Neonatology pp 1681-1701 | Cite as

Fetal Infections: Rubella, HIV, HCV, HBV, and Human Parvovirus B19

  • Pier Angelo TovoEmail author
  • Stefania Bezzio
  • Clara Gabiano
Reference work entry


Congenital rubella (CR) infection leads to damage in over 80% of fetuses during the first trimester of pregnancy, in 25–34% of cases in the second trimester, while no malformations occur in the third trimester CR syndrome is characterized by cardiac, ocular, and hearing defects, although any organ may be affected. All women of child-bearing age should have natural or vaccine-induced immunity to the virus. Mother-to-child transmission (MTCT) of HIV has decreased from 18% down to 1% in bottle-fed infants with adoption of preventive interventions. These include: prenatal antiretroviral (ARV) prophylaxis, administration of ARV during delivery and avoidance of breast feeding. An early combined ARV treatment of HIV-infected infants offers the great benefits of a longer asymptomatic period and of a prolonged survival. No interventions are currently available to prevent MTCT of HCV, that is estimated to be about 5%. The natural history of HCV infection is relatively benign in childhood. More than 90% of HBV exposed infants develop chronic infection. Administration of HBV vaccine and specific immunoglobulins at birth followed by the 3-dose vaccine series has reduced the MTCT rate by about 90%. Primary maternal infection with parvovirus B19 is associated with asymptomatic fetal infection, hydrops fetalis, intrauterine death, and birth defects. In the first and second trimester the MTCT rate is about 30%. In case of hydrops or signs of anemia, intrauterine trasfusions are recommended.


  1. Abdel-Hady M, Kelly D (2014) Chronic hepatitis B in children and adolescents: epidemiology and management. Paediatr Drugs 15:311–317CrossRefGoogle Scholar
  2. Abdel-Hady M, Bunn SK, Sira J et al (2011) Chronic hepatitis C in children – review of natural history at a national Centre. J Viral Hepat 18:e535–e540CrossRefGoogle Scholar
  3. Ayoub WS, Keeffe EB (2011) Review article: current antiviral therapy of chronic hepatitis B. Aliment Pharmacol Ther 34:1145–1158CrossRefGoogle Scholar
  4. Barth H (2015) Hepatitis C virus: is it time to say goodbye yet? Perspectives and challenges for the next decade. World J Hepatol 7:725–737CrossRefGoogle Scholar
  5. Bekhit MT, Greenwood PA, Warren R et al (2009) In utero treatment of severe fetal anaemia due to parvovirus B19 in one fetus in a twin pregnancy-a case report and literature review. Fetal Diagn Ther 25:153–157CrossRefGoogle Scholar
  6. Berti E, Thorne C, Noguera-Julian A et al (2015) The new face of the pediatric HIV epidemic in western countries: demographic characteristics, morbidity and mortality of the pediatric HIV-infected population. Pediatr Infect Dis J 34:S7–S13CrossRefGoogle Scholar
  7. Best JM (2007) Rubella. Semin Fetal Neonatal Med 12:182–192CrossRefGoogle Scholar
  8. Bouthry E, Picone O, Hamdi G et al (2014) Rubella and pregnancy: diagnosis, management and outcomes. Prenat Diagn 34:1246–1253CrossRefGoogle Scholar
  9. Briand N, Jasseron C, Sibiude J et al (2013) Cesarean section for HIV-infected women in the combination antiretroviral therapies era, 2000–2010. Am J Obstet Gynecol 209:335.e1–335.12CrossRefGoogle Scholar
  10. Brown RS, McMahon BJ, Lok ASF et al (2016) Antiviral therapy in chronic hepatitis B viral infection during pregnancy: a systematic review and meta-analysis. Hepatology 63:319–333CrossRefGoogle Scholar
  11. Calitri C, Gabiano C, Galli L et al (2014) The second generation of HIV-1 vertically exposed infants: a case series from the Italian register for paediatric HIV infection. BMC Infect Dis 14:277. Available at Scholar
  12. CDC – Surveillance of congenital rubella syndrome (2014) Vaccines: congenital rubella syndrome – manual for the surveillance of vaccine-preventable diseases (Chapter 15).
  13. Centers for Disease Control and Prevention (1994) Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Recomm Rep 43:1–20Google Scholar
  14. Cheung KW, Seto MTJ, Wong SF (2013) Towards complete eradication of hepatitis B infection from perinatal transmission: review of the mechanisms of in utero infection and the use of antiviral treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol 169:17–23CrossRefGoogle Scholar
  15. Chiappini E, Galli L, Gabiano C et al (2006) Early triple therapy vs mono or dual therapy for children with perinatal HIV infection. JAMA 295:626–628PubMedGoogle Scholar
  16. Clemente MG, Vajro P (2016) An update on the strategies used for the treatment of chronic hepatitis B in children. Expert Rev Gastroenterol Hepatol 16:1–10Google Scholar
  17. Cottrel EB, Chou R, Wasson N et al (2013) Reducing risk for mother–to-child transmission of hepatitis C virus: a systematic review for the U.S. preventive services task force. Ann Intern Med 158:109–113CrossRefGoogle Scholar
  18. de Jong EP, Walther FJ, Kroes AC et al (2011) Parvovirus B19 infection in pregnancy: new insights and management. Prenat Diagn 31:419–425CrossRefGoogle Scholar
  19. Dijkmans AC, de Jong EP, Dijkmans BA et al (2012) Parvovirus B19 in pregnancy: prenatal diagnosis and management of fetal complications. Curr Opin Obstet Gynecol 24:95–101CrossRefGoogle Scholar
  20. Dunkelberg JC, Berkley EM, Thiel KW et al (2014) Hepatitis B and C in pregnancy: a review and recommendations for care. J Perinatol 34:882–891CrossRefGoogle Scholar
  21. Duszak RS (2009) Congenital rubella syndrome-major review. Optometry 80:36–43CrossRefGoogle Scholar
  22. Ehrhardt S, Xie C, Guo N et al (2015) Breastfeeding while taking lamivudine or tenofovir disoproxil fumarate: a review of the evidence. Clin Infect Dis 60:275–278CrossRefGoogle Scholar
  23. England K, Pembrey L, Tovo PA et al (2005) Growth in the first 5 years of life is unaffected in children with perinatally-acquired hepatitis C infection. J Pediatr 147:227–232CrossRefGoogle Scholar
  24. European Paediatric Hepatitis C Virus Network (2005) Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis 41:45–51CrossRefGoogle Scholar
  25. Garazzino S, Calitri C, Versace A et al (2014) Natural history of vertically acquired HCV infection and associated autoimmune phenomena. Eur J Pediatr 173:1025–1031CrossRefGoogle Scholar
  26. Gentile I, Borgia G (2014) Vertical transmission of hepatitis B virus: challenges and solutions. Int J Womens Health 6:605–611PubMedPubMedCentralGoogle Scholar
  27. Gower E, Estes C, Blach S et al (2014) Global epidemiology and genotype distribution of hepatitis C virus infection. J Hepatol 61:S45–S57CrossRefGoogle Scholar
  28. Grant GB, Reef SE, Dabbagh A et al (2015) Global progress toward rubella and congenital rubella syndrome control and elimination – 2000-2014. MMWR Morb Mortal Wkly Rep 64:1052–1055CrossRefGoogle Scholar
  29. Haber BA, Block JM, Jonas MM et al (2009) Recommendations for screening, monitoring and referral of pediatric chronic hepatitis B. Pediatrics 124:1007–1014CrossRefGoogle Scholar
  30. Indolfi G, Mangone G, Bartolini E et al (2014) Interleukin 28B rs12979860 single nucleotide polymorphism predicts spontaneous clearance of hepatitis C virus in children. J Pediatr Gastroenterol Nutr 58:666–668CrossRefGoogle Scholar
  31. Jonas M, Mizerski J, Badia IB et al (2002) Clinical trial of lamivudine in children with chronic hepatitis B. N Engl J Med 346:1706–1713CrossRefGoogle Scholar
  32. Jonas MM, Block JM, Haber BA et al (2010) Treatment of children with chronic hepatitis B virus infection in the United States: patient selection and therapeutic options. Hepatology 52:2192–2205CrossRefGoogle Scholar
  33. Jonas MM, Lok AS, McMahon BJ et al (2016) Antiviral therapy in management of chronic hepatitis B viral infection in children: a systematic review and meta-analysis. Hepatology 63:307–318CrossRefGoogle Scholar
  34. Kourtis AP, Ellington S, Pazol K et al (2014) Complications of cesarean deliveries among HIV-infected women in the United States. AIDS 28:2609–2618CrossRefGoogle Scholar
  35. Kurbegov AC, Sokol RJ (2009) Hepatitis B therapy in children. Expert Rev Gastroenterol Hepatol 3:39–49CrossRefGoogle Scholar
  36. Lambert N, Strebel P, Orenstein W et al (2015) Rubella. Lancet 385:2297–2307CrossRefGoogle Scholar
  37. Lamont RF, Sobel JD, Vaisbuch E et al (2011) Parvovirus B19 infection in human pregnancy. BJOG 118:175–186CrossRefGoogle Scholar
  38. Lee A, Rajanayagam J, Abdel-Hady M (2015) Chronic hepatitis C infection in children: current treatment and new therapies. J Clin Transl Hepatol 3:36–41CrossRefGoogle Scholar
  39. Lindenburg IT, van Kamp IL, Oepkes D (2014) Intrauterine blood transfusion: current indications and associated risks. Fetal Diagn Ther 36:263–271CrossRefGoogle Scholar
  40. Ma L, Alla NR, Li X, Mynbaev OA, Shi Z (2014) Mother-to-child transmission of HBV: review of current clinical management and prevention strategies. Rev Med Virol 24:396–406CrossRefGoogle Scholar
  41. Mack CL, Gonzales-Peralta RP, Gupta N et al (2012) Diagnosis and management of hepatitis C infection in infants, children and adolescents. J Pediatr Gastroenterol Nutr 54:838–855CrossRefGoogle Scholar
  42. Mok J, Pembrey L, Tovo PA et al (2005) When does mother to child transmission of hepatitis C virus occur? Arch Dis Child Fetal Neonatal Ed 90:F156–F160CrossRefGoogle Scholar
  43. Neu N, Duchon J, Zachariah P (2015) TORCH infections. Clin Perinatol 42:77–103CrossRefGoogle Scholar
  44. Ohmer S, Honegger J (2016) New prospects for the treatment and prevention of hepatitis C in children. Curr Opin Pediatr 28:93–100CrossRefGoogle Scholar
  45. Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children (2016) Guidelines for the use of antiretroviral agents in pediatric HIV infection. Available at Accessed 19 Mar 2016
  46. Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children (2013) Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. Department of Health and Human Services. Available at Accessed 26 Mar 2016
  47. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission (2015) Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. Available at Accessed 19 Mar 2016
  48. Pawlowska M, Halota W (2007) Rapid viral response during treatment of chronic hepatitis B with pegylated interferon alfa-2a in children–preliminary report. Przegl Epidemiol 61:427–431PubMedGoogle Scholar
  49. Pembrey L, Newell ML, Tovo PA, EPHN Collaborators (2005) The management of HCV infected pregnant women and their children European paediatric HCV network. J Hepatol 43:515–525CrossRefGoogle Scholar
  50. Polywka S, Pembrey L, Tovo PA et al (2006) Accuracy of HCV-RNA PCR tests for diagnosis or exclusion of vertically acquired HCV infection. J Med Virol 78:305–310CrossRefGoogle Scholar
  51. Schwarz KB (2003) Pediatric issues in new therapies for hepatitis B and C. Curr Gastroenterol Rep 5:233–239CrossRefGoogle Scholar
  52. Schweitzer A, Horn J, Mikolajczyk RT (2015) Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 386:1546–1555CrossRefGoogle Scholar
  53. Selvapatt N, Ward T, Bailey H et al (2015) Is antenatal screening for hepatitis C virus cost-effective? A decade’s experience at a London Centre. J Hepatol 63:797–804CrossRefGoogle Scholar
  54. Shah U, Kelly D, Chang MH et al (2009) Management of chronic hepatitis B in children. J Pediatr Gastroenterol Nutr 48:399–404CrossRefGoogle Scholar
  55. Sollai S, Noguera-Julian A, Galli L et al (2015) Strategies for the prevention of mother to child transmission in western countries. An update. Pediatr Infect Dis J 34:S14–S30CrossRefGoogle Scholar
  56. Suzuki M, Tajiri H, Tanaka Y et al (2016) Peginterferon therapy in children with chronic hepatitis C: a nationwide, multi-center study in Japan, 2004–2013. J Pediatr Gastroenterol Nutr 63:88–93CrossRefGoogle Scholar
  57. Thio CL, Guo N, Xie C et al (2015) Global elimination of mother-to-child transmission of hepatitis B: revisiting the current strategy. Lancet Infect Dis 1:981–985CrossRefGoogle Scholar
  58. Tovo PA, de Martino M, Gabiano C et al (1992) Prognostic factors and survival in children with perinatal HIV-1 infection. The Italian register for HIV infections in children. Lancet 339:1249–1253CrossRefGoogle Scholar
  59. Tovo PA, Calitri C, Scolfaro C et al (2016) Vertically acquired hepatitis C virus infection: correlates of transmission and disease progression. World J Gastroenterol 22:1–11CrossRefGoogle Scholar
  60. Vodkin I, Patton H (2014) Management of hepatitis B virus infection during pregnancy. Minerva Gastroenterol Dietol 60:205–214PubMedGoogle Scholar
  61. Vynnycky E, Adams EJ, Cutts FT et al (2016) Using seroprevalence and immunisation coverage data to estimate the global burden of congenital rubella syndrome, 1996–2010: a systematic review. PLoS One 11:e0149160CrossRefGoogle Scholar
  62. Weiffenbach J, Bald R, Gloning KP et al (2012) Serological and virological analysis of maternal and fetal blood samples in prenatal human parvovirus b19 infection. J Infect Dis 205:782–788CrossRefGoogle Scholar
  63. Yi P, Chen R, Huang Y, Zhou RR, Fan XG (2016) Management of mother-to-child transmission of hepatitis B virus: propositions and challenges. J Clin Virol 77:32–39CrossRefGoogle Scholar
  64. Zhang ZH, Wu CC, Chen XW et al (2016) Genetic variation of hepatitis B virus and its significance for pathogenesis. World J Gastroenterol 22:126–144CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Pier Angelo Tovo
    • 1
    Email author
  • Stefania Bezzio
    • 2
  • Clara Gabiano
    • 2
  1. 1.Department of PediatricsUniversity of Turin, Regina Margherita Childrens Hospital, AOU Città della Salute e della Scienza di TorinoTurinItaly
  2. 2.Department of PediatricsUniversity of TurinTurinItaly

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