United States and European consensus views differ on the place of routine ultrasound scans during pregnancy and the validity of such scans as screening tests for fetal malformations in the general population is still under debate. Four ultrasound laboratories from Obstetric and Gynecology departments of Belgian University hospitals and affiliated hospitals have conducted a prospective study from 1984 to 1989 to compare the anomalies discovered in ultrasonic screening of the fetus with the anomalies of the neonates. Of 16,370 pregnant women at normal risk for congenital anomalies attending the antenatal clinics of these hospitals, 16,072 have had at least one ultrasound screening for congenital anomalies (98.5%). Congenital anomalies, single or multiple and 'minor' or 'major', were clearly defined in order to allow comparisons. The excluded congenital anomalies were listed as defined in the Eurocat Register. A total of 381 fetuses (2.3%) were structurally abnormal. Of the 381, 154 were correctly detected by ultrasound (sensitivity 40.4%). Altogether 15,972 fetuses were true negatives (specificity 99.9%). Eight (0.05%) were false positive for congenital anomalies. The positive predictive value was 95.1% and the negative predictive value was 98.6%. Ultrasound diagnoses were correctly achieved before 23 weeks of gestation for 21% of the anomalies. The gestational age, operator and technical dependence of ultrasound screening for congenital anomalies is discussed.

Five ultrasound laboratories from Obstetrics and Gynecology departments of Belgian university hospitals or affiliated institutions conducted a prospective study from 1984 to 1992 in which the results of prenatal ultrasound examinations were compared to examination reports of the neonates. The results of the period 1984-89 (PI) have been published previously, and those of the period 1990-92 (PII) are presented here. Some very minor congenital anomalies, as listed and defined in the EUROCAT Register, were excluded. Of 26,147 pregnant women at normal risk for congenital anomalies, 25,046 had at least one ultrasound scan (96%). A total of 616 fetuses were structurally abnormal (prevalence 2.42%), and 685 abnormalities were recorded. The sensitivity of the ultrasound test was 40.4% in PI and 51.1% in PII for abnormal fetuses (p < 0.05), and 45% (PI) and 64% (PII) for abnormalities (p < 0.01). The specificity was 99.9% and the positive and negative predictive values were 94.2% and 98.6%, respectively; these values did not differ significantly between the two periods. The sensitivity for the detection of anomalies before 23 weeks increased from 21% in PI to 41% in PII, indicating an improvement in the early detection of fetal abnormalities.

Perinatal outcome of pregnancies caused by assisted reproduction technique (ART) is substantially worse when compared with pregnancies following natural conception. We investigated the possible risks of non-IVF ART on perinatal health. We conducted a retrospective cohort study with two exposure groups: a study group of pregnancies after controlled ovarian stimulation (COS), with or without artificial insemination (AI), and a naturally conceived comparison group. We used the data from the regional registry of all hospital deliveries in the Dutch-speaking part of Belgium during the period from January 1993 until December 2003 to investigate differences in perinatal outcome of singleton and twin pregnancies. 12 021 singleton and 3108 twin births could be selected. Naturally conceived subjects were matched for maternal age, parity, fetal sex and year of birth. The main outcome measures were duration of pregnancy, birth weight, perinatal morbidity and perinatal mortality. Our overall results showed a significantly higher incidence of prematurity (<32 and <37 weeks), low and very low birth weight, transfer to the neonatal intensive care unit and most neonatal morbidity parameters for COS/AI singletons. Twin pregnancies resulting from COS/AI showed an increased rate of neonatal mortality, assisted ventilation and respiratory distress syndrome. After excluding same-sex twin sets, COS/AI twin pregnancies were at increased risk for extreme prematurity and very low birth weight. In conclusion, COS/AI singleton and twin pregnancies are significantly disadvantaged compared to naturally conceived children.

Original research article INTRODUCTIONConventional karyotyping has been considered the gold standard for routine prenatal genetic diagnosis for many decades now, allowing for microscopic visualization and inspection of chromosomes and thus detection of numerical and structural chromosomal rearrangements. The main limitations are the resolution achieved by G-banding, which is limited to 5-10 Mb at best, and the requirement for cultured cells, needing a minimum of 8-10 days. The introduction of targeted methods of analysis such as fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) overcome the time constraints and resolution limitations inherent to karyotyping but do not provide a genome-wide analysis.1 More recently, molecular karyotyping using genomic microarrays has reached mainstream use in the postnatal diagnostic setting, providing a genome-wide screen for genomic imbalances at a far superior resolution to karyotyping.2 A number of studies have demonstrated the feasibility of prenatal diagnosis by genomic arrays using a variety of platforms, 3-7 but challenges remain in applying high-resolution genomic arrays to prenatal diagnosis. 6,8,9 One of the major ethical issues often raised is how to deal with variants of uncertain significance (VOUS) or risk loci, the detection of which leads to additional challenges for genetic counseling of parents. Furthermore, array analysis may reveal an imbalance for known "risk loci" where the future penetrance is uncertain or may be associated with variable expression. The penetrance risks for a number of recurrent copy-number variations (CNVs) have been estimated based on the frequencies in patients and controls. [10][11][12] However, although it is possible to calculate a populationbased risk, it is impossible in the prenatal setting to predict the phenotypic outcome in the child. Purpose:To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound. Methods: Patients referred for prenatal diagnosis due to ultrasound anomalies underwent analysis by array comparative genomic hybridization as the first-tier diagnostic test.Results: A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization. Array analysis revealed causal imbalances in a total of 9.6% of patients (n = 37). Submicroscopic copy-number variations were detected in 2.6% of patients (n = 10/37), and arrays added valuable information over conventional karyotyping in 3.9% of patients (n = 15/37). We highlight a novel advantage of arrays; a 500-kb paternal insertional translocation is the likely driver of a de novo unbalanced translocation, thus improving recurrence risk calculation in this family. Variants of uncertain significance were revealed in 1.6% of patients (n = 6/383). Conclusion:We demonstrate the added value of chromosomal microarrays for prenatal diagnosis in the presence of ultrasound anomalies. We advocate reporting back on...

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