An Examination of Familial Data for Associated Birth-order Effects in the Presence of Malformations of the Central Nervous System.

INTRODUCTION A number of investigations have been made of the estimation of the incidence of central nervous system (CNS) malformations. Several of these studies (e.g. McKeown and Record, Ciba Foundation, 1960) have stressed the association of malformations (e.g. spina bifida with anencephalus or hydrocephalus). The possible effects of birth order upon these malformations have been commented upon by several authors, but the conclusions seem to vary according to the author. Thus Record and McKeown (1949), on the basis of their examination of 930 cases of malformations in Birmingham, considered that the risk of a CNS malformation increased considerably at the first parity and beyond the sixth, but was approximately constant in the interval. These authors stated that maternal age did not appear to be associated with the incidence of malformations. On the other hand, Ingalls, Pugh, and McMahon (1954), in their study of Rhode Island hospital data, stated that for anencephalus and spina bifida the incidence appeared to drop from the first to the second parity, but then increased with subsequent sibs. The analysis of Scottish data by Edwards (1958) suggests an increased risk in primogeniture for anencephalus but further analysis for spina bifida and hydrocephalus was not done in view of limited data. It is of interest therefore to examine systematically certain available series of family data for the occurrence of possibly significant birth-order effects, especially when two or more sibs were affected with various CNS malformations. The familial data examined using a common classification of CNS malformations are set out in Table I: