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In the United States, it is estimated that 1% to 4% of pregnant women are infected with hepatitis C virus, which carries approximately a 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of this document is to discuss the current evidence, provide updated recommendations regarding screening, review treatment, and address management of hepatitis C virus during pregnancy. The following are the Society for Maternal-Fetal Medicine’s recommendations: (1) We suggest that third trimester assessment of fetal growth may be performed, but antenatal testing is not indicated in the setting of hepatitis C virus diagnosis alone (GRADE 2C); (2) we suggest screening for viral hepatitis in patients with a diagnosis of intrahepatic cholestasis of pregnancy at an early gestational age or with high levels of bile acids (GRADE 2C); (3) we recommend that obstetrical providers screen all pregnant patients for hepatitis C virus by testing for anti–hepatitis C virus antibodies in every pregnancy (GRADE 1B); (4) we suggest that obstetrical care providers screen hepatitis C virus–positive pregnant patients for other sexually transmitted infections (if not done previously), including human immunodeficiency virus, syphilis, gonorrhea, chlamydia, and hepatitis B virus (GRADE 2C); (5) we recommend vaccination against hepatitis A and B viruses (if not immune) for patients with hepatitis C virus (GRADE 1B); (6) we recommend that direct-acting antiviral regimens only be initiated in the setting of a clinical trial during pregnancy and that people who become pregnant while taking a direct-acting antiviral should be counseled in a shared decision-making framework about the risks and benefits of continuation (GRADE 1C); (7) we suggest that if prenatal diagnostic testing is requested, patients are counseled that data regarding the risk of vertical transmission are reassuring but limited (GRADE 2C); (8) we recommend against cesarean delivery solely for the indication of hepatitis C virus (GRADE 1B); (9) we suggest that obstetrical care providers avoid internal fetal monitors and early artificial rupture of membranes when managing labor in patients with hepatitis C virus unless necessary in the course of management (ie, when unable to trace the fetal heart rate with external monitors and the alternative is proceeding with cesarean delivery) (GRADE 2B); (10) we recommend that hepatitis C virus status not alter standard breastfeeding counseling and recommendations unless nipples are cracked or bleeding (GRADE 1A).
A recent national multicenter prospective cohort study from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network estimated a seroprevalence of 0.24% among all women.
Because of concern for the increasing prevalence of HCV in pregnancy and its implications for pregnant patients and their newborns, updated guidelines for universal screening in pregnancy have been issued by the Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force (USPSTF).
US Preventive Services Task Force Screening for hepatitis C virus infection in adolescents and adults: US Preventive Services Task Force recommendation statement.
The Society for Maternal-Fetal Medicine (SMFM) endorses alignment with these recommendations.
The primary mode of HCV transmission is percutaneous exposure to blood from injection of illicit drugs. Other modes of transmission include vertical transmission (mother to child); sharing of contaminated devices for noninjection drug use; exposure to infected blood through occupational exposures, tattoo needles, or other means; and sexual intercourse (specifically increased in the setting of multiple partners).
Joint panel from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2020.
Two primary concerns related to HCV in pregnancy are addressed in this document: (1) effect of pregnancy on maternal disease progression and (2) effect of the disease on pregnancy outcomes, including mother-to-infant transmission of HCV.
What is the natural course of hepatitis C virus infection?
HCV can cause both acute and chronic hepatitis. The first 6 months after exposure to HCV is referred to as acute HCV infection. Acute HCV infection is asymptomatic in 75% of cases; when symptoms occur, they include abdominal pain, nausea, anorexia, jaundice, and malaise.
Those who do not clear the virus and do not receive treatment will develop chronic HCV infection. Chronic infection accounts for most HCV-associated morbidity and mortality. As with the acute stage of infection, chronic HCV infection is usually asymptomatic, although it can cause progressive liver damage. Without treatment, 15% to 30% of patients with chronic HCV infection develop cirrhosis within 20 years, although rates vary widely by study; 27% of those with cirrhosis develop hepatocellular carcinoma (HCC) within 10 years.
In comparison, among patients with cirrhosis treated with antiviral medications and who achieve a sustained virologic response (SVR), only 5% develop HCC within 10 years.
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators.
In addition, there is a clear causal relationship between chronic HCV infection and extrahepatic diseases, including cryoglobulinemic vasculitis, lymphoma, cardiovascular diseases, insulin resistance, and type 2 diabetes mellitus.
What is the impact of pregnancy on chronic hepatitis C?
Data regarding the impact of pregnancy on chronic HCV are mixed and inconclusive. Multiple studies have found that serum levels of alanine aminotransferase (ALT) typically decrease during the second and third trimesters of pregnancies complicated by HCV infection and then return to prepregnancy levels after delivery.
Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women.
In contrast, serum levels of HCV RNA may increase in infected patients during the second and third trimesters of pregnancy. A case-control study of 26 HCV-infected pregnant women compared with 12 HCV-infected nonpregnant women demonstrated an increase in HCV RNA among the pregnant women during the second and third trimesters.
In contrast, in an observational study of 65 HCV-positive women followed through pregnancy and after delivery, there were no changes in the viral load.
It is biologically plausible that HCV RNA levels could increase during pregnancy due to a relative alteration of the maternal immune response. Because hepatocellular damage caused by chronic HCV infection may be immune mediated rather than directly caused by viral cytotoxicity, alterations of the maternal immune response in pregnancy may reduce the amount of hepatocellular damage caused by HCV, which may account for the observed decrease in ALT levels.
Histologic evidence of the effects of pregnancy on HCV infection is also inconclusive. Some data suggest that pregnancy may be associated with a decrease in HCV-mediated hepatic injury. Di Martino et al
showed a beneficial effect of pregnancy on the progression of fibrosis, as determined by liver biopsy, in a retrospective cohort study of 157 pregnant women with chronic HCV infection. In particular, they found that a history of pregnancy was independently associated with a lower likelihood of fibrosis progression.
compared liver biopsy samples from 12 HCV-positive women obtained before and after delivery with samples from 12 nonpregnant HCV-positive women as controls. The mean period between initial and final biopsies was 4 years. During this time, 83% of pregnant patients showed deterioration in their necroinflammatory score, and 42% showed deterioration in their fibrosis score. In comparison, the rates for controls were 25% and 8%, respectively.
These conflicting data highlight a need for additional study of the progression of fibrosis during pregnancy.
What is the impact of hepatitis C virus on obstetrical and neonatal outcomes?
Although HCV infection is associated with both adverse maternal and neonatal outcomes, many confounding comorbidities in the pregnant population often complicate these associations. A population-based, retrospective cohort study from Washington state compared 506 HCV-positive pregnant women with 2022 HCV-negative pregnant controls. In multivariable analysis, after controlling for maternal age, race, tobacco use, alcohol use, drug use, and prenatal care usage, it was found that infection with HCV was associated with small-for-gestational-age infants, low birthweight of <2500 g, admission to the neonatal intensive care unit, and need for assisted ventilation.
Another population-based retrospective cohort study of all births in Florida compared 988 HCV-positive women with 1,669,370 controls. In multivariate analysis, after adjusting for maternal age, marital status, educational level, maternal race or ethnicity, tobacco use during pregnancy, drug abuse during pregnancy, and parity, it was found that HCV infection was associated with poor birth outcomes, including preterm birth and low birthweight.
A recent systematic review and meta-analysis, including these 2 studies and 5 others, reported that maternal HCV infection was associated with fetal growth restriction and low birthweight (Figure 1).
Based on these findings, we suggest that third trimester assessment of fetal growth may be performed, but antenatal testing is not indicated in the setting of HCV diagnosis alone (GRADE 2C).
Figure 1Meta-analysis of infants of hepatitis C virus–positive women
in addition to a population-based cohort study using the Nationwide Inpatient Sample, report higher rates of gestational diabetes in HCV-infected women than uninfected women.
this association was limited to women with excessive weight gain during pregnancy. In another population-based, retrospective cohort study, Salemi et al
found that maternal HCV infection was associated with infant feeding difficulties and other adverse neonatal outcomes, including cephalohematoma, brachial plexus injury, fetal distress, intraventricular hemorrhage, and neonatal seizures.
Intrahepatic cholestasis of pregnancy (ICP) is also more prevalent in patients with chronic HCV infection than in uninfected patients.
The incidence of ICP in the general obstetrical population is 0.2% to 2.5%, whereas the odds of developing ICP are 20-fold higher in HCV-infected pregnant women.
Given the increased risk of stillbirth associated with ICP, recognizing and diagnosing ICP in any pregnant woman is important. However, it is unclear whether ICP is more severe or associated with higher rates of stillbirth in the setting of HCV. We suggest screening for viral hepatitis in patients with a diagnosis of ICP at an early gestational age or with high levels of bile acids (GRADE 2C). We empirically suggest that this screening be performed if the diagnosis of ICP is made at <24 weeks of gestation or if bile acids are ≥100 μmol/L.
As of 2021, a multicenter, prospective observational cohort study is in progress to evaluate pregnancy outcomes of patients with HCV; it is anticipated that this study will answer many unresolved questions regarding HCV in pregnancy. Outcomes being studied include vertical transmission, preterm delivery, gestational diabetes, preeclampsia, cholestasis, and infant birthweight (ClinicalTrials.gov: NCT01959321).
What is the rate of vertical transmission of hepatitis C virus?
Vertical transmission refers to viral transmission from mother to infant during pregnancy, delivery, or the neonatal period. At present, vertical transmission of HCV is the leading cause of HCV infection in children.
One-third to one-half of mother-to-child transmission of HCV seems to occur in utero before the last month of pregnancy; the remaining cases of transmission are thought to occur either in the last month of pregnancy or during delivery.
published a meta-analysis examining rates of vertical transmission of HCV stratified by whether women were coinfected with HIV. Pooling the results of 17 studies of women with chronic HCV infection who were HIV-negative, the risk of vertical transmission was 5.8%. In contrast, based on the results of 8 studies, the risk of vertical transmission in HIV-positive women was almost doubled at 10.8%. The increased risk of vertical transmission in HIV-positive pregnant patients may be caused by increased HCV viral load resulting from HIV-mediated immunosuppression.
However, now that the use of combined active antiretroviral therapy in pregnant patients with HIV is common in developed countries, the risk of vertical transmission of HCV in coinfected patients seems to be lower (4%–8.5%).
included 15 studies with a total of 473 children born to women who were HCV antibody positive yet RNA negative. Only 1 of the 473 children was diagnosed with vertically acquired HCV infection. However, vertical transmission from HCV RNA–negative patients has been reported by others,
European Pediatric Hepatitis C Virus Network A significant sex--but not elective cesarean section--effect on mother-to-child transmission of hepatitis C virus infection.
In addition, whether the level of HCV viremia correlates with the risk of transmission has yet to be determined. Several studies have shown that higher viral loads correlate with an increased risk of transmission,
Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women.
Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1.
Importantly, these studies involved small numbers (3%–5%) of vertically infected infants born to patients who were HCV RNA positive or with anti-HCV antibodies. Further data will be critical in assessing the frequency of vertical transmission from HCV RNA–negative patients.
Screening
Who should be screened for hepatitis C virus during pregnancy?
Because the prevalence of HCV infection among women of childbearing age has increased by 161% in the last decade and because risk-based screening misses almost 50% of HCV cases, screening recommendations are changing to be more inclusive.
Similarly, emerging data suggest that 85% to 90% of neonates with HCV are not identified with the current strategies, thus impacting the ability to treat these infants.
Expected and actual case ascertainment and treatment rates for children infected with hepatitis C in Florida and the United States: epidemiologic evidence from statewide and nationwide surveys.
Importantly, a recent cost-analysis model demonstrated that universal prenatal HCV screening improved health outcomes of women with HCV infection and identification of neonates with infection and was cost-effective, even in areas with very low prevalence.
US Preventive Services Task Force Screening for hepatitis C virus infection in adolescents and adults: US Preventive Services Task Force recommendation statement.
The USPSTF specifically notes that pregnant individuals should be screened but does not recommend a screening frequency due to a paucity of data on which to base such recommendations. Early identification of patients who are HCV positive during pregnancy can potentially facilitate more efficient linkage to care and treatment in the postpartum period, as none of the antiviral therapies recommended for HCV infection are approved for use during pregnancy. The postpartum period is a critical time for patients to access curative therapy. In alignment with the recommendations from the CDC and the USPSTF and based on the data mentioned earlier, we recommend that obstetrical providers screen all pregnant patients for HCV by testing for anti-HCV antibodies in every pregnancy (GRADE 1B). The timing of when to screen during pregnancy is somewhat arbitrary; screening in the first trimester would theoretically bring the most patients to attention at the earliest time.
What is the ideal screening test for hepatitis C virus?
The diagnosis of HCV infection depends on the detection of anti-HCV antibodies and HCV RNA. Anti-HCV antibodies usually develop 2 to 6 months after exposure, during the acute phase of infection, and persist throughout life.
The standard screening test for HCV is an anti-HCV antibody test. A positive test result indicates one of the following: the patient has active HCV infection (acute or chronic), the patient has had a past infection that has resolved, or the result is a false positive.
Joint panel from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2020.
Thus, a positive antibody test result can indicate the patient is currently positive, was positive, or is negative. For this reason, a positive anti-HCV antibody result should be followed by a quantitative nucleic acid test for HCV RNA. The recombinant immunoblot assay is no longer available or recommended (Figure 2). If a patient who had a negative test result for HCV RNA within the past 6 months is newly found to be viremic, acute HCV infection is confirmed. If a patient with no previous testing for hepatitis C has a positive test result for both anti-HCV antibodies and HCV RNA, it is not possible based on the test results alone to distinguish acute from chronic HCV infection. If the anti-HCV antibody test result is positive and the HCV RNA test result is negative, distinguishing a false-positive antibody test from a previous infection requires testing for anti-HCV antibodies with a different antibody assay platform (such as polymerase chain reaction or immunoblot) (Figure 2).
Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention.
If the anti-HCV antibody test result on the different platform is positive, then the infection can be considered cleared (20% of all infections clear).
Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention.
The asterisk represents that HCV antibody assays vary according to their antigens, test platforms, and performance characteristics, so biologic false positivity is unlikely to be exhibited by more than one test when multiple tests are used on a single specimen. Note: repeat HCV RNA testing if the person tested is suspected of having HCV exposure within the past 6 months or has clinical evidence of HCV disease or if there is concern regarding the handling or storage of the test specimen. Modified from the Centers for Disease Control and Prevention, available at https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6218a5.htm?s_cid=mm6218a5_w#fig.
HCV, hepatitis C virus; RNA, ribonucleic acid.
Society for Maternal-Fetal Medicine. SMFM Consult Series #56: Hepatitis C in pregnancy. Am J Obstet Gynecol 2021.
Once hepatitis C is diagnosed, what additional evaluation should be performed?
Because there are no formalized pregnancy-specific guidelines for laboratory testing in HCV infection, SMFM has adapted guidelines from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) for pregnancy.
Joint panel from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2020.
For pregnant patients with confirmed active HCV infection, a quantitative HCV RNA test should be performed to determine the baseline viral load. Basic laboratory testing to evaluate the extent of liver disease should include the following laboratory tests: bilirubin, ALT, aspartate aminotransferase, albumin, platelet count, and prothrombin time. Testing for HCV genotype should also be performed if not done previously to help plan future treatment (Box).
Recommended laboratory tests for confirmed active HCV infection in pregnancy
•
Liver function tests (AST, ALT, bilirubin)
•
Albumin
•
Platelet count
•
Prothrombin time
•
Quantitative HCV RNA
•
HCV genotype (if not previously obtained)
•
STI screening (HIV, syphilis, gonorrhea, chlamydia, and HBV)
ALT, alanine aminotransferase; AST, aspartate aminotransferase; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; STI, sexually transmitted infection.
Society for Maternal-Fetal Medicine. SMFM Consult Series #56: Hepatitis C in pregnancy. Am J Obstet Gynecol 2021.
In light of common risk factors, we suggest that obstetrical care providers screen HCV-positive pregnant patients for other sexually transmitted infections (if not done previously), including HIV, syphilis, gonorrhea, chlamydia, and hepatitis B virus (HBV) (GRADE 2C). The CDC, IDSA, and AASLD recommend screening for HIV and HBV specifically in this scenario.
Joint panel from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2020.
HBV has overlapping risk factors for HCV and can lead to accelerated liver damage and adverse effects during pregnancy. Hepatitis A virus (HAV) infection can also worsen hepatic damage if present with HCV infection. Pregnant patients with HCV should be screened for immunity to HAV. The Advisory Committee on Immunization Practices recommends that patients with HCV infection who are found to be nonimmune to HBV or HAV be vaccinated against both of these infections,
which is safe to do during pregnancy. We recommend vaccination against HAV and HBV (if not immune) for patients with HCV (GRADE 1B).
What are the principles of medical management of hepatitis C virus?
Any woman who receives a diagnosis of HCV infection during pregnancy should ideally be referred to a specialist experienced in the management of hepatitis to establish long-term care.
HCV is a genetically diverse RNA virus; it has 6 different genotypes that affect the choice and efficacy of treatment regimens. The goal of treatment is to achieve SVR, defined as undetectable HCV RNA 12 to 24 weeks after completing treatment. Because 99% of patients who achieve SVR remain HCV RNA negative during long-term follow-up, treatment that achieves SVR is considered curative. In patients who do not have cirrhosis, SVR is associated with resolution of liver disease. In patients with cirrhosis, regression of hepatic fibrosis may be seen, and the risk of complications, such as hepatic failure, HCC, and portal hypertension, while still possible, is lower than in untreated individuals.
The use of even modest amounts of alcohol has been associated with progression of liver disease in patients with HCV. Thus, patients with HCV, including pregnant patients, should refrain from using alcohol.
For patients with advanced liver disease, dosage adjustments may be required for some medications. For patients with HCV who have normal hepatic function, dosage adjustments in most prescription and over-the-counter medications are not required. Patients do not need to avoid acetaminophen, although it is advisable to set a lower maximum daily dosage of 2 g rather than 4 g in patients with cirrhosis related to HCV.
Patients with HCV should receive counseling about transmission prevention, such as avoidance of sharing personal hygiene articles (eg, razors, nail clippers, scissors, toothbrushes) with close contacts and avoidance of needle sharing in the setting of intravenous drug use.
Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention.
Serial laboratory surveillance of liver function or serial viral load assessment during pregnancy in HCV-positive patients is generally not recommended. As discussed previously, serum levels of ALT tend to decrease during the second and third trimesters of pregnancy.
Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women.
Should hepatitis C virus be treated during pregnancy?
Currently, none of the antiviral therapies recommended for HCV infection are approved for use during pregnancy. Among nonpregnant women, according to guidelines released in 2016 by AASLD/ISDA, direct-acting antiviral (DAA) regimens are first-line treatments because they typically achieve SVR rates of >90%, are tolerated better than interferon-based regimens, and require a shorter duration of treatment.
Joint panel from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2020.
Specific treatment regimens are beyond the scope of this document but are based on genotype, presence of cirrhosis, and previous treatments. Treatment is recommended for all patients with chronic HCV infection, except those with short life expectancies that cannot be extended by treatment.
Joint panel from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2020.
Studies are limited on the effects of second-generation DAA therapy in pregnancy. There are no adequate human data regarding any of these antiviral medications, and safety data come entirely from animal reproduction studies. Due to the lack of human studies, no DAA therapy has yet been approved to treat HCV infection in pregnancy.
Given the availability of ribavirin-free DAA regimens that demonstrated high efficacy in nonpregnant adults and no adverse fetal effects in animal studies, the assessment of these regimens for use in pregnancy should be actively investigated. A phase 1 trial assessing ledipasvir plus sofosbuvir for the treatment of chronic HCV infection during pregnancy showed 100% cure rates, large declines in viral loads within 10 to 21 days of starting treatment, and no clinically meaningful adverse effects on the mother/infant dyad.
In the meantime, until more data exist, if a patient becomes pregnant while taking one of the DAA therapies, they should be counseled that animal data do not suggest teratogenic risk, but human data are lacking.
In these scenarios, shared decision-making regarding risks and benefits of cessation vs continuation should occur. We recommend that DAA regimens should be initiated only in the setting of a clinical trial during pregnancy and that people who become pregnant while taking a DAA should be counseled in a shared decision-making framework about the risks and benefits of continuation (GRADE 1C). Referral to a hepatologist or infectious disease specialist during pregnancy for patients with HCV may be considered because it can help to expedite therapy after pregnancy.
Methods to reduce vertical transmission
Is prenatal diagnostic testing safe in patients with hepatitis C virus?
Amniocentesis does not seem to increase the risk of vertical transmission, although this conclusion is based on small sample sizes and limited data that have not addressed the potential impact of viral load.
No association between amniocentesis and vertical transmission was found in a case-control study of 51 HCV-infected children that evaluated risk factors for vertical transmission or in a case series of 22 HCV-positive women who underwent amniocentesis.
No studies have been published on the risk of vertical transmission of HCV with other prenatal testing modalities, including chorionic villus sampling. We suggest that if prenatal diagnostic testing is requested, patients are counseled that data regarding the risk of vertical transmission are reassuring but limited (GRADE 2C). When the need or desire for diagnostic testing arises in patients with HCV, shared decision-making regarding the limited data should occur.
Does mode of delivery affect the risk of vertical transmission?
Vaginal delivery has not been shown to be a risk factor for vertical transmission of HCV. Cottrell et al
published a systematic review in 2013 that included 14 observational studies evaluating the association between mode of delivery and vertical transmission of HCV. Eleven studies compared the risk of transmission between vaginal and cesarean delivery without differentiating between elective and emergent cesarean deliveries; of these, 10 found no association between mode of delivery and transmission rate. Two studies specifically compared cesarean delivery before the onset of labor with vaginal or emergent (after onset of labor) cesarean delivery. There was no difference in the risk of vertical transmission according to mode of delivery in either of these 2 studies.
European Pediatric Hepatitis C Virus Network A significant sex--but not elective cesarean section--effect on mother-to-child transmission of hepatitis C virus infection.
Moreover, a 2011 meta-analysis of studies on HCV vertical transmission by mode of delivery found no significant difference (pooled odds ratio, 1.1; 95% CI, 0.45–2.67). This meta-analysis did not distinguish between elective and emergent cesarean deliveries and included 8 studies, all of which were observational rather than prospective.
Because all published studies on the mode of delivery and the risk of vertical transmission of HCV are observational and most did not assess viral load at the time of delivery, these results should be interpreted cautiously.
We recommend against cesarean delivery solely for the indication of HCV (GRADE 1B).
Does labor management affect the risk of vertical transmission?
Several factors in labor management may be associated with an increased risk of vertical transmission of HCV, namely, prolonged rupture of membranes, internal fetal monitoring, and episiotomy. One study reported that membrane rupture for >6 hours was associated with an increased risk of vertical transmission.
Another study found that the median duration of membrane rupture was significantly longer among women who transmitted HCV to their infants than among those who did not (28 vs 16 hours; P=.03).
Transmission of hepatitis C virus to infants of human immunodeficiency virus-negative intravenous drug-using mothers: rate of infection and assessment of risk factors for transmission.
Regarding invasive fetal monitoring, a retrospective study including 710 HCV-infected women and a prospective study including 242 HCV-infected women both reported that internal fetal monitoring was associated with an increased risk of transmission compared with no internal monitoring.
European Pediatric Hepatitis C Virus Network Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus.
One of these studies also found that episiotomy was significantly associated with an increased risk of vertical transmission (adjusted odds ratio, 4.2; 95% CI, 1.24–14.16).
Based on the available evidence, we suggest that obstetrical care providers avoid internal fetal monitors and early artificial rupture of membranes when managing labor in patients with HCV unless necessary in the course of management (ie, when unable to trace the fetal heart rate with external monitors and the alternative is proceeding with cesarean delivery) (GRADE 2B). Based on these data, another potential benefit of screening all pregnant patients for HCV is the potential impact of an HCV diagnosis on intrapartum and neonatal management.
Expectant management of ruptured membranes should be avoided at term. There are inadequate data regarding the risk of perinatal HCV transmission with expectant management in the setting of prolonged preterm premature rupture of membranes (PPROM). Therefore, usual obstetrical management for PPROM should not be altered because of maternal HCV infection.
It is unclear whether a patient with a positive HCV antibody and a negative viral load should be managed in labor in the same fashion as one with a detectable viral load. We suggest that negative confirmatory HCV antibody test results be considered a false positive; thus, the additional precautions suggested earlier are likely unnecessary. However, if the confirmatory test result is positive or if the test was not performed, until further data are available, it may be safest in labor to follow the same suggestions as in a patient with a positive viral load because of the theoretical possibility of intermittent viral shedding.
Postnatal care related to hepatitis C virus
Is breastfeeding safe in patients with hepatitis C?
Breastfeeding does not seem to affect the risk of vertical transmission of HCV. A systematic review including 14 cohort studies did not find an association between breastfeeding and HCV transmission.
We recommend that HCV status not alter standard breastfeeding counseling and recommendations unless nipples are cracked or bleeding (GRADE 1A). In those with cracked or bleeding nipples, breast milk should be expressed and discarded.
How should infants born to hepatitis C virus–positive patients be screened for hepatitis C virus infection?
Because anti-HCV antibodies can be transmitted across the placenta to the fetus, the presence of anti-HCV antibodies in a neonate’s serum soon after delivery is not diagnostic of neonatal infection. In a prospective study of vertical transmission of HCV that included 235 uninfected infants, anti-HCV antibodies were found in 96.8% of infants at birth, 15.3% at the age of 12 months, 1.6% at the age of 18 months, and 1.0% at the age of 24 months.
This study defined infants as HCV infected if they were positive for HCV RNA on at least 2 occasions at the age of ≥1 month or older or if they were anti-HCV positive at the age of 24 months.
The American Academy of Pediatrics and CDC recommend screening of infants born to HCV-positive women for anti-HCV antibodies at the age of >18 months or for HCV RNA on 2 occasions in infants at the age of >1 month.
Committee on Infectious Diseases American Academy of Pediatrics. Hepatitis C.
in: Kimberlin D.W. Brady M.T. Jackson M.A. Long S.S. Red Book: 2018 Report of the Committee on Infectious Diseases. American Academy of Pediatrics,
Itasca, IL2018: 428-434
We suggest that third trimester assessment of fetal growth may be performed, but antenatal testing is not indicated in the setting of HCV diagnosis alone.
2C Weak recommendation, low-quality evidence
2
We suggest screening for viral hepatitis in patients with a diagnosis of ICP at an early gestational age or with high levels of bile acids.
2C Weak recommendation, low-quality evidence
3
We recommend that obstetrical providers screen all pregnant patients for HCV by testing for anti-HCV antibodies in every pregnancy.
We suggest that obstetrical care providers screen HCV-positive pregnant patients for other sexually transmitted infections (if not done previously), including HIV, syphilis, gonorrhea, chlamydia, and HBV.
2C Weak recommendation, low-quality evidence
5
We recommend vaccination against HAV and HBV (if not immune) for patients with HCV.
We recommend that DAA regimens only be initiated in the setting of a clinical trial during pregnancy and that people who become pregnant while taking a DAA should be counseled in a shared decision-making framework about the risks and benefits of continuation.
1C Strong recommendation, low-quality evidence
7
We suggest that if prenatal diagnostic testing is requested, patients are counseled that data regarding the risk of vertical transmission are reassuring but limited.
2C Weak recommendation, low-quality evidence
8
We recommend against cesarean delivery solely for the indication of HCV.
We suggest that obstetrical care providers avoid internal fetal monitors and early artificial rupture of membranes when managing labor in patients with HCV unless necessary in the course of management (ie, when unable to trace the fetal heart rate with external monitors and the alternative is proceeding with cesarean delivery).
2B Weak recommendation, moderate-quality evidence
10
We recommend that HCV status not alter standard breastfeeding counseling and recommendations unless nipples are cracked or bleeding.
1A Strong recommendation, high-quality evidence
DAA, direct-acting antiviral; HBV, hepatitis B virus; HCV, hepatitis C virus; ICP, intrahepatic cholestasis of pregnancy.
Society for Maternal-Fetal Medicine. SMFM Consult Series #56: Hepatitis C in pregnancy. Am J Obstet Gynecol 2021.
Society for Maternal-Fetal Medicine (SMFM). Electronic address: [email protected] Society for Maternal-Fetal Medicine Special Statement: grading of Recommendations Assessment, Development, and Evaluation (GRADE) update.
Benefits clearly outweigh risks and burdens or vice versa.
Consistent evidence from well-performed, randomized controlled trials, or overwhelming evidence of some other form. Further research is unlikely to change confidence in the estimate of benefit and risk.
Strong recommendation that can apply to most patients in most circumstances without reservation. Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present.
Benefits clearly outweigh risks and burdens, or vice versa.
Evidence from randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise), or very strong evidence of some other research design. Further research (if performed) is likely to have an impact on confidence in the estimate of benefit and risk and may change the estimate.
Strong recommendation that applies to most patients. Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present.
1C. Strong recommendation, low-quality evidence
Benefits seem to outweigh risks and burdens, or vice versa.
Evidence from observational studies, unsystematic clinical experience, or randomized controlled trials with serious flaws. Any estimate of effect is uncertain.
Strong recommendation that applies to most patients. Some of the evidence base supporting the recommendation is, however, of low quality.
2A. Weak recommendation, high-quality evidence
Benefits closely balanced with risks and burdens.
Consistent evidence from well-performed randomized controlled trials or overwhelming evidence of some other form. Further research is unlikely to change confidence in the estimate of benefit and risk.
Weak recommendation; best action may differ depending on circumstances or patients or societal values.
Benefits closely balanced with risks and burdens; some uncertainty in the estimates of benefits, risks, and burdens.
Evidence from randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise), or very strong evidence of some other research design. Further research (if performed) is likely to have an effect on confidence in the estimate of benefit and risk and may change the estimate.
Weak recommendation; alternative approaches likely to be better for some patients under some circumstances.
2C. Weak recommendation, low-quality evidence
Uncertainty in the estimates of benefits, risks, and burdens; benefits may be closely balanced with risks and burdens.
Evidence from observational studies, unsystematic clinical experience, or randomized controlled trials with serious flaws. Any estimate of effect is uncertain.
Very weak recommendation, other alternatives may be equally reasonable.
Best practice
Recommendation in which either (1) there is an enormous amount of indirect evidence that clearly justifies strong recommendation (direct evidence would be challenging, and inefficient use of time and resources, to bring together and carefully summarize), or (2) recommendation to the contrary would be unethical.
Society for Maternal-Fetal Medicine. SMFM Consult Series #56: Hepatitis C in pregnancy. Am J Obstet Gynecol 2021.
Joint panel from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2020.
Committee on Infectious Diseases American Academy of Pediatrics. Hepatitis C.
in: Kimberlin D.W. Brady M.T. Jackson M.A. Long S.S. Red Book: 2018 Report of the Committee on Infectious Diseases. American Academy of Pediatrics,
Itasca, IL2018: 428-434
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators.
Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women.
Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1.
Expected and actual case ascertainment and treatment rates for children infected with hepatitis C in Florida and the United States: epidemiologic evidence from statewide and nationwide surveys.
Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention.
Transmission of hepatitis C virus to infants of human immunodeficiency virus-negative intravenous drug-using mothers: rate of infection and assessment of risk factors for transmission.
in: Kimberlin D.W. Brady M.T. Jackson M.A. Long S.S. Red Book: 2018 Report of the Committee on Infectious Diseases. American Academy of Pediatrics,
Itasca, IL2018: 428-434
All authors and committee members have filed a conflict of interest disclosure delineating personal, professional, business, or other relevant financial or nonfinancial interests that might be perceived as a real or potential conflict of interest in relation to this publication. Any substantial conflicts of interest have been addressed through a process approved by the Society for Maternal-Fetal Medicine (SMFM) Board of Directors. SMFM has neither solicited nor accepted any commercial involvement in the specific content development of this publication.
This document has undergone an internal peer review through a multilevel committee process within SMFM. This review involves critique and feedback from the SMFM Publications and Document Review Committees and final approval by the SMFM Executive Committee. SMFM accepts sole responsibility for the document content. SMFM publications do not undergo editorial and peer review by the American Journal of Obstetrics & Gynecology. The SMFM Publications Committee reviews publications every 18 to 24 months and issues updates as needed. Further details regarding SMFM publications can be found at www.smfm.org/publications.
SMFM recognizes that obstetric patients have diverse gender identities and is striving to use gender-inclusive language in all of its publications. SMFM will be using terms such as “pregnant person/persons” or “pregnant individual/individuals” instead of “pregnant woman/women” and will use the singular pronoun “they.” When describing study populations used in research, SMFM will use the gender terminology reported by the study investigators.
All questions or comments regarding the document should be referred to the SMFM Publications Committee at [email protected]
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