Quadruplet pregnancy outcome with and without fetal reduction: Danish national cohort study (2008-2018) and comparison with dichorionic twins.

OBJECTIVES: To perform a nationwide study of quadrichorionic quadriamniotic (QCQA) quadruplet pregnancies and to compare the pregnancy outcome in those undergoing fetal reduction with non-reduced quadruplets and dichorionic diamniotic (DCDA) twin pregnancies from the same time period. METHODS: This was a retrospective Danish national register-based study performed using data from the national Danish Fetal Medicine Database, which included all QCQA quadruplets and all non-reduced DCDA twin pregnancies with an estimated due date between 2008 and 2018. The primary outcome measure was a composite of adverse pregnancy outcomes, including pregnancy loss or intrauterine death of one or more fetuses. Secondary outcomes included gestational age at delivery, the number of liveborn children, preterm delivery before 28, 32 and 37 gestational weeks and birth weight. Data on pregnancy complications and baseline characteristics were also recorded. Outcomes were compared between reduced and non-reduced quadruplet pregnancies, and between DCDA pregnancies and quadruplet pregnancies reduced to twins. A systematic literature search was performed to describe and compare previous results with our findings. RESULTS: Included in the study were 33 QCQA quadruplet pregnancies, including three (9.1%) non-reduced pregnancies, 28 (84.8%) that were reduced to twin pregnancy and fewer than three (6.1%) that were reduced to singleton pregnancy, as well as 9563 DCDA twin pregnancies. Overall, the rate of adverse pregnancy outcome was highest in non-reduced quadruplets (66.7%); it was 50% in quadruplets reduced to singletons and 10.7% in quadruplets reduced to twins. The proportion of liveborn infants overall was 91.1% of the total number expected to be liveborn in quadruplet pregnancies reduced to twins. This was statistically significantly different from 97.6% in non-reduced dichorionic twins (P = 0.004), and considerably higher than 58.3% in non-reduced quadruplets. The rates of preterm delivery < 28, < 32 and < 37 weeks were decreased in quadruplets reduced to twins compared with those in non-reduced quadruplet pregnancies. Quadruplets reduced to twins did not achieve equivalent pregnancy outcomes to those of DCDA twins. CONCLUSION: This national study of QCQA quadruplets has shown that multifetal pregnancy reduction improves pregnancy outcome, including a decreased rate of preterm delivery and higher proportion of liveborn children. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence and detection rate of major congenital heart disease in twin pregnancies in Denmark.

OBJECTIVE: To investigate the national prevalence and prenatal detection rate (DR) of major congenital heart disease (mCHD) in twin pregnancies without twin-to-twin transfusion syndrome (TTTS)-associated CHD in a Danish population following a standardized prenatal screening program. METHODS: This was a national registry-based study of data collected prospectively over a 10-year period. In Denmark, all women with a twin pregnancy are offered standardized screening and surveillance programs in addition to first- and second-trimester screening for aneuploidies and malformation, respectively: monochorionic (MC) twins every 2 weeks from gestational week 15 and dichorionic (DC) twins every 4 weeks from week 18. The data were retrieved from the Danish Fetal Medicine Database and included all twin pregnancies from 2009-2018, in which at least one fetus had a pre- and/or postnatal mCHD diagnosis. mCHD was defined as CHD requiring surgery within the first year of life, excluding ventricular septal defects. All pregnancy data were pre- and postnatally validated in the local patient files at the four tertiary centers covering the entire country. RESULTS: A total of 60 cases from 59 twin pregnancies were included. The prevalence of mCHD was 4.6 (95% CI, 3.5-6.0) per 1000 twin pregnancies (1.9 (95% CI, 1.3-2.5) per 1000 live births). The prevalences for DC and MC were 3.6 (95% CI, 2.6-5.0) and 9.2 (95% CI, 5.8-13.7) per 1000 twin pregnancies, respectively. The national prenatal DR of mCHD in twin pregnancies for the entire period was 68.3%. The highest DRs were in cases with univentricular hearts (100%) and the lowest with aortopulmonary window, total anomalous pulmonary venous return, Ebstein's anomaly, aortic valve stenosis and coarctation of the aorta (0-25%). Mothers of children with prenatally undetected mCHD had a significantly higher body mass index (BMI) compared to mothers of children with a prenatally detected mCHD (median, 27 kg/m2 and 23 kg/m2 , respectively; P = 0.02). CONCLUSIONS: The prevalence of mCHD in twins was 4.6 per 1000 pregnancies and was higher in MC than DC pregnancies. The prenatal DR of mCHD in twin pregnancies was 68.3%. Maternal BMI was higher in cases of prenatally undetected mCHD. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence of chromosomal disorders in cases with congenital heart defect: registry-based study from Denmark between 2008 and 2018.

OBJECTIVE: To estimate the prevalence of chromosomal conditions in all fetuses and children with major congenital heart defect (CHD) in Denmark between 2008 and 2018. METHODS: This was a national registry-based study including all singleton pregnancies with a prenatally or postnatally diagnosed major CHD usually requiring surgery within the first year after birth and a due date between July 2008 and December 2018 in Denmark. Data were retrieved from the Danish Fetal Medicine Database (DFMD) and the Danish Cytogenetic Central Register (DCCR) in October 2020. The DCCR contains information on all prenatal and postnatal genetic analyses, including karyotyping, chromosomal microarray, polymerase chain reaction, multiplex ligation-dependent probe amplification and fluorescence in-situ hybridization. All cases were reviewed by a clinical geneticist, and genetic changes were classified as pathogenic, likely pathogenic, variant of uncertain significance, likely benign or benign. Pathogenic and likely pathogenic variants were considered to be abnormal. Cases with CHD without any registered chromosomal analysis reported were considered genetically normal. Isolated CHD was defined as a case with major CHD without any other structural malformations detected prenatally or postnatally. Results are given as n (%). Comparisons between isolated and non-isolated cases were performed using logistic regression analysis, and data are presented as odds ratios (ORs) with 95% CIs. RESULTS: A total of 8482 cases with any cardiovascular diagnosis were retrieved from the DFMD. Twins (n = 112) and minor CHD cases (n = 6921) were excluded, resulting in 1449 cases with major CHD. Of the included cases, 918 (63.4%) underwent chromosomal analysis. An abnormal test result was found in 187 cases, giving a prevalence of a chromosomal condition of 12.9% (95% CI, 11.2-14.7%) among all cases with major CHD. The highest prevalence of a chromosomal condition was found in cases with pulmonary atresia with intact ventricular septum and those with truncus arteriosus (both 28.6%), while the lowest prevalence was found in cases with transposition of the great arteries (2.2%) and congenitally corrected transposition of the great arteries (0%). In isolated cases of transposition of the great arteries, the prevalence of a chromosomal condition was 0.6%. The overall OR for a chromosomal condition in non-isolated cases compared with isolated cases was 2.72 (95% CI, 1.90-3.88). CONCLUSIONS: We found an overall prevalence of a chromosomal condition of 12.9% among cases with major CHD in a national cohort with a high participation rate in first- and second-trimester screening, without employing whole genome and whole exome sequencing. The prevalence of a chromosomal condition varied considerably according to CHD diagnosis and presence of associated extracardiac malformations. These findings are important for prenatal counseling. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal cardiac biometry and flow assessment in fetuses with bicuspid aortic valve at 20 weeks' gestation: multicenter cohort study.

OBJECTIVE: To investigate prenatal changes in cardiac biometric and flow parameters in fetuses with bicuspid aortic valve (BAV) diagnosed neonatally compared with controls with normal cardiac anatomy. METHODS: This analysis was conducted as part of the Copenhagen Baby Heart Study, a multicenter cohort study of 25 556 neonates that underwent second-trimester anomaly scan at 18 + 0 to 22 + 6 weeks' gestation and neonatal echocardiography within 4 weeks after birth, in Copenhagen University Hospital Herlev, Hvidovre Hospital and Rigshospitalet in greater Copenhagen, between April 2016 and October 2018. From February 2017 (Rigshospitalet) and September 2017 (Herlev and Hvidovre hospitals), the protocol for second-trimester screening of the heart was extended to include evaluation of the four-chamber view, with assessment of flow across the atrioventricular valves, sagittal view of the aortic arch and midumbilical artery and ductus venosus pulsatility indices. All images were evaluated by two investigators, and cardiac biometric and flow parameters were measured and compared between cases with BAV and controls. All cases with neonatal BAV were assessed by a specialist. Maternal characteristics and first- and second-trimester biomarkers were also compared between the two groups. RESULTS: Fifty-five infants with BAV and 8316 controls with normal cardiac anatomy were identified during the study period and assessed using the extended prenatal cardiac imaging protocol. There were three times as many mothers who smoked before pregnancy in the group with BAV as in the control group (9.1% vs 2.7%; P = 0.003). All other baseline characteristics were similar between the two groups. Fetuses with BAV, compared with controls, had a significantly larger diameter of the aorta at the level of the aortic valve (3.1 mm vs 3.0 mm (mean difference, 0.12 mm (95% CI, 0.03-0.21 mm))) and the pulmonary artery at the level of the pulmonary valve (4.1 mm vs 3.9 mm (mean difference, 0.15 mm (95% CI, 0.03-0.28 mm))). Following conversion of the diameter measurements of the aorta and pulmonary artery to Z-scores and Bonferroni correction, the differences between the two groups were no longer statistically significant. Pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) was significantly lower in the BAV group than in the control group (0.85 vs 1.03; P = 0.04). CONCLUSIONS: Our findings suggest that fetuses with BAV may have a larger aortic diameter at the level of the aortic valve, measured in the left-ventricular-outflow-tract view, and a larger pulmonary artery diameter at the level of the pulmonary valve, measured in the three-vessel view, at 20 weeks' gestation. Moreover, we found an association of maternal smoking and low PAPP-A MoM with BAV. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Do chorionic villus samplings (CVS) or amniocenteses (AC) induce RhD immunisation? An evaluation of a large Danish cohort with no routine administration of anti-D after invasive prenatal testing.

OBJECTIVE: To evaluate the risk of inducing RhD immunisation in pregnancies of RhD-negative mothers with an RhD-positive fetus undergoing chorionic villus samplings (CVS) or amniocenteses (AC). DESIGN, SETTING AND POPULATION: Registry-based study in a Danish cohort which has not been given rhesus prophylaxis. METHODS: Data were retrieved from the Department of Clinical Immunology at Rigshospitalet. All RhD-negative women carrying an RhD-positive fetus with screen test results from weeks 8-12 and weeks 25-29 were linked to data from the Danish Fetal Medicine Database. Data were divided into cases where no invasive prenatal diagnostic procedure was performed, cases that had AC performed, and cases that had CVS performed. MAIN OUTCOME MEASURES: A comparison of the proportion of women who developed RhD immunisation between the two screen tests. RESULTS: The cohort consisted of 10 085 women: 9353 had no invasive procedures performed, 189 had AC and 543 had CVS performed. No women were immunised spontaneously or due to the procedure between the first and second screen test in the group with no procedure performed, or in the AC group. One woman was immunised in the CVS group. When comparing the proportion of women who was immunised in the CVS group with the no invasive test group a non-significant difference was found (P = 0.055). CONCLUSION: The RhD immunisation rate before gestational weeks 25-29 in RhD-negative women carrying an RhD-positive fetus is very low, even in women undergoing prenatal invasive testing without rhesus prophylaxis. TWEETABLE ABSTRACT: The RhD immunisation rate during pregnancy is very low even in women undergoing prenatal invasive testing.

Maternal exposure to UV filters: associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes.

BACKGROUND: Several chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo. Exposure to these chemicals, especially during prenatal development, is of concern. OBJECTIVES: To examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes. METHODS: Prospective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined. RESULTS: Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T3), thyroxine (T4), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group. CONCLUSIONS: Widespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children's health.

Presence of benzophenones commonly used as UV filters and absorbers in paired maternal and fetal samples.

BACKGROUND: Previous studies have demonstrated widespread exposure of humans to certain benzophenones commonly used as UV filters or UV absorbers; some of which have been demonstrated to have endocrine disrupting abilities. OBJECTIVES: To examine whether benzophenones present in pregnant women pass through the placental barrier to amniotic fluid and further to the fetal blood circulation. METHODS: A prospective study of 200 pregnant women with simultaneously collected paired samples of amniotic fluid and maternal serum and urine. In addition, unique samples of human fetal blood (n=4) obtained during cordocentesis: and cord blood (n=23) obtained at delivery, both with paired maternal samples of serum and urine collected simultaneously, were used. All biological samples were analyzed by TurboFlow-liquid chromatography - tandem mass spectrometry for seven different benzophenones. RESULTS: Benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-methyl-benzophenone (4-MBP), and 4-hydroxy-benzophenone (4-HBP) were all detectable in amniotic fluid and cord blood samples and except 4-HBP also in fetal blood; albeit at a low frequency. BP-1 and BP-3 were measured at ~10-times lower concentrations in fetal and cord blood compared to maternal serum and 1000-times lower concentration compared to maternal urine levels. Therefore BP-1 and BP-3 were only detectable in the fetal circulation in cases of high maternal exposure indicating some protection by the placental barrier. 4-MBP seems to pass into fetal and cord blood more freely with a median 1:3 ratio between cord blood and maternal serum levels. Only for BP-3, which the women seemed to be most exposed to, did the measured concentrations in maternal urine and serum correlate to concentrations measured in amniotic fluid. Thus, for BP-3, but not for the other tested benzophenones, maternal urinary levels seem to be a valid proxy for fetal exposure. CONCLUSIONS: Detectable levels of several of the investigated benzophenones in human amniotic fluid as well as in fetal and cord blood calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of these compounds in order for better assessment of the risk to the developing fetus.

Contingent first-trimester screening for aneuploidies with cell-free DNA in a Danish clinical setting.

OBJECTIVES: The primary aim of this study was to compare the screening performance for trisomy 21 (T21) between combined first-trimester screening (cFTS) with referral for invasive testing at a T21 risk ≥ 1 in 300, and contingent screening consisting of referral for invasive testing at a cFTS-T21 risk ≥ 1 in 100 and referral for cell-free DNA (cfDNA) testing at a cFTS-T21 risk between 1 in 100 and 1 in 1000. Secondary aims were to compare the incidence of fetuses diagnosed with trisomy 18 (T18), trisomy 13 (T13) or sex chromosome aneuploidy, and examine the association between fetal fraction of cfDNA in maternal blood and maternal/fetal characteristics. METHODS: Women with a singleton pregnancy and a cFTS-T21 risk of ≥ 1 in 1000 were recruited consecutively from two Danish hospitals between August 2014 and May 2015. First-trimester combined screening was based on maternal age, nuchal translucency thickness and levels of pregnancy-associated plasma protein A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG). Blood samples for cfDNA testing were analyzed for risks of T21, T18, T13 and sex chromosomal aneuploidies. cfDNA analysis was conducted blinded to the cFTS assessment and karyotype results. Pregnancy outcomes and pre- and postnatal karyotypes were obtained from the Danish Fetal Medicine Database. RESULTS: Among 6449 women who underwent cFTS risk assessment, 869 (13.5%) had a T21 risk of ≥ 1 in 1000 and 597 were included for cfDNA testing. Among these, there were 15 cases of T21, one case of T18 and two cases of T13. The sensitivity for detection of T21 was 100% using both screening strategies, while specificity increased significantly (P < 0.0001) from 97.0% using the cFTS strategy to 98.8% using the contingent approach. The sensitivity for detection of T21, T18 and T13 increased from 94.4% using the cFTS strategy to 100% using the contingent approach, with overlapping CIs, while specificity increased significantly (P < 0.0001) from 97.1% for cFTS to 98.9% for the contingent strategy. Seven pregnancies were categorized as being at increased risk of a sex chromosomal aneuploidy by cfDNA testing but chromosome analysis was discordant, corresponding to a false-positive rate of 1.2%. The fetal fraction decreased significantly with increasing maternal weight and increased significantly with the level of ß-hCG and PAPP-A and among female fetuses, in both univariate and multivariate analyses. CONCLUSIONS: In a clinical setting with efficient cFTS, contingent screening offering women with a cFTS risk of ≥ 1 in 100 an invasive test and women with a risk from 1 in 100 to 1 in 1000 a cfDNA test had the same sensitivity for T21, T18 and T13, but significantly increased specificity, when compared with offering an invasive test to all women with a risk of ≥ 1 in 300. Implementing contingent screening would therefore reduce significantly the number of invasive tests performed at no loss of sensitivity. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Varying Inundation Regimes Differentially Affect Natural and Sand-Amended Marsh Sediments.

Climate change is altering sea level rise rates and precipitation patterns worldwide. Coastal wetlands are vulnerable to these changes. System responses to stressors are important for resource managers and environmental stewards to understand in order to best manage them. Thin layer sand or sediment application to drowning and eroding marshes is one approach to build elevation and resilience. The above- and below-ground structure, soil carbon dioxide emissions, and pore water constituents in vegetated natural marsh sediments and sand-amended sediments were examined at varying inundation regimes between mean sea level and mean high water (0.82 m NAVD88 to 1.49 m NAVD88) in a field experiment at Laws Point, part of the Plum Island Sound Estuary (MA). Significantly lower salinities, pH, sulfides, phosphates, and ammonium were measured in the sand-amended sediments than in the natural sediments. In natural sediments there was a pattern of increasing salinity with increasing elevation while in the sand-amended sediments the trend was reversed, showing decreasing salinity with increasing elevation. Sulfide concentrations generally increased from low to high inundation with highest concentrations at the highest inundation (i.e., at the lowest elevations). High pore water phosphate concentrations were measured at low elevations in the natural sediments, but the sand-amended treatments had mostly low concentrations of phosphate and no consistent pattern with elevation. At the end of the experiment the lowest elevations generally had the highest measures of pore water ammonium. Soil carbon dioxide emissions were greatest in the sand-amended mesocosms and at higher elevations. Differences in coarse root and rhizome abundances and volumes among the sediment treatments were detected with CT imaging, but by 20 weeks the natural and sand-amended treatments showed similar total belowground biomass at the intermediate and high elevations. Although differences in pore water nutrient concentrations, pH, salinity, and belowground root and rhizome morphology were detected between the natural and sand-amended sediments, similar belowground productivity and total biomass were measured by the end of the growing season. Since the belowground productivity supports organic matter accumulation and peat buildup in marshes, our results suggest that thin layer sand or sediment application is a viable climate adaptation action to build elevation and coastal resiliency, especially in areas with low natural sediment supplies.

Maxillary length in 11- to 26-week-old normal fetuses studied by 3D ultrasound.

OBJECTIVES: The objective of this article is to investigate normal prenatal maxillary length using 3D ultrasound and to correlate this with previously reported results for the mandible and the biparietal diameter (BPD). METHODS: Seventy-two 3D ultrasound volumes from normal pregnancies in 52 volunteers (gestational age: 11-26 weeks) were obtained using a GE Voluson 730 Expert 3D scanner. Maxillary length and BPD were measured. Growth velocity and rate were calculated. Maxillary values were correlated with BPD and previously reported mandibular values. RESULTS: The mean total maxillary length ranged from 7.4 ± 2.7 mm at 11 weeks to 33.1 ± 2.7 mm at 26 weeks. Maxillary growth velocity can be described using a linear model. The correlation between maxillary and mandibular length, and BPD was high (R = 0.85-0.88). There was no statistically significant difference in the growth velocity between maxilla and mandible, whereas the velocity of the increase in BPD growth was significantly larger than that of the jaws. However, the growth rate was larger for the jaws than for the BPD. CONCLUSIONS: Normative measures for the maxilla in 11- to 26-week-old fetuses are presented. Change in maxillary length was described using a linear model. The maxillary and mandibular growth velocities and rates were similar but differ from those of the BPD.

Screening performance for trisomy 21 comparing first trimester combined screening and a first trimester contingent screening protocol including ductus venosus and tricuspid flow.

OBJECTIVE: To compare the standard first trimester combined risk assessment for trisomy 21 with a contingent screening protocol including tricuspid flow and ductus venosus flow. MATERIAL AND METHOD: Women with singleton pregnancies and a first trimester combined risk assessment>1:1000 were included. They all had additional assessment of the ductus venosus and the tricuspid flow. We compared screening performance in two screening strategies: (a) First trimester combined screening strategy based on the individual risk results from the routine screening test and (b) Contingent screening strategy based on a combination of the routine test results and additional ultrasound markers. RESULTS: We included 917 women in the study, 894 in the euploid group and 23 in the trisomy 21 group. Using a contingent screening strategy resulted in a significant decrease in screen positive rate from 48.3% to 17.7% (p<0.001) in the studied population. There was no statistical difference in detection rate between the two screening strategies. CONCLUSION: There is increasing evidence in favour of using additional ultrasound markers as part of contingent screening protocols in the first trimester. We do suggest performing further studies in routine clinical settings to provide validation of the available risk algorithms.

Relative prevalence of upper respiratory tract obstructive disorders in two breeds of harness racehorses (185 cases: 1998-2006).

REASONS FOR PERFORMING STUDY: Two genetically and phenotypically distinct horse breeds are used for harness racing in Scandinavia: the Standardbred (SB) and Coldblooded Trotter. These racehorses have identical environmental, management and racing conditions. Therefore, this study was undertaken to identify and compare the relative prevalence of upper respiratory tract (URT) obstructive disorders in these 2 breeds. OBJECTIVES: To determine whether these 2 phenotypically different breeds of harness racehorses have different predispositions for URT disorders. METHODS: Retrospective study of 88 Norwegian Coldblooded Trotters (NCT) and 97 SBs referred to this hospital for URT evaluation between 1998 and 2006. Case records of all horses diagnosed with an URT disorder during resting endoscopy, and all horses undergoing high-speed treadmill videoendoscopy (HSTV) with one or more periods of induced poll flexion were evaluated. The relative prevalence of URT disorders between the 2 breeds was analysed using a Fisher's exact test. RESULTS: There was a significant (P<0.05) breed predisposition regarding 6 URT disorders. Bilateral dynamic laryngeal collapse associated with poll flexion and flaccid epiglottis was significantly more frequent in the NCT. Alar fold collapse and nasopharyngeal collapse were significantly more frequent in SBs. Epiglottic entrapment and nasal flutter were only diagnosed in the SBs. Dynamic disorders were more common than resting disorders in both breeds. CONCLUSION: URT obstructive disorders (dynamic laryngeal collapse associated with poll flexion, flaccid epiglottis, pharyngeal collapse, alar fold collapse, nasal flutter and epiglottic entrapment) are breed related, indicating an anatomic or functional cause. Periods of induced poll flexion during HSTV was essential to declare harness racehorses free of URT disorders. POTENTIAL RELEVANCE: Further anatomic or physiological studies comparing these breeds could potentially provide insight into the pathogenesis of certain URT obstructive disorders. Induced poll flexion should be included in routine HSTV examinations of all harness racehorses.

Maternal smoking, obesity and male fetal sex predispose to a large nuchal translucency thickness in healthy fetuses.

OBJECTIVES: Our aim was to evaluate the effect of fetal sex, smoking and body mass index (BMI) on nuchal translucency (NT). METHODS: We analyzed data from 7,357 women with a normal singleton live birth outcome with information on smoking, BMI and sex of the infant. NT measurements were converted to multiples of the median (MoM(NT)) using a previously reported linear regression analysis. RESULTS: The odds ratio (OR) for MoM(NT) >95th centile was 1.5 (95% CI 1.2-1.9) for smokers compared to nonsmokers and 1.4 (95% CI 1.1-1.7) for male fetuses compared to female fetuses. Obese women (BMI ≥30) had an increased OR for a large NT of 1.7 (95% CI 1.2-2.6) compared to normal weight women. Obese smokers carrying a male fetus had an OR of 4.2 (95% CI 1.7-10.1) of a MoM(NT) >95th centile compared to normal weight nonsmoking women with a female fetus. The effects of smoking, obesity status and fetal sex were independent of each other. CONCLUSIONS: Smoking, obesity and male sex are associated to a MoM(NT) >95th centile. This may affect screening performance and entail unnecessary anxiety in these women. Further investigations, including fetuses with adverse outcome, are needed.

Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for microdeletion syndromes and subtelomere imbalances.

OBJECTIVE: The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader-Willi/Angelman, Miller-Dieker, Smith-Magenis, 1p-, Williams), the reciprocal microduplication syndromes and imbalance at the subtelomere regions of chromosomes in a routine prenatal setting. METHOD: A total of 530 prenatal samples were analysed by commercial MLPA kits (SALSA P064, P036 and P069) in addition to rapid aneuploidy testing and G-band karyotyping. RESULTS: Among the prenatal samples with a normal metaphase karyotype, nine submicroscopic imbalances were detected: seven 22q11 deletions (Velocardiofacial/DiGeorge syndrome), one 15q11 deletion (Prader-Willi syndrome) and one terminal deletion of the short arm of chromosome 4 (Wolf-Hirschhorn syndrome). All imbalances were found in amniocentesis (AC) taken due to fetal structural malformation and/or other ultrasound scan (US) detected abnormality. The diagnostic yield was 4.1% in the subgroup with structural malformation and 1.6% in the subgroup with other US abnormality. CONCLUSION: The data set substantiates that additional MLPA analyses for selected microdeletions and subtelomere imbalances are valuable in routine prenatal diagnostics, when a malformation(s) and/or other abnormalities are detected by US. In contrast, the additional MLPA analyses gave no diagnostic yield in case of increased nuchal translucency (NT).

Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype.

Dogs represent an excellent comparative model for autoimmune thyroiditis as several dog breeds develop canine lymphocytic thyroiditis (CLT), which is clinically similar to Hashimoto's thyroiditis in human. We obtained evidence that dog leukocyte antigen (DLA) class II genotype function as either genetic risk factor that predisposes for CLT or as protective factor against the disease. Genetic diversity at their DLA-DRB1, -DQA1, and -DQB1 loci were defined and potential association to major histocompatibility complex II haplotypes and alleles was analyzed. Giant Schnauzers carrying the DLA-DRB1*01201/DQA1*00101/DQB1*00201 haplotype showed an increased risk (odds ratio of 6.5) for developing CLT. The same risk haplotype has, to date, been observed in three different breeds affected by this disease, Giant Schnauzer, Dobermann, and Labrador Retriever, indicating that it is a common genetic risk factor in a variety of breeds affected by this disease. Importantly, protection for development of the disease was found in dogs carrying the DLA-DRB1*01301/DQA1*00301/DQB1*00501 haplotype (odds ratio of 0.3).

Increased nuchal translucency with normal karyotype: a follow-up study of 100 cases supplemented with CGH and MLPA analyses.

OBJECTIVE: To evaluate whether high-resolution comparative genomic hybridization (HR-CGH) and subtelomeric and syndrome-specific multiplex ligation-dependent probe amplification (MLPA) would detect minor chromosomal aberrations in fetuses with increased nuchal translucency thickness (NT) and normal karyotype on conventional karyotyping. METHODS: Chorionic villus samples from 100 fetuses with NT > or = 99(th) percentile and normal G-banding analysis and MLPA for detection of aneuploidies for chromosomes 13, 18, 21, X and Y were included. Examinations were supplemented by HR-CGH and MLPA for syndromes and subtelomeric regions. Pregnancy outcome was followed up. RESULTS: Among 80 liveborn children who were followed up, three (4%) had syndromes involving mental retardation, including a case of Sotos syndrome caused by a de novo mutation. 15% of fetuses were lost during pregnancy due to abnormalities and termination. The rate of adverse outcome overall was 18%. HR-CGH and MLPA did not detect any chromosomal aberrations associated with the syndromes. CONCLUSION: The rate of adverse outcome was similar to levels recorded in the literature. Using CGH and MLPA did not increase the detection rate of genetic disease, which supports the current approach of repeated ultrasound examinations in these high-risk pregnancies.

Prenatal 3D ultrasound diagnostics in cleidocranial dysplasia.

A 34-year-old Caucasian woman with cleidocranial dysplasia (CCD) and a known family history of CCD was referred for an ultrasound examination in the first trimester of her second pregnancy. Molecular genetic analysis of the RUNX2 gene was non-informative. A routine 2D ultrasound examination carried out at a local hospital at gestational age 12 weeks showed no signs of CCD. A 3D ultrasound examination in week 15+4 showed a fetus with typical CCD features including large fontanelles, lack of nasal bones, clavicles without the typical S-form, as well as severe delay in calvarial ossification, especially in the midline. Serial 3D ultrasound examinations during pregnancy confirmed the diagnosis, and over time the manifestations became even more distinct. The diagnosis was clinically confirmed at birth. This case suggests that the typical craniofacial CCD traits, including wide unmineralized areas in the calvarial midline and missing nasal bones, are easily recognizable using 3D ultrasound as early as in week 15.