Adeno-associated virus DNA in human gestational trophoblastic disease.

Previous studies had shown a correlation between infection with the human adeno-associated virus (AAV) and spontaneous abortion in early pregnancy. Furthermore, AAV DNA had been detected in cells of the human trophoblast lines, Jeg-3, JAr, and BeWo, in cells of the human amnion line, FL, and in trophoblasts from amnion fluids. Infectious AAV virions could be isolated from amnion fluids. To further analyse AAV infection during pregnancy, we tested material from Gestational Trophoblastic Disease for the presence of AAV DNA. With 63 tissue samples from patients from Brazil, including 49 hydatiform moles and 14 choriocarcinomas, nested PCR was performed to detect the presence of AAV DNA. In addition, 15 samples from spontaneous abortions were analysed. AAV DNA was found in 43 samples (28/49 hydatiform moles, 4/14 choriocarcinomas, 11/15 miscarriage material). These findings confirm AAV infection of embryo-derived tissue in humans and further suggest a role of AAV in miscarriage and trophoblastic disease.

Trisomy 10: ultrasound features and natural history after first trimester diagnosis.

We report on the ultrasound features and natural history of trisomy 10. At 12 weeks' gestation in a routine scan examination, the fetus presented with increased nuchal translucency thickness, mild skin oedema, bilateral pleural effusion, marked micrognathia, cardiomegaly, unilateral talipes and reversed A-wave in the ductus venosus blood flow. Karyotyping on chorionic villus sampling (CVS) led to the diagnosis of trisomy 10, which was confirmed by fetal blood sampling at 22 weeks' gestation. As the parents opted to continue with the pregnancy, the natural history and following ultrasound features are described. This is the third case of trisomy 10 in the literature reporting on the physical features. The most frequent ultrasound findings presented in trisomy 10 are increased nuchal translucency, micrognathia, renal agenesis, facial cleft, limbabnormalities, cardiac defects and early severe growth retardation.

First-trimester screening for chromosomal abnormalities by fetal nuchal translucency in a Brazilian population.

OBJECTIVES: To examine the detection rate of chromosomal abnormalities using nuchal translucency (NT) thickness in a Brazilian population. METHODS: This was a prospective study of 2996 singleton pregnancies with a live fetus at 10-14 weeks of gestation attending for routine antenatal care in a teaching hospital in Brazil. Fetal crown-rump length (CRL) and NT thickness were measured and the risks for trisomy 21 were calculated by a combination of maternal age and fetal NT with the use of software provided by The Fetal Medicine Foundation. Sensitivity and positive predictive values for different risk cut-offs were calculated. RESULTS: Chromosomal defects were diagnosed in 22 cases, including 10 cases of trisomy 21. The estimated risk based on maternal age and fetal NT was 1 in 300 or greater in 222 (7.4%) cases and these included nine of 10 (90.0%) pregnancies with trisomy 21 and nine of 12 (75.0%) pregnancies with other chromosomal defects. The NT was above the 95th centile in 5.8% of cases and this group included 70% of the trisomy 21 cases. CONCLUSION: A combination of maternal age and fetal NT provides an effective method of screening for chromosomal defects. The performance of the test in a Brazilian population is similar to that in Britain.

Prevalence of 'high risk' human papillomavirus in the lower genital tract of Brazilian gravidas.

The presence of high-risk human Papillomavirus types 16, 18 and 33 was examined in 125 pregnant patients with abnormal Papanicolau smears. Specimens of cervicovaginal cells were analyzed by a simplified method of slot-blot hybridization. The overall prevalence of those viral sequences was 48%, being: 22.4% of HPV16, 17.6% of HPV18, 4.0% for double HPV16 and 18 infestation and 4.0% of HPV33. Their prevalence in HPV positive cervical sample was alone respectively 46.6%, 36.6%, 8.3% and 8.3%. Besides the high incidence of those carcinogenic types and intense viral proliferation, a rapid progression from CIN to carcinoma was clinically observed in four pregnant patients. Our data may reinforce the idea that progesterone has a positive role to the persistence and transformation of 'high risk' HPV, particularly of HPV16. The enhanced detection of potentially malignant types during pregnancy should warn on the importance of early diagnosis and treatment of papillomatosis.

Human genital tissues containing DNA of adeno-associated virus lack DNA sequences of the helper viruses adenovirus, herpes simplex virus or cytomegalovirus but frequently contain human papillomavirus DNA.

The detection of DNA of the helper virus-dependent adeno-associated virus type 2 (AAV-2) in biopsies of material from spontaneous abortion and in tissue samples from the uterus raises the question of whether sequences of known helper viruses can be detected simultaneously within the same specimen despite the lack of histological evidence for the presence of lytic viruses. Therefore, we performed PCR analyses with primers detecting DNA sequences of viruses (adenovirus, herpes simplex virus and human cytomegalovirus) known for their helper activity in the replication of adeno-associated viruses. In addition, PCR was performed to detect DNA of human papillomaviruses (HPV), which were recently shown to be able to help AAV replication in vitro. In no cases were sequences of the known helper viruses found. However, HPV DNA was detected in approximately 60% of paraffin sections from uterus biopsies and cervical lesions containing AAV DNA and in approximately 70% of material from early miscarriage. This finding suggests that HPV may be a helper virus for AAV.

Presence of human papillomavirus DNA in amniotic fluids of pregnant women with cervical lesions.

Amniotic fluids from 37 pregnant women with cervical lesions indicative of human papillomavirus (HPV) infection, detected by histology and slot hybridization, were collected at different times during pregnancy and assayed for HPV using the polymerase chain reaction. HPV DNA amplification was obtained in 24 of 37 samples using general primers. Of the 24 positive cases, 13, 5, and 0 were of HPV types 16, 18, and 33, respectively, as determined by using specific anticontamination primers. A correlation between viral DNA amplification and the cervical intraepithelial neoplasia grade was noted. The age of the pregnant women also seemed important for the putative transplacental HPV transmission. At the moment we are not able to evaluate the significance to the fetus of this early contact with the human papillomaviruses; further investigation is necessary to assess the involvement of these viruses in some embryonal and fetal pathology.

Possible prodromes of human papillomavirus uterine cervix infection.

We present two case reports and mention four others with similar clinical, pathological and laboratory findings which suggest that viremia could possibly occur in some human papillomavirus (HPV) infections. Fever, general indisposition or arthralgia associated with micturition difficulties or dysuria appear to be the symptoms accompanying this viremia. After a period of time these symptoms disappear and the infection shows typical HPV uterine cervix symptoms. The diagnosis of HPV infection was confirmed by histological analysis and DNA hybridization of biopsy material from the cervical lesions. These clinical findings may introduce a new avenue for the investigation of viral physiopathology.