An epidemiologic study on congenital malformations in Nagoya.

The subjects analysed in the present study were 41 ,835 total births in Nagoya in 1965, consisting of 41,028 live births and 807 la te stillbirths. Among the stillbirths 42 babies were the malformed and of 644 deaths in the subsequent four years 96 deaths with malformations were identified. Average linking rate of death and live birth certificates was 96.1 percent. The incidences of congenital malformations per 1,000 births were 3.30 in total births, 2.34 in live births and 52.04 in late stillbirths. Those in the cardiovascular system were 1.20 in total births, 1.17 in live births and 2.48 in late stillbirths. The corresponding figures were 0.93, 0.34 and 30.98 in the central system and 0.69, 0.56 and 7.43 in the alimentary system, respectively. Significantly greater relative risks were observed with shorter gestational period, lower birth weight and higher birth order. They were also noted in older working mothers with heavy physical loads, twin births and illegitimate births. Analyses by major anatomical system revealed significantly greater relative risks with shorter gestational period in the cardiovascular, central nervous and alimentary systems, with lower birth weight in the cardiovascular system and with higher birth order in the central nervous system. Paternal age and parental age difference exerted insignificant effects on malformations, though an increasing tendency of risk with advancing paternal age and with wider parental age difference was interestingly noted in the malformations of the central nervous system. INTRODUCfION The importance of congenital malformations not only in clinical medicine, but also in public health is clearly recognized from the following aspects. 1. Despite the remarkable decrease in deaths from infectious diseases, deaths from congenital malformations have not been reduced appreciably, but show a tenden~*oo~, *H~Z, fi~~~, ~ffi ~ Received for publication July 2, 1975. 43 44 K. AOKI ET AL. cy to increase over the decades. (1 ) 2. Congenital malformations are the first killer of infants under one year of age. (1) 3. Approximately forty percent of early fetal deaths are supposed to be due to malformations. (2) 4. Congenital malformations are the second most commn consumer of pediatric hospital beds. (3) 5. Economic and psychological burdens of parents with malformed babies are beyond all imagination. 6. There has been increasing interest in congenital malformations, with many reports on phocomelia due to thalidomide and on german measles syndrome. 7. Very little attention has been paid to the prevention, early detection and rehabilitation of the affected children by health authorities at large. Though congenital malformations and monstrosities were recognized and depicted in artistic expressions of primitive people, (4) the door of their origin has been mysteriously locked and decorated by superstitions and fears, for centuries. Only in recent years was it opened more and more widely by the advances in medical science, especially in medical genetics, in experimental teratology and in the epidemiology of teratogenesis. Congenital malformations are now etiologically considered as the outcome of intricate interaction between host and environment. This indicates the importance and urgency of epidemiological investigations in this particular field. In Japan, population based epidemiological investigations are very few. This rarity encouraged the authors to undertake a series of works on the epidemiology of congenital malformations in a metropolitan area, Nagoya. The preliminary report of the present investigation has already been presented by one of the authors (T.T.). (5) In this paper the results of further statistical analyses are included, and the authors intend: I. To demonstrate the frequency and distribution of congenital malformations by major anatomical system; 2. To compare the frequency distributions of some contributing factors to congenital malformations between malformed and non-malformed babies; 3. To evaluate the importance of each specific factor by one of the statistical procedures, relative risk. MATERIALS AND METHODS The present study was based on 41,835 total births registered in Nagoya in 1965, which consisted of 41,028 live births and 807 late stillbirths (after eighth month of pregnancy), excluding the babies born to the mothers of foreign nationality. Live born babies were followed once or twice a year by linking the live birth certificates with the death certificates by the end of 1968. Six hundred seventy deaths were observed during the follow-up period. Among them the death certificates of 644 deaths were successfully linked with EPIDEMIOLOGY OF CONGENITAL MALFORMATIONS 45 their birth certificates, attaining the linking rate of 98.7% in 1965,96.1% in 1966, 87.8% in 1967 and 76.3% in 1968. The average linking rate was 96.1 percent. Twenty six deaths which failed in linking were finally identified as babies born out of Nagoya in 1965 and died in Nagoya thereafter. The information available on stillbirth, live birth and death certificates were all examined for each baby. These were residence, birth date, sex, illegitimacy, gestational period, birth weight, single or multiple birth, place of delivery, attendant at birth, birth order, parental age, parental occupation, wedlock duration, date of death, cause of death and stillbirth, autopsy or operation findings and so forth. Cause of death or stillbirth and autopsy or operation findings were deliberately and systematically looked over on each death or stillbirth certificate. The baby was assigned as "malformed" when any form of malformation was listed as either underlying or contributing cause of death and also when malformation was detected in case of autopsy or operation performed. Forty two babies (males 19, females 22 and unknown 1) among 807 late stillbirths and 96 babies (males 49 and females 47) among 644 deaths after live births were finally identified as malformed babies in this study. All statistical analyses and data processing were accomplished by the FACOM 230-60 computer at Nagoya University Computation Center and by the HITAC201 computer at Department of Epidemiology, Aichi Cancer Center Research Institute. RESULTS I Fequency of congenital malformations by major anatomical system and type of malformation (Table 1) One hundred and thirty eight malformed babies in total birth were distributed as follows: 36.2% in the cardiovascular system, 28.3% in the central nervous system, 21.0% in the alimentary system and 14.5% in miscellaneous organs. It was interestingly noted that in live births the cardiovascular system accounted for one half of the malformed, whereas in stillbirths the central nervous system accounted for about 60% of the malformed. And it was also worth noting that in the central nervous system 10 of 14 malformed in live births were hydrocephalus, whereas 15 of 25 malformed in stillbirths were anencephalus. Sex difference in frequency of congenital malformations by major anatomical system was not revealed, but some interesting sex differences were observed in some specific malformations. Three cases of tetralogy of Fallot in live births were all females. Five cases of spina bifida in total birth were all males. Four of5 cases of cleft lip and/or palate were males and 3 of 4 cases of Down's syndrome were females. Multiple malformations were observed in 8 cases: 4 cases in live birth; hydrocephalus with spina bifida (2), congenital heart disease with atresia of bile duct (I) and congenital heart disease with perineal fissure (I), and 4 cases in stillbirths;