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Objective:  To investigate the predictive value of maternal serum pregnancy-associated plasma protein A (PAPP-A), free β subunit of human chorionic gonadotrophin (fβ-hCG), placental protein 13 (PP13), placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12), for first-trimester identification of early-onset pre-eclampsia., Design:   Nested case-control study., Setting:   Routine first-trimester screening for trisomy 21 in the Netherlands., Population:   Eighty-eight women who developed pre-eclampsia or haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 34 weeks of gestation and 480 controls., Methods:   PP13, PlGF and ADAM12 were measured in stored first-trimester serum, previously tested for PAPP-A and fβ-hCG. All marker levels were expressed in multiples of the gestation-specific normal median (MoMs). Model predicted detection rates for fixed false-positive rates were obtained for statistically significant markers alone and in combination., Main Outcome Measures:   Development of pre-eclampsia or HELLP syndrome., Results:  PP13 and PlGF were reduced in women with pre-eclampsia, with medians 0.68 MoM and 0.73 MoM respectively (P < 0.0001 for both). PAPP-A was reduced (median 0.82 MoM, P < 0.02) whereas ADAM12 and fβ-hCG did not differ between control women and those with pre-eclampsia. In pre-eclampsia complicated by a small-for-gestational-age fetus, all markers except fβ-hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model-predicted pre-eclampsia detection rate for a combination of PP13 and PlGF was 44% and 54%, respectively, for a fixed 5% and 10% false-positive rate., Conclusion:  This study demonstrates that PP13 and PlGF in the first-trimester might be promising markers in risk assessment for early pre-eclampsia/HELLP syndrome but for an adequate screening test additional characteristics are necessary.

Objective: The Dutch Centre for Population Research has specified quality demands for nuchal translucency (NT) measurement in The Netherlands. We performed an analysis of the quality of NT measurement in 2005-2006 and its influence on screening performance., Methods: This was a retrospective study of records of NT measurements (n = 27,738) obtained between January 2005 and December 2006 retrieved from the Dutch National Institute for Public Health and the Environment (RIVM). The performance of each individual operator was analyzed with regard to the quality standards, which involved calculation of operator-specific median NT-multiples of the median (MoM) values. For the entire population of operators, a curve was determined describing the relationship between crown-rump length and NT. Detection rates (DR) and false-positive rates (FPR) for Down syndrome were modeled with this new curve and compared to those originally obtained using previously published reference data., Results: Only 22% of all operators met the quality requirement of performing more than 150 NT measurements per year. However, no relationship was found between the number of measurements per operator and their median NT-MoM. The mean of all operator-specific median NT-MoM values was 0.94 (target value 1.0). Overall, operators with The Fetal Medicine Foundation certificate measured a significantly higher median NT-MoM (mean of operator-specific medians, 0.98) as compared to the non-certified operators (0.92). During the study period, the monthly median NT-MoM of all operators rose steadily, from 0.86 in January 2005 to 0.96 in December 2006. Recalculation of the risk for Down syndrome after adjusting the reference NT medians using our own data led to a modeled 4% increase in DR at a 5% FPR., Conclusion: Improved monitoring of NT measurement put into effect during the study period seems to have led to an improvement in the accuracy of measurements. Strict quality demands, continued monitoring and scrupulous evaluation of individual operators is likely to lead to an even better performance.

Objectives: To determine whether children with prenatally diagnosed mild pyelectasis have more urinary tract morbidity during childhood than children without this finding., Methods: Case-control study in children with pyelectasis (anteroposterior diameter of the fetal renal pelvis of 5-10 mm). A validated questionnaire was sent to the parents of 208 cases and 416 matched controls., Results: The questionnaire was returned by 146 cases and 250 controls. There was a male predominance in the case group (p = < 0.0001). There was no difference in voiding habits or in prevalence of urinary tract infections (UTI). The prevalence of UTI was high: 11.6% in cases and 10.0% in controls. The only difference was a higher prevalence of constipation in the case group (p = 0.003). Postnatally, 41 children had an ultrasound examination and 16 were referred to a paediatrician or urologist: 3 had persisting pyelectasis, 3 had a recurrent UTI and 1 required surgery (a pyeloplasty). Four of the controls were referred to a paediatrician or urologist: 3 had recurrent UTI and 1 had urinary incontinence., Conclusion: Children with a mild fetal pyelectasis do not have more urinary tract morbidity during childhood than children without this finding. Therefore, there seems to be no need for additional investigation after birth., (Copyright 2005 John Wiley & Sons, Ltd.)

Objectives: To determine the incidence and type of associated urogenital anomalies in children with a unilateral multicystic kidney and to assess in children with nephrectomy the additional diagnostic value of cystoscopy and, in girls, of colposcopy., Methods: This was a follow-up study of 100 fetuses with antenatally detected unilateral multicystic kidneys. After ultrasound confirmation of the diagnosis within a few days after birth voiding cystourethrography and isotope scan were performed in 83 of the surviving children to exclude vesicoureteral reflux and to establish renal function. Eighty-one children underwent nephrectomy and, prior to surgery, all underwent cystoscopy and girls also underwent colposcopy., Results: Seventy-five children had one or more additional urogenital anomalies: 39 had anomalies of the contralateral kidney, 40 had anomalies of the ipsilateral kidney and 30 had one or more anomalies of the lower urogenital tract. With cystoscopy 54 anomalies of the genitourinary tract were detected in 48 children and with colposcopy three anomalies were detected in 35 girls. Eighty-one children had a nephrectomy or heminephrectomy and 33 of them needed other urological intervention. Thirteen fetuses died (mostly from agenesis of the contralateral kidney) and six infants had no surgery at all., Conclusion: Children with a unilateral multicystic kidney are at considerable risk of having other urogenital anomalies. When cystoscopy and colposcopy are added to routine investigations the rate of detection of anomalies is 75%, twice that reported in the literature., (Copyright 2005 ISUOG)

Objective: To determine the long-term prognosis of antenatally detected renal tract anomalies in order to optimize parental counseling., Methods: This was a follow-up study of all renal tract abnormalities detected antenatally in a Level 3 ultrasound department between 1986 and 2001. Follow-up data (median age, 8 years) were retrieved from the records of the Paediatric Urology Department or the attending pediatrician., Results: A urinary tract anomaly was detected in 408 fetuses. There were four false-positive diagnoses. From two children follow-up data were incomplete, leaving 402 cases for analysis. A chromosomal abnormality was present in 7/81 (8.6%) fetuses that had karyotyping. Termination of pregnancy was performed in 55 (13.7%) cases and a further 66 (16.4%) children died during the perinatal period and up to 1 year of age. In 106/121 (26.4% of all fetuses) deceased children the cause of death was directly related to the renal tract anomaly. In the 281 surviving children a total of 545 renal tract anomalies were diagnosed postnatally, requiring a total of 381 surgical interventions in 156 infants. Outcome in survivors was generally good, with impaired renal function in nine infants and hypertension in three (4% of the survivors)., Conclusions: Congenital renal tract anomalies are associated with a high mortality rate, especially when they are structural developmental anomalies of the kidneys. Survivors require multiple operations, but the outcome is generally favorable. Ultrasound diagnosis, especially when made early, of non-lethal urinary tract anomalies may prevent additional renal damage by timing of delivery and early postnatal treatment., (Copyright 2005 ISUOG.)

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., (Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd.)

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.

Objectives: To determine whether classification of discordant growth between fetal twins allows risk stratification in monochorionic twin pregnancies., Methods: In 12 twin-to-twin transfusion syndrome (TTTS) pregnancies and 12 cases that were suspected of developing the syndrome, fetal growth was determined by serial standard sonography. Fetal growth was expressed as the difference-average-ratio (DAR), defined as the difference in estimated fetal weight between both twins divided by their average weight. In each case, we determined the maximum value of DAR and the rate of change of DAR using a least squares linear fit of the estimated fetal weights., Results: For the TTTS cases the maximum value of DAR was 0.44 +/- 0.21 versus 0.52 +/- 0.13 for the suspected TTTS cases (P = 0.25). The rate of change of DAR was 0.052 +/- 0.034 per week for the TTTS versus 0.0055 +/- 0.0092 for the suspected TTTS cases (P = 0.0004). After laser therapy, DAR decreased in four successful cases, with a rate of change of -0.0146 +/- 0.0093 per week, but increased further in one unsuccessful case, due to patent anastomoses. In the seven TTTS cases treated with amnioreduction, DAR did not decrease; in one of two suspected TTTS cases the DAR decreased slightly. In the nine amnioreduction cases, the average rate of change of DAR was 0.067 +/- 0.083 per week. This was significantly different from the four successful laser cases (P = 0.01)., Conclusions: The rate of change of DAR, but not DAR itself, has prognostic value for the development of suspected TTTS pregnancies, for the onset and severity of TTTS and for the efficacy of therapy. This parameter is derived from routine sonography examination and may contribute to risk stratification in monochorionic twin pregnancies.