Search

Objective: To evaluate the performance of first-trimester measurement of fetal nuchal translucency (NT) in the detection of severe congenital heart defects (CHDs).Methods: During the study period of 1 January 2008 - 31 December 2011, NT was measured in 31,144 women as a part of voluntary first-trimester screening program for Down's syndrome in Northern Finland. NT was measured by personnel trained on the job by the experienced staff. No certification or annual audits are required in Finland. However, the recommendation is that the examiner should perform 200 scans on average per year. Severe CHD was classified as a defect requiring surgery in the first year of life or a defect that led to the termination of the pregnancy. All severe CHDs diagnosed during the study period in Northern Finland could not be included in this study since all women did not participate in the first-trimester screening and some cases were missing important data.Results: Fourteen (17.7%) out of 79 severe CHDs were found with NT cutoff of 3.5 mm. Amongst the 79 severe CHD cases, there were 17 chromosomal abnormalities. With NT cutoffs of 2.0 and 1.5 mm the detection rates would have increased to 25.3% (n = 20) and 46.8% (n = 37). Using a randomly selected control group of 762 women with normal pregnancy outcomes, false positive rates (FPRs) were calculated. For NT cutoffs of 1.5, 2.0 and 3.5 mm, the FPRs were, 18.5, 3.3 and 0.4%, respectively.Conclusions: A greater than 3.5 mm NT measurement in the first-trimester ultrasound is an indication to suspect a fetal heart defect but its sensitivity to detect severe CHD is poor. In our study, only 17.7% of severe CHDs would have been detected with an NT cutoff of 3.5 mm. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the performance of first trimester maternal serum glycosylated (Sambucus nigra lectin-reactive) fibronectin in prediction of gestational diabetes mellitus (GDM). Methods: In this case–control study, first trimester maternal serum glycosylated fibronectin and fibronectin were measured in 19 women who consequently developed GDM and in 59 control women with normal pregnancy outcomes. Adiponectin was used as a reference protein to evaluate relation of glycoprotein to SNA-lectin-reactive assay format. Samples were taken during gestational weeks 9+6–11+6. Data concerning GDM was obtained from the National Institute for Health and Welfare, which records the pregnancy outcomes of all women in Finland. Results: There was no difference in maternal serum glycosylated fibronectin concentrations between women with consequent GDM [447.5 μg/mL, interquartile range (IQR) 254.4–540.9 μg/mL] and control women (437.6 μg/mL, IQR 357.1–569.1 μg/mL). Maternal serum fibronectin levels were significantly lower in GDM group (224.2 μg/mL, IQR 156.8–270.6 μg/mL), compared to the control group (264.8 μg/mL, IQR 224.6–330.6 μg/mL, p < 0.01). There was no difference in assay formats for adiponectin. Conclusion: There was no association between first trimester maternal serum glycosylated (SNA-reactive) fibronectin and GDM. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the performance of first trimester screening for Down syndrome in women less than 35 years of age (study group) and in women aged 35 years or more (control group) in an unselected low-risk population. Methods The study group comprised a total of 63 945 women who participated in the first trimester combined screening in public health care in Finland during the study period of 1 May 2002 to 31 December 2008. Women at the age of 35 or more ( n = 13 004) were controls. Prevalence of Down syndrome, detection rate, false positive rate and number of invasive procedures needed to detect a single case of Down syndrome were analyzed in both groups. Results The overall prevalence of Down syndrome ( n = 73) in the study group was 1:876. The number of detected cases was 54. The detection rate was 74.0% with a false positive rate of 2.8%. Number of invasive procedures needed to detect a single case of Down syndrome was 33. In the control group, the detection rate was 87.0% with a false positive rate of 11.9%. The number of invasive procedures needed to detect a single case of Down syndrome was 15. The differences in detection rate and false positive rate were significant, P < 0.012, P < 0.001, respectively. Conclusion The overall detection rate given for the entire population is an overestimate for a woman younger than the age of 35, which should be taken into consideration when counselling women of that age. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs). Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down's syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland. Results: Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively. Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans. [ABSTRACT FROM AUTHOR]

Objective: Maternal thrombophilia is a risk factor for adverse pregnancy outcomes. The aim of this study was to elucidate the controversial role of fetal and paternal thrombophilia in the development of severe placenta-mediated pregnancy complications.Study Design: The study group comprised 126 mothers, 72 fetuses and 58 fathers. 111 mothers, 50 fetuses and 91 fathers acted as controls. 106 couples were selected to study the thrombophilias of paternal inheritance, 58 from the study group and 48 from the control group. The prevalence of factor V Leiden mutation, prothrombin G20210 A mutation and homozygous 10-methylenetetrahydrofolate reductase C677 T mutations were compared between the study and control groups to study whether maternal, fetal or paternal thrombophilias increase the risk of severe preeclampsia, intrauterine growth restriction, placental abruption and stillbirth.Results: The total prevalence of fetal thrombophilic mutations was 8.3% in the study group and 14.0% in the control group. Paternal prevalence of thrombophilic mutations was 6.8% and 4.3%, respectively. There were no statistical differences between fetal or paternal thrombophilic mutations between the study and control groups.Conclusion: Fetal or paternal factor V Leiden mutation is not associated with severe placenta-mediated pregnancy complications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficacy of first-trimester markers--pregnancy-associated plasma protein A (PAPPA), free human chorionic gonadotropin β (fhCGβ), alpha-fetoprotein (AFP), placental growth factor (PIGF), and soluble tumor necrosis factor receptor-1 (sTNFR1) together with maternal characteristics (MC) for prediction of early-onset preeclampsia (EOPE). METHODS: During 2005-2010, the abovementioned biomarkers were analyzed with logistic regression analysis in 64 EOPE and 752 control subjects to determine whether these biomarkers separately and in combination with MC would predict development of EOPE. RESULTS: PAPPA, fhCGβ, and PIGF levels were lower, whereas AFP and sTNFR1 levels were higher in mothers with EOPE compared to controls. The combination of all markers with MC (age, weight, and smoking status) detected 48% of the mothers with EOPE, with a 10% false-positive rate (FPR). CONCLUSIONS: First-trimester maternal serum levels of PAPPA, fhCGβ, AFP, PIGF, and sTNFR1, together with MC, are predictive of development of subsequent EOPE. These markers, along with MC, form a suitable panel for predicting EOPE. [ABSTRACT FROM AUTHOR]

Objective To compare the efficacy of fetal nuchal translucency screening, maternal serum screening and combined screening for Down syndrome. Design A prospective study. Setting University hospital and its public health care district in Northern Finland. Population A total of 35 314 women participated in the first-trimester screening for Down syndrome within the public healthcare system in 2002-08. There were 95 pregnancies involving Down syndrome. Serum samples were obtained from 35 314 women, nuchal translucency was measured in 27 144 pregnancies and full combined screening was performed in those pregnancies, including 76 involving Down syndrome. Methods The adjusted estimated risk for Down syndrome was calculated using the Perkin Elmer Auto DELFIA® time-resolved fluoroimmunoassay kit for the measurement of pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin. Nuchal translucency was measured by trained personnel in a university or district hospital. Risk cut-off figures 1:250 and 1:300 at term were used. Main outcome measures Differences in detection rate, false-positive rate, positive and negative predictive values between nuchal translucency screening, serum screening and combined screening. Results Using the risk cut-off figure 1:250, the detection rates for serum screening, nuchal translucency screening and combined screening were 64.2, 64.5 and 72.4%, respectively and the false-positive rates were 7.8, 4.4 and 4.0%, respectively. Conclusions Combined screening is the method of choice for Down syndrome screening in Finland. [ABSTRACT FROM AUTHOR]

Objective: To investigate first trimester levels of ADAM12 in trisomy 18 and 13 pregnancies and whether incorporating ADAM12 in the LifeCycle™ risk calculation program of trisomy 18 and trisomy 13 screenings can improve the detection rates of trisomies 18 and 13. Methods: ADAM12 was incorporated in the LifeCycle™ risk calculation program. A specific algorithm with cut-off of 1:200 for screening of trisomies 18 and 13 was employed. Detection rates for trisomies 18 and 13 were calculated. Results: There was a significant difference in ADAM12 levels between trisomy 18 pregnancies and controls during the gestation weeks 9 + 0 - 10 + 6, but not thereafter. In trisomy 13 pregnancies there was no difference in weeks 9 + 0 - 10 + 6, but there was in 11 + 0 - 12 + 6. The specific algorithms for trisomies 18 and 13 combined with algorithm for trisomy 21 yielded detection rates of 73.7% and 66.7%, respectively. The combined false positive rate was 4.6%. Adding ADAM12, the detection rate for trisomy 18 was the same, at 73.7% and for trisomy 13, at 66.7%. Conclusion: ADAM12 did not improve the detection rate. [ABSTRACT FROM AUTHOR]

Objective. To examine the performance of first-trimester combined screening after adding the specific algorithms for trisomies 18 and 13 in the Down syndrome screening program for chromosomal abnormalities other than trisomy 21 and to determine the outcomes of such pregnancies. Design. A retrospective study. Setting. Oulu University Hospital, Finland. Population. Pregnant women ( n=56 076) participating voluntarily in first-trimester combined Down syndrome screening in Northern and Eastern Finland during the study period 1 June 2002 to 31 December 2008. Methods. The data of all known cases of chromosomal abnormalities other than trisomy 21 were collected. Main Outcome Measures. Risk algorithms for trisomies 21, 18 and 13 were used for the calculation of patient-specific risks for certain chromosomal abnormalities. Algorithms were based on maternal age, crown-rump length, nuchal translucency, and measurement of free β-human chorionic gonadotrophin and pregnancy-associated plasma protein-A. Detection rates and false-positive rates were calculated. Results. A total of 27 cases of trisomy 18, 11 cases of trisomy 13 and 30 cases of other chromosomal abnormalities were analyzed. The algorithm for Down syndrome detected 55.6% of trisomy 18 cases, 36.4% of trisomy 13 cases and 60.0% of other chromosomal abnormalities. When specific risk algorithms were added, the detection rates improved for trisomy 18 (74.0%) and for trisomy 13 (54.5%), with only a slight increase of the false-positive rate of 0.2%. The detection rate for other chromosomal abnormalities did not improve. Conclusions. Adding the trisomy 18 algorithm to the Down screening program resulted in the detection of five additional trisomy 18 cases. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the performance of first-trimester combined screening in 5-year periods according to maternal age in a low-risk population. Design. A prospective study. Setting: Multicenter study in Finland. Population: A total of 76 949 voluntary women with singleton pregnancies participated in first-trimester combined screening in public healthcare between 1 May 2002 and 31 December 2008. Methods. The serum samples were analyzed using the PerkinElmer AutoDELFIA® time-resolved fluoroimmunoassay kit for the measurement of pregnancy-associated plasma protein-A and free beta-human chorionic gonadotropin. Nuchal translucency was measured by trained personnel (midwives or physicians) in a university or central hospital. Main Outcome Measures. Performance, detection rate, false positive rate and the number of invasive procedures needed to detect a single case of Down's syndrome were analyzed. Results. There was a direct connection between maternal age and the prevalence of Down's syndrome with a low prevalence in young women being 1:1 193 in the 25-29 age group and 1:150 in the 35-39 age group. Consequently, for a fixed false positive rate of 5%, the number of invasive procedures needed to detect one case of Down's syndrome is higher in younger women to achieve the same detection rate. Conclusions: In combined first trimester screening the risk for Down's syndrome is individual, varying with maternal age. This should be taken into consideration when counseling women. [ABSTRACT FROM AUTHOR]

Background: We wished to investigate the correlation between a new Down screening marker ADAM12 (a disintegrin and metalloproteinase-12) and pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) during the first trimester of pregnancy. Methods: ADAM12, PAPP-A and fbeta-hCG were measured in 225 serum samples of randomly chosen pregnancies with completely normal outcome. The samples were taken between pregnancy weeks 9+0 and 12+6. Results: The ADAM12 levels tended to increase with advanced gestational age and the highest levels were detected at pregnancy week 12. The ADAM12 levels correlated with PAPP-A levels. After weight correction and logarithmic transformation the multiples of median (MoM) of ADAM12 still correlated with the MoMs of PAPP-A and also with the MoMs of fbeta-hCG. Smokers had lower ADAM12 levels than non-smokers. Conclusion: The secretion of ADAM12 seems to resemble the secretion of PAPP-A in the end of the first trimester. Accordingly ADAM12 appears not to be a separate marker independent of PAPP-A. It remains to be assessed whether adding ADAM12 in Down screening risk calculation will reduce the false positive rate during the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Aims: Adiponectin and leptin are members of the adipocytokine family. Adiponectin promotes and leptin inhibits apoptosis and both are regulators of angiogenesis. Adipocytokines and their receptors are expressed in the placenta, and in the pre-eclamptic (PE) mother the serum levels of both are higher than in healthy ones. Our aim was to study the expression of adiponectin, leptin, their receptor genes and apoptosis in severely PE and normal placentas. Methods: The study group comprised 13 PE mothers and their 16 healthy controls. Placental biopsies were taken during cesarean section, the RNA was extracted and micro-array study was performed, followed by PCR and apoptosis studies. Results: The placental expression level of the leptin and adiponectin receptor 1 genes was significantly higher in PE mothers than in controls. No significant changes were observed in the levels of the adiponectin, adiponectin receptor 2 and Leptin receptor genes. The expression of the Adiponectin gene was low. The rate of apoptosis was higher in the PE placentas. Conclusions: The activity of placental adipocytokines and their receptor genes in severe PE may suggest an important role in placental angiogenesis. Placental apoptosis induced by adiponectin could be mediated via the ADIPOR1-receptor. [ABSTRACT FROM AUTHOR]

Aim. The normal endovascular invasion of trophoblast cells and spiral artery remodeling are impaired in pre-eclampsia. Neither the circulating factor secreted by the placenta nor the cause of the widespread endothelial dysfunction in pre-eclampsia has yet been identified. In an attempt to identify novel factors, we performed a gene expression profiling study of placental tissue from women with and without pre-eclampsia. Material and methods. The study group comprised two pre-eclamptic patients with intrauterine growth restriction while the control group comprised three healthy women with uncomplicated pregnancies. Gene expression was studied using Affymetrix Human Genome U133 Plus 2 micro arrays. We focused on genes associated with angiogenesis. Some of the micro array analysis results were verified using real-time reverse transcription polymerase chain reaction (RT-PCR). Results. Gene expression profiling revealed that the expression level of nine genes - ECGF1, JAG1, Palladin, COL18A1, TNFSF12, VEGF, ANPEP, PDGFRA and SERPIN12 - was downregulated whereas the level of four genes - EPAS1, FLT1, SIGLE10 and ANG4 - was upregulated in the study group compared with the control group. The real-time RT-PCR results from JAG1, COL18A1 and FLT1 genes were in accordance with the gene expression results. Conclusion. Our results show new targets for research to understand the mechanisms leading to pre-eclampsia. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the natural history of myomas in familial cases and to compare the tendencies of myomas between familial and non-familial cases. Study design: Subjects with familial and non-familial myomas were identified from the hospital records and the reliable details of the myomas were collected. Results: In the familial cases there are several myomas, four or more. In the non-familial cases, there is usually only one single myoma, which is bigger than in familial cases. In the familial group, the diagnosis and surgery was made earlier. In the familial group, there were more pregnancies and less infertility problems. Conclusion: There is a significant difference in the natural history of the familial and non-familial cases. In familial cases, subjects have four or more myomas while in non-familial cases the fibroid is single and large. [Copyright &y& Elsevier]

We investigated the association of first trimester low maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels with small-for-gestational age (SGA) newborns and stillbirths (SBs) in a retrospective national population-based register study. The study group comprised 921 women with the lowest 5% PAPP-A levels (≤0.3 MoM) and the control group comprising 18,615 women with PAPP-A levels >0.3 MoM. In the study group there were 35 (3.8%) and in the control group 213 SGA newborns (1.1%), respectively (OR, 3.41; 95% CI, 2.37-4.91). There were 9 (1.0%) and 51 (0.3%) cases of SBs in the study and control groups, respectively ( p < 0.002; OR, 3.59; 95% CI, 1.76-7.32). Low PAPP-A is a risk factor for SGA and SB. [ABSTRACT FROM AUTHOR]

The characteristics of the Finnish parturient have changed in recent years. The mean age of mothers at first delivery is now 29.3 years and the number of women > 35 years of age has increased to 19%. This shift has led to an increase in the prevalence of Down's syndrome. Between 1 January 2002 and 31 December 2006, there were 795 cases of Down's syndrome (27/10,000) in the Finnish Register of Congenital Malformations. The distribution of Down's syndrome in terminated pregnancies and newborns was analyzed in 5-year periods based on maternal age. The distribution of Down's syndrome cases in younger women (< 35 years) and in older women (≥35 years) at the time of delivery was compared. The majority of new Down's syndrome cases occurred in the group having older women (61.1%), even though 35 years is the arbitrary threshold. [ABSTRACT FROM AUTHOR]