COVID-19 Serostatus Does Not Affect the Intrauterine Transfer of Micronutrients and Fatty Acids or Maternal–Fetal Lymphocyte Cell Composition: An Observational Study

Abstract

Objective

Studies on the effects of coronavirus disease 2019 (COVID-19) on pregnant mothers and their newborns, specifically in relation to their micronutrient status, fatty acids (FAs), and inflammatory status are sparse. We hypothesized that COVID-19 infection would adversely affect the transfer of nutrients, and FAs from mothers to their fetuses via the umbilical cord and maternal–fetal distribution of inflammatory cells. This study aimed to determine the effect of COVID-19 on micronutrients, inflammatory markers, and FAs profiles in pregnant mothers and their newborns' cord blood.

Study Design

This was a cross-sectional study of 212 pregnant mothers in the third trimester and their newborns, recruited after testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serostatus. Peripheral blood of mothers and cord blood were collected at birth and analyzed for vitamin B12 (Vit B12), folic acid, 25(OH)D3, FAs, and peripheral blood mononuclear cells. Student's t-test or analysis of variance (ANOVA) was used to express statistical significance. Non-normal data were tested using the Mann–Whitney U test and Kruskal–Wallis test, with proportions compared with the chi-square test.

Results

Vit B12 levels were significantly low and adrenic acid levels significantly high in COVID-19 seropositive mothers while 25(OH)D3 was significantly low in seropositive cord blood. Irrespective of COVID-19 serostatus, folate, vit B12, saturated FA levels were significantly high in cord blood indicating their increased transfer from mothers to the fetus. However, monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA) levels were significantly lower in cord blood. Irrespective of COVID-19 serostatus, CD4⁺ T helper cells (percentage of lymphocytes) were significantly higher in cord blood, while NK cells, NK-T cells, and CD8⁺ T-cytotoxic cells—percentage of lymphocytes—were significantly lower in cord blood when compared with corresponding mother's blood.

Conclusion

The results indicate that while COVID-19 did not impede the transfer of essential nutrients such as MUFA and PUFA from mother to fetus, or affect maternal–fetal immune cell responses, it did appear to affect the levels of vit B12, vitamin D, and adrenic acid.

Key Points

• COVID-19 did not impede essential fatty acids transfer through cord blood.

• COVID-19 affected maternal-fetal immune responses.

• COVID-19 affected vitB12, vitamin D and adrenic acid levels.

Keywords

COVID-19 - pregnant mothers - cord blood - micronutrients - fatty acids - peripheral blood mononuclear cells

^* These authors have contributed equally to the work and share senior authorship.

Publication History

Received: 11 July 2024

Accepted: 20 November 2024

Article published online:
24 December 2024

• References

• 1 Coronavirus disease (COVID-19). Accessed December 6, 2024 at: https://www.who.int/news-room/fact-sheets/detail/coronavirus-disease-(covid-19)
• 2 Gu J, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol 2007; 170 (04) 1136-1147
• 3 Datta SD, Talwar A, Lee JT. A proposed framework and timeline of the spectrum of disease due to SARS-CoV-2 infection: illness beyond acute infection and public health implications. JAMA 2020; 324 (22) 2251-2252
• 4 Gu J, Taylor CR. Acute immunodeficiency, multiple organ injury, and the pathogenesis of SARS. Appl Immunohistochem Mol Morphol 2003; 11 (04) 281-282
• 5 Koutsakos M, Rowntree LC, Hensen L. et al. Integrated immune dynamics define correlates of COVID-19 severity and antibody responses. Cell Rep Med 2021; 2 (03) 100208
• 6 Thevarajan I, Nguyen THO, Koutsakos M. et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 2020; 26 (04) 453-455
• 7 Hariyanto TI, Kurniawan A. Anemia is associated with severe coronavirus disease 2019 (COVID-19) infection. Transfus Apher Sci 2020; 59 (06) 102926
• 8 Angelidi AM, Belanger MJ, Lorinsky MK. et al. Vitamin D status is associated with in-hospital mortality and mechanical ventilation: a cohort of COVID-19 hospitalized patients. Mayo Clin Proc 2021; 96 (04) 875-886
• 9 Maghbooli Z, Sahraian MA, Ebrahimi M. et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS One 2020; 15 (09) e0239799
• 10 Calder PC. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim Biophys Acta 2015; 1851 (04) 469-484
• 11 Husson MO, Ley D, Portal C. et al. Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids. J Infect 2016; 73 (06) 523-535
• 12 Surekha MV, Suneetha N, Balakrishna N. et al. Impact of COVID-19 during pregnancy on placental pathology, maternal and neonatal outcome - a cross-sectional study on anemic term pregnant women from a tertiary care hospital in southern India. Front Endocrinol (Lausanne) 2023; 14: 1092104
• 13 Fan BE, Chong VCL, Chan SSW. et al. Hematologic parameters in patients with COVID-19 infection. Am J Hematol 2020; 95 (06) E131-E134
• 14 Wessling-Resnick M. Crossing the iron gate: why and how transferrin receptors mediate viral entry. Annu Rev Nutr 2018; 38 (01) 431-458
• 15 Jacobson W, Wreghitt TG, Saich T, Nagington J. Serum folate in viral and mycoplasmal infections. J Infect 1987; 14 (02) 103-111
• 16 Im JH, Je YS, Baek J, Chung MH, Kwon HY, Lee JS. Nutritional status of patients with COVID-19. Int J Infect Dis 2020; 100: 390-393
• 17 Ministry of Health and Family Welfare (MoHFW) Government of India. Anaemia Mukt Bharat. Intensified National Iron Plus Initiative (I-NIPI). Operational guidelines for Programme Managers. New Delhi: MoHFW, Government of India; 2018
• 18 Troen AM, Mitchell B, Sorensen B. et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006; 136 (01) 189-194
• 19 Wacker M, Holick MF. Vitamin D - effects on skeletal and extraskeletal health and the need for supplementation. Nutrients 2013; 5 (01) 111-148
• 20 Brenner H, Holleczek B, Schöttker B. Vitamin D insufficiency and deficiency and mortality from respiratory diseases in a cohort of older adults: potential for limiting the death toll during and beyond the COVID-19 pandemic?. Nutrients 2020; 12 (08) 2488
• 21 Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Publ Health 2020; 13: 1373-1380
• 22 Petrelli F, Luciani A, Perego G, Dognini G, Colombelli PL, Ghidini A. Therapeutic and prognostic role of vitamin D for COVID-19 infection: a systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol 2021; 211: 10588
• 23 Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96 (07) 1911-30 [Erratum in: J Clin Endocrinol Metab. 2011;96(12):3908]
• 24 Sinaci S, Ocal DF, Yucel Yetiskin DF. et al. Impact of vitamin D on the course of COVID-19 during pregnancy: a case control study. J Steroid Biochem Mol Biol 2021; 213: 105964
• 25 Liu J, Li S, Liu J. et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763
• 26 Andrikopoulou M, Madden N, Wen T. et al. Symptoms and critical illness among obstetric patients with coronavirus disease 2019 (COVID-19) infection. Obstet Gynecol 2020; 136 (02) 291-299
• 27 Garcia-Flores V, Romero R, Xu Y. et al. Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2. Res Sq [Preprint] 2021; rs.3.rs-362886
• 28 So J, Wu D, Lichtenstein AH. et al. EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: a randomized, double-blind, crossover study. Atherosclerosis 2021; 316: 90-98
• 29 Sibley CP. Understanding placental nutrient transfer–why bother? New biomarkers of fetal growth. J Physiol 2009; 587 (Pt 14): 3431-3440
• 30 Hay G, Clausen T, Whitelaw A. et al. Maternal folate and cobalamin status predicts vitamin status in newborns and 6-month-old infants. J Nutr 2010; 140 (03) 557-564
• 31 Jobarteh ML, McArdle HJ, Holtrop G, Sise EA, Prentice AM, Moore SE. mRNA levels of placental iron and zinc transporter genes are upregulated in Gambian women with low iron and zinc status. J Nutr 2017; 147 (07) 1401-1409
• 32 Liu NQ, Hewison M. Vitamin D, the placenta and pregnancy. Arch Biochem Biophys 2012; 523 (01) 37-47
• 33 Herrera E. Metabolic changes in diabetic pregnancy. In: Djelmis J, Desoye G, Ivanisevic M. eds. Diabetology of Pregnancy. Basel: Karger; 2005: 34-45
• 34 Zornoza-Moreno M, Fuentes-Hernández S, Carrión V. et al. Is low docosahexaenoic acid associated with disturbed rhythms and neurodevelopment in offsprings of diabetic mothers?. Eur J Clin Nutr 2014; 68 (08) 931-937
• 35 Larqué E, Demmelmair H, Berger B, Hasbargen U, Koletzko B. In vivo investigation of the placental transfer of (13)C-labeled fatty acids in humans. J Lipid Res 2003; 44 (01) 49-55
• 36 Borsani E, Della Vedova AM, Rezzani R, Rodella LF, Cristini C. Correlation between human nervous system development and acquisition of fetal skills: an overview. Brain Dev 2019; 41 (03) 225-233