BACKGROUND:Congenital heart disease is present in 44-56% of fetuses with Down syndrome (DS). There are, however, signs that hearts in DS without apparent structural heart defects also differ from those in the normal population. We aimed to compare the atrioventricular (AV) septum and valves in 3 groups: DS without AV septal defect (DS no-AVSD), DS with AVSD (DS AVSD) and control hearts.METHODS:The ventricular septum, membranous septum and AV valves were examined and measured in histological sections of 15 DS no-AVSD, 8 DS AVSD and 34 control hearts. In addition, the ventricular septum length was measured on ultrasound images of fetal (6 DS AVSD, 9 controls) and infant (10 DS no-AVSD, 10 DS AVSD, 10 controls) hearts.RESULTS:The membranous septum was 3 times larger in DS no-AVSD fetuses compared to control fetuses, and valve dysplasia was frequently (64%) observed. The ventricular septum was shorter in patients with DS both with and without AVSD, as compared to the control group.CONCLUSION:DS no-AVSD hearts are not normal as they have a larger membranous septum, shorter ventricular septum and dysplasia of the AV valves as compared to control hearts.

Congenital heart diseases (CHD) are the most commonly overlooked lesions in prenatal screening programs. Real-time two-dimensional ultrasound (2DUS) is the conventionally used tool for fetal echocardiography. Although continuous improvements in the hardware and post-processing software have resulted in a good image quality even in late first trimester, 2DUS still has its limitations. Four-dimensional ultrasound with spatiotemporal image correlation (STIC) is an automated volume acquisition, recording a single three-dimensional (3D) volume throughout a complete cardiac cycle, which results in a four-dimensional (4D) volume. STIC has the potential to increase the detection rate of CHD. The aim of this study is to provide a practical overview of the possibilities and (dis)advantages of STIC. A review of literature and evaluation of the current status and clinical value of 3D/4D ultrasound in prenatal screening and diagnosis of congenital heart disease are presented.

Objectives-The purpose of this study was to determine whether the morphologic characteristics and area of the semilunar valves in healthy fetuses and fetuses with cardiac defects can be visualized by using spatiotemporal image correlation (STIC).Methods-Spatiotemporal image correlation volumes from 74 healthy fetuses were recorded in 5 examinations between the 15th and 36th weeks of pregnancy. Second, we recorded STIC volumes from 64 fetuses with various cardiac defects. The quality of the volumes was rated. The areas of the aortic and pulmonary valves were measured in systole by rendering the valves on 4-dimensional sonography. The number of leaflets was examined. Longitudinal data analysis using linear mixed models was performed.Results-Two hundred ninety-three volumes from normal hearts were examined. In 82.5%, the quality of the normal volumes was sufficient. Visualization of the valve opening was feasible in 96.1% of the normal hearts and 97.4% of the abnormal hearts. The success rate of visualization of the pulmonary and aortic valve leaflets was dependent on the gestational age, with the highest percentage (72.1% in normal hearts) at 19 to 24 weeks. Longitudinal regression analysis showed a positive relationship of the aortic and pulmonary valve areas with gestational age (P <.0001) and fetal biometric measurements (P <.0001). Fifty-eight abnormal volumes were examined. Cardiac defects with abnormal valve areas due to aortic and pulmonary stenosis could be clearly visualized by using STIC.Conclusions-Examination of the morphologic characteristics of the semilunar valves using STIC is feasible, which is difficult when using 2-dimensional sonography. With increasing implementation of 4-dimensional sonography, the understanding of rendered images might be useful for anyone practicing fetal echocardiography.

Case report A 28-year-old pregnant woman presented to the VU University Medical Center at 8 weeks ’ gestation for prenatal counselling. Her partner was diagnosed with infantile hypertrophic neuropathy causing delayed motor development of the legs, paresis of wrist extensors and fl exion contractures of hands and mild mental retardation. He walked without assistance and was independent in activities of daily life. No genetic tests had been performed. Aft er consultation with a clinical geneticist the partner was suspected for D é jerine – Sottas syndrome. He chose to be tested and a c.1075 C  T mutation (R359W) in the EGR2 gene was identifi ed, causative for D é jerine – Sottas syndrome. Aft er counselling they opted for chorion villus biopsy, which revealed an EGR2 gene mutation. Following counselling by clinical geneticist and paediatric neurologist, the parents decided to continue the pregnancy. No sonographic signs of structural abnormalities were found at 12 and 19 weeks ’ gestation. At 30 weeks ’ gestation she presented with decreased fetal movements. Ultrasound examination including 60-min assessment of postural and motor development was performed. Diff erentiation into specifi c movement patterns was decreased (8/16)(de Vries et al. 1982), quality of the general movements, and isolated leg and arm movements showed reduced variation in amplitude, speed, direction and/or participation. Quantity of general movements was decreased (Table I). At our multidisciplinary meeting the need for caesarean section due to the fetal breech position and hypotonia as well as for neonatal surveillance were agreed upon. At 33 weeks ’ gestation a 60-min ultrasound examination with postural and motor assessment was performed, showing normal posture and similar decrease in diff erentiation into 10 specifi c movement patterns. Qualitative performance of the general movements was limited in all aspects. Leg movements during general movements and isolated leg movements were solely generated from the hip joints without participation of the knees. At 39 2 weeks ’ gestation a daughter was born by caesarean section, Apgar scores were 2/7/8 aft er 1/5/10 min, respectively. She was admitted to the neonatal ward with neurological symptoms of hypotonia, decreased movements, absent grasp refl ex and an inspiratory stridor due to bilateral vocal cord paralysis. A tracheal cannula was inserted for respiratory support. Cranial ultrasound revealed normal brain parenchyma and no signs of intra-cerebral haemorrhage. Brainstem auditory evoked potentials during the fi rst week of life, using an automated system (Natus Medical Inc., San Carlos, USA), were found to be normal. At 5 days postpartum a 30-min observation with postural and motor assessment was performed in behavioural state II/IV. Both legs were almost continuously in an extended position, with seldom knee fl exion. Decreased movement diff erentiation (8/16)(de Vries, Visser, & Prechtl 1982), abnormal quality of the general movements and isolated leg movements were visualised. Th e quality of the general movements was reduced. Th e quality of the isolated leg movements showed, besides decreased © 2015 Taylor & Francis Group, LLC ISSN 0144-3615 print/ISSN 1364-6893 online

Chromosomal abnormalities involving an interstitial or a terminal deletion of 3q26.33 and/or 3q27 have rarely been described. Here we report on a fetus of 22+1 weeks’ gestational age with severe intrauterine growth restriction and multiple abnormalities detected by ultrasound examination. Post-mortem molecular cytogenetic investigation (array-comparative genomic hybridization) identified a de-novo interstitial ∼6.17 Mbp microdeletion of 3q26.33q27.3. The clinical and molecular findings in this patient are compared with the previous literature on cases with overlapping interstitial 3q-deletions (seven cases in total). The common phenotype observed in patients with a microdeletion involving 3q26.33q27.3 includes severe prenatal and postnatal growth retardation (including microcephaly), developmental delay, central nervous system anomalies, and several facial characteristics (abnormally shaped ears, broad nasal tip, epicanthal folds, micrognathia/retrognathia, short philtrum). No genotype–phenotype correlation could be established for severe (intrauterine) growth retardation. We conclude that deletions of 3q26.33q27.3 are associated with a profoundly abnormal phenotype, with severe intrauterine growth retardation as its most striking feature.

Our aim is to evaluate the feasibility to examine the morphology and area of the atrioventricular (AV) valves in normal fetuses and fetuses with cardiac defects using spatiotemporal image correlation (STIC).

Congenital heart disease is present in 44–56% of fetuses with Down's syndrome (DS). There are, however, signs that hearts in DS without apparent structural heart defects also differ from the normal population. Sonic hedgehog signaling may be involved in the pathogenesis of AVSD in DS. We aimed to compare the atrioventricular septum and the valves in 3 groups: DS without atrioventricular septal defect (‘DS no-AVSD'), DS with AVSD (‘DS AVSD') and control hearts. The ventricular septum, membranous septum and the AV valves were examined in histological sections of 15 ‘DS no-AVSD', 8 ‘DS AVSD' and 34 ‘control' hearts (10–22 weeks GA). The ventricular septum length was measured on ultrasound images of fetal (6 ‘DS AVSD', 9 ‘controls') and infant (10 ‘DS no-AVSD', 10 ‘DS AVSD', 10 ‘controls') hearts. The membranous septum volume was 3 times larger in ‘DS no-AVSD' fetuses (panel B) compared to controls and valve dysplasia (panel D) was frequently (64%) observed. In DS fetuses with AVSD fibrous tissue was observed at the top of the ventricular septum (3 cases). The ventricular septum was shorter in patients with DS both with (0.7 times the length of controls, p = 0.001) and without AVSD (0.78 times the size of controls, p < 0.001). In contrast to controls, in ‘DS no-AVSD' fetuses clear expression of Gli1,an effector of sonic hedgehog signaling, was present in dysplastic AV valves and membranous septum (2/4 cases). Supporting information can be found in the online version of this abstract Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ABSTRACTObjectiveThe differential insertion of the atrioventricular valves is the ultrasonographic representation of the more apical attachment of the tricuspid valve to the septum with respect to the mitral valve. A linear insertion is present when both valves form a linear continuum and has been suggested as a marker for atrioventricular septal defects (AVSDs). The objective of this study was to evaluate the anatomical substratum of differential and linear insertions of the atrioventricular valves in normal fetal hearts and fetal hearts with an AVSD.MethodsThe extent and position of the fibrous skeleton and attachment of the atrioventricular valves to the septum were studied in histological sections of 17 normal hearts and four hearts with an AVSD from 10 + 0 weeks' gestation to 3 days postpartum with various immunohistochemical tissue markers. In addition, spatiotemporal image correlation (STIC) volumes of 10 normal hearts and STIC volumes of eight hearts with an AVSD at 13 + 6 to 35 + 5 weeks' gestation were examined.ResultsThe differential insertion of the atrioventricular valves was visible in normal hearts in the four‐chamber plane immediately beneath the aorta, but nearer the diaphragm a linear insertion was found. In hearts with an AVSD, a linear appearance was observed in the four‐chamber plane immediately beneath the aorta. Towards the diaphragm, however, first a differential insertion and, more caudally, a linear insertion was found.ConclusionsBoth differential and linear insertions can be found in normal fetal hearts and fetal hearts with AVSD, depending on the plane in which the four‐chamber view is visualized. Therefore, measurement of the differential insertion is likely to be useful only in experienced hands. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

ABSTRACT Objectives The objectives of this study were to develop reference values for the distance between the atrioventricular valves, called differential insertion of the atrioventricular valves (DIAVV), in normal fetuses using four‐dimensional ultrasound with spatio‐temporal image correlation and to explore if DIAVV measurement can differentiate between normal hearts and hearts with cardiac defects. Methods The DIAVV was analysed longitudinally following a measurement protocol in 74 fetuses between 15 and 36 weeks gestational age. The DIAVV was measured in an apical four‐chamber view of the heart in end‐diastole. Furthermore, the DIAVV was measured in 70 fetuses with cardiac defects. Results In total, 337 normal and 70 abnormal spatio‐temporal image correlation volumes were examined. Longitudinal regression analysis revealed a positive relationship of the DIAVV with gestational age and fetal biometry ( p < 0.0001). The DIAVV of fetuses with double outlet right ventricle, truncus arteriosus, atrioventricular septal defects, Ebstein and tetralogy of Fallot all differed from normal fetuses ( p < 0.05). Conclusion Measurement of the DIAVV is a promising tool; however, a well‐defined measurement protocol should be followed to accomplish the correct plane and exact moment in the cardiac cycle. This study presents new nomograms following this measurement protocol and reports an abnormal DIAVV in a wide spectrum of congenital heart disease. © 2014 John Wiley & Sons, Ltd.

What's already known about this topic? Distal ductal origin of a pulmonary artery is typically diagnosed during infancy, after closure of the arterial duct. This condition is associated with significant morbidity and mortality. What does this study add? Our case is the first to show that distal ductal origin of a pulmonary artery can be detected before birth. Prenatal detection enables preservation of the patency of the pulmonary artery for an efficient surgical reconstruction at later age.

The exact incidence of scar endometriosis is unknown. The aim of this study is to determine the incidence of endometriosis in the abdominal wall following a caesarean section. Women who underwent surgery for scar endometriosis after a caesarean section and the total number of women with caesarean sections in The Haga Teaching Hospital, a gynaecologic centre in The Netherlands, were identified by the national obstetric registration and pathology archive in the period January 1995 to December 2008. Clinical data were collected from the existing hospital records. Twenty-nine women were diagnosed with scar endometriosis after a caesarean section, and 3,047 women underwent one or more caesarean sections, resulting in an incidence of scar endometriosis of 0.95 %. None of the women had a history of endometriosis. Symptoms were pain (94.0 %), cyclic with menstruation (50.0 %) and swelling of the scar (89.0 %). Mean time between caesarean delivery and symptoms was 4.1 years. No recurrence occurred. This study reveals a higher incidence of endometriosis in the scar of a caesarean section than described in current literature. To improve the detection rate, more attention to medical history and physical examination is mandatory. A higher incidence warrants research into the pathophysiology and prevention of endometriosis in the scar of a caesarean section.

Objective To evaluate the clinical accuracy of four-dimensional (4D) echocardiography in the detailed prenatal diagnosis of congenital heart disease (CHD) in a telemedicine setting.

The tricuspid valve has a more apical attachment to the interventricular septum than the mitral valve, called differential insertion of the atrioventricular valves (DIAVV). Measurement of the DIAVV could be a tool to detect cardiac defects. Our aim is to evaluate the DIAVV in normal fetuses and fetuses with cardiac defects by four-dimensional ultrasound (4DUS) using spatio-temporal imaging correlation (STIC). DIAVV was studied longitudinally in 74 fetuses to create nomograms, in five examinations during each pregnancy between the 15th and 36th week, by a STIC volume. The DIAVV was measured in an apical four chamber view of the heart in end systole. DIAVV was measured by placing one caliper on the junction of the inferior portion of the mitral valve with the interventricular septum and a second caliper on the junction of the superior portion of the tricuspid valve with the interventricular septum. Longitudinal data analysis was performed using linear mixed models. So far in 32 fetuses with various cardiac defects the DIAVV was measured. 335 STIC volumes of normal hearts were examined. Longitudinal regression analysis revealed a positive relationship of the DIAVV (0.13 mm per week, 95% CI 0.12–0.13) with gestational age (P < 0.001) and fetal biometry (0.09 mm increased by 100 gr EFW, P < 0.001). The mean predicted value of the DIAVV for 20 weeks GA is 1.78 mm (95% CI 1.72–1.84). The fetuses with cardiac defects showed variable DIAVV. No relationships between the types of defects and the size of DIAVV existed, except for the endocardial cushion defects. Compared to earlier cross-sectional studies this longitudinal study presents nomograms for DIAVV by 4DUS compared to 2DUS. The advantage of STIC is the possibility to rotate the fetal heart in apical position and to determine the exact moment of end systole (closure of the atrioventricular valves) by moving through the heart cycle. The nomograms could help in the detection of congenital heart defects like endocardial cushion defects.

To evaluate the clinical accuracy of four-dimensional (4D) echocardiography in the detailed prenatal diagnosis of congenital heart disease in a telemedicine setting. Ten second trimester spatio-temporal image correlation (STIC) volumes were sent to 3 tertiary care centers with expertise in 4D echocardiography. Observers were asked to provide the diagnosis, the post-processing modalities used, the time spent on examination and to give a rating of the confidence for the diagnosis on a 5-point Likert scale. A diagnostic scoring system was used to value different aspects of the heart defects. The results were compared to neonatal echocardiography or post-mortem findings. In 2 cases all observers correctly diagnosed all details of the volume datasets. The observer with the best performance reached perfect agreement in 6 cases and nearly perfect agreement in 3 cases. The volumes were most frequently studied by sectional planes and were analyzed in a median time of 11.0 (range 2.5–30.0) minutes. The median confidence score was 4.0 (range 1.0–5.0). In a telemedicine setting using STIC volumes, fetal cardiac anomalies can be diagnosed correctly by an expert. However, details required for adequate counseling and planning of postnatal care may be missed. STIC by telemedicine is a promising modality, although not accurate enough for exclusive use in clinical decision making regarding treatment, prognosis or termination of pregnancy. OP15.01: Table 1. Median diagnostic score, time and confidence score of the observers in diagnosing congenital heart disease by spatio-temporal image correlation