CDC's 2023 Recommendations for Hepatitis C Testing of Infants Exposed Before Birth

Eliminating hepatitis C is a national priority, and infants are being missed. From 2010 to 2021, acute and chronic hepatitis C virus (HCV) infections rose in the United States. Acute infections more than tripled among people of reproductive age: from 0.8 to 2.5 per 100,000 among those aged 20–29, and from 0.6 to 3.5 among those aged 30–39, closely tied to the opioid crisis. As infections during pregnancy rise, so do infections passed to babies: about 6%–7% of infants exposed during pregnancy or delivery acquire HCV. A cure, direct-acting antiviral (DAA) treatment, is FDA-approved from age 3, yet many infected children are never tested or linked to care.

Rates of laboratory-confirmed acute hepatitis C by age group, United States, 2006–2021. CDC.

Why a new approach

In 2020 CDC recommended universal hepatitis C screening for adults, including during every pregnancy. For exposed children, the standard was an antibody test at 18 months or older, because antibodies passed from the mother can persist until then. But that strategy was missing most of them:

• in a review of studies, a median of only 30.1% of exposed children were tested, and about 70% of those aged 18 months or older went untested; one surveillance study found just 16% tested;
• far more families attend well-child visits at 2–6 months than at 18 months;
• modern nucleic acid tests (NATs) for HCV RNA are highly sensitive and specific from age 2 months: one test at 2–6 months is enough, with a detectable result confirming infection and an undetectable one ruling it out;
• in treatment studies, a median 98.1% of children aged 3–17 with chronic HCV were cured.

A CDC economic model compared strategies. Testing known exposed infants with a NAT at 2–6 months was the only strategy that both saved money and improved health, saving about $469,671 a year nationally (assuming 3.6 million births, 0.64% to people with HCV) while diagnosing more children and preventing liver disease. Testing every infant regardless of exposure improved outcomes but cost $38 million to $129 million more a year.

The review also weighed harms, most often confusion over results (intermittent virus, false positives and negatives), cost and stigma, and concluded the benefits outweigh them.

The four recommendations

CDC recommends testing all infants and children born to a pregnant person with current (detectable HCV RNA) or probable (reactive antibody, RNA result unavailable) HCV infection:

1. Test at 2–6 months with a NAT for HCV RNA.
2. Refer every infant or child with detectable HCV RNA to a provider with expertise in pediatric hepatitis C.
3. No further follow-up is needed for an undetectable HCV RNA result at or after 2 months, unless clinically warranted.
4. Catch up exposed children not yet tested: a NAT for HCV RNA at 7–17 months; at 18 months or older, an antibody test with automatic ("reflex") RNA testing if it is reactive.

Testing algorithm for perinatally exposed infants, 2023. CDC.

Testing algorithm for exposed children aged 18 months or older not tested before. CDC.

Other situations

The recommendations did not directly assess children whose mothers' status is unknown, but testing (from 2 months by NAT, or from 18 months by antibody with reflex) would benefit:

• siblings of children with perinatal exposure born to the same parent, unless the parent was known to be HCV-negative in the earlier pregnancy;
• children separated from their birth parent, such as those in foster care or safely surrendered at birth;
• infants whose mother was at risk of acute infection during pregnancy, such as through injection drug use, and wasn't tested near delivery.

Follow-up and reporting

• Children with detectable HCV RNA at or after 2 months should be managed with a pediatric hepatitis C expert and retested before treatment to confirm chronic infection; treatment can start at age 3 (AASLD-IDSA guidance).
• Parents can be reassured when a child has undetectable RNA at 2 months or older, a nonreactive antibody test at 18 months or older, or a reactive antibody with undetectable RNA (likely past transmission or leftover maternal antibody, but no current infection). Retesting is reasonable if signs of hepatitis appear later.
• Report perinatal hepatitis C cases to state or local health departments.

How this differs from other guidance

As of 2023, AASLD-IDSA, NASPGHAN and the American Academy of Pediatrics recommend antibody testing at 18 months or older (with RNA testing at 2 months or later in some cases), and the American Academy of Family Physicians two RNA tests at 2–6 months or an antibody test at 15 months or older. CDC chose the earlier window because of rising pediatric hepatitis C, high loss to follow-up, and the effectiveness and cost-effectiveness of early RNA testing.

Looking ahead

If DAA treatment becomes approved and widely used in pregnancy, fewer babies will be infected. More is needed on the prevalence of HCV in pregnancy, the natural history of perinatal infection, and why exposed children aren't tested or referred, along with support for health department programmes and for educating pediatric providers about testing, treatment, stigma, counselling and the safety of breastfeeding.

Sources

• Panagiotakopoulos L, Sandul AL, Conners EE, Foster MA, Nelson NP, Wester C. "CDC Recommendations for Hepatitis C Testing Among Perinatally Exposed Infants and Children — United States, 2023," MMWR Recommendations and Reports 72(4). https://www.cdc.gov/mmwr/volumes/72/rr/rr7204a1.htm
• The original's social-media graphic, built on a stock photograph, is not reproduced here.