Uterine leiomyomas in hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome can be identified through distinct clinical characteristics and typical morphology.

INTRODUCTION: Hereditary leiomyomatosis and renal cell cancer (HLRCC) constitute a tumor susceptibility syndrome caused by germline mutations in the fumarate hydratase (FH) gene. The most common features are leiomyomas of the uterus and the skin. The syndrome includes a predisposition to early-onset, aggressive renal cell cancer. It is important to identify women with HLRCC among other uterine leiomyoma patients in order to direct them to genetic counseling and to identify other affected family members. MATERIAL AND METHODS: We conducted a nationwide historical study to identify typical clinical characteristics, uterine leiomyoma morphology, and immunohistochemistry for diagnosing HLRCC. The study included 20 women with a known FH germline mutation and 77 women with sporadic uterine leiomyomas. The patient records of all women were reviewed to obtain clinical details regarding their leiomyomas. Uterine leiomyoma tissue specimens from 43 HLRCC-related leiomyomas and 42 sporadic leiomyomas were collected and prepared for histology analysis. A morphologic description was performed on hematoxylin & eosin-stained tissue slides, and immunohistochemical analysis was carried out for CD34, Bcl-2, and p53 stainings. RESULTS: The women with HLRCC were diagnosed with uterine leiomyomas at a young age compared with the sporadic leiomyoma group (mean 33.8 years vs. 45.4 years, P < 0.0001), and their leiomyomas occurred as multiples compared with the sporadic leiomyoma group (more than four tumors 88.9% vs. 30.8%, P < 0.0001). Congruently, these women underwent surgical treatment at younger age compared with the sporadic leiomyoma group (mean 37.3 years vs. 48.3 years, P < 0.0001). HLRCC leiomyomas had denser microvasculature highlighted by CD34 immunostaining when compared with the sporadic leiomyoma group (112.6 mean count/high-power field, SD 20.8 vs. 37.4 mean count/high-power field, SD 21.0 P < 0.0001) and stronger anti-apoptotic protein Bcl-2 immunostaining when compared with the sporadic leiomyoma group (weak 4.7%, moderate 44.2%, strong 51.2% vs. 26.2%, 52.4%, 21.4%, respectively, P = 0.003). No differences were observed in p53 staining. CONCLUSIONS: Women with HLRCC may be identified through the distinct clinical characteristics: symptomatic and numerous leioymyomas at young age, and morphologic features of FH-mutant leiomyomas, aided by Bcl-2 and CD34 immunohistochemistry. Further, distinguishing individuals with a germline FH mutation enables proper genetic counseling and regular renal monitoring.

Glycosylated fibronectin as a first trimester marker for gestational diabetes.

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.

Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

OBJECTIVE: To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. STUDY DESIGN: Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. RESULTS: Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. CONCLUSION: There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

Uterine fibroids and cardiovascular risk.

STUDY QUESTION: Are uterine fibroids associated with increased cardiovascular risk? SUMMARY ANSWER: This study reports an association between increased serum lipids and metabolic syndrome with an increased risk of uterine fibroids. WHAT IS KNOWN ALREADY: Recent studies suggest similarities in biological disease mechanisms and risk factors for fibroids and atherosclerosis: obesity, hypertension and abnormal serum lipids. These findings are awaiting confirmation that a population-based follow-up study could offer with extensive health examination data collection linked with a national hospital discharge register. STUDY DESIGN, SIZE, DURATION: The Northern Finland Birth Cohort (NFBC1966) is a population-based long-term follow-up study including all children with estimated date of delivery in 1966 in the Northern Finland area. The data were collected from national registries, postal questionnaires and clinical health examinations. The study population for this study comprised all females included in the NFBC1966 that underwent an extensive clinical health examination at age 46 years (n = 3635). PARTICIPANTS/MATERIALS, SETTING, METHODS: All females included in the NFBC1966 who were alive and traceable (n = 5118) were invited for the 46-year follow-up study; 3268 (63.9%) responded, returned the postal questionnaire and attended the clinical examination. Uterine fibroid cases were identified through the national hospital discharge register that has data on disease diagnoses based on WHO ICD-codes. Uterine fibroid codes, ICD-9: 218 and ICD-10: D25 were used for case identification. Self-reported fibroid cases were identified through the postal questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 729 fibroid cases were identified, including 293 based on hospital discharge registries. With adjustment for BMI, parity, education and current use of exogenous hormones the risk of prevalent fibroids rose significantly for every 1 mmol/l increase in LDL (OR = 1.13, 95% CI: 1.02-1.26 for all cases) and triglycerides (OR = 1.27, 95% CI: 1.09-1.49 for all cases). Metabolic syndrome associated with hospital discharge-based fibroid diagnosis (OR = 1.48, 95% CI: 1.09-2.01). Additionally every 1 unit increase in waist-hip ratio associated with fibroids (OR = 1.32, 95% CI: 1.10-1.57). LIMITATIONS, REASONS FOR CAUTION: The case ascertainment may present some limitations. There was likely an under-identification of cases and misclassification of some cases as controls; this would have diluted the effects of reported associations. The data analysed were cross-sectional and therefore cause and effect for the associations observed cannot be distinguished. WIDER IMPLICATIONS OF THE FINDINGS: Increased serum lipids and metabolic syndrome are associated with increased risk of uterine fibroids. Along with central obesity these findings add to an increased risk for cardiovascular disease among women with fibroids. These observations may suggest that there are shared predisposing factors underlying both uterine fibroids and adverse metabolic and cardiac disease risk, or that metabolic factors have a role in biological mechanisms underlying fibroid development. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Academy of Finland, University Hospital Oulu, University of Oulu, Finland, Northern Finland Health Care Foundation, Duodecim Foundation, ERDF European Regional Development Fund-Well-being and health: Research in the Northern Finland Birth Cohort 1966. The authors declare no conflict of interest.

First-trimester maternal serum ADAM12-s and PAPP-A levels are altered in pregnancies conceived after assisted reproduction techniques (ART).

OBJECTIVE: The objective of this article is to estimate whether the maternal serum levels of A disintegrin and metalloprotease domain 12 (ADAM12-s), pregnancy-associated plasma protein-A (PAPP-A), and free beta human chorionic gonadotrophin (fß-hCG) are altered in assisted reproduction techniques (ART) pregnancies. METHOD: A retrospective cohort study with a control group was performed. Two hundred eighty-three ART pregnancies and 1008 controls were studied. The patients were divided into groups according to the type of conception: (1) controls, (2) fresh embryo transfer (ET) following controlled ovarian stimulation (COH) and in vitro fertilization (IVF), (3) fresh ET following COH and intracytoplasmic sperm injection (ICSI), (4) frozen ET during natural menstrual cycle (NC-FET), and (5) frozen ET using hormone replacement therapy. The cases and controls were matched for gestational and maternal age and for the storage time of the samples. RESULTS: The ADAM12-s levels were statistically significantly higher in the entire ART group, IVF and ICSI groups, and NC-FET group when compared with those in the controls. The PAPP-A levels were decreased only in the ICSI group compared with those in the controls. fß-hCG levels were not altered in assisted pregnancies. The ADAM12-s levels tended to increase with advanced gestational age. ADAM12-s levels were correlated with PAPP-A and fß-hCG levels in several subgroups of ART pregnancies. CONCLUSION: ADAM12-s and PAPP-A levels are altered in several subgroups of ART pregnancies. Larger studies are required to confirm these findings.

Risk of Adverse Outcomes in Euploid Pregnancies With Isolated Short Fetal Femur and Humerus on Second-Trimester Sonography.

OBJECTIVES: The purpose of this study was to evaluate pregnancies with isolated short fetal femur and humerus on second-trimester sonography. Short fetal long bones are known to be associated with aneuploidy and structural anomalies. In this study, we wanted to show the risk of adverse pregnancy outcomes in euploid and nonanomalous pregnancies. METHODS: Singleton pregnancies with short femur and humerus were included. Pregnancies with normal fetal bone lengths and age-matched mothers were selected as controls. RESULTS: The study group included 30 pregnancies with short fetal femur and humerus, and the control group included 60 normal pregnancies. The overall odds ratio for an adverse pregnancy outcome in the study group was 24.9. Preterm delivery occurred significantly more frequently (odds ratio, 20.8; P < .001), and one-third of pregnancies were complicated by preeclampsia. In the group with short long bones, the odds ratio for a pathologic umbilical Doppler flow pattern was 45.2 (P < .001), and birth weight was significantly lower (P < .001). Also, 3 (10.3%) stillbirths and 4 (13.3%) cases of early neonatal death were recorded in this group. These complications were not recorded in the control group. The risk of emergency cesarean delivery was significantly higher in the group with short long bones (odds ratio, 11.8; P < .001). CONCLUSIONS: The risk of adverse pregnancy outcomes is significant in euploid and nonanomalous pregnancies with isolated short long bones. Close follow-up is needed during pregnancy.

Comparison of combined, biochemical and nuchal translucency screening for Down syndrome in first trimester in Northern Finland.

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 AutoDELFIA® time-resolved fluoroimmunoassay kit for the measurement of pregnancy-associated plasma protein-A and free ß-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.

Strong family history of uterine leiomyomatosis warrants fumarate hydratase mutation screening.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and renal cell cancer. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. A Finnish family with nine closely related women with uterine leiomyomas was detected by an alert gynecologist. No cutaneous or renal cell tumors were reported in the family when it was referred to genetic analyses. Samples were available from seven patients, and a novel germline FH mutation was detected in five of them. Mutation carriers were symptomatic, had multiple tumors and were diagnosed at an early age. This study emphasizes the importance of considering FH mutation screening when gynecologists encounter families with multiple severe uterine leiomyoma cases. Due to possibility of phenocopies more than one patient should be tested. Early mutation detection allows regular screening of the mutation carriers and enables early detection of possible highly aggressive renal tumors. It may also affect family planning as multiple myomas at early age may significantly reduce fertility.

Effect of parity and fetal sex on placental and luteal hormones during early first trimester.

OBJECTIVE: Earlier studies have shown that maternal hormone secretion during late first or second trimester may be affected by gravidity. We examined the luteoplacental hormone secretion during 5-11 weeks of gestation in relation to gravidity. METHOD: Forty-one naturally conceived pregnancies underwent weekly assessment of serum human chorionic gonadotrophin, progesterone and 17-OH progesterone, estradiol, testosterone, and pregnancy-associated plasma protein A levels. In addition, the volume and the vasculature of the dominant ovary with corpus luteum were assessed with the use of a 3-dimensional power Doppler ultrasonography. Areas under the curve for hormonal and ultrasonographic parameters were calculated. RESULTS: Twenty-two out of the 41 women were pregnant for the first time. All the pregnancies were uncomplicated and resulted in term deliveries of appropriately grown newborns. During pregnancy weeks 5-11, the secretion (area under the curve) of human chorionic gonadotrophin (6.54 ± 0.03 vs 6.39 ± 0.05, p = 0.010), progesterone (3.49 ± 0.02 vs 3.36 ± 0.03, p = 0.003), and 17-OH progesterone (2.73 ± 0.03 vs 2.62 ± 0.03, p = 0.013) were higher in primigravid than in multigravid women. No other differences were detected between primigravid and multigravid women. CONCLUSION: The placental function already differs between primigravid and multigravid women during the first weeks of pregnancy, which reflects the corpus luteal function.

False-negative results in routine combined first-trimester screening for down syndrome in Finland.

We analyzed the frequency and possible causes of false-negative (Fn) screening results in first-trimester combined Down syndrome screening in Finland. During the study period (May 1, 2002, to December 31, 2008), 76,949 voluntary women with singleton pregnancies participated in screening. Maternal age at screening, week of gestation, levels of pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotropin (fß-hCG), and nuchal translucency (NT) measurement were compared and statistically analyzed between true-positive (Tp) and Fn cases. There were a total of 188 Down syndrome cases (1:409) in the screened population; 154 confirmed Tp and 34 Fn cases. Most Fn cases (n = 25) occurred at 12 + 0 to 13 + 6 weeks' gestation and only nine Fn cases presented between 10 and 11 weeks' gestation. According to the logistic regression analysis, the NT measurement was the most powerful discriminating factor in Fn screening results and accounted for 37.2% of Fn results. The second most important factor was fß-hCG, adding 14.0% to R(2), followed by PAPP-A, which contributed a further 14.3%. The chosen parameters explain 83.9% of Fn results, but 16.1% remain due to unknown factor(s). All investigated parameters contributed to Fn screening results, but fetal NT was the most discriminating factor leading to an Fn screening result.

First trimester biochemistry at different maternal ages.

BACKGROUND: The performance of first trimester biochemical screening was compared at different pregnancy weeks and maternal ages during 2002-2008 in a screened population of 76,949 women. METHODS: The detection rates, as well as the median multiples of a median (MOMs) of free ß-human chorionic gonadotropin (free ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A), were compared between completed gestational weeks 8-13 and between different maternal ages separated into 5-year groupings. RESULTS: The number of singleton Down syndrome pregnancies was 221. The median age of the screened women was 30 years and the proportion of women aged ≥ 35 years 16.9%. The median age of the women with a Down syndrome pregnancy was 37 years. In women aged <35 years, the biochemical markers provided a detection rate of only 38.6%, whereas in women aged ≥ 35 years, the biochemical markers detected 82.7% of cases (p<0.01). CONCLUSIONS: Biochemical screening works best amongst women aged ≥ 35 years. For younger mothers aged <35 years, combined screening should be the method of choice.

Screening and outcome of chromosomal abnormalities other than trisomy 21 in Northern Finland.

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 ß-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.

More invasive procedures are done to detect each case of Down's syndrome in younger women.

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 76949 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.

Prevalence of Down's syndrome in a pregnant population in Finland.

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 (> or =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.

Low maternal PAPP-A is associated with small-for-gestational age newborns and stillbirths.

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 (< or =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.

Maternal serum ADAM12 levels correlate with PAPP-A levels during the first trimester.

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.

Fetal nuchal translucency in severe congenital heart defects: experiences in Northern Finland.

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.

First trimester combined screening biochemistry in detection of congenital heart defects.

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fß-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 fß-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 fß-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fß-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 fß-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.

Placenta-mediated pregnancy complications are not associated with fetal or paternal factor V Leiden mutation.

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.