Health of the Newborn and Breastfeeding during the COVID-19 Pandemic: A Literature Review

Abstract

Objective The present article presents a literature review concerning the microbiota of breast milk and the influence of epigenetics in the susceptibility to COVID-19.

Methods A literature review.

Results Breastfeeding transfers microbiota, nutrients, diverse white blood cells, prebiotics, hormones, and antibodies to the baby, which provide short- and long-term immunological protection against several infectious, gastrointestinal, and respiratory illnesses. The little evidence available shows that breast milk very rarely carries the SARS-CoV-2 virus, and even in those cases, it has been discarded as the source of contagion.

Conclusion The reviewed studies show evidence of a beneficial effect of breastfeeding and highlights its importance on the current pandemic due to the immune reinforcement that it provides. Breastfed individuals showed better clinical response due to the influence on the microbiota and to the nutritional and immune contribution provided by breast milk, compared with those who were not breastfed.

Resumo

Objetivo O presente artigo apresenta uma revisão de literatura sobre a microbiota do leite materno e a influência da epigenética na suscetibilidade à COVID-19.

Métodos Revisão de literatura.

Resultados A amamentação transfere microbiota, nutrientes, diversos glóbulos brancos, prebióticos, hormônios e anticorpos para o bebê, os quais proporcionam proteção imunológica de curto e longo prazo contra diversas doenças infecciosas, gastrointestinais e respiratórias. As poucas evidências disponíveis mostram que o leite materno transporta muito raramente o vírus SARS-CoV-2, e mesmo nestes casos, ele foi descartado como fonte de contágio.

Conclusão Os estudos revisados mostram evidências de um efeito benéfico da amamentação e destacam sua importância na atual pandemia devido ao reforço imunológico que ela proporciona. Os indivíduos amamentados mostraram melhor resposta clínica devido à influência sobre a microbiota, e à contribuição nutricional e imunológica proporcionada pelo leite materno, em comparação com aqueles que não o foram.

Keywords

breast milk - COVID-19 - microbiota - neonate - SARS-CoV-2 - bacterial colonization - pregnancy

Palavras-chave

leite materno - COVID-19 - microbiota - neonato - SARS-CoV-2 - colonização bacteriana - gestação

Publication History

Received: 17 April 2021

Accepted: 01 October 2021

Article published online:
31 January 2022

• References

• 1 Kirtsman M, Diambomba Y, Poutanen SM, Malinowski AK, Vlachodimitropoulou E, Tony WParks. et al. Probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection. CMAJ 2020; 192 (24) E647-E650
• 2 Groß R, Conzelmann C, Müller JA, Stenger S, Steinhart K, Kirchhoff F. et al. Detection of SARS-CoV-2 in human breastmilk. Lancet 2020; 395 (10239): 1757-1758
• 3 Yang N, Che S, Zhang J, Wang X, Tang Y, Wang J. et al; COVID-19 Evidence and Recommendations Working Group. Breastfeeding of infants born to mothers with COVID-19: a rapid review. Ann Transl Med 2020; 8 (10) 618
• 4 Grant MJ, Booth A. A typology of reviews: an analysis of 14 review types and associated methodologies. Health Info Libr J 2009; 26 (02) 91-108
• 5 Martins-Filho PR, Santos VS, Santos Jr HP. To breastfeed or not to breastfeed? Lack of evidence on the presence of SARS-CoV-2 in breastmilk of pregnant women with COVID-19. Rev Panam Salud Publica 2020; 44: e59
• 6 Lackey KA, Pace RM, Williams JE, Bode L, Donovan SM, Järvinen KM. et al. SARS-CoV-2 and human milk: What is the evidence?. Matern Child Nutr 2020; 16 (04) e13032
• 7 Dong Y, Chi X, Hai H, Sun L, Zhang M, Xie W-F. et al. Antibodies in the breast milk of a maternal woman with COVID-19. Emerg Microbes Infect 2020; 9 (01) 1467-1469
• 8 Vivanti AJ, Vauloup-Fellous C, Prevot S, Zupan V, Suffee C, Do JCao. et al. Transplacental transmission of SARS-CoV-2 infection. Nat Commun 2020; 11 (01) 3572
• 9 Sisman J, Jaleel MA, Moreno W, Rajaram V, Collins RRJ, Savani RC. et al. Intrauterine transmission of SARS-COV-2 infection in a preterm infant. Pediatr Infect Dis J 2020; 39 (09) e265-e267
• 10 Lubbe W, Botha E, Niela-Vilen H, Reimers P. Breastfeeding during the COVID-19 pandemic - a literature review for clinical practice. Int Breastfeed J 2020; 15 (01) 82
• 11 Fox A, Marino J, Amanat F. et al. Evidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-19. Medrxiv. 2020
• 12 Avila D, Avila Satagg F, Karchmer S. Origen fetal de las enfermedades del adulto. In: Avila D, Karchmer S, Mardones F, Salazar L. editores. Origen fetal de las enfermedades del adulto. Guayaquil: FLAMP; 2019: 44-54
• 13 Cerini C, Aldrovandi GM. Breast milk: proactive immunomodulation and mucosal protection against viruses and other pathogens. Future Virol 2013; 8 (11) 1127-1134
• 14 Forbes JD, Azad MB, Vehling L, Tun HM, Konya TB, Guttman DS. et al. Canadian Healthy Infant Longitudinal Development (CHILD) Study Investigators. Association of exposure to formula in the hospital and subsequent infant feeding practices with gut microbiota and risk of overweight in the first year of life. JAMA Pediatr 2018; 172 (07) e181161
• 15 He Y, Wang J, Li F, Shi Y. Main clinical features of COVID-19 and potential prognostic and therapeutic value of the microbiota in SARS-CoV-2 infections. Front Microbiol 2020; 11: 1302
• 16 Román Collazo CA, Cabrera Castro V, Andrade Campoverde DP, Flores García MS. Alimentación neonatal asociada a sobrepeso y obesidad en niños y adolescentes de Cuenca, Ecuador. Rev Haban Cienc Méd [Internet]. 2018 [cited 2021 Mar 18];17(4):628-40. Available from: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1729-519X22018000400630
• 17 Flores N, Villegas E, Villacís D, Fornasini M, Cifuentes SG, Narváez L. et al. Concentrations of immunoglobulin A, interleukin-6, and tumor necrosis factor in breastmilk of adolescent and adult mothers in Quito, Ecuador: a cohort study. Breastfeed Med 2014; 9 (02) 107-108
• 18 Thompson AL. Caesarean delivery, immune function and inflammation in early life among Ecuadorian infants and young children. J Dev Orig Health Dis 2019; 10 (05) 555-562
• 19 Zamaniyan M, Ebadi A, Aghajanpoor Mir S, Rahmani Z, Haghshenas M, Azizi S. Preterm delivery in pregnant woman with critical COVID-19 pneumonia and vertical transmission. Prenat Diagn 2020; •••
• 20 Lima-Rogel V, Cervantes-Duran F, Mejía-Elizondo A. et al. Transmisión vertical de SARS-CoV-2 en recién nacidos de embarazo gemelar triple. Rev Latinoam Perinatol 2020; 23 (03) 369
• 21 World Health Organization. Breastfeeding and COVID-19 [Internet]. 2020 [cited 2021 Mar 18]. Available from: https://www.who.int/news-room/commentaries/detail/breastfeeding-and-covid-19
• 22 Fu C, Lu L, Wu H, Shaman J, Cao Y, Fang F. et al. Placental antibody transfer efficiency and maternal levels: specific for measles, coxsackievirus A16, enterovirus 71, poliomyelitis I-III and HIV-1 antibodies. Sci Rep 2016; 6: 38874
• 23 Wampach L, Heintz-Buschart A, Fritz JV, Ramiro-Garcia J, Habier J, Herold M. et al. Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential. Nat Commun 2018; 9 (01) 5091
• 24 Kloc M, Ghobrial RM, Kuchar E, Lewicki S, Kubiak JZ. Development of child immunity in the context of COVID-19 pandemic. Clin Immunol 2020; 217: 108510
• 25 Yu Y, Xu J, Li Y, Hu Y, Li B. Breast milk-fed Infant of COVID-19 pneumonia mother: a case report. Res Sq 2020; . Preprint
• 26 Le Doare K, Holder B, Bassett A, Pannaraj PS. Mother's milk: a purposeful contribution to the development of the infant microbiota and immunity. Front Immunol 2018; 9: 361
• 27 Cortez J, Makker K, Kraemer DF, Neu J, Sharma R, Hudak ML. Maternal milk feedings reduce sepsis, necrotizing enterocolitis and improve outcomes of premature infants. J Perinatol 2018; 38 (01) 71-74
• 28 Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S, Marques Jr ETDA. et al. Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe 2016; 19 (05) 705-712
• 29 Niller HH, Tarnai Z, Decsi G, Zsedényi A, Bánáti F, Minarovits J. Role of epigenetics in EBV regulation and pathogenesis. Future Microbiol 2014; 9 (06) 747-756
• 30 Gou W, Fu Y, Yue L. et al. Gut microbiota may underlie the predisposition of healthy individuals to COVID-19. Medrxiv. 2020
• 31 Esteki-Zadeh A, Karimi M, Strååt K, Ammerpohl O, Zeitelhofer M, Jagodic M. et al. Human cytomegalovirus infection is sensitive to the host cell DNA methylation state and alters global DNA methylation capacity. Epigenetics 2012; 7 (06) 585-593
• 32 Ojo-Okunola A, Nicol M, du Toit E. Human breast milk bacteriome in health and disease. Nutrients 2018; 10 (11) 1643
• 33 Di Pierro F. A possible probiotic (S. salivarius K12) approach to improve oral and lung microbiotas and raise defenses against SAR S-CoV-2. Minerva Med 2020; 111 (03) 281-283
• 34 Zhang T, Cui X, Zhao X, Wang J, Zheng J, Zheng G. et al. Detectable SARS-CoV-2 viral RNA in feces of three children during recovery period of COVID-19 pneumonia. J Med Virol 2020; 92 (07) 909-914
• 35 Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H. et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020; 159 (03) 944-955.e8
• 36 Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P. et al. Severe Covid-19 GWAS Group. Genomewide association study of severe Covid-19 with respiratory failure. N Engl J Med 2020; 383 (16) 1522-1534
• 37 Sciensano. Fact sheet: COVID-19 disease (SARS-CoV-2 virus) [Internet]. 2020 [cited 2021 Feb 12]. Available from: https://covid-19.sciensano.be/sites/default/files/Covid19/COVID-19_fact_sheet_ENG.pdf
• 38 Tollefsbol T. Handbook of epigenetics: the new molecular and medical genetics. London: Academic Press; 2017
• 39 Hussain A, Yadav S, Hadda V, Suri TM, Tiwari P, Mittal S. et al. Covid-19: a comprehensive review of a formidable foe and the road ahead. Expert Rev Respir Med 2020; 14 (09) 869-879
• 40 Gupta A, Madhavan MV, Sehgal K, Sehgal K, Nair N, Mahajan S. et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020; 26 (07) 1017-1032
• 41 Schäfer A, Baric RS. Epigenetic landscape during coronavirus infection. Pathogens 2017; 6 (01) 8
• 42 Gralinski LE, Menachery VD, Morgan AP, Totura AL, Beall A, Kocher J. et al. Allelic variation in the toll-like receptor adaptor protein Ticam2 contributes to SARS-Coronavirus pathogenesis in mice. G3 (Bethesda) 2017; 7 (06) 1653-1663
• 43 Pruimboom L. Methylation pathways and SARS-CoV-2 lung infiltration and cell membrane-virus fusion are both subject to epigenetics. Front Cell Infect Microbiol 2020; 10: 290
• 44 Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395 (10229): 1033-1034
• 45 Xia S, Liu M, Wang C, Xu W, Lan Q, Feng S. et al. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res 2020; 30 (04) 343-355
• 46 Alsaadi EAJ, Neuman BW, Jones IM. A fusion peptide in the spike protein of MERS coronavirus. Viruses 2019; 11 (09) 825
• 47 Küry P, Nath A, Créange A, Dolei A, Marche P, Gold J. et al. Human endogenous retroviruses in neurological diseases. Trends Mol Med 2018; 24 (04) 379-394
• 48 Dupressoir A, Lavialle C, Heidmann T. From ancestral infectious retroviruses to bona fide cellular genes: role of the captured syncytins in placentation. Placenta 2012; 33 (09) 663-671
• 49 Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I. et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A 2020; 117 (13) 7001-7003
• 50 Corley MJ, Ndhlovu LC. DNA methylation analysis of the COVID-19 host cell receptor, Angiotensin I Converting Enzyme 2 gene (ACE2) in the respiratory system reveal age and gender differences. Preprints 2020; 2020030295
• 51 Pinto BGG, Oliveira AER, Singh Y, Jimenez L, Gonçalves ANA, Ogava RLT. et al. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. J Infect Dis 2020; 222 (04) 556-563
• 52 Zill P, Baghai TC, Schüle C, Born C, Früstück C, Büttner A. et al. DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression. PLoS One 2012; 7 (07) e40479
• 53 Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong J-C, Turner AJ. et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res 2020; 126 (10) 1456-1474
• 54 Holmes Jr L, Lim A, Comeaux CR, Dabney KW, Okundaye O. DNA methylation of candidate genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in essential hypertension: a systematic review and quantitative evidence synthesis. Int J Environ Res Public Health 2019; 16 (23) 4829
• 55 Sawalha AH, Zhao M, Coit P, Lu Q. Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients. Clin Immunol 2020; 215: 108410
• 56 Pique-Regi R, Romero R, Tarca AL, Luca F, Xu Y, Alazizi A. et al. Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?. Elife 2020; 9: e58716
• 57 Melnik BC, Schmitz G. Milk's role as an epigenetic regulator in health and disease. Diseases 2017; 5 (01) 12
• 58 Hartwig FP, Loret de Mola C, Davies NM, Victora CG, Relton CL. Breastfeeding effects on DNA methylation in the offspring: A systematic literature review. PLoS One 2017; 12 (03) e0173070
• 59 Glinsky G. Genomics-guided molecular maps of coronavirus targets in human cells: a path toward the repurposing of existing drugs to mitigate the pandemic. arXiv:2003.13665 [Preprint]. 2020 [cited 2021 Feb 10]. Available from: https://arxiv.org/abs/2003.13665
• 60 Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res 2020; 32 (07) 1195-1198
• 61 Maruotti A, Belloc F, Nicita A. Comments on: The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res 2020; 32 (08) 1621-1623
• 62 Sfera A, Fayard L, Osorio C, Price A. Epigenetic interventions for brain rejuvenation: anchoring age-related transposons. Neural Regen Res 2018; 13 (04) 635-636
• 63 Hassan FU, Rehman MS, Khan MS, Ali MA, Javed A, Nawaz A. et al. Curcumin as an alternative epigenetic modulator: mechanism of action and potential effects. Front Genet 2019; 10: 514
• 64 Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 2008; 65 (11) 1631-1652
• 65 Cavezzi A, Troiani E, Corrao S. COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review. Clin Pract 2020; 10 (02) 1271
• 66 Kappert K, Jahić A, Tauber R. Assessment of serum ferritin as a biomarker in COVID-19: bystander or participant? Insights by comparison with other infectious and non-infectious diseases. Biomarkers 2020; 25 (08) 616-625
• 67 Kaufman-Szymczyk A, Majewski G, Lubecka-Pietruszewska K, Fabianowska-Majewska K. The role of sulforaphane in epigenetic mechanisms, including Interdependence between histone modification and DNA methylation. Int J Mol Sci 2015; 16 (12) 29732-29743
• 68 Khan MA, Islam ABMMK. SARS-CoV-2 proteins exploit host's genetic and epigenetic mediators for the annexation of key host signaling pathways. Front Mol Biosci 2021; 7: 598583
• 69 Hou Y, Zhao J, Martin W, Kallianpur A, Chung MK, Jehi L. et al. New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis. BMC Med 2020; 18 (01) 216
• 70 Li Q, Cao Z, Rahman P. Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations. Mol Genet Genomic Med 2020; 8 (08) e1344
• 71 Strafella C, Caputo V, Termine A, Barati S, Gambardella S, Borgiani P. et al. Analysis of ACE2 genetic variability among populations highlights a possible link with COVID-19-related neurological complications. Genes (Basel) 2020; 11 (07) 741
• 72 Benetti E, Tita R, Spiga O, Ciolfi A, Birolo G, Bruselles A. et al. GEN-COVID Multicenter Study. ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. Eur J Hum Genet 2020; 28 (11) 1602-1614
• 73 Paz-y-Miño C. Covid 19, genes, genomas y algo más. RutaKritica [Internet]. 2020 [cited 2020 Jan 10]. Available from: https://rutakritica.org/blog/2020/03/28/covid-19-genes-genomas-y-algo-mas/
• 74 COVID-19 Host Genetics Initiative. The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur J Hum Genet 2020; 28 (06) 715-718
• 75 Darbeheshti F, Rezaei N. Genetic predisposition models to COVID-19 infection. Med Hypotheses 2020; 142: 109818
• 76 Bhatt H. Should COVID-19 mother breastfeed her newborn child? A literature review on the safety of breastfeeding for pregnant women with COVID-19. Curr Nutr Rep 2021; 10 (01) 71-75
• 77 Demirci JR. Breastfeeding support in the time of COVID-19. J Perinat Neonatal Nurs 2020; 34 (04) 297-299
• 78 Calil VMLT, Krebs VLJ, Carvalho WB. Guidance on breastfeeding during the Covid-19 pandemic. Rev Assoc Med Bras (1992) 2020; 66 (04) 541-546