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The most important step, however, is the determination of the relevance of the positive skin reaction observed, for which the potential cross reactions also should be considered

These previous studies [12,13,14,15,16,17] had several limitations such as the inclusion of relatively small number of cases, especially for rare type of congenital anomalies (i.e., being underpowered to detect small or moderate risk effect), the use of case-control design (i.e., being more prone to selection bias), or insufficient adjustment for potential confounders (i.e., being more prone to confounding bias)

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