Methodological approaches to evaluate teratogenic risk using birth defect registries: advantages and disadvantages

POLETTA, FA; LOPEZ-CAMELO, JORGE SANTIAGO; GILI, JA; LEONCINI, E; CASTILLA, E; MASTROIACOVO, P

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 vol. 7

1932-6203

Background: Different approaches have been used in case-control study designs to estimate maternal exposure to medications and the risk of birth defects. However, the performance of each design of birth-defect surveillance programmes has not yet been reported. The aim of this study was to evaluate the scope and limitations of three case-control approaches to assess the teratogenic risk of birth defects in mothers exposed to anti-epileptic drugs, insulin, or acetaminophen. Methodology/ Principal Findings: We studied 110,814 non-malformed newborns and 58,514 live newborns with birth defects who were registered by the Latin American Collaborative Study of Congenital Anomalies (ECLAMC) between 1967 and 2008. Four matched controls were selected for each case and three different control groups were used: healthy newborns (HEALTHY), malformed newborns (SICK), and exposed cases only (ECO). Lin?Ls concordance correlation coefficient (?Ïc) and the Bland-Altman limits of agreement were calculated as a measure of agreement between the three designs. There were no concordance correlations between the HEALTHY and ECO designs, and the average odds ratio differences ranged from 2.09 to 9.24 for the three evaluated medicines. The overestimations observed for HEALTHY design were increased as higher odds ratio values were given, with a high and statistically significant correlation between the difference and the mean. On the contrary, the concordance correlations obtained between the SICK and ECO designs were quite good, with no significant differences in the average risks. Conclusions: The HEALTHY method shows a high rate of false-positive results. The SICK and ECO methods do not estimate the true population risk except under certain assumptions. However, the SICK method is useful for determining the specificity of teratogenic agents, whereas the ECO method could be a good approach to estimate the aetiological heterogeneity of a defect under study.