[Show abstract][Hide abstract] ABSTRACT: To evaluate the modeled predictive value of three current screening markers (pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), and nuchal translucency (NT)) and four potential screening markers (a disintegrin and metalloprotease 12 (ADAM12), total hCG, placental protein 13 (PP13), and placental growth factor (PlGF)) for Down syndrome using different screening strategies.
All markers were measured in stored first-trimester serum of 151 Down syndrome cases and 847 controls. All marker levels were expressed as gestational age-specific multiples of the median (MoMs) and comparisons were made using the Mann-Whitney U-test. Detection rates (DRs) for fixed false-positive rates (FPRs) were modeled using different screening strategies.
Significantly different median MoMs for Down syndrome cases compared to controls were found for PAPP-A (0.49 vs. 1.00; P < 0.0001), free β-hCG (1.70 vs. 1.01; P < 0.0001), ADAM12 (0.89 vs. 1.00; P < 0.0001), total hCG (1.28 vs. 1.00; P < 0.0001), PlGF (0.80 vs. 1.00; P < 0.0001) and NT (1.74 vs. 1.01; P < 0.0001). The lower PP13 MoM in Down syndrome cases (0.91 vs. 1.00) was not statistically significant (P = 0.061). Adding the four new markers to the current screening strategy (i.e. first-trimester combined test) led to an increase in DR from 77% to 80% at a 5% FPR. The modeled application of a two-sample screening strategy (with some markers assessed early and others later in the first trimester) increased the DR to 89%. In a two-step contingent screening model, using an intermediate risk range of 1 in 100 to 1 in 2000 at biochemical screening (using all markers), the overall DR was 77%, but it was predicted that only 33% of women would require referral for NT measurement.
First-trimester Down syndrome screening may be improved by adding new markers to the current screening test and by applying different screening strategies. The application of a two-sample screening model resulted in the highest predicted DR, but this should be confirmed in population-based prospective studies.
Ultrasound in Obstetrics and Gynecology 08/2011; 38(2):134-9. · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have shown the capability of ultrasound to demonstrate fetal cortical development. For practical application, it would be useful to have more insight into the physiological progress of cortical folding. A longitudinal study was undertaken to grade fetal cortical development and to study physiological asymmetry by means of a simple scoring system. The reproducibility of the scoring system and the differences between two-dimensional (2D) and three-dimensional (3D) ultrasound were also examined.
A cohort of 28 patients was examined by 2D and 3D ultrasound from 20 to 40 weeks of gestation. The development of selected fissures, sulci and cortical areas were graded from 0 to 5. One examination per week of gestation was randomly selected for evaluation of intraobserver and interobserver variation.
Two-hundred and fifteen ultrasound examinations were performed in 28 patients. The development of the different cortical areas is presented. The intraobserver and interobserver agreement for assessment of grade was good. Asymmetry was common between 24 and 28 weeks, especially in female fetuses. The right parieto-occipital fissure tended to be more advanced and the left calcarine and cingulate sulci tended to be more advanced. No clinically or statistically significant differences were found between 2D and 3D ultrasound.
Evaluation of cortical development by means of a simple scoring system is feasible and reproducible. Asymmetrical development of sulci, previously only described in vitro, has now also been demonstrated in vivo. 3D ultrasound was equally accurate and repeatable and no more time consuming than 2D ultrasound.
Ultrasound in Obstetrics and Gynecology 12/2010; 36(6). · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the distributions of pregnancy-associated plasma protein A (PAPP-A), the free beta subunit of human chorion gonadotrophin (fbeta-hCG), A Disintegrin and Metalloprotease 12 (ADAM12) and Placental Protein 13 (PP13) in first trimester twin pregnancies.
Serum marker concentrations were measured in monochorionic and dichorionic twin pregnancies and singleton controls to study differences in multiples of the gestation-specific normal medians (MoMs).
Median PAPP-A and fbeta-hCG MoMs were 2.03 and 1.87 for monochorionic twins (n = 116) and 2.18 and 1.89 for dichorionic twins (n = 650). Furthermore, ADAM12 and PP13 MoMs were 1.66 and 1.56 for monochorionic twins (n = 51) and 1.64 and 1.53 for dichorionic twins (n = 249). No statistically significant differences between monochorionic and dichorionic twin pregnancies were found. Correlations between markers in these pregnancies did not differ from singletons.
For first-trimester screening, different parameters for monochorionic and dichorionic twin pregnancies is not necessary. Furthermore, if ADAM12 and PP13 will be adopted as screening markers, the presented median MoM values, standard deviations and correlation coefficients for twin pregnancies may contribute to a proper twin risk estimation.
[Show abstract][Hide abstract] ABSTRACT: To determine whether Placental Protein 13 (PP13) could be an additional marker in first trimester screening for aneuploidies.
To evaluate differences in multiples of the gestation-specific normal median (MoMs), PP13 concentrations were measured in serum samples from Down syndrome, trisomy 18 and 13 affected pregnancies and euploid singleton pregnancies (four for each case matched for duration of storage, maternal weight and age).
The PP13 MoM in Down syndrome cases (n = 153) was 0.91 [not statistically significant from controls (n = 853); P = 0.06; Wilcoxon rank sum test, two-tail]. PP13 MoMs were decreased in trisomy 18 (n = 38-median MoM 0.64; P < 0.0001) and trisomy 13 cases (n = 23-median MoM 0.46; P < 0.0001). There was a slight upward trend in MoM values of the Down syndrome cases with gestational weeks. The PP13 MoM was significantly correlated with the pregnancy associated plasma protein-A MoM and the free beta-subunit of human chorion gonadotrophin (fbeta-hCG) MoM.
PP13 does not seem to be a good marker for Down syndrome. PP13 MoMs are, however, significantly lower in trisomy 18 and 13 pregnancies. The addition of PP13 to the current screening test could be valuable for improving the discrimination of aneuploid from euploid pregnancies.
[Show abstract][Hide abstract] ABSTRACT: To determine which prenatal ultrasound findings can predict survival and mental and motor functioning in children with spina bifida.
Prenatal ultrasound examinations of all liveborn children who were prenatally diagnosed with spina bifida between 1997 and 2002 at the University Medical Centre, Utrecht (n = 41) were retrospectively reviewed for lesion level, head circumference, ventriculomegaly, scoliosis and talipes. These measures were correlated with postnatal anatomical (as assessed by magnetic resonance imaging (MRI)) and functional lesion levels, survival and motor and mental outcome at 5 years of age. The capacity of prenatal ultrasonography to determine lesion level was also assessed in all fetuses diagnosed with spina bifida from 2006-2007 (n = 18).
Nineteen infants died before the age of 5 years. Multivariate regression analysis showed that higher lesion level and head circumference > or = the 90th percentile on prenatal ultrasound examination were independent predictors of demise (P < 0.05 and P = 0.01, respectively). None of the ultrasound features was a predictor of motor or mental functioning. Ultrasound predicted anatomical lesion level within one level of the postnatal findings in 50% of the first cohort and 89% of the second cohort (P < 0.01). The level of the anatomical lesion as assessed by postnatal MRI differed from the functional lesion by as many as six vertebral levels.
Lesion level and head circumference on prenatal ultrasound are predictive of survival in children with spina bifida. No predictors were found for mental or motor function at the age of 5 years.
Ultrasound in Obstetrics and Gynecology 09/2009; 34(3):253-8. · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this prospective longitudinal study was to evaluate the growth of the fetal cerebellar volume by means of 3-D ultrasound to evaluate whether there is a difference between the volumes of the left and right cerebellar hemispheres, and to evaluate the intra- and interobserver reliability of two different techniques of volume measurement. Three-dimensional ultrasound examinations were performed every two to three weeks on 27 fetuses between 20 and 40 weeks' gestation. Measurements of the total cerebellar volume and of the left and right cerebellar hemispheres were done using the multiplanar technique. Multilevel analysis was used to determine the growth of cerebellar volume based on individual developmental trajectories and compare the volume of the right and left hemispheres of the cerebellum. The intra- and interobserver reliability was calculated for the multiplanar and VOCAL techniques in a subgroup of 10 fetuses. A nonlinear growth curve of cerebellar volume in normal pregnancy was generated. The cerebellar growth per two-week decreased from a gain of 51% of the first measurement at 20 weeks to a gain of 16% of the first measurement at 38 weeks. The left cerebellar hemisphere was significantly larger (12.3%, p < 0.01) than the right. The intraclass correlation coefficient for the measurements by the two techniques was 0.99. Intraobserver reliability: the intraclass correlation coefficient for the measurements using the multiplanar technique was 0.96 and 0.97 and for VOCAL it was 0.98 and 0.97 for the two observers, respectively. Interobserver reliability: the intraclass correlation coefficient for the measurements using the multiplanar technique was 0.97 and for VOCAL 0.98. Longitudinal growth curves based on individual developmental trajectories were generated for the cerebellar volume. The left fetal cerebellar hemisphere was found to be significantly larger than the right. Both multiplanar and VOCAL techniques had a good intra- and interobserver reliability and yielded very similar results.
Ultrasound in medicine & biology 06/2009; 35(8):1284-9. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the performance of the first-trimester combined test between 2004 and 2006 compared to a previous period to investigate changes in time and identify reasons for sub-optimal performance.
Serum samples were analysed for pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorionic gonadotrophin (f beta-hCG). Nuchal translucency (NT) was measured between 10 and 14 weeks. Tests were considered screen positive, if their calculated Down syndrome (DS) risk was at least 1 in 250 at term.
A total of 20,293 singleton pregnancies were included in the analysis. The median maternal age fell from 35.7 to 34.3 years. The overall median weight-corrected multiple of the median (MoM) values of PAPP-A and f beta-hCG were 1.12 and 1.03, respectively. The median MoM value of NT was 0.89 and increased from 0.82 to 0.96. Sixty-six DS cases were detected by the screening test. The detection rate (DR) for DS was 75.9%, with a FPR of 3.3%.
The performance of the first-trimester test has improved over the years. A better performance of the NT measurement was the main reason, although NT assessment should further be improved. In addition, a better setting of the medians for the biochemical parameters may contribute to a higher DR.
[Show abstract][Hide abstract] ABSTRACT: To examine the predictive value of cervical length as measured by transvaginal sonography (TVS) in supine and upright maternal positions for the mode of delivery and induction-to-delivery interval after induction of labor at term, and to compare these measurements with the Bishop score and its predictive value.
TVS for cervical length measurement in the supine and upright positions and digital examination of the cervix were performed in 68 nulliparous and 34 parous women before induction of labor at term. In assessing the predictive value of the Bishop score and TVS parameters for a vaginal delivery after labor induction only nulliparous women were included in the analysis, since all the parous women delivered vaginally. Both nulliparous and parous women were included in the analysis of the induction-to-delivery interval. The method of labor induction, oxytocin or prostaglandin, was determined on the basis of the pre-induction Bishop score.
Logistic regression analysis showed in nulliparous women that only the cervical length measured in the upright position was a significant predictor of the need for Cesarean section (odds ratio 1.14; 95% CI, 1.02-1.27). The areas under the receiver-operating characteristics curve in predicting the need for Cesarean section because of failure to progress were higher for the cervical length, both in supine and upright positions, than for the Bishop score (0.66, 0.68 and 0.46, respectively). Only the Bishop score correlated significantly with the induction-to-delivery interval in both nulliparous and parous women. However, this may have been due to a selection bias, as no significant correlation with Bishop score was found when the oxytocin and prostaglandin induction-to-delivery intervals were analyzed separately.
Our results suggest that maternal postural change might improve the accuracy of sonographically-measured cervical length for predicting a vaginal delivery after induction of labor at term. However, our results need to be confirmed in a larger and more homogeneous population.
Ultrasound in Obstetrics and Gynecology 02/2009; 33(2):213-20. · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective. Our objective was to investigate the outcome of neonates with idiopathic polyhydramnios in the first year after birth.
Methods. All patients diagnosed in the Erasmus Medical Centre Rotterdam and the University Medical Centre Utrecht between January 2000 and April 2005 with idiopathic polyhydramnios were studied. The outcome variables included mode of delivery, pre-term delivery, birth weight, macrosomia, large-for-gestational-age (weight > p90), neonatal or infant mortality and infant morbidity at 1 year after delivery. These were related to antenatal findings, including the onset of polyhydramnios and ultrasonographic evidence of macrosomia (estimated fetal weight > p90).
Results. Polyhydramnios was diagnosed at a mean gestational age (± s.d.) of 31.0 ± 4.9 weeks. The mean gestational age at birth (± s.d.) was 37.9+3.7 weeks. Macrosomia at birth was present in 25.3% (22/88). Sixty-three of 88 infants were in good health 1 year after birth; 20 infants had an abnormality and 5 children had died. Macrosomia and detection of polyhydramnios in the third trimester was associated significantly with a good outcome.
Conclusion. In neonates with idiopathic polyhydramnios, abnormalities were detected during the first year of life in 28.4%. Detection of polyhydramnios in the second trimester and low or normal birth weight are risk factors for associated abnormalities.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 12/2008; · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This report provides an overview of 15 years prenatal screening for Down syndrome (DS).
Between 1991 and 2005, blood samples for the triple test were sent for analysis to our laboratory. Test results were considered screen-positive for neural tube defects (NTDs) if the serum alpha-1-fetoprotein > or = 2.50 MoM for singleton pregnancies or screen-positive for DS if the calculated risk was at least 1 in 250.
As many as 42 554 tests were performed. Data on the pregnancy outcome were available for 30 290 screening tests (71.2%). In 1991, most requests (93%) came from the university hospitals; thereafter a shift toward midwives occurred. Until 2001, the number of requests rose to 3500 a year. Most samples were collected between 15 and 17 weeks of gestation. The median age of women for whom a test was requested increased from 30.5 to 34.5. The detection rate (DR) for DS remained stable over the years (80%), with a false positive rate of about 13%. The DR for Trisomy 13, 18, and NTD was 50, 68, and 70%, respectively.
Based on the results of this study, the triple test may be considered a fairly good second trimester screening test. Here it is shown that health practitioners got more acquainted with the test through the years. This may have served the swift introduction of a formal national screening program that started in January 2007.
[Show abstract][Hide abstract] ABSTRACT: To investigate the reliability of, and patient satisfaction with, transperineal cervical length measurement during the third trimester of pregnancy and to compare these with measurement during the mid-trimester, using transvaginal sonographic imaging of the cervix as a reference.
Women attending an outpatient clinic for cervical length measurement before 29 weeks or after 35 weeks of gestation were examined by transvaginal and transperineal ultrasound and the results compared. Preference for either method was indicated by both sonographers and patients.
Seventy-one patients participated in the study, 23 in the second and 48 in the third trimester of pregnancy. There was failure to obtain a clear image on transperineal ultrasound in 30% of mid-trimester pregnancies, and in 19% of third-trimester cases. Elevation of the patient's hips improved the image in five out of 10 women in whom the scan was repeated following a postural change. Transvaginal cervical length measurements could be obtained in all cases. There was a strong correlation between transvaginal and transperineal measured cervical length (Pearson's correlation coefficient = 0.85). Sonographers preferred transvaginal images of the cervix irrespective of whether they were obtained in the second or third trimester. Transperineal ultrasound was judged as not or mildly painful by most women, but transvaginal ultrasound was preferred.
Transvaginal ultrasound is the least painful, most feasible, and probably most accurate method with which to measure cervical length in the third trimester of pregnancy. Transperineal ultrasound is a feasible alternative, although its application in clinical practice is restricted by the need for an experienced sonographer.
Ultrasound in Obstetrics and Gynecology 10/2008; 32(5):657-62. · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether estimation of gestational age (GA) in the context of first-trimester Down syndrome screening is standardized in the Netherlands.
This was a retrospective study, carried out between January 2005 and December 2006, of women who underwent first-trimester Down syndrome screening (n = 40,730) based on GA, maternal serum analysis and nuchal translucency (NT) measurement. Date of the last menstrual period (LMP), dating scan information including measurement of crown-rump length (CRL), NT thickness and name of the sonographer were recorded for all pregnancies. The accuracy of estimation of GA was evaluated by comparing the GA based on the LMP with that estimated from the CRL, using relevant subsets of the database. A survey of 104 sonographers was performed to further investigate the findings of the preceding analysis.
In 44% of all first-trimester combined tests the estimation of GA was based on the dating scan; the method of determination of GA was unknown in 23%. In 15% of all cases a dating scan was recorded but was not used to provide the estimation of GA at blood sampling. Detailed analysis showed that a consistent methodology for the estimation of GA from CRL was not maintained within hospitals and obstetric practices. For a single CRL, the reported GA differed by up to 10 days. Finally, it was demonstrated that individual sonographers reported different GAs for a given CRL.
Currently, estimation of GA in the first trimester in the Netherlands is not standardized. To improve the performance of prenatal screening for Down syndrome, estimation of GA should be based on ultrasound examination, with one nationally accepted CRL curve.
Ultrasound in Obstetrics and Gynecology 09/2008; 32(5):607-11. · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to predict spontaneous onset of labor by serial transvaginal ultrasound measurement of cervical length (CL) in a homogeneous population of nulliparous women at term.
162 nulliparous women with singleton fetuses in cephalic presentation were examined at weekly intervals from 36 weeks' gestation to delivery. CL was measured by transvaginal ultrasound in the supine and upright positions.
There was a significant decrease in CL in the last 12 days prior to delivery. However, this decrease was small with substantial variation between individuals. Women with spontaneous onset of labor could be divided into three different groups: those with unchanged CL before delivery; those with a fall in CL in the last 2 weeks prior to delivery; and those with a gradual change in CL starting before the last 2 weeks prior to delivery. A single CL measurement below 30 mm between 37 and 38 weeks of gestation predicted spontaneous onset of labor before 41 weeks' gestation with a sensitivity of 46%, specificity of 78%, positive predictive value (PPV) of 82%, negative predictive value (NPV) of 40% in the supine position; and sensitivity of 53%, specificity of 72%, PPV of 81%, NPV of 40% in the upright position.
Between 37 and 38 weeks' gestation, spontaneous onset of labor before 41 weeks can be predicted by a CL measurement, but with low sensitivity and NPV. Inter-individual variations in CL and in CL changes are large, which hampers the value of single and repeated CL measurements for the prediction of spontaneous onset of labor at term.
Ultrasound in Obstetrics and Gynecology 09/2008; 32(5):652-6. · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the 36th week of gestation a large aortico-right ventricular tunnel with an otherwise structurally normal heart was diagnosed by fetal echocardiography. This report describes for the first time the impact of the timely prenatal diagnosis of an aortico-right ventricular tunnel followed by successful management in early infancy.
Fetal Diagnosis and Therapy 02/2007; 22(5):335-8. · 2.30 Impact Factor