{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T06:21:16Z","timestamp":1784010076337,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious immune-mediated condition, seen 3\u20135 weeks after COVID-19. Maternal SARS-CoV-2 may potentially cause a similar hyperinflammatory syndrome in neonates due to transplacental transfer of antibodies. We reviewed the perinatal history, clinical features, and outcomes of 20 neonates with features consistent with MIS-C related to maternal SARS-CoV-2 in Kolhapur, India, from 1 September 2020 to 30 April 2021. Anti-SARS-CoV-2 IgG and IgM antibodies were tested in all neonates. Fifteen singletons and five twins born to eighteen mothers with a history of COVID-19 disease or exposure during pregnancy presented with features consistent with MIS-C during the first 5 days after birth. Nineteen were positive for anti-SARS-CoV-2 IgG and all were negative for IgM antibodies. All mothers were asymptomatic and therefore not tested by RTPCR-SARS-CoV-2 at delivery. Eighteen neonates (90%) had cardiac involvement with prolonged QTc, 2:1 AV block, cardiogenic shock, or coronary dilatation. Other findings included respiratory failure (40%), fever (10%), feeding intolerance (30%), melena (10%), and renal failure (5%). All infants had elevated inflammatory biomarkers and received steroids and IVIG. Two infants died. We speculate that maternal SARS-CoV-2 and transplacental antibodies cause multisystem inflammatory syndrome in neonates (MIS-N). Immunomodulation may be beneficial in some cases, but further studies are needed.<\/jats:p>","DOI":"10.3390\/children8070572","type":"journal-article","created":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T22:34:36Z","timestamp":1625438076000},"page":"572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Neonatal Multisystem Inflammatory Syndrome (MIS-N) Associated with Prenatal Maternal SARS-CoV-2: A Case Series"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-8839","authenticated-orcid":false,"given":"Ravindra","family":"Pawar","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Dr. D Y Patil Medical College Hospital and Research Institute, Kolhapur 416003, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Gavade","sequence":"additional","affiliation":[{"name":"Masai Children\u2019s Hospital, Kolhapur 416002, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivedita","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. D Y Patil Medical College Hospital and Research Institute, Kolhapur 416003, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3688-0738","authenticated-orcid":false,"given":"Vijay","family":"Mali","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. D Y Patil Medical College Hospital and Research Institute, Kolhapur 416003, MH, India"},{"name":"NICE Advanced Neonatal Care Centre and Children\u2019s Clinic, Kolhapur 416008, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol","family":"Girwalkar","sequence":"additional","affiliation":[{"name":"Ratna NICU, Kolhapur 416003, MH, India"},{"name":"Department of Pediatrics, Apple Saraswati Multispeciality Hospital, Kolhapur 416003, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyankatesh","family":"Tarkasband","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Apple Saraswati Multispeciality Hospital, Kolhapur 416003, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjog","family":"Loya","sequence":"additional","affiliation":[{"name":"Masai Children\u2019s Hospital, Kolhapur 416002, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Chavan","sequence":"additional","affiliation":[{"name":"Masai Children\u2019s Hospital, Kolhapur 416002, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narendra","family":"Nanivadekar","sequence":"additional","affiliation":[{"name":"Niramay Pediatric Nursing Home and Eye Care Centre, Kolhapur 416001, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Shinde","sequence":"additional","affiliation":[{"name":"Samarth Nursing Home, Kolhapur 416002, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uday","family":"Patil","sequence":"additional","affiliation":[{"name":"Masai Children\u2019s Hospital, Kolhapur 416002, MH, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-2155","authenticated-orcid":false,"given":"Satyan","family":"Lakshminrusimha","sequence":"additional","affiliation":[{"name":"UC Davis Children\u2019s Hospital, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"ref_1","unstructured":"(2021, June 24). WHO COVID-19 Dashboard. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jpeds.2020.04.062","article-title":"The curious case of coronavirus disease 2019 (COVID-19) in children","volume":"222","author":"Gupta","year":"2020","journal-title":"J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/apa.15271","article-title":"Why is COVID-19 so mild in children?","volume":"109","author":"Brodin","year":"2020","journal-title":"Acta Paediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1055\/s-0040-1710512","article-title":"COVID-19 in Newborns and Infants-Low Risk of Severe Disease: Silver Lining or Dark Cloud?","volume":"37","author":"Rawat","year":"2020","journal-title":"Am. J. Perinatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1001\/jama.2020.10369","article-title":"Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2","volume":"324","author":"Whittaker","year":"2020","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1016\/S0140-6736(20)31103-X","article-title":"An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: An observational cohort study","volume":"395","author":"Verdoni","year":"2020","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1161\/CIRCULATIONAHA.120.048360","article-title":"Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic","volume":"142","author":"Belhadjer","year":"2020","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S2352-4642(20)30215-7","article-title":"Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: A multicentre observational study","volume":"4","author":"Davies","year":"2020","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nakra, N.A., Blumberg, D.A., Herrera-Guerra, A., and Lakshminrusimha, S. (2020). Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. Children, 7.","DOI":"10.3390\/children7070069"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.cell.2020.09.016","article-title":"The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19","volume":"183","author":"Consiglio","year":"2020","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1097\/INF.0000000000003149","article-title":"Multisystem Inflammatory Syndrome in Infants<12 months of Age, United States, May 2020\u2013January 2021","volume":"40","author":"Tsang","year":"2021","journal-title":"Pediatric Infect. Dis. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.15585\/mmwr.mm6932e2","article-title":"COVID-19-Associated Multisystem Inflammatory Syndrome in Children\u2014United States, March\u2013July 2020","volume":"69","author":"Bryant","year":"2020","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"McCarty, K.L., Tucker, M., Lee, G., and Pandey, V. (2020). Fetal Inflammatory Response Syndrome Associated With Maternal SARS-CoV-2 Infection. Pediatrics.","DOI":"10.1542\/peds.2020-010132"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Divekar, A.A., Patamasucon, P., and Benjamin, J.S. (2021). Presumptive Neonatal Multisystem Inflammatory Syndrome in Children Associated with Coronavirus Disease 2019. Am. J. Perinatol.","DOI":"10.1055\/s-0041-1726318"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e162","DOI":"10.1097\/INF.0000000000003054","article-title":"COVID-19-Related Potential Multisystem Inflammatory Syndrome in Childhood in a Neonate Presenting as Persistent Pulmonary Hypertension of the Newborn","volume":"40","author":"Paul","year":"2021","journal-title":"Pediatric Infect. Dis. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S2352-4642(21)00055-9","article-title":"Multisystem inflammatory syndrome in a neonate, temporally associated with prenatal exposure to SARS-CoV-2: A case report","volume":"5","author":"Kappanayil","year":"2021","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"652857","DOI":"10.3389\/fped.2021.652857","article-title":"Case Report: Neonatal Multi-System Inflammatory Syndrome Associated With SARS-CoV-2 Exposure in Two Cases From Saudi Arabia","volume":"9","author":"Shaiba","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e018007","DOI":"10.1161\/JAHA.120.018007","article-title":"Cardiac Abnormalities Seen in Pediatric Patients During the SARS-CoV2 Pandemic: An International Experience","volume":"9","author":"Clark","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_19","unstructured":"CDC (2021, June 25). Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C). Available online: https:\/\/www.cdc.gov\/mis-c\/hcp\/."},{"key":"ref_20","unstructured":"AAP (2021, June 25). Multisystem Inflammatory Syndrome in Children (MIS-C) Interim Guidance, Available online: https:\/\/services.aap.org\/en\/pages\/2019-novel-coronavirus-covid-19-infections\/clinical-guidance\/multisystem-inflammatory-syndrome-in-children-mis-c-interim-guidance\/."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1007\/s13312-020-1852-4","article-title":"Perinatal-Neonatal Management of COVID-19 Infection\u2014Guidelines of the Federation of Obstetric and Gynaecological Societies of India (FOGSI), National Neonatology Forum of India (NNF), and Indian Academy of Pediatrics (IAP)","volume":"57","author":"Chawla","year":"2020","journal-title":"Indian Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.echo.2016.03.017","article-title":"A New Z Score Curve of the Coronary Arterial Internal Diameter Using the Lambda-Mu-Sigma Method in a Pediatric Population","volume":"29","author":"Kobayashi","year":"2016","journal-title":"J. Am. Soc. Echocardiogr. Off. Publ. Am. Soc. Echocardiogr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Alsaleem, M. (2020). Intravenous Immune Globulin Uses in the Fetus and Neonate: A Review. Antibodies, 9.","DOI":"10.3390\/antib9040060"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1111\/j.1651-2227.2009.01279.x","article-title":"Necrotizing enterocolitis following the use of intravenous immunoglobulin for haemolytic disease of the newborn","volume":"98","author":"Navarro","year":"2009","journal-title":"Acta Paediatr."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Whitworth, H.B., Sartain, S.E., Kumar, R., Armstrong, K., Ballester, L., Betensky, M., Cohen, C., Diaz, R., Diorio, C., and Goldenberg, N.A. (2021). Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C. Blood.","DOI":"10.1182\/blood.2020010218"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lakshminrusimha, S., Hudak, M., Dimitriades, V., and Higgins, R.D. (2021). Multisystem Inflammatory Syndrome (MIS-C) in Neonates (MIS-N) Following Maternal SARS CoV-2 COVID-19 Infection. Am. J. Perinatol., (editorial under review).","DOI":"10.1055\/a-1682-3075"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gray, K.J., Bordt, E.A., Atyeo, C., Deriso, E., Akinwunmi, B., Young, N., Medina Baez, A., Shook, L.L., Cvrk, D., and James, K. (2021). COVID-19 vaccine response in pregnant and lactating women: A cohort study. Am. J. Obstet. Gynecol.","DOI":"10.1101\/2021.03.07.21253094"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00296-020-04749-4","article-title":"Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: Immunological mechanisms, clinical manifestations and management","volume":"41","author":"Kabeerdoss","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Anderson, E.M., Diorio, C., Goodwin, E.C., McNerney, K.O., Weirick, M.E., Gouma, S., Bolton, M.J., Arevalo, C.P., Chase, J., and Hicks, P. (2020). SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19. J. Pediatric. Infect. Dis. Soc.","DOI":"10.1101\/2020.08.17.20176552"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Vella, L.A., Giles, J.R., Baxter, A.E., Oldridge, D.A., Diorio, C., Kuri-Cervantes, L., Alanio, C., Pampena, M.B., Wu, J.E., and Chen, Z. (2021). Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19. Sci. Immunol., 6.","DOI":"10.1126\/sciimmunol.abf7570"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.cell.2020.09.034","article-title":"Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)","volume":"183","author":"Gruber","year":"2020","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zeng, H., Xu, C., Fan, J., Tang, Y., Deng, Q., Zhang, W., and Long, X. (2020). Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. JAMA J. Am. Med. Assoc.","DOI":"10.1001\/jama.2020.4861"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Flannery, D.D., Gouma, S., Dhudasia, M.B., Mukhopadhyay, S., Pfeifer, M.R., Woodford, E.C., Triebwasser, J.E., Gerber, J.S., Morris, J.S., and Weirick, M.E. (2021). Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios. JAMA Pediatr.","DOI":"10.1001\/jamapediatrics.2021.0038"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.cell.2020.12.027","article-title":"Compromised SARS-CoV-2-specific placental antibody transfer","volume":"184","author":"Atyeo","year":"2021","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1055\/s-0041-1726390","article-title":"COVID-19 Vaccine Considerations during Pregnancy and Lactation","volume":"38","author":"Blumberg","year":"2021","journal-title":"Am. J. Perinatol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shimabukuro, T.T., Kim, S.Y., Myers, T.R., Moro, P.L., Oduyebo, T., Panagiotakopoulos, L., Marquez, P.L., Olson, C.K., Liu, R., and Chang, K.T. (2021). Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N. Engl. J. Med.","DOI":"10.1097\/01.aoa.0000796052.11696.42"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/AOG.0000000000004339","article-title":"Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19)","volume":"137","author":"Metz","year":"2021","journal-title":"Obstet. Gynecol."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/7\/572\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:25:28Z","timestamp":1760163928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/7\/572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,2]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["children8070572"],"URL":"https:\/\/doi.org\/10.3390\/children8070572","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,2]]}}}