Clinical epidemiology of skeletal dysplasias in South America.

Currently accepted birth prevalence for osteochondrodysplasias (OCD) of about 2/10,000 is based on few studies from small series of cases. We conducted a study based on more than 1.5 million births. OCD cases were detected from 1,544,496 births occurring and examined in 132 hospitals of ECLAMC (Latin American Collaborative Study of Congenital Malformations) between 2000 and 2007. Cases were detected and registered according to a pre-established protocol, and then ranked in four diagnostic evidence levels (DEL), according to available documentation. For the analysis of risk factors, a healthy control sample born in the same period was used. OCD was diagnosed in 492 newborns, resulting in a prevalence per 10,000 of 3.2 (95% CI: 2.9-3.5). Perinatal lethality (stillbirths plus early neonatal deaths) occurred in 50% of cases. Prenatal ultrasound diagnosis was made in 73% of cases (n = 359). Among 211 cases from the best documented group (DEL-1) and according to international classification, 33% of cases fit into the G-25 (osteogenesis imperfecta), 29% in Group-1 (FGFR3), and 8% in Group-18 (Bent bones). The prevalence of the main OCD types were: OI-0.74 (0.61-0.89); thanatophoric dysplasia-0.47 (0.36-0.59); and achondroplasia-0.44 (0.33-0.55). Paternal age (31.2 ± 8.5), parity (2.6), and parental consanguinity rate (5.4%) were higher in cases than in controls (P < 0.001). In conclusion, the OCD overall prevalence of 3.2 per 10,000 found seems to be more realistic than previous estimates. This study also confirmed the high perinatal mortality, and the association with high paternal age, parity, and parental consanguinity rate.

Conjoined twins: a worldwide collaborative epidemiological study of the International Clearinghouse for Birth Defects Surveillance and Research.

Conjoined twins (CT) are a very rare developmental accident of uncertain etiology. Prevalence has been previously estimated to be 1 in 50,000 to 1 in 100,000 births. The process by which monozygotic twins do not fully separate but form CT is not well understood. The purpose of the present study was to analyze diverse epidemiological aspects of CT, including the different variables listed in the Introduction Section of this issue of the Journal. The study was made possible using the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) structure. This multicenter worldwide research includes the largest sample of CT ever studied. A total of 383 carefully reviewed sets of CT obtained from 26,138,837 births reported by 21 Clearinghouse Surveillance Programs (SP) were included in the analysis. Total prevalence was 1.47 per 100,000 births (95% CI: 1.32-1.62). Salient findings including an evident variation in prevalence among SPs: a marked variation in the type of pregnancy outcome, a similarity in the proportion of CT types among programs: a significant female predominance in CT: particularly of the thoracopagus type and a significant male predominance in parapagus and parasitic types: significant differences in prevalence by ethnicity and an apparent increasing prevalence trend in South American countries. No genetic, environmental or demographic significant associated factors were identified. Further work in epidemiology and molecular research is necessary to understand the etiology and pathogenesis involved in the development of this fascinating phenomenon of nature.

Preferential associations between oral clefts and other major congenital anomalies.

OBJECTIVES: To identify preferential associations between oral clefts (CL = cleft lip only, CLP = cleft lip with cleft palate, CP = cleft palate) and nonoral cleft anomalies, to interpret them on clinical grounds, and, based on the patterns of associated defects, to establish whether CL and CLP are different conditions. DESIGN AND SETTINGS: Included were 1416 cleft cases (CL = 131, CLP = 565, CP = 720), among 8304 live- and stillborn infants with multiple congenital anomalies, from 6,559,028 births reported to the International Clearinghouse for Birth Defects Surveillance and Research by 15 registries between 1994 and 2004. Rates of associated anomalies were established, and multinomial logistic regressions applied to identify significant associations. RESULTS: Positive associations with clefts were observed for only a few defects, among which anencephaly, encephaloceles, club feet, and ear anomalies were the most outstanding. Anomalies negatively associated with clefts included congenital heart defects, VATER complex (vertebral defects, imperforate anus, tracheoesophageal fistula, and radial and renal dysplasia), and spina bifida. CONCLUSION: The strong association between all types of clefts and anencephaly seems to be attributable to cases with disruptions; the association between CP and club feet seems to be attributable to conditions with fetal akinesia. Some negative associations may depend on methodologic factors, while others, such as clefts with VATER components or clefts with spina bifida, may depend on biological factors. The different patterns of defects associated with CL and CLP, indicating different underlying mechanisms, suggest that CL and CLP reflect more than just variable degrees of severity, and that distinct pathways might be involved.

Reduction of birth prevalence rates of neural tube defects after folic acid fortification in Chile.

To verify whether the decreasing neural tube defects birth prevalence rates in Chile are due to folic acid fortification or to pre-existing decreasing trends, we performed a population survey using a network of Estudio Colaborativo Latino Americano de Malformaciones Congenitas (ECLAMC, Latin American Collaborative Study of Congenital Malformations) maternity hospitals in Chile, between the years 1982 and 2002. Within each maternity hospital, birth prevalence rates of spina bifida and anencephaly were calculated from two pre-fortification periods (1982-1989 and 1990-2000), and from one fortified period (2001-2002). There was no historical trend for spina bifida birth prevalence rates before folic acid fortification, and there was a 51% (minimum 27%, maximum 66%) decrease in the birth prevalence rates of this anomaly in the fortified period. The relative risks of spina bifida were homogeneous among hospitals in the two period comparisons. There was no historical trend for the birth prevalence of anencephaly comparing the two pre-fortified periods, but the relative risks were heterogeneous among hospitals in this comparison. There was a 42% (minimum 10%, maximum 63%) decrease in the birth prevalence rate of anencephaly in the fortified period as compared with the immediately pre-fortified period, with homogeneous relative risks among hospitals. Within the methodological constraints of this study we conclude that the birth prevalence rates for both spina bifida and anencephaly decreased as a result of folic acid fortification, without interference of decreasing secular trends.