Viral infections in pregnancy

Viral infections are a common complication of pregnancy and in some cases, can have profound effects for the unborn fetus. The human herpesvirus family is composed of large, enveloped DNA viruses that have close structural similarity. The family includes the herpes simplex viruses types 1 and 2, varicella zoster virus, Epstein Barr virus, cytomegalovirus (CMV), and human herpes viruses types 6, 7 and 8. These viruses all share the ability to establish latency and reactivate at a later time. Structural fetal abnormalities can result from intrauterine infection and transmission of the infection during the pregnancy or at the time of delivery can result in important neonatal disease. Human parvovirus B19 is a DNA virus with strong tropism for erythroid precursors and infection during pregnancy can result in fetal hydrops and stillbirth. The causative agents of hepatitis are hepatotropic viruses termed hepatitis A, B, C, D (deltavirus) and E. All except hepatitis B virus are RNA viruses. Vertical transmission of maternal infection with hepatitis B and C can result in significant long term sequelae.     

Hepatitis B and pregnancy: An update review article

Chronic hepatitis B, as a global health problem, is a disease that begins in the prenatal period and its complications gradually become clear later in life. About 5% of women worldwide are carriers of chronic hepatitis B virus(HBV). The most common method of transmission of HBV around the world is from mother to infant. This article aims to review the unique challenges of hepatitis B in pregnancy. Data for this review were collected from our previous studiesand experiences plus various data banks, such as Pub Med, EMBASE, ISI Web of science, Scopus, Google Scholar and Iranian databases. A comprehensive search was performed using the combinations of the keywords to review relevant literature and higher education journals. All published data up to February 2014 have been included in this review. This article addresses several interesting aspects. First, hepatitis B in pregnancy can vary regarding prevalence, virus behavior, prenatal transmission and outcome of the pregnancy. Second, the women of reproductive age with chronic HBV remain a major source for continued spread of the virus. Finally, pregnant women need screening in prenatal care to enable early intervention when necessary.     

Hepatitisinfektion in der Schwangerschaft und bei der Geburt

The most common cause of jaundice in pregnancy is viral hepatitis, potentially accompanied by temporary dysfunction of the liver. Whereas acute viral hepatitis in pregnancy frequently describes an asymptomatic course, thereby only rarely affecting the fetus, some of the known hepatitis viruses might cause severe morbidity in the neonatal period particularly when the infection is noted near term or sub partu. However, efforts have been made in order to reduce the number of acute neonatal infections (hepatitis B immune globulin and vaccine). Conversely, no immunoprophylaxis for hepatitis C is available yet, although the vertical transmission rate is low. Perinatal transmission of hepatitis E is unusual, but maternal disease is often severe. The clinical relevance of the commonly found hepatitis G virus remains unknown. Liver inflammation caused by other viruses, toxic agents or autoimmune hepatitis are rare conditions in pregnancy.     

Management of viral hepatitis A,C, D and E in pregnancy

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.     

Viral hepatitis: from A to E, and beyond?

Identification of hepatitis viruses A-E has enabled researchers to investigate the epidemiology, pathogenesis, sequelae, and possible means of prevention of these infections. This knowledge also provides a basis for further study of the pathological significance of candidate hepatitis viruses. With improvements in hygiene in many parts of the world, hepatitis A virus infection has decreased markedly. However, this success has the unintended consequence of rendering a large percentage of the younger population susceptible to hepatitis A virus infection. Fortunately, effective active immunization for hepatitis A virus is now available. Hepatitis B remains a common condition, especially in Asia and Africa which have high prevalences of chronic infection. Chronic hepatitis B carriers serve as reservoirs of infection for the community and are at risk of chronic liver disease and hepatocellular carcinoma. A mass immunization program in Taiwan has been remarkably successful in reducing the prevalence of chronic hepatitis B infection. Genotypes of the hepatitis B viruses may be associated with the severity of liver disease and the responses to therapies. Hepatitis C is another important cause of death worldwide. The infection easily becomes refractory and the chronicity contributes to the development of cirrhosis and hepatocellular carcinoma. Although no effective immunization is currently available for hepatitis C, it can be controlled by preventative measures and recently developed interferon-based treatments, especially in combination with ribavirin. The prevalence of hepatitis D has markedly decreased in the last decade and new cases are now rarely encountered. Hepatitis E is endemic in limited areas and travel to these areas appears to be the main risk factor for contracting the infection. Several new candidate hepatitis viruses have been identified, including GB virus-C, TT virus, and SEN virus, but none of these has been shown to cause hepatitis, and they may be passenger viruses.     

131例乙肝孕妇行介入性产前诊断的垂直传播风险分析

目的了解行介入性诊断的乙肝孕妇发生垂直传播的风险情况。方法回顾性分析2017年7月至2018年6月间来广东省妇幼保健院产前诊断科行介入性产前诊断、符合纳入标准的乙肝表面抗原(HBsAg)阳性孕妇及其所生婴儿的临床资料,总结不同穿刺类型、不同穿刺指征、是否合并乙肝e抗原(HBeAg)阳性等情况下的母婴垂直传播风险。结果本研究共纳入131例(含双胎5例)乙肝孕妇和136例所生婴儿,共3例(2.21%)在乙肝联合免疫后依然被检出感染乙肝;HBeAg阴性和HBeAg阳性孕妇所生婴儿发生感染的几率分别为1.09%(1/92)和5.71%(2/35);乙肝病毒DNA定量超过106IU/ml和107IU/ml的垂直传播率分别为4.35%(1/23)和5.00%(1/20);行羊膜腔穿刺术、脐静脉穿刺术和绒毛吸取术的乙肝孕妇发生垂直传播的几率分别为1.11%(1/90)、2.56%(1/39)和14.29%(1/7);因超声异常表现和其他非超声异常指征行介入性产前诊断孕妇发生垂直传播的风险分别为2.82%(2/71)和1.54%(1/65);10例孕妇孕期接受了抗病毒治疗,该10例所生婴儿均未发生感染。结论乙肝孕妇行介入性产前诊断有发生母婴垂直传播的风险,仍需大样本研究进一步探讨。     

Prevention of vertical hepatitis B transmission by hepatitis B immunoglobulin in the third trimester of pregnancy.

OBJECTIVE: To explore the possible efficacy of using hepatitis B immunoglobulin (HBIG) during the third trimester of pregnancy to prevent intrauterine transmission of hepatitis B virus (HBV). METHODS: Of 469 pregnant women testing positive for hepatitis B surface antigens (HBsAg), 126 had hepatitis B e antigen (HBeAg) and 343 did not. RESULTS: There were women who declined to be treated with HBIG in these 2 groups. Among infants born to HBeAg-positive mothers, the rates of those testing positive for HBsAg at birth and at the 6-month visit were significantly lower when the mothers had been treated with HBIG (P<0.05). Among infants born to HBeAg-negative mothers, however, no significant differences were found whether the mothers had been treated or not. Furthermore, all newborns received HBIG treatment and the first dose of a vaccination schedule within 12 h of birth. At the 6-month visit the protective anti-HBs rates were only 32.3% among infants whose mothers were HBeAg-positive and 56.2% among those whose mothers were HBeAg-negative when their mothers had not been treated with HBIG during pregnancy, whereas the corresponding rates were as high as 75.8% and 88.7% when the mothers had been treated. CONCLUSION: Maternal administration of HBIG is effective in preventing intrauterine fetal HBV infection in HBsAg-positive, HBeAg-positive pregnant women and in improving immune response to hepatitis B vaccine in infants born to HBV carriers.     

Reiseschutzimpfungen für Schwangere und Frauen mit Kinderwunsch

Infectious diseases are a potential source of maternal and fetal morbidity and mortality. Prior to international travels, pregnant women and women actively attempting to become pregnant should seek specific counselling regarding necessary travel immunizations. This is especially important if their travel destination is a country with areas endemic for malaria, yellow fever, tuberculosis, hepatitis, human immunodeficiency virus-associated diseases, leishmaniosis, toxoplasmosis, filariosis, Japanese encephalitis, rubella, typhus, leptospirosis, Dengue fever, Helicobacter pylori gastritis, and trypanosomiasis. Toxoid vaccinations, inactivated vaccinations, and immunoglobulins may be administered during pregnancy, whereas live vaccinations are contraindicated. Recommended vaccinations during pregnancy are tetanus, diphtheria, and pertussis in case of an insufficient immunization status, as well as the seasonal influenza vaccination. Specific travel vaccinations include all standard vaccinations. In addition, hepatitis A, yellow fever, and polio in certain countries with endemic areas according to World Health Organization (WHO) specifications are recommended. Some countries may have additional vaccination regulations regarding cholera and meningococcus. Vaccinations “per indication” are required if the travel destination is an area with specific locally increased risks for typhoid, rabies, tick-borne encephalitis, influenza A/H5N1, Japanese encephalitis, cholera, or yellow fever. There is no effective vaccination against the zika virus. Thus, pregnant women and women actively attempting to become pregnant should refrain from travelling to countries endemic for zika virus.     

The influence of contamination of culture medium with hepatitis B virus on the outcome of in vitro fertilization pregnancies.

Heat-inactivated human serum is added to the culture medium used for in vitro fertilization and other forms of assisted conception. Because one batch of pooled serum contained hepatitis B virus, an epidemic occurred among women participating in the treatment program. Seventy-nine women had serologic proof of hepatitis B infection. This incident gave the opportunity to study the effect of hepatitis B virus on pregnancy outcome and the newborn. The situation is unique because the preimplantation embryo was exposed to hepatitis B virus or the pregnancy was complicated by a (sub)clinical infection. Twenty-four women were or became pregnant while having an acute hepatitis B infection. Five pregnancies ended in abortion. The remaining 19 pregnancies ended in the birth of 24 children. No evidence for any harmful effect of exposure to hepatitis B virus in the embryonic or fetal period on the newborn could be found.     

Hepatitis B – chronic carrier status and pregnancy outcomes: An obstetric perspective

Antenatal screening for hepatitis B surface antigen (HBsAg) only identifies women with hepatitis B virus (HBV) infection for neonatal immunoprophylaxis. It does not reflect the phase of chronic infection, viral genotype and activity, hepatic inflammation, or other co-existing liver disorders. Coinfection with other viruses and micro-organisms may also be present. These factors in various combinations can impact pregnancy outcomes, and they are probably responsible for the conflicting literature on this issue. Pregnancy complications may interact with maternal HBV infection and hepatitis flares, leading to serious and lethal complications. Hepatitis flares are common especially postpartum, and they are unpredictable and unpreventable with antiviral treatment. Evidence on the association between HBsAg seropositivity with gestational diabetes mellitus, preterm birth, increased foetal growth, and reduced pregnancy hypertensive disorders is stronger than other adverse pregnancy outcomes. Baseline assessment of liver function, and viral markers and activity, can delineate the truly high-risk pregnancies for close monitoring.     

Pandemic H1N1 2009 (swine flu) and pregnancy

H1N1 pandemic influenza is a novel strain of the influenza A virus. It is widely known as swine flu. Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery. The median duration of illness is around seven days. This influenza typically affects the younger age group i.e. from the ages of 5–65 years but the age groups of below 5 years and above 65 are particularly prone to severe complications. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the third trimester. Antiviral drugs are effective against the virus and are not contraindicated in pregnancy and breastfeeding. Vaccines have now been developed and are offered to pregnant women. Safety issues have been examined by regulatory authorities and the vaccines have been determined to be safe for administration in all trimesters of pregnancy.     

妊娠合并乙型肝炎病毒感染孕妇胎儿窘迫发病原因分析

目的：探讨妊娠合并乙型肝炎病毒（HBV）感染孕妇胎儿窘迫的病因、预后及治疗方法。方法：对81例妊娠期HBV表面抗原（HBsAg）、HBVe抗原（HBeAg)、HBV核心抗体（HBcAb)和HBV DNA均阳性,肝功能正常的孕妇及其新生儿（研究组）,85例无肝炎病毒感染,肝功能正常的孕妇及新生儿（对照组）的临床资料、血清学检查结果、胎盘病理检查结果和胎儿预后进行分析,并对研究组中76例婴儿在出生后0、1、6月龄时分别注射酵母菌重组乙型肝炎疫苗10μg,24月龄时检测婴儿HBV表面抗体（HBsAb),以评价母婴HBV阻断效果。结果：（1）研究组胎儿窘迫的发生率为38．3％,对照组为16．5％,两组比较差异有显著性（P＜0．05）。（2）HBV感染胎盘可导致绒毛膜血管病。（3胎儿窘迫者,24月龄时母婴阻断率为78．6％,无胎儿窘迫者母婴HBV阻断率为91．7％,两 者比较,差异有显著性（P＜0．05）。结论：妊娠合并HBV感染,可引起胎盘绒毛膜血管病,致使胎盘功能下降,临床表现为胎儿窘迫、进而导致HBV母婴阻断失败。     

Cytomegalovirus hepatitis during pregnancy

Background: Although cytomegalovirus (CMV) is an uncommon cause of viral hepatitis during pregnancy, a definitive diagnosis is important because of the potential for congenital CMV. In the case reported here, a diagnosis of hepatitis caused by CMV was made after the more common viral pathogens had been ruled out. Case: A 17-year-old, 12-week pregnant patient was evaluated for fever and right upper quadrant tenderness. A serologic evaluation revealed elevated liver function levels and a positive maternal serology for CMV IgM. A diagnosis of hepatitis caused by CMV was made after the more common viral pathogens and drug-induced hepatitis had been ruled out. She was counseled about the potential effects of CMV on her fetus.Conclusion: A step-wise approach to the diagnosis of viral hepatitis during pregnancy is needed to determine the etiology because a potential teratogenic virus may be involved.     

Chronic hepatitis B infection and pregnancy

It is estimated that 350 to 400 million individuals worldwide are chronically infected with hepatitis B virus (HBV). In regions of high endemicity, many of these are females of reproductive age who are an important source for perinatal transmission. There are a number of issues specific to the women of childbearing age who have chronic HBV infection, including the safety of antiviral therapy during pregnancy and breast-feeding, the changes in the immune system during pregnancy and postpartum that may impact on the natural history of HBV, and the emerging role of antivirals to reduce perinatal transmission of HBV. For women in their reproductive years who require treatment, many of the available antivirals have not been studied in pregnant or breast-feeding women and their use requires the development of a carefully considered strategy, considering the impact of both the disease and treatment on the mother and fetus/infant. The purpose of this article is to (1) review data regarding the mechanisms and timing of perinatal HBV infection; (2) review data on interventions, particularly antiviral therapy, to reduce perinatal transmission beyond the protection afforded by hepatitis B immunoglobulin and vaccination; (3) summarize the immunological changes associated with pregnancy and the potential effect these may have on the natural history of HBV infection; and (4) summarize the information currently available for antiviral therapy available for HBV treatment, focusing specifically on safety data pertaining to reproduction, pregnancy, and breast-feeding. TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians. LEARNING OBJECTIVES: After completing this CME activity physicians should be better able to classify the interventions to reduce mother-to-child transmission of hepatitis B including antivirals, caesarean section, hepatitis B immunoglobulin and hepatitis B vaccine, assess the immunological changes associated with pregnancy and the potential effect this may have on the natural history of HBV infection and apply the information currently available for antiviral therapy licensed for HBV treatment, focusing specifically on safety data in pregnancy and during breastfeeding.     

Ausgewählte tropische Infektionskrankheiten in der Schwangerschaft

About 500,000 pregnant women and 4 million babies die during the first 4 weeks of life every year, and in the last 3 months of pregnancy 4 million babies are stillborn; 99% of these deaths occur in developing countries, reflecting the poor standard of medical care and hygiene. The high mortality of pregnant women and newborns is due to malnutrition, bleeding, anemia, hypertension, miscarriage, abortion, obstructed labor, and infections. High-risk infections for pregnant women and their unborn children are Plasmodium falciparum malaria, helminthic infections, hemorrhagic fever viruses, hepatitis E, but also toxoplasmosis, tetanus, puerperal sepsis, and HIV. Pregnant women should be discouraged from traveling to tropical areas and countries with poor standards of hygiene and medical care. When undertaking a journey, pregnant travelers should be vaccinated against tetanus, poliomyelitis, diphtheria, measles, mumps, rubella, and varicella. Depending on the destination prophylaxis or vaccinations for malaria, hepatitis A and B, typhoid fever, yellow fever, meningococci, rabies, and Japanese encephalitis are recommended. If possible, all these vaccines should be administered before the pregnancy.     

Fetale Virusinfektionen

Infections during pregnancy may adversely affect pregnancy outcome and child health. They may be associated with fetal death, preterm delivery, congenital defects, and an increased risk of perinatal morbidity and mortality. The risk of intrauterine transmission and fetal disease depends on the nature of the pathogen, type of maternal infection (primary, recurrent, or chronic infection), and gestational age at time of fetal infection. The most important viruses that may cause symptomatic fetal infections are human cytomegalovirus (CMV), human parvovirus B19 (B19V), varicella-zoster virus (VZV), and rubella virus (RV). Available preventive measures (e.g., active or passive immunization, exposure or postexposure prophylaxis) and treatment options as well as modern serological and virological diagnostics should be thoroughly used to minimize the risk of sequelae associated with prenatal viral infections..     

Measles in pregnancy: a review

Although measles is usually considered a benign viral disease of childhood, people may be affected whatever their age with severe pneumologic or neurologic consequences are more frequent before 5 years old and after 20 years old. The consequences of a congenital measles, defined as a newborn eruption within 10 days after birth, can be dramatic. The incidence of measles has significantly decreased since first vaccines were introduced in the late 1960s. In France, active immunization for measles is proposed since 1983. Since the beginning of 2008, France has been experiencing a measles outbreak with more than 17,000 notified cases. The current measles outbreak affects more particularly very young children and young adults and, among these, pregnant women. Measles during pregnancy may be severe mainly due to pneumonia. Measles is associated with a risk of miscarriage and prematurity, but congenital anomalies have not been described. If rash occurs near term, the consequences of congenital measles could be severe. Prevention of measles in pregnant women is based on improving immunization coverage, currently insufficient to eradicate virus circulation. The aim of this review is to state on the latest data concerning measles virus, give latest vaccine recommendations, and also to suggest management of measles contact or measles infection during pregnancy.     

Is preeclampsia an infectious disease?

BACKGROUND: Studies have suggested a strong paternal factor in the etiology of preeclampsia. If preeclampsia is caused by an infectious agent transmitted by the woman's partner, seronegative women who may experience primary infection in pregnancy should be at increased risk of preeclampsia as compared to previously infected women. The aim of this study was to assess the impact of being seronegative for some viruses transmitted by close contact on the risk of developing preeclampsia. METHODS: Nine hundred and seventy-eight women were randomly drawn from a basic study population of 35,940 pregnant women in Norway. A serum sample drawn at the first antenatal visit was analyzed for specific IgG antibodies against herpes simplex virus type-2, cytomegalovirus and Epstein-Barr virus. For comparison, antibody status against Toxoplasma gondii was also assessed. Information on preeclampsia in pregnancy was obtained through linkage to the Medical Birth Registry of Norway. RESULTS: Thirty-three (3%) women developed preeclampsia. The risk of developing preeclampsia seemed to be increased for women who were seronegative for the viruses studied. Seronegativity for Toxoplasma gondii did not show such a pattern. INTERPRETATION: Women who are seronegative for antibodies against viral agents transmitted through close contact seem more likely to develop preeclampsia. This finding indicates that women who are seronegative to such agents may acquire primary infection in pregnancy, and subsequently be at increased risk of preeclampsia. This hypothesis could represent a new approach to the causes of preeclampsia, and encourage search for yet unidentified microbes as a possible causal factor.     

人巨细胞病毒在妊娠期筛查中的意义

人巨细胞病毒是一种在人体各种器官和组织中广泛存在的病毒。先天性的巨细胞病毒感染是新生儿视力障碍、先天性感音神经性耳聋、病毒性肝炎、病毒性肺炎等疾病的常见原因。妊娠期针对高危孕妇和胎儿进行筛查是临床干预的重要环节。