RESUMO
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.
Assuntos
Anormalidades Múltiplas/epidemiologia , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Anencefalia/epidemiologia , Anus Imperfurado/epidemiologia , Pé Torto Equinovaro/epidemiologia , Anormalidades Congênitas/epidemiologia , Orelha/anormalidades , Encefalocele/epidemiologia , Saúde Global , Cardiopatias Congênitas/epidemiologia , Humanos , Recém-Nascido , Rim/anormalidades , Vigilância da População , Sistema de Registros/estatística & dados numéricos , Disrafismo Espinal/epidemiologia , Coluna Vertebral/anormalidades , Natimorto/epidemiologia , Fístula Traqueoesofágica/epidemiologiaRESUMO
Nausea and vomiting are very common during pregnancy, mainly throughout the first trimester. Metoclopramide is a dopamine receptor blocking drug that is commonly used to treat nausea and vomiting. The aim of this prospective study was to investigate the effect on the fetus of intrauterine exposure to metoclopramide. One hundred and seventy-five women who received metoclopramide and consulted 6 teratogen information centers in Israel, Italy, Brazil, and Canada were studied. Women exposed to metoclopramide were paired for age, smoking and alcohol consumption habits with women exposed to nonteratogens. Women in the metoclopramide group had a significantly higher rate of premature births (8.1%) as compared with the control group (2.4%) ( p = 0.02, relative risk = 3.37, 95% confidence interval 1.12-10.12). Rates of major malformations in the metoclopramide group (4.4%) did not differ from controls (4.8%) ( p = 0.84, relative risk = 0.91, 95% confidence interval 0.34-2.45). According to our findings, metoclopramide use during the first trimester of pregnancy does not appear to be associated with an increased risk of malformations, spontaneous abortions, or decreased birth weight, however, larger studies are needed to confirm these observations.