Implementation of the INTERGROWTH-21st Project in Brazil.

The Latin American site in the INTERGROWTH-21(st) Project was Pelotas, Brazil, with approximately 4000 births per year. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from four hospitals, covering 99% of births in the city. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from one of the largest private ultrasound clinics in the city and 30 smaller, private, antenatal clinics serving middle to high socio-economic status women. Among this site's major challenges was the recruitment of women for FGLS from numerous different clinics. Several public relations activities were conducted to improve collaborative efforts between the research team and obstetricians, paediatricians and community leaders in Pelotas.

Standardization of fetal ultrasound biometry measurements: improving the quality and consistency of measurements.

OBJECTIVE: To assess whether a standardization exercise prior to commencing a fetal growth study involving multiple sonographers can reduce interobserver variation. METHODS: In preparation for an international study assessing fetal growth, nine experienced sonographers from eight countries participated in a standardization exercise consisting of theoretical and practical sessions. Each performed a set of seven standard fetal measurements on pregnant volunteers at 20-37 weeks' gestation, and these were repeated by the lead sonographer; all measurements were taken in a blinded fashion. After this the sonographers had hands-on practice and feedback sessions on other volunteers. This process was repeated three times. Measurement differences between sonographers and the lead sonographer, expressed as a gestational-age-specific Z-score, between the first and third scans were compared using the Wilcoxon signed ranks test, and variance was assessed using Pitman's test. Interobserver agreement was also assessed using the intraclass correlation coefficient (ICC), and all images were scored for quality in a blinded fashion. RESULTS: At baseline the level of agreement and image scoring were high. A significant reduction in the differences between sonographers and the lead sonographer were seen for fetal biometry overall (head circumference, abdominal circumference and femur length) between the first and third scans (median Z-scores, 0.46 and 0.24; P = 0.005), and a reduction in the variance was also observed (P < 0.001). The ICCs for measurement pairs for every fetal measurement showed a clear trend of increasing ICC (better agreement) with consecutive training scan sessions, although no improvement in image scores was seen. CONCLUSION: Even for experienced sonographers, a standardization exercise before starting a study of fetal biometry can improve consistency of measurements. This could be of relevance for studies assessing fetal growth in multicenter sites.

7q35q36.3 deletion and concomitant 20q13.2q13.33 duplication in a newborn: familiar case.

OBJECTIVE: Array-CGH is a powerful tool in identifying and characterizing complex genomic rearrangements smaller than 5-10 megabase (Mb), for which classical cytogenetic approaches are not sensitive enough. The use of Array-CGH has increased of 10-20% the detection rate of unbalanced cryptic rearrangements, such as deletions and/or duplications. PATIENTS AND METHODS: We present here the first report of a patient with 7q35q36.3 microdeletion and concomitant 20q13.2q13.33 microduplication detected by array-CGH and confirmed by reiterative FISH experiments associated with dysmorphism, development delay, Long QT syndrome (LQTS), complex congenital heart disease, pulmonary hypertension, hypotonia, respiratory distress, cognitive deficit. RESULTS: We proved that this unbalanced rearrangement was due to an adjacent-1 segregation that occurred in the mother, carrier of a balanced translocation between chromosomes 7 and 20. The same unbalanced rearrangements were also found in the proband's maternal uncle, who had been given a clinical diagnosis of Dandy-Walker/Rubinstein-Taybi syndromes in the past. Given the above-mentioned observations, the proband's uncle is not affected by Dandy-Walker/Rubinstein-Taybi syndromes, but by a genomic syndrome highlighted by array-CGH. CONCLUSIONS: The Array-CGH allowed us to understand that the loss of several genes is expressed with clinical manifestations due to the concomitance of several syndromes, each related to the malfunction of a "specific disease gene". For these reasons, the genotype-phenotype correlation in these cases is more complex. This study confirms that the array-CGH is useful in identifying pathologies that were considered idiopathic until a few years ago.