Seasonality of pre-ovulatory non-disjunction and the aetiology of Down syndrome. A European collaborative study.

Six series of patients with Down syndrome (DS) from different European countries, altogether 287 cases, were divided into four categories according to parental origin of the additional chromosome 21 and meiotic division in which the nondisjunction had occurred. The monthly birth or conception frequencies per category were analysed by graph and compared with the total birth curve by Watson's adaptation of the Kolmogorov-Smirnov statistic for cyclic trends. Unexpectedly, the non-disjunctions during maternal meiosis I (63%), by far the largest category, occurred more frequently during the seasonal "restoration" and "inhibition" phase of the "ovulatory seasons" and less frequently when the ovulation rate is stabilized. The graph of the maternal meiosis II patients (17%) also seemed to conform to this phenomenon, though less obviously. In contrast to this, the paternal DS graph (20%) was very divergent, although a seasonal cluster of non-disjunctions may also occur here. From these findings a seasonal disturbance of preovulatory ripening of the ovum emerges as a possible cause of the first (and second) meiotic non-disjunction. Seasonal periodicity of the prolactin concentration in women and "transient hyperprolactinaemia", shown to be allied to delayed ovulation, may be related to these seasonal DS conception clusters.