妊娠期风疹病毒感染对孕妇及胎儿的影响

目的 探讨妊娠期妇女风疹病毒的感染状况及对胎儿的影响。方法 应用酶联免疫吸附方法对1471例孕妇进行风疹病毒IgG,IgM抗体检测;对其中3例引产和死产的胎儿组织及胎盘行组织切片和电子显微镜检查,并用逆逆录-聚合酶链反应（RT-PCR）技术检测风疹病毒核酸。结果 76.1%(1119/1471)的孕妇风疹病毒IgG阳性;7.4%(109/1471)的孕妇风疹病毒IgM阳性,14.1%(208/1471)的孕妇风疹病毒IgG,IgM阴性;2.4%(35/1471)的孕妇风疹病毒IgG,IgM阳性。7例跟踪随访孕妇中,2例出现死胎,1例要求引产;1例引产胎儿的心肌组织细胞和2例死胎的心肌,肝,脑组织细胞及胎盘中均发现风疹病毒颗粒,并经RT-PCR检测到风疹病毒核酸。结论 妊娠期7.4%的孕妇可感染风疹病毒,并导致胎儿宫内感染,造成胎儿不同程度的损伤或严重的先天性风疹综合征。     

Studies on the management of pregnant women having high hemagglutination inhibition (HI) antibody titer of rubella virus in the first trimester examination of rubella virus antibody in the pregnant women having high HI titer by different methods and prognosis of their infants after birth

Several serological studies of rubella virus (RV) infection were carried out on sera of 45 pregnant women having RV hemagglutination inhibition (HI) antibody titer more than 1:512 in the first trimester, including a follow-up study of these women's pregnancies. In order to detect RV-specific IgM antibody, various procedures were employed as follows: Complement fixation test (CF), HI test after treatment of the sera with Protein-A (ProA-HI), enzyme linked immunosorbent assay (ELISA) by indirect or sandwich procedures and several tests using fractionated sera by sucrose density gradient ultracentrifugation (SDG). Positive ratios found with the CF test and ProA-HI were 26.7% and 20.0%, respectively. In indirect ELISA, 4 cases were positive for RV-specific IgM, but all sera were negative in sandwich ELISA and SDG tests. Both RV isolation from urine of some infants and detection of high RV-specific IgM antibody in cord sera failed to be positive. Of 44 pregnancies, 4 cases resulted in spontaneous abortion and all others in normal delivery. These forty normal infants had no sign of congenital rubella syndrome, but one case among them showed polysyndactyly . The results obtained here seemed to indicate that sandwich ELISA is the most valuable and convenient method among the tested procedures for clinically determined diagnosis of recent RV infection in pregnant women having a high HI antibody titer.     

Characteristics and serology of pregnant women with cytomegalovirus immunoglobulin G seroconversion during pregnancy in Japan

ObjectiveInvestigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection.Materials and methodsWe retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection.ResultsTwenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p < 0.001). Titers of CMV IgM at IgG seroconversion were higher in women without (median 8.66) than with (median 6.54) congenital infection (p = 0.045). The congenital infection rate was high when IgM titers at IgG seroconversion were low (47.1% with 4.00–12.00 titers and 100% with 1.21–3.99 IgM titers) (p = 0.048).ConclusionsNulliparous pregnant teenagers have a high risk of CMV IgG seroconversion and the CMV IgM titer at IgG seroconversion may help predict the occurrence of fetal congenital CMV infection.     

Cytomegalovirus and rubella seroprevalence in pregnant women in Izmir/Turkey: follow-up and results of pregnancy outcome

Purpose

It is aimed to determine the Rubella and CMV prevalence in the pregnant women in Izmir and to research the effect of these infections on the course of pregnancy in the pregnant women exposed to infection during pregnancy.

Methods

The pregnant women applied to pregnancy outpatient department during 2001?C2008 have been examined with enzyme-linked fluorescent assay (VIDAS; bioMérieux) method in terms of Rubella and CMV IgM and IgG antibodies and CMV IgG avidity test.

Results

Totally 5,959 pregnant women were included in the study. The seropositivity rates for Rubella and CMV were found as 97.8 and 98.3?%, IgM positivity rates were found as 0.37 and 0.18?%, respectively. Curettage was recommended to the pregnant women in which Rubella IgM positivity was detected in the first trimester of the pregnancy. Eight of the pregnant women in which IgM was found as positive after the 20th week of pregnancy were examined and three intrauterine growth retardation, one hypospadias and three normal deliveries were seen in these pregnant women. Any congenital anomaly finding was not detected in the pregnant women with positive CMV IgM.

Conclusions

Seroprevalence values are high for Rubella and CMV in our region. It can be recommended not to check the pregnant women routinely for this purpose with the good implementation of Rubella vaccine programs.     

CMV Infection and Pregnancy

Cytomegalovirus (CMV) occurs in 0.2?% to 2.2?% of all live births and is the most common cause of intrauterine infection and the leading infectious cause of sensorineural hearing loss and mental retardation. This article reviews literature that relate to the pathogenesis, diagnosis, and treatment of this disease for pregnant women and their fetus. Primary maternal CMV infection during pregnancy has a much higher rate of mother-to-fetus transmission and causes symptoms at birth and long-term disability than nonprimary infection. In addition, some research has shown that children with congenital CMV infection following first-trimester maternal infection are more likely to have severe sequelae. The prenatal diagnosis of fetal CMV infection includes serological testing (IgM detection and IgG avidity assay), amniocentesis, and ultrasound examination. The combination of the presence of CMV IgM antibodies and low CMV IgG avidity, along with maternal or fetal symptoms is used for the diagnosis of a primary maternal infection. Amniocentesis should be complemented until approximately 20-21?weeks of gestation to increase the sensitivity. Because ultrasound abnormalities are only found in less than 25?% of infected fetuses, ultrasound is as a relatively poor predictor of symptomatic congenital infection. CMV hyperimmunoglobulin also may be considered when the pregnant women are confirmed as primary CMV infection with low IgG avidity and amniotic fluid is found to contain CMV or CMV DNA. There is no consensus on the benefit of prenatal administration of ganciclovir into the umbilical vein.     

Routine Screening for Rubella and CMV Antibodies During Pregnancy: Is it Justifiable?

Background

Rubella and cytomegalovirus (CMV) screening during pregnancy is routinely carried out in India. However, its value has been questioned due to the absence of clearly effective intervention.

Objectives

This retrospective study evaluates the usefulness of rubella and CMV antibody screening during pregnancy.

Materials and Methods

Serum samples received from pregnant women and children were tested for rubella- and CMV-specific IgM antibodies by capture ELISA. The data were analyzed to determine the incidence of rubella and CMV infection during pregnancy and in congenital infections.

Results

In asymptomatic pregnant females (n = 505), rubella positivity was 3.16 % and in women with bad obstetric history (BOH) (n = 220), it was 7.72 %, while CMV positivity was 5.9 % in both asymptomatic pregnant women and in women with BOH. In children (n = 200), the overall positivity for rubella- and CMV-specific IgM antibodies was 15 and 25 %, respectively. A declining trend was observed in the incidence of both rubella and CMV infections in pregnant women and in women with BOH. In children, the incidence of congenital rubella syndrome has declined, but the incidence of CMV infection has remained almost the same in 5 years.

Conclusion

The incidence of rubella has reduced over the past 5 years and can further be prevented by providing direct protection to women and school girls with rubella vaccines. Primary CMV infection in pregnancy is the main problem, and due to the unavailability of efficient and safe treatment, routine antenatal screening for rubella and CMV should be reserved for women with obstetric complications only.     

Serological study of rubella in pregnancy: two years of experience in Palermo (1984-1986)

A serological survey was carried out by means of an ELISA capture-immunoassay for IgM and by means of the haemagglutino-inhibition method or ELISA for IgG antibodies on 715 women in fertile age and on 12 patients suffering from rubella or rubella-like syndrome. Fetal serum samples were obtained at fetoscopy from 4 pregnant women at different gestational age. The overall results show that although the high percentage (greater than 80.0%) of anti-rubella positive women in fertile age in our country, 18 out of 54 women in pregnancy, having had contacts with people affected by rubella or rubella-like syndrome, showed a seroconversion for rubella virus. The outcome of the pregnancy in these patients is known for 11 cases only: six women decided for abortion, four had a normal baby and one, mother of twins, bore an apparently healthy child the other one being dead 4 hrs after the delivery owing to fetal respiratory distress. Conclude this study some considerations on the necessity to emphasize the opportunity for a mass vaccination program and on the importance for more than one serological test to discriminate among different rubella-like syndromes.     

Rubella-specific IgM in reinfection and risk to the fetus

A case of reinfection with the wild rubella virus in the 8th gestational week is reported. The patient had preexisting hemagglutination inhibition antibodies of low titer following immunization with rubella vaccine. Reinfection was accompanied by clinical symptoms and the presence of rubella-specific immunoglobulin M (IgM) of high titer. Following termination of pregnancy no rubella virus could be isolated from the fetal tissues and the fetal blood contained no specific IgM antibodies. These results should encourage the use of cordocentesis before decision on interruption of pregnancy.     

A prospective study of primary cytomegalovirus infection during pregnancy: final report

In a 7-year prospective study cytomegalovirus (CMV) was shown to infect approximately twice as many pregnant women as did rubella virus. Fetal loss occurred in 4/26 (15%) early CMV infections which was seven-fold higher than the rate found in controls (16/744; 2.2%). There was no evidence that fetal loss resulted from intrauterine transmission of virus. Fifty-eight women experienced primary CMV infection and congenital infection was found in nine (20%) of the 46 infants from whom clinical samples were obtained. Transmission of virus was found in 20%, 0% and 40% in the first, second and third trimesters respectively. All babies were normal at birth but two have so far developed definite intellectual impairment attributable to cytomegalovirus infection. The mothers of both of these cases were infected after the fetus had become legally viable. We conclude that the lessons learned from studying rubella infection during pregnancy cannot be applied to cytomegalovirus; in particular, we could find no evidence that termination of pregnancy should be offered to women with early CMV infections.     

The detection of CMV in amniotic fluid and cervicovaginal smear samples by real-time PCR assay in prenatal diagnosis

Objective: There is no specific antiviral therapy or a vaccine, which could be safely administered to the pregnant women with primary human cytomegalovirus (CMV) infection. Therefore, prenatal diagnosis has a critical role in the management of pregnancy, complicated by this disease. In this study, we investigated the prevalence and clinical consequences of human CMV infection from cervicovaginal smear and amniotic fluid samples of pregnant women by using real-time polymerase chain reaction (RT-PCR) assay, in one of the Obstetrics and Gynecology outpatient clinics of Turkey. The identification of reliable prognostic markers of fetal disease remains the main purpose and a major challenge on this issue. Methods: Two hundred and six samples, of which 135 were cervicovaginal smear and 71 were amniotic fluid, were enrolled in the study. The DNAs of the samples were extracted by using Roche Diagnostic (Roche, Germany) kit and amplifications of these DNAs were studied by using Light-Cycler system (Roche Germany) as being quantitative. Anti-CMV IgM antibodies in the samples were studied by both MEIA (Imx system, Abbot Laboratories, USA) and a commercial ELISA kit (Radim SPA, Italy) while anti-CMV IgG antibodies were studied by MEIA (Axsym system, Abbot Laboratories, USA). Results: Human CMV DNA was found to be positive in 1.5% (2 in 135) of cervicovaginal smear and 1.4% (1 in 71) of amniotic fluid samples by RT-PCR. IgM and IgG were found to be negative in all of the cervicovaginal smear samples by both MEIA and ELISA, while IgG antibody was found to be positive in only one of the amniotic fluid samples by MEIA. Conclusion: With RT-PCR assay, we have found the prevalence of human CMV in pregnant women similar to epidemiologic reports, which have been described earlier. Whereas the fetus with positive amniotic fluid in favor of human CMV had an intrauterine growth restriction resulted in intrauterine exitus, no symptoms were observed in the infants of the other two pregnant women with positive RT-PCR results. The fact that the clinical consequence of the newborn whose amniotic fluid evaluation revealed human CMV infection by RT-PCR made us think that this molecular diagnosis method may be a reliable assay in prenatal diagnosis of this pathogen.     

Seropositivity of cytomegalovirus, parvovirus and rubella in pregnant women and recurrent aborters in Leningrad County, Russia.

BACKGROUND: The objectives of this paper were to assess the prevalence of different viral infections in relation to late abortions, stillbirths, and congenital malformations in sera from Russian pregnant women and recurrent aborters in order to establish basic knowledge for future pregnancy care. METHODS: Patients were recruited at the Women's Clinic, Leningrad Regional Hospital during the period March-June 1995. One group of normally pregnant women (Group 1; n=182) and one group of recurrent aborters (Group 2; n=127) were evaluated, including demographic, medical, clinical, and serological data. RESULTS AND CONCLUSIONS: The mean age of the two groups was 27.1 and 28.2 years, respectively. The mean number of deliveries was low (0.4 and 0.5, respectively). Thirty-one point six percent of Group 1 and 41.9% of Group 2 were daily smokers. The group of normally pregnant women had a significantly increased frequency of induced abortions compared to the recurrent aborters, while the recurrent aborters reported more genital infections. There was little difference in total antibodies to cytomegalovirus (CMV) (78.0% and 81.1%, respectively) or B19 IgG (75.3% and 66.9%, respectively) between the groups, while the normal pregnant women had a significantly higher prevalence of rubella antibodies (77.5% and 59.8%, respectively). Our results indicate that less women remain susceptible to primary CMV infection in pregnancy in Russia compared to western Europe and North America. The prevalence of B19 IgG was slightly lower than data from Sweden. Natural immunization against rubella virus was lower than in other, unvaccinated female populations. Vaccination strategies for rubella are now initiated in the Russian Federation. Results from this study are utilized in a federally supported, comprehensive pregnancy care project of North-West Russia.     

Antenatal Screening for Congenital Infection with Rubella, Cytomegalovirus and Toxoplasma

Summary: The sera of 3,463 pregnant women were screened, at the first antenatal visit, for antibodies to rubella, cytomegalovirus (CMV) and Toxoplasma gondii. Rubella antibodies were detected in 97.5%, CMV antibodies in 71% and toxoplasma antibodies in 45% of women. Asymptomatic toxoplasmosis occurred during pregnancy in 3 of 609 (0.5%) and primary CMV infection in 5 of 338 (1.5%) initially seronegative women whose sera were retested at the end of their pregnancies. The observed incidence of toxoplasmosis was similar to that calculated on the basis of the age-related prevalence of antibodies found in this study. On the basis of these observations it is estimated that congenital toxoplasmosis and congenital CMV infection due to primary maternal infection each occurs in up to 2/1,000 infants in this community. Very few of these infants have obvious abnormalities at birth, but follow-up studies elsewhere have shown that many of them suffer significant long-term sequelae.     

Seroprevalence of other antibodies (herpes, CMV, rubella, varicella, hepatitis B and C, syphilis, chlamydia, mumps, toxoplasmosis) in HIV-positive patients

We attempted to determine the seropositivity of HIV-positive patients to other antibodies (herpes, CMV, rubella, varicella, hepatitis B, hepatitis C, syphilis, chlamydia, mumps, toxoplasmosis). The study was carried out at the Prenatal Diagnosis and Therapy Centre of a Tertiary Hospital in Lagos, Nigeria. A total of 70 patients (50 females and 20 males) attending the centre between June 1997 and December 2005 who were screened and found to be HIV-seropositive were further screened for herpes simplex IgG/IgM, CMV IgG/IgM, rubella IgG/IgM, varicella IgG/IgM, mumps IgG/IgM, toxoplasmosis IgG/IgM, chlamydia IgG/IgM, hepatitis B and hepatitis C IgG/IgM using ELISA kits and syphilis (THPA) using the HAE method. Our study showed that a large number of HIV-positive patients are carriers of other antibodies and should be screened for them before therapy.     

Congenital cytomegalovirus infection following primary maternal infection in the third trimester

Objective  To determine the effect of primary cytomegalovirus (CMV) infection in the third trimester on fetal outcome.
Design  Observational study.
Setting  Four perinatal departments in tertiary hospitals in Israel.
Population  Twenty-eight women with primary CMV infection acquired after 25 weeks of gestation.
Methods  Prenatal evaluation included amniocentesis and ultrasonographic examinations. Maternal infection was determined from seroconversion and presence of low avidity anti-CMV immunoglobulin G after 25 weeks of gestation. Fetal CMV infection was diagnosed from CMV isolated or CMV DNA amplified from the amniotic fluid. Neonatal infection was established from CMV presence in their urine or anti-CMV IgM was in their peripheral blood immediately after birth. All liveborn neonates underwent cerebral ultrasonography, hearing assessment, and psychomotor development evaluation. Infected neonates were followed up for a median of 36 months (range 6–36 months).
Main outcome measures  Intrauterine CMV infection and neonatal CMV disease throughout follow up.
Results  Vertical transmission of CMV was documented in 21 (75%) of the 28 pregnancies. None of the 20 live infected newborn had symptomatic congenital infection. One pregnancy was terminated at 34 weeks following evidence of prenatal infection. Most of the patients (75%) had CMV serology test due to clinical signs of CMV disease.
Conclusions  Although CMV infection during the third trimester of pregnancy is highly transmissible, sequelae were not found among infected offspring.     

Post partum rubella vaccination and anti-D prevention]

The effectiveness of a routinely performed puerperal rubella vaccination was tested. Additional a possible adverse influence of simultaneously administered anti-D immunoglobulin on the effectiveness of the rubella vaccination was examined. Rubella antibody titers (HHT) in pregnant women were determined; after delivery puerperal women with titers of less or equal 1:16 were selected for rubella vaccination. 2 1/2 to 3 months later rubella antibody titers were done again. 15% of 130 vaccinated women did not show a conversion of the former negative titer or a low titer of 1:8 remained. Also reductions of the antibody titers were seen. When simultaneously rubella vaccination and anti-D immunoglobulin was administered only in 1 case out of 27 patients a negative titer remained after vaccination. The used anti-D immunoglobulin contained rubella antibodies of a titer 1:256 to 1:512; according to experimental studies, this concentration should not have any influence to the immunologic response of rubella vaccination. Our practic results could not confirm the reservations concerning simultaneous rubella vaccination and anti-D prophylaxis.     

妊娠早期巨细胞病毒感染和产前诊断案例分析

目的 分析妊娠早期动态定量检测巨细胞病毒（cytomegalovirus,CMV）抗体水平的意义,为临床医师对妊娠期CMV筛查和诊断提供参考依据。 方法 随机抽取2021年1—12月在惠州市中心人民医院妇产科门诊进行常规妊娠期检查的孕妇810例为研究对象。所有孕妇均在妊娠12周内采用电化学发光法定量检测CMV的IgG和IgM,间隔1~2周复查1次。结合2次抗体定量结果判断孕妇是否感染和感染类型。对诊断为CMV感染并引产的胎儿做病理分析。 结果 810例样本中CMV感染者为801例,其中既往感染者为783例（96.7%）,CMV原发感染和复发感染各1例,原发感染率和复发感染率均约为0.1%,IgM持续阳性共16例（2.0%）;CMV未感染者9例（1.1%）。1例引产胎儿病理诊断为播散性先天性CMV感染。结论 妊娠早期动态定量检测CMV抗体可反映孕妇感染情况和感染类型,有效排除临床诊治中的干扰,避免过度医疗干预。科学规范的妊娠期CMV检测是出生缺陷防控的核心所在。     

Prenatal diagnosis and outcome of congenital cytomegalovirus infection in twin pregnancies

OBJECTIVE: To study the outcome of 20 twin pregnancies with evidence of primary or recurrent cytomegalovirus (CMV) infection during pregnancy. DESIGN: Observational study. SETTING: Two tertiary perinatal departments in Israel. POPULATION: Twenty women with twin pregnancies who were referred because of serologic investigation indicating CMV infection. Seventeen women had evidence of primary CMV infection, and three women appeared to have recurrent CMV infection. METHODS: Prenatal diagnosis was made by amniocentesis of both sacs after 21 weeks of gestation. CMV isolation was performed by culture on fibroblasts, shell vial technique and polymerase chain reaction (PCR) amplification of CMV DNA. After birth, the neonatal urine and saliva were cultured for CMV. MAIN OUTCOME MEASURES: Intrauterine CMV infection defined as positive PCR at amniotic fluid analysis and congenital CMV infection defined as positive CMV cultures after birth. RESULTS: Except for one, all women underwent amniocentesis of both gestational sacs. In 14 (70%) women, no evidence of vertical transmission to any of the 28 fetuses was found and none of the newborns had evidence of congenital CMV infection. Intrauterine infection was detected by amniocentesis in five women and by ultrasound findings with positive maternal serology in one. In three women, CMV was detected in only one amniotic sac. In five of our six total cases, both twins were found to have congenital CMV infection at birth, all of whom had dichorionic-diamniotic placentation, three fused and two separate. CONCLUSIONS: In twin gestations, as in singletons, intrauterine and congenital CMV infection occurs in about 30% of women with primary or recurrent infection. The placenta type did not predict if one or both twins would be infected. Our data do not exclude the possibility that intrauterine transmission of the virus from one fetus to the other can occur.     

Fetal risk associated with rubella vaccine: implications for vaccination of susceptible women

The Centers for Disease Control has maintained a register of women who received rubella vaccine within three months before or three months after conception to follow prospectively the outcome of pregnancy and to quantitate the risks to the fetus from the vaccine virus. The data indicate that rubella vaccine can cross the placenta and rarely can infect the fetus. However, no abnormalities consistent with congenital rubella syndrome have been noted in 144 infants whose susceptible mothers received the RA 27/3 rubella vaccine, the only vaccine available in the United States since 1979. Although the observed risk of defects consistent with congenital rubella syndrome is zero, there is a statistical theoretic risk of a congenital rubella syndrome-like defect; the maximum theoretic risk is 2.6%. These findings indicate that vaccination of nonpregnant postpubertal women who lack either serologic proof of immunity or a written record of vaccination on or after the first birthday can be done safely and effectively. Whereas congenital rubella infection will disappear from the United States as vaccinated children enter the childbearing years, if these practices are followed elimination of congenital rubella infection will be hastened.     

Seroprevalence, incidence of prenatal infections and reliability of maternal history of varicella zoster virus, cytomegalovirus, herpes simplex virus and parvovirus B19 infection in South-Western Finland

Objective   To study seroprevalence and incidence and fetal transmission of varicella zoster virus (VZV), cytomegalovirus (CMV), herpes simplex virus (HSV) types 1 and 2 and parvovirus B19 infections during pregnancy and to evaluate the reliability of maternal past history of VZV, HSV and parvovirus infections.
Design   Prospective study of parturient women.
Setting   South-Western Finland.
Participants   Five hundred and fifty-eight parturient women.
Methods   IgG and IgM antibodies against VZV, CMV, HSV-1 and -2, and parvovirus B19 were measured from maternal serum in the first trimester and at delivery and from cord serum, mother's own information of her past infections was compared with her serological status.
Main outcome measures   Seroprevalence, seroconversions and fetal transmission of VZV, CMV, HSV and parvovirus B19, reliability of maternal history of VZV, HSV and parvovirus B19.
Results   Seroprevalences were 96.2% for VZV, 56.3% for CMV, 54.3% for HSV, 46.8% for HSV-1, 9.3% for HSV-2 and 58.6% for parvovirus B19. Parity was associated with CMV seropositivity, maternal age differed only between HSV-2 seropositive and seronegative women, while area of residence (urban or rural) had no effect. Six seroconversions were observed: two VZV, one CMV and three parvovirus infections. No cases of primary HSV infections occurred. Fetal transmission was observed in two cases of parvovirus infection. No infants with anti-CMV IgM antibodies were born to CMV immunised women. False positive history of chickenpox was given only by 1.5% of the women, history of herpes infections was less reliable, and history of parvovirus infection was unreliable.
Conclusions   Seroprevalence and the risk of viral infections during pregnancy cannot be extrapolated from one pregnant population to another.