Clinical utility of non-invasive prenatal testing in pregnancies with ultrasound anomalies.

OBJECTIVE: To evaluate the application of non-invasive prenatal testing (NIPT) as an alternative to invasive diagnostic prenatal testing in pregnancies with abnormal ultrasound findings. METHODS: This was a retrospective analysis of 251 singleton and multiple pregnancies at high risk for fetal chromosomal abnormality based on findings at sonographic examination, in which NIPT was performed as a first-tier genetic test. NIPT was performed by massively parallel sequencing of cell-free DNA in maternal plasma, allowing genome-wide detection of whole-chromosome, as well as partial, autosomal aneuploidy. Sex chromosomes were not analyzed, according to the current protocol in Dutch laboratories. RESULTS: NIPT was performed at a median gestational age of 20 weeks, indicated by the presence of multiple congenital anomalies (n = 13), isolated structural anomalies (n = 57), increased nuchal translucency ≥ 3.5 mm (n = 58), soft markers (n = 73), growth restriction (n = 40) and other anomalies (n = 10). NIPT results were normal in 224 (89.2%) pregnancies, inconclusive in one (0.4%) and abnormal in 26 (10.4%). Most genetic aberrations detected by NIPT were common whole-chromosome aneuploidies: trisomy 21 (n = 13), trisomy 18 (n = 6) and trisomy 13 (n = 3). Four further NIPT results were abnormal; one was suspected of being confined placental mosaicism and one was of maternal origin. In those with normal NIPT results, sonographic follow-up or examination of the newborn indicated the need for diagnostic genetic testing in 33/224 (14.7%) pregnancies. Clinically relevant genetic aberrations were revealed in 7/224 (3.1%) cases, two of which were whole-chromosome aneuploidies: trisomy 13 and monosomy X. As sex chromosomal aberrations are not included in NIPT analysis, the latter cannot be considered a false-negative result. Other discordant findings were subchromosomal aberrations (< 20 megabases, n = 2) and monogenic aberrations (n = 3). CONCLUSIONS: NIPT should not be recommended for genetic evaluation of the etiology of ultrasound anomalies, as both resolution and sensitivity, or negative predictive value, are inferior to those of conventional karyotyping and microarray analysis. Nonetheless, some pregnant women consider NIPT to be an acceptable alternative to invasive diagnostic testing. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of Multifetal Pregnancy Reduction in Women with a Dichorionic Triamniotic Triplet Pregnancy to a Singleton Pregnancy: A Retrospective Nationwide Cohort Study.

OBJECTIVE: To study the pregnancy outcomes of women with a dichorionic triamniotic triplet pregnancy that was reduced to a singleton pregnancy and to review the literature. METHODS: We performed a nationwide retrospective cohort study. We compared time to delivery and perinatal mortality in dichorionic triplet pregnancies reduced to singletons with ongoing dichorionic triplet pregnancies and primary singleton pregnancies. Additionally, we reviewed the literature on the subject. RESULTS: We studied 46 women with a reduced dichorionic triplet pregnancy and 42 women with an ongoing dichorionic triplet pregnancy. Median gestational age at delivery was 38.7 vs. 32.8 weeks, respectively (p < 0.001). Delivery <24 weeks occurred in 9 (19.6%) women with a reduced triplet pregnancy and 4 (9.5%) with an ongoing triplet pregnancy (p = 0.19). Perinatal survival rates between the reduced group and the ongoing triplet group were not significantly different. CONCLUSION: Multifetal pregnancy reduction in women with a dichorionic triplet pregnancy to a singleton pregnancy prolongs median gestational age at birth. No statistically significant association was found with miscarriage and perinatal survival rates.

Pregnancy outcome after fetal reduction in women with a dichorionic twin pregnancy.

STUDY QUESTION: What are the pregnancy outcomes for women with a twin pregnancy that is reduced to a singleton pregnancy? SUMMARY ANSWER: Fetal reduction of a twin pregnancy significantly improves gestational age at birth and neonatal birthweight, however at an increased risk of pregnancy loss and preterm delivery. WHAT IS KNOWN ALREADY: Women with a multiple pregnancy are at increased risk for preterm delivery. Fetal reduction can be considered in these women. STUDY DESIGN, SIZE, AND DURATION: Retrospective cohort study of 118 women with a twin pregnancy reduced to a singleton pregnancy between 2000 and 2010. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: We compared the outcome of pregnancy in consecutive women with a dichorionic twin pregnancy that was reduced to a singleton pregnancy to that of women with a dichorionic twin pregnancy that was managed expectantly and women with a primary singleton pregnancy. Reductions were performed between 10-23(6/7) weeks' gestation by intracardiac or intrathoracic injection of potassium chloride, mostly for congenital anomalies. We compared median gestational age, pregnancy loss <24 weeks, preterm delivery <32 weeks, neonatal birthweight and perinatal deaths. MAIN RESULTS AND THE ROLE OF CHANCE: We studied 118 women with a twin pregnancy that was reduced to a singleton, 818 women with an ongoing dichorionic twin pregnancy and 611 women with a primary singleton pregnancy. Loss of the entire pregnancy <24 weeks and preterm delivery occurred significantly more in the reduction group compared with the ongoing twin group (11.9 versus 3.1% <24 weeks, P< 0.001 and 18.6 versus 11.5% <32 weeks, respectively, P < 0.001). In the reduction group, the percentage of women without any surviving child was significantly higher compared with the ongoing twin and primary singleton group (14.4, 3.4 and 0.7%, respectively, P < 0.001). Median gestational age was 38.9 weeks (interquartile range (IQR) 34.7-40.3) for reduced pregnancies, 37.1 weeks (IQR 35.3-38.1) for ongoing twin pregnancies and 40.1 (IQR 39.1-40.9) for primary singletons (P < 0.001 for all comparisons). LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were its retrospective character, and the fact that indications for reduction were heterogeneous. WIDER IMPLICATIONS OF THE FINDINGS: In women with a dichorionic twin pregnancy fetal reduction increases median gestational age only at considerable risk of complete early pregnancy loss. STUDY FUNDING/COMPETING INTERESTS: The study was not funded. None of the authors has conflicts of interest.

Prenatal examination of the area and morphology of the atrioventricular valves using four-dimensional ultrasound in normal and abnormal hearts.

OBJECTIVE: 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). METHODS: Atrioventricular valves were analyzed longitudinally in STIC volumes of 74 normal fetuses between the 15th and 36th week of pregnancy. The valve area was measured in a rendered view in diastole, the number of valve leaflets in systole. Longitudinal data analysis was performed using linear mixed models. Fifty fetuses with cardiac defects were examined. RESULTS: Examination of 355 STIC volumes of normal fetuses showed in 82.5% sufficient quality. The tricuspid valve leaflets were seen in 200 (68.3%) volumes and the mitral valve leaflets in 219 (74.7%) volumes. The tricuspid valve showed in 61.1% a round, 29.0% rectangle, and 8.9% elliptical shape and the mitral valve in 60.1% round, 28.0% rectangle, and 10.9% elliptical. Regression analysis revealed a positive relationship of the valve area with gestational age (p < 0.0001). Most heart defects with stenosis showed an area below the 5th percentile. CONCLUSION: Prenatal examination of the morphology and area of the AV valves using four-dimensional ultrasound is feasible. A rectangular valve opening is normal, which was visualized in about one third of the normal fetuses.

Differential and linear insertion of atrioventricular valves: a useful tool?

OBJECTIVE: The 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. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: Both 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.

Differential insertion of the atrioventricular valves: measurement protocol to detect various congenital heart defects.

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.

Age independent first trimester screening for Down syndrome: improvement in test performance.

OBJECTIVE: The aim of this study was to compare screening performance for Down syndrome of the absolute risk (AR) method to the first trimester combined test (FCT) at different maternal ages. METHODS: There was a retrospective analysis of 32,448 FCT. AR was defined as final risk divided by maternal age risk. RESULTS: The likelihood of receiving a true prediction was comparable between both methods in all age groups. With the AR method, two extra Down syndrome cases were detected in women <30 years, three cases were missed in women ≥36 years, and the likelihood of receiving a false prediction decreased overall (OR 0.82, CI 0.77-0.87; P < 0.0001), in women aged 36-40 years (0.45, CI 0.41-0.51; P < 0.0001), in women aged 41-45 years (0.18, CI 0.13-0.26; P < 0.0001) and increased in women aged ≤25 years (2.12, CI 1.52-2.96; P < 0.004). CONCLUSIONS: The AR method results in a significant decreased likelihood of receiving a false prediction with a comparable likelihood of receiving a true prediction. Thus, fewer invasive diagnostic tests will be performed. It will take away the misunderstanding about differences in screening performance for women of different ages. This might lead to a higher uptake of first trimester screening resulting in a more efficient screening policy.

Interobserver agreement in detailed prenatal diagnosis of congenital heart disease by telemedicine using four-dimensional ultrasound with spatiotemporal image correlation.

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. METHODS: Ten second-trimester spatiotemporal image correlation (STIC) volumes were sent to three observers in different tertiary care centers with expertise in 4D echocardiography. The 10 volumes were selected based on the type of diagnosis to cover a wide spectrum of CHD anomalies, and also included one normal fetal heart. Observers were asked to provide the diagnosis, the postprocessing modalities used and the time spent on examination, and to give a rating of the confidence for the diagnosis on a 5-point Likert scale. They were free to consult other colleagues, including pediatric cardiologists, but were blinded to the prenatal diagnosis and the neonatal outcome. A diagnostic scoring system was used to evaluate different aspects of the heart defects. The results were compared with neonatal echocardiography or postmortem findings ('gold standard'). RESULTS: In two cases all observers correctly diagnosed all details of the volume datasets. The observer with the best performance reached perfect agreement in six cases and nearly perfect agreement in three. The volumes were most frequently studied by sectional planes and were analyzed in a median time of 11.0 (range, 2.5-30.0) min. The median confidence score was 4.0 (range, 1.0-5.0). CONCLUSIONS: 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.

First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia.

OBJECTIVE: To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). METHODS: PlGF concentration was retrospectively measured in first trimester serum specimens of 23 cases of early-onset PE (<34 weeks), 26 cases of IUGR (birth weight < 5th centile) and 5 controls per case. Levels were adjusted for gestational age (GA), ethnicity and smoking to obtain multiples of the expected median (MoM). Logistic regression was used to assess PlGF, PAPP-A and maternal characteristics as potential predictors of early-onset PE and IUGR. RESULTS: PlGF MoM levels were significantly lower in the early-onset PE group (P < 0.0001) compared with controls, but not in the IUGR group. PAPP-A MoM levels were significantly lower in the IUGR group (P < 0.01) compared with controls but not in the early-onset PE group. PlGF significantly improved the ability of systolic blood pressure at the first prenatal visit to predict early-onset PE [achieving a receiver-operating characteristics curve with area under the curve (AUC) of 0.8]. Combining systolic blood pressure at the first prenatal visit and PlGF did not significantly improve the predictive ability compared with PlGF alone (AUC = 0.83). CONCLUSION: Serum PlGF is an acceptable marker in first trimester screening for early-onset PE, but a poor marker in screening for IUGR. Screening performance of serum PAPP-A is poor for both early-onset PE and IUGR.

Reliability of fetal cardiac volumetry using spatiotemporal image correlation: assessment of in-vivo and in-vitro measurements.

OBJECTIVE: To assess the reliability of measurement of fetal cardiac ventricular volume, stroke volume, and ejection fraction with four-dimensional ultrasound using spatiotemporal image correlation (STIC). METHODS: Volume datasets were collected from two sources: 24 from fetuses over a range of gestational ages and 12 from a miniature balloon model. Datasets were analyzed by three observers, repeatedly in 12 fetal datasets and all balloon datasets. Volume calculations were obtained by manually tracing multiple parallel slices (three-dimensional (3D) slice method). Measurement error was assessed by calculating standard errors of measurement (SEM) and coefficients of variation (CV). Reliability was assessed by calculating interobserver and intraobserver intraclass correlation coefficients (ICC). RESULTS: Measurement errors of balloon volumes were small and reliability was good (SEM

Validation of volume measurements for fetal echocardiography using four-dimensional ultrasound imaging and spatiotemporal image correlation.

OBJECTIVES: To assess the accuracy and reliability of four-dimensional (4D) ultrasound imaging using spatiotemporal image correlation (STIC) employing three different techniques to measure volumes in vitro. METHODS: Customized miniature balloons attached to a pump system were used to mimic fetal cardiac chambers. After the balloon model had been immersed in a bath filled with viscous gel, 4D datasets were acquired and three methods were used for volume analysis: three dimensional (3D) slice method, Virtual Organ Computer-aided AnaLysis (VOCAL) and VOCAL combined with inversion mode. Accuracy and measurement error were measured as the difference between the volume measurements and the actual volumes. Intraobserver reliability was assessed by computing coefficients of variation (CV) and intraclass correlation (ICC). RESULTS: Measurement of 76 different volumes, ranging from 0.30 to 4.95 mL, resulted in a total of 912 measurements. The 3D slice method had a mean error of -3.3%, the inversion method underestimated the volumes with a mean error of -6.1%, and VOCAL had a mean error of -2.9%. The 3D slice method had the best agreement (95% limits of agreement (LOA), -11.2 to 4.7%), followed by VOCAL (95% LOA, -14.1 to 8.3%); the inversion mode demonstrated the worst agreement (95% LOA, -21.4 to 9.2%). All three methods were reliable with CV < 10% and ICC > 0.95. CONCLUSIONS: 4D ultrasonography with STIC is a feasible and accurate method for calculating volumes of 0.30 mL upwards. In an in-vitro model the 3D slice method proved accurate, was the least time consuming, had the best reliability and had the smallest LOA. This method may prove useful when applied to in-vivo investigations.

First trimester maternal serum ADAM12s levels in twin pregnancies.

BACKGROUND: A disintegrin and metalloprotease 12s (ADAM12s) is a potential first trimester serum marker for fetal trisomy and adverse pregnancy outcome in singletons. In this study, ADAM12s levels in first trimester serum of uncomplicated and complicated twins were evaluated. METHODS: ADAM12s was studied in maternal serum of 215 twin pregnancies, collected between 2004 and 2008. ADAM12s was measured 'blind to outcome' using AutoDelfia (PerkinElmer, Turku, Finland). As a reference, data from 2423 singletons were used. RESULTS: The median ADAM12s level was increased in euploid twins [1.61 multiples of the median (MoM); n = 209] compared with singletons. The median ADAM12s MoM was significantly lower in monochorionic (1.36 MoM; n = 41) compared with dichorionic twins (1.67 MoM; n = 168) (Mann-Whitney U test, p = 0.005). Trisomy 21 was identified in two pregnancies. Median ADAM12s MoM in twins complicated by hypertensive disorders (1.77 MoM, n = 35) or small for gestational age fetus (1.54 MoM; n = 24) was not significantly different from uncomplicated twins (1.64 MoM; n = 134). CONCLUSION: Median ADAM12s MoM in euploid twins was increased compared with singletons. Monochorionic had significantly lower median ADAM12s MoM than dichorionic twins. Median ADAM12s MoMs were not significantly different in twins complicated by hypertensive disorders or small for gestational age fetus compared with uncomplicated twins.

First-trimester serum marker distribution in singleton pregnancies conceived with assisted reproduction.

OBJECTIVE: To evaluate marker distribution of free beta-human chorionic gonadotrophin (fbeta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in singleton pregnancies conceived by assisted reproduction techniques (ART). METHODS: In vitro fertilization (IVF) (n = 203) and intracytoplasmic sperm injection (ICSI) (n = 192) cases from a database of 14 645 first-trimester combined tests (overall study group) were selected and matched to 1164 controls for gestational age at sample date and maternal age. RESULTS: In the IVF group and ICSI group, lnPAPP-A was lower (IVF 6.74 vs 7.08; P = 0.0001; ICSI 6.59 vs 7.07; P = 0.0001) compared with the matched controls. Lnfbeta-hCG was lower in the IVF group (3.75 vs 3.90; P = 0.005) but not significantly different in the ICSI group (3.87 vs 3.93; P = 0.27). The computed correction factors for PAPP-A and fbeta-hCG were 1.42 and 1.17 for the IVF group and 1.56 and 1.05 for the ICSI group.The false-positive rate (FPR) in the IVF and ICSI group compared with the matched controls was higher (IVF 10.3% vs 8.6% and ICSI 10.9% vs 7.5%). In the overall age-biased [maternal age significantly lower compared with all ART and control groups] study group the FPR was 6.8%. CONCLUSION: The increase in FPR in the ART groups can be explained by decreased PAPP-A values. Therefore, an adjustment in risk analysis for Down syndrome is suggested.

Understanding decidual vasculopathy and the link to preeclampsia: A review.

Preeclampsia is the archetype of a spectrum of clinical disorders related to abnormal placental development or function, characterized by placental histological lesions. Among those lesions, decidual vasculopathy is a term used to describe lesions of maternal spiral arteries, which are encountered on placental examination in about half of the women with preeclampsia. The morphological features of the lesions include perivascular lymphocytic infiltration, fibrinoid necrosis and foam cell incorporation within the vessel wall. Due to the resemblance of the latter characteristic to atherosclerosis, they are alternatively termed acute atherosis. Decidual vasculopathy correlates with worse maternal and neonatal outcomes, as well as placental pathology. In this article, we review the available literature on decidual vasculopathy and address the pitfalls in histological analysis of the lesions, including the varying definitions of the lesions and sample collection methods. We also discuss the current evidence on the etiology of the lesions and propose a novel hypothesis linking the three etiological pathways to the formation of decidual vasculopathy and, ultimately, the emergence of the heterogeneous group of placental dysfunction disorders, known as the great obstetric syndromes.

Fetal cardiac function assessed with four-dimensional ultrasound imaging using spatiotemporal image correlation.

OBJECTIVES: The goal of this study was to use spatiotemporal image correlation (STIC) to provide reference values for left and right ventricle volumes, and indices of fetal cardiac function. METHODS: In this prospective longitudinal study, STIC volumes were acquired periodically from 12 weeks of gestation onwards. The STIC volumes were frozen in end-systole and end-diastole, and volumetric data were measured by manual tracing and summation of multiple slices. These ventricle volumes were used to calculate stroke volume, ejection fraction and cardiac output. RESULTS: Some 202 STIC volumes of 63 fetuses were included in the analysis. Mean left and right ventricle stroke volume increased from 0.02 mL at 12 weeks to 1.41 mL and 1.46 mL, respectively, at 30 weeks, while the mean right to left stroke volume ratio remained stable at around 1.2. Mean left and right ventricle cardiac output increased from 2.40 mL/min and 2.60 mL/min at 12 weeks to 197.74 mL/min and 204.81 mL/min, respectively, at 30 weeks. Both left and right mean ejection fraction remained constant at around 0.45 with advancing gestational age. Bland-Altman analysis showed a coefficient of variation for measured stroke volume of 13.7%. CONCLUSIONS: This study establishes reference values for fetal cardiac volumes and indices for fetal cardiac function from 12 to 30 weeks of gestation using STIC. STIC seems to overcome many of the pitfalls of conventional ultrasound methods and has the potential to become the method of choice.

Jugular lymphatic sacs in first-trimester fetuses with normal nuchal translucency.

OBJECTIVE: To assess the ultrasonographic appearance of the jugular lymphatic sacs (JLS) in first-trimester fetuses with a normal nuchal translucency (NT). METHODS: Seventy-five fetuses with a normal NT thickness (< 95(th) percentile) were examined weekly between 11 and 17 weeks of gestation. After measurement of the NT thickness, the neck region was examined using both transvaginal and transabdominal ultrasonography for the presence of JLS. If present, their dimensions were measured in three directions and the volume was calculated using the formula for a spheroid. Data were analyzed using multilevel analysis. RESULTS: Seventy-five fetuses were evaluated and a total of 243 ultrasound examinations of the neck region were performed. In 25 (33%) of the 75 fetuses, the JLS could be observed once or more than once. In 19 fetuses JLS were visualized once, in five fetuses twice and in one fetus three times. In total, the JLS were visualized 32 times (n = 15 bilaterally, n = 15 only the left JLS and n = 2 only the right JLS). Relatively greater NT thickness was associated with a higher probability of the presence of JLS, although this was not statistically significant (NT < 1 mm, probability 0.07; NT 1-2 mm, probability 0.15, P = 0.10; NT > 2 mm, probability 0.20, P = 0.08). Gestational age was predictive for the presence of JLS, with the highest probability between 13 and 15 weeks of gestation (P < 0.01). No relationship was found between gestational age and the volumes of the left and right JLS. CONCLUSION: The JLS can be visualized on ultrasound examination in a significant proportion of fetuses with normal NT, most often between 13 and 15 weeks of gestation, and this does not seem to be associated with any abnormality in these fetuses.

ADAM12s as a first-trimester screening marker of trisomy.

OBJECTIVE: To evaluate the potential of maternal serum A Disintegrin And Metalloprotease 12-S (ADAM12s) as an additional marker for the combined test in the Dutch first-trimester national Down syndrome (DS) screening program. METHODS: Serum samples were collected between 2004 and 2007 as part of the national program. A total of 218 singleton cases of trisomy 21 (DS), 62 trisomy 18 (Edwards syndrome) and 29 trisomy 13 (Patau syndrome) were identified. All cases were matched with controls for gestation, maternal weight and maternal age. The serum concentration of ADAM12s was determined 'blind' to outcome and expressed in multiples of the gestation-specific median for controls (MoM). RESULTS: The median ADAM12s was 1.00 MoM in controls and in the DS cases at 8, 9, 10, 11, 12, 13 weeks it was 0.45 (n = 3), 0.73 (22), 0.74 (53), 0.85 (37), 0.92 (71), 1.06 (32) MoM, respectively. The median for trisomy 18 was 0.85 MoM and for trisomy 13 0.63 MoM. CONCLUSION: The ADAM12s MoM values were clearly reduced in early first-trimester for all trisomies. However, the screening performance for DS did not greatly improve adding ADAM12s. ADAM12s could be an additional biochemical marker for first-trimester screening for trisomies other than DS.

Doppler velocimetry of the ductus arteriosus in normal fetuses and fetuses suspected for pulmonary hypoplasia.

OBJECTIVE: The purpose of this study was to determine whether the pulsatility index (PI) of the ductus arteriosus could predict the occurrence of pulmonary hypoplasia secondary to congenital disorders or complications during pregnancy. SAMPLE AND METHODS: In this longitudinal study, 78 uncomplicated pregnancies and 43 pregnancies complicated by various disorders or complications with regard to pulmonary hypoplasia were studied by Doppler sonography between 18 and 35 weeks of gestation. A PI >97.5th percentile was considered abnormal. RESULTS: Using a multilevel modelling, the reference curve of the PI of the ductus arteriosus was created based on 301 measurements. Of the 43 complicated pregnancies, 21 infants (49%) were diagnosed with pulmonary hypoplasia on postmortem examination and/or the clinical and radiological presentation. Using the PI, a sensitivity of 38%, a specificity of 95%, a positive predictive value of 89% and a negative predictive value of 62% were found. CONCLUSION: The PI of the ductus arteriosus is not useful in predicting the occurrence of pulmonary hypoplasia secondary to congenital disorders or complications during pregnancy.

A systematic analysis of the feasibility of four-dimensional ultrasound imaging using spatiotemporal image correlation in routine fetal echocardiography.

OBJECTIVES: To investigate the feasibility of incorporating spatiotemporal image correlation (STIC) into a tertiary fetal echocardiography program. METHODS: During the study period all pregnant women fitting our inclusion criteria were enrolled consecutively. Four sonographers participated in the study, one of whom had substantial previous experience of STIC volume acquisition and three of whom did not. STIC volumes were acquired within the time slot allocated for the usual examination and all attempts were recorded. STIC volumes were assessed on acquisition conditions, the quality (as defined by a checklist of cardiac structures that could be visualized), and the rendering abilities. Furthermore, possible learning effects and the influence of experience with STIC on volume acquisition were studied. RESULTS: STIC volume acquisition was successful in 75.7% (112/148) of cases in which it was attempted. The more experienced sonographer had a higher success rate in STIC volume acquisition (experienced vs. less experienced, 88.4% vs. 70.5%, P = 0.02). Of all analyzed STIC volumes, 64.8% were of high or sufficient quality. STIC volume quality and rendering ability correlated strongly with the acquisition conditions. High-quality STIC volumes successfully rendered the intracardiac septa in 84.6% of cases. The coronal atrioventricular plane was rendered in 12/26 cases (46.2%). CONCLUSIONS: This study shows that incorporation of STIC volume acquisition into the daily practice of a tertiary fetal echocardiography program is feasible. Sonographers do not have to be specifically experienced in three- or four-dimensional ultrasound imaging to acquire high-quality STIC volumes. For successful STIC acquisition and subsequent successful analysis, correct acquisition conditions are of major importance. Finally, our results demonstrate that STIC is as susceptible as conventional two-dimensional ultrasound imaging to individual variations and limitations in scanning windows.

Congenital diaphragmatic hernia: 2D lung area and 3D lung volume measurements of the contralateral lung to predict postnatal outcome.

OBJECTIVES: The aim of the study was to evaluate the prognostic utility of 2D lung area and 3D lung volume measurements of the contralateral lung in infants with congenital diaphragmatic hernia. METHODS: At 18-37 weeks' gestation between 1 and 5 scans of the contralateral fetal lung were obtained in 6 pregnancies complicated by congenital diaphragmatic hernia (5 left- and 1 right-sided). Lung volume measurements were compared with reference curves for gestational age and estimated fetal weight obtained from uncomplicated pregnancies. Lung area measurements were compared with reference nomograms. RESULTS: Three infants survived and 3 died. Lung volume measurements versus gestational age were beneath the 5th percentile for the nonsurviving infants and within the normal ranges for the surviving infants. When comparing the observed/expected lung volume and lung area ratios of the first measurements with the ratios at the last visit before birth, the ratios of the infants who subsequently died decreased whereas the ratios of the infants who survived remained unchanged or increased. CONCLUSIONS: In the case of congenital diaphragmatic hernia, 3D lung volume measurements seem to be a good predictor of outcome but longitudinal measurement also provides important additional information. Larger studies are necessary to confirm these results.