Biomedical subjects
Publications and source records attributed to P Ammälä.
We report a fetus with atelencephaly, bilateral radial aplasia/hypoplasia, ventriculoseptal defect and megacolon, this combination of anomalies being consistent with the diagnosis of XK-aprosencephaly syndrome. The facial dysmorphology of this fetus differs from that previously reported and together with reports on overlapping phenotypes suggests an extension of the XK-aprosencephaly spectrum.
The cause of stillbirth and preterm delivery is often unknown. We studied the prevalence of Chlamydia trachomatis antibodies in mothers with stillbirth and preterm labor. Serum specimens from 72 mothers with stillbirth after the 21st gestational week, and from 48 mothers with preterm delivery between gestational weeks 23 and 29, both from the greater Helsinki area, and cord blood from 96 consecutive liveborn deliveries at the Department of Obstetrics and Gynecology, the University of Helsinki, were studied for antibodies to C. trachomatis immunotypes CJHI, GFK and BED by microimmunofluorescence test. The prevalence of C. trachomatis antibodies was highest, 33.3%, in mothers with stillbirth, 18.8% in mothers with preterm delivery, and 10.4% in cord blood. The IgM seropositivity rate was high among mothers with preterm delivery (8.3%). We conclude that C. trachomatis IgG antibodies are frequently detected in sera from mothers with stillbirth, suggesting past infection, while mothers with preterm delivery often have serum IgM antibodies, suggesting of acute infection.
BACKGROUND: To re-evaluate the impact of socioeconomic status and human cytomegalovirus (HCMV) seroprevalence during pregnancy, we carried out a population-based cohort study. METHODS: IgG and IgM antibodies to HCMV and IgG avidity were studied by enzyme-linked immunosorbent assay (ELISA) in three different socioeconomic areas (SEA) in the 9-12th week of pregnancy of 1088 consecutive mothers. RESULTS: The overall IgG seropositivity was 70.7%, ranging from 60.9 to 76.4% in 'upper' to 'lower' SEA (P = 0.0004). The HCMV IgM seropositivity was 4.0%, ranging from 3.8% in the 'upper' and 'intermediate' SEA to 4.6% in the 'lower' SEA. Serologically acute cases, defined by low avidity of IgG, represented 1.7% of the pregnancies in the 'upper' SEA compared with 1.0 and 1.1% in the other two areas. In the 'lower' SEA there were twice as many recurrent infections as in the others, 3.6 versus 1.7%. The low impact of age did not increase after elimination of the effects of SEA and parity. Miscarriages were associated neither with IgG nor with IgM positivity, although the percentage of >/=2 miscarriages was 8.8% in seronegative women compared with 11.2% and 13.6% in IgG- and IgM-positive women. CONCLUSIONS: Social environment seems to be the most powerful factor, predicting both IgG seroprevalence and recurrences during pregnancy.
Explore the source record for details and available documents.
A 13q isodisomy in a balanced karyotype: 45,XY,-13,-13, + i(13)(q10) was found in cultured amniocytes studied because of advanced maternal age. The isochromosome was monocentric and a new mutation as both parents had normal chromosomes. Fetal blood was studied to exclude 13-trisomy mosaicism. All (100) lymphocytes studied had the same karyotype with i(13)(q10) as the amniocytes. To determine the origin of the isochromosome, six microsatellite markers from 13q were analysed: D13S175, D13S166, D13S162, AC224, COLAC1 and D13S122. The results indicated that the i(13)(q10) was of paternal origin and isodisomic. The father had a risk of 1/20 for being a carrier for an autosomal recessive, progressive brain disorder, variant late infantile neuronal ceroid lipofuscinosis (CLN5). The risk for the fetus for this disorder of chromosome 13 was excluded by haplotype analysis. A healthy child was born at week 40 of pregnancy, supporting the idea that there are no paternally imprinted genes on chromosome 13q. Analysis of extra embryonal tissue (four samples studied) revealed the same balanced karyotype with the i(13)(q10)pat chromosome. According to the cytogenetic and molecular studies, the origin of the isochromosome 13 could be a transverse centromere cleavage at the paternal meiosis II or at an early mitosis.
AIMS: To evaluate the relation between Chlamydia trachomatis infection and stillbirth, placental tissue was studied for the presence of C trachomatis. METHODS: Paraffin wax embedded placental tissue of a stillbirth fetus, born at the 36th week of gestation to a 21 year old mother with high serum antibody titres to C trachomatis immunotypes during pregnancy and who was culture positive to C trachomatis three years previously, was studied by in situ hybridisation, polymerase chain reaction, and immunohistochemistry for the presence of C trachomatis. RESULTS: C trachomatis was detected in placental specimens by in situ hybridisation and alkaline phosphatase antialkaline phosphatase staining in several sections, whereas control tissues were uniformly negative, indicating the presence of C trachomatis nucleic acid and antigen in the placenta. CONCLUSION: This is the first reported case in which C trachomatis has been demonstrated in the human placenta.
BACKGROUND: The favorable attitude among the public towards prenatal diagnostics in Finland allowed us to start a trial on population basis when screening for Down's syndrome by maternal serum markers and age was introduced. METHODS: Screening by maternal serum markers for Down's syndrome was offered to all 17,200 pregnant women in the Helsinki area during the study period of 2.5 years. Screening due to advanced maternal age, 37 years or more, was continued as previously, and 1133 pregnant mothers used this option. Alpha-fetoprotein, human chorionic gonadotrophin, and during the first year also unconjugated estriol were used as markers. RESULTS: The uptake of serum screening was 84%. The proportion of false positive results i.e. risk for Down's syndrome, 1:350 or more at term, was initially 5.7%. After ultrasound scan 4.1% of the mothers remained 'screen positive'. The amniocentesis or chorionic villus sampling uptake was 98.4%. Ten out of eighteen cases of Down's syndrome were detected by maternal serum screening, sensitivity 56%, 95% CI 31-79%. Other chromosomal abnormalities were found in three cases, and there were four cases of mosaicisms confined to the placenta. These were trisomies 16, 7 and 2, and tetraploidy. Elevated serum alpha-fetoprotein was found initially in 0.7% of the cases. One case of congenital nephrosis of the Finnish type and ten other, mainly structural, abnormalities were detected by high AFP. CONCLUSIONS: The screening was well received by the mothers. The detection rate of 56% is in the same range as in previous studies. Ultrasound scan before the test would effectively lower the false positive rate caused by incorrect timing.
Explore the source record for details and available documents.
In Finland the local authorities are responsible for the provision of prenatal diagnostic services for the communities or the community pays for the visits of its citizens to the larger hospitals. The local authorities have autonomy in making the policies for prenatal diagnosis, which leads to an uneven availability of the services, i.e. availability of ultrasound (US) screening, maternal serum screening, and age limits for fetal chromosome studies due to advanced maternal age. The municipalities receive Government aid for health care. In all areas, US screening and screening for fetal chromosome anomalies either by advanced maternal age only or maternal serum screening are arranged. Families with special problems are sent to five university hospitals for prenatal diagnostic services. To make possible the prenatal diagnosis of the autosomal recessive diseases belonging to the Finnish disease heritage, a special effort has been made on their molecular genetics. The uptake level of ultrasound screening is on average 90%. In cases of abnormal findings, the patients are referred to central or university hospitals for further examinations. The uptake of amniocentesis (AC) or chorionic villus sampling (CVS) due to advanced maternal age is 50-85%. The high numbers come from southern and urban parts of the country. The uptake for maternal serum screening is probably of the similar or of even higher order. In addition to the public services, private prenatal diagnosis, US, maternal serum screening, AC and CVS are available in all parts of Finland.
OBJECTIVE: The relationship between stillbirths and infections during pregnancy. METHODS: Antibodies to 13 different viruses and to Mycoplasma pneumoniae, Treponema pallidum, Toxoplasma gondii, and Chlamydia trachomatis, psittaci, and pneumoniae were studied from sera of 42 mothers with stillbirth and of matched case-control pregnancies. RESULTS: Elevated antibody levels to Chlamydia trachomatis and human parvovirus B19 were observed in seven mothers with stillbirth as compared with one in matched case controls (p-0.03 and p < 0.06, Fisher's exact one- and two-tailed p values). By a novel EIA test for C. trachomatis, based on synthetic polypeptide, 15 positive cases were detected in patients compared to seven in controls. Placental calcifications and fetal growth retardation appeared more often (p < 0.001 and p < 0.05, respectively) in the C. trachomatis- associated cases than in the others. There was no significant relation between stillbirth and the other antibodies. CONCLUSIONS: We suggest C. trachomatis as a hitherto unrecognized possible cause of still-births besides human parvovirus B19. A new EIA test for C. trachomatis, one covering all strains, is promising and makes the future assays more convenient, and may thus make it possible to reduce the rate of stillbirths.
At 12 weeks of gestation, a combination of atypical hydrocephalus with absent mid-line structures and club foot was detected during transvaginal ultrasound examination. These findings were diagnostic of hydrolethalus syndrome and were confirmed after subsequent termination of the pregnancy. This is the first known case of first-trimester prenatal diagnosis of hydrolethalus syndrome.
Congenital toxoplasmosis results from maternal primary infection during pregnancy. In our serologic screening study 42 of 16,733 pregnant women had findings suggestive of primary infection. Here we document the outcome of their offspring, 37 of 39 liveborn children. After 12 months postnatally, serologically verified congenital toxoplasmosis appeared in 4 children. All these children had persisting IgG at the age of 12 months by both the dye test and the IgG enzyme-linked immunosorbent assay. All the congenitally infected infants had also specific IgM and IgA and showed significant increases in avidity of specific IgG during the 12-month follow-up. One of them had a unilateral retinal scar and intracranial calcifications. An additional 3 infants of the mothers with primary infection during early pregnancy presented with unilateral retinal scars but without seroresponses during the first 12 months of life. Maternal high avidity of IgG during the first trimester is a strong indicator against primary infection during pregnancy; the fetuses of such mothers are at low risk for congenital toxoplasmosis.
An infant with congenital diaphragmatic hernia was given 2 mg vecuronium bromide intramuscularly in utero 40 min before vaginal delivery at 40 weeks gestation. At birth the infant had complete muscle relaxation, which facilitated decompression of the bowel and surgical correction. Prenatal muscle relaxation may improve the care of infants with congenital diaphragmatic hernia.
Congenital toxoplasmosis is a risk for fetus both in 'low' and 'high risk' areas. A cost-benefit analysis based on data from a Finnish prospective study (20.3% seropositivity of pregnant mothers and incidence of 2.4/1,000 seronegative pregnancies) and on Finnish cost data was performed to compare the no-screening and screening alternatives for primary toxoplasma infections during pregnancy. A maternal-feto transmission risk of 40%, effectiveness of treatment of 50%, and discount rate of 4% were used as other baseline probabilities. The calculations were carried out by decision analysis combined with sensitivity analysis. The total annual costs of congenital toxoplasmosis without screening amount to US$ 128/pregnancy/year, and with systematic serological screening, US$ 95/pregnancy. Thus screening reduces the costs by 25%. The present value of net savings in Finland would be US$ 2.1 million every year. A one-way sensitivity analysis showed that screening together with health education is preferable to health education without screening if the incidence of maternal primary infections exceeds 1.1/1,000 and effectiveness of treatment is better than 22.1%. Screening for toxoplasma infections during pregnancy is economically worthwhile even in a country with a low incidence. A scheme of systematic screening for maternal primary toxoplasma infections combined with health education should be considered.
A total of 800 patients were randomized at the 9th to 11th week of pregnancy either for transcervical chorionic villus sampling (CVS) on the day of trial entry or for amniocentesis (AC) at the 16th week. The indication for fetal karyotyping was maternal age in 94 per cent of the cases; the mean maternal age was 39.2 years. An adequate sample was obtained in 98.3 per cent of the cases in the CVS group and in all cases in the AC group. Retesting was indicated in 3.3 per cent of the CVS cases. An abnormal karyotype was found in 6.1 per cent of the CV samples and in 4.5 per cent of the amniotic fluid samples. There was one false-positive chromosome result in both groups. Twelve (3.1 per cent) miscarriages occurred by the 22nd week of pregnancy in the CVS group in pregnancies intended to continue. No difference was seen between the groups for total fetal loss rates. The number of surviving infants in the CVS group was 92.2 per cent and in the AC group 91.7 per cent (rate difference 0.5 per cent (95 per cent confidence interval -3.3 to 4.3)). In our study, both the diagnostic accuracy and the risk of fetal loss were equal in the CVS and AC groups.
Explore the source record for details and available documents.
A case of HLA identical twins with one affected by congenital heart block is reported. Both twins, as their mother, had more than 12-fold higher anti-Ro antibody titers compared to healthy controls, but no differences were observed between the affected and the healthy baby. It is possible that there is a third factor causing the manifestation of this disease.
Serodiagnostic methods were evaluated in prenatal screening for primary Toxoplasma infections acquired during pregnancy in the Helsinki area. Altogether 44,181 sera were obtained consecutively during each trimester from 16,733 mothers. All IgG-containing samples were first examined by a sensitive mu-capture (IgM) ELISA, and positive results were reassessed by IgM immunoblotting and indirect IgM ELISA. An assay measuring the avidity of toxoplasma IgG was used for the first time under screening conditions. Patients suspected to have recent toxoplasmosis were reexamined by IgA ELISA and selectively by the differential agglutination assay (HS/AC test) and IgE ELISA; 16 women with diagnostic increases in IgG titer, 36 with IgM fulfilling strict specificity criteria, and 25 with IgG of low avidity were identified. The measurement of IgG avidity was a highly specific and sensitive method suitable for verification of acute primary Toxoplasma infections during pregnancy.