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Maternal DHA Impact on Child Neurodevelopment

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Lipids".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 30049

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Guest Editor
Faculty of Medicine, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
Interests: lipids and brain development; fatty acid uptake system in human placenta; angiogenesis; feto-placental growth and development; DHA and cell growth and proliferation; lipid nutrition; eicosanoids; cardiovascular health; platelet function
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Special Issue Information

Dear colleagues,

The developmental environment of the fetus is dependent on two major factors: maternal nutritional state and placental function. Maternal long-chain polyunsaturated fatty acids (LCPUFAs) and their metabolites are involved in every stage of pregnancy by supporting cell growth and development, cell signaling, and modulating other critical aspects of structural and functional processes. Long-chain fatty acids stimulate early placentation by enhancing angiogenesis in placental trophoblasts via various growth factors, LCPUFA metabolites, and fatty-acid-binding proteins. Inadequate placental angiogenesis and trophoblast invasion of the maternal decidua and uterine spiral arterioles leads to structural and functional deficiency of the placenta, which contributes to overall fetal growth and the development of important organs such as the brain. During the third trimester of pregnancy, placental preferential transport of maternal plasma LCUPFAs such as docosahexaenoic acid (22:6 n-3; DHA), and arachidonic acid (20:4n-6) is of critical importance for fetal growth and development. DHA is essential for normal healthy brain development, maintenance, and function. Many studies have shown that DHA metabolism and signaling systems are involved in neurogenesis, anti‐nociceptive effects, anti‐apoptotic effects, synaptic plasticity, Ca2+ homeostasis, and in the functioning of nigrostriatal pathways. Several metabolites of DHA are also involved in several processes, but full mechanisms are not yet known. Long-chain fatty acids mainly cross the placental microvillous and basal membranes via the plasma membrane fatty acid transport system. Maternal diet, metabolic disease, obesity, and diabetes can affect the expression of placental nutrient transporter activities. Studies strongly suggest that maternal dietary deficiency of DHA during pregnancy increases the risk for neurocognitive disorders. Fetal DHA inadequacy and its impact on child neurodevelopment has been observed. Several randomized trials of maternal DHA supplementation in pregnancy have been carried out. Maternal dietary deficiency of n‐3 fatty acids during development in utero and in the postnatal state has detrimental effects on cognitive abilities. Fetal DHA inadequacy and its impact on child neurodevelopment have been observed. 

The objective of this Special Issue on “Placental Transport of Maternal DHA to the Fetus and the Impact on Child Neurodevelopment ” is to showcase the latest research focusing on the impact of maternal diet, metabolic diseases, diabetes, and the status  on placental fatty acid and transport in fetal brain development and knock-on effects on child cognition as well as intervention studies with LCPUFAs during pregnancies with consideration of fetal outcome. 

This Special Issue is intended to provide a contemporary summary of current knowledge while providing guidance for future research in the field. 

Prof. Asim K. Duttaroy
Guest Editor

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Keywords

  • DHA
  • human placenta
  • fetus
  • brain development
  • maternal diet
  • diabetes
  • metabolic disease
  • fatty acid transport
  • neurodevelopment
  • feto-placental growth
  • placentation

Published Papers (6 papers)

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Editorial

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2 pages, 171 KiB  
Editorial
Special Issue “Maternal DHA Impact on Child Neurodevelopment”
by Asim K. Duttaroy
Nutrients 2021, 13(7), 2209; https://doi.org/10.3390/nu13072209 - 27 Jun 2021
Cited by 1 | Viewed by 1882
Abstract
In this special issue, we have focused on the maternal docosahexaenoic acid, 22:6n-3 (DHA), on children’s neurodevelopment [...] Full article
(This article belongs to the Special Issue Maternal DHA Impact on Child Neurodevelopment)

Research

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12 pages, 887 KiB  
Article
Prenatal Maternal Docosahexaenoic Acid (DHA) Supplementation and Newborn Anthropometry in India: Findings from DHANI
by Shweta Khandelwal, Dimple Kondal, Monica Chaudhry, Kamal Patil, Mallaiah Kenchaveeraiah Swamy, Gangubai Pujeri, Swati Babu Mane, Yashaswi Kudachi, Ruby Gupta, Usha Ramakrishnan, Aryeh D. Stein, Dorairaj Prabhakaran and Nikhil Tandon
Nutrients 2021, 13(3), 730; https://doi.org/10.3390/nu13030730 - 25 Feb 2021
Cited by 7 | Viewed by 3551
Abstract
Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from low- and middle-income countries (LMICs) is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14–20 weeks’ gestation [...] Read more.
Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from low- and middle-income countries (LMICs) is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14–20 weeks’ gestation at enrollment) in India to test the effectiveness of 400 mg/day algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 were enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 × 2 = 400 mg/day) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (≤20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n = 478 and placebo; n = 479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo groups for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p = 0.54), length (47.3 ± 2.0 vs. 47.5 ± 2.0 cm, p = 0.13), or head circumference (33.7 ± 1.4 vs. 33.8 ± 1.4 cm, p = 0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p = 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400 mg/day DHA did not impact the offspring‘s birthweight, length, or head circumference. Full article
(This article belongs to the Special Issue Maternal DHA Impact on Child Neurodevelopment)
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15 pages, 750 KiB  
Article
Effect of Maternal Docosahexaenoic Acid (DHA) Supplementation on Offspring Neurodevelopment at 12 Months in India: A Randomized Controlled Trial
by Shweta Khandelwal, Dimple Kondal, Monica Chaudhry, Kamal Patil, Mallaiah Kenchaveeraiah Swamy, Deepa Metgud, Sandesh Jogalekar, Mahesh Kamate, Gauri Divan, Ruby Gupta, Dorairaj Prabhakaran, Nikhil Tandon, Usha Ramakrishnan and Aryeh D. Stein
Nutrients 2020, 12(10), 3041; https://doi.org/10.3390/nu12103041 - 03 Oct 2020
Cited by 13 | Viewed by 4571
Abstract
Intake of dietary docosahexaenoic acid (DHA 22:6n-3) is very low among Indian pregnant women. Maternal supplementation during pregnancy and lactation may benefit offspring neurodevelopment. We conducted a double-blind, randomized, placebo-controlled trial to test the effectiveness of supplementing pregnant Indian women (singleton gestation) from [...] Read more.
Intake of dietary docosahexaenoic acid (DHA 22:6n-3) is very low among Indian pregnant women. Maternal supplementation during pregnancy and lactation may benefit offspring neurodevelopment. We conducted a double-blind, randomized, placebo-controlled trial to test the effectiveness of supplementing pregnant Indian women (singleton gestation) from ≤20 weeks through 6 months postpartum with 400 mg/d algal DHA compared to placebo on neurodevelopment of their offspring at 12 months. Of 3379 women screened, 1131 were found eligible; 957 were randomized. The primary outcome was infant neurodevelopment at 12 months, assessed using the Development Assessment Scale for Indian Infants (DASII). Both groups were well balanced on sociodemographic variables at baseline. More than 72% of women took >90% of their assigned treatment. Twenty-five serious adverse events (SAEs), none related to the intervention, (DHA group = 16; placebo = 9) were noted. Of 902 live births, 878 were followed up to 12 months; the DASII was administered to 863 infants. At 12 months, the mean development quotient (DQ) scores in the DHA and placebo groups were not statistically significant (96.6 ± 12.2 vs. 97.1 ± 13.0, p = 0.60). Supplementing mothers through pregnancy and lactation with 400 mg/d DHA did not impact offspring neurodevelopment at 12 months of age in this setting. Full article
(This article belongs to the Special Issue Maternal DHA Impact on Child Neurodevelopment)
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Review

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28 pages, 2219 KiB  
Review
Maternal Supply of Both Arachidonic and Docosahexaenoic Acids Is Required for Optimal Neurodevelopment
by Sanjay Basak, Rahul Mallick, Antara Banerjee, Surajit Pathak and Asim K. Duttaroy
Nutrients 2021, 13(6), 2061; https://doi.org/10.3390/nu13062061 - 16 Jun 2021
Cited by 38 | Viewed by 7014
Abstract
During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although the structural and functional roles of DHA in brain [...] Read more.
During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural–functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, the importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA, in supporting the optimal brain development and growth and functional roles in the brain. Full article
(This article belongs to the Special Issue Maternal DHA Impact on Child Neurodevelopment)
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21 pages, 880 KiB  
Review
Towards an Optimized Fetal DHA Accretion: Differences on Maternal DHA Supplementation Using Phospholipids vs. Triglycerides during Pregnancy in Different Models
by Antonio Gázquez and Elvira Larqué
Nutrients 2021, 13(2), 511; https://doi.org/10.3390/nu13020511 - 04 Feb 2021
Cited by 6 | Viewed by 3345
Abstract
Docosahexaenoic acid (DHA) supplementation during pregnancy has been recommended by several health organizations due to its role in neural, visual, and cognitive development. There are several fat sources available on the market for the manufacture of these dietary supplements with DHA. These fat [...] Read more.
Docosahexaenoic acid (DHA) supplementation during pregnancy has been recommended by several health organizations due to its role in neural, visual, and cognitive development. There are several fat sources available on the market for the manufacture of these dietary supplements with DHA. These fat sources differ in the lipid structure in which DHA is esterified, mainly phospholipids (PL) and triglycerides (TG) molecules. The supplementation of DHA in the form of PL or TG during pregnancy can lead to controversial results depending on the animal model, physiological status and the fat sources utilized. The intestinal digestion, placental uptake, and fetal accretion of DHA may vary depending on the lipid source of DHA ingested by the mother. The form of DHA used in maternal supplementation that would provide an optimal DHA accretion for fetal brain development, based on the available data obtained most of them from different animal models, indicates no consistent differences in fetal accretion when DHA is provided as TG or PL. Other related lipid species are under evaluation, e.g., lyso-phospholipids, with promising results to improve DHA bioavailability although more studies are needed. In this review, the evidence on DHA bioavailability and accumulation in both maternal and fetal tissues after the administration of DHA supplementation during pregnancy in the form of PL or TG in different models is summarized. Full article
(This article belongs to the Special Issue Maternal DHA Impact on Child Neurodevelopment)
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25 pages, 990 KiB  
Review
Maternal Docosahexaenoic Acid Status during Pregnancy and Its Impact on Infant Neurodevelopment
by Sanjay Basak, Rahul Mallick and Asim K. Duttaroy
Nutrients 2020, 12(12), 3615; https://doi.org/10.3390/nu12123615 - 25 Nov 2020
Cited by 41 | Viewed by 8648
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Maternal DHA Impact on Child Neurodevelopment)
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