This is a secondary analysis of a multicenter observational study of HCV in pregnancy [2]. Gravid individuals were eligible if they were found to be antibody-positive for HCV. To evaluate the predictive ability of early HCV PCR testing, only infants with both 2–6-month HCV PCR and ≥18-month HCV antibody or PCR results were included. We calculated sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values. As defined in our previous work, perinatal transmission of HCV was defined as either an infant who demonstrated HCV RNA at age 2–6 months or was found to be HCV RNA or antibody positive at 18–24 months of life. Sensitivity was defined as the proportion of children who demonstrated anti-HCV antibodies and/or were PCR-positive at ≥18 months and were PCR-positive at 2–6 months. Specificity was defined as the proportion of infants who were anti-HCV or PCR-negative at ≥18 months and were PCR-negative at 2–6 months. Confidence intervals (CIs) for specificity and sensitivity were calculated based on the Wilson score method and for likelihood ratios based on bootstrapping methods [15].

Of 772 children with perinatal HCV exposure, 333 (43%) had HCV laboratory results at both 2–6 months and ≥18 months (Figure 1). Of those 333 children, 13 (4%) had a positive PCR test at 2–6 months, of whom 13 were confirmed HCV-positive at ≥18 months. Of the remaining 320 children with a negative PCR test at 2–6 months, 318 were confirmed to be anti-HCV–negative and 2 were anti-HCV–positive at ≥18 months. These 2 children were PCR-negative at 18 months. Thus, the specificity and sensitivity of early postnatal PCR testing was 100% (95% CI, 98.8%–100%) and 86.7% (95% CI, 62.1%–96.3%), respectively. Values were as follows: positive likelihood ratio, infinity (97.1–infinity); negative likelihood ratio, 0.13 (0–0.34); positive predictive value, 100% (77.2%–100%); negative predictive value, 99.4% (97.8%–99.8%). A post hoc sensitivity analysis was performed that included the 2 children who were anti-HCV–positive and PCR-negative as part of the HCV-negative group, as they clinically would not require treatment for HCV. This post hoc analysis yielded a sensitivity of 100% (95% CI, 77.2%–100.0%) and specificity of 100% (95% CI, 98.8%–100.0%).

Screening guidelines for children exposed to HCV have recently changed, supported by a single but compelling study. The previous study conducted at a children’s hospital showed that a single PCR test for HCV RNA at 2–6 months had sensitivity of 100% (95% CI, 87.5%–100%) and specificity of 100% (95% CI, 98.3%–100%) for the diagnosis of perinatally acquired HCV [14]. Our findings enhance current CDC recommendations for children perinatally exposed to HCV. Our work demonstrates sensitivity and specificity similar to those estimated by Gowda et al for the ability of early HCV RNA testing to diagnose perinatally acquired HCV infection. By our case definitions, our sensitivity is less than previously demonstrated, but case definitions and clinical utility are likely different. We noted that 2 children in our cohort were HCV antibody–positive at 18 months but PCR-negative. We know that these antibody tests were performed at 18 months exactly, and no follow-up antibody was available to us. Additionally, no repeat PCR testing was available to lend insight. It is possible that the infants were exposed to RNA early, cleared the virus, and developed HCV antibody in response. Consistent with published experience, an alternative notion is that this could represent persistently circulating maternal antibody [14, 16]. Depending on the natural history, whether or not the antibody present at 18 months demonstrates perinatal transmission or persistent maternal antibody is debatable. Clinically, this distinction is insignificant given that in the absence of circulating RNA, no child in this cohort who required treatment for perinatal infection was missed using a single RNA test at 2–6 months. In addition, no child would have been prematurely dismissed from care based on the results of a 2–6-month PCR test. Future studies that focus on the fundamental differences in children, differences in perinatal exposures, or differences in long-term follow-up could shed light on the natural history of those children who were found to be RNA-negative at 2–6 months and HCV antibody–positive/RNA-negative at 18 months.

Though limited by sample size, bias due to loss to follow-up, and availability of complete testing for the entire cohort, our findings contribute evidence to substantiate the current screening recommendation for children perinatally exposed to HCV. Ideally, earlier identification of children with perinatally acquired HCV will lead to improved linkage to care and ultimately cure. Ongoing surveillance will be necessary to evaluate the impact of this screening strategy and contribution to the goal of HCV elimination by 2030.

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.