J W Wladimiroff's research while affiliated with Leiden University Medical Centre and other places

To assess the impact of prenatal compared with postnatal diagnosis on outcome for liveborn infants with an isolated or with a non-isolated omphalocele. This was a retrospective analysis of 101 prenatally and 45 postnatally diagnosed cases of omphalocele. Cases were collected from the ultrasound database of the Division of Obstetrics and Prenatal Medicine and the patient database of the Department of Pediatric Surgery. Following confirmation at delivery or autopsy, prenatally diagnosed omphaloceles included 21 isolated cases, 44 non-isolated cases with a normal karyotype and 36 non-isolated cases with an abnormal karyotype. Of the prenatally diagnosed apparently isolated cases (n = 31), 12 (39%; 95% CI, 22-58%) revealed associated anomalies after delivery. Liveborn infants with an isolated omphalocele had significantly worse short-term morbidity following prenatal diagnosis (n = 14) compared with diagnosis at birth (n = 29), having a lower gestational age at delivery, lower Apgar scores, longer duration of ventilation and parenteral nutrition, more readmissions and a longer hospital stay. The prenatally diagnosed subset contained more infants with a giant omphalocele (9/14 vs. 3/29, P = 0.001) and liver herniation (8/14 vs. 6/29, P = 0.02). The outcome of liveborn infants with a non-isolated omphalocele diagnosed prenatally (n = 17) was not different from that of those diagnosed at birth (n = 16), except for a greater need for ventilation and parenteral nutrition in the prenatal subset. When counseling patients with a prenatal diagnosis of isolated omphalocele, it is important to remember that over one third could turn out to have associated anomalies. Liveborn infants with an isolated omphalocele detected prenatally have worse short-term morbidity than do cases detected at birth. Those with non-isolated omphaloceles detected prenatally have an increased need for ventilation and parenteral nutrition compared with those detected at birth.

European Practice in Gynaecology and Obstetrics is a series of books conceived and endorsed by the European Board and College of Obstetrics and Gynaecology (EBCOG). The topics chosen for each volume are those of significant clinical interest where treatment is changing in response to research findings and developments in practice. The volume editor and contributing authors are European specialists invited to contribute because of their expertise in their field. The books concentrate on various types of management used in European practice as well as published results. The authors present treatments for which a consensus exists and - when there is no consensus - they discuss the key elements of the controversy. Each book provides a review of the basic science, recent concepts in pathophysiology, clinical aspects, treatment and unresolved problems or controversies, as well as the major recent references. A final section provides multiple-choice questions for each chapter.

To determine whether the pre- or postnatal diagnosis of either isolated or non-isolated duodenal obstruction (DO) is associated with different outcomes. A single-center retrospective analysis was carried out of 91 cases diagnosed with a DO between January 1991 and June 2003. Data on the diagnosis, treatment and outcomes of the cases were gathered, and differences between the groups were analyzed. Twenty-eight cases of DO were diagnosed before and 63 after birth. Of 15 presumed isolated cases in the prenatally diagnosed group, four revealed associated or chromosomal anomalies after birth. The types of obstruction present were significantly different between the prenatally (n = 11) and postnatally (n = 27) detected subsets of isolated DO. The prenatally detected subset displayed a lower median gestational age at delivery, lower median birth weight and a higher prematurity rate (8/11 vs. 8/27). The diagnosis of DO occurred significantly later in the postnatally detected subset than the postnatal confirmation of the diagnosis in the prenatally detected cases. In the non-isolated cases of DO, no difference was found in the type of chromosomal or associated anomaly or the type of obstruction between the prenatally detected (n = 17) and postnatally detected subsets (n = 36). Trisomy 21 was present in 7/17 (41%) vs. 22/36 (61%) cases, respectively. Two terminations and three intrauterine deaths occurred in the prenatal non-isolated subset. The liveborn infants from the prenatally detected non-isolated subset (n = 12) showed a significantly higher prematurity rate (9/12 vs.14/36), lower median birth weight and earlier confirmation of diagnosis after delivery. After surgery, outcome was similar between both subsets of isolated and non-isolated DO. All the infants with an isolated DO survived. Neonatal death occurred in three prenatally and five postnatally diagnosed cases with non-isolated DO. The outcome of prenatally and postnatally diagnosed DO is not essentially different despite more prematurity and a lower birth weight in the former. Of the prenatally detected cases of DO assumed to be isolated, 25% revealed additional chromosomal or associated anomalies after delivery, which influenced outcome.

The objectives of this study were to estimate fetal blood pressure non-invasively from two-dimensional color Doppler-derived aortic blood flow and diameter waveforms, and to compare the results with invasively derived human fetal blood pressures available from the literature. Aortic pressures were calculated from digitally recorded color Doppler cineloops of the fetal descending aorta by applying the Womersley model in combination with the two-element Windkessel model, assuming constant pulse wave velocity during the second half of pregnancy. The results were compared with invasively derived human fetal blood pressures obtained from the literature. In 21 normal pregnancies the estimated mean aortic pressure regression line increased linearly from 28 mmHg at 20 weeks of gestation to 45 mmHg at 40 weeks of gestation. The pulse pressure based on the regression line increased linearly from 21 mmHg at 20 weeks of gestation to 29 mmHg at 40 weeks of gestation. The aortic compliance exhibited a log linear relationship with the gestational age and a statistically significant eightfold increase was observed between 20 and 40 weeks. The aortic downstream peripheral resistance exhibited an exponentially decaying relationship across the same gestational age range. Non-invasively derived aortic systolic and diastolic aortic pressures were comparable with previously reported invasively derived systolic and diastolic umbilical arterial pressures; however, the mean pressures differed significantly from those reported in the umbilical artery in a separate study. The aortic systolic pressures calculated in this study were significantly higher than invasively derived left ventricular systolic pressures that have been previously reported in the literature. This study demonstrates the feasibility of estimating arterial blood pressure in the human fetus. The method described is of potential use in assessing fetal blood pressure non-invasively, particularly for studying relative changes with time.

We report a three-generation family with nine patients affected by a combination of cardiac abnormalities and left isomerism which, to our knowledge, has not been described before. The cardiac anomalies include non-compaction of the ventricular myocardium, bradycardia, pulmonary valve stenosis, and secundum atrial septal defect. The laterality sequence anomalies include left bronchial isomerism, azygous continuation of the inferior vena cava, polysplenia and intestinal malrotation, all compatible with left isomerism. This new syndrome is inherited in an autosomal dominant pattern. A genome-wide linkage analysis suggested linkage to chromosome 6p24.3-21.2 with a maximum LOD score of 2.7 at marker D6S276. The linkage interval is located between markers D6S470 (telomeric side) and D6S1610 (centromeric side), and overlaps with the linkage interval in another family with heterotaxy reported previously. Taken together, the genomic region could be reduced to 9.4 cM (12 Mb) containing several functional candidate genes for this complex heterotaxy phenotype.

IntroductionHypothesesAntithesesHemodynamicsComputational fluid dynamics (CFD)Expression of genes responsive to shear stressConclusions

Objectives Fluid mechanical forces affect cardiac development. In the chicken embryo, permanent obstruction of the right lateral vitelline vein by clipping reduces the mechanical load on the embryonic myocardium, which has been shown to induce a spectrum of outflow tract anomalies. Insight into the effects of this intervention on the mechanical function of the developing myocardium could contribute to a better understanding of the relationship between hemodynamics and cardiac morphogenesis. We aimed to explore the effects of clipping on intrinsic systolic and diastolic ventricular function at stage 24 in the chicken embryo Methods Cardiac pressure–volume relationships enable load‐independent quantification of intrinsic ventricular systolic and diastolic properties. We determined ventricular function by pressure–volume loop analysis of in‐ovo stage‐24 chicken embryos ( n = 15) 2 days after venous obstruction at 2.5 days of incubation (stage 17, venous clipped embryos). Control embryos ( n = 15) were used for comparison. Results End‐systolic volume was significantly higher in clipped embryos (0.36 ± 0.02 µL vs. 0.29 ± 0.02 µL, P = 0.002). End‐systolic and end‐diastolic pressure were also increased compared with control animals (2.93 ± 0.07 mmHg vs. 2.70 ± 0.08 mmHg, P = 0.036 and 1.15 ± 0.06 mmHg vs. 0.82 ± 0.05 mmHg, P < 0.001, respectively). No significant differences were demonstrated for other baseline hemodynamic parameters. Analysis of pressure–volume relationships showed a significantly lower end‐systolic elastance in the clipped embryos (slope of end‐systolic pressure–volume relationship: 2.91 ± 0.24 mmHg/µL vs. 7.53 ± 0.66 mmHg/µL, P < 0.005) indicating reduced contractility. Diastolic stiffness was significantly increased in the clipped embryos (slope of end‐diastolic pressure–volume relationship: 1.54 ± 0.21 vs. 0.60 ± 0.08, P < 0.005), indicating reduced compliance. Conclusion Venous obstruction apparently interferes with normal myocardial development, resulting in impaired intrinsic systolic and diastolic ventricular function. These changes in ventricular function may precede morphological derangements observed in later developmental stages. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.