Pediatric Annals

EXTENT OF THE BIRTH DEFECTS PROBLEM

J William Flynt, JR, MD

Abstract

1 . Nishimura, H., Takano, K., Tanimura, T., Yasuda, M., and Uchida, T. High incidence of several malformations in the early human embryos as compared with infants. Bid. Neonat. 10 (1966), 93.

2. Mclntosh, R., Merrit, K. K., Richards, M. R., Samuels. M. H., and Bellows, M. T. The incidence of congenital malformations; a study of 5,964 pregnancies. Pediatrics 14 (1954), 505-522.

3. Hamerton, J. L, Ray, M., Abbott, J.. WiIMamson, C., and Ducasse, G. C. Chromosome studies in a neonatal population. Cañad. Med. Ass. J. 106 (1972), 776-779.

4. Polani, P. E. The incidence of chromosomal malformations. Proc. Roy. Soc. Med. 63 (1970), 50-52.

5. Carr, D. H. Geneiic basis of abortion. Ann. Rev. Geneiic 5 (1971), 65-80.

6. U.S. Dept. of Health, Education, and Wellare. V/taf Stat/sifcs of ine United Stetes, 1968.

7. U.S. Dept. of Health, Education, and Welfare, Public Health Service, HSMHA, National Center for Health Statistics. Monthly Vital Statistics Report 20 (1972), 5.

8. Childs, B.. Miller. S. M., and Beam. A. G. Gene Mutation as a Cause of Human Disease. H. E. Button, and M. I. Harris, eds. In Mutagenic Effects ol Environmental Contaminants. New York: Academic Press, 1972. 3-14.

9. Worid Health Organization. Genetic Disorders: Prevention, Treatment and Rehabilitation. Report of a WHO Scientific Group on Prevention, Treatment, and Rehabilitation in Genetic Disorders. WHO Tech. Rep. Ser. No. 497, Geneva, 1972.

10. McCrory, W. W. Child Health in the United Slates. Quart. Rev. Pediat. 15 (1960), 94.

11. Stickle, G. Health is indivisible. In National Foundation-March of Dimes Conference for Community Leaders, Boston, Mass., 1971.

12. U.S. Dept. of Health, Education, and Welfare. Mental Retardation Source Book. DHEW Publication No. (OS) 73-81. Office of Mental Retardation Coordination, Sept. 1972, 1.

13. U.S. Dept. of Health, Education, and Welfare, Rehabilitation Services Administration, Forty-sixth Annual (FY 1971) Census of Patients in Mental Institutions. In preparation.

14. Wilson, J. G. Present status of drugs as teratogens in man. Teratology 7 (1973), 3-16,

15. Warkany, J. Environmental Factors. In Congenital Mallormations. Chicago: Year Book Medical Publishers, 1971,61.

16. Carter, C. O. An ABC oí Medical Genetics. Boston: Little, Brown and Co., 1969.

17. Motulsky, A. G. Frequency of sickling disorders in U.S. blacks. New Eng. J. Med. 288 (1973). 31-33.

18. Brunecky, Z. The incidence and genetics of cystic fibrosis. J. Med. Genetics 9 (1972), 33-37.

19. Leonard, C. O., Chase, G. A., and Childs, B. Genetic counseling: a consumer's view. New Eng. J. Med. 287 (1972), 433-439.

20. Carter, C. 0., Roberts, J. A. F., Evans, K. A., and Buck, A. R. Genetic clinic: a follow-up. Lancet 1 (1971), 281-285.

21. Lubs, H. A., and Ruddle, F. H. Chromosomal abnormalities in the human population: estimation of rates based on New Haven newborn study. Science (1970), 495-497.

22. Sergovich, F. R., Valentine, G. H., Chen, A. T. L, Kinch, R. A. H.. and Smout, M. S. Chromosome aberrations in 2,159 consecutive newborn babies. New Eng. J. Med. 280 (1969). 851 -855.

23. Hatfield, E. M. Blindness in infants and children. Sight Saving Review 42 (1972), 69-89.

TABLE 1

Reported Incidence of Selected Birth Defect Categories with Estimated Numbers of Affected United States Infants Born in 1972

TABLE 2

Frequency of Chromosome Abnormalities Among 23,328 Newborns…

Birth defects include a host of heterogeneous conditions sharing in common an origin at the time of conception or during gestation. Individually, most defects are rare, but collectively they cause significant morbidity and mortality, which provides the best justification for including such a variety of conditions under one term.

Six overlapping categories (Table 1) are commonly used to classify these disorders : structural malformations, genetically-determined defects, chromosomal abnormalities, mental retardation, deafness, and blindness. These disorders are only part of the total problem. A number of diseases, including hypertension, diabetes, arteriosclerosis, schizophrenia, and gout also have genetic determinants that justify their inclusion as part of the birth defect problem. These occur primarily in later life and are generally of little clinical consequence to the pediatrician. However, they are mentioned only to emphasize the breadth of the birth defects problem and will not be dealt with further in this paper.

TYPES OF DEFECTS

The most common defects are the structural malformations. Their incidence is given here conservatively, albeit somewhat arbitrarily, as five per cent (Table 1). An estimated 163,000 infants affected with such defects were born in 1972. Mental retardation was only slightly less frequent, occurring once in approximately 30 births or in some 109,000 infants born last year.

Following these in decreasing order of frequency were the categories of genetic disorders, chromosomal abnormalities, congenital deafness, and blindness. Affected infants often have two or more of these defects simultaneously, so that no total incidence can be derived from these estimates. However, allowing for some overlap of defect categories, we may estimate that approximately seven per cent of all liveborn infants have one of these defects. In the United States last year, an estimated 230,000 affected infants were born.

The defects noted after birth are of foremost concern to the physician and others involved with the care and treatment of affected individuals.

However, these must be considered as only part of a continuum that begins with conception. The structural malformations and chromosomal abnormalities present in infants at birth are only a fraction of those occurring in all conceptions. Such defects are responsible for the elimination of a substantial number of embryos and fetuses in early gestation.

A study of embryos obtained by abortion for social reasons notes a higher incidence of structural anomalies than in fetuses at term.1 Other workers report an incidence of malformations among stillborn infants of 16 per cent, over twice as high as among the liveborn.2 No less than 3.5 per cent of all recognized pregnancies carry a chromosomal abnormality, and because of the low incidence (0.5 per cent) among newborns, the majority must be lost in early pregnanCV.3' <

In a composite of studies totaling over 1,500 abortions, the overall frequency of chromosomal error is noted to be 24 per cent.5 Of interest is the observation that the types of chromosomal errors among abortuses differ from those noted after birth. Triploidy, autosomal trisomies, and XO sex chromosomes are commonly seen in abortions, but are rare among liveborn infants.4 Survivors to birth have, for the most part, sex chromosome errors; trisomy D, E, or G; or asymptomatic translocations.

The severity of birth defects is also a spectrum that extends forward from conception. Some structural malformations and chromosomal abnormalities result in the elimination of affected conceptuses. Fetuses with other defects, such as anencephaly or renal or pulmonary agenesis, may survive through gestation, but cannot live in an extrauterine environment. Still other less severe defects are compatible with birth and immediate survival, but take a later toll in a range of handicaps causing death or needing medical, educational, social, and community support.

IMPACT

No single measurement can totally encompass the extent of birth defects in this country, and estimates are necessarily based on fragmentary data collected for selected defects or categories in variously circumscribed populations. Morbidity and mortality statistics do not generally allow for clear identification of specific defects or causes, but nevertheless are valuable for estimates of impact on the total population.

Congenital malformations rank as one of the major causes of death in pediatrie age groups.6 They are the second most common cause of death in infants and in the one to five year age group, while deaths from malformations among children ages 5 to 15 years are exceeded in frequency only by accidents and malignant neoplasms (Figure 1). In 1968,, malformations accounted for 14.5 per cent of infant deaths. The proportion of infant deaths caused by malformations has risen from five per cent in 1910. Although some of the increase comes from improved recognition and diagnosis, it also comes from the decrease in deaths from other diseases. A rising standard of living, the use of immunizations, and improved diagnosis and medical care have all served to markedly reduce mortality from infectious diseases. In 1910, 29 per cent of infant deaths were caused by diarrhea and enteritis, contrasted to 1.4 per cent in 1968.°

Figure 1. Death rates for infants and children under age 15 years for three leading causes of death, United States, 1968. Source: U.S. DHEW, Vital Statistics, 1968.

Figure 1. Death rates for infants and children under age 15 years for three leading causes of death, United States, 1968. Source: U.S. DHEW, Vital Statistics, 1968.

malformation-related mortality rates have also declined coincident with improved diagnosis and care from 40 per 10,000 livebirths in 1950 to 28 per 10,000 in 1971. 7 these data reflect the improved care available to the malformed infant, but also note that congenital malformations have become of increasing relative importance as a cause of infant mortality.

Birth defects also exert considerable impact on morbidity among children and adults. known genetic diseasesincluding some structural malformations, chromosomal abnormalities, and other disorders with known inheritance patterns- account for seven per cent of admissions to one u.s. pediatrie hospital. conditions considerea likely to have significant genetic influences caused another 20 per cent of admissions.8

Similar figures are noted in a Canadian hospital, where 29 per cent of patients between age one day and 18 years are admitted because of genetic disease.9 Structural malformations necessitate 43 per cent of admissions to the pediatrie service at a Midwestern university hospital.10 It has been estimated that each year birth defects necessitate hospitalization of nearly 1.2 million persons in the U.S. at a cost of over $800 million.11

There are an estimated six million retarded persons in the United States.12 In 1971, approximately 21O7OOO retarded patients were housed in public institutions and an additional 30,000 were cared for in private facilities.12·13 At an estimated annual cost per patient of $7,500, the expense of maintaining these institutionalized patients for one year amounts to roughly $1.8 billion.

ETIOLOGY

The etiologies of birth defects are many and varied. They are generally divided into environmental or genetic factors. These may act alone or in concert to produce a particular defect. To add to the complexities of understanding etiologic mechanisms, one factor may result in several defects, and a variety of etiologic agents are capable of producing the same defect. For example, rubella virus typically causes structural malformations, mental retardation, deafness, and blindness, while among the several causes of cataracts are the rubella virus, galactosemia, Down's syndrome, and Albright's hereditary osteodystrophy.

Such variations in manifestations and overlap in etiologies point clearly to the difficulties in dealing only with total defects or defect categories. Among cases with structural malformations, the etiology is unknown in 65 to 70 per cent. Patterns of genetic transmission account for 20 per cent, chromosomal abnormalities are noted in five per cent, and environmental factors such as radiation, infection, drugs, and chemicals are responsible for another 5 to 10 per cent.14 For more details on environmental causes of malformations, two recent reviews are suggested.14.15

GENETIC DISORDERS

The genetic disorders encompass a variety of conditions that fall into two types of inheritance patterns. The first type is characterized by the typical Mendelian dominant, recessive, or sex-linked inheritance patterns. Nearly 1,000 conditions falling under this type have been described and characterized, including structural abnormalities affecting all organ systems, biochemical defects, deafness, blindness, and syndromes of multiple malformations.16 Individually, most of these disorders are rare, occurring on the order of one in 10,000 to one in one million births. However, a few are found more commonly in selected populations. These include sickle cell anemia, which affects about 1 in 600 blacks; Tay-Sachs disease, which occurs in one of 3,500 Jewish infants; and cystic fibrosis, the most common genetic disorder among whites, noted with a frequency of about one in 2,500 births.9, 17, 18

Table

TABLE 1Reported Incidence of Selected Birth Defect Categories with Estimated Numbers of Affected United States Infants Born in 1972

TABLE 1

Reported Incidence of Selected Birth Defect Categories with Estimated Numbers of Affected United States Infants Born in 1972

The second inheritance pattern involves a number of, rather than one, gene loci that determine expression of the disorder; the genetic component is polygenic. Furthermore, in polygenically inherited conditions, environmental factors also modify expression of the genes so that the etiology is considered multifactorial·- manifesting both genetic and environmental components.

The following structural malformations are considered to have multifactorial origins: anencephaly, spina bifida, cleft lip with or without cleft palate, talipes equinovarus, congenital dislocated hip, heart malformations, and pyloric stenosis. The pattern of inheritance and the defects with this pattern are of particular importance. Identification of the environmental factors contributing to the etiology of these defects may provide avenues for developing preventive measures.

Table

TABLE 2Frequency of Chromosome Abnormalities Among 23,328 Newborns

TABLE 2

Frequency of Chromosome Abnormalities Among 23,328 Newborns

There also needs to be appreciation that the above defects have genetic components and that recurrence risks exist among families having affected infants. The families deserve to know these risks in order to make informed decisions about future childbearing. In general, the risks are less than 10 per cent, and decisions regarding further children seem based on the burden of the disease rather than on the magnitude of the risk.19'20 However, in special situations, such as a history of two affected children vor an affected parent, the risks are of higher magnitude and may be sufficient to deter parents from having other children.

CHROMOSOMAL ABNORMALITIES

The frequency of chromosomal abnormalities has been noted as approximately one in 200 Hveborn infants (Table 2).3 In a combined series of over 23,000 newborns, 41 per cent of the chromosomal abnormalities involve extra or absent X or Y sex chromosomes. Among 48 infants so affected, 39 (81 per cent) are males with XYY or XXY karyotypes. Nine infants are females; eight have XXX and one has XO (Turner's syndrome).

The second most common error in this series of newborns involves 36 cases with structural translocations of the chromosomes. Down's syndrome (Trisomy G) is noted in 0.99 per 1,000 newborns or about one in 1,000 liveborns. Trisomies of the E and D group chromosomes are observed less commonly, with frequencies of one in 7,700 and one in 11,000 infants, respectively. These results suggest that autosomal trisomies of D and E chromosomes are somewhat less common than previously thought.21,22

RECENT ADVANCES

Efforts to reduce the extent of birth defects are in general directed toward the identification of new causes, particularly drugs and infectious agents; improvements in methods of prenatal and postnatal care, to lessen morbidity and mortality; and development and implementation of preventive measures.

Three notable developments in preventive measures have become available in recent years. The development of Rh-immune globulin, licensed in 1968, has made possible the virtual eradication of Rh-hemolytíc disease in the newborn with its attendant fetal and infant mortality and morbidity. Similarly, proper use of rubella vaccine can ensure that women of childbearing age are either immune or at little risk of rubella virus exposure in the community. This can prevent maternal infection and protect the developing fetus from acquiring congenital rubella. In addition, genetic counseling and prenatal diagnosis coupled with selective abortion are becoming more widely used to reduce the number of infants born with genetic or chromosomal disorders.

It seems evident that the common feature among birth defects is their diversity. Since preventive measures are for the most part directed toward individual types of defects or etiologies, no quick or marked reduction in the birth defect problem can be expected. Indeed the reduction will most likely be gradual, but hopefully progressive, as more causes of defects become preventable.

BIBLIOGRAPHY

1 . Nishimura, H., Takano, K., Tanimura, T., Yasuda, M., and Uchida, T. High incidence of several malformations in the early human embryos as compared with infants. Bid. Neonat. 10 (1966), 93.

2. Mclntosh, R., Merrit, K. K., Richards, M. R., Samuels. M. H., and Bellows, M. T. The incidence of congenital malformations; a study of 5,964 pregnancies. Pediatrics 14 (1954), 505-522.

3. Hamerton, J. L, Ray, M., Abbott, J.. WiIMamson, C., and Ducasse, G. C. Chromosome studies in a neonatal population. Cañad. Med. Ass. J. 106 (1972), 776-779.

4. Polani, P. E. The incidence of chromosomal malformations. Proc. Roy. Soc. Med. 63 (1970), 50-52.

5. Carr, D. H. Geneiic basis of abortion. Ann. Rev. Geneiic 5 (1971), 65-80.

6. U.S. Dept. of Health, Education, and Wellare. V/taf Stat/sifcs of ine United Stetes, 1968.

7. U.S. Dept. of Health, Education, and Welfare, Public Health Service, HSMHA, National Center for Health Statistics. Monthly Vital Statistics Report 20 (1972), 5.

8. Childs, B.. Miller. S. M., and Beam. A. G. Gene Mutation as a Cause of Human Disease. H. E. Button, and M. I. Harris, eds. In Mutagenic Effects ol Environmental Contaminants. New York: Academic Press, 1972. 3-14.

9. Worid Health Organization. Genetic Disorders: Prevention, Treatment and Rehabilitation. Report of a WHO Scientific Group on Prevention, Treatment, and Rehabilitation in Genetic Disorders. WHO Tech. Rep. Ser. No. 497, Geneva, 1972.

10. McCrory, W. W. Child Health in the United Slates. Quart. Rev. Pediat. 15 (1960), 94.

11. Stickle, G. Health is indivisible. In National Foundation-March of Dimes Conference for Community Leaders, Boston, Mass., 1971.

12. U.S. Dept. of Health, Education, and Welfare. Mental Retardation Source Book. DHEW Publication No. (OS) 73-81. Office of Mental Retardation Coordination, Sept. 1972, 1.

13. U.S. Dept. of Health, Education, and Welfare, Rehabilitation Services Administration, Forty-sixth Annual (FY 1971) Census of Patients in Mental Institutions. In preparation.

14. Wilson, J. G. Present status of drugs as teratogens in man. Teratology 7 (1973), 3-16,

15. Warkany, J. Environmental Factors. In Congenital Mallormations. Chicago: Year Book Medical Publishers, 1971,61.

16. Carter, C. O. An ABC oí Medical Genetics. Boston: Little, Brown and Co., 1969.

17. Motulsky, A. G. Frequency of sickling disorders in U.S. blacks. New Eng. J. Med. 288 (1973). 31-33.

18. Brunecky, Z. The incidence and genetics of cystic fibrosis. J. Med. Genetics 9 (1972), 33-37.

19. Leonard, C. O., Chase, G. A., and Childs, B. Genetic counseling: a consumer's view. New Eng. J. Med. 287 (1972), 433-439.

20. Carter, C. 0., Roberts, J. A. F., Evans, K. A., and Buck, A. R. Genetic clinic: a follow-up. Lancet 1 (1971), 281-285.

21. Lubs, H. A., and Ruddle, F. H. Chromosomal abnormalities in the human population: estimation of rates based on New Haven newborn study. Science (1970), 495-497.

22. Sergovich, F. R., Valentine, G. H., Chen, A. T. L, Kinch, R. A. H.. and Smout, M. S. Chromosome aberrations in 2,159 consecutive newborn babies. New Eng. J. Med. 280 (1969). 851 -855.

23. Hatfield, E. M. Blindness in infants and children. Sight Saving Review 42 (1972), 69-89.

TABLE 1

Reported Incidence of Selected Birth Defect Categories with Estimated Numbers of Affected United States Infants Born in 1972

TABLE 2

Frequency of Chromosome Abnormalities Among 23,328 Newborns

10.3928/0090-4481-19731001-04

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