Incidence of anencephalus, spina bifida, and hydrocephalus related to birth rank and maternal age.

Several investigators have stressed the importance of genetic factors in the aetiology of malformations of the central nervous system, and some have even advanced hypotheses describing the genetic mechanisms involved. Such hypotheses are speculative, and the role of environmental events should continue to receive evaluation. Association of characteristics of the offspring with birth order or with maternal age is provisional evidence of the operation of environmental influences in causation; in addition, such data may provide clues for the elucidation of the more specific environments involved. The weight of previously published evidence relating congenital malformations of the central nervous system to birth rank and maternal age suggests that both variables influence the occurrence of these anomalies. Penrose (1946), using a modification of the Greenwood-Yule method, found an increasing frequency of a group of central nervous malformations (anencephalus, spina bifida, and hydrocephalus) with advancing maternal age. After correction for the effect of maternal age, occurrence was somewhat excessive in the first birth rank and at birth ranks 7 and over. Malpas (1937) analysed the distribution of anencephaly (44 cases among 13,964 deliveries) according to maternal age, and found the defect to occur about ten times more frequently in the age group 46-50 than in the age group 16-20. Book and Rayner (1950) surveyed the protocols of 67 cases of anencephaly without finding any significant relation of the defect to advancing age or birth rank. Schwidde (1952) and Polman (1950) have also reported negative findings. Buchi (1950) identified 2,922 malformed infants among some 160,000 births