Distributions of current and new first-trimester Down syndrome screening markers in twin pregnancies.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Placental protein 13 as a first trimester screening marker for aneuploidy.

OBJECTIVE: To determine whether Placental Protein 13 (PP13) could be an additional marker in first trimester screening for aneuploidies. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Fetal cerebellar volume and symmetry on 3-d ultrasound: volume measurement with multiplanar and vocal techniques.

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.

First-trimester Down syndrome screening performance in the Dutch population; how to achieve further improvement?

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Fifteen years of triple tests in The Netherlands; the life cycle of a screening test.

OBJECTIVE: This report provides an overview of 15 years prenatal screening for Down syndrome (DS). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Audit of prenatal and postnatal diagnosis of isolated open spina bifida in three university hospitals in The Netherlands.

OBJECTIVE: To audit the current Dutch policy of prenatal detection of isolated open spina bifida based on offering detailed ultrasound examination only on indication. METHODS: A retrospective analysis of prenatally diagnosed isolated spina bifida cases and of newborns diagnosed with this condition was carried out in three university hospitals. The data were collected from databases and clinical records of the departments of prenatal diagnosis, obstetrics, neonatology, child neurology and neurosurgery of the three centers. RESULTS: Between January 1996 and December 1999, 88 cases of isolated open spina bifida were diagnosed prenatally by ultrasound investigation. Thirty-eight cases (43%) were diagnosed before the 24th week of gestation. Of these, 35 (92%) ended in termination of the pregnancy at the parents' request. Of the remaining 50 cases (57%) diagnosed after the 24th week of gestation, eight (16%) pregnancies were terminated beyond the legal limit for termination due to the severity of the condition. Of the 88 cases of isolated spina bifida, 25 infants (28%) were still alive at the age of 4 years. In the same audit period 112 newborn infants with isolated open spina bifida were admitted to the neonatology, child neurology, or neurosurgery ward of the three centers. Of these cases, 47 (42%) had been diagnosed prenatally and 65 (58%) were an unexpected finding at birth. In 24 infants (21%) surgical treatment was withheld because of the severity of the condition and predicted poor outcome, whereas the remaining 88 infants (79%) underwent surgical repair. CONCLUSION: The current practice in The Netherlands of offering ultrasound screening to high-risk patients only leads to the early detection of a minority of cases of spina bifida. Most cases are diagnosed either after the 24th week of gestation or they remain undiagnosed until after birth. When spina bifida is diagnosed before the 24th week of gestation the vast majority of parents opt for termination. In order to reduce the birth prevalence of spina bifida in The Netherlands the introduction of a policy of routine ultrasound screening should be considered.

[Congenital complete atrioventricular block in children: pathogenesis and clinical outcomes]. / Het congenitale complete atrioventriculaire blok bij kinderen: pathogenese en kliniek.

Congenital complete atrioventricular block (CCAVB) is induced by the placental transmission of maternal anti-SS-A/Ro and anti-SS-B/La antibodies during the second trimester of pregnancy where they cause inflammatory injury to the foetal heart. Anti-SS-A/Ro and anti-SS-B/La antibodies can be detected in most mothers of children with CCAVB. However, the chance of an antibody-positive woman giving birth to a child with CCAVB is 1-5% and the chance of this recurring is 16%. In addition to the maternal antibodies, foetal and environmental factors may also play a role in the pathogenesis. CCAVB is associated with high morbidity and mortality during the foetal and neonatal period. Pacemaker implantation is indicated in approximately 60% of these children, after the development of symptoms related to bradycardia, although the timing of this is controversial. The effectiveness of therapeutic intervention in the uterus has yet to be determined. A conservative approach is advisable with respect to the use of corticosteroids.