Acute Hepatitis A Infection in Pregnancy Is Associated With High Rates of Gestational Complications and Preterm Labor

doi:10.1053/j.gastro.2006.01.007

Gastroenterology

Volume 130, Issue 4, April 2006, Pages 1129-1134

https://doi.org/10.1053/j.gastro.2006.01.007 Get rights and content

Background & Aims: Hepatitis A virus (HAV) infection is the most common cause of acute hepatitis but is rarely reported during pregnancy. Our aim was to evaluate the impact of acute HAV infection on pregnancy outcome. Methods: Consecutive admissions of 79,458 pregnant females during a 25-year period were retrospectively reviewed. Results: Thirteen cases of second and third trimester HAV infection were found and evaluated. Nine of the 13 patients (69%) developed gestational complications, including premature contractions (n = 4), placental separation (n = 2), premature rupture of membranes (n = 2), and vaginal bleeding (n = 1). In 8 of these patients, complications led to preterm labor, at a median of 34 gestational weeks (range, 31–37 weeks). Delivery was vaginal in 12 of the 13 cases; fetal distress was noted in a single case, and meconium in amniotic fluid in 2 cases. Median birth weight was 1778 grams and 3040 grams in preterm and term deliveries, respectively (P < .05). Child outcome was favorable in all cases. In 4 cases, neonatal serum HAV RNA levels were measured and found negative. The presence of fever and hypoalbuminemia were associated with delivery at an earlier gestational week. There was a positive relation between gestational week at diagnosis of HAV infection and birth week (r = 0.68, P = .02), suggesting a causality relationship. All mothers featured full recovery from HAV infection. Conclusions: Acute HAV infection during pregnancy is associated with high risk of maternal complications and preterm labor. HAV serology and maternal vaccination during prepregnancy evaluation should be considered in areas of the world in which susceptible adult populations exist.

Section snippets

Patients

We reviewed the computerized diagnoses of all pregnant patients who were admitted to Hadassah-Hebrew University Medical Center, Mount Scopus Campus, Jerusalem, Israel, between the years 1980 and 2005. The participating hospital serves as primary, secondary, and tertiary medical care facility. Included were patients who presented with HAV-induced acute hepatitis during pregnancy, diagnosed by positive anti-HAV immunoglobulin (Ig)M serology and absence of other etiologies for acute liver injury.

Baseline Characteristics of the Study Population

At the Hadassah-Hebrew University Medical Center, Mount Scopus Campus, 79,458 deliveries were carried out during 1980–2005. Thirty-four cases of acute hepatitis were recognized among hospitalized pregnant individuals. Among these, 13 cases of acute hepatitis caused by HAV infection were identified by a combination of acute elevation of serum aminotransferase activity, positive IgM anti-HAV serology, and absence of other causes of acute hepatitis. The 21 cases of non-HAV acute hepatitis were

Discussion

This retrospective study, focusing on the clinical characteristics of acute HAV hepatitis during pregnancy, reveals that HAV infection during second and third trimester of pregnancy is associated with a high rate of gestational complications and preterm labor. Furthermore, in our study, a causal relationship between HAV infection and preterm labor is suggested by the temporal association between the 2 events. Considering the relatively mild nature of maternal disease noticed in our subjects,

References (29)

C.N. Shapiro et al.
Epidemiology of hepatitis Aseroepidemiology and risk groups in the USA
Vaccine
(1992)
S.P. Jaiswal et al.
Viral hepatitis during pregnancy
Int J Gynaecol Obstet
(2001)
A. Medhat et al.
Acute viral hepatitis in pregnancy
Int J Gynaecol Obstet
(1993)
S.K. Acharya et al.
Fulminant hepatitis in a tropical populationclinical course, cause, and early predictors of outcome
Hepatology
(1996)
J.P. Hieber et al.
Hepatitis and pregnancy
J Pediatr
(1977)
R.S. McDuffie et al.
Fetal meconium peritonitis after maternal hepatitis A
Am J Obstet Gynecol
(1999)
E. Leikin et al.
Intrauterine transmission of hepatitis A virus
Obstet Gynecol
(1996)
D. Gillis et al.
Adult infection with hepatitis A despite declining endemicityin favor of adult vaccination
Vaccine
(2002)
M.S. Khuroo
Study of an epidemic of non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type
Am J Med
(1980)
M.S. Khuroo et al.
Incidence and severity of viral hepatitis in pregnancy
Am J Med
(1981)

M.S. Khuroo et al.

Vertical transmission of hepatitis E virus

Lancet

(1995)

B. Duff et al.

Hepatitis A vaccineready for prime time

Obstet Gynecol

(1998)

B.P. Bell et al.

The diverse patterns of hepatitis A epidemiology in the United States—implications for vaccination strategies

J Infect Dis

(1998)

G. Livni et al.

Seroepidemiology of hepatitis A antibodies among children’s hospital staff

Pediatr Infect Dis J

(2002)

Cited by (110)

EASL Clinical Practice Guidelines on the management of liver diseases in pregnancy
2023, Journal of Hepatology
Liver diseases in pregnancy comprise both gestational liver disorders and acute and chronic hepatic disorders occurring coincidentally in pregnancy. Whether related to pregnancy or pre-existing, liver diseases in pregnancy are associated with a significant risk of maternal and fetal morbidity and mortality. Thus, the European Association for the Study of Liver Disease invited a panel of experts to develop clinical practice guidelines aimed at providing recommendations, based on the best available evidence, for the management of liver disease in pregnancy for hepatologists, gastroenterologists, obstetric physicians, general physicians, obstetricians, specialists in training and other healthcare professionals who provide care for this patient population.
Hepatitis during pregnancy
2023, Comprehensive Guide to Hepatitis Advances
Viral hepatitis is one of the more commonly diagnosed viral infections in pregnancy. Globally, it causes 1.34 million deaths per year. There are more than five subtypes of hepatitis that were being identified, namely Hepatitis A, B, C, D, and E. They have different routes of transmission with various impacts during pregnancy, which require individualized management during pregnancy. This chapter describes each type of hepatitis and its maternal, fetal, and perinatal implications.
Treatment and prevention of viral hepatitis in pregnancy
2022, American Journal of Obstetrics and Gynecology
Viral hepatitis in pregnancy may be caused by many types of viruses that cause systemic infection or target hepatocytes in their pathogenesis. Because viral hepatitis during pregnancy may represent acute or chronic infection or the reactivation of a prior infection, a high clinical suspicion, medical history review, and awareness of risk factors for the acquisition of infection are important management principles. The route of infection varies widely and ranges from fecal-oral transmission for the hepatitis A and E viruses to vertical transmission for hepatitis B, blood-borne transmission for hepatitis C, and sexual transmission for the herpes simplex virus. For this reason, the exposure details about travel, food preferences, drug use, and sexual contacts are important to elicit. Although routine prenatal screening is recommended for chronic viral hepatitis caused by hepatitis B and C, most other causes of viral hepatitis in pregnancy are detected in the setting of compatible signs and symptoms (fatigue, abdominal discomfort, jaundice, scleral icterus) or incidentally noted transaminitis on routine labs. Serologic testing is helpful for diagnosis with molecular testing as indicated to guide the management of hepatitis B and C. Preventive vaccines for hepatitis A and B with established safety of use in pregnancy are recommended for women who are at risk of acquisition. Postexposure prophylaxis for hepatitis A is a single dose of immunoglobulin and vaccination can be used if immunoglobulin G is not available. Antiviral therapy with tenofovir disoproxil fumarate is recommended as prophylaxis in pregnant women with active hepatitis B and an elevated viral load (>200,000 IU/mL) during the third trimester to prevent vertical transmission. The neonate exposed to hepatitis B at birth should receive immunoglobulin G and a monovalent birth dose vaccine within 12 hours, followed by completion of the 3-dosage vaccine series. The prevalence of hepatitis C in women of reproductive age has increased in the United States, and the role of antiviral therapy during pregnancy is of great interest. Cesarean delivery is not currently recommended for the sole purpose of reducing vertical transmission risk in pregnant women with viral hepatitis. Breastfeeding is recommended in women with hepatitis A, B, and C. New and promising prevention and treatment options for hepatitis B and C are under investigation. Investigators and regulatory authorities should ensure that these clinical trials for promising antivirals and vaccines are designed to include pregnant and lactating women.
Viral Hepatitis in pregnancy
2021, European Journal of Obstetrics and Gynecology and Reproductive Biology
The global prevalence of viral hepatitis is very high and seems to be rising over the years. The infection can profoundly affect pregnant women causing significant maternal and perinatal morbidity and mortality with some strains much worse than others.
Hepatitis A (HAV) and E (HEV) which are transmitted mainly through the faecal-oral route present as acute hepatitis during pregnancy and are responsible for most local epidemic outbreaks. HAV infection remains self-limiting during pregnancy, while HEV has a higher prevalence and causes significant morbidity. It is also associated with a very high maternal mortality rate (20 %) and requires special attention in endemic areas. HEV vaccines do exist, but the WHO has yet to approve them for general use. Hepatitis B is the most prevalent form and is part of the ante-natal screening program. The presence of HBeAg is associated with high viral loads and infectivity. Antiviral therapy, preferably tenofovir (TDF), is recommended for mothers with viral load ≥ 200,000 IU/mL₂), with the neonates receiving both active and passive immunisations. Hepatitis C and D are usually found as chronic infections in the pregnant and non-pregnant populations. Screening for hepatitis C during pregnancy and its subsequent management is still unsettled, but the introduction of direct-acting antiviral (DAA) drugs will change the picture if their safety is established in pregnancy. HDV is an incomplete virus linked to HBV and cannot establish an infection on its own. Controlling HBV is paramount to controlling HDV. HEV is quite prevalent and looked upon as hepatotropic. It seems to be quite prevalent in some blood donor populations and has a high co-infection rate with HCV. It has a high Mother-to-Child-Transmission (MTCT) but causes little or no illness in infected infants, and antenatal screening is not justified.
This review summarises the prevalence, clinical picture, maternal, perinatal effects, and the management and prevention of hepatitis A, B, C, D, E and G viral infections during pregnancy.
Management of viral hepatitis A, C, D and E in pregnancy
2020, Best Practice and Research: Clinical Obstetrics and Gynaecology
Viral hepatitis can cause significant maternal and neonatal morbidity and mortality. Hepatitis A and E mainly present as acute hepatitis during pregnancy, while hepatitis C and D are usually found as chronic infection in pregnant women. Hepatitis A remains self-limiting during pregnancy while hepatitis E has a higher prevalence and manifests with a rigorous course in pregnant women. Screening of hepatitis C during pregnancy and its subsequent management during pregnancy are still a debatable topic. New treatments of hepatitis C and E require further evaluation for use in pregnancy. This review summarizes the prevalence, clinical manifestations, maternal, foetal and neonatal effects, and the management of hepatitis A, C, D and E viral infection during pregnancy.
Safety evaluation of adverse events following vaccination with Havrix, Engerix-B or Twinrix during pregnancy
2020, Vaccine
Vaccination of pregnant women against hepatitis A virus (HAV) or hepatitis B virus (HBV) may benefit the mother and the fetus but is not routinely recommended. However, the risk associated with vaccination should be weighed against the risk of HAV or HBV infection. Data on safety profiles after hepatitis A, B or combined AB immunization during pregnancy are limited.
We searched the GSK Worldwide Safety Database for adverse events (AEs) following immunization of pregnant women with HAV (Havrix, GSK), HBV (Engerix-B, GSK) or the combined hepatitis AB (Twinrix, GSK) vaccine since market authorization through 31 January 2018, covering at least 25 years. AE reports (spontaneous, post-marketing surveillance and clinical trial cases) in the GSK Worldwide Safety Database were identified using a systematic search and were reviewed by clinicians to ascertain pregnancy status at time of vaccination and characterize adverse pregnancy outcomes, including pregnancy-related AEs and AEs in infants regardless of the causality assessment.
Overall, 613, 700 and 363 pregnancies with exposure to Havrix, Engerix-B and Twinrix, respectively, were reported. Of these, 378, 339 and 194 were analyzed. The most frequently identified pregnancy outcomes were live infants (288, 223 and 151), spontaneous abortions (43, 57 and 26) and elective terminations (25, 24 and 9). A total of 19, 29 and 10 cases of congenital anomalies were reported. Of these, 17, 20 and 7 were major birth defects. The most commonly reported pregnancy-related AE and AE in infants were premature delivery (28) and jaundice (11), respectively. No maternal deaths were reported. Congenital anomalies were reported in all recorded infant deaths.
This review did not indicate any concerning pattern of adverse pregnancy outcomes following exposure to any of the 3 vaccines during pregnancy.

View all citing articles on Scopus

View full text

Clinical-liver, pancreas, and biliary tractAcute Hepatitis A Infection in Pregnancy Is Associated With High Rates of Gestational Complications and Preterm Labor

Section snippets

Patients

Baseline Characteristics of the Study Population

Discussion

Vaccine

Int J Gynaecol Obstet

Int J Gynaecol Obstet

Hepatology

J Pediatr

Am J Obstet Gynecol

Obstet Gynecol

Vaccine

Am J Med

Am J Med

Lancet

Obstet Gynecol

The diverse patterns of hepatitis A epidemiology in the United States—implications for vaccination strategies

J Infect Dis

Seroepidemiology of hepatitis A antibodies among children’s hospital staff

Pediatr Infect Dis J

Clinical-liver, pancreas, and biliary tract
Acute Hepatitis A Infection in Pregnancy Is Associated With High Rates of Gestational Complications and Preterm Labor