Viral Hepatitis in Pregnancy
WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).
Viral hepatitis complicates 0.2% of all pregnancies. It is one of the most serious infections that can occur in pregnant women. Six different forms of viral hepatitis have now been defined. The most common viral agents causing hepatitis in pregnancy are hepatitis A virus, hepatitis B virus, hepatitis C (non-A, non-B hepatitis virus), and Epstein-Barr virus. Delta agent hepatitis has also received increasing attention as a cause of hepatitis.
This chapter addresses various types of hepatitis, their implications during pregnancy, the risk of perinatal transmission and treatment. The immunization recommendations of the Centers for Disease Control and Prevention (CDC) are also discussed with special focus on health care workers (1).
Natural History, Epidemiology of Viral Hepatitis:
1. Hepatitis A:
Approximately one third cases of acute hepatitis are caused by hepatitis A virus. It may occur sporadically or in epidemics. The virus usually is transmitted by person-to person contact through fecal-oral contamination. Poor hygiene, poor sanitation and intimate personal and sexual contact facilitate transmission. Hepatitis A is caused by an RNA virus, belongs to picornavirus group. Its incubation period ranges from 15 to 50 days; the mean is 28-30 days. Excretion of virus in stool normally begins approximately 2 weeks prior to the onset of clinical symptoms and is complete within 3 weeks following clinical symptoms. No known carrier state exists for the virus. Both blood and stool are infectious during the 2-6 week incubation period. Hepatitis A is endemic in Southeast Asia, Africa, Central America, Greenland, Mexico and Middle East.
Serious complications of hepatitis A are uncommon. Among all acutely ill patients who require hospitalization, the overall fatality rate does not exceed 2-1,000 cases in the USA. Hepatitis A immune globulin is recommended for household contacts and contacts in day care centers and custodial institutions. It should be given as soon as possible, if given after more than 2 weeks of exposure, it is ineffective. A vaccine is available, which may be taken during pregnancy.
Specific Tests: the diagnosis of acute hepatitis A is confirmed by detecting IgM antibodies to the virus. IgG antibodies to hepatitis A virus will persist in patients with previous exposure to the virus.
2. Hepatitis B:
Hepatitis B infection occurs throughout the world. In the United States, it is responsible for 40-50% of all cases of hepatitis. Acute hepatitis B occurs in 1-2/1,000 pregnancies. Chronic hepatitis is present in 5-15/1,000 pregnancies, but is more prevalent among certain ethnic groups (Asians, Insuits). Hepatitis B is caused by a small DNA virus. The intact virus is termed the Dane particle. Hepatitis B surface antigen (HBsAg) is present on the surface of the virus and also circulates freely in the serum in spherical and filamentous forms. The middle portion of the Dane particle contains hepatitis B core antigen (HBcAg). The core antigen is present in hepatocytes and does not circulate in the serum. Hepatitis B e antigen (HBeAg) is encoded by the same portion of the viral genome that codes for the core antigen. The presence of HBeAg indicates an extremely high viral inoculum and active virus replication. The incubation period of hepatitis B is 6 weeks to 6 months.
Hepatitis B is transmitted by parenteral and sexual contact. Individuals at greatest risk of becoming infected are those who have multiple sexual partners, inject drugs percutaneously, or have sexual partners who engage in these risk-taking behaviors. Other important risk factors are receipt of blood products and household or institutional contact. The mortality associated with acute hepatitis B is approximately 1%. Of patients who become infected, 85-90% experience complete resolution of their physical findings and develop protective levels of the antibody. The other 10-15% of patients becomes chronically infected; they continue to have detectable serum levels of HBsAg but are asymptomatic and have no biochemical evidence of hepatic dysfunction. In 15-30% of those chronically infected, viral replication continues and is manifested by persistence of the e-antigen and active viral DNA synthesis. These individuals are at risk for the subsequent development of chronic or persistent hepatitis and cirrhosis, and approximately 4,000 to 5,000 die annually of complications of chronic liver disease, including hepatocellular carcinoma.
The virus is contained in most body secretions. Because hepatitis B virus is highly pathogenic and infectious perinatal transmission of infection occurs with disturbing regularity. About 10-20% of women who are seropositive for HBsAg transmit the virus to their neonates in the absence of immunoprophylaxis. In the women who are seropositive for both HBsAg and HBeAg, the frequency of vertical transmission increases to about 90%. When maternal infection occurs in the first trimester, up to 10% of neonates will be seropositive for HBsAg. In women acutely infected in the third trimester, 80-90% of offspring will be infected. Between 85-90% of perinatal transmission of hepatitis B virus occur as a consequence of intrapartum exposure of the infant to contaminated blood and genital tract secretions. The remaining cases result from hematogenous transplacental dissemination, breast feeding, and close postnatal contact between the infant and the infected parent (5).
Infants of women who are HBsAg positive at the time of delivery should receive both hepatitis B immune globulin (HBIG) and hepatitis B vaccine within 12 hours of birth, followed by two more injections of hepatitis B vaccine in the first 6 months of life.
Specific Tests: in the acute stage the surface antigen and the IgM antibody to the core antigen is present. The presence of e-antigen is indicative of an exceptionally high viral inoculum and active virus replication, and implies high degree of infectivity. Chronic hepatitis B virus infection is characterized by the persistence of the surface antigen in the liver and serum. The time of infection can be evaluated by measuring IgG and IgM antibodies to HBcAg. Typically the IgG hepatitis B core antibody (HBcAb) appears 6 months of more after infection, with the IgM moiety being predominant at that time. Anti-HBc (IgM) may be helpful in HBsAg negative patients in whom hepatitis B is strongly suspected.
3. Hepatitis C:
Hepatitis C virus (previously termed non-A, non-B hepatitis) is a single-stranded RNA virus that appears to infect as much as 0.6% of the pregnant population. The principle risk factor for acquiring hepatitis C virus are the same as for hepatitis B. The incubation period is usually 7-8 weeks but may vary from 3-21 weeks. A chronic state for hepatitis C exists. Approximately 50% of patients with acute hepatitis C develop biochemical evidence of chronic liver disease. Of these individuals, at least 20% subsequently have chronic active hepatitis or cirrhosis. Approximately 7-8% of hepatitis C virus-positive women transmit hepatitis C virus to their offspring. Vertical transmission of hepatitis C may be more likely if the mother also is infected with human immunodeficiency virus (HIV).
Currently, no method has been found to prevent prenatal transmission. Many experts believe that hepatitis C virus-positive women should not breastfeed because there is a 2-3% risk of vertical transmission. Unlike hepatitis B, antibodies to hepatitis C are not protective.
Specific Tests: it is confirmed by identifying the antibody to hepatitis C virus. However antibody may not be present until 6-16 weeks after the onset of clinical illness. Hepatitis C viral RNA can be detected by polymerase chain reaction assay of serum soon after infection as well as in chronic disease.
4. Hepatitis D
Hepatitis D requires hepatitis B virus for replication and expression and so occurs only in people already infected with hepatitis B. In acute hepatitis B, once HBsAg clears the bloodstream, so does hepatitis D. Approximately 20-25% of chronic hepatitis B virus carriers ultimately are coinfected with hepatitis D virus. In acute hepatitis D, immunoglobulin M (IgM) antibodies against hepatitis D predominate, whereas IgG antibodies may be found in chronic infections. 70-80% patients infected by chronic hepatitis D ultimately develop cirrhosis and portal hypertension, 15% of whom suffer an unusually rapid progression to cirrhosis within 2 years of the initial onset of acute illness. Mortality due to hepatic failure is about 25%.
Vertical transmission of hepatitis D virus has been documented. Transmission is uncommon, however, because the measures used to prevent perinatal infection with hepatitis B virus are almost uniformly effective in preventing infection by hepatitis D.
Specific Tests: identification of the IgM antibody to hepatitis D virus. D antigenemia usually persists in patients with chronic hepatitis D despite the appearance of the IgG antibody to the virus. Thus, as in hepatitis C and HIV infection, viremia and end-organ damage can continue despite the presence of the antibody to the virus.
5. Hepatitis E:
The epidemiologic features of hepatitis E are similar to those of hepatitis A. Although the disease has been reported rarely in the United States, it is endemic in several developing countries, similar to those mentioned for hepatitis A. In India and Burma it is reported that 10-18% of pregnant women with hepatitis E died as a complication of their infection. Acute hepatitis E can be a serious disease; it usually is self-limiting and does not result in carrier state. Hepatitis E is transmitted via contaminated food and water, and vertical transmission has been reported.
Specific Tests: the diagnosis of infection with hepatitis E is by documentation of virus-specific antibodies.
6. Hepatitis G:
Hepatitis G infection is more likely in people already infected with hepatitis B or C or who have a history of intravenous drug use and HIV. Vertical transmission is high and hepatitis G probably does not cause chronic active hepatitis or cirrhosis.
Specific Tests: the diagnosis of infection with hepatitis G is by documentation of virus- specific antibodies.
The clinical picture of hepatitis is highly variable; most patients have asymptomatic infection, while a few may present with fulminating disease and die within few days. The usual subjective symptoms in patients with acute hepatitis are malaise, fatigue, anorexia, nausea and right upper quadrant or epigastric pain. Typical findings include jaundice, upper abdominal tenderness, and hepatomegaly. Many cases of hepatitis do no have jaundice. The patient's urine usually is darkened, and the stool may be acholic. In cases of fulminating hepatitis signs of coagulopathy and encephalopathy may be evident.
In the cases of hepatitis A or E, there may be history of recent travel to an endemic area or exposure to an infected person. Hepatitis B, C, D, or G typically ensues after parenteral exposure to contaminated blood or sexual contact with an infected partner. The initial phase of infection, patients with hepatitis D are indistinguishable from individuals with acute hepatitis B. The patients infected with hepatitis B, C or D virus whose acute symptoms resolve, some become chronic carrier of viral antigens. The same may be true for hepatitis G. Although most viral hepatitis carriers initially are asymptomatic, up to one third subsequently develop chronic active or persistent hepatitis or cirrhosis. Once cirrhosis ensues, patients demonstrate the typical sings of end-stage liver disease, such as jaundice, muscle wasting, ascites, spider angioma, palmar erythema, and hepatic encephalopathy. Hepatitis C is probably the leading cause of hepatocellular carcinoma in the United States.
The diagnosis is made using the previously described serologic markers. Jaundice, a primary symptom of hepatitis infection, also occurs with numerous other disorders. The differential diagnosis of viral hepatitis should include the following clinical conditions (2). In acute hepatitis marked increase in the serum concentration of alanine aminotransferase (ALT, previously SGPT) and asparate aminotransferase (AST, previously SGOT) is seen. In addition, the serum bilirubin concentration often is increased. Patients who are severely ill, coagulation abnormalities and hyperammonemia also may be present. Initial evaluation includes the tests for: anti-HA IgM, HBsAg and HC PCR. In selected patients, additional testing can include anti-HBc IgM, HD PCR, anti-HE, and anti-HG. Liver biopsy is rarely indicated in pregnancy.
Differential Diagnosis of Jaundice in Pregnancy:
|Viral hepatitis||Mild to marked elevation in serum transaminases Positive viral serology Prominent inflammatory infiltrate with hepatocellular disarray|
|Acute fatty liver of pregnancy||Minimal elevation in transaminases Little if any inflammatory infiltrate with prominent microvesicular fat deposition|
|Toxic injury||History of drug exposure (eg; tetracycline, isoniazid, erythromycin, alpha methyldopa)|
|Cholestasis of pregnancy||Pruritis Elevation of bile salts Cholestasis with little inflammation|
|Severe Preeclampsia||Hypertension, edema, proteinuria, oliguria Elevated blood urea nitrogen, creatinine, uric acid, transaminases, and lactate dehydrogenase Thrombocytopenia|
|Mononucleosis||Flue-like illnessPositive heterophile antibodyElevated transaminases|
|Cytomegalovirus (CMV) hepatitis||CMV antibodies Positive viral culture or polymerase chain reaction Elevated transaminases|
|Autoimmune hepatitis||Antinuclear antibodies, liver-kidney microsomal antibodies Elevated transaminases|
Supportive Treatment: Bed-rest should be instituted during the acute phase of the illness. If nausea, vomiting or anorexia is prominent, intravenous hydration and general supportive measures are instituted. Fluid and electrolyte abnormalities should be corrected. If a coagulopathy is present, administration of erythrocytes, platelets, and clotting factors such as fresh frozen plasma or cryoprecipitate may be necessary. Infected women should avoid intimate contact with household members and sexual partners until these individuals receive appropriate prophylaxis outlines as follows.
- Hepatitis A: currently no antiviral agent is available for treatment of acute hepatitis A. An inactivated-virus vaccine that is safe in pregnancy is available. Women at risk for infection with hepatitis A, such as those traveling to endemic areas, should be vaccinated. For post-exposure prophylaxis, a single intramuscular dose of 1 mL should be administered as soon as possible. Administration of immune globulin more than 2 weeks after exposure is not effective in preventing or ameliorating the severity of hepatitis A. Immune globulin does not pose a risk to either a pregnant woman or her fetus, and therefore preparation should be administered during pregnancy if indicated.
- Hepatitis B: although interferon alfa has been shown to alter the natural history of acute hepatitis B, C and D, it should be avoided in pregnancy. Prevention of infection is of paramount importance. Specific immunotherapy with hepatitis B immune globulin (HBIG) has been effective.
Vaccination: pregnancy is not a contraindication to vaccination. In fact, susceptible pregnant women who are at risk for hepatitis B infection should be specifically targeted for vaccination. Currently available vaccines prepared from yeast cultures by using recombinant DNA technology, poses no risk of transmission of HIV infection. They are highly immunogenic and result in sero-conversion in more than 95% of recipients. Individuals who have been exposed to hepatitis B virus before they are vaccinated should receive passive immunization with HBIG and undergo the immunization series. When exposure has occurred as a result of sexual contact, the patient should receive a single dose of HBIG within 14 days of contact. The preparation is administered intramuscularly in a dose of 0.06 mL/kg. For prophylaxis after percutaneous or mucous membrane injury, treatment should include an initial injection of HBIG, followed by a second dose 1 month later.
Perinatal Management: the maternal course of viral hepatitis is unaltered by pregnancy, but the incidence of premature labor and delivery is increased. The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend hepatitis B virus screening for all pregnant women (3). The combination of passive and active immunization has been particularly effective in reducing the frequency of perinatal transmission of hepatitis B virus. Several investigations conducted in Asian nations have shown that passive and active immunization of the newborn is 85-95% effective in preventing perinatal transmission of hepatitis B virus. Pregnant women should be routinely tested for HBsAg during an early prenatal visit. Women in high-risk groups who initially test negative for hepatitis B virus should be targeted for vaccination if they have not been vaccinated previously. Seropositive women should be encouraged to inform their children and sexual partners of the need for testing and vaccination. Serum transaminases should be measured in seropositive women to detect biochemical evidence of chronic active hepatitis. If the test results are abnormal or if the liver is palpable, the patient should be evaluated further to determine whether the disease is acute or chronic. The physician responsible for the care of a newborn delivered to a mother with chronic hepatitis B should be informed of the mother's carrier status so that the appropriate doses of hepatitis B virus vaccine and HBIG can be given as soon as possible following delivery. Fetal infection in utero is rare, but the neonate may be exposed to the virus at delivery and the virus may be spread by breast-feeding (4).
- Hepatitis C and D: treatment with interferon alfa produced clinical improvement in 28-46% of patients with chronic hepatitis C and D. The relapse rate is shown to be about 50% with in 6 months.
Precautions for Health Care Workers:
Approximately 12,000 health care workers in the United States contract hepatitis B virus infection as a result of an occupational injury each year. Of these individual about 200 experience a fulminating course and die. Another 1,000-1,200 become chronic carriers of the surface antigen. The principal mechanism of transmission of hepatitis B virus from patient to health care worker is through injury from a sharp object, such as a needle or scalpel, which is contaminated with infected blood. Another important, but less frequent, mechanism of transmission is a splash injury, resulting in contact between skin or mucosal surfaces and contaminated secretions or blood.
Physicians and other health care workers should use standard precautions to reduce their risk of acquiring hepatitis B virus infection. The preliminary element of universal precautions is the use of appropriate barrier precautions by all health care personnel to prevent the exposure of their skin and mucous membranes to the blood or other body fluids of any patient. Most important, all health care workers who may have direct or indirect exposure to patients should be immunized.
Invasive prenatal diagnostic procedures for patients with chronic hepatitis:
The risk of transmission through amniocentesis appears to be low for women who are chronically infected with hepatitis B or hepatitis C, although the number of exposed cases in the literature is small. Of the 115 women reported to be positive for hepatitis B surface antigen who underwent second trimester amniocentesis, the rate of neonatal infection was no different than in women who did not have an amniocentesis. All of the infants received hepatitis B vaccination and immunoprophylaxis beginning at birth (7). There is only one series of 22 hepatitis C virus (HCV)-positive women reported in the literature who underwent second-trimester amniocentesis. No infants in this series were found to be hepatitis C RNA positive on postnatal testing. This group included one woman with hepatitis C RNA-positive amniotic fluid (8). Data are insufficient in literature to assess the risk of chorionic villus sampling in these women or to estimate the risk of fetal infection among women with anterior placentas, those who are hepatitis B e antigen-positive, or those with high hepatitis B or hepatitis C viral loads. Because of the limited information regarding the risk of invasive procedures in women chronically infected with hepatitis B or hepatitis C, it would be prudent to discuss non-invasive screening options with these women.
Special considerations for intrapartum care for maternal hepatitis infection:
Between 85% and 95% of perinatal transmission of hepatitis B virus (HBV) occur as a consequence of intrapartum exposure of the infant to infected blood and genital tract secretions. The remaining cases result from hematogenous transplacental dissemination and close postnatal contact between the infant and the infected parent. Risk factors for intrauterine HBV infection have been reported to include maternal hepatitis B e antigen (HBeAg) seropositivity, history of threatened preterm labor, higher hepatitis B surface antigen (HBsAg) and HBV DNA titers, and the presence of HBV DNA in villous capillary endothelial cells (5)(6). Adequate data regarding the risk of transmission with operative vaginal delivery or internal fetal monitoring are not available to make recommendations. The route of delivery has not shown to influence the risk of vertical hepatitis C virus (HCV) transmission (2)(8). Cesarean delivery should be performed in HCV-infected women only for obstetric indications. This study reports a vertical transmission rate for hepatitis C of 4.1%. These results do not support a recommendation of planned cesarean to reduce vertical transmission of hepatitis C infection (12).
Breastfeeding for infants of women with hepatitis:
In hepatitis A virus (HAV)-infected women, breastfeeding is permissible with appropriate hygienic precautions. Although immune globulin has been administered to newborns in specific situations, the efficacy of this practice has not been established. Breastfeeding is not contraindicated for women who are hepatitis B surface antigen (HBsAg) positive at the time of delivery. In addition, breastfeeding is not contraindicated in women chronically infected with HBV if the infant receives HBIG passive prophylaxis and vaccine active prophylaxis (3)(9). There are no data from which to make a recommendation for HBeAg positive patients. In addition, breastfeeding has not been associated with an increased risk of neonatal HCV infection, and therefore is not contraindicated in HCV-infected mother (11). Breastfeeding was not detrimental to newborns of hepatitis E virus (HEV)-infected women in one recent series of 93 pregnancies. In this cohort, anti-HEV antibody and HEV RNA were present in clostral samples, but at significantly lower levels than in maternal serum (10). In summary, breastfeeding is not contraindicated in women with HAV infection with appropriate hygienic precautions, in those chronically infected with hepatitis B if the infant receives HBIG passive prophylaxis and vaccine active prophylaxis, or in women with HCV infection.
Monitoring the Hepatitis B Control Goal:
In 2005, the World Health Organization (WHO) Western Pacific Region adopted the hepatitis B control goal of reducing the hepatitis B surface antigen seroprevalence in children at least 5 years of age to less than 2% by 2012. Universal infant immunization with three doses of hepatitis B vaccine, including a timely birth dose, is the key recommended strategy. Measuring seroprevalence in children at least 5 years of ages takes into account the period when the risk of acquiring a chronic infection is highest and provides an indicator that can be monitored in the short term, within 5 years of vaccine introduction, and which correlates strongly with the long-term consequences of hepatitis B. A time-bound supranational hepatitis B control goal was chosen to create a sense of political urgency for strengthening routine immunization services and improving access to delivery care as well as providing resources for hepatitis B vaccination. Consequently, the program strategies selected are not stand-alone but also contribute to strengthening health systems. Independent certification of achievement of the control goal, hitherto used mainly for eradication goals, is planned for all countries.
In 2007, certification guidelines were developed to define the procedures and criteria to be used in each country for independently validating the achievement of the hepatitis B control goal (13). Certification will be based on measuring the HBsAg seroprevalence using a nationally representative serosurvey in children at least 5 years of age who were born after the start of the nationwide infant vaccination program. However, the guidelines recommend that the serosurvey should be conducted only after vaccination coverage with three doses of hepatitis B vaccine, including a timely birth dose, has been high enough for at least 5 years. While the serosurvey in children at least 5 years of age will document the impact of the vaccination coverage achieved 5 years earlier, subsequently the hepatitis B control certification status will be assessed by regular monitoring of vaccine coverage data.
Impact of setting a time-bound goal for hepatitis B control in the WHO Western Pacific Region on political commitment and national policy (14):
Increased political commitment:
- In 2005, China recognized hepatitis B as one of four priority communicable diseases, along with HIV/AIDS, schistosomiasis, and tuberculosis.
- China issued a national hepatitis B control plan in 2006 and adopted the more ambitious target of reducing the HBsAg seroprevalence to less than 1% among 5-year-old children by 2010.
- The Governments of China and Viet Nam started fully financing hepatitis B vaccines after the end of GAVI Alliance support in 2006 and 2007, respectively.
- In 2006, the Philippines made a commitment to provide 100% funding for hepatitis B vaccination for the first time.
Greater equality within and between countries:
- In 2005, China passed a law abolishing user fees for all immunizations offered as part of WHO's Extended Program on Immunization (EPI), thereby increasing access to hepatitis B vaccine among poor population groups.
- With committed financing in developing countries, such as Cambodia, China, and the Philippines and Viet Nam, the gap between developed and developing countries have closed.
Change in national policy:
- In 2005, Mongolia started providing the birth dose of the hepatitis B vaccine within 24 hours of birth, replacing its earlier policy of giving it within 24-48 hours.
- The Philippines changed its hepatitis B immunization schedule so that the first hepatitis B vaccine dose is administered within 24 hours of birth rather at 6 weeks of age.
- In 2006, Viet Nam changed the schedule for the first dose of hepatitis B vaccine from within 7 days of birth to within 24 hours.
To date, most supranational time-bound disease-specific goals have focused on eradicable diseases and were driven by the cost savings that could be achieved after eradication. Early assessment showed that adopting the regional goal led to greater political commitment, with reduced inequalities in hepatitis B vaccination between and within countries. Previous declining trends in routine immunization coverage also show signs of reversal and there is major progress in providing timely birth doses. A similar approach may be relevant to countries in Africa and South Asia that have a high hepatitis B disease burden faltering routine immunization and poor access to skilled delivery care.
Hepatitis A is an uncommon complication of pregnancy and is not associated with perinatal transmission. Hepatitis B virus infection is more common and clearly poses a serious risk to the household contacts and neonates of infected mothers. All pregnant patients should be tested for hepatitis B virus. Universal vaccination of all neonates with hepatitis B vaccine is now recommended. Infants delivered to HBsAg seropositive mothers also should receive HBIG and vaccination immediately after birth. Hepatitis C and D, which are transmitted parenterally and by sexual contact, have been associated with vertical transmission. No immunoprophylaxis currently is available for neonates of mothers with hepatitis C or E virus. Immunization against hepatitis B is protective against vertical transmission of hepatitis D. Hepatitis E is quite rare in the United States and is quite similar to hepatitis A.
- World Health Organization
- Centers for Disease Control and Prevention
- National Institutes of Health
Viral Hepatitis: A through E and beyond
- Centers for Disease Control and Prevention. Recommended adult immunization schedule: United States, October 2006-September 2007. Atlanta (GA): CDC 2006. Available at: http://www.cdc.gov/. Retrieved July 16, 2009
- ACOG Practice Bulletin. Viral hepatitis in pregnancy. Number 86, October 2007
- Mast EE, Margolis HS, Fiore AE et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) [published erratum appears in MMWR Morb Mortal Wkly Rep 2006,55:158-9]. MMWR Recomm Rep 2005;54(RR-16):1-31
- Updated U. S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for post exposure prophylaxis. Centers for Disease Control and Prevention. MMWR Recomm Rep 2001; 50 (RR-11):1-52. (Level III)
- Xu DZ, Yan YP, Choi BC et al. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol 2002;67:20-26. (Level II-2)
- Towers CV, Asrat T, Rumney P. The presence of hepatitis B surface antigen and deoxyribonucleic acid in amniotic fluid and cord blood. Am J Obstet Gynecol 2001;184:1514-1518
- Scott JD, Gretch DR. Molecular diagnostics of hepatitis C virus infection. JAMA 2007;297:724-732. (Level III)
- Mast EE, Hwang LY, Seto DS et al. Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J Infect Dis 2005;192:1880-1889. (Level II-2)
- American Academy of Pediatrics, American College of Obstetricians and Gynecologists. Breastfeeding handbook for physicians. Elk Grove Village (IL): AAP; Washington, DC: ACOG; 2006. (Level III)
- Chibber RM, Usmani MA, Al-Sibai MH. Should HEV infected mothers breast feed? Arch Gynecol Obstet 2004;270:15-20. (Level II-2)
- Breastfeeding: maternal and infant aspects. ACOG Committee Opinion No. 361. American College of Obstetricians and Gynecologists. Obstet Gynecol 2007;109:479-480. (Level III)
- McMenamin MB, Jackson AD, Lambert J, et al. Obstetric management of hepatitis C-positive mothers: analysis of vertical transmission in 559 mother-infant pairs. Am J Obstet Gynecol 2008;199:315.e1-315e5
- Guidelines for certification of achievement of hepatitis B control goal in the Western Pacific Region. Manila: World Health Organization Regional Office for the Western Pacific; 2007
- Rani M, Yang B, Nesbit R. Hepatitis B control by 2012 in the WHO Western Pacific Region: rationale and implications. Bull World Health Organ 2009;87:707-713
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