Multiple Congenital Anomalies after Assisted Reproductive Technology in Japan (between 2004 and 2009)

Multiple congenital anomalies (MCAs) are defined as two or more unrelated major structural malformations that cannot be explained by an underlying syndrome or sequence. The percentage and combination patterns of MCAs were analyzed using the European surveillance of congenital anomalies computer algorithms for nationwide data on congenital anomalies after assisted reproductive technology between 2004 and 2009 in Japan. There were a total of 177,548 pregnancies and 124,846 live births. About 7% (96/1,324) were MCAs. Although most maternal/neonatal outcomes between the isolated cases group and the MCAs group were similar, higher early neonatal death rate was observed in the MCAs group than in the isolated cases group (9.8% versus 3.7%, resp.). Regarding the major organ system subcategory in ICD-10, the rate of MCAs was around 30% in “congenital malformations of eye, ear, face, and neck,” “congenital malformations of the respiratory system,” and “congenital malformations of genital organs.” On the other hand, the rate of MCAs was less than 10% in “congenital malformations of the circulatory system.” The combination patterns of diseases were widely varied. Of them, two or three diseases of the circulatory system, the digestive system, and the musculoskeletal system tended to co-occur in the same individuals. 1. Introduction Association among congenital malformations is a concept introduced to designate the nonrandom tendency of some malformations to occur together more often than expected by chance, without being components of known syndromes [1]. The utility of monitoring for patterns of multiple congenital anomalies (MCAs) has been increasingly recognized [2–6]. The possible reasons for this association are the results of known syndromes, as a consequence of a single primary anomaly, and known or unknown factors causing MCAs. This kind of coexistence is called comorbidity in general, and it is important to clarify the genetic/environmental background of associated malformations. According to Garne et al. [7], MCAs are defined as two or more unrelated major structural malformations that cannot be explained by an underlying syndrome or sequence. Since etiologic heterogeneity may complicate epidemiologic analyses designed to identify risk factors for congenital anomalies, case classification, which uses knowledge of embryologic and pathogenic mechanisms [8], is important to make case groups more homogeneous [9]. Wellesley et al. [10] produced a hierarchical method of classifying congenital anomalies into eight groups for inclusion of the source of data