Charitha Gowda1,2, Stephanie Smith1, Linda Crim1, Katherine Moyer3, Pablo J Sánchez1,4,5, Jonathan R Honegger1,6. 1. Division of Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children's Hospital-The Ohio State University College of Medicine, Columbus, Ohio, USA. 2. Partners For Kids, Nationwide Children's Hospital, Columbus, Ohio, USA. 3. Division of Pediatric Infectious Diseases, Inova Children's Hospital, Falls Church, Virginia USA. 4. Division of Neonatology, Department of Pediatrics, Nationwide Children's Hospital-The Ohio State University College of Medicine, Columbus, Ohio, USA. 5. Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA. 6. Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Abstract
BACKGROUND: Most US children with perinatal hepatitis C virus (HCV) exposure fail to receive the recommended anti-HCV antibody test at age ≥18 months. Earlier testing for viral RNA might facilitate increased screening, but sensitivity of this approach has not been established. We hypothesized that modern HCV-RNA RT-PCR platforms would adequately detect infected infants. METHODS: Nationwide Children's Hospital electronic health records from 1/1/2008 to 30/6/2018 were reviewed to identify perinatally exposed infants tested by HCV-RNA RT-PCR at age 2-6 months. Diagnostic performance was determined using a composite case definition: (1) infected children had positive repeat HCV-RNA testing or positive anti-HCV at age ≥24 months; (2) uninfected children lacked these criteria and had negative anti-HCV at age ≥18 months. RESULTS: 770 perinatally exposed infants underwent HCV-RNA testing at age 2-6 months. Of these, 28 (3.6%) tested positive; viremia was confirmed in all who underwent repeat testing (n = 27). Among 742 infants with negative HCV-RNA results, 226 received follow-up anti-HCV testing at age ≥18 months, of whom 223 tested negative. Three children had low-positive anti-HCV results at age 18-24 months that were negative upon retesting after age 24 months, possibly indicating waning maternal antibodies. Using the composite case definitions, early HCV-RNA screening demonstrated sensitivity of 100% (87.5-100%, Wilson-Brown 95% CI) and specificity of 100% (98.3-100%). CONCLUSIONS: Modern HCV-RNA RT-PCR assays have excellent sensitivity for early diagnosis of perinatally acquired infection and could aid HCV surveillance given the substantial loss to follow-up at ≥18 months of age.
BACKGROUND: Most US children with perinatal hepatitis C virus (HCV) exposure fail to receive the recommended anti-HCV antibody test at age ≥18 months. Earlier testing for viral RNA might facilitate increased screening, but sensitivity of this approach has not been established. We hypothesized that modern HCV-RNA RT-PCR platforms would adequately detect infected infants. METHODS: Nationwide Children's Hospital electronic health records from 1/1/2008 to 30/6/2018 were reviewed to identify perinatally exposed infants tested by HCV-RNA RT-PCR at age 2-6 months. Diagnostic performance was determined using a composite case definition: (1) infected children had positive repeat HCV-RNA testing or positive anti-HCV at age ≥24 months; (2) uninfected children lacked these criteria and had negative anti-HCV at age ≥18 months. RESULTS: 770 perinatally exposed infants underwent HCV-RNA testing at age 2-6 months. Of these, 28 (3.6%) tested positive; viremia was confirmed in all who underwent repeat testing (n = 27). Among 742 infants with negative HCV-RNA results, 226 received follow-up anti-HCV testing at age ≥18 months, of whom 223 tested negative. Three children had low-positive anti-HCV results at age 18-24 months that were negative upon retesting after age 24 months, possibly indicating waning maternal antibodies. Using the composite case definitions, early HCV-RNA screening demonstrated sensitivity of 100% (87.5-100%, Wilson-Brown 95% CI) and specificity of 100% (98.3-100%). CONCLUSIONS: Modern HCV-RNA RT-PCR assays have excellent sensitivity for early diagnosis of perinatally acquired infection and could aid HCV surveillance given the substantial loss to follow-up at ≥18 months of age.
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