title: Preferential associations between oral clefts and other major congenital anomalies.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: ECLAMC (Latin American Collaborative Study of Congenital Malformations) at Hospital Materno Infantil Ramón Sardá, Buenos Aires, Argentina. mrittler@fibertel.com.ar
authors.forename: Monica
authors.initials: M
authors.lastname: Rittler
authors.forename: Jorge S
authors.initials: JS
authors.lastname: López-Camelo
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castilla
authors.forename: Eva
authors.initials: E
authors.lastname: Bermejo
authors.forename: Guido
authors.initials: G
authors.lastname: Cocchi
authors.forename: Adolfo
authors.initials: A
authors.lastname: Correa
authors.forename: Melinda
authors.initials: M
authors.lastname: Csaky-Szunyogh
authors.forename: Ron
authors.initials: R
authors.lastname: Danderfer
authors.forename: Catherine
authors.initials: C
authors.lastname: De Vigan
authors.forename: Hermien
authors.initials: H
authors.lastname: De Walle
authors.forename: Maria
authors.initials: M
authors.lastname: da Graça Dutra
authors.forename: Fumiki
authors.initials: F
authors.lastname: Hirahara
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Frías
authors.forename: Paul
authors.initials: P
authors.lastname: Merlob
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Mutchinick
authors.forename: Annukka
authors.initials: A
authors.lastname: Ritvanen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Robert-Gnansia
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Scarano
authors.forename: Csaba
authors.initials: C
authors.lastname: Siffel
authors.forename: Claude
authors.initials: C
authors.lastname: Stoll
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Mastroiacovo
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology*; D000757:Anencephaly / Q000453:epidemiology; D001006:Anus, Imperforate / Q000453:epidemiology; D002971:Cleft Lip / Q000453:epidemiology*; D002972:Cleft Palate / Q000453:epidemiology*; D003025:Clubfoot / Q000453:epidemiology; D000013:Congenital Abnormalities / Q000453:epidemiology; D004423:Ear / Q000002:abnormalities; D004677:Encephalocele / Q000453:epidemiology; D014943:Global Health; D006330:Heart Defects, Congenital / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000002:abnormalities; D011159:Population Surveillance; D012042:Registries / Q000706:statistics & numerical data; D016135:Spinal Dysraphism / Q000453:epidemiology; D013131:Spine / Q000002:abnormalities; D050497:Stillbirth / Q000453:epidemiology; D014138:Tracheoesophageal Fistula / Q000453:epidemiology