The baby looked perfect: healthy term male, weight at the 60th percentile, normal exam. The mother, a 26-year-old diagnosed with hepatitis C virus (HCV) infection during her pregnancy, looked alternately hopeful and horrified as I explained what implications her infection could have for her baby.
“Most babies will be fine,” I explained. “Of all mothers with hepatitis C infection, just under 6% will pass the infection on to their babies.” Transmission rates are twice as high in infants born to women with high HCV viral loads or those coinfected with HIV. The risk of transmission from women with undetectable HCV RNA is almost zero. Unfortunately, this mother did not fall into that category.
This scenario is increasingly common in exam rooms across the country. The Centers for Disease Control and Prevention (CDC) estimates that 3.5 million people in the United States are infected with HCV, but at least half do not know their infection status.Thanks in part to the heroin and prescription opioid epidemics, HCV infection is increasingly common among women of childbearing age. From 2009 to 2014, the prevalence of HCV infection among U.S. women giving birth nearly doubled, with the highest rates in Appalachian regions, according to the CDC. In Kentucky, where this mother and I live, HCV detection in women of childbearing age, defined as having a positive antibody or RNA test, increased more than 200% between 2009 and 2011, and the proportion of infants born to HCV-positive mothers increased 124%, according to the CDC.
Referrals to my group’s practice for perinatal HCV exposure have exploded: some weeks, we’ll see as many as ten exposed babies in our outpatient office.At that moment, however, I didn’t have time to be concerned about the numbers. My focus was one mother and her newborn baby.
“What if my baby is one of the unlucky ones who gets infected?” the mother asked, cuddling her infant. “What then?”
We know a lot about the course of hepatitis C in adults. An estimated 75%-86% of those infected will go on to develop chronic infection. Long-term sequelae include cirrhosis, liver failure, and hepatocellular carcinoma.
The course of HCV in children appears to be different. Twenty-five percent to 40% of vertically infected children will spontaneously clear their infection, most by 2 years of age. Occasionally, that might not happen until 7 years of age. Most who are chronically infected experience few symptoms, and fortunately cirrhosis and liver failure rarely present in childhood.
In a large cohort of Italian children, half of whom were thought to be infected perinatally, less than 2% progressed to decompensated cirrhosis after 10 years of infection.
According to the CDC, most children infected at birth “do well during childhood,” but more research is needed to understand the long-term effects of perinatal hepatitis C in children.
New antivirals have revolutionized the care of HCV-infected adults and now offer the hope of cure for up to 90%. None of these drugs are currently approved for use in children younger than 12 years, although clinical trials are underway. Because most cases of HCV in children are indolent, some children may not require treatment until adulthood.
July 28th was World Hepatitis Day and this year’s theme was Eliminate Hepatitis. To eliminate the problem of hepatitis C in children, pediatricians and others involved in the care of children need to get involved.
We need to know the scope of the problem
Since 2015, Kentucky has mandated reporting of all HCV-infected pregnant women and children through age 60 months, as well as all infants born to all HCV-infected women. At present though, there is substantial variability in state reporting requirements. We likely need a standardized case definition for perinatal HCV and national reporting criteria.
We need some clear guidance about testing during pregnancy
This should come from public health authorities, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists.Jonathan Mermin, MD, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, has said, “Women are screened throughout pregnancy for many conditions that threaten their health.An expectant mother at risk for hepatitis C deserves to be tested. Knowing her status is the only way she can access the best hepatitis care and treatment both for herself and her baby.”
Yet, routine hepatitis C testing is not recommended during pregnancy, in part because there are no established interventions to prevent mother-to-child transmission of HCV. Instead, women are to be screened for risk factors and tested if they are present. As we learned with hepatitis B and HIV, risk factor screening is hard and misses individuals who are infected.
We need to ensure that HCV-exposed infants are identified and followed appropriately.
In a study of HCV-exposed infants born to women in Philadelphia, 84% did not receive adequate testing for HCV infection. In human terms, 537 children were born to HCV-positive mothers during the study period and 4 of 84 (5%) children tested were found to be infected. Assuming that 5% of HCV-exposed infants will develop chronic infection, 23 additional children were undiagnosed and, therefore, were not being followed for potential sequelae.
HCV-infected mothers in this study were more likely than non-infected mothers to be socioeconomically disadvantaged specifically, unmarried, less educated, and publicly insured suggesting that access to care may have played a role. When you add in drug use as a common risk factor for HCV infection, it is easy to understand why some at-risk infants are lost to follow-up.
Investigators in the Philadelphia study suggested that there might be more to the story. They proposed that pediatricians might be unaware of the need for testing because they had not been alerted to the mother’s HCV status by the obstetrician, the birthing hospital, or the mother herself.
Finally, they theorized that many pediatricians “may be unaware or skeptical of the guidelines for testing children exposed to HCV.” This is a problem that we can solve.
I finished the visit with this mother by reassuring her that she could breastfeed her infant as planned as long as she did not have cracked or bleeding nipples. I also explained the schedule for testing. A 2002 National Institutes of Health consensus statement recommends that infants perinatally exposed to HCV have two HCV RNA tests between 2 and 6 months of age and/or be tested for HCV antibodies after 15 months.
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Practice Guidelines for Diagnosis and Management of Hepatitis C Infection in Infants, Children, and Adolescents recommend testing for HCV antibodies at 18 months of age (J Pediatr Gastroenterol Nutr. 2012 Jun;54:838-55).
If a family requests earlier testing, a serum HCV RNA test can be done as early as 2 months of age. If positive, NASPGHAN recommends testing after 12 months of age to evaluate for chronic infection.
My practice has adopted the National Institutes of Health consensus statement approach because many of the families we see experience significant anxiety about the diagnosis, and this mother was no exception. As noted in the expert guidelines, this was a situation in which “early exclusion of HCV infection is reassuring and may be worth the added expense.”
“So first test at 2 months?” she asked. “Until then, we can’t do anything but wait?”
It is estimated that there are 23,000 to 46,000 U.S. children living with HCV. The wait for pediatricians is over. HCV is a pediatric disease now, and we need to educate ourselves about diagnosis and management. A first step might be to begin asking expectant mothers and the mothers of newborns if they know their HCV status.