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M Lappalainen

Publications and source records attributed to M Lappalainen.

At least 37 records · Page 2Linked to original sources

Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children's sequelae at age 1 year.

OBJECTIVE: Toxoplasmosis during pregnancy can cause fetal infection, with unpredictable sequelae in later life. We measured the effects of prenatal antibiotic therapy on the fetomaternal transmission of Toxoplasma gondii and on the appearance of sequelae in the congenitally infected child at age 1 year. STUDY DESIGN: In a multicenter study we investigated consecutive women with Toxoplasma seroconversion during pregnancy. Data were obtained from 144 women recruited in 5 different Toxoplasma reference centers. Through multivariate analysis we assessed the association between transmission and appearance of sequelae as a function of the following parameters: estimated gestational age at infection, administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy. RESULTS: Sixty-four of the 144 women (44%) gave birth to a congenitally infected infant. Multivariate analysis showed that transmission was predicted neither by whether antibiotics had been administered nor by the time lapse between infection and the start of antibiotic therapy, but only by the gestational age at which maternal infection occurred (P <.0001). Sequelae were found in 19 children (13%), 9 of whom (6%) had severe sequelae. Administration of antibiotics was predictive of the absence of sequelae (P =.026, odds ratio 0.30, 95% confidence interval 0.104-0.863), in particular the absence of severe sequelae (P =.007, odds ratio 0.14, 95% confidence interval 0.036-0.584). The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P =. 021). CONCLUSION: Prenatal antibiotic therapy after toxoplasmosis during pregnancy had no impact on the fetomaternal transmission rate but reduced the rate of sequelae among the infected infants. The early start of treatment resulted in a significant reduction in the number of severely affected infants.

Animals↗

Prenatal diagnosis of congenital toxoplasmosis: a multicenter evaluation of different diagnostic parameters.

OBJECTIVE: Our purpose was to evaluate different methods of diagnosing congenital toxoplasmosis prenatally by amniocentesis and cordocentesis. STUDY DESIGN: In a retrospective multicenter study, we investigated consecutive women who had seroconversion for Toxoplasma gondii during pregnancy and who underwent either amniocentesis or cordocentesis or both to obtain a prenatal diagnosis of fetal toxoplasmosis. Data were obtained from 122 patients recruited in 6 different European Toxoplasma reference centers. Infants born to these mothers were followed up until 1 year of age to confirm or exclude congenital toxoplasmosis. Sensitivity, specificity, positive predictive value, and negative predictive value were measured for the following parameters: (1) detection of the parasite in amniotic fluid by mouse inoculation, (2) detection of the parasite in amniotic fluid by in vitro cell culture, (3) detection of Toxoplasma deoxyribonucleic acid in amniotic fluid by a polymerase chain reaction assay, (4) detection of the parasite in fetal blood by mouse inoculation, (5) detection of specific immunoglobulin M antibodies in fetal blood, and (6) detection of specific immunoglobulin A antibodies in fetal blood. RESULTS: The polymerase chain reaction test performed on amniotic fluid had the highest level of sensitivity (81%) and also a high level of specificity (96%). The combination of the polymerase chain reaction test and mouse inoculation of amniotic fluid increased sensitivity to 91%. The sensitivity of immunoglobulins M and A in fetal blood was 47% and 38%, respectively. In congenitally infected fetuses a negative correlation was observed between positive serologic parameters and gestational age at the time of maternal infection and at prenatal diagnosis. CONCLUSION: Congenital toxoplasmosis is best predicted by prenatal examination with the combination of T gondii polymerase chain reaction and mouse inoculation of amniotic fluid. The role of cordocentesis in the diagnosis of congenital toxoplasmosis is limited.

Amniocentesis↗

Diagnosis of congenital toxoplasmosis in the neonatal period: A multicenter evaluation.

OBJECTIVE: To evaluate different laboratory tests used to diagnose congenital toxoplasmosis in the neonatal period. STUDY DESIGN: A retrospective multicenter study of 294 pregnant women who experienced seroconversion for Toxoplasma gondii and subsequently delivered live-born infants. Fetal infection was assessed via specific IgM and IgA antibodies (cord and neonatal blood) and detection of T gondii in placenta and cord blood by mouse inoculation. RESULTS: Ninety-three (32%) of the 294 infants were congenitally infected. The sensitivity of IgA in cord blood and in neonatal blood was 64% and 66%; the sensitivity of IgM was 41% and 42%, respectively. Mouse inoculation of the placenta and cord blood had sensitivities of 45% and 16%. Positive results of the serologic tests in congenitally infected children correlated significantly with the gestational age at the time of maternal infection but was not significantly influenced by the administration of specific antiparasitic treatment during pregnancy. CONCLUSION: Specific T gondii IgA antibody is a more sensitive test than IgM for detecting congenital toxoplasmosis in the neonatal period. The overall specificity is better for serologic tests performed on neonatal blood than for those on cord blood. Neonatal screening with IgM or IgA antibodies will not detect the majority of children with congenital toxoplasmosis when the maternal infection occurred before the 20th week of pregnancy.

Anti-Bacterial Agents↗

Serological evaluation of herpes simplex virus type 1 and type 2 infections in pregnancy.

OBJECTIVE: Serological evaluation of herpes simplex virus infections during pregnancy. METHODS: 2991 serum samples were obtained during 1st, 2nd, and 3rd trimester from 997 pregnant women. Baculovirus expressed glycoproteins gG1 (HSV-1) and gG2 (HSV-2) were used as antigens in ELISA for HSV-1 and HSV-2 IgG and IgA antibodies. RESULTS: The prevalence of HSV-1 gG1 antibodies was 70% and that of HSV-2 gG2 antibodies 16%. Among susceptible women we found five (0.6%) cases with serological evidence of primary HSV-2 infection during pregnancy. Evidence of active HSV-1 infection was found in nine (0.9%) cases. Decline of HSV-2 gG2 IgG antibody levels during pregnancy was pronounced compared with HSV-1 gG1 IgG antibody levels (p < 0.01); also the proportion of seroreversions was considerably higher among HSV-2 seropositives (25%) than among HSV-1 seropositives (3%) (p < 0.001). CONCLUSIONS: HSV-2 gG2 IgG antibodies were readily distinguished from HSV-1 gG1 IgG antibodies by the glycoprotein gG ELISAs. Serological assays for gG2 antibodies should guard against the decline of specific antibodies during pregnancy.

Adult↗

A second European collaborative study on polymerase chain reaction for Toxoplasma gondii, involving 15 teams.

In order to investigate the accuracy and practicability of the polymerase chain reaction (PCR) in the antenatal diagnosis of congenital toxoplasmosis, a collaborative study involving 15 European laboratories was performed under the auspices of the Biomed 2 Programme of the European Community. Each team received 12 aliquots (four negative, eight positive) of 'artificial samples' made of amniotic fluid spiked with tachyzoites of the RH strain of Toxoplasma gondii. Each team performed its own PCR protocol (all were different). Nine of the 15 laboratories were able to detect a single parasite, but two of the 15 found all samples negative. Four of the 15 laboratories found one or more control samples to be falsely positive. This study highlights the lack of homogeneity between PCR protocols and performance and underlines the need for an external quality assurance scheme which could provide 'reference' samples that could be used by any laboratory wanting to establish and maintain an accurate diagnostic test based on PCR.

Amniotic Fluid↗

Radiological signs in newborns exposed to primary Toxoplasma infection in utero.

A total of 44 181 serum samples from 16 733 pregnant women were analyzed for findings suggesting primary Toxoplasma infection. Thirty-seven newborns exposed to maternal primary Toxoplasma infection in utero were studied prospectively with ultrasound, CT, and MRI for signs of intrauterine infection. Their mothers had been treated during pregnancy, and all infants were treated. The children were assigned to three groups according to their mothers' serological status, and the radiological results were compared with the clinical outcome. Although radiological signs were scarce, ultrasound findings combined with maternal serology were found to be significantly related to clinical outcome.

Abdomen↗

Maternal serum screening for Down's syndrome on population basis.

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.

Adult↗

Interlaboratory comparison of polymerase chain reaction for the detection of Toxoplasma gondii DNA added to samples of amniotic fluid.

To investigate the accuracy of the polymerase chain reaction (PCR) method for the detection of Toxoplasma gondii in clinical specimens, aliquots of amniotic fluid to which known amounts of Toxoplasma gondii DNA had been added were tested by five European Centres. Four laboratories were able to detect DNA at levels equivalent to ten tachyzoites or less, including two that detected DNA equivalent to a single parasite. Two laboratories erroneously found one of eight negative control samples to be positive. These findings confirm that the high level of sensitivity associated with the PCR method can be readily achieved under routine laboratory conditions, but they also underscore the potential for both false-positive and false-negative findings to occur. Furthermore, the results confirm the urgent need for an external quality assurance scheme to support laboratories employing PCR in a clinical context for the detection of Toxoplasma gondii.

Amniotic Fluid↗

Hepatitis C genotypes in Finland determined by RFLP.

Genotyping of hepatitis C virus (HCV) is important because of its clinical and epidemiological implications. We report here the distribution of HCV genotypes in various patient groups in Finland using a rapid and reliable HCV typing method based on restriction fragment length polymorphism (RFLP) of the amplified DNA from the 5' non-coding region of the genome. The reaction product from the primary, diagnostic PCR (nested, one tube system) was used in genotyping. From 264 Finnish sera we identified HCV genotypes 1a (14%), 1b (24%), 2b (20%). 3a (41%) and 1a + 1b (1%). Only one patient with genotype 2a was identified. From four Egyptian blood donors, types 1b and 4 were found. Genotype 3a was more often associated with i.v. drug abuse and younger age profile (less than 30 years).

Adult↗

Experiences of mothers participating in maternal serum screening for Down's syndrome.

The participation rate in a maternal serum screening for trisomy 21 was 84% in the Helsinki trial. Six hundred and twenty-five mothers who had a positive result and a random sample of 245 mothers who had a negative result took part in the opinion survey. Ninety-five percent of the first and 97% of the second group considered the screening tests as very or quite useful. However, 12% of those with a positive result would decide against taking the test if they could reconsider, whereas 100% of those with a negative result would take it again. Too little information about the test, worries and stress, unnecessary in cases of false timing, difficult decision-making, and anxiety while awaiting the results of the chromosome study were the main complaints. More information at all stages, earlier testing, ultrasound timing before the serum test, and fast results were considered essential.

Adult↗

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.

Base Sequence↗

Cost-benefit analysis of screening for toxoplasmosis during pregnancy.

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.

Cost-Benefit Analysis↗