Prenatal diagnosis in Finland.

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.

Prenatal diagnosis and fetal pathology of aspartylglucosaminuria.

The prenatal diagnosis of aspartylglucosaminuria (AGU), a lysosomal storage disorder of glycoprotein degradation, was made by demonstrating the deficiency of N-aspartylglucosaminidase on cultured cells from a midterm amniotic fluid sample. Four other amniotic fluid studies from at-risk pregnancies gave a normal or a heterozygote level of enzyme activity. These pregnancies have gone to term and the delivery of healthy babies. The pregnancy with the affected fetus was terminated and the prenatal diagnosis was verified by enzyme assays on cord blood lymphocytes, cultured cells from skin biopsy, and from placental villi. Electron microscopic evidence of lysosomal storage was seen in several organs of the fetus with the notable exception of the central nervous system. The undifferentiated mesenchymal fibroblasts particularly were heavily loaded with cytoplasmic inclusions in skin, liver, kidney, and placenta.

Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery.

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.

Chlamydia trachomatis infection in mothers with preterm delivery and in their newborn infants.

We studied Chlamydia trachomatis infection in mothers with preterm delivery and intrauterine transmission of the infection to their offspring. Forty-one mothers with preterm labour and their newborn infants (n=50) were studied for the presence of C. trachomatis infection using microimmunofluorescence test for detection of serum antibodies against C trachomatis and polymerase chain reaction for detection of C. trachomatis-specific DNA in mucosal swabs. Antibodies to C trachomatis were found in serum of 12 mothers (29%). Five of fourteen mothers had C. trachomatis DNA in cervical specimens. Eighteen neonates were born to the 14 mothers with positive serology and/or C. trachomatis DNA. C. trachomatis DNA was detected in specimens from 10 of the 18 neonates (55.5%). Three of the available cord blood samples contained C trachomatis IgM antibodies. Our results strongly suggest that mothers and their preterm babies may benefit from screening for active C. trachomatis infection.

Outcome of children after maternal primary Toxoplasma infection during pregnancy with emphasis on avidity of specific IgG. The Study Group.

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.

Human cytomegalovirus seroprevalence in three socioeconomically different urban areas during the first trimester: a population-based cohort study.

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.

Chlamydia trachomatis detected in human placenta.

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.

Pathologic fetal heart rate associated with poor metabolic control in diabetic pregnancies.

Nonstress fetal heart rate (FHR) recording was used as a primary test to detect fetal distress in 145 pregnant women with insulin-dependent diabetes. Testing was performed every second day beginning with the 32nd week of pregnancy and daily after the 34th week until delivery. One hundred eighteen (81.4%) had normal, nine (6.2%) suspicious, and 18 (12.4%) pathologic FHR recordings. Poor metabolic control of diabetes was observed in 25 (17.2%) of the 145 pregnancies during the last trimester of pregnancy. Nine of these 25 women (35%) with poor metabolic control had a suspicious or pathologic FHR recording, which was significantly more frequent (P less than .02) than in women with good metabolic control (18 of 120, 15%). The mean value (+/- SD) of hemoglobin AIc during the last trimester in diabetic women with pathologic FHR records was 7.63 +/- 0.87%, which was significantly higher (P less than .02) than in diabetic women with normal FHR records (6.91 +/- 0.83%). None of the 145 fetuses monitored died in utero. It was concluded that no obvious iatrogenic morbidity was caused by early intervention in cases with pathologic FHR recordings.

Congenital heart block in one of the HLA identical twins.

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.

A fetus suggesting an extension of theXK-aprosencephaly spectrum phenotype.

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.

Antepartum non stress cardiotocography and quantified short term variability of foetal heart rate in high-risk pregnancies.

The clinical significance of non-stress cardiotocography (CTG) and antepartum quantified short-term variability (differential index = DI) of foetal heart rate (FHR) were assessed for prediction of foetal outcome in 461 high-risk pregnancies. The analysis of FHR variability were made by a microprocessor based on-line method which utilizes abdominal foetal electrocardiogram (aFECG) as a triggering signal. In 24 pregnancies no acceptable aFECG was obtained. CTG was classified as pathological in 167 pregnancies (36%), and DI was abnormal in 74 pregnancies (15%) in the last test before delivery. Foetal distress developed in 97 pregnancies. There were no antepartum foetal deaths, but six newborn infants died (perinatal mortality 1.3%). CTG was more sensitive but less predictive, and less specific than DI. Risk of foetal distress after a pathological CTG was 8.9 times that after a normal CTG (relative risk, p less than 0.001), and after a pathological DI 8.0 times that after a normal DI (p less than 0.001). Both tests were pathological in 64, and both normal in 265 cases. The risk of foetal distress after combined pathological tests was 20.3 times that after normal combined tests (p less than 0.001). These results suggest that prediction of foetal outcome may be improved by combining CTG and DI. Since the false abnormal rate of CTG was high, further evaluation is required. DI picked out 74 of 86 cases with false abnormal CTGs. These results suggest that DI could be used for further testing of abnormal CTGs.