Vertical Transmission of Hepatitis C in Opioid-Using Mothers

Vertical transmission of hepatitis C occurs when a pregnant woman with chronic hepatitis C (HCV) infection transmits the virus to her baby during pregnancy or at the time of birth. Whilst vertical transmission of HCV is not common, the increasing numbers of women of childbearing age who are infected with HCV, many with recent injection opioid use, makes this a clinically significant issue. Pregnancy provides a unique opportunity to identify HHC in women, plan for tests of infant infection, and to commence effective, well-tolerated and curative treatment with DAAs soon after delivery. The greatest preventable harm would be losing these families of view between the antenatal period, time of delivery and the paediatric follow-up appointments.

However, all of this can change in an instant. Holding a baby in your arms for the very first time can change a mother’s life. The bond and love that a mother has for her child is unlike anything else. This experience can inspire a mother to make changes to her life including things she never thought she could do in order to provide the best life for her child. With appropriate medical and social work input, a mother can tackle hepatitis C and tackle drug and alcohol misuse in order to be there for their child. With support, a mother can recover from both hepatitis C and any drug or alcohol addiction in order to provide the best start in life for their child.

Why It Matters

There is growing evidence that the proportion of HCV infection occurring in younger individuals is increasing, with the majority of new HCV infections due to injection drug use. Therefore, it is increasingly likely that women with HCV will become pregnant requiring antenatal care to be a key point for detection and planning for prevention and/or treatment of HCV. Many individuals with chronic HCV are asymptomatic for years and may not have come forward for testing unless providers offer screening to their patients. Pregnancy-related screening represents one of the few opportunities for these individuals to be offered HCV testing.

Vertical transmission is rare; however, the long-term consequences of missing a case of early infection can be severe. Individuals with active HCV infection are the only ones who can potentially transmit infection to an infant. While most individuals with chronic HCV infection are actively infected and very few will transmit infection to their infant, for those infants who do become infected, missed cases of early infection can lead to years of silent chronic hepatitis C followed by severe liver inflammation, cirrhosis and hepatocellular carcinoma. Identification of early infection provides the opportunity for appropriate monitoring of sequelae and potential cure in the future.

A practical number clinicians can remember

The risk of mother to child transmission of HCV has been reported to be in the single digits in studies where mother to child transmission of HCV has been detected. The risk may be increased in women with poorly controlled HIV infection and high levels of HCV viral load. There is no vaccine to prevent HCV infection. There is no medication shown to be safe in pregnancy to reduce the risk of mother to child transmission of HCV. A systems approach would be the best strategy to address mother to child transmission of HCV, starting with early diagnosis of HCV infection in women, decreasing preventable exposures to mother and baby during delivery, and appropriate testing and follow-up of children until the child is confirmed to be infected or excluded from risk of infection.

For women who use opioids, pregnancy presents an opportunity for frequent contact with healthcare and social service providers over several months to address medical and psychosocial needs associated with opioid use disorder and other medical and treatment needs, as well as housing, nutrition and follow-up with the newborn after hospital discharge. This contact can occur through a variety of settings and programs such as prenatal clinics, medication-assisted treatment (MAT) programs and social support programs, as well as through the hospital-based delivery unit. All of these points of contact need to be coordinated to address the mother’s and newborn’s medical and substance use treatment needs and their mental health needs.

Screening tests are not administered in a timely manner or results are not reviewed. For a variety of reasons including lack of transportation, uneven phone access, stigma, custody disputes and poor transition between obstetric and pediatric healthcare providers, many newborns do not receive the tests they need. As a result, the early detection of infection and disease in the baby is missed, and the trust that families have in their healthcare providers is eroded.

Public health impact extends beyond a single pregnancy

It is crucial to identify and treat the HCV infection in women of childbearing age to prevent long-term consequences of chronic liver disease and future perinatal exposures. While initial concerns were the side effects and incomplete efficacy for treating HCV infection in nonpregnant women, current HCV therapy achieves cure rates greater than 95% in a short treatment course. Each cured mother and child reduces transmission of HCV to partners, children and other contacts in the community, which can be further reduced and possibly eliminated along with transmission of HIV, hepatitis C and injection drug equipment sharing through the use of harm reduction strategies as well as evidence-based treatment of opioid use disorder.

Who It Affects

The new guidelines affect people who are pregnant with HCV infection, as well as their children. A history of opioid injection at least once in a person’s lifetime is a major risk factor for HCV transmission. However, it is important that we not make assumptions about people’s behavior, and always provide respectful and quality care to individuals with a history of opioid use.

Patients and families**

The challenges experienced by families with children with a parent who uses substances may manifest differently than those experienced by families who are not affected by parental substance use. Families may experience unique combinations of medical and psychosocial challenges during the prenatal and pediatric periods that affect access to and quality of health care. For example, housing instability and food insecurity, intimate partner violence, parental depression and anxiety, and limited access to quality child care may all affect these families. Many parents are afraid that if they disclose their substance use during the prenatal period or with their young child, they will be punished and lose custody of their children. In clinical practice with these families, Trauma-informed, non-judgmental clinical practice is not an optional nice extra, but rather a core clinical competency.

Children of mothers with risk for HCV infection require a plan for testing and an educational process. Infants of mothers with HCV infection have the potential of transferring maternal antibody to the infant and can confuse the diagnosis in the first few months of life. The parents of these children and their families need a clear explanation of the tests; a copy of the testing plan written and explained to them; and reminders to them as to what test is going to be administered; how and when they will receive their results; and what they are supposed to do in the case of positive or unclear results.

Clinicians across multiple disciplines**

Follow up to follow up for women with HCV infection follow’s gaps between obstetric, addiction, primary care and pediatric teams. Obstetric teams need to order the prenatal HCV screening test and confirm active HCV infection in the woman. Addiction specialists and harm reduction programs and organizations can increase linkage to care and support safe practices. Pediatric teams need to know the schedule for testing children born to HCV infected women and what those test results mean in terms of action. Family physicians can play a major role in the postpartum period to initiate curative therapy for women with HCV infection.

Health systems, payers, and public health**

Policies and practices of hospitals and clinics can also have an impact on pregnant women and their children. Decisions made by hospital administrators and clinical staff can affect whether or not tests for HCV are ordered early enough in a woman’s pregnancy, whether her doctors have access to the results of those tests to determine whether or not she is actively infected with the virus, and whether tests for HCV are ordered for her baby. Decisions regarding the usability of EMRs, public health reporting, and referrals for treatment and other services for individuals with HCV can also affect whether exposed infants receive monitoring for HCV. The policies of health plans and other payers can affect whether or not individuals have access to effective medicines to cure HCV as well as other supportive services that ensure all of a patient’s medical providers have the appropriate information about a patient’s HCV infection and that she has appropriate access to all of her medical care.

Administrative barriers can delay cure. Patients/individuals receiving cure in the obstetric setting may encounter several barriers before or at time of delivery, including multiple specialist visits to determine best course of treatment, lengthy prior authorization, or delays in treatment until patient is sober. These administrative obstacles can add to an already chaotic and overwhelming postpartum experience and delay detection of infection symptoms for years.

What Changes

While new drugs and updated policies are in the works to address the challenges of perinatal HCV, there are many steps that health systems and clinicians can take in the interim to improve the care of HCV-infected women and their infants. A good perinatal HCV program includes HCV screening of women of childbearing age, appropriate transitions in care between health care providers, and a plan and procedure for testing infants for HCV. But let’s not forget the ultimate goal: a postpartum cure for HCV infection.

1) Make screening routine early in every pregnancy

All pregnant women should receive universal screening for hepatitis C as part of their prenatal care, ideally at the first prenatal visit. Benefits of universal screening compared with risk-based screening include reduced stigma and improved detection, because the need to rely on risk disclosure is eliminated. Clinical judgment and guidance from organizations in one’s locality then can help providers decide whether to offer repeat testing to women with ongoing risk factors for HCV infection (e.g., injection drug use, a partner with HCV infection).

2) Make counseling consistent and applicable. If you continuously tell families the same general messages, they are unlikely to implement any of the advice.

Healthcare providers should provide patients with full and balanced counselling about their HCV infection. Women with HCV infection should be counselled by their healthcare providers, partners and family members that they will be well informed about what HCV infection means for them and their baby and what to expect after delivery. Women with HCV infection and their partners should be informed that the majority of women with chronic HCV will not transmit HCV to their babies, that only active HCV infection can be transmitted and that there is no indication for the routine use of antiviral treatment of HCV in pregnancy in most settings. Importantly, women should be informed that effective treatment and cure of HCV are available after delivery.

Families with a mother or other family member who has HCV should receive accurate and supportive information about expressing and giving breast milk. HCV is not efficiently transmitted through human milk, except for the usual precautions to avoid transmission of HCV to nipple skin if cracked or bleeding. Mothers with HCV and their babies should have the option to continue to breastfeed or to begin to breastfeed. In addition, women with HCV and their families may want to know about precautions to avoid exposure to blood in the home from other family members and about ways to avoid exposure to blood when shaving or brushing their teeth.

3) Safe birth and newborn care practices appropriate for ones community and avoiding unnecessary medical interventions.

HCV infection in itself is not an indication for a change in delivery practices and the majority of women with HCV infection would be suitable for routine obstetric management. HCV is not an indicated reason for cesarean delivery for prevention of maternal infection. However, in order to avoid potentially infectious maternal blood exposures to the infant and health care providers, avoidable blood exposures associated with internal fetal monitoring could be decreased unless specific indications for such monitoring exist. Decisions would need to be individualized for each woman and situation.

At time of delivery, we strive to give the family a clean handoff to their newborn and themselves after their baby is born. This is different than only charting in the medical history that the baby’s mother has a diagnosis of COVID-19. Ideally, we would document whether the newborn was tested for COVID-19 and the pediatrician’s scheduled follow-up. A simple and clear plan for discharge as well as the newborn’s schedule for testing would decrease confusion for all parties.

4) Test for infant and then follow up on the test.

Infant testing should reflect the biology of infant development and the realities of follow up in mother-infant pairs. Testing for maternal antibodies in early infancy is not very useful as maternal antibody levels decline before the infant’s age at testing. Thus, viral testing is indicated in early infancy, particularly in the first months of life. Many programs start with a nucleic acid test (NAT) for HCV RNA in the early months of life with subsequent testing with RNA or DNA based assays as indicated in later months of life. Alternatively, testing for antibodies to HCV at or after 18 months of age with confirmatory viral testing for any positive result is also acceptable.

The best test plan is the one that gets implemented. Implementing an early viral test during routine well-child care visits such as an annual well baby visit can help ensure that high-risk families do not miss crucial visits with their health care provider. Utilizing systems such as standing orders and electronic reminders to providers, nurses, families, or others can assist in ensuring timely viral testing. Including a care coordinator to track test results and notify families and public health of results and any necessary follow up can further streamline the process and help ensure that families receive test results and necessary public health follow up. In cases where a test is missed, having a plan to re-engage families rather than waiting for them to contact their provider or public health department can also be important.

Even for infant infection, the referral process should be supportive. Pediatric hepatitis expertise is unique and valuable but can be wasted if the family has to travel too far for the specialist or wait too long for an appointment. Consider how you might offer consults by telehealth, work in shared care with general pediatrics, and have a standard referral template. Even if the children will not require any immediate treatment for hepatitis in early childhood, the families want to know that and they want to be informed and educated as to what signs of liver disease to be monitoring for, as well as what plan might be in place for future initiation of antiviral treatment.

5) Prioritize postpartum cure with direct-acting antivirals

The postpartum period is a lost opportunity to potentially cure the mother and prevent the transmission of hepatitis C to her children. Direct-acting antiviral-based treatment for hepatitis C is now typically a short course of oral pills for a short duration with greater than 95% sustained virologic response rates in most adults. While safety data in pregnancy are still somewhat limited, treatment is typically planned for the postpartum period and potentially timed around the decision to continue or stop breastfeeding depending on country and guidelines/recommendations.

Provide HCV treatment pre-delivery in order to avoid a postpartum drop-off in care for women. Develop a process to schedule the postpartum HCV treatment visit either prior to discharge or at the newborn follow-up visit. Plan for common barriers to care for pregnant and postpartum women such as transportation, childcare, insurance, mental health treatment and/or substance use treatment. For patients on medication for opioid use disorder, schedule HCV treatment appointments to coincide with visits for medication for opioid use disorder.

6) Integrate treatment of opioid use disorder and harm reduction strategies into your practice and policies.

Addressing opioid use disorder is critical when treating HCV to ensure successful treatment outcomes and to prevent reinfection. Evidence-based treatment of opioid use disorder, such as opioid agonist therapy (OAT), has been shown to reduce the risk of overdose and improve stability for individuals with substance use disorder. In addition to treatment, providing harm reduction services like syringe service programs (where legal and available), safer injection education, and naloxone distribution and education can prevent new HCV infections as well as other infectious diseases.

Greater rewards will be realized by investing in a trauma-informed approach rather than a punitive one. Nonpunitive treatment of women with a history of substance abuse increases open discussion of symptoms and problems, fosters good therapeutic relationships, and promotes return for scheduled postpartum visits and infant testing. Program design and staff training should include ways to decrease stigma, promote respectful communication, and maintain confidentiality.

7) Strengthen systems: reminders, registries, and accountability

Many programs find it most effective to treat perinatal HCV as a tracked care pathway and not just a lab result (i.e. a one-time finding in a woman’s medical record). In addition to putting the flagged pathway in the EHR and automatically ordering the lab test for the infant at the correct age, some programs have registries and track all exposed infants. Staff then knows who to contact to track down a woman who has a scheduled visit that she has missed. Programs also track metrics such as: percent of exposed infants have completed testing by age X.

Policy and coverage can enhance progress more quickly. Removing steps such as prior authorization where not indicated, covering postpartum prescribing of effective antiviral treatment by obstetricians and other primary care providers when indicated, and covering case management and care coordination can result in higher cure rates and lower long-term costs.

References:

https://www.cdc.gov/mmwr/volumes/66/wr/mm6642a3.htm https://pubmed.ncbi.nlm.nih.gov/31292149/