Journal of Pediatric Neurology 2024; 22(05): 419-423
DOI: 10.1055/s-0044-1786785
Review Article

Cerebral Malformations Related to Coronavirus Disease 2019 during Pregnancy

Santiago Presti
1   Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy
,
Federica Dierna
1   Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy
,
Antonio Zanghì
2   Department of Medical and Surgical Sciences and Advanced Technologies, Research Center for Surgery of Complex Malformation Syndromes of Transition and Adulthood, University of Catania, Catania, Italy
,
Michele Vecchio
3   Department of Biomedical and Biotechnological Sciences, Rehabilitation Unit, University of Catania, Catania, Italy
,
Salvatore Lavalle
4   Chair of Radiology, Department of Medicine and Surgery, Kore Universisty, Enna, Italy
,
Elena R. Praticò
5   Unit of Pediatrics, Carpi Hospital, Carpi, Italy
,
Martino Ruggieri
6   Department of Clinical and Experimental Medicine, Unit of Clinical Pediatrics, University of Catania, Catania, Italy
,
Agata Polizzi
7   Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy
› Author Affiliations

Abstract

The pandemic of severe-acute-respiratory-syndrome-related coronavirus (SARS-CoV-2) has shown a wide spectrum of possible consequences in children, ranging from asymptomatic patients to the development of severe conditions, such as multisystem inflammatory syndrome in children and encephalopathies related to cytokine storm. Specifically, neurological and neuroimaging abnormalities, ranging from mild-to-the severe ones, have been documented in children as well, such as postinfectious immune-mediated acute disseminated encephalomyelitis, myelitis, neural enhancement, cranial nerve enhancement, and cortical injury, also without neurological symptoms. Considering the neurotropism of coronaviruses and SARS-CoV-2, which has been well described in the literature, we reviewed the literature reporting possible cerebral malformation in neonates due to the infection of SARS-CoV-2 in pregnancy. Coronavirus disease 2019 (COVID-19) during pregnancy might develop cerebral disorders in several ways. Articles in English in the literature were screened using the following search terms: (1) “brain malformations” AND “COVID-19”; (2) “cerebral malformations” AND “COVID-19”; (3) brain malformations AND “Sars-Cov-2”; (4) “cerebral malformations “AND “Sars-Cov-2.” Considering the congenital brain malformation found in newborns exposed to infection of SARS-Cov-2 pre- or neonatally, we identified one paper which reported three neonates with cerebral malformation. Although sporadic, cerebral malformations like atypical signals in white matter with delayed myelination, brain dysplasia/hypoplasia with delayed myelination, and unusual signals in the periventricular regions have been documented.



Publication History

Received: 05 December 2023

Accepted: 04 April 2024

Article published online:
13 May 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children (Basel) 2020; 7 (07) E69
  • 2 Ranieri C, Di Tommaso S, Loconte DC. et al. In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS). Neurogenetics 2018; 19 (02) 77-91
  • 3 Rajapakse N, Dixit D. Human and novel coronavirus infections in children: a review. Paediatr Int Child Health 2021; 41 (01) 36-55
  • 4 Pratico AD, Longo L, Mansueto S. et al. Off-label use of drugs and adverse drug reactions in pediatric units: a prospective, multicenter study. Curr Drug Saf 2018; 13 (03) 200-207
  • 5 Pensato U, Muccioli L, Cani I. et al. Brain dysfunction in COVID-19 and CAR-T therapy: cytokine storm-associated encephalopathy. Ann Clin Transl Neurol 2021; 8 (04) 968-979
  • 6 Kumar D, Verma S, Mysorekar IU. COVID-19 and pregnancy: clinical outcomes; mechanisms, and vaccine efficacy. Transl Res 2023; 251: 84-95
  • 7 Lindan CE, Mankad K, Ram D. et al; ASPNR PECOBIG Collaborator Group. Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study. Lancet Child Adolesc Health 2021; 5 (03) 167-177
  • 8 Al-Kuraishy HM, Al-Gareeb AI, Albezrah NKA. et al. Pregnancy and COVID-19: high or low risk of vertical transmission. Clin Exp Med 2023; 23 (04) 957-967
  • 9 Zombori L, Bacon M, Wood H. et al. Severe cortical damage associated with COVID-19 case report. Seizure 2021; 84: 66-68
  • 10 Pavone P, Briuglia S, Falsaperla R. et al. Wide spectrum of congenital anomalies including choanal atresia, malformed extremities, and brain and spinal malformations in a girl with a de novo 5.6-Mb deletion of 13q12.11-13q12.13. Am J Med Genet A 2014; 164A (07) 1734-1743
  • 11 Tian T, Wu J, Chen T. et al. Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations. JCI Insight 2022; 7 (04) e155827
  • 12 Pavone P, Praticò AD, Ruggieri M. et al. Acquired peripheral neuropathy: a report on 20 children. Int J Immunopathol Pharmacol 2012; 25 (02) 513-517
  • 13 Singer TG, Evankovich KD, Fisher K, Demmler-Harrison GJ, Risen SR. Coronavirus infections in the nervous system of children: a scoping review making the case for long-term neurodevelopmental surveillance. Pediatr Neurol 2021; 117: 47-63
  • 14 Pratico AD, Ruggieri M, Falsaperla R, Pavone P. A probable topiramate-induced limbs paraesthesia and rigid fingers flexion. Curr Drug Saf 2018; 13 (02) 131-136
  • 15 Douaud G, Lee S, Alfaro-Almagro F. et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 2022; 604 (7907) 697-707
  • 16 Pavone P, Nigro F, Falsaperla R. et al. Hemihydranencephaly: living with half brain dysfunction. Ital J Pediatr 2013; 39: 3
  • 17 Pavone P, Praticò AD, Gentile G. et al. A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features. Eur J Med Genet 2016; 59 (05) 283-289
  • 18 Sawlani V, Scotton S, Nader K. et al. COVID-19-related intracranial imaging findings: a large single-centre experience. Clin Radiol 2021; 76 (02) 108-116
  • 19 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Rediagnosing one of Smith's patients (John McCann) with “neuromas tumours” (1849). Neurol Sci 2017; 38 (03) 493-499
  • 20 Egbert AR, Cankurtaran S, Karpiak S. Brain abnormalities in COVID-19 acute/subacute phase: a rapid systematic review. Brain Behav Immun 2020; 89: 543-554
  • 21 Incorpora G, Pavone P, Castellano-Chiodo D, Praticò AD, Ruggieri M, Pavone L. Gelastic seizures due to hypothalamic hamartoma: rapid resolution after endoscopic tumor disconnection. Neurocase 2013; 19 (05) 458-461
  • 22 Moonis G, Filippi CG, Kirsch CFE. et al. The spectrum of neuroimaging findings on CT and MRI in adults with COVID-19. AJR Am J Roentgenol 2021; 217 (04) 959-974
  • 23 Vitaliti G, Praticò AD, Cimino C. et al. Hepatitis B vaccine in celiac disease: yesterday, today and tomorrow. World J Gastroenterol 2013; 19 (06) 838-845
  • 24 Racicot K, Mor G. Risks associated with viral infections during pregnancy. J Clin Invest 2017; 127 (05) 1591-1599
  • 25 Leonardi S, Praticò AD, Lionetti E, Spina M, Vitaliti G, La Rosa M. Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac children. World J Gastroenterol 2012; 18 (40) 5729-5733
  • 26 Paterson RW, Brown RL, Benjamin L. et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain 2020; 143 (10) 3104-3120
  • 27 Palano GM, Praticò AD, Praticò ER. et al. Intossicazione accidentale da alcol etilico in un lattante di 30 giorni. Quadro clinico e follow-up neurologico. Minerva Pediatr 2007; 59 (03) 275-279
  • 28 Katal S, Balakrishnan S, Gholamrezanezhad A. Neuroimaging and neurologic findings in COVID-19 and other coronavirus infections: a systematic review in 116 patients. J Neuroradiol 2021; 48 (01) 43-50
  • 29 Fiumara A, Lanzafame G, Arena A. et al. COVID-19 pandemic outbreak and its psychological impact on patients with rare lysosomal diseases. J Clin Med 2020; 9 (09) 2716
  • 30 Fotuhi M, Mian A, Meysami S, Raji CA. Neurobiology of COVID-19. J Alzheimers Dis 2020; 76 (01) 3-19
  • 31 Sapuppo A, Pavone P, Praticò AD, Ruggieri M, Bertino G, Fiumara A. Genotype-phenotype variable correlation in Wilson disease: clinical history of two sisters with the similar genotype. BMC Med Genet 2020; 21 (01) 128
  • 32 Bulfamante G, Bocci T, Falleni M. et al. Brainstem neuropathology in two cases of COVID-19: SARS-CoV-2 trafficking between brain and lung. J Neurol 2021; 268 (12) 4486-4491
  • 33 Praticò AD, Leonardi S. Immunotherapy for food allergies: a myth or a reality?. Immunotherapy 2015; 7 (02) 147-161
  • 34 Haidar MA, Shakkour Z, Reslan MA. et al. SARS-CoV-2 involvement in central nervous system tissue damage. Neural Regen Res 2022; 17 (06) 1228-1239
  • 35 Salafia S, Praticò AD, Pizzo E, Greco F, Di Bella D. Hemiconvulsion-hemiplegia-epilepsy syndrome. Magnetic resonance findings in a 3-year-old boy. Neurol Neurochir Pol 2013; 47 (06) 584-589
  • 36 Jha NK, Ojha S, Jha SK. et al. Evidence of coronavirus (CoV) pathogenesis and emerging pathogen SARS-CoV-2 in the nervous system: a review on neurological impairments and manifestations. J Mol Neurosci 2021; 71 (11) 2192-2209
  • 37 Praticò AD, Ruggieri M. COVID-19 vaccination for children: may be necessary for the full eradication of the disease. Pediatr Res 2021; 90 (06) 1102-1103
  • 38 Hoffman MC, Freedman R, Law AJ, Clark AM, Hunter SK. Maternal nutrients and effects of gestational COVID-19 infection on fetal brain development. Clin Nutr ESPEN 2021; 43: 1-8
  • 39 Praticò AD, Mistrello G, La Rosa M. et al. Immunotherapy: a new horizon for egg allergy?. Expert Rev Clin Immunol 2014; 10 (05) 677-686
  • 40 Mednick SA, Machon RA, Huttunen MO, Bonett D. Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychiatry 1988; 45 (02) 189-192
  • 41 Praticò AD, Falsaperla R, Comella M, Belfiore G, Polizzi A, Ruggieri M. Case report: a gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth. Front Pediatr 2023; 11: 1101026
  • 42 O'Callaghan E, Sham P, Takei N, Glover G, Murray RM. Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic. Lancet 1991; 337 (8752) 1248-1250
  • 43 Praticò AD. COVID-19 pandemic for pediatric health care: disadvantages and opportunities. Pediatr Res 2021; 89 (04) 709-710
  • 44 Brown AS, Schaefer CA, Wyatt RJ. et al. Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: a prospective birth cohort study. Schizophr Bull 2000; 26 (02) 287-295
  • 45 Hornig M, Bresnahan MA, Che X. et al. Prenatal fever and autism risk. Mol Psychiatry 2018; 23 (03) 759-766
  • 46 Werenberg Dreier J, Nybo Andersen AM, Hvolby A, Garne E, Kragh Andersen P, Berg-Beckhoff G. Fever and infections in pregnancy and risk of attention deficit/hyperactivity disorder in the offspring. J Child Psychol Psychiatry 2016; 57 (04) 540-548
  • 47 Han VX, Patel S, Jones HF. et al. Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review. Transl Psychiatry 2021; 11 (01) 71
  • 48 Rasile M, Lauranzano E, Mirabella F, Matteoli M. Neurological consequences of neurovascular unit and brain vasculature damages: potential risks for pregnancy infections and COVID-19-babies. FEBS J 2022; 289 (12) 3374-3392
  • 49 Naidu SAG, Clemens RA, Pressman P, Zaigham M, Davies KJA, Naidu AS. COVID-19 during pregnancy and postpartum. J Diet Suppl 2022; 19 (01) 78-114
  • 50 Shanes ED, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA. Placental pathology in COVID-19. Am J Clin Pathol 2020; 154 (01) 23-32
  • 51 Wang S, Guo L, Chen L. et al. A case report of neonatal 2019 coronavirus disease in China. Clin Infect Dis 2020; 71 (15) 853-857
  • 52 Marinho PS, da Cunha AJLA, Chimelli L. et al. Case report: SARS-CoV-2 mother-to-child transmission and fetal death associated with severe placental thromboembolism. Front Med (Lausanne) 2021; 8: 677001
  • 53 Mullins E, Perry A, Banerjee J. et al; PAN-COVID Investigators. Pregnancy and neonatal outcomes of COVID-19: the PAN-COVID study. Eur J Obstet Gynecol Reprod Biol 2022; 276: 161-167
  • 54 Suleri A, Blok E, Durkut M. et al. The long-term impact of elevated C-reactive protein levels during pregnancy on brain morphology in late childhood. Brain Behav Immun 2022; 103: 63-72
  • 55 Leyser M, Marques FJP, Nascimento OJMD. Potential risk of brain damage and poor developmental outcomes in children prenatally exposed to SARS-COV-2: a systematic review. Rev Paul Pediatr 2021; 40: e2020415
  • 56 Zeng LK, Zhu HP, Xiao TT. et al. Short-term developmental outcomes in neonates born to mothers with COVID-19 from Wuhan, China. World J Pediatr 2021; 17 (03) 253-262
  • 57 Christian KM, Song H, Ming GL. Pathophysiology and mechanisms of Zika virus infection in the nervous system. Annu Rev Neurosci 2019; 42: 249-269
  • 58 Mavigner M, Raper J, Kovacs-Balint Z. et al. Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques. Sci Transl Med 2018; 10 (435) eaao6975
  • 59 Nem de Oliveira Souza I, Frost PS, França JV. et al. Acute and chronic neurological consequences of early-life Zika virus infection in mice. Sci Transl Med 2018; 10 (444) eaar2749
  • 60 Mlakar J, Korva M, Tul N. et al. Zika virus associated with microcephaly. N Engl J Med 2016; 374 (10) 951-958
  • 61 Pastuszak AL, Levy M, Schick B. et al. Outcome after maternal varicella infection in the first 20 weeks of pregnancy. N Engl J Med 1994; 330 (13) 901-905
  • 62 Katz VL, McCoy MC, Kuller JA, Hansen WF. An association between fetal parvovirus B19 infection and fetal anomalies: a report of two cases. Am J Perinatol 1996; 13 (01) 43-45
  • 63 Courtier J, Schauer GM, Parer JT, Regenstein AC, Callen PW, Glenn OA. Polymicrogyria in a fetus with human parvovirus B19 infection: a case with radiologic-pathologic correlation. Ultrasound Obstet Gynecol 2012; 40 (05) 604-606
  • 64 Frenkel LD, Gomez F, Sabahi F. The pathogenesis of microcephaly resulting from congenital infections: why is my baby's head so small?. Eur J Clin Microbiol Infect Dis 2018; 37 (02) 209-226
  • 65 Yazigi A, De Pecoulas AE, Vauloup-Fellous C, Grangeot-Keros L, Ayoubi JM, Picone O. Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature. J Matern Fetal Neonatal Med 2017; 30 (03) 274-278
  • 66 Diogo MC, Glatter S, Binder J, Kiss H, Prayer D. The MRI spectrum of congenital cytomegalovirus infection. Prenat Diagn 2020; 40 (01) 110-124
  • 67 Zhang XY, Fang F. Congenital human cytomegalovirus infection and neurologic diseases in newborns. Chin Med J (Engl) 2019; 132 (17) 2109-2118
  • 68 Swanson EC, Schleiss MR. Congenital cytomegalovirus infection: new prospects for prevention and therapy. Pediatr Clin North Am 2013; 60 (02) 335-349
  • 69 Fa F, Laup L, Mandelbrot L, Sibiude J, Picone O. Fetal and neonatal abnormalities due to congenital herpes simplex virus infection: a literature review. Prenat Diagn 2020; 40 (04) 408-414