model based on these five risk factors. The area under the curve, specificity, and sensitivity of the model in predicting postpartum depression in patients with pregnancy-induced hypertension was 0.867 (95% confidence interval: 0.828-0.935), 0.676, and 0.889, respectively. The average absolute error was 0.037 (Hosmer-Lemeshow test χ2 = 10.739, P = 0.217). VAD during pregnancy and puerperium, family history of hypertension, maternal intestinal flora imbalance, EPA, and DHA affect postpartum depression in patients with pregnancy-induced hypertension.

Growth and adiposity in newborns study (GAINS): The influence of prenatal DHA supplementation protocol

BackgroundObesity and central fat mass (FM) accrual drive disease development and are related to greater morbidity and mortality. Excessive gestational weight gain (GWG) increases fetal fat accretion resulting in greater offspring FM across the lifespan. Studies associate greater maternal docosahexaenoic acid (DHA) levels with lower offspring FM and lower visceral adipose tissue during childhood, however, most U.S. pregnant women do not consume an adequate amount of DHA. We will determine if prenatal DHA supplementation is protective for body composition changes during infancy and toddlerhood in offspring exposed to excessive GWG. Methods and designInfants born to women who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE; NCT 02626299) will be invited to participate. Women were randomized to either a high 1000 mg or low 200 mg daily prenatal DHA supplement starting in the first trimester of pregnancy. Offspring body composition and adipose tissue distribution will be measured at 2 weeks, 6 months, 12 months, and 24 months using dual energy x-ray absorptiometry. Maternal GWG will be categorized as excessive or not excessive based on clinical guidelines. DiscussionEffective strategies to prevent obesity development are lacking. Exposures during the prenatal period are important in the establishment of the offspring phenotype. However, it is largely unknown which exposures can be successfully targeted to have a meaningful impact. This study will determine if prenatal DHA supplementation modifies the relationship between maternal weight gain and offspring FM and FM distribution at 24 months of age. Ethics and disseminationThe University of Kansas Medical Center Institutional Review Board (IRB) approved the study protocol (STUDY00140895). The results of the trial will be disseminated at conferences and in peer reviewed publications.Trial registration: ClinicalTrials.gov ID: NCT03310983

Risk and Benefit of Decreasing Seafood Consumption in Japan-Docosahexaenoic Acid, Methylmercury and Infant IQ.

National statistics show that seafood consumption in Japan is decreasing since the mid-1990s. The risks and benefits of this decreasing seafood consumption was assessed in this study. Intake of docosahexaenoic acid (DHA) and methylmercury (MeHg) of women of childbearing age were estimated by using seafood consumption data of women of age 20-39 in the period 2011-2019 and seafood DHA and MeHg content data to find significantly (p < 0.05) decreasing intake of DHA (2.8 mg/day per year) and MeHg (0.19 μg Hg/day per year) in this period. The effect of the decreasing maternal DHA and MeHg intake on infant IQ was estimated by using the equation developed by the FAO/WHO. Net IQ change (the difference in IQ gain by DHA and IQ loss by MeHg) was constant or even increasing, depending on the assumption, in this period while seafood consumption was significantly decreasing. This was due to the decreasing adverse effect of MeHg, along with saturated DHA-derived benefits on infant IQ, even at the decreased seafood consumption of Japanese women of childbearing age. It was indicated that the recent decreasing trend in seafood consumption in Japan did not have an unfavorable effect on infant IQ.

Self-Reported Intake and Circulating EPA and DHA Concentrations in US Pregnant Women.

In the United States, pregnant women have low concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are essential for fetal development. Although maternal blood provides accurate polyunsaturated fatty acid (PUFA) concentrations, venipuncture is expensive and not always accessible. PUFA-containing foods consumption, both omega-3 ad omega-6 is supposed to reflect in the status (plasma, RBC, adipose tissue) of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). De novo synthesis of DHA and EPA during pregnancy is supposed to be higher compared to pre and/or post-pregnancy periods. Thus, this study aimed to determine the association between maternal self-reported dietary intake of foods high in DHA and EPA, along with vegetable oils as a source of omega-6 fatty acids, with maternal blood DHA and EPA concentrations. Pregnant women (13-16 weeks gestation) were recruited and asked to complete a food-frequency questionnaire (FFQ) and blood draw at enrollment and 36 weeks. Circulating concentrations of DHA and EPA were quantified and change scores were calculated. Correlations were done to determine associations between FFQ results and EPA/DHA maternal blood concentrations. Regression analyses were run to examine significant predictors of the main outcomes. Overall, PUFA-food consumption and RBC's DHA levels decreased from early to late pregnancy; self-reported PUFA-rich food consumption positively correlated with DHA and EPA levels. DHA concentration was predicted by self-reported PUFA-rich oils (sunflower/soy/corn/olive) consumption, but EPA concentration was predicted by maternal BMI. These findings suggest that EPA and DHA consumption decreased across pregnancy and the FFQ can be utilized as an effective method for estimating PUFA blood concentration during pregnancy.

EBNEO commentary: Maternal high-dose DHA supplementation and neurodevelopment in infants born before 29 weeks' gestation.

This was a planned follow-up study of the Canadian multicentre, randomised, double-blind, placebo-controlled superiority trial, Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck). Enrolment in the primary study occurred from 2015 to 2018. A total of 457 infants were included in the final analysis.1, 2 At 18–22 months' corrected age, neurodevelopmental outcomes as assessed by Bayley-III cognitive, language, and motor composite scores were not statistically significant between the treatment and placebo groups.1 The rates of death before 18–22 months' corrected age, cerebral palsy, hearing impairment and visual impairment were also not statistically significant between the two groups.1 Some aspects may bias study results towards the null. First, approximately half the infants in both groups received intravenous docosahexaenoic acid (DHA). This was on average for 21–23 days, in the form of DHA-rich lipids. Second, there may have been additional enteral DHA supplementation in both groups. At 6 weeks postmenstrual age, infants received a median of 130–133 mL/kg/day of expressed breast milk.1 This suggests that many infants at this age were receiving supplemental nutrition, such as donor breast milk or formula. Formula frequently contains DHA.3 The use of fortifier, which also contains DHA, was not commented on.4 The total fatty acid levels in breast milk at 14 days post-delivery were, on average, similar between the groups. In the treatment group DHA composed on average 0.97% of total fatty acids in breast milk at 14 days post-delivery, and in the placebo group, 0.35%.1 The authors note the hypothesis that sole DHA supplementation may cause an imbalance between the long-chain polyunsaturated fatty acids (LCPUFAs), potentially negating the benefits of high-dose DHA supplementation.1 Indeed, expert consensus statements recommend that preterm infants are supplemented with multiple LCPUFAs, such as DHA and arachidonic acid.4, 5 Due to the lower frequency of severe intraventricular haemorrhage (IVH) in the DHA group, a post hoc sensitivity analysis excluding participants with severe IVH was completed. This did not change the primary findings. Subgroup analysis found that for neonates born <27 weeks' gestation, those in the treatment group had a higher language score (mean difference 5.06, 95% CI 0.08–10.03; p = 0.05). This analysis was not adjusted for the imbalance in frequency of IVH.1 Further study limitations are well documented by the authors. This includes a suboptimal sample size limiting study interpretation, as enrolment for the MOBYDIck trial was terminated early due to concern that DHA was associated with bronchopulmonary dysplasia.1 Additionally, the sample size was chosen for the primary outcome of the MOBYDIck trial, and therefore has limited ability to detect differences in the primary outcome of this study. Despite the theoretical benefit of LCPUFA supplementation for preterm infants, several randomised controlled trials and a Cochrane systematic review have found little, if any, clinical neurodevelopmental effect.4, 6-9 This study is important as there is limited data on very preterm and extremely preterm infants. Based on this trial, maternal supplementation with high-dose DHA in breastfed infants born before 29 weeks' gestational age does not improve neurodevelopmental outcomes at 18–22 months' corrected age. URL LINK: https://ebneo.org/ebneo-commentary-maternal-dha-and-nd DV wrote the initial draft with AK providing key input. All authors revised the paper for critical scientific content. Open access publishing facilitated by The University of Adelaide, as part of the Wiley - The University of Adelaide agreement via the Council of Australian University Librarians. AK receives funding from the Australian National Health and Medical Research Council (NHMRC) (APP1161379). The contents of this paper are solely the responsibility of the individual authors and do not reflect the views of the NHMRC. The authors have no conflicts of interest to declare.

Prenatal choline supplementation improves biomarkers of maternal docosahexaenoic acid (DHA) status among pregnant participants consuming supplemental DHA: a randomized controlled trial

ABSTRACTBackgroundDietary methyl donors (e.g., choline) support the activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, which generates phosphatidylcholine (PC) molecules enriched in DHA that are exported from the liver and made available to extrahepatic tissues.ObjectivesThis study investigated the effect of prenatal choline supplementation on biomarkers of DHA status among pregnant participants consuming supplemental DHA.MethodsPregnant participants (n = 30) were randomly assigned to receive supplemental choline intakes of 550 mg/d [500 mg/d d0-choline + 50 mg/d deuterium-labeled choline (d9-choline); intervention] or 25 mg/d (25 mg/d d9-choline; control) from gestational week (GW) 12–16 until delivery. All participants received a daily 200-mg DHA supplement and consumed self-selected diets. Fasting blood samples were obtained at baseline, GW 20–24, and GW 28–32; maternal/cord blood was obtained at delivery. Mixed-effects linear models were used to assess the impact of prenatal choline supplementation on maternal and newborn DHA status.ResultsCholine supplementation (550 vs. 25 mg/d) did not achieve a statistically significant intervention × time interaction for RBC PC-DHA (P = 0.11); a significant interaction was observed for plasma PC-DHA and RBC total DHA, with choline supplementation yielding higher levels (+32–38% and +8–11%, respectively) at GW 28–32 (P < 0.05) and delivery (P < 0.005). A main effect of choline supplementation on plasma total DHA was also observed (P = 0.018); its interaction with time was not significant (P = 0.068). Compared with controls, the intervention group exhibited higher (P = 0.007; main effect) plasma enrichment of d3-PC (d3-PC/total PC). Moreover, the ratio of d3-PC to d9-PC was higher (+50–67%; P < 0.001) in the choline intervention arm (vs. control) at GW 20–24, GW 28–32, and delivery.ConclusionsPrenatal choline supplementation improves hepatic DHA export and biomarkers of DHA status by bolstering methyl group supply for PEMT activity among pregnant participants consuming supplemental DHA. This trial is registered at www.clinicaltrials.gov as NCT03194659.

Interaction between maternal dietary fat intake, breast milk omega-3 fatty acids and infant growth during the first year of life.

Long chain fatty acids (LCFA) of human milk (HM) might be associated with different patterns of weight gain in infancy. This study aims to examine the interaction between maternal dietary fat intake, breast milk content of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) with infant growth during the first year of life. This longitudinal study was conducted among 215 Iranian mother-infant pairs. The infants were followed up from birth to 12 months of age. Trained healthcare providers measured infant anthropometrics including weight, length and head circumference at birth, 2, 4, 6 and 12 months of age. Breast hind milk samples were collected in the morning through hand expression between 6 and 12 weeks postpartum. Maternal dietary intake was assessed using a 3-day dietary record. Linear mixed effects models were performed to determine the interaction between maternal dietary fat intake, the breast milk content of EPA and DHA with infant growth. Further adjustments were applied for potential confounders. Mean and standard deviation (SD) of maternal age and body mass index were 29.70 (5.24) years and 24.47 (4.42)kg/m2 , respectively. Mean (SD) of infant birth weight was 3177.50 (413.20)g, and 50% were boys. An inverse interaction existed between maternal dietary fat intake and breast milk EPA with infant 4-month weight (β: -366.2, P-value: 0.01). We found a significant association of maternal dietary fat intake and infant 6-month weight (β: 22.5, P-value: 0.04). An inverse interaction was documented between maternal dietary fat intake and breast milk DHA with infant weight at 12-month of age (β: -95.3, P-value: 0.02). We found a significant association between maternal dietary fat intake and infant length at 12-month (β: 0.06, P-value: 0.02). We found an inverse interaction between maternal dietary fat intake and breast milk omega-3 fatty acids with infant weight at 4 and 12 months of age. Although longer follow-up of growth indices is recommended, these findings suggest functional relevance of HM composition to infant growth.

Maternal High-Dose DHA Supplementation and Neurodevelopment at 18-22 Months of Preterm Children.

To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA). Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex. Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex. Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.

Polyunsaturated Fatty Acids in Mother, Infant, and Placental Tissue, and Their Relationship With Pre-Pregnancy BMI

ObjectivesMaternal obesity produces inflammation, which may result in adverse pregnancy outcomes such as preterm birth. Polyunsaturated fatty acids (PUFA), including omega-6 (n-6) and omega-3 (n-3) fatty acids, regulate inflammation and may mitigate the negative effects of inflammation. Previous studies report higher n-6 and lower n-3 PUFA concentration in early to mid-pregnancy for individuals with higher pre-pregnancy BMI (pBMI). However, the relationship between PUFA concentration at delivery and pBMI are not well understood. The purpose of this study is to determine the relationship between pBMI and maternal plasma, umbilical cord plasma, and placental PUFA concentrations, as well as PUFA intrauterine transfer percentage (IUTP).MethodsFollowing IRB approval, maternal plasma, umbilical cord plasma, and placental samples were collected at delivery from 55 maternal-infant dyads. IUTPs for each PUFA (linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA)) were calculated as [cord blood]/[maternal blood] × 100. Spearman's correlations assessed relationships between PUFA levels, PUFA IUTP, and pBMI. Linear regression models were adjusted for smoking status. A p-value < 0.05 was considered statistically significant.ResultsThe mean pBMI for our cohort was 28.7 kg/m2. Preceding pregnancy, 21% of mothers were normal or underweight, 36% overweight, and 43% obese. Maternal LA (R = −0.3, p = 0.03), maternal DHA (R = −0.27, p = 0.04), and placental EPA (R = −0.42, p = 0.02) were significantly correlated with maternal pBMI. After adjusting for smoking status, no correlations remained significant. PUFA cord levels and PUFA IUTP were not correlated to pBMI.ConclusionsTo our knowledge, this is the first study exploring relationships between pBMI and PUFA levels at delivery. Our findings contrast with previous research reporting correlations between PUFA levels and pBMI in early to mid-pregnancy. The effects of pBMI on PUFA status may be most prominent early in pregnancy. Future research should explore the relationship between pBMI and PUFA levels across all stages of pregnancy.Funding SourcesUNMC Pediatrics Department; Child Health Research Institute.

Impact of Maternal Omega-3 Fatty Acid Intake on Ovine Placental and Fetal Tissue Metabolism

ObjectivesDietary supplementation of omega-3 fatty acids such as docosahexaenoic acid (DHA) during pregnancy is often recommended to support optimal fetal brain development and cognitive function of the offspring. DHA supplementation also influences cardiometabolic risk parameters in adults, but its effect on fetal metabolism and subsequent risk is poorly understood. The aim of this study was to determine the effects of maternal DHA supplementation (MDS) on placental and fetal nutrient handling during pregnancy.MethodsWhite-faced ewes were fed either a control diet (Show-rite NewCo Lamb Feed) or a DHA-supplemented diet (control diet + 3% w/w algae-derived DHA) from 2–3 weeks before pregnancy until mid-gestation (75 days), after which a C-section was performed to collect the placenta and fetal tissues for metabolic analyses.ResultsMDS significantly increased serum DHA levels and decreased serum triglycerides in the uterine (maternal) circulation, but not umbilical (fetal) circulation. Nevertheless, MDS resulted in significant DHA enrichment of the placenta and all fetal tissues examined, and differentially affected the protein expression of the four major fatty acid transport proteins FATP1, FATP4, CD36 and FABP in placenta, muscle, liver and heart, but had no effect on kidney or brain. Consistent with these findings, MDS tended to increase the capacity for fat over pyruvate oxidation in fetal muscle and heart, but favored a greater capacity for glucose uptake and oxidation in fetal liver.ConclusionsThis study is the first to validate use of an ovine model for investigating the impact of maternal DHA supplementation on fetal metabolism and development. Results demonstrate a complex tissue-specific effect of MDS on fetal tissue carbohydrate and fatty acid metabolism that favors a greater capacity for serum glucose disposal and fatty acid oxidation. Whether these changes ultimately impact nutrient metabolism and cardiometabolic risk in the offspring later in life merits further investigation.Funding SourcesColorado Agricultural Experiment Station.

Effects of maternal docosahexaenoic acid supplementation on brain development and neurodevelopmental outcomes of breastfed preterm neonates: protocol for a follow-up at preschool age of a randomised clinical trial (MOBYDIckPS)

IntroductionDocosahexaenoic acid (DHA), an omega-3 fatty acid, is important for brain development with possible implications in neurodevelopmental outcomes. In the two-arm, randomised, double-blind, placebo-controlled Maternal Omega-3 Supplementation to Reduce Bronchopulmonary...

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial

Introduction: The aim of the study was to determine the effect of a maternal docosahexaenoic acid (DHA) supplementation during lactation, compared with a placebo, on the neonatal growth profile of breastfed very preterm infants. Methods: Preterm infants’ growth profile, growth velocity from birth to 36 weeks’ postmenstrual age (PMA), and growth at 36 weeks’ PMA were pre-specified secondary outcomes of a randomized placebo-controlled trial conducted in 16 Canadian neonatal intensive care units (2015–2018). Lactating mothers who delivered before 29 weeks’ gestation were given 1.2 g of DHA daily or a placebo within 72 h of delivery and up to 36 weeks’ PMA. Analyses were performed using a linear regression model with generalized estimating equations. Results: 461 mothers and their 528 infants (DHA, N = 273; placebo, N = 255) were included with mean gestational age of 26.5 weeks (standard deviation [SD] = 1.6); 275 (52.1%) were males; mean birth weight was 895 g (SD = 240). DHA interaction with sex was significant on weight profile (interaction p < 0.001), weight velocity (interaction p = 0.05), and weight at 36 weeks’ PMA (interaction p = 0.02). Females in the DHA group gained more weight compared to the placebo group (mean difference [MD], 52.6 g [95% confidence interval [CI]: 24.5–80.8], p < 0.001). Weight velocity was significantly higher in females of the DHA group (MD, 3.4 g/kg/day [95% CI: 0.6–6.2], p = 0.02). At 36 weeks’ PMA, the weight of males in the DHA group was significantly smaller (MD, −88.9 g [95% CI: −166.2 to −11.6], p = 0.02). Conclusion: DHA positively affected female infants’ neonatal weight profile and velocity and negatively affected male infants’ weight at 36 weeks’ PMA.

Placental Nutrient Transporters and Maternal Fatty Acids in SGA, AGA, and LGA Newborns From Mothers With and Without Obesity.

Adverse environmental factors in early life result in fetal metabolic programming and increased risk of adult diseases. Birth weight is an indirect marker of the intrauterine environment, modulated by nutrient availability and placental transport capacity. However, studies of placental transporters in idiopathic birth weight alterations and in maternal obesity in relation to neonatal metabolic outcomes are scarce. We aimed to analyze the placental nutrient transporter protein expression in small (SGA, n = 14), adequate (AGA, n = 18), and large (LGA n = 10) gestational age term for newborns from healthy or obese mothers (LGA-OB, n = 9) and their association with maternal fatty acids, metabolic status, placental triglycerides, and neonatal outcomes. The transporter expression was determined by Western blot. The fatty acid profile was evaluated by gas chromatography, and placental triglycerides were quantified by an enzymatic colorimetric method. GLUT1 was higher in LGA and lower in SGA and positively correlated with maternal HbA1c and placental weight (PW). SNAT2 was lower in SGA, while SNAT4 was lower in LGA-OB. FATP1 was lower in SGA and higher in LGA. SNAT4 correlated negatively and FATP1 correlated positively with the PW and birth anthropometry (BA). Placental triglycerides were higher in LGA and LGA-OB and correlated with pregestational BMI, maternal insulin, and BA. Maternal docosahexaenoic acid (DHA) was higher in SGA, specifically in male placentas, correlating negatively with maternal triglycerides, PW, cord glucose, and abdominal perimeter. Palmitic acid (PA) correlated positively with FATP4 and cord insulin, linoleic acid correlated negatively with PA and maternal cholesterol, and arachidonic acid correlated inversely with maternal TG and directly with FATP4. Our study highlights the importance of placental programming in birth weight both in healthy and obese pregnancies.

Effects of maternal intake of docosahexaenoic acid on febrile status epilepticus and increased susceptibility to seizures after growth

Febrile seizures are caused by an abrupt increase in body temperature. They are sometimes recurrent, and the more seizures are triggered, the higher the risk of epilepsy and psychiatric disorders increase after growing up. Prevention of febrile seizure is considered to be one of the effective countermeasures in protecting the future health of children. Docosahexaenoic acid (DHA) is an important nutrient especially during pregnancy and childhood and is reported to suppress several types of epilepsy. Therefore, we challenged maternal DHA intake to prevent febrile seizures and secondary epilepsy after growth in mice. We used a heat chamber for febrile seizure induction. Intake of DHA during pregnancy and infancy increased the amount of DHA in the brain of offspring. DHA prolonged the seizure latency and increased body temperature at which the first seizure occurred, indicating that maternal DHA intake decreases febrile seizure sensitivity. The mice with febrile status epilepticus showed increased susceptibility to seizures induced by pentylenetetrazol. DHA intake during infancy suppressed the appearance of excitatory electroencephalography and prolonged the seizure latency. Collectively, DHA intake during pregnancy and infancy is of significance in protecting infant from seizures as well as conserving health after growth.

Fatty acid compositions of immature and mature testis are differently responsive to dietary docosahexasenoic acid during development in rats exposed to prenatal ethanol

BackgroundEthanol (EtOH) exposure impairs, but docosahexaenoic acid (DHA) supports testis functions. This study investigated whether dietary DHA and prenatal EtOH exposure affected fatty acid profiles equally in immature and mature testis during developmental stages. MethodsFemale rats were exposed to ± EtOH (3g/kg BW, twice a day via gavage) throughout pregnancy, while consuming a diet supplemented ± DHA (1.4%, w/w). Pups were continued on their mother's diet after weaning with testes collected for fatty acid analysis at different stages of reproductive development, at gestational day 20 (GD20) and postnatal day (PD) 4, 21, 49, and 90, to present fetal, neonatal, weaning, prepubertal and adult stages, respectively. ResultsRegardless of EtOH exposure, dietary DHA significantly increased in testis DHA at all ages, with testis at weaning and prepuberty being more responsive to the diet (p<0.0002). Immature testis at GD20 and PD4 contained more DHA than n-6 docosapentaenoic acid (n-6 DPA) compared to mature testis while being well responsive to the maternal DHA diet through gestation and lactation. The level of n-6 very long chain fatty acids and (VLCFA) and n-6 DPA, distinctively increased from weaning and prepuberty, respectively, and were not reduced by the DHA diet at prepuberty and adulthood. Prenatal EtOH minimally affected testis fatty acids during development. ConclusionImmature and mature testis responds differently to dietary DHA. The age around sexual maturity might be a critical time for dietary intervention as testis was more responsive to diet at this time point. The increase in DPA and n-6 VLCFA in matured testis while not affected by dietary DHA, indicates their critical roles in male reproductive function in rodents.