Submitted Successfully!
Thank you for your contribution! You can also upload a video entry related to this topic through the link below:
Check Note
Ver. Summary Created by Modification Content Size Created at Operation
1 Supplementation with MMS plus DHA in pregnant women can complement dietary intake and significantly improve maternal DHA and vitamin D status. This finding is important in light of the essential roles of DHA in the developing brain of the fetus, in visual + 746 word(s) 746 2020-08-18 06:25:13 |
2 format correct Meta information modification 746 2020-08-19 04:42:10 | |
3 format correct Meta information modification 746 2020-08-19 04:42:32 |
Micronutrients and DHA during Pregnancy
Upload a video

 First randomized trial of multiple micronutrients and DHA in pregnant women during second and third trimester.

Supplementation complemented dietary intake and increased maternal DHA.

Vitamin D levels increased with supplementation but decreased in controls.

 Results are clinically relevant as DHA is vital for fetal neurodevelopment.

Micronutrients DHA vitamin D pregnancy
Contributor :
View Times: 237
Revisions: 3 times (View History)
Update Time: 19 Aug 2020

1. Introduction

During pregnancy, an adequate maternal dietary intake is essential to meet the increased nutritional demands required to maintain metabolism and support fetal development [1]. Micronutrients such as folic acid and other B vitamins, vitamin D, vitamin C, calcium, copper, magnesium, iodine, selenium, zinc, and iron all have vital roles throughout all stages of pregnancy [2][3][4]. Poor dietary intake or deficiencies in both micro- and macronutrients can have adverse effects on pregnancy outcomes and neonatal health [5], including an increased risk of neural tube defects, preeclampsia, miscarriage, and low birth weight [6][7]. Many women are at risk of insufficient nutrient intake in industrialized as well as developing countries [8][9][10]. Therefore, micronutrient supplementation is frequently recommended during pregnancy to help improve pregnancy outcomes in the mother and child [11][12]. International guidelines (i.e., from the World Health Organization) currently recommend supplementation of iron and folic acid (0.4 mg/day) during pregnancy for the purpose of improving pregnancy outcomes and for reducing the risk of neural tube defects and maternal anemia in pregnancy [13]. Recently, there have been extensive scientific and medical discussions around the need to include vitamin D as a standard nutrient to be supplemented during pregnancy, due to low intake. Vitamin D regulates calcium and phosphate body stores and is therefore critical for bone health [14]. Furthermore, low concentrations of blood vitamin D in pregnant women have been associated with pregnancy complications [15][16].

In addition to micronutrients, a balanced macronutrient intake is recommended. In particular, the long-chain polyunsaturated fatty acids (LCPUFAs) found at high concentrations within the brain and central nervous system are essential for the development of the fetal brain [17]. Docosahexaenoic acid (DHA)—representing the largest proportion of LCPUFAs in the brain and retina—plays a key role during the pre- and early postnatal period [17][18][19][20]. After the first trimester, when the neural tube has closed and grey matter begins to form [21], DHA begins to rapidly accumulate in the brain [18][22]; accumulation continues for up to two years [23][24].

2. Development

However, the human body is not efficient at producing essential LCPUFAs [22], and maternal concentrations decrease over the course of gestation [25]. Of note, the levels of DHA available to the fetus during pregnancy are governed by the diet of the mother [17][26][27][28]. Studies suggest that consumption of a diet rich in omega-3 LCPUFAs including DHA may have a reduced risk of common pregnancy complications such as intrauterine growth restriction, preeclampsia, and preterm deliveries [29][30][31]. Supplementation with DHA can also increase the expression of fatty acid transport proteins, thus increasing transport through the placenta and improving the fatty acid status of both the mother and child [32][33].

Meta-analyses have demonstrated that there are clinical benefits associated with prenatal multiple micronutrient [34] and LCPUFA supplementation [35] during pregnancy. However, there is limited data on the effects of prenatal supplementation in industrialized countries, particularly when used in combination. Clinical guidelines for pregnant women tend to focus on single nutrients for supplementation [36][37]. Given the interest in the potential beneficial effects of supplementation with micronutrients and DHA during pregnancy, we carried out a randomized trial to evaluate the effects of multiple micronutrients plus DHA supplementation during the second and third trimesters of pregnancy on maternal biomarkers compared with no supplementation in the control group in an industrialized country. The primary variable, i.e., the concentration of DHA (weight percent of total fatty acids (wt% TFA)) in maternal red blood cells (RBC), was considered indicative of LCPUFA status. Secondary explorative variables were other biomarkers of fatty acid and oxidative status, vitamin D, and anthropometric parameters of infants at delivery. We included vitamin D status as a secondary endpoint to investigate whether vitamin D supplementation is needed to maintain adequate status, and whether the levels of vitamin D in the supplement would be sufficient to maintain an adequate status. We hypothesized that supplementation might help to improve maternal DHA and vitamin D status in a healthy population of pregnant women, whereas dietary intake would be insufficient to meet the increased needs during pregnancy.

3. Conclusions

Supplementation with MMS plus DHA in pregnant women can complement dietary intake and significantly improve maternal DHA and vitamin D status. This finding is important in light of the essential roles of DHA in the developing brain of the fetus, in visual development, and in immunomodulation.


  1. Cazzola, R.; Russo-Volpe, S.; Miles, E.A.; Rees, D.; Banerjee, T.; Roynette, C.E.; Wells, S.J.; Goua, M.; Wahle, K.W.; Calder, P.C.; et al. Age-and dose-dependent effects of an eicosapentaenoic acid-rich oil on cardiovascular risk factors in healthy male subjects. Atherosclerosis 2007, 193, 159–167.
  2. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D; The National Academies Press: Washington, DC, USA, 2011.
  3. Ramakrishnan, U.; Grant, F.K.; Goldenberg, T.; Bui, V.; Imdad, A.; Bhutta, Z.A. Effect of Multiple Micronutrient Supplementation on Pregnancy and Infant Outcomes: A Systematic Review. Paediatr. Perinat. Epidemiol. 2012, 26, 153–167.
  4. Cetin, I.; Bühling, K.; Demir, C.; Kortam, A.; Prescott, S.L.; Yamashiro, Y.; Yarmolinskaya, M.; Koletzko, B. Impact of Micronutrient Status during Pregnancy on Early Nutrition Programming. Ann. Nutr. Metab. 2019, 74, 269–278.
  5. Berti, C.; Cetin, I.; Agostoni, C.; Desoye, G.; Devlieger, R.; Emmett, P.M.; Ensenauer, R.; Hauner, H.; Herrera, E.; Hoesli, I.; et al. Pregnancy and Infants’ Outcome: Nutritional and Metabolic Implications. Crit. Rev. Food Sci. Nutr. 2014, 56, 82–91.
  6. Cetin, I.; Berti, C.; Calabrese, S. Role of micronutrients in the periconceptional period. Hum. Reprod. Updat. 2009, 16, 80–95.
  7. Ramakrishnan, U.; Grant, F.; Goldenberg, T.; Zongrone, A.; Martorell, R. Effect of women’s nutrition before and during early pregnancy on maternal and infant outcomes: A systematic review. Paediatr. Perinat. Epidemiol. 2012, 26, 285–301.
  8. Blumfield, M.L.; Hure, A.; Smith, R.; Collins, C.E.; MacDonald-Wicks, L. A systematic review and meta-analysis of micronutrient intakes during pregnancy in developed countries. Nutr. Rev. 2013, 71, 118–132.
  9. Elmadfa, I.; Meyer, A.; Nowak, V.; Hasenegger, V.; Putz, P.; Verstraeten, R.; Remaut-DeWinter, A.M. European Nutrition and Health Report; Karger Medical and Scientific Publishers: Basel, Switzerland, 2009; Volume 62, pp. 1–405.
  10. Parisi, F.; Laoreti, A.; Cetin, I. Multiple Micronutrient Needs in Pregnancy in Industrialized Countries. Ann. Nutr. Metab. 2014, 65, 13–21.
  11. Gernand, A.D.; Schulze, K.J.; Stewart, C.P.; West, K.P.; Christian, P. Micronutrient deficiencies in pregnancy worldwide: Health effects and prevention. Nat. Rev. Endocrinol. 2016, 12, 274–289.
  12. Schaefer, E. Micronutrient Deficiency in Women Living in Industrialized Countries during the Reproductive Years: Is there a Basis for Supplementation with Multiple Micronutrients? J. Nutr. Disord. Ther. 2016, 6.
  13. World Health Organization; e-Library of Evidence for Nutrition Actions (eLENA). Daily Iron and Folic Acid Supplementation during Pregnancy. Available online: (accessed on 31 July 2020).
  14. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. 7, Vitamin D; National Academies Press: Washington, DC, USA, 1997. Available online: (accessed on 31 July 2020).
  15. Mulligan, M.L.; Felton, S.K.; Riek, A.E.; Bernal-Mizrachi, C. Implications of vitamin D deficiency in pregnancy and lactation. Am. J. Obstet. Gynecol. 2010, 202, e421–e429.
  16. Dovnik, A.; Mujezinović, F. The Association of Vitamin D Levels with Common Pregnancy Complications. Nutrients 2018, 10, 867.
  17. Rees, A.; Sirois, S.; Wearden, A. Prenatal maternal docosahexaenoic acid intake and infant information processing at 4.5mo and 9mo: A longitudinal study. PLoS ONE 2019, 14, e0210984.
  18. Agostoni, C.; Nobile, M.; Ciappolino, V.; DelVecchio, G.; Tesei, A.; Turolo, S.; Crippa, A.; Mazzocchi, A.; Altamura, C.A.; Brambilla, P. The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD. Int. J. Mol. Sci. 2017, 18, 2608.
  19. Echeverría, F.; Valenzuela, R.; Hernandez-Rodas, M.C.; Valenzuela, A. Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources. Prostaglandins Leukot. Essent. Fat. Acids 2017, 124, 1–10.
  20. Weiser, M.J.; Butt, C.M.; Mohajeri, M.H. Docosahexaenoic Acid and Cognition throughout the Lifespan. Nutrients 2016, 8, 99.
  21. Darnell, D.; Gilbert, S.F. Neuroembryology. Wiley Interdiscip. Rev. Dev. Biol. 2016, 6, e215.
  22. Delgado-Noguera, M.F.; Calvache, J.A.; Cosp, X.B.; Kotanidou, E.P.; Galli-Tsinopoulou, A. Supplementation with long chain polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers for improving child growth and development. Cochrane Database Syst. Rev. 2015, CD007901.
  23. Carlson, S.E.; Colombo, J. Docosahexaenoic Acid and Arachidonic Acid Nutrition in Early Development. Adv. Pediatr. 2016, 63, 453–471.
  24. Innis, S.M. The Role of Dietary n–6 and n–3 Fatty Acids in the Developing Brain. Dev. Neurosci. 2000, 22, 474–480.
  25. Al, M.D.M.; Van Houwelingen, A.C.; Kester, A.D.; Hasaart, T.H.; De Jong, A.E.P.; Hornstra, G. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br. J. Nutr. 1995, 74, 55–68.
  26. Grantham-McGregor, S.; Cheung, Y.B.; Cueto, S.; Glewwe, P.; Richter, L.; Strupp, B. Developmental potential in the first 5 years for children in developing countries. Lancet 2007, 369, 60–70.
  27. McCann, J.C.; Ames, B.N. Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. Am. J. Clin. Nutr. 2005, 82, 281–295.
  28. Innis, S.M. Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. J. Pediatr. 2003, 143, 1–8.
  29. Englund-Ögge, L.; Brantsæter, A.; Sengpiel, V.; Haugen, M.; Birgisdottir, B.E.; Myhre, R.; Meltzer, H.M.; Jacobsson, B. Maternal dietary patterns and preterm delivery: Results from large prospective cohort study. BMJ 2014, 348, g1446.
  30. Larqué, E.; Gil-Sánchez, A.; Prieto-Sánchez, M.T.; Koletzko, B. Omega 3 fatty acids, gestation and pregnancy outcomes. Br. J. Nutr. 2012, 107 (Suppl. 2), S77–S84.
  31. Rogers, L.K.; Valentine, C.J.; Keim, S.A. DHA supplementation: Current implications in pregnancy and childhood. Pharmacol. Res. 2012, 70, 13–19.
  32. Larqué, E.; Krauss-Etschmann, S.; Campoy, C.; Hartl, D.; Linde, J.; Klingler, M.; Demmelmair, H.; Caño, A.; Gil, A.; Bondy, B.; et al. Docosahexaenoic acid supply in pregnancy affects placental expression of fatty acid transport proteins. Am. J. Clin. Nutr. 2006, 84, 853–861.
  33. Decsi, T.; Campoy, C.; Koletzko, B. Effect of N-3 Polyunsaturated Fatty Acid Supplementation in Pregnancy: The Nuheal Trial. Pharm. Biotechnol. 2005, 569, 109–113.
  34. Keats, E.C.; Haider, B.A.; Tam, E.; Bhutta, Z. A Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst. Rev. 2019, 3, CD004905.
  35. Middleton, P.; Gomersall, J.S.; Gould, J.F.; Shepherd, E.; Olsen, S.F.; Makrides, M. Omega-3 fatty acid addition during pregnancy. Cochrane Database Syst. Rev. 2018, 11, CD003402.
  36. FIGO Working Group on Good Clinical Practice in Maternal-Fetal Medicine Good clinical practice advice: Micronutrients in the periconceptional period and pregnancy. Int. J. Gynecol. Obstet. 2019, 144, 317–321.
  37. World Health Organization. Nutrition and Pregnancy. Available online: (accessed on 30 April 2020).
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 237
Revisions: 3 times (View History)
Update Time: 19 Aug 2020
Table of Contents


    Are you sure to Delete?

    Video Upload Options

    Do you have a full video?
    If you have any further questions, please contact Encyclopedia Editorial Office.
    Schaefer, E. Micronutrients and DHA during Pregnancy. Encyclopedia. Available online: (accessed on 30 September 2022).
    Schaefer E. Micronutrients and DHA during Pregnancy. Encyclopedia. Available at: Accessed September 30, 2022.
    Schaefer, Ella. "Micronutrients and DHA during Pregnancy," Encyclopedia, (accessed September 30, 2022).
    Schaefer, E. (2020, August 18). Micronutrients and DHA during Pregnancy. In Encyclopedia.
    Schaefer, Ella. ''Micronutrients and DHA during Pregnancy.'' Encyclopedia. Web. 18 August, 2020.