{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:31:17Z","timestamp":1776403877169,"version":"3.51.2"},"reference-count":43,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["HD104644"],"award-info":[{"award-number":["HD104644"]}]},{"name":"NIH","award":["T32DK007658"],"award-info":[{"award-number":["T32DK007658"]}]},{"name":"NIH","award":["P30DK048520"],"award-info":[{"award-number":["P30DK048520"]}]},{"name":"training grant in Nutrition","award":["HD104644"],"award-info":[{"award-number":["HD104644"]}]},{"name":"training grant in Nutrition","award":["T32DK007658"],"award-info":[{"award-number":["T32DK007658"]}]},{"name":"training grant in Nutrition","award":["P30DK048520"],"award-info":[{"award-number":["P30DK048520"]}]},{"name":"Colorado Nutrition Obesity Research Center","award":["HD104644"],"award-info":[{"award-number":["HD104644"]}]},{"name":"Colorado Nutrition Obesity Research Center","award":["T32DK007658"],"award-info":[{"award-number":["T32DK007658"]}]},{"name":"Colorado Nutrition Obesity Research Center","award":["P30DK048520"],"award-info":[{"award-number":["P30DK048520"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Introduction: An optimal fetal supply of docosahexaenoic acid (DHA) is critical for normal brain development. The relationship between maternal DHA intake and DHA delivery to the fetus is complex and is dependent on placental handling of DHA. Little data exist on placental DHA levels in pregnancies supplemented with the recommended dose of 200 mg\/d. Our objective was to determine how prenatal DHA at the recommended 200 mg\/d impacts maternal, placental, and fetal DHA status in both normal-weight and high-BMI women compared to women taking no supplements. Methods: Maternal blood, placenta, and cord blood were collected from 30 healthy pregnant women (BMI 18.9\u201343.26 kg\/m2) giving birth at term. Red blood cells (RBCs) and villous tissue were isolated, and lipids were extracted to determine DHA content by LC-MS\/MS. Data were analyzed by supplement group (0 vs. 200 mg\/d) and maternal BMI (normal weight or high BMI) using two-way ANOVA. We measured maternal choline levels in maternal and cord plasma samples. Results: Supplementation with 200 mg\/d DHA significantly increased (p &lt; 0.05) maternal and cord RBC DHA content only in pregnancies complicated by high BMI. We did not find any impact of choline levels on maternal or cord RBC phospholipids. There were no significant differences in total placental DHA content by supplementation or maternal BMI (p &gt; 0.05). Placental levels of phosphatidylinositol (PI) and phosphatidic acid containing DHA species were higher (p &lt; 0.05) in high-BMI women without DHA supplementation compared to both normal-BMI and high-BMI women taking DHA supplements. Conclusion: Maternal DHA supplementation at recommended doses cord increased RBC DHA content only in pregnancies complicated by higher BMI. Surprisingly, we found that obesity was related to an increase in placental PI and phosphatidic acid species, which was ameliorated by DHA supplementation. Phosphatidic acid activates placental mTOR, which regulates amino acid transport and may explain previous findings of the impact of DHA on placental function. Current recommendations for DHA supplementation may not be achieving the goal of improving fetal DHA levels in normal-weight women.<\/jats:p>","DOI":"10.3390\/nu16172934","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T07:59:40Z","timestamp":1725263980000},"page":"2934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Maternal Docosahexaenoic Acid Supplementation Alters Maternal and Fetal Docosahexaenoic Acid Status and Placenta Phospholipids in Pregnancies Complicated by High Body Mass Index"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-6339","authenticated-orcid":false,"given":"Katie L.","family":"Bidne","sequence":"first","affiliation":[{"name":"Departments of Obstetrics and Gynecology, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7089-691X","authenticated-orcid":false,"given":"Karin","family":"Zemski Berry","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2163-9756","authenticated-orcid":false,"given":"Mairead","family":"Dillon","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-9480","authenticated-orcid":false,"given":"Thomas","family":"Jansson","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa L.","family":"Powell","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA"},{"name":"Departments of Pediatrics, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"808","DOI":"10.3945\/ajcn.112.050021","article-title":"DHA supplementation and pregnancy outcomes","volume":"97","author":"Carlson","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.biochi.2010.05.005","article-title":"Docosahexaenoic acid (DHA) and the developing central nervous system (CNS)\u2014Implications for dietary recommendations","volume":"93","author":"Guesnet","year":"2011","journal-title":"Biochimie"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3945\/ajcn.114.101071","article-title":"Prenatal supplementation with DHA improves attention at 5 y of age: A randomized controlled trial","volume":"104","author":"Ramakrishnan","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1051\/rnd:2005047","article-title":"Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults","volume":"45","author":"Burdge","year":"2005","journal-title":"Reprod. Nutr. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Fulgoni, V.L., Kris-Etherton, P.M., and Mitmesser, S.H. (2018). Dietary Intakes of EPA and DHA Omega-3 Fatty Acids among US Childbearing-Age and Pregnant Women: An Analysis of NHANES 2001\u20132014. Nutrients, 10.","DOI":"10.3390\/nu10040416"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Thompson, M., Hein, N., Hanson, C., Smith, L.M., Anderson-Berry, A., Richter, C.K., Stessy Bisselou, K., Kusi Appiah, A., Kris-Etherton, P., and Skulas-Ray, A.C. (2019). Omega-3 Fatty Acid Intake by Age, Gender, and Pregnancy Status in the United States: National Health and Nutrition Examination Survey 2003\u20132014. Nutrients, 11.","DOI":"10.3390\/nu11010177"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/glia.24088","article-title":"N-3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development","volume":"70","author":"Leyrolle","year":"2022","journal-title":"Glia"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Basak, S., Mallick, R., Banerjee, A., Pathak, S., and Duttaroy, A.K. (2021). Maternal Supply of Both Arachidonic and Docosahexaenoic Acids Is Required for Optimal Neurodevelopment. Nutrients, 13.","DOI":"10.20944\/preprints202104.0665.v3"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1001\/jama.2010.1507","article-title":"Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: A randomized controlled trial","volume":"304","author":"Makrides","year":"2010","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.3390\/nu5072777","article-title":"The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: A review","volume":"5","author":"Kuratko","year":"2013","journal-title":"Nutrients"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41390-021-01742-w","article-title":"Prenatal docosahexaenoic acid effect on maternal-infant DHA-equilibrium and fetal neurodevelopment: A randomized clinical trial","volume":"92","author":"Gustafson","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.3945\/ajcn.115.124651","article-title":"Effect of omega-3 supplementation on placental lipid metabolism in overweight and obese women","volume":"103","author":"Puchowicz","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rasool, A., Mahmoud, T., Mathyk, B., Kaneko-Tarui, T., Roncari, D., White, K.O., and O'Tierney-Ginn, P. (2022). Obesity downregulates lipid metabolism genes in first trimester placenta. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-24040-9"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1093\/ajcn\/nqac147","article-title":"Prenatal choline supplementation improves biomarkers of maternal docosahexaenoic acid (DHA) status among pregnant participants consuming supplemental DHA: A randomized controlled trial","volume":"116","author":"Klatt","year":"2022","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1908S","DOI":"10.3945\/ajcn.110.001230","article-title":"Placental transfer of fatty acids and fetal implications","volume":"94","author":"Larque","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","first-page":"394","article-title":"A potential role for lysophosphatidylcholine in the delivery of long chain polyunsaturated fatty acids to the fetal circulation","volume":"1864","author":"Kramer","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Powell, T.L., Barentsen, K., Vaughan, O., Uhlson, C., Zemski Berry, K., Erickson, K., Faer, K., Chassen, S.S., and Jansson, T. (2023). Knockdown of Placental Major Facilitator Superfamily Domain Containing 2a in Pregnant Mice Reduces Fetal Brain Growth and Phospholipid Docosahexaenoic Acid Content. Nutrients, 15.","DOI":"10.3390\/nu15234956"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1210\/jc.2017-01384","article-title":"Docosahexaenoic Acid Supplementation in Pregnancy Modulates Placental Cellular Signaling and Nutrient Transport Capacity in Obese Women","volume":"102","author":"Lager","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"C738","DOI":"10.1152\/ajpcell.00196.2014","article-title":"Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids","volume":"307","author":"Lager","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.1210\/jc.2002-020311","article-title":"Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways","volume":"87","author":"Ramsay","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.placenta.2014.01.003","article-title":"Maternal obesity is associated with a lipotoxic placental environment","volume":"35","author":"Saben","year":"2014","journal-title":"Placenta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1194\/jlr.D700041-JLR200","article-title":"Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics","volume":"49","author":"Matyash","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1007\/s00726-015-2019-9","article-title":"Three-minute method for amino acid analysis by UHPLC and high-resolution quadrupole orbitrap mass spectrometry","volume":"47","author":"Nemkov","year":"2015","journal-title":"Amino Acids"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Young, I.E., Parker, H.M., Cook, R.L., O\u2019Dwyer, N.J., Garg, M.L., Steinbeck, K.S., Cheng, H.L., Donges, C., Franklin, J.L., and O\u2019Connor, H.T. (2020). Association between Obesity and Omega-3 Status in Healthy Young Women. Nutrients, 12.","DOI":"10.3390\/nu12051480"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00232-016-9909-y","article-title":"Features of the Phosphatidylinositol Cycle and its Role in Signal Transduction","volume":"250","author":"Epand","year":"2017","journal-title":"J. Membr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1042\/BJ20090428","article-title":"Immunocytochemical techniques reveal multiple, distinct cellular pools of PtdIns4P and PtdIns(4,5)P(2)","volume":"422","author":"Hammond","year":"2009","journal-title":"Biochem. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1016\/j.febslet.2011.11.016","article-title":"Substrate specificity of diacylglycerol kinase-epsilon and the phosphatidylinositol cycle","volume":"585","author":"Shulga","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1074\/jbc.R800059200","article-title":"Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis","volume":"284","author":"Carman","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1091\/mbc.01-11-0540","article-title":"The major sites of cellular phospholipid synthesis and molecular determinants of Fatty Acid and lipid head group specificity","volume":"13","author":"Henneberry","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1189\/jlb.2VMA1215-577R","article-title":"Contribution of CD14 and TLR4 to changes of the PI(4,5)P2 level in LPS-stimulated cells","volume":"100","author":"Plociennikowska","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_31","first-page":"4096","article-title":"LPS-induced clustering of CD14 triggers generation of PI(4,5)P2","volume":"128","author":"Plociennikowska","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.18388\/pb.2018_129","article-title":"Lipid-mediated regulation of pro-inflammatory responses induced by lipopolysaccharide","volume":"64","author":"Kwiatkowska","year":"2018","journal-title":"Postepy Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3931","DOI":"10.1007\/s00018-015-1982-3","article-title":"DAG tales: The multiple faces of diacylglycerol--stereochemistry, metabolism, and signaling","volume":"72","author":"Eichmann","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000381224","article-title":"Fatty Acids, Obesity and Insulin Resistance","volume":"8","author":"Arner","year":"2015","journal-title":"Obes. Facts"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.placenta.2010.12.023","article-title":"Placental structure and inflammation in pregnancies associated with obesity","volume":"32","author":"Roberts","year":"2011","journal-title":"Placenta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1093\/humrep\/dev173","article-title":"Saturated fatty acids enhance TLR4 immune pathways in human trophoblasts","volume":"30","author":"Yang","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1194\/jlr.M033050","article-title":"Oleic acid stimulates system A amino acid transport in primary human trophoblast cells mediated by toll-like receptor 4","volume":"54","author":"Lager","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"361","DOI":"10.5483\/BMBRep.2014.47.7.088","article-title":"Phosphoinositide turnover in Toll-like receptor signaling and trafficking","volume":"47","author":"Le","year":"2014","journal-title":"BMB Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1074\/jbc.C111.328559","article-title":"Phospholipase Cgamma-2 and intracellular calcium are required for lipopolysaccharide-induced Toll-like receptor 4 (TLR4) endocytosis and interferon regulatory factor 3 (IRF3) activation","volume":"287","author":"Chiang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fba.2023-00113","article-title":"Oleic acid stimulation of amino acid uptake in primary human trophoblast cells is mediated by phosphatidic acid and mTOR signaling","volume":"6","author":"Silva","year":"2024","journal-title":"FASEB Bioadv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ejphar.2016.04.024","article-title":"Mechanisms for the activation of Toll-like receptor 2\/4 by saturated fatty acids and inhibition by docosahexaenoic acid","volume":"785","author":"Hwang","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1194\/jlr.M200361-JLR200","article-title":"Differential modulation of Toll-like receptors by fatty acids: Preferential inhibition by n-3 polyunsaturated fatty acids","volume":"44","author":"Lee","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6303","DOI":"10.1074\/jbc.M116.772988","article-title":"Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid","volume":"292","author":"Menon","year":"2017","journal-title":"J. Biol. Chem."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/2934\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:46:58Z","timestamp":1760111218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/2934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,2]]},"references-count":43,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["nu16172934"],"URL":"https:\/\/doi.org\/10.3390\/nu16172934","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,2]]}}}