Reproducibility of echocardiographic measurements of human fetal left ventricular volumes and ejection fractions using four-dimensional ultrasound with the spatio-temporal image correlation modality.

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.

Left ventricular isovolumic relaxation and renin-angiotensin system in the growth restricted fetus.

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.

Fetal hemodynamic adaptive changes related to intrauterine growth: the Generation R Study.

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.

The outcome of gastroschisis after a prenatal diagnosis or a diagnosis only at birth. Recommendations for prenatal surveillance.

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.

The endothelin-1 pathway and the development of cardiovascular defects in the haemodynamically challenged chicken embryo.

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.

Application of the magnitude-squared coherence function between uterine and umbilical flow velocity waveforms for predicting placental dysfunction: a preliminary study.

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.

Impact of decision-making in a multidisciplinary perinatal team.

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.

Technology assessment and knowledge brokering: the case of assisted reproduction in The Netherlands.

OBJECTIVES: Even when policy makers show interest and evidence-informed and convincing HTA studies are available, use of assessment products is not guaranteed. In this article, we report our experience with knowledge brokering to foster evidence-informed policy making on cost-effective treatment and reimbursement of assisted reproduction in The Netherlands. METHODS: From earlier work in the field of knowledge brokering, we foresaw the need for a deliberative strategy to manage the inherent tension between scientific rigor demanded by researchers and responsiveness to real-time needs demanded by policy makers. Therefore, we structured the process in three distinct steps: (i) agreement about the main messages from the research, (ii) analysis of the policy context and of the meaning of the main messages for the actors involved, and (iii) an invitational meeting to make recommendations for action. RESULTS: One of the recommendations that would require changes in ministerial policy was followed up instantly, whereas the other recommendation is still under debate. The Dutch Society of Obstetrics and Gynecology activated the revision of two guidelines. The patient organization uses the new scientific insights in informing members and the public. Closing the loop, The Netherlands Organisation for Health Research and Development (ZonMw) funded research to close knowledge gaps that became apparent in the process. CONCLUSIONS: Knowledge brokering is a promising approach to bring HTA into practice. We conclude that the methodologies to feed research results into the policy process are still in an incipient stage and need further development.

Survival after non-aggressive obstetric management in cases of severe fetal anomalies: a retrospective study.

OBJECTIVE: Obstetricians may choose to refrain from interventions aimed at sustaining fetal life (i.e., non-aggressive obstetric management) when the fetus has an extremely poor prognosis. However, if the infant is then born alive, crucial neonatal management decisions then have to be made. We sought empirical data concerning such perinatal end-of-life decisions. Firstly, to describe survival during delivery and after birth following non-aggressive obstetric management, and secondly, to describe neonatal management in infants born alive after non-aggressive obstetric management. DESIGN: Retrospective descriptive study. SETTING: Tertiary centre. POPULATION: Eighty-one infants born to women who opted for a non-aggressive obstetric management policy because of sonographically diagnosed severe fetal anomaly. METHODS: Data were collected from obstetric and neonatal records, as well as ultrasound reports. MAIN OUTCOME MEASURES: Survival, neonatal management and health status after birth. RESULTS: Relevant data were available for 78/80 (98%) infants. Six (8%) infants died in utero, 16 (21%) died during delivery (11 from cephalocentesis) and 56 (72%) were born alive. Life-sustaining neonatal treatment was initiated in 29 (52%) of the live-born infants. Twenty-three of these 29 (79%) infants died within six months of birth. Of the 27 live-born infants who did not receive neonatal life-sustaining treatment, 25 (93%) died. Eight infants survived; all with severe health problems. CONCLUSION: Life-sustaining neonatal support after non-aggressive obstetric management in the presence of severe fetal malformation has little impact on survival.

Parental decision-making after ultrasound diagnosis of a serious foetal abnormality.

OBJECTIVE: The purpose of this article is to provide clinicians who are involved in the field of foetal medicine with a comprehensive overview of theories that are relevant for the parental decision-making process after ultrasound diagnosis of a serious foetal abnormality. METHODS: Since little data are available of parental decision-making after ultrasound diagnosis of foetal abnormality, we reviewed the literature on parental decision-making in genetic counselling of couples at increased genetic risk together with the literature on general decision-making theories. The findings were linked to the specific situation of parental decision-making after an ultrasound diagnosis of foetal abnormality. RESULTS: Based on genetic counselling studies, several cognitive mechanisms play a role in parental decision-making regarding future pregnancies. Parents often have a binary perception of risk. Probabilistic information is translated into two options: the child will or will not be affected. The graduality of chance seems to be of little importance in this process. Instead, the focus shifts to the possible consequences for future family life. General decision-making theories often focus on rationality and coherence of the decision-making process. However, studies of both the influence of framing and the influence of stress indicate that emotional mechanisms can have an important and beneficial function in the decision-making process. CONCLUSION: Cognitive mechanisms that are elicited by emotions and that are not necessarily rational can have an important and beneficial function in parental decision-making after ultrasound diagnosis of a foetal abnormality. Consequently, the process of parental decision-making should not solely be assessed on the basis of its rationality, but also on the basis of the parental emotional outcome.

Systolic and diastolic ventricular function assessed by pressure-volume loops in the stage 21 venous clipped chick embryo.

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.

Ultrasound diagnosis of fetal anomalies: an analysis of perinatal management of 318 consecutive pregnancies in a multidisciplinary setting.

OBJECTIVES: The objectives of this study are to analyse the perinatal management decisions made in a multidisciplinary setting following the prenatal diagnosis of fetal anomalies and to evaluate to what extent, in clinical practice, decisions about obstetric management are attuned to those about neonatal management. METHODS: Data on perinatal management of 318 consecutive singleton pregnancies presented to a multidisciplinary perinatal team in a tertiary centre were collected retrospectively. RESULTS: The multidisciplinary perinatal team decided upon non-aggressive obstetric management in 20% of the cases and consented to termination of pregnancy in 10% of the cases. The multidisciplinary perinatal team decided upon neonatal management in 112(36%) of all fetuses. In 100(89%) of these fetuses, standard neonatal management, and in 12(11%), no neonatal life-sustaining treatment was decided upon. Implementation of the decisions of the multidisciplinary perinatal team on the various management modalities ranged from 88 to 100%. CONCLUSION: The multidisciplinary perinatal team worked well in making decisions about obstetric management. In 30% of the cases, this concerned end-of-life decisions. However, for the majority of cases, the perinatal team did not plan neonatal management before birth and thereby did not attune obstetric and neonatal management to each other. This probably reflects the different attitudes towards end-of-life decisions between obstetricians and neonatologists. However, to ensure a consistent perinatal management, a multidisciplinary perinatal team has to make prenatal decisions about both obstetric and neonatal management.

C825T polymorphism in the human G protein beta 3 subunit gene and preeclampsia; a case control study.

OBJECTIVE: Recently, a polymorphism of the gene encoding for the G protein beta3-subunit (GNB3) has been described. The T allele of this polymorphism (825T) is associated with endothelium dysfunction. Endothelium dysfunction has been described in women with preeclampsia. We, therefore, tested the hypothesis that in women who have had preeclampsia the T allele is more prevalent than in controls. STUDY DESIGN: We conducted a case-control study of 157 women with preeclampsia during 1991-1996. Cases and controls were tested for the presence of 825T by genotyping. Logistic regression methods were used for data analysis. RESULTS: The frequency of the T allele of the GNB3 gene was similar in cases (0.30) and controls (0.27) (odds ratio 1.24, 95% confidence interval 0.88-1.75). Compared to controls, we found a high frequency of the T allele in patients with the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (odds ratio 4.25, 95% confidence interval 1.12-16.05). CONCLUSION: The frequency of the T allele of the GNB3 gene, which serves as a marker for endothelium dysfunction, was not different between women with preeclampsia and controls. Women with the HELLP syndrome had a high frequency of the T allele. This suggests that this polymorphism in the GNB3 gene does not contribute to endothelium dysfunction in women with preeclampsia while it does contribute in women with the HELLP syndrome.

Obstetricians' agreement on fetal prognosis after ultrasound diagnosis of fetal anomalies.

INTRODUCTION: After ultrasound diagnosis of a severe fetal anomaly is made, difficult decisions may arise regarding obstetric management. Guidelines have been developed to support obstetricians in decision-making. However, it is unknown to what extent in the clinical situation, guidelines are actually supportive. OBJECTIVES: We aimed at: (1) determining whether obstetricians in the presence of a fetal anomaly are able to classify fetal prognosis according to guidelines; (2) establishing inter- and intra-observer agreement regarding fetal prognosis. METHODS: We used three categories of fetal prognosis: category 1: the infant has no chance of survival and the abnormalities cannot be treated (1.1); or the infant has a chance of extra-uterine survival but post-natal use of life-prolonging medical treatment is considered futile (1.2); category 2: the infant has a chance of extra-uterine survival and post-natal use of life-prolonging medical treatment, if necessary, is considered beneficial. Five senior obstetricians categorized 100 case descriptions of severe fetal abnormalities, which were classified again after five months. RESULTS: Four obstetricians were able to classify 98% or more of cases. In 67% of cases, four or all obstetricians agreed on fetal prognosis. The overall kappa coefficient was 0.48 (moderate agreement). The differences between obstetricians represented systematic differences in opinions on how to classify cases. Intra-observer agreement was 82 to 97%. CONCLUSION: Obstetricians were usually able to classify fetal prognosis according to guidelines, but in a substantial number of cases, there was a disagreement reflecting systematic differences between obstetricians.

Epinephrine affects hemodynamics of noninnervated normal and all-trans retinoic acid-treated embryonic chick hearts.

OBJECTIVE: To study the acute effect of epinephrine on hemodynamics of noninnervated normal and retinoic-acid-treated embryos. DESIGN: Prospective interventional study design. METHODS: A total of 190 stage 15 (50-55 h of incubation) chick embryos were randomly treated with 1 microg all-trans retinoic acid and reincubated. At stage 20 (day 3) and stage 24 (day 4), dorsal aortic flow velocities were measured with a 20-MHz pulsed Doppler velocity meter, in normal and retinoic-acid-treated embryos. Flow velocity waveforms were assessed both before and after the administration of epinephrine (5 or 10 microg). RESULTS: Epinephrine caused a significant increase (p < 0.05) in heart rate, peak and mean velocities, peak acceleration, peak and mean blood flows, stroke volume and dorsal aortic area of both stage 20 and stage 24 normal and retinoic-acid-treated chick embryos. However, before epinephrine administration, stage 24 retinoic-acid-treated embryos displayed a significantly lesser increase in all outcome variables with the exception of dorsal aortic area. This was even observed after epinephrine administration. The effect of retinoic acid on cardiac output could not be compensated by epinephrine application. CONCLUSION: Epinephrine affects hemodynamics in both normal embryos and retinoic-acid-treated embryos prior to sympathetic innervation. A significant difference in hemodynamics exists between stage 24 normal and retinoic-acid-treated embryos. The underlying mechanism for the observed hemodynamic changes will need to be investigated.

Ventricular diastolic filling characteristics in stage-24 chick embryos after extra-embryonic venous obstruction.

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.

Three-dimensional sonographic measurement of normal fetal brain volume during the second half of pregnancy.

OBJECTIVES: This study was undertaken to develop a three-dimensional (3D) ultrasound method of measuring fetal brain volume. STUDY DESIGN: Serial 3D sonographic measurements of fetal brain volume were made in 68 normal singleton pregnancies at 18 to 34 weeks of gestation. A comparison was made with fetal brain volume estimates from two-dimensional (2D) sonographic measurement of head circumference and published postmortem fetal brain weights. RESULTS: Coefficient of variation for fetal brain volume (3D) caused by differences between repeated tests was 10.2% and between analyses of the same recorded volume 2.2%. Median brain volume increases from 34 mL at 18 weeks to 316 mL at 34 weeks. Median brain weight represented approximately 15% of total fetal weight. The 3D ultrasound-derived brain weight is larger than postmortem brain weight. However, this is not so for brain weight derived from total fetal weight at autopsy. A good agreement between 3D and 2D brain volume was found. CONCLUSION: Sonographic measurement of fetal brain volume demonstrated an acceptable intraobserver variability and a nearly 10-fold increase during the second half of gestation.

Assessment of fetal liver volume and umbilical venous volume flow in pregnancies complicated by insulin-dependent diabetes mellitus.

OBJECTIVES: To determine fetal liver volume and its relation with umbilical venous volume flow and maternal glycosylated haemoglobin (HbA1c) in pregnancies complicated by diabetes mellitus type I. DESIGN: A cross sectional matched control study. Obstetric out patient clinic, Erasmus MC-University Medical Centre, Rotterdam. POPULATION: Data from fetuses of diabetic women (n = 32; 18-36 weeks) were compared with data from normal controls (n = 32) matched for gestational age. METHODS: Umbilical venous cross sectional area (mm(2)) and time-averaged velocity (mm/s Doppler) were determined for calculation of volume flow (mL/min) and flow per kilogram fetal weight (mL/min/kg). Umbilical artery pulsatility index was determined. Fetal liver volume measurements were obtained using a Voluson 530-D. MAIN OUTCOME MEASURES: Fetal liver volume, umbilical venous volume flow and downstream impedance. RESULTS: A statistically significant difference between fetuses of diabetic women and normal controls was found for liver volume (mean [SD]: 45.9 [34.0] vs 38.3 [28.7] mL), abdominal circumference (22.2 [6.6] vs 21.3 [5.6] cm), estimated fetal weight (1162 [898] vs 1049 [765] g) and fetoplacental weight ratio (0.22 vs 0.19) and liver volume/estimated fetal weight ratio (4.13% [0.007] vs 3.62% [0.009]). Umbilical venous volume flow (mL/min) and umbilical artery pulsatility index were not essentially different between the two study groups, but umbilical venous volume flow per kilogram fetal weight was lower (P < 0.05) in the diabetes group (94.3 [26.1] mL/min kg) compared with normal controls (109.5 [28.0] mL/min/kg). A positive correlation existed between fetal liver volume and maternal HbA1c (P = 0.002). CONCLUSIONS: Measurement of fetal liver volume by three-dimensional ultrasound may play a role in identifying fetal growth acceleration in diabetic pregnancies. Fetal liver volume increase is positively related to maternal HbA1c levels reflecting degree of maternal glycemic control. Fetal liver volume normalised for estimated fetal weight is significantly higher in the fetuses of diabetic women. In the present study, umbilical venous volume flow and fetoplacental downstream impedance are not different between diabetic and normal pregnancies.

Long-term psychological impact of carrying a BRCA1/2 mutation and prophylactic surgery: a 5-year follow-up study.

PURPOSE: To explore long-term psychosocial consequences of carrying a BRCA1/2 mutation and to identify possible risk factors for long-term psychological distress. PATIENTS AND METHODS: Five years after genetic test disclosure, 65 female participants (23 carriers, 42 noncarriers) of our psychological follow-up study completed a questionnaire and 51 participants were interviewed. We assessed general and hereditary cancer-related distress, risk perception, openness to discuss the test result with relatives, body image and sexual functioning. RESULTS: Carriers did not differ from noncarriers on several distress measures and both groups showed a significant increase in anxiety and depression from 1 to 5 years follow-up. Carriers having undergone prophylactic surgery (21 of 23 carriers) had a less favorable body image than noncarriers and 70% reported changes in the sexual relationship. A major psychological benefit of prophylactic surgery was a reduction in the fear of developing cancer. Predictors of long-term distress were hereditary cancer-related distress at blood sampling, having young children, and having lost a relative to breast/ovarian cancer. Long-term distress was also associated with less open communication about the test result within the family, changes in relationships with relatives, doubting about the validity of the test result, and higher risk perception. CONCLUSION: Our findings support the emerging consensus that genetic predisposition testing for BRCA1/2 does not pose major mental health risks, but our findings also show that the impact of prophylactic surgery on aspects such as body image and sexuality should not be underestimated, and that some women are at risk for high distress, and as a result, need more attentive care.

Acutely altered hemodynamics following venous obstruction in the early chick embryo.

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.