Brian MacMahon

THE FAMILIAL INCIDENCE OF CONGENITAL MALFORMATION OF THE HEART

It is generally believed that the incidence of congenital malformation of the heart is raised in relatives of affected individuals. The evidence in support of this view consists mainly of isolated records of families with more than one affected member (Courter et al., 1948, refer to 63 reported cases), but a few examples have been noted in the course of investigations of large series of patients (for example, by Abbott, 1927; Dogramaci and Green, 1947; Campbell, 1949; and Lamy and Schweisguth, 1950, among others). Such observations are suggestive, but scarcely justify a confident assertion that incidence in relatives is raised, since both the numbers of relatives at risk and the incidence of affected in the related general populations were unknown. In the present communication we give the numbers of affected and unaffected relatives of a series of patients with various congenital cardiac malformations. All known affected relatives were recorded during the enquiry, but observations on incidence are restricted to brothers, sisters, parents, and first cousins of propositi. The data suggest that incidence of congenital malformation of the heart is raised in sibs, but is not raised in parents and cousins of affected individuals.

Incidence of Anencephalus, Spina Bifida, and Hydrocephalus Related to Birth Rank and Maternal Age

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 GreenwoodYule 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

Influence of Birth Order and Maternal Age on the Human Sex Ratio at Birth

Data published by the U.S. Bureau of the Census in the 1940s and the British National Office of Vital Statistics in the 1930s and 1940s has been used to examine the influence of birth order and maternal age on the sex ratio at birth. In view of the substantially different sex ratios of whites and nonwhites the 2 groups have been considered separately. Among the conclusions for white births are: 1) the sex ratio of live births decreases with both increasing birth rank and maternal age; 2) when birth rank if fixed no consistent association with maternal age is seen but the downward trend remains in each maternal age group; and 3) the sex ratio of stillbirths is high at the extremes of birth rank and maternal age. For nonwhite births the statistics show that: 1) when the association between maternal age and birth order is separted the sex ratio of live births shows no consistent relationship to maternal age but does show an increase from birth order 1 to birth order 2 then it declines with increasing birth rank; and 2) stillbirths show a U-shaped trend with both birth rank and maternal age. The base of the U is at higher birth ranks and maternal ages than for whites.

Evidence of post-natal environmental influence in the aetiology of infantile pyloric stenosis.

The fact that the risk of infantile pyloric stenosis is related to position in family suggests that the environment influences the incidence of the disease, since there is no reason to suppose that inherited differences are affected by birth order, while examples of both pre-natal and post-natal environmental effects associated with birth order are well known (McKeown, MacMahon and Record, 1951a and b). The observation that size of the pyloric tumour is highly correlated with age at operation (McKeown et al., 1951c) supports the view that the tumour develops after birth, but does not, of course, exclude the possibility that the environmental influence (suggested by the association of incidence with birth rank) is exerted before birth. The present communication provides evidence that this environmental effect is post-natal by showing first that immediately after birth the disease is equally common in all birth ranks (it is not until about the third week that the incidence in firstborn is significantly raised), and secondly that symptoms appear earlier in domiciliary than in hospital births.

Infantile hypertrophic pyloric stenosis in parent and child.

In a recent report, Carter and Powell (1954) recorded 12 examples of pyloric stenosis in parent and child, and drew attention to the increased risk of the disease in offspring of parents who were themselves affected. In examining their observations we noted that the risk to the child seemed to be greater if the affected parent was the mother; but the number of cases was small, and the matter evidently required investigation in a larger series. Nielsen (1954) has since recorded nine examples of pyloric stenosis in parent and child, to which we have been able to add a further 12. The results support the conclusion that the risk is raised in children of affected parents, and suggest that it is much higher if the affected parent is the mother.

Congenital Pyloric Stenosis: An Investigation of 578 Cases

In the case of pyloric stenosis, the collection of this information now raises no insuperable difficulty, and if knowledge (of such matters as the association of the malformation with maternal age and birth rank) is still incomplete, it is because inquiries have usually been based on hospital births for which the population of related births is unknown. In the present investigation we have attempted to overcome this difficulty by the following methods: (1) A series of Birmingham children with pyloric stenosis has been assembled by examination of the records of all Birmingham hospitals which admit children, for the 10-year period 1940-49. f (It was, of course, necessary to exclude children whose homes were not in Birmingham.) The series can be regarded as complete in so far as

Secular Changes in the Incidence of Malformations of the Central Nervous System

In a previous communication (Record and McKeown, 1949) it was noted that in Birmingham the incidence of anencephalus and spina bifida decreased during the years 1940-47, while the incidence of hydrocephalus remained fairly constant. It was tentatively suggested that this decrease might be correlated with changes in the parity distribution of births, since it was shown that the incidence of anen cephalus and spina bifida is associated with birth order. We propose here to examine this suggestion more critically, making use of statistics for additional years and of more detailed information than was previously available about the parity distribution of the general population of births. Table I (see Fig. 1) gives the incidence of malformations of the central nervous system notified as stillbirths or infant deaths in Birmingham for the period 1936-49. Anencephalus associated with spina bifida is classified under anencephalus, and spina bifida with hydrocephalus under spina bifida. During the years 1940-49 the incidence of anencephalus and spina bifida fell sharply; the incidence of hydrocephalus showed no consistent variation. The significance of these changes * In receipt of a personal grant from the Medical Research Council. TABLE I Incidence (per thousand total births) of Malformations of the Central Nervous System Birmingham, 1936-49 _