http://repub.eur.nl/res/aut/875/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/34879/ 2012-01-01T00:00:00Z Objectives: To determine the reproducibility, both reliability and agreement, of measurements of fetal left ventricular parameters from volumes obtained by spatio-temporal image correlation (STIC) acquisition applying virtual organ computer-aided analysis (VOCAL) and Simpson's rule (method of discs). Furthermore the success rate of STIC acquisition was determined. Study design: In 84 pregnancies between 20 and 34 weeks of gestation the fetal heart was scanned using the STIC modality. An optimal four-chamber view in end-diastole and end-systole was obtained. Left ventricular end-diastolic volume, left ventricular end-systolic volume, stroke volume and ejection fraction were determined. For calculations based on Simpson's rule only one plane was traced, whereas for VOCAL six planes were traced. To quantify the reliability intraclass correlation coefficients were calculated for both intra- and inter-observer measurements. Agreement of measurements was evaluated by Bland-Altman plots. Results: The STIC volumes of 54 women (64%) were excluded from the study because of poor quality, leaving 30 volumes for further analysis. Intraclass correlation coefficients for intra-observer reliability for VOCAL and Simpson were 0.99 and 0.99 for left ventricular end-diastolic volume, 0.95 and 0.92 for left ventricular end-systolic volume, 0.98 and 0.97 for stroke volume, 0.76 and 0.77 for ejection fraction, respectively. Intraclass correlation coefficients for inter-observer reliability for VOCAL and Simpson were 0.97 and 0.86 for left ventricular end-diastolic volume, 0.97 and 0.86 for left ventricular end-systolic volume, 0.95 and 0.81 for stroke volume, 0.68 and 0.63 for ejection fraction, respectively. According to Bland-Altman plots, the mean percentage difference and 95% limits of intra- and inter-observer agreement for left ventricular stroke volume measurements using VOCAL were -0.2 (-25.1, 24.7)% and 2.8 (-34.2, 39.8)%, respectively. For left ventricular stroke volume measured with Simpson versus VOCAL the mean percentage difference and 95% limits of agreement were -1.8 (-22.1, 18.5)%. Conclusions: 4D STIC enables reproducible measurements of left ventricular volumes. Reliability of the VOCAL mode is not essentially different from the single-plane method used in Simpson's rule. The large percentage of poor quality STIC volumes and the wide limits of inter-observer agreement would create obstacles for the clinical applicability of this technique. http://repub.eur.nl/res/pub/28188/ 2010-12-01T00:00:00Z Objectives To assess the impact of prenatal compared with postnatal diagnosis on outcome for liveborn infants with an isolated or with a non-isolated omphalocele. Methods 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. Results 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. Conclusion 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. Copyright http://repub.eur.nl/res/pub/30005/ 2008-11-01T00:00:00Z Objectives To determine whether the pre- or postnatal diagnosis of either isolated or non-isolated duodenal obstruction (DO) is associated with different outcomes. Methods 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. Results 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. Conclusions 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. Copyright http://repub.eur.nl/res/pub/30025/ 2008-10-01T00:00:00Z Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. Copyright http://repub.eur.nl/res/pub/15255/ 2008-09-01T00:00:00Z Objective: To determine left ventricular isovolumic relaxation time (LV IRT) in normally developing and growth restricted fetuses (FGR) as an indicator of fetal cardiac afterload and neonatal systolic blood pressure. Study design: A prospective longitudinal study in 124 normally developing and 47 growth restricted fetuses (FGR). LV IRT, fetal heart rate (FHR) and umbilical artery pulsatility index (PI) were determined at 2-3 week intervals starting at 22-26 weeks of gestation until delivery. Renin and angiotensin I levels were measured by radioimmunoassay in umbilical venous blood after delivery. Systolic blood pressure was measured at day 1 and day 5 of postnatal life. To evaluate the association between LV IRT, gestational age and FHR, bivariate regression analyses were performed. Results: Mean LV IRT (62 ± 8 ms) was 29 percent longer in FGR as compared to the normal subset (47 ± 6 ms) at all gestational ages (p < 0.001). Mean postnatal active plasma renin level (7.78 ± S.D. 1.03 ng/ml) and postnatal angiotensin I level (4.21 ± 0.70 ng/ml) in the FGR subset were significantly higher (p < 0.001) than in the normal subset (4.81 ± 1.04 ng/ml, renin and 2.69 ± 0.44 ng/ml, angiotensin I). There was a significant difference (p < 0.01) in systolic blood pressure between the two subsets on postnatal day 1 (FGR 52 ± 6 mmHg vs. normal 46 ± 4 mmHg) and day 5 (FGR 76 ± 5 mmHg vs. normal 60 ± 6 mmHg). Conclusion: Left ventricular isovolumic relaxation time may act as a sensitive index of increased arterial afterload in the growth retarded fetus and may herald raised systolic blood pressure in the early neonatal period. http://repub.eur.nl/res/pub/29724/ 2008-07-01T00:00:00Z Objectives: To establish in infants with gastroschisis whether outcome is different when comparing a prenatal diagnosis with a diagnosis only at birth with the intention to develop a prenatal surveillance protocol. Intestinal atresia established after birth and preterm versus term delivery were studied as risk factors. Study design: All 24 fetuses and 9 infants diagnosed with gastroschisis and referred to our tertiary center between January 1991 and June 2003 were studied retrospectively. Results: The infants of the prenatal subset delivered at our tertiary center and 18 survived. There were two pregnancy terminations, three intrauterine deaths at 19, 33 and 36 weeks respectively and one neonatal death. All nine infants in the postnatal subset survived. Eight were out born and one was delivered at our tertiary center. Prenatal bowel dilatation did not correlate with outcome. Between the prenatal and postnatal subset no significant difference in outcome of live-born infants was established. For four infants with intestinal atresia a significant difference was demonstrated for induction of preterm labour (P < 0.05), duration of parenteral nutrition (P < 0.01), number of additional surgical procedures (P < 0.001) and length of hospital stay (P < 0.01). The fifteen infants born prior to 37 weeks of gestation spent a significantly longer period in hospital compared to those delivered at term. When the cases with bowel atresia were excluded this difference was no longer present. Five of the 33 cases were diagnosed with associated anomalies which mainly involved the urinary tract. Conclusion: Neonatal outcome of live born infants following a prenatal diagnosis of gastroschisis is not different from a diagnosis at birth. The presence of intestinal atresia is the most important prognostic factor for morbidity. The supplemental value of prenatal diagnosis to the outcome of infants with gastroschisis may be in the prevention of unnecessary intrauterine death and detection of intestinal complications. A proposed surveillance protocol for fetuses with gastroschisis focused on intrauterine signs of pending distress such as a dilated stomach, intra abdominal bowel dilatation with peristalsis, notches in the umbilical artery Doppler signal, development of polyhydramnios and an abnormal CTG registration may improve outcome. http://repub.eur.nl/res/pub/29110/ 2008-02-05T00:00:00Z Background-It has been suggested that an adverse fetal environment increases susceptibility to hypertension and cardiovascular disease in adult life. This increased risk may result from suboptimal development of the heart and main arteries in utero and from adaptive cardiovascular changes in conditions of reduced fetal growth. The aim of the present study was to evaluate whether reduced fetal growth is associated with fetal circulatory changes and cardiac dysfunction. Methods and Results-This study was embedded in a population-based, prospective cohort study starting in early fetal life. Fetal growth characteristics and fetal circulation variables were assessed with ultrasound and Doppler examinations in 1215 healthy women. The fetal circulation was examined in relation to estimated fetal weight. Higher placental resistance indices were strongly associated with decreased fetal growth. Cerebral resistance showed a gradual decline with reduced fetal growth. Cardiac output, peak systolic velocity of the outflow tracts, and cardiac compliance showed a gradual reduction with diminished fetal growth, whereas intraventricular pressure gradually increased. Conclusions-Decreased fetal growth is associated with adaptive fetal cardiovascular changes. Cardiac remodeling and cardiac output changes are consistent with a gradual increase in afterload and compromised arterial compliance in conditions of decreased fetal growth. These changes have already begun to occur before the stage of clinically apparent fetal growth restriction and may contribute to the increased risk of cardiovascular disease in later life. (Circulation. 2008;117:649-659.). http://repub.eur.nl/res/pub/29624/ 2008-01-01T00:00:00Z 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. http://repub.eur.nl/res/pub/36543/ 2007-12-01T00:00:00Z Background/Aims: Ligating the right lateral vitelline vein of chicken embryos (venous clip) results in cardiovascular malformations. These abnormalities are similar to malformations observed in knockout mice studies of components of the endothelin-1 (ET-1)/endothelin-converting enzyme-1/endothelin- A receptor pathway. In previous studies we demonstrated that cardiac ET-1 expression is decreased 3 h after clipping, and ventricular diastolic filling is disturbed after 2 days. Therefore, we hypothesise that ET-1-related processes are involved in the development of functional and morphological cardiovascular defects after venous clip. Methods: In this study, ET-1 and endothelin receptor antagonists (BQ-123, BQ-788 and PD145065) were infused into the HH18 embryonic circulation. Immediate haemodynamic effects on the embryonic heart and extra-embryonic vitelline veins were examined by Doppler and micro-particle image velocimetry. Ventricular diastolic filling characteristics were studied at HH24, followed by cardiovascular morphologic investigation (HH35). Results: ET-1 and its receptor antagonists induced haemodynamic effects at HH18. At HH24, a reduced diastolic ventricular passive filling component was demonstrated, which was compensated by an increased active filling component. Thinner ventricular myocardium was shown in 42% of experimental embryos. Conclusion: We conclude that cardiovascular malformations after venous clipping arise from a combination of haemodynamic changes and altered gene expression patterns and levels, including those of the endothelin pathway. Copyright http://repub.eur.nl/res/pub/36411/ 2007-09-01T00:00:00Z 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 http://repub.eur.nl/res/pub/36069/ 2007-07-01T00:00:00Z To examine whether the magnitude-squared coherence between uterine and umbilical blood flow velocity waveforms can, in conjunction with estimated fetal weight, uterine and umbilical pulsatility indices, fetal and maternal heart rates, diastolic notching and the amniotic fluid index, create a sensitive and specific model for the prediction of placental dysfunction. Binary logistic prediction models are created for preeclampsia, pregnancy induced hypertension and intrauterine growth restriction in a study group of 284 unselected midtrimester pregnancies. In each study group, the median value of derived parameters were compared with the uncomplicated pregnancy control group. The magnitude-squared coherence function between the uterine and umbilical flow velocity waveforms was found to be a statistically significant predictor of preeclampsia during the midtrimester of pregnancy. The magnitude-squared coherence did not improve the prediction of intrauterine growth restriction or pregnancy induced hypertension. The inclusion of magnitude-squared coherence as one of the prediction parameters may improve the early identification of pregnancies subsequently complicated by preeclampsia. (E-mail: p.struijk@erasmusmc.nl). http://repub.eur.nl/res/pub/36491/ 2007-04-01T00:00:00Z Objective: To explore longitudinally the development of the fetal skull base using three-dimensional (3D) sonography. Methods: Serial 3D sonographic measurements of anterior skull base length, posterior cranial fossa length and skull base angle were made in 126 normal singleton pregnancies at 18-34 weeks of gestation. In a sub-study of 22 pregnancies, intraobserver variability was determined. Regression analysis for repeated measurements was performed by means of the random coefficients model. Results from an earlier publication on brain volume were extended to the total patient cohort. Results: Measurements were technically successful in 69-94% of cases. The coefficient of variation for differences between repeated tests within women was 3.5-7.6% and between repeated analyses of the same recorded volume it was 3.0-5.1%. A statistically significant gestational age-related increase was established for both the anterior skull base length and the posterior cranial fossa length and the skull base angle showed a small but significant flexion of about 6°. A higher increment in posterior cranial fossa length relative to anterior skull base angle was established. A significant quadratic relationship could be established for both anterior skull base length (P < 0.0001) and posterior cranial fossa length (P < 0.0001) but not for skull base angle, relative to brain volume. Conclusion: The reproducibility was acceptable for all fetal skull base measurements. The more pronounced growth in posterior cranial fossa length relative to anterior skull base length is influenced by brain growth. The small flexion of the skull base angle, however, may be caused by other factors. Copyright http://repub.eur.nl/res/pub/36497/ 2007-03-01T00:00:00Z Objective: This study was undertaken to employ craniofacial pattern profile analysis in fetal facial clefts and to evaluate the craniofacial variability index (CVI) in distinguishing between isolated and syndromal clefts. Methods: Three-dimensional (3D) sonographic assessment of 16 different fetal craniofacial measurements was performed in each of eight pregnancies complicated by an isolated facial cleft and seven pregnancies with a syndromal cleft. The measurements covered various aspects of facial width, depth and height. Measured values were compared to gestational age-specific normal values for calculation of Z-scores and the CVI. The number of abnormal Z-scores, i.e. < -2 or > +2, found among the measured values and the CVI in the group of isolated facial clefts were compared to those in the group with syndromal clefts. Results: The CVI could be calculated in 14 of 15 fetuses (93%). More abnormal Z-scores and a higher mean CVI were found in the group with more severe (bilateral) facial clefts. Most abnormal values were found in the facial width measurements. Syndromal cleft lip/palate was associated with significantly more abnormal Z-scores and a higher mean CVI than isolated cleft lip/palate (P < 0.05). Conclusion: Craniofacial variability index may be a valuable tool for distinguishing between isolated and syndromal fetal cleft lip/palate. Copyright http://repub.eur.nl/res/pub/36502/ 2007-03-01T00:00:00Z Objective: This study was undertaken to develop a craniofacial pattern profile analysis by three-dimensional (3D) ultrasound and to introduce a craniofacial variability index (CVI) which can assist in the evaluation of fetal facial anatomy. Methods: Serial 3D sonographic measurements of 16 different fetal craniofacial parameters were performed at 18-34 weeks of gestation in 126 normal singleton pregnancies. In another six pregnancies complicated by fetal abnormality, a single 3D recording was obtained. The 16 measurements cover various aspects of the facial anatomy, such as width, depth and height. For each parameter, regression analysis was performed to calculate gestational age-specific Z-scores and normal limits for the CVI (the latter quantifies the variability between the 16 Z-scores). Results: The 95th percentile of normal CVI data increased from 1.08 at 18 weeks to 1.27 at 34 weeks of gestation. The CVI was situated above the 95th percentile in three out of six fetuses with abnormalities. In abnormal subjects, 2-8 of 16 parameters showed abnormal values. Conclusions: Craniofacial pattern profile analysis and the CVI may aid in the evaluation of fetal facial anatomy. They could be a valuable tool in syndrome delineation and for distinguishing between normal and abnormal craniofacial development. Copyright http://repub.eur.nl/res/pub/35848/ 2007-02-01T00:00:00Z Objectives: (1) To describe the characteristics of decision-making about management of unborn infants with serious anomalies by a multidisciplinary perinatal team. (2) To evaluate the impact of multidisciplinary team discussions on the degree to which decisions about the management of unborn infants with serious anomalies are supported. (3) To evaluate the impact of the team discussions on the arguments used by physicians for their preferences concerning management. Methods: Prospective analysis of 78 cases discussed within the multidisciplinary perinatal team of a tertiary centre by means of an anonymous one-page questionnaire with structured questions pertaining to the opinion of the responder on medical management of each case. Results: We did not find systematic differences between specialties prior to the discussion of cases. However, discussion with the multidisciplinary perinatal team improved decision-making about management of unborn infants with serious anomalies by enhancing the degree of support for the decisions taken. The discussions of the team did not change the physicians' arguments mentioned for their preferences. Conclusion: Multidisciplinary team discussions improve decision-making about management of unborn infants with serious congenital anomalies. Copyright http://repub.eur.nl/res/pub/13550/ 2005-01-01T00:00:00Z Cardiac pressure-volume relations enable quantification of intrinsic ventricular diastolic and systolic properties independent of loading conditions. The use of pressure-volume loop analysis in early stages of development could contribute to a better understanding of the relationship between hemodynamics and cardiac morphogenesis. The venous clip model is an intervention model for the chick embryo in which permanent obstruction of the right lateral vitelline vein temporarily reduces the mechanical load on the embryonic myocardium and induces a spectrum of outflow tract anomalies. We used pressure-volume loop analysis of the embryonic chick heart at stage 21 (3.5 d of incubation) to investigate whether the development of ventricular function is affected by venous clipping at stage 17, compared with normal control embryos. Steady state hemodynamic parameters demonstrated no significant differences between the venous clipped and control embryos. However, analysis of pressure-volume relations showed a significantly lower end-systolic elastance in the clipped embryos (slope of the end-systolic pressure-volume relation: 5.68 +/- 0.85 versus 11.76 +/- 2.70 mm Hg/microL, p < 0.05), indicating reduced contractility. Diastolic stiffness tended to be increased in the clipped embryos (slope of end-diastolic pressure-volume relation: 2.74 +/- 0.56 versus 1.67 +/- 0.21, p = 0.103), but the difference did not reach statistical significance. The results of the pressure-volume loop analysis show that 1 d after venous obstruction, development of ventricular function is affected, with reduced contractility. Pressure-volume analysis may be applied in the chick embryo and is a sensitive technique to detect subtle alterations in ventricular function. http://repub.eur.nl/res/pub/8402/ 2004-01-01T00:00:00Z Alteration of extra-embryonic venous blood flow in stage-17 chick embryos results in well-defined cardiovascular malformations. We hypothesize that the decreased dorsal aortic blood volume flow observed after venous obstruction results in altered ventricular diastolic function in stage-24 chick embryos. A microclip was placed at the right lateral vitelline vein in a stage-17 (52-64 h of incubation) chick embryo. At stage 24 (4.5 days of incubation), we measured simultaneously dorsal aortic and atrioventricular blood flow velocities with a 20-MHz pulsed-Doppler velocity meter. The fraction of passive and active filling was integrated and multiplied by dorsal aortic blood flow to obtain the relative passive and active ventricular filling volumes. Data were summarized as means +/- S.E.M. and analyzed by t-test. At similar cycle lengths ranging from 557 ms to 635 ms (P>0.60), dorsal aortic blood flow and stroke volume measured in the dorsal aorta were similar in stage-24 clipped and normal embryos. Passive filling volume (0.07+/-0.01 mm(3)) was decreased, and active filling volume (0.40+/-0.02 mm(3)) was increased in the clipped embryo when compared with the normal embryo (0.15+/-0.01 mm(3), 0.30+/-0.01 mm(3), respectively) (P<0.003). In the clipped embryos, the passive/active ratio was decreased compared with that in normal embryos (P<0.001). Ventricular filling components changed after partially obstructing the extra-embryonic venous circulation. These results suggest that material properties of the embryonic ventricle are modified after temporarily reduced hemodynamic load. http://repub.eur.nl/res/pub/8403/ 2003-01-01T00:00:00Z In the venous clip model specific cardiac malformations are induced in the chick embryo by obstructing the right lateral vitelline vein with a microclip. Clipping alters venous return and intracardiac laminar blood flow patterns, with secondary effects on the mechanical load of the embryonic myocardium. We investigated the instantaneous effects of clipping the right lateral vitelline vein on hemodynamics in the stage-17 chick embryo. 32 chick embryos HH 17 were subdivided into venous clipped (N=16) and matched control embryos (N=16). Dorsal aortic blood flow velocity was measured with a 20 MHz pulsed Doppler meter. A time series of eight successive measurements per embryo was made starting just before clipping and ending 5h after clipping. Heart rate, peak systolic velocity, time-averaged velocity, peak blood flow, mean blood flow, peak acceleration and stroke volume were determined. All hemodynamic parameters decreased acutely after venous clipping and only three out of seven parameters (heart rate, time-averaged velocity and mean blood flow) showed a recovery to baseline values during the 5h study period. We conclude that the experimental alteration of venous return has major acute effects on hemodynamics in the chick embryo. These effects may be responsible for the observed cardiac malformations after clipping. http://repub.eur.nl/res/pub/9835/ 2002-01-01T00:00:00Z OBJECTIVES: To determine the value of pulmonary artery Doppler velocimetry relative to fetal biometric indices and clinical correlates in the prenatal prediction of lethal lung hypoplasia (LH) in prolonged (>1 week) oligohydramnios. METHODS: Forty-two singleton pregnancies with oligohydramnios associated with premature rupture of membranes ([PROM]; n = 31) or bilateral renal pathology (n = 11) were examined using color-coded Doppler ultrasound in a cross-sectional study design. Mean gestational age was 28.0 +/- 4.3 weeks (range: 20-36 weeks). Thoracic, cardiac, and abdominal circumference and the largest vertical amniotic fluid pocket were measured. Pulsed Doppler measurements of the arterial pulmonary branches were made at the level of the cardiac 4-chamber view. Diagnosis of LH was based on clinical, radiologic, and pathologic criteria. Clinicians were blinded to the prenatal measurements. RESULTS: The prevalence of lethal LH was 43%. In the PROM subset, combination of onset of PROM at <or =20 weeks, duration of oligohydramnios at > or =8 weeks, and degree of oligohydramnios at < or =1 cm presented the highest clinical prediction rate for lethal LH. For both the total group and the PROM subset, the highest prediction rate for lethal LH was presented by thoracic circumference/abdominal circumference ratio, peak systolic velocity in the proximal branch, and time-averaged and end-diastolic velocity in the middle branch of the pulmonary artery. In the PROM subset, the combination of all 3 clinical, biometric, and Doppler parameters revealed the most favorable combination to predict lethal LH (positive predictive value: 100%; accuracy: 93%; and sensitivity: 71%). CONCLUSION: Doppler velocimetry may detect changes in pulmonary artery waveforms in the presence of LH but fails to be the ultimate test for the prenatal prediction of lethal LH. The best prediction can be achieved by combining clinical, biometric, and Doppler parameters. http://repub.eur.nl/res/pub/9911/ 2002-01-01T00:00:00Z PURPOSE: To establish reproducibility and normal values for fetal hepatic volume and its significance in identification of fetal growth restriction relative to head and upper abdominal circumferences according to a cross-sectional study design. MATERIALS AND METHODS: Pregnant women (n = 135) underwent ultrasonography. The coefficient of variation (CV) for hepatic volume scans obtained at 0 and 20 minutes and hepatic area tracings, performed twice for each scan, was determined (n = 20; range, 23-36 weeks). Normal data for hepatic volume and head and upper abdominal circumferences were obtained (n = 85; range, 20-36 weeks) and related to data from growth-restricted fetuses (birth weight < P5 centile; n = 24; range, 22-36 weeks). RESULTS: CV was 2.9% for volume scans and 1.6% for area tracings. In 85 uncomplicated cases, mean fetal hepatic volume (P50 centile) was 9.7 mL +/- 4.4 (SD) at 20 weeks and 96.4 mL +/- 8.2 at 36 weeks of gestation. In 24 growth-restricted fetuses, hepatic volume, head circumference, and upper abdominal circumference expressed as percentages of the normal P50 centile were 45%, 90%, and 82%, respectively. Mean difference in hepatic volume between fetal growth restriction and normal fetal development, as expressed with the z score, -4.32 +/- 1.4, was significantly different (P <.05) from that for head circumference, -3.04 +/- 1.3, but not from that for upper abdominal circumference, -4.7 +/- 1.2. Fetal hepatic measurement was obtained in 109 pregnancies. CONCLUSION: Acceptable reproducibility exists for hepatic volume determinations. In fetal growth restriction, reduction is more pronounced for hepatic volume than for head or upper abdominal circumference; hepatic volume is a better discriminator than head circumference but not upper abdominal circumference. http://repub.eur.nl/res/pub/31851/ 2000-12-01T00:00:00Z Objectives: To establish the nature and gestational age dependency of flow velocity waveforms from fetal middle and distal arterial pulmonary branches in the second half of normal pregnancy and to determine repeatability and inter-relationship of flow velocity waveform recordings from proximal, middle and distal arterial pulmonary branches. Design: Cross-sectional study. Subjects/methods: A total of 111 singleton normal pregnancies between 20 and 40 weeks of gestation were studied using a color-coded Doppler ultrasound system. Pulmonary waveforms were obtained at the level of the fetal cardiac four-chamber view. Repeatability was tested from two recordings at 15 min time-intervals in 25 separate normal pregnancies. Results: Acceptable repeatability of flow velocity waveforms from fetal arterial pulmonary branches was established with coefficients of variation below 15%. The nature of middle arterial pulmonary flow velocity waveforms was similar to that of proximal waveforms and showed a gestational age-related change for diastolic velocity parameters, peak systolic/peak diastolic ratio and pulsatility index. The distal arterial pulmonary branch displayed a monophasic forward flow velocity profile throughout the cardiac cycle. All velocity parameters of the distal branch remained unchanged with advancing gestation, with the exception of the pulsatility index. Significant inter-pulmonary changes were found for all pulmonary arterial waveform parameters. Conclusions: Alteration in pulmonary vascular resistance may play a role in gestational age-related changes, whereas changes in vessel branching/diameter and in the distance between the heart and more distal arterial pulmonary vessels may cause inter-pulmonary differences. http://repub.eur.nl/res/pub/8703/ 1997-01-01T00:00:00Z OBJECTIVES: This study assessed the potential impact of fetal ultrasound screening on the number of newborns affected by cardiac anomalies. METHODS: A decision model was developed that included the prevalence and history of congenital heart disease, characteristics of ultrasound, risk of abortion, and attitude toward pregnancy termination. Probabilities were obtained with a literature survey; sensitivity analysis showed their influence on expected outcomes. RESULTS: Presently, screening programs may prevent the birth of approximately 1300 severely affected newborns per million second-trimester pregnancies. However, over 2000 terminations of pregnancy would be required, 750 of which would have ended in intrauterine death or spontaneous abortion. Further, 9900 false-positive screening results would occur, requiring referral. Only the sensitivity of routine screening and attitude toward termination of pregnancy appeared to influence the yield substantially. CONCLUSIONS: The impact of routine screening for congenital heart disease appeared relatively small. Further data may be required to fully assess the utility of prenatal screening.