Zika-Virus-Infektion in der Gynäkologie und Geburtshilfe

The Zika virus is transmitted predominantly via the bite of infected mosquitoes. Sexual transmission is also possible. In up to 80?% of cases, the course of infection is asymptomatic or oligosymptomatic, the majority of symptoms lasting for only 7 days. The most important symptoms are skin reactions, fever, arthralgia or arthritis-like complaints, and nonpurulent conjunctivitis. The Zika virus is associated with various neurologic diseases (e.g., Guillain–Barré syndrome) in adults, as well as with fetal microcephaly during pregnancy. Whereas the risk of microcephaly resulting from infection during the first trimester has been estimated between 1 and 47?%, the corresponding risk due to infection in the second and third trimesters appears to be negligible. Pregnant women who have recently travelled in endemic regions could be tested. Extended ultrasound examinations are recommended for all pregnant women who live or have travelled in a Zika virus endemic region. Mothers testing positive should undergo sequential ultrasound examinations every 3–4 weeks. Symptomatic treatment of manifest disease employs analgesics and antipyretics, as well as ample fluid intake. Pregnant women should avoid business trips and private travel to Zika virus endemic regions. If this is unavoidable, precautionary measures should be taken to guard against mosquito bites. Since sexual transmission is possible, male partners of pregnant women, who live in or travel to Zika virus endemic regions, should either refrain from sexual intercourse or use condoms for the entire duration of the pregnancy.     

The Zika Virus and Pregnancy

Purpose of Review

Following the recent association of Zika virus with microcephaly in Brazil, there has been a multitude of studies attempting to elucidate the relationship between Zika virus infection in pregnancy and congenital anomalies. The American Congress of Obstetricians and Gynecologists (ACOG), the U.S. Centers for Disease Control and Prevention (CDC), and the Society for Maternal Fetal Medicine (SMFM) have all issued guidelines governing the screening and management of pregnant patients with Zika exposure. These guidelines have rapidly evolved as the scientific evidence supporting causation of microcephaly in cases of Zika Virus infection has continued to mount. The purpose of this article is to review the current guidelines and the available evidence on which they are based.

Recent Findings

A series of experiments on animals and human cell lines have demonstrated that Zika virus is neurotropic. Further, examinations of amniotic fluid, fetal tissues, and placenta have confirmed the ability of Zika virus to cross the placenta. With the currently available evidence, the CDC has recently concluded that Zika virus infection in pregnancy is a cause of microcephaly.

Summary

Recently, it has become clear that Zika virus infection during pregnancy is responsible for congenital brain anomalies and microcephaly in the offspring. What remains unclear is the rate of vertical transmission from mother to fetus, the risk of microcephaly, and other CNS anomalies in fetuses when maternal infection is proven and the time from exposure or infection to clinical manifestations including ultrasound anomalies. Further studies are needed to answer these important questions.

     

Viral infection,proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection

Purpose

Attention is increasingly focused on the potential mechanism(s) for Zika virus infection to be transmitted from an infected mother to her fetus. This communication addresses current evidence for the role of the placenta in vertical transmission of the Zika virus.

Methods

Placentas from second and third trimester fetuses with confirmed intrauterine Zika virus infection were examined with routine staining to determine the spectrum of pathologic changes. In addition, immunohistochemical staining for macrophages and nuclear proliferation antigens was performed. Viral localization was identified using RNA hybridization. These observations were combined with the recent published results of placental pathology to increase the strength of the pathology data. Results were correlated with published data from experimental studies of Zika virus infection in placental cells and chorionic villous explants.

Results

Placentas from fetuses with congenital Zika virus infection are concordant in not having viral-induced placental inflammation. Special stains reveal proliferation and prominent hyperplasia of placental stromal macrophages, termed Hofbauer cells, in the chorionic villi of infected placentas. Zika virus infection is present in Hofbauer cells from second and third trimester placentas. Experimental studies and placentae from infected fetuses reveal that the spectrum of placental cell types infected with the Zika virus is broader during the first trimester than later in gestation.

Conclusions

Inflammatory abnormalities of the placenta are not a component of vertical transmission of the Zika virus. The major placental response in second and third trimester transplacental Zika virus infection is proliferation and hyperplasia of Hofbauer cells, which also demonstrate viral infection.

     

New emerging blood-borne hepatitis viral pathogens and the feasibility of passing thorough the placenta: an appraisal

In countries with a high prevalence of blood-borne pathogen infections, transmission to infants commonly occurs from an infected mother during pregnancy. Maternal diseases caused by bacteria, viruses and parasites may sometimes be transmitted vertically. For many pathogens, several questions remain unanswered about the pathogenesis of vertical transmission, the relative risk associated with each mode of transmission, the rate of transmission from mother to child, and the factors that might contribute to the efficiency of transmission. There is also a need to quantify the contribution made by intrauterine versus intrapartum events. Here, the feasibility of some new emerging blood-borne hepatitis viral pathogens (hepatitis G virus, hepatitis SEN virus and hepatitis TT virus) passing through the placenta was analyzed based on a consideration of nonostructure level. Based on the particle size as a single factor, it is hereby proposed that the transmission of the studied viruses via the placenta is difficult. Possible infection due to other processes, especially intrapartum infection due to micro-trauma delivery, similar to HIV infection, might be a more important route of vertical transmission.     

Apoptosis in placentas from human T-lymphotropic virus type I-seropositive pregnant women: a possible defense mechanism against transmission from mother to fetus.

OBJECTIVE: The mechanism by which the placenta serves as the barrier against mother-to-fetus transmission of microorganisms remains to be elucidated. Programmed cell death, apoptosis, is considered a cellular defense mechanism against infection. The hypothesis of this study is that apoptosis of human T-lymphotropic virus type I (HTLV-I)-infected placental villous cells is involved in the defense mechanism against mother-to-fetus transmission of HTLV-I. METHODS: Apoptosis was compared in term placentas from eight HTLV-I-seropositive pregnant women and eight HTLV-I-seronegative pregnant women by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method. In addition, an in vitro cocultivation with an HTLV-I-infected lymphocyte cell line (MT-2 cells) was performed to examine whether placental villous cells were infected with HTLV-I and apoptosis was induced. RESULTS: The incidence of apoptosis-positive cells (nuclei) in placentas from the HTLV-I-seropositive pregnant women was higher than in the HTLV-I-seronegative pregnant women (P < .02). Cocultivation with MT-2 cells showed that trophoblast cells were able to be infected with HTLV-I and that apoptosis was induced in the placental villous cells. CONCLUSION: HTLV-I infection induces apoptosis in the placenta. We speculate that apoptosis may be involved in the defense mechanism of the placenta against mother-to-fetus transmission of HTLV-I.     

Adverse outcomes of pregnancy-associated Zika virus infection

The spread of Zika virus to the Americas was accompanied by surge in the number of infants with CNS abnormalities leading to a declaration of a health emergency by the WHO. This was accompanied by significant responses from governmental health agencies in the United States and Europe that resulted in significant new information described in the natural history of this perinatal infection in a very short period of time. Although much has been learned about Zika virus infection during pregnancy, limitations of current diagnostics and the challenges for accurate serologic diagnosis of acute Zika virus infection has restricted our understanding of the natural history of this perinatal infection to infants born to women with clinical disease during pregnancy and to Zika exposed infants with obvious clinical stigmata of disease. Thus, the spectrum of disease in infants exposed to Zika virus during pregnancy remains to be defined. In contrast, observations in informative animal models of Zika virus infections have provided rational pathways for vaccine development and existing antiviral drug development programs for other flaviviruses have resulted in accelerated development for potential antiviral therapies. This brief review will highlight some of the current concepts of the natural history of Zika virus during pregnancy.     

Timing and Mechanism of Perinatal Human Immunodeficiency Virus-1 Infection

Summary: There is sufficient evidence indicating a higher vertical HIV-1 transmission rate in the last trimester and during labour compared with the first trimester. Antiretroviral therapy either single or in combination given to the mother during the last trimester and delivery can reduce the viral load in the maternal circulation. Vertical HIV-1 transmission during delivery can be minimized by appropriate timing and route of delivery. Elective Caesarean section before the onset of labour with an intact bag of forewaters provides the least mother-to-fetus microtransfusion compared to other modes of delivery. Since an effective combination of HIV-1 immunoglobulin and HIV-1 vaccine given to the HIV-1 exposed newborns to prevent HIV-1 transmission similar to the viral hepatitis B model is not firmly established at present, postexposure antiretroviral prophylaxis and nonbreast-feeding are advocated for infants born from the HIV-1 infected mothers. In cases of advanced stage of maternal HIV-1 infection, and in developing areas where malnutrition prevails, an adequate supply of essential micronutrients is proposed as an adjunctive measure to reduce HIV-1 perinatal transmission.     

Update on the management of hepatitis B and C infections in the neonatal period

Hepatitis B virus and hepatitis C virus have received a significant amount of attention in recent years, and both viruses share a significant amount of similarities with one another beyond just that they both primarily target the liver. In recent years, cases of both infections have been fueled by a nationwide epidemic of injection drug use. Most relevant to this audience, they are both transmitted from mother to child. The increased cases in young adults combined with mother to child transmission translate into more exposed infants that will need to be managed and followed. Screening of pregnant women for hepatitis B infection coupled with appropriate treatment and prophylaxis measures are incredibly effective to preventing transmission. Prevention of hepatitis C infection is not yet possible, but advances in antiviral therapy make interruption of transmission a future possibility.     

The ever-evolving epidemiologic concepts of human immunodeficiency virus infections.

Human immunodeficiency virus infection has now reached epidemic proportions in both industrialized and nonindustrialized countries. Two preventive measures remain of questionable benefit: mandatory testing and partner notification. Sexually transmitted diseases and cervical ectopy may be risk factors for heterosexual transmission, now the most frequent mode of transmission of human immunodeficiency virus worldwide. Smokable freebase cocaine, the use of which is increasing in many cities in industrialized countries, is associated with acquisition of sexually transmitted diseases and human immunodeficiency virus infection. In addition to perinatal transmission of human immunodeficiency virus, postnatal transmission via breastfeeding has been demonstrated in association with a recent acquisition of human immunodeficiency virus by the mother. Intriguingly, in multiple pregnancies, first-born twins of human immunodeficiency virus-infected mothers could be at higher risk of infection than second-born twins. Nosocomial transmission of human immunodeficiency virus, both from infected patients to health professionals and from infected health professionals to patients, is a matter of concern and justifies preventive measures.     

Mother-to-child transmission of hepatitis C virus: recent news about the benefit of caesarean sections

The rate of mother-to-infant transmission for hepatitis C virus is estimated to be around 5% of viraemic mothers and represents an important route of HCV infection among children. Transmission is possible in utero but the highest risk of infection is at or near the time of delivery because of an important blood transmission of hepatitis C virus. Mothers with high levels of HCV-RNA and co-infected for human immunodeficiency virus are documented to have risk factors for vertical transmission of HCV. Thus, for these, the mode of delivery must be discussed even if there are no precise recommendations. Among obstetrical risk factors, the results of literature fail to prove a benefit of elective caesarean delivery in the aim to reduce the vertical transmission of HCV. However, obstetrical situations with a high risk of blood contact between mother and foetus must be considered and if possible evicted.     

Hepatitis C virus in pregnancy: case reports and literature review

Background: Hepatitis C virus (HCV) is now recognized as the cause of 90% of non-A, non-B (NANB) hepatitis. This virus is responsible for a large percentage of chronic persistent and chronic active hepatitis in the United States. Parenteral and sexual transmission are well described, so a significant population of pregnant patients is at risk. Vertical transmission of the virus to the fetus is dependent upon the level of maternal viremia.Case: The cases described in the following report demonstrate that fulminant disease may present in pregnancy. They also demonstrate the cofactors promoting the severity of illness, methods of diagnosis, potential treatment, and outcome of the infection.Conclusion: HCV may be encountered in pregnancy. Although most acute-phase illness will be self limiting, some patients will manifest liver failure during gestation. Because vertical transmission to the fetus is possible, the pediatrician should be informed of the maternal disease. Chronic hepatitis is almost the rule rather than the exception, so patients require close postpartum follow-up. Interferon, which may alter the course of the chronic disease, has been used on rare occasions in pregnancy.     

妊娠寨卡病毒感染对胎儿脑/神经系统发育的影响

近年来,南美洲寨卡病毒（Zika virus）流行,同时该地区吉兰-巴雷综合征（Guillain-Barré syndrome）、新生儿小头畸形发病率明显升高。截至2016年3月,疫情共波及美洲33个国家和地区,超过19万人疑似感染。另外,欧洲、亚洲诸国也均有输入性病例的报道。妊娠寨卡病毒感染与胎儿神经系统发育异常存在着高度的相关性,这已引起了全球范围的密切关注。寨卡病毒影响胎儿神经系统发育的机制可分为直接和间接两条途径：①寨卡病毒可通过血-胎盘屏障,且病毒具有嗜神经性,直接影响胎儿的神经系统发育;②寨卡病毒通过其他介质间接影响胎儿的神经系统发育,如通过胎儿炎症反应介质或免疫交叉反应产生的抗体等。虽然具体机制目前尚未完全明确,但现阶段及时阐明妊娠寨卡病毒感染对胎儿神经系统发育的影响及防控该病毒在中国境内的传播,将具有极为重要的临床意义和长远的社会意义。     

Hepatitis B and C virological tests: interpretation and practical results in women

Chronic Hepatitis C or B infection can lead to liver cirrhosis and hepatocellular carcinoma. In women, these viral infections can be responsible for transmission to the spouse and to the child during delivery. Concerning the hepatitis C virus, the factors most strongly associated with infection are injection-drug use and blood transfusion before 1991. The risk of mother-to-infant transmission of hepatitis C virus is uncommon (5 per cent): except for the viral eradication before pregnancy, there is no preventive measure to propose. Pregnancy is not contra-indicated. Hepatitis C virus transmission by sexual contact in steady monogamous partnerships is low (< 1 per cent). In most developed parts of the world where the prevalence of chronic hepatitis B infection is low, most infections occur among high-risk adult populations including injection drug users and multiple heterosexual partners. On the contrary, in high prevalence areas, infection occurs during either the perinatal period or early in childhood. The risk of maternal-infant contamination is high, from 20 to 90 per cent according to the viral load. Vaccination prevents risk of infection and is strongly advised to persons at high risk of infection. Universal vaccination of infants is highly recommended.     

Hepatitis C in obstetrics and gynecology.

Because of the risk of perinatal transmission and possible sexual transmission, it is important for obstetrician-gynecologists to keep abreast of the rapidly expanding literature on hepatitis C. Acute hepatitis C represents about 5% of all reported cases of hepatitis. Approximately 50% of acute infections progress to chronic liver disease. Risk factors for infection include intravenous (IV) drug use (21-42% of cases), previous blood transfusion (6-17%), and multiple sexual partners (6%); 40-50% of cases have no identified risk factors. The seroprevalence of anti-hepatitis C antibody is 70.8% in IV drug users, 11.6% in patients with human immunodeficiency virus, 8.8% in prostitutes, 1.2% in hospital personnel, and 0.5-1.4% in volunteer blood donors. The risk of transmission to the neonate depends on the trimester at exposure. No perinatal transmission has been shown after acute maternal infection in the second trimester. Based on the few reported cases, chronic maternal infection or acute infection in the third trimester may result in neonatal infection rates of 45-87.5%. Universal screening is probably not cost-effective because the prevalence is low and over 70% of screening tests can be falsely positive using the currently approved assay. Selective screening of high-risk patients is recommended.     

Hepatitis B: Treatment to prevent perinatal transmission

Hepatitis B remains a significant health issue and a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Transmission of the hepatitis B virus, despite the availability of the vaccine, still occurs, particularly in the perinatal setting. Studies have shown that mothers with active viremia especially those with very high viral levels (>10? copies/mL or >10? IU/mL) are at increased risk of hepatitis B virus transmission, even with appropriate immunoprophylaxis at birth. With the development of new and relatively safe oral antiviral therapies, assessment with the mother about the risks and benefits of antiviral therapy should be discussed in those with highest transmission risk.     

Impact of Zika virus for infertility specialists: current literature,guidelines, and resources

In the past 2 years, Zika virus has emerged from obscurity onto the world stage—traversing and transcending clinical specialties, basic science disciplines, and public health efforts. The spread of Zika virus has serious implications for the specialty of reproductive endocrinology and infertility. Our patients, practices, and labs—worldwide and specifically in the USA—have been impacted by this teratogenic, sexually transmitted, largely asymptomatic virus. While the World Health Organization’s Public Emergency of International Concern designation has lapsed as major epidemics have subsided and understanding of risks is in part clarified, the acute and long-term threat to pregnant patients is not over. The risk of wider spread in the USA is not insignificant, the subtler and long-ranging consequences beyond microcephaly are not fully known, large geographic areas of risk still contain naïve populations, and whether Zika will continue to be an intermittent risk in endemic areas is uncertain. Staying up to date with the burgeoning research on Zika virus is an important objective for the infertility specialist. Here, we review in detail the most relevant recent developments, discuss applicable guidelines, and propose strategies for contributing to a reduction in the risk and burden of Zika virus.     

Hepatitis B vaccine in pregnancy: maternal and fetal safety

Perinatal transmission of hepatitis B (HB) virus occurs if the mother has had acute HB infection during late pregnancy or in the first months postpartum, or if the mother is a chronic HB antigen carrier. Vertical transmission from chronic carriers exceeds 90% and accounts for up to 40% of the world chronic carriers in endemic areas. Hepatitis in pregnancy is not associated with increased abortion rate, stillbirth, or congenital malformation. However, prematurity seems to be increased if hepatitis is acquired in the last trimester. Sixty percent of pregnant women who acquire acute HB infections at or near delivery will transmit the HB virus to their offspring. Although infection is rarely symptomatic, 70 to 90% of the babies will remain chronically infected into adult life and be prone to cirrhosis and hepatocellular carcinoma. Because of such high risks and the safety and efficacy (seroconversion 90 to 100%) of HB vaccine in preventing HB infection, it is recommended that HB vaccine be given to pregnant women at high risk. However, its safety to the fetus is not well documented. Only one human study reports the safety and efficacy of Heptavax, but only when administered (to 72 pregnant women) in the last trimester of pregnancy when embryopathy cannot occur. We report pregnancy outcome in ten women, mostly health care personnel or patients traveling to endemic areas exposed to the vaccine during the first trimester of pregnancy. No congenital abnormalities were observed and all the infants are physically and developmentally normal for their ages at 2 to 12 months. Although small, this cohort suggests safe use of the vaccine in early pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Routine hepatitis C virus screening in pregnancy: a cost-effectiveness analysis

OBJECTIVE: The purpose of this study was to determine whether routine hepatitis C virus screening in pregnancy is cost-effective. STUDY DESIGN: A decision tree with Markov analysis was developed to compare 3 approaches to asymptomatic hepatitis C virus infection in low-risk pregnant women: (1) no hepatitis C virus screening, (2) hepatitis C virus screening and subsequent treatment for progressive disease, and (3) hepatitis C virus screening, subsequent treatment for progressive disease, and elective cesarean delivery to avert perinatal transmission. Lifetime costs and quality-adjusted life years were evaluated for mother and child. RESULTS: In our base case, hepatitis C virus screening and subsequent treatment of progressive disease was dominated (more costly and less effective) by no screening, with an incremental cost of 108 US dollars and a decreased incremental effectiveness of 0.00011 quality-adjusted life years. When compared with no screening, the marginal cost and effectiveness of screening, treatment, and cesarean delivery was 117 US dollars and 0.00010 quality-adjusted life years, respectively, which yields a cost-effectiveness ratio of 1,170,000 US dollars per quality-adjusted life year. CONCLUSION: The screening of asymptomatic pregnant women for hepatitis C virus infection is not cost-effective.     

ACOG Committee Opinion. Number 332, May 2006 (replaces No. 203, July 1998): Hepatitis B and hepatitis C virus infections in obstetrician-gynecologists

Hepatitis B and hepatitis C may be transmitted form patients to health care workers and from health care workers to patients. To reduce the risk, all obstetrician-gynecologists who provide clinical care should receive hepatitis B virus vaccine. Obstetrician-gynecologists who are hepatitis B surface antigen positive and e antigen positive should not perform exposure prone procedures until they have sought counsel from an expert review panel. Because the risk of hepatitis C virus transmission is lower than that of hepatitis B virus transmission, routine testing of health care workers is not recommended, and hepatitis C virus-positive health care workers are not required to restrict professional activities.     

Hepatitis C-Implications in Pregnancy

Hepatitis C is a single-stranded RNA virus chat is transmitted primarily through transfusion of blood or blood products, or through the sharing of contaminated needles among injection-drug users. Heterosexual transmission of the virus has been reported. It is uncommon. Vertical transmission of the virus from mother to infant has also been reported but there are no large scale studies evaluating this. The literature suggests a vertical transmission rate of about six percent, but there is some recent evidence to suggest chat wornen with high titres of virus (which is uncommon) may transmit at a higher rate. Treatment for chronic persistent hepatitis C is currently interferon-alpha, but its use has not been investigated in pregnancy. Pregnant patients in high risk groups (intravenous drug users, recipients of multiple transfusions, undiagnosed hepatitis) should be screened for hepatitis C. Currently, there are no proven regimens available to decrease the likelihood of transmission. Investigators have not been able to isolate the hepatitis C virus from breast milk, therefore, there is no good evidence to advise women to avoid breastfeeding.