Prenatal detection of rubella-specific IgM in fetal sera

Serum specimens were obtained by fetoscopy at 19-25 weeks' gestation from four fetuses whose mothers had had confirmed rubella earlier in pregnancy. They were tested for rubella-specific IgM by antibody capture radioimmunoassay. No specific IgM was detected in one fetus and a healthy infant was delivered at term. Specific IgM was detected in the other three fetuses. In one case the level was low (1 unit) and this pregnancy went to term resulting in a neonate with clinical and laboratory evidence of congenital rubella infection. The remaining two fetuses had 2.8 and 2.4 units of specific IgM and the pregnancies were terminated. Blood obtained from these two fetuses after abortion showed levels of 5.4 and 2.9 units respectively. No specific IgM was detected in sera from eleven other fetuses aborted because of maternal rubella but five of these cases were terminated before 19 weeks and in five the interval between rash and abortion was three weeks or less. The results show that the human fetus can produce detectable specific IgM antibody by 19-20 weeks' gestation after exposure to rubella several weeks earlier. However, a larger study is required to define the reliability of fetoscopic blood sampling for the diagnosis of intrauterine infection.     

A serological testing algorithm for the diagnosis of primary CMV infection in pregnant women

OBJECTIVES: Serological diagnosis of CMV primary infection is usually based on the detection of specific IgM antibody. However, as the presence of IgM antibody is not always correlated with primary infection, measurement of IgG avidity must be performed. The aim of our study was to evaluate the best procedure for serological diagnosis of CMV primary infection. In other words, is it better to first search for IgM antibody, and, if positive, then measure IgG avidity, or first measure IgG avidity without the detection of IgM antibody? MATERIALS: CMV-IgM detection and CMV-IgG avidity measurement were performed on 310 IgG positive sera from pregnant women. RESULTS: CMV-IgM antibody was detected positive for 9 of 310 sera. Using CMV-IgG avidity index (AI), dating of infection was difficult in 81/310 cases (26%), while it failed in only 3/310 cases using CMV-IgM plus CMV-IgG AI. CONCLUSION: The diagnosis of primary CMV infection can be based on the detection of CMV-IgM antibody first and then on the measurement of CMV-IgG AI.     

Is there an association between fetal viral infection and fetal malformation? I. Detection of specific IgM antibodies in the serum of malformed fetuses

Determinations of IgG and IgM antibodies specific for cytomegalovirus (CMV), herpes simplex virus (HSV1), herpes simplex virus (HSV2), varicella-zoster virus (VZV), rubella, echo, Coxsackie and morbilli viruses were performed in 20 sera from malformed fetuses. Demonstration of a fetal infection by increased fetal serum IgM permits linkage to a detected fetal malformation. In parallel, 14 maternal sera and 17 amniotic fluid samples were examined. Laser nephelometry (a quantitative method) was used for the determination of IgM and IgG class immunoglobulins. None of the fetal sera were found to contain IgM class antibodies specific for the viral antigens studies. While IgM CMV-specific antibodies were present in one maternal serum, the specific IgM was absent in the fetus. The absence of specific IgM antibodies appears to warrant the conclusion that the malformed fetuses were uninfected by any of the above viruses. IgM antibodies were detected in two fetal sera by quantitative methods. The IgM antibodies present in two fetuses probably were generated in response to some other introduced antigen.     

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。     

Detection of sperm-bound antibodies in the male partners of infertile couples using the immunobead test

The aim of this investigation was to determine the incidence of sperm-bound antibodies in the male partners of an unselected infertile population using an immunologically specific test (IBT). With this method 34 out of 450 infertile men (7.55%) were positive for one or more of the immunoglobulins IgA, IgG and IgM. For IgG and IgA, the majority of antibody binding was located on the entire sperm with a minor amount bound to the head or tail. For the IgM, the majority of the binding was detected to the tail tip, and tail binding was observed only in a minority of cases.     

妊娠晚期孕产妇柯萨奇病毒感染筛查结果分析

用间接免疫荧光染色法，对４２２例妊娠晚期孕产妇血清中柯萨奇Ｂ组病毒（ＣｏｘＢ）筛查，阳性者２１例，其感染率为５％，其中在我院分娩１２例，全部使用干扰素治疗，有３例用药后病毒检查由阳性转阴性，提示可能与应用干扰素抗病毒及调节机体免疫功能有关。胎儿出生后查脐血ＣｏｘＢ阴病毒特异性ＩｇＭ抗体，结果无１例垂直感染。据此作者认为：在柯萨奇病毒流行季节，孕产妇的普遍筛查，对控制病源的传播具有重要意义。     

Neonatal screening for congenital toxoplasmosis in a cohort of 165 women infected during pregnancy and influence of in utero treatment on the results of neonatal tests

The aim of this study was to determine the performances of methods used for the neonatal diagnosis of congenital toxoplasmosis. We included 165 pregnant women infected during pregnancy over a 10-year period. Fifty-seven cases of congenital toxoplasmosis were demonstrated (34.5%). Neonatal diagnosis gave positive results in 50 cases (88%). Parasites were isolated from placenta or cord blood in 61% of the infected newborns, more frequently from placenta (60%) than from cord blood (43%). This method was the only criterion of infection in 18% of these infected infants. The detection of specific IgM and IgA antibodies performed on 42 sera of infected infants allowed the diagnosis of congenital infection in 34 cases (81%). IgA antibodies were more frequently detected (60%) than specific IgM (50%). Neonatal and prenatal screening were carried out for 143 pregnant women. This combination diagnosed 39 of 40 infected infants (98%). Prenatal diagnosis identified 30 of 40 cases (75%). Nine cases were diagnosed through neonatal screening and one case with the postnatal follow-up. When prenatal diagnosis was positive, pyrimethamine and sulfadoxine were administered to the mothers (25 cases) in addition to spiramycin. Toxoplasma gondii was less frequently isolated in the placenta and the cord blood of these women (32% and 19%, respectively) than in women treated by spiramycin alone (83% and 63%) proving the antiparasitic action of these drugs. In conclusion, neonatal screening combining parasite detection in placenta and immunological methods on cord blood is essential particularly when prenatal diagnosis is negative. Therefore, when this diagnosis is positive, a treatment with pyrimethamine and sulfamide can be started in the first month of life.     

Immunoglobulins and monoclonal anti-blastocyst antibodies in the mouse uterine secretion during the early pre-implantation period

A Sepharose bead blot technique was used to study immunoglobulins in the uterine secretion of mice during the pre-implantation stage. Secretion collected by Sepharose beads contained IgA, IgG, and IgM. The method could be made ten-fold more sensitive by using anti-mouse IgG or IgM conjugated to Sepharose beads. It has also been demonstrated that when injected intravenously, biotinylated purified immunoglobulins, both non-specific mouse myeloma IgG and IgM and specific antiblastocyst IgG and IgM, is able to pass into the uterine cavity of the mouse. It was further shown that when injected systemically, anti-blastocyst antibodies can reach the blastocyst. Functionally active specific antibodies against morulae and/or blastocysts may, therefore, be able to influence the pre- and peri-implantation development of the embryo and could serve as a useful model for experiments directed towards the identification of immunological contraceptive procedures.     

一氧化氮与妊娠早期人巨细胞病毒宫内活动性感染的关系

目的　探讨一氧化氮与妊娠早期人巨细胞病毒 (HCMV)宫内活动性感染的关系。方法　选取既往有自然流产、死胎、胎儿畸形、胎儿生长受限等异常妊娠史并行人工流产术的早孕妇女 81例 ,应用逆转录 聚合酶链反应技术检测其胎盘绒毛组织HCMV mRNA的表达 ;酶联免疫吸附试验法测定其血清HCMV IgM ;原位杂交法检测其蜕膜巨噬细胞诱生型一氧化氮合酶 (iNOS) mRNA的表达并行定量分析。结果　 (1) 81例孕妇中有 6例胎盘绒毛组织HCMV mRNA阳性 ,14例血清HCMV IgM阳性 ,阳性率为 17 3 % (14/ 81)。依据HCMV mRNA与HCMV IgM检测结果 ,81例孕妇分为 3组 :Ⅰ组 :HCMV mRNA与HCMV IgM均阳性 5例 ,其宫内传播率为 3 5 7% (5 / 14) ;Ⅱ组 :HCMV mRNA阴性而HCMV IgM阳性 9例 ;Ⅲ组 :HCMV mRNA与HCMV IgM均阴性 66例。另有 1例HCMV IgM阴性者其胎盘绒毛组织HCMV mRNA阳性。 (2 )Ⅰ组患者蜕膜iNOS mRNA呈强表达 ,其吸光度值为 0 412±0 0 19,明显高于Ⅱ组的 0 172± 0 0 3 3与Ⅲ组的 0 167± 0 0 3 3 ,Ⅰ组与Ⅱ组及Ⅲ组比较 ,差异有显著性(P <0 0 5 ) ;Ⅱ组与Ⅲ组比较 ,差异无显著性 (P >0 0 5 )。 1例HCMV IgM阴性而胎盘绒毛组织HCMV mRNA阳性者 ,蜕膜iNOS mRNA也呈强表达 ,其吸光度值为 0 40 3。结论　一氧化氮可     

Dengue fever during pregnancy. Cases report

Dengue is known as an endemic disease of tropical and subtropical regions. It was considered a disease very frequent on kids, but recently an increase was reported on adult people. Some of these cases were related to pregnant women, for that reason, we decided to check eight cases, including just the mothers who presented dengue virus infection through ELISA IgM. IgG and ELISA IgM studies. Five products were determined between 3 and 9-born-babies. Eight cases of dengue were analyzed during pregnancy, three cases of fever dengue and five cases of hemorrhagic dengue; main complications detected were threat of abortion, and premature labour, postsurgical bleeding with desiccant haematoma of uterine artery, oligohydramnios, as well as pleural effusion, two of the neonates were classified as septic for presenting fever. In no case, IgG or IgM for fever dengue was detected in neonates.     

Anti-annexin V IgM and IgG autoantibodies and the risk of idiopathic recurrent spontaneous miscarriage

Anti-annexin V antibodies have been identified as risk factors for recurrent spontaneous miscarriage (RSM) in some, but not all previous studies. We investigated the association between anti-annexin IgM and IgG in RSM cases and control women. Blood samples from 244 women with idiopathic RSM, and 283 multi-parous control women were tested for anti-annexin V antibodies by ELISA. A significant elevation in anti-annexin V IgM and IgG was seen in the RSM cases. An increased prevalence of elevated anti-annexin V IgM and to a lesser extent anti-annexin V IgG was seen in RSM patients. Receiver operating characteristic analysis indicated that the area under the curve for anti-annexin V IgM was 0.916, and for anti-annexin V IgG was 0.725. A systematic shift in anti-annexin V IgM and IgG distributions toward higher values occurred in RSM women, which was confirmed by percentile analysis. For each of the anti-annexin V isotypes, the adjusted odds ratio increased as the percentile value increased; the strongest risk was for anti-annexin V IgM, in which the 99th percentile (P99) was associated with a 165-fold higher risk than P50, and for anti-annexin V IgG where P99 was associated with a 38-fold higher risk than P50. In addition, a higher prevalence of elevated anti-annexin V IgM and anti-annexin V IgG was seen in RSM cases than in control women. We conclude that anti-annexin V IgM and IgG antibody positivity are independent risk factors for RSM.     

Parvovirus B19 infection in pregnancy studied by maternal viral load and immune responses

OBJECTIVES: Facilitate risk assessment of vital complications in fetuses of pregnancies affected by acute parvovirus B19 (B19V) infection. DESIGN: Study of the natural course of maternal B19V infection in four cases, from early pregnancy on. SETTING: University Medical Center in the Netherlands. POPULATION: Pregnant mothers attending obstetric services. METHODS: Serial measurements of the maternal and fetal or neonatal viral load and antibody responses. MAIN OUTCOME MEASURES: Maternal and fetal/neonatal serum B19V viral DNA load and specific IgM and IgG antibodies in maternal serum. RESULTS: Peak viral load levels occurred within 1 week after maternal infection and peak IgM levels were observed 1 week after the peak viral load levels. Approximation of IgG and IgM ratios usually took place 4 weeks after infection. Vertical transmission occurred 1-3 weeks after maternal infection, suggesting that fetal infection occurs during the maternal peak viral load. CONCLUSIONS: Maternal B19V DNA load levels and IgM responses are useful to estimate the risk of parvovirus B19-associated fetal complications. The maternal peak viral load directly precedes the onset of fetal infection and may be used to indicate the stage of intrauterine B19V infection.     

Antenatal diagnosis of congenital toxoplasmosis: evaluation of the biological parameters in a cohort of 286 patients

Objective To evaluate the biological parameters obtained by cordocentesis and amniocentesis in the antenatal diagnosis of congenital toxoplasmosis.
Design Nine-year retrospective study.
Setting Parasitology Laboratory, Department of Obstetrics and Gynaecology and Department of Paediatrics, Centre Hospitalo-Universitaire, Montpellier, France.
Participants Two hundred and eighty-six pregnant women infected with toxoplasmosis between 7 and 34 weeks of gestation.
Methods Detection of abnormalities by ultrasound examination. Detection in fetal blood of Toxoplasma , of specific IgM and IgA and of nonspecific biological markers. Detection in amniotic fluid of Toxoplasma.
Results Out of 286 antenatal diagnoses, 211 were negative (1st group), 40 were positive (2nd group) and led to 8 medical abortions, and 35 were uncertain (3rd group). In the 1st and 3rd groups respectively, 7 (3.3 %) and 5 (14.3 %) cases of congenital toxoplasmosis were observed. Overall, 52 cases of congenital toxoplasmosis were detected: 12 were clinically apparent, 36 subclinical (of which 12 were in groups 1 and 3) and 4 were lost to follow up.
Conclusion There is substantial importance in making the diagnosis of toxoplasmosis antenatally in order to limit the number of medical abortions. In our series, the most accurate predictor was the detection of the fetal antibody response (specific IgM and IgA) to Toxoplasma.     

Commercial laboratory IgM testing for Toxoplasma gondii in pregnancy: a 20-year experience

OBJECTIVE: This study was performed to review the clinical utility of commercial laboratory Toxoplasmosis-specific IgM testing during pregnancy and outcomes of the gestation at our institution. METHODS: A retrospective review of all women referred for suspected acute Toxoplasma gondii infection during pregnancy from 1984 through 2004 was performed. Women were diagnosed with suspected acute toxoplasmosis based on commercial laboratory serologic antibody testing. All women had blood sent to a recognized reference laboratory for antibody testing within 2 weeks of the commercial laboratory results. The study protocol was approved by the Institutional Review Board. Chi-square analysis were used with a significance of P < .05. RESULTS: A total of 130 women were evaluated during the study period with 116 IgM positive results from the commercial laboratories. The commercial laboratory antibodies were as follows: IgM positive with IgG negative (n = 20), IgM positive with IgG positive (n = 96), and IgM negative with IgG positive (n = 14). There was a significant reduction in the IgM positive results when comparing commercial laboratory (n = 116) with the reference laboratory results (n = 28; p < .001). Acute toxoplasmosis infection was diagnosed in 7 (5%) of the women. All cases of acute toxoplasmosis infection had a positive commercial laboratory IgM result. The false positive rate for the commercial laboratory IgM was 88.6% and the diagnostic indices were sensitivity 100%, specificity 11.4%, positive predictive value 6% and negative predictive value 100%. CONCLUSION: Commercial laboratory Toxoplasmosis-specific IgM is associated with a high false positive rate. The commercial and reference laboratory IgM results identified all cases of acute toxoplasmosis infection. Commercial laboratories reflexively obtaining reference laboratory confirmation of positive results could reduce costs associated with testing, referrals, retesting, and invasive procedures.     

Sero-epidemiological survey of virus infections in pregnant women of the Changchun district

ELISA method was used to detect Rubella virus specific IgG in serum for 315 pregnant women. Susceptible cases with negative IgG was found in 8.9% (28/315) and recently infected cases was found in 6.0% (19/315). Serum CMV-IgG was assayed for 476 pregnant women. Forty-two cases (8.8%) were found to be negative. The cord serum CMV-IgM positive rate was 2.3% (6/259). Serum Herpes Simplex virus (HSV) IgG was assayed in 384 pregnant women. The negative rate for Type II virus was 26.8% (103/384) and that for Type II virus was 18.0% (53/295). In the cord serum the HSV-Type II and Type IgM was positive each in one case among 212 newborn babies. The results of this preliminary survey indicate that the sero-immunologic estimation of specific globulin is helpful in early detection of intrauterine infection.     

Pattern of parvovirus B 19 infection during different trimesters of pregnancy in Kuwait

OBJECTIVE: Aims of this study were to determine the IgG and IgM seropositivity to parvovirus B19 during the three trimesters of pregnancy. METHODS: Initially, a total of 1,047 pregnant women were included in a prospective study. Blood samples were obtained from 343, 406 and 298 cases in the first, second and third trimesters, respectively. To study the incidence of seroconversion, a second sample of blood was obtained 2-4 weeks later from the first 100 cases, who were IgG and IgM negative in the first trimester. RESULTS: The seroprevalence of parvovirus B19 IgG and IgM was 53.3% and 2.2%, respectively. The incidence of seroconversion was 16.5%. The rate of fetal loss was 15.4% in patients with acute infection, all of which occurred in the first two trimesters. CONCLUSIONS: The percentage of IgG positive cases is significantly higher in first and second trimesters compared to the third trimester. The seroconversion rate was 16.5%.     

Viral infections and pregnancy: contribution of amniotic fluid and blood samples]

The main viral infections prenatally detected in fetuses are: cytomegalovirus, parvovirus B19, rubella virus and varicellazoster virus infections. Prenatal diagnosis is based on the direct detection of the virus by culture (CMV), of its antigens or of its genome, essentially by PCR. This direct detection can be done either on fetal blood or on amniotic fluid. Prenatal diagnosis can also be performed by detection of specific IgM in fetal blood (rubella). Non specific markers of viral infection can also help in diagnosis. At the present time, prenatal diagnosis is essentially based on the detection of the viral genome in amniotic fluid. In order to better appreciate the severity of fetal infections, some groups have tried to identify prognostic markers of these infections. The viral load as well as the level of specific IgM could play a role in certain infections (CMV).     

Prevention and treatment of congenital toxoplasmosis: organization protocol

AIM: Prevention and treatment of congenital toxoplasmosis are still a matter of debate among obstetricians, pediatricians and epidemiologists. There is no consensus about antenatal screening and diagnostic tests, nor there is about treatment for presumed infection in pregnancy. As an example of this type of organisation for health care delivery, a regional model has been promoted as a multidisciplinary approach for prenatal diagnosis of congenital toxoplasmosis. The model had been designed on the national guidelines of the National Health Institute (Istituto Superiore di Sanità, ISS). METHODS: Suspected maternal infections are referred and seen as outpatients at our centre on a specific day of the week; maternal investigation (specific IgG, IgM, IgA and IgG avidity titres) are performed at the Institute of Virology of the University of Bari, and patients are started on spiramycin. All cases of true or presumed seroconversion are counselled for amniotic fluid sampling and the sample is sent to ISS. In cases of late seroconversion and positive amniotic fluid results, patients are prescribed pyrimethamine+sulphonamide+folinic acid and alternate spiramycin until the end of pregnancy. A fetal-neonatal follow-up is performed in all cases. RESULTS: During the period 1999-2001, 180 cases of presumed toxoplasmosis infection have been referred (average 60 cases per year). We have been able to reclute, since the adoption of the national network protocol, 1/3 of presumed regional cases with a positive increasing trend. CONCLUSION: The service for prenatal diagnosis of toxoplasma gondii infection has definitely benefitted from the adoption of this protocol, which combines adherence to a national network and pays respect to regional requirements.     

孤立性轻度侧脑室增宽胎儿的产前诊断及预后

目的：探讨孤立性轻度侧脑室增宽胎儿的产前诊断结果及临床预后,为临床咨询提供指导。方法：对61例超声诊断为孤立性轻度侧脑室增宽的胎儿,回顾性分析其产前诊断结果;随访其生后情况。结果：①61例产前诊断中,3例（4.92%）染色体核型异常,包括2例21-三体综合征和1例47,XXY;50例行脐血弓形虫、巨细胞病毒及风疹病毒-IgM检测,仅1例脐血风疹病毒-IgM阳性。定期随访的55例中,8例因各种因素终止妊娠,包括3例染色体核型异常和1例脐血风疹病毒-IgM阳性;47例活产儿中,1例生后发现多发畸形,1例新生儿期死亡,2例伴有生长发育障碍,43例（91.49%）生长发育正常。结论：对孤立性轻度侧脑室增宽胎儿,建议行产前诊断及感染项目检测,排除染色体异常和先天感染,绝大多数胎儿预后良好。     

High levels of IgM antibodies specific for Toxoplasma gondii in pregnancy 12 years after primary toxoplasma infection. Case report

A case of high levels of specific IgM antibodies registered by the immunosorbent agglutination assay (ISAgA) in a pregnant woman with a history of toxoplasmosis is reported. The patient had acute lymphoglandular toxoplasmosis diagnosed serologically by increases in the specific antibody titer detected by the Sabin-Feldman test (SFT) and pathohistologically 12 years before pregnancy. In pregnancy, she had stable titers of specific antibodies registered by the SFT, enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody test (IFAT), indirect hemagglutination test (IHAT) and direct agglutination test. Specific IgM antibodies were detected by the ISAgA but not by the IgM-IFAT, IgM-ELISA and IgM-IHAT. She had a normal pregnancy and gave birth to a clinically healthy baby who had a negative ISAgA finding at 7 days of age. This case indicates that ISAgA is not necessarily a marker of recent infection and is therefore not reliable for the diagnosis of toxoplasmosis in pregnancy.