Preferential associations between oral clefts and other major congenital anomalies.
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.
Rittler
Monica
M
ECLAMC (Latin American Collaborative Study of Congenital Malformations) at Hospital Materno Infantil Ramón Sardá, Buenos Aires, Argentina. mrittler@fibertel.com.ar
López-Camelo
Jorge S
JS
Castilla
Eduardo E
EE
Bermejo
Eva
E
Cocchi
Guido
G
Correa
Adolfo
A
Csaky-Szunyogh
Melinda
M
Danderfer
Ron
R
De Vigan
Catherine
C
De Walle
Hermien
H
da Graça Dutra
Maria
M
Hirahara
Fumiki
F
Martínez-Frías
María Luisa
ML
Merlob
Paul
P
Mutchinick
Osvaldo
O
Ritvanen
Annukka
A
Robert-Gnansia
Elisabeth
E
Scarano
Gioacchino
G
Siffel
Csaba
C
Stoll
Claude
C
Mastroiacovo
Pierpaolo
P
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