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Infections of the ] (HCV) in ]ren and ] are less understood than those in other adults. Worldwide, the prevalence of HCV infection in pregnant women and children has been estimated to 1-8% and 0.05-5% respectively.<ref name=Arshad2011>{{cite journal|vauthors=Arshad M, El-Kamary SS, Jhaveri R |year=2011 |title=Hepatitis C virus infection during pregnancy and the newborn period--are they opportunities for treatment? |journal=Journal of Viral Hepatitis |volume=18|issue=4|pages=229–236 |doi=10.1111/j.1365-2893.2010.01413.x |pmid=21392169|s2cid=35515919 }}</ref> The vertical transmission rate has been estimated to be 3-5% and there is a high rate of spontaneous clearance (25-50%) in the children. Higher rates have been reported for both vertical transmission (18%, 6-36% and 41%).<ref name=Hunt1997>{{cite journal|vauthors=Hunt CM, Carson KL, Sharara AI |year=1997|title=Hepatitis C in pregnancy |journal=Obstet Gynecol |volume=89 |issue=5 Pt 2 |pages=883–890 |doi=10.1016/S0029-7844(97)81434-2|pmid=9166361|s2cid=23182340}}</ref><ref name=Thomas1998>{{cite journal |vauthors=Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ |year=1998 |title=A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection |journal=Int J Epidemiol |volume=27 |issue=1 |pages=108–117 |doi=10.1093/ije/27.1.108 |pmid=9563703|doi-access=free }}</ref> and prevalence in children (15%).<ref name=Fischler2007>{{cite journal |author=Fischler B |year=2007 |title=Hepatitis C virus infection |journal=Semin Fetal Neonatal Med |volume=12 |issue=3 |pages=168–173 |doi=10.1016/j.siny.2007.01.008 |pmid=17320495}}</ref> |
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'''HCV (Hepatitis C) infections in children and pregnancy''' are less understood than in adults. |
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In ], transmission around the time of birth is now the leading cause of HCV infection. In the absence of virus in the mother's blood, transmission seems to be rare.<ref name="Thomas1998"/> Factors associated with an increased rate of infection include ] of longer than 6 hours before delivery and procedures exposing the infant to maternal blood.<ref name=Indolfi2009>{{cite journal |vauthors=Indolfi G, Resti M |year=2009 |title=Perinatal transmission of hepatitis C virus infection |journal=J Med Virol |volume=81 |issue=5 |pages=836–843 |doi=10.1002/jmv.21437 |pmid=19319981|s2cid=21207996 }}</ref> ]s are not recommended. ] is considered safe if the nipples are not damaged. Infection around the time of birth in one child does not increase the risk in a subsequent pregnancy. All genotypes appear to have the same risk of transmission. |
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==Epidemiology== |
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HCV infection is frequently found in children who have previously been presumed to have non-A, non-B ] and ] ].<ref name="González-Peralta1997">{{cite journal |author=González-Peralta RP |year=1997 |title=Hepatitis C virus infection in pediatric patients |journal=Clin Liver Dis |volume=1 |issue=3 |pages=691–705 |doi=10.1016/s1089-3261(05)70329-9 |pmid=15560066}}</ref> The presentation in childhood may be asymptomatic or with elevated ].<ref name=Suskind2004>{{cite journal |vauthors=Suskind DL, Rosenthal P |title=Chronic viral hepatitis |journal=Adolesc Med Clin |year=2004 |volume=15 |issue=1|pages=145–58, x-xi |doi= 10.1016/j.admecli.2003.11.001|pmid=15272262}}</ref> While infection is commonly asymptomatic both ] with ] and ] may occur in childhood. |
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Worldwide the prevalence of ] (HCV) infection in pregnant women and children has been estimated to 1-8% and 0.05-5% respectively.<ref name=Arshad2011>{{cite journal|author=Arshad M, El-Kamary SS, Jhaveri R |year=2011 |title=Hepatitis C virus infection during pregnancy and the newborn period--are they opportunities for treatment? |journal=J Viral Hepat |volume=18|issue=4|pages=229–236 |doi=10.1111/j.1365-2893.2010.01413.x }}</ref> The vertical transmission rate has been estimated to be 3-5% and there is a high rate of spontaneous clearance (25-50%) in the children. Higher rates have been reported for both vertical transmission (18%, 6-36% and 41%).<ref name=Hunt1997>{{cite journal|author=Hunt CM, Carson KL, Sharara AI |year=1997|title=Hepatitis C in pregnancy |journal=Obstet Gynecol |volume=89 |issue=5 Pt 2 |pages=883–890 }}</ref><ref name=Thomas1998>{{cite journal |author=Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ |year=1998 |title=A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection |journal=Int J Epidemiol |volume=27 |issue=1 |pages=108–117 }}</ref> and prevalence in children (15%).<ref name=Fischler2007>{{cite journal |author=Fischler B |year=2007 |title=Hepatitis C virus infection |journal=Semin Fetal Neonatal Med |volume=12 |issue=3 |pages=168–173 }}</ref> |
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==Diagnosis== |
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Guidelines for the investigation of babies born to ] positive mothers have been published.<ref name=Resti2003>{{cite journal |author=Resti M, Bortolotti F, Vajro P, Maggiore G, Committee of Hepatology of the Italian Society of Pediatric Gastroenterology and Hepatology |year=2003 |title=Guidelines for the screening and follow-up of infants born to anti-HCV positive mothers |journal=Dig Liver Dis |volume=35 |issue=7 |pages=453–457 |doi=10.1016/s1590-8658(03)00217-2|pmid=12870728 }}</ref> |
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:In children born to hepatitis C virus ] positive but hepatitis C virus RNA negative mothers, the ] and hepatitis C virus antibodies should be investigated at 18-24 months of life. If both the alanine aminotransferase value is normal and hepatitis C virus antibody is not found, follow up should be interrupted.{{cn|date=November 2022}} |
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It has been estimated that 240,000 children in the United States have antibodies to the hepatitis C virus and that 68,000 to 100,000 are chronically infected.<ref name=Jonas2002>Jonas MM (2002) Children with hepatitis C. Hepatology 36(5 Suppl 1):S173-178</ref> In Australia it has been estimated that 125-250 children are infected vertically with HCV each year.<ref name=Kesson2002>Kesson AM (2002) Diagnosis and management of paediatric hepatitis C virus infection. J Paediatr Child Health 38(3):213-218</ref> |
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:In children born to hepatitis C virus RNA positive mothers, alanine aminotransferase and hepatitis C virus RNA should be investigated at 3 months of age. Of these{{cn|date=November 2022}} |
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;Transmission |
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::(1) hepatitis C virus RNA positive children should be considered infected if ] is confirmed by a second assay performed by the 12th month of age |
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In developed countries transmission around the time of birth is now the leading cause of HCV infection in children. All genotypes appear to have the same risk of transmission. In the absence of virus in the mother's blood transmission seems to be rare.<ref name=Thomas1998>{{cite journal |author=Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ |year=1998 |title=A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection |journal=Int J Epidemiol |volume=27 |issue=1 |pages=108–117}}</ref> |
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Factors associated with an increased rate of infection include membrane rupture of longer than 6 hours before delivery and procedures exposing the infant to maternal blood.<ref name=Indolfi2009>{{cite journal |author=Indolfi G, Resti M |year=2009 |title=Perinatal transmission of hepatitis C virus infection |journal=J Med Virol |volume=81 |issue=5 |pages=836–843 |doi=10.1002/jmv.21437}}</ref> Caesarean sections are not recommended. Transmission is 2- to 4-fold higher in women coinfected with ].<ref name=Jain2007>Jain S, Goharkhay N, Saade G, Hankins GD, Anderson GD (2007) Hepatitis C in pregnancy. Am J Perinatol 24(4):251-256</ref> |
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;Breast feeding |
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Breast feeding is considered safe if the nipples are not damaged. |
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;Subsequent pregnancies |
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Infection around the time of birth in one child does not increase the risk in a subsequent pregnancy. |
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;Antenatal screening |
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This has been considered in the UK but expert opinion is currently against it.<ref name=Pembrey2003>Pembrey L, Newell ML, Peckham C (2003) Is there a case for hepatitis C infection screening in the antenatal period? J Med Screen 10(4):161-168</ref> |
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==Clinical course in pregnancy== |
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Acute hepatitis C is a rare event in pregnancy.<ref name=Floreani2013>Floreani A (2013) Hepatitis C and pregnancy. World J Gastroenterol 19(40):6714-6720</ref> |
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In chronic cases a significant reduction in mean alanine aminotransferase levels may occur albeit with a rebound during the postpartum period. The viral RNA levels may rise toward the end of pregnancy. |
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] counts may be lower than normal in ~10% of cases.<ref name=Monteith2013>Monteith C, Ainle FN, Cooley S, Lambert JS, Kelleher B, Jackson V, Eogan M (2013) Hepatitis C virus-associated thrombocytopenia in pregnancy: impact upon multidisciplinary care provision. J Perinat Med 4:1-4 doi: 10.1515/jpm-2013-0080</ref> |
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There is an increased risk of cholestasis during pregnancy.<ref name=Locatelli1999>Locatelli A, Roncaglia N, Arreghini A, Bellini P, Vergani P, Ghidini A (1999) Hepatitis C virus infection is associated with a higher incidence of cholestasis of pregnancy. Br J Obstet Gynaecol 106(5): 498–500</ref> |
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There is no increased risk of miscarriage in chronic carriers but there is an increased risk of preterm birth, low birth weight and congenital anomalies.<ref name=Connell2011>Connell LE, Salihu HM, Salemi JL, August EM, Weldeselasse H, Mbah AK (2011) Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes. Liver Int 31(8):1163-1170 doi: 10.1111/j.1478-3231.2011.02556.x </ref> |
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The ] recommendations state that ] does not appear to significantly increase the risk of vertical transmission but that women in whom this proceedure is being carried out upon should be warned of this possibility.<ref name=Davies2003>Davies G ''et al'' Society of Obstetricians and Gynaecologists of Canada (2003) Amniocentesis and women with hepatitis B, hepatitis C, or human immunodeficiency virus. J Obstet Gynaecol Can 25:145-48, 149-52</ref> Other non invasive methods should be used in preference where possible. If amniocentesis is required every effort should be made to avoid penetration of the ]. |
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It is also recommended that pregnant women with Hepatitis C should avoid ] and ]. Vaccination for Hepatitis A and/or B should be carried out in accordance with the usual local guidelines. |
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==Clinical course in children== |
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HCV infection is frequently found in children who have previously been presumed to have non-A, non-B hepatitis and cryptogenic liver disease.<ref name=González-Peralta1997>{{cite journal |author=González-Peralta RP |year=1997 |title=Hepatitis C virus infection in pediatric patients |journal=Clin Liver Dis |volume=1 |issue=3 |pages=691–705 }}</ref> The presentation in childhood may be asymptomatic or with elevated liver function tests.<ref name=Suskind2004>{{cite journal |author=Suskind DL, Rosenthal P |title=Chronic viral hepatitis |journal=Adolesc Med Clin |volume=15 |issue=1|pages=145–58, x-xi }}</ref> While infection is commonly asymptomatic both ] with liver failure and ] may occur in childhood. |
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Children tend to have a lower viral load, lower alanine transferase values and milder histological derangement compared to adults with chronic hepatitis C.<ref name=Sibal2002>Sibal A, Mishra D, Arora M (2002) Hepatitis C in childhood. J Indian Med Assoc 100(2):93-98</ref> |
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The prognosis for those infected by blood transfusion or perinatally appears to be worse than for those without known risk factors.<ref name=Broide2006>Broide E, Kimchi NA, Scapa E (2006) Chronic hepatitis C infection in children. Minerva Gastroenterol Dietol 52(2):187-193</ref> |
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==Diagnosis in neonates and infants== |
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Guidelines for the investigation of babies born to hepatitis C positive mothers have been published.<ref name=Resti2003>{{cite journal |author=Resti M, Bortolotti F, Vajro P, Maggiore G, Committee of Hepatology of the Italian Society of Pediatric Gastroenterology and Hepatology |year=2003 |title=Guidelines for the screening and follow-up of infants born to anti-HCV positive mothers |journal=Dig Liver Dis |volume=35 |issue=7 |pages=453–457}}</ref> |
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:In children born to hepatitis C virus antibody positive but hepatitis C virus RNA negative mothers, the ] and hepatitis C virus antibodies should be investigated at 18-24 months of life. If both the alanine aminotransferase value is normal and hepatitis C virus antibody is not found, follow up should be interrupted. |
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:In children born to hepatitis C virus RNA positive mothers, alanine aminotransferase and hepatitis C virus RNA should be investigated at 3 months of age. Of these |
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::(1) hepatitis C virus RNA positive children should be considered infected if viremia is confirmed by a second assay performed by the 12th month of age |
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::(2) hepatitis C virus RNA negative children with abnormal alanine aminotransferase should be tested again for viremia at 6-12 months and for antibodies to the hepatitis C virus at 18 months |
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::(2) hepatitis C virus RNA negative children with abnormal alanine aminotransferase should be tested again for viremia at 6-12 months and for antibodies to the hepatitis C virus at 18 months |
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::(3) hepatitis C virus RNA negative children with normal alanine aminotransferase should be tested for antibodies to the hepatitis C virus and have their alanine aminotransferase reestimated at 18-24 months. They should be considered non infected if both the alanine aminotransferase is normal and the antibody levels to the hepatitis C virus are undetectable. |
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::(3) hepatitis C virus RNA negative children with normal alanine aminotransferase should be tested for antibodies to the hepatitis C virus and have their alanine aminotransferase reestimated at 18-24 months. They should be considered non infected if both the alanine aminotransferase is normal and the antibody levels to the hepatitis C virus are undetectable. |
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:The presence of anti hepatitis C virus antibody beyond the 18th month of age in a never viremic child with normal alanine aminotransferase is likely consistent with past hepatitis C virus infection. |
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:The presence of anti hepatitis C virus antibody beyond the 18th month of age in a never viremic child with normal alanine aminotransferase is likely consistent with past hepatitis C virus infection.{{cn|date=November 2022}} |
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==Treatment== |
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==Treatment== |
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Treatment of children has been with ] and ].<ref name=Hu2010>{{cite journal |vauthors=Hu J, Doucette K, Hartling L, Tjosvold L, Robinson J |title=Treatment of hepatitis C in children: a systematic review |journal=PLOS ONE |date=Jul 13, 2010 |volume=5 |issue=7 |pages=e11542 |doi=10.1371/journal.pone.0011542 |pmid=20644626 |pmc=2903479 |bibcode=2010PLoSO...511542H |doi-access=free }}</ref> The response to treatment is similar to that in adults.<ref name=Serranti2011>{{cite journal |vauthors=Serranti D, Buonsenso D, Ceccarelli M, Gargiullo L, Ranno O, Valentini P |year=2011 |title=Pediatric hepatitis C infection: to treat or not to treat...what's the best for the child? |journal=Eur Rev Med Pharmacol Sci |volume=15 |issue=9 |pages=1057–1067|pmid=22013729 }}</ref> It shows a similar dependence on the genotype. Recurrence after ] is universal and the outcomes after transplant are usually poor.<ref name=Rumbo2006>{{cite journal |vauthors=Rumbo C, Fawaz RL, Emre SH, Suchy FJ, Kerkar N, Morotti RA, Shneider BL |year=2006 |title=Hepatitis C in children: a quaternary referral center perspective |journal=J Pediatr Gastroenterol Nutr |volume=43 |issue=2 |pages=209–216 |doi=10.1097/01.mpg.0000228117.52229.32|pmid=16877987 |s2cid=38432144 |doi-access=free }}</ref> |
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In children treatment should be initiated within 12 weeks of the detection of the viral RNA if viral clearance has not occurred within this time.<ref name=Lagging2012>{{cite journal |vauthors=Lagging M, Duberg AS, Wejstål R, Weiland O, Lindh M, Aleman S, Josephson F, ((Swedish Consensus Group)) |year=2012 |title=Treatment of hepatitis C virus infection in adults and children: updated Swedish consensus recommendations |journal=Scand J Infect Dis |volume=44 |issue=7 |pages=502–521 |doi=10.3109/00365548.2012.669045 |pmid=26624849 |pmc=4732459 }}</ref> Given the difficulties with establishing a diagnosis of hepatitis C infection in infancy, this recommendation does not apply to infants.{{cn|date=August 2022}} |
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;Pregnancy |
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Currently treatment for hepatitis C during pregnancy is not recommended as the interferon and ribavirin combination is contraindicated during pregnancy. |
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Although interferon alone appears to be relatively safe in pregnancy before using it a clear and compelling case should be made for its use. Given that pregnancy is of limited duration and that is does not seem to affect the natural history of Hepatitis C infection it seems unlikely that interferon should be used during pregnancy and that treatment should be deferred until after delivery. |
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Ribavirin is absolutely contraindicated during pregnancy as it is highly teratogenic. |
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;Children |
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Treatment of children has been with ] and ].<ref name=Hu2010>{{cite journal |author=Hu J, Doucette K, Hartling L, Tjosvold L, Robinson J |year=2010 |title=Treatment of hepatitis C in children: a systematic review |journal=PLoS One |date=2010 Jul 13 |volume=5 |issue=7 |pages=e11542 |doi=10.1371/journal.pone.0011542 }}</ref> In general children tolerate the treatment well.<ref name=Rao2005>Rao GS, Molleston JP (2005) Children with hepatitis C. Curr Gastroenterol Rep 7(1):37-44</ref> The response to treatment is similar to that in adults.<ref name=Serranti2011>{{cite journal |author=Serranti D, Buonsenso D, Ceccarelli M, Gargiullo L, Ranno O, Valentini P |year=2011 |title=Pediatric hepatitis C infection: to treat or not to treat...what's the best for the child? |journal=Eur Rev Med Pharmacol Sci |volume=15 |issue=9 |pages=1057–1067}}</ref> It shows a similar dependence on the genotype. Recurrence after transplant is universal and the outcomes after transplant is usually poor.<ref name=Rumbo2006>{{cite journal |author=Rumbo C, Fawaz RL, Emre SH, Suchy FJ, Kerkar N, Morotti RA, Shneider BL |year=2006 |title=Hepatitis C in children: a quaternary referral center perspective |journal=J Pediatr Gastroenterol Nutr |volume=43 |issue=2 |pages=209–216 }}</ref> |
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Treatment with inferferon alone produces a response rate of ~40%.<ref name=Lacaille2002>Lacaille F (2002) Chronic hepatitis C virus infection in children. Arch Pediatr 9(5):539-542</ref> |
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In children treatment should be initiated within 12 weeks of the detection of the viral RNA if viral clearance has not not occurred within this time.<ref name=Lagging2012>{{cite journal |author=Lagging M, Duberg AS, Wejstål R, Weiland O, Lindh M, Aleman S, Josephson F; Swedish Consensus Group |year=2012 |title=Treatment of hepatitis C virus infection in adults and children: updated Swedish consensus recommendations |journal=Scand J Infect Dis |volume=44 |issue=7 |pages=502–521 |doi=10.3109/00365548.2012.669045 }}</ref> Given the difficulties with establishing a diagnosis of hepatitis C infection in infancy, this recommendation does not apply to infants. |
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Both pegylated interferon and ribavirin are unsuitable for use in pregnancy and infancy: newer methods of treatment are urgently required. |
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Both ] and ] are unsuitable for use in pregnancy and infancy: newer methods of treatment are urgently required.{{cn|date=August 2022}} |
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==References== |
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==References== |
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{{Pregnancy}} |
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In children treatment should be initiated within 12 weeks of the detection of the viral RNA if viral clearance has not occurred within this time. Given the difficulties with establishing a diagnosis of hepatitis C infection in infancy, this recommendation does not apply to infants.