Abstract
ECLAMC: Latin American Study of Congenital Malformations examined 4,157,224 births (1967–2000), detecting 370 newborns with suspected holoprosencephaly (HPE): 182 (49.2%) had only craniofacial defects; 99 (26.8%) had defects in other systems; (15.1%) had chromosomal anomalies; 5 (1.4%) had recognized syndromes; and 28 (7.6%) had isolated median cleft lip. The latter group was excluded from subsequent analyses because of epidemiological differences from the other groups. The birth prevalence rate (BPR) of isolated HPE was homogeneous among the 11 sampled countries, increasing from 0.5/10,000 births to 1/10,000 births between 1967 and 2000, suggesting improved ascertainment, mainly after 1996. Microtia, cleft lip/palate, and microstomia were preferentially associated with HPE, but cleft palate only was not. Maternal diabetes was more prevalent in HPE than in controls when adding the isolated and associated groups (OR: 3.5; 95% CI: 0.9–16.2). Maternal flu was more prevalent in isolated HPE (OR: 3.6; 0.9–16.6) and in isolated plus associated HPE (OR: 2.8; 1.0–7.9) than in controls. A second series of better documented HPE cases, 179 in number (2.2/10,000), ascertained from 827,968 births occurring from 2000 to 2003, was used for phenotypic definition of cerebral and facial anomalies. In 83 of 174 HPE cases with specified cerebral defects, 40% were alobar, 43% were semilobar, and 17% were lobar. All cases of cyclopia, ethmocephaly, and cebocephaly were of the alobar or semilobar types. Female excess occurred in the total sample, but not within the subgroups themselves because of their small sample sizes. Neither alobar HPE nor cyclopia was associated with female predilection. Among the 174 HPE cases, 39% had neither oral clefting nor a severe dysmorphic face. Of facial phenotypes, 26% had cyclopia, ethmocephaly, or cebocephaly; 25% had premaxillary agenesis; and 10% had cleft lip and palate or cleft palate only. Cyclopia was not associated with oral clefts; 6 of 8 cases of ethmocephaly had cleft palate; 6 of 20 cases of cebocephaly had oral clefts; 4 of 20 cases had premaxillary agenesis; and 2 of 20 cases had cleft palate. © 2007 Wiley‐Liss, Inc.