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Social Biology Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hsbi19
Congenital Malformations in the American Indian a
a
Jerry D. Niswander , Mark V. Barrow & Glenn J. Bingle
a
a
Genetics and Epidemiology Section, Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research , National Institutes of Health , Bethesda , Maryland Published online: 23 Aug 2010.
To cite this article: Jerry D. Niswander , Mark V. Barrow & Glenn J. Bingle (1975) Congenital Malformations in the American Indian, Social Biology, 22:3, 203-215, DOI: 10.1080/19485565.1975.9988168 To link to this article: http://dx.doi.org/10.1080/19485565.1975.9988168
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sublicensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Congenital Malformations in the American Indian
Jerry D. Niswander, Mark V. Barrow, and Glenn J. Bingle
Downloaded by [UQ Library] at 18:29 13 March 2015
Genetics and Epidemiology Section Laboratory of Developmental Biology and Anomalies National Institute of Dental Research National Institutes of Health Bethesda, Maryland
The relative frequency of congenital malformations in various population groups has received considerable attention in recent years. The problems associated with comparing malformation rates in various groups are well recognized and have been discussed in depth by many authors (Neel, 1958; Stevenson et al., 1966; Morton et al., 1967; Kennedy, 1967; Lilienfeld, 1970). Despite the problems of comparability, a variety of hypotheses and models have been set forth which relate to the etiology of such malformations. Comparison of malformation rates among races and of the effects of interracial crosses has been of particular interest in understanding the genetic basis of birth defects. Thus, in studies of Japanese infants, Neel (1958) observed that the total malformation rate was similar to those reported in other diverse populations, even though rates for specific malformations varied considerably. Subsequently, he proposed that a significant fraction of human congenital defects might be segregants from multilocal homeostatic systems. Morton et al. (1967) in a study of racial crosses in Hawaii obtained similar results in regard to total rate
of malformation among different races. However, their data showed no effect of outcrossing and "therefore no evidence that multiple homozygous 'phenodeviants' are of importance in the etiology of congenital defects" (p. 112). More recently, Carter (1970) suggested that the proposition that the total malformation rate is constant among racial groups may not be true. The purpose of the present report is to document the overall malformation rate as well as frequencies of certain specific malformations in the American Indian. Since the American Indian is considered a migrant population long separated from its parental stock, comparison of these results with those available for other Mongoloid groups is of interest. A further objective of this paper is to examine the effects of admixture on the malformation frequencies from this population. A preliminary report of a part of these data has been published previously (Adams and Niswander, 1968). MATERIALS AND METHODS
From July, 1964, to July, 1969, copies of the birth records of all American Indians and the Alaskan natives born in Indian
203
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204
Niswander, Barrow, and Bingle
Health Service hospitals were obtained for this study. The Indian Health Service operates a system of 51 hospitals. The inpatient capacities of these facilities range from 6 to 276 beds (Figure 1). All use an identical recording form which includes a newborn physical examination section completed by the attending physician. A discharge summary containing parental tribal affiliation, residence, and other vital statistics, along with a list of coded diagnoses and/or operative procedures relating to the infant was also available. We estimate that approximately one-half of all American Indian births occur within the Indian Health Service (IHS) hospital system. More than 95 per cent of those families residing on federal reservations or within the 51 service unit areas utilize the IHS hospitals. The majority of those births for which we have no record represent families who have migrated to urban centers or areas not served by IHS. Many of these families do receive medical care under contract from local hospitals. However, because of the nommiformity in records and reporting systems and the difficulty in defining the base population served by such hospitals, no attempt was made to include this source of data. The sample reported here represents a nearly complete ascertainment of Indian live births (95 per cent) on major federal reservations and therefore should contain no important ascertainment biases, such as preferential selection by choosing to utilize IHS facilities for delivery. The degree of representativeness of these data compared to that for nonreservation population is difficult to define. VARIABLES REFLECTING OUTCOME OF PREGNANCY
During the period covered by this study, a total of 44,269 infant births was reported from IHS hospitals. These births are sum-
Social Biology TABLE 1
44,269 BIRTHS m INDIAN HEALTH SERVICE HOSPITALS, JULY 1964 TO JUNE 1969 '
Births Total Indian births Normal Single Multiple Stillborn With major malformations Single Multiple Stillborn With minor malformations Single Multiple Stillborn Total Non-Indian births Normal* Major malformed Minor malformed Stillborn
No. 43,830 41,463 40,659 69S 109 813 788 IS 10 1,554 1,526 28 439 402 7 29 1
* Contains 1 twin pair.
marized in Table 1. Newborn records were not routinely completed for stillborn infants. Because of the gross underreporting of stillborns and their importance in evaluating malformation frequencies, an attempt was made to supplement the hospital data. Thus, certificates of all recorded Indian fetal deaths occurring in Arizona between July, 1967, and July, 1969, were reviewed and tabulated. The classification of malformations follows that used in a preliminary report (Adams and Niswander, 1968) and is in accordance with that of Neel (1958), Stevenson et al. (1966), Morton et al. (1967), and Woolf and Turner (1969). The designation of a major versus minor abnormality is arbitrary, but corresponds to these cited studies. Since no information was available after discharge from the hospital, we have no method by which to assess neonatal deaths that occurred after hospitalization. Nevertheless, 398 liveborn infants died before discharge—usually within the first day of life. This group is referred to as "newborn deaths." The data include 348 twin pairs and one
Vol. 22, No. 3
Congenital Malformations
205
U. S . PEPARTMENT OF HEALTH, EPUCATION,'AND WELFARE Public HtaUh Suivicz DIVISION OF IUVIAN HEALTH
Downloaded by [UQ Library] at 18:29 13 March 2015
Area Offices and Hospitals
• Scmbiola Iodiu Rutmtkm Serricef Adminlotici) Fiom the Oklthonu InUu HciUli AIM Offici.
FIG. 1.—Location of Indian Health Service hospitals and area offices.
set of triplets. The twin data will be discussed in detail in another report (Morgan and Niswander, unpublished). VARIABLES RELATING TO EPIDEMIOLOGICAL AND GENETIC CHARACTERISTICS OF THE SAMPLE
The independent variables considered include a variety of indicators and measures of social, medical, demographic, and genetic factors with potential influence on pregnancy outcome. Specifically, we included sex of the infant, year of birth, maternal age, number of previous pregnancies, absence of prenatal care, legitimacy, maternal serology, nonhospital birth, residence (on and off reservation), and endogamy (parents of same or different linguistic group). If no information pertaining to the father appeared on the records, the birth was
considered illegitimate. Infants born outside of IHS hospitals, but admitted within 48 hours received regular newborn records. The newborn record contains space for recording tribal affiliation of both mother and father. If the parents were of different tribes, the child was arbitrarily assigned to the father's tribe. Since 95 different tribal groups were encountered, it was necessary to classify tribes into more discrete groups. The tribes were grouped by major language families following classifications given by Hodge (1912), Swanton (1925), and Wissler (1938). Six specific language groups were delineated: Aleut-Eskimo, Athabascan, Algonquian, Iroquoi-Muskhogean, Hokan-Siouan, and Uto-Aztecan. These six groups encompassed over 90 per cent of the sample with "other" and non-Indians com-
Niswander, Barrow, and Bingle
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206
Social Biology
prising the remainder. The original geo- blood was recorded in finer fractions, it was graphic distribution of these language arbitrarily rounded down to the nearest groups was modified from Underhill (19S3) one-eighth. Since ABO and Rh blood types and is shown in Figure 2. The eight lan- of the mother are included on the newborn guage groups were coded by use of seven record, it was possible to obtain an overall "dummy" variables indicating deviations appraisal of the reliability of the stated from the Uto-Aztecans (Uto-Aztecan, X i - degree of blood. For each mother's degreeX 7 = 0; Athabascan, Xi = 1, X2-X7 = 0; of-blood category (0-8), frequencies of the Aleut-Eskimo, Xx = 0, X 2 = 1, X3-X7 = B and r alleles were calculated. Assuming that both alleles are absent in pure Indians 0; etc.). and that all intermixture was Caucasian, Information relating to non-Indian adadmixture estimates were calculated for mixture was available from the newborn each "blood" category using 0.074 and record as "degree of Indian blood" and was 0.387 as the respective Caucasian frequenrecorded as a fraction for each parent. For cies of B and r. A high degree of correlaanalytic purposes, the degree of Indian tion was obtained between stated degree blood was coded in eights (0, non-Indian; of blood and admixture estimates based 8, full blood) with the infant scored as the upon blood typing (Figure 3). Although the average of the parents. If the degree of
^ B Eskimo Aleut EZ3 Athabascan E2D Algonquin ESHokan Sioux CED Uto-Azlecan
FIG. 2.—Geographic distribution of major linguistic groups of North American Indians. (Reprinted from Redman's America by Ruth Underhill by permission of the University of Chicago Press. Copyright © 19S4 by The University of Chicago. All rights reserved.)
Vol. 22, No. 3 w
lOOp
Q
a
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Congenital Malformations
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—
IAN A DMI
—
Weighted Regression (r and B)
S3I
a: u. 80 fc o UENC
UJ
60
S
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o u. o UJ 40
d
2o d
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—
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100
I
I
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I
87.5 75.0 62.5 50.0 37.5 25.0 12.0 PERCENT CAUCASIAN ADMIXTURE BASED ON REPORTED DEGREE OF BLOOD
0
Fie. 3.—Relationship between estimate of Caucasian admixture based on the individual's stated degree of blood (X coordinate) and an estimate based on r and B allele frequencies (Y coordinate within degree of blood categories.
degree of blood clearly underestimates admixture, particularly at the lower levels, it does appear that degree of blood is a justifiable measure of intermixture. In addition to the general descriptive data presented, we have employed stepwise regression to analyze total as well as selected specific malformation rates for effects of (1) linguistic groups, (2) medical-cultural variables, and (3) non-Indian intermixture. Our approach was first to test for differences between linguistic groups using the seven "dummy" variables (as previously mentioned). This procedure considers variation among groups in the regression model. After linguistic group variables were added, the various significant medical-cultural variables were added in stepwise fashion. The next step was to introduce the
child's degree of blood into the regression equation. If the effect of the child's admixture was not significant, the analysis was terminated. If the child's degree of blood was significant, we introduced the square of this term and tested for deviation from additivity; then as a separate procedure, we entered the mother's degree of blood to obtain information regarding maternal effects. This methodology results in a test of genetic admixture which is to an extent free of concomitant environmental variation. RESULTS
A listing of all major malformed infants by organ system is presented in Table 2. Infants with anomalies of more than one system are so classified. Among the 43,711 liveborn infants, 803 or 1.84 per cent had
Niswander, Barrow, and Bingle
208 TABLE 2
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MAJOR MALFORMATIONS AMONG 43,711 LTVEBORN AMERICAN INDIAN INFANTS AS DIAGNOSED IN INDIAN HEALTH SERVICE HOSPITALS ON "NEWBORN MEDICAL RECORDS"
Major Malformations No. Musculo-skeletal system—single malformations Clubfoot 64 Dislocation of hip 27 Diaphragmatic hernia 9 Polydactyly 93 Syndactyly 8 Phocomelia 1 Hemimelus 4 Ectrodactyly 3 Torticollis 2 Craniostenosis 5 Constructive bands of digits 1 Atrophic fingers 4 Absent pectoralis major 1 Rudimentary feet 1 "Buckled" ribs 1 "Claw" feet 1 Clubhand 1 Deformed femur 1 Facial asymmetry 1 Facial cleft 1 Inguinal hernia (female) 3 Total 232 Musculo-skeletal system—Multiple malformations Dislocated fingers; dislocated knees 1 Dislocated hip; subluxation of knee . . . 1 Polydactyly; rudimentary digits 1 "Lobster claw" deformity of hands; lobster claw deformity of feet 2 Clubfoot; "lobster claw" deformity of hand; absent forearm 1 Clubfoot; hand deformity 1 Clubfoot; dislocation of hip 3 Clubfoot; hypoplasia of radius; absent digits 1 Polydactyly; syndactyly 2 Hypoplastic pectoralis major; malformed hand 1 Total 14 Respiratory system Aplasia of lung 1 Choanal atresia 5 Tracheal stenosis 1 Total 7 Cardiovascular system Congenital heart disease (all types incl. undetermined) 121 Hemic and lymphatic system Cystic hygroma 1 Digestive system—single malformations Branchial cleft cyst 4 Cleft lip ± cleft palate 72 Cleft palate 23 Agenesis of mandible 1 Micrognathia 2 Midline cleft of maxillary gingiva . . . . 4 Intestinal obstruction ' 9 Atresia of small intestine (incl. pyloric stenosis) 15
Social Biology
TABLE 2 (Continued) Major Malformations No. Imperforate anus; recto-vaginal fistula 2 Anal stenosis 2 Omphalocele 6 Atresia of esophagus 1 Tracheo-esophageal fistula 5 Performation of small intestine 1 Total 147 Digestive system—Multiple malformations Imperf orate anus; recto-vaginal fistula Tracheo-esophageal fistula; atresia ani 1 Total 3 Urogenital system Persistent cloaca 1 Polycystic kidney 2 Bladder neck obstruction 3 Hypospadius 30 Extraversion of bladder with patent urachus 1 Pseudohermaphroditisim (incl. adrenogenital syndrome) 8 Bladder, diverticulum 1 Total 46 Nervous system—Single malformations Microcephalus S Hydrocephalus 14 Anencephalus 7 Encephalocele 1 Occipital meningocele 4 Spina bifida Simple 2 With meningocele 9 With meningocyelocele 11 With meningocyelocele; hydrocephalus 2 Bilateral paresis of legs* 2 Total 57 Nervous system—multiple malformations Hydrocephalus; encephalocele 1 Hydrocephalus; agenesis of corpus callosum; meningomyelocele 1 Total 2 Organs of special sense: eye Cataract 3 Corneal opacity 6 Glaucoma 2 Proptosis 1 Total 12 Organs of special sense: ear Microtia/atresia of auditory canal . . . . 21 Integumentary system Albinism 10 Hemangioma 6 Aplasia cutis congenita 2 Ichthyosis congenita 1 Total 19 Endocrine system Congenital goiter 2 Syndromes or recognizable disease entities Achondroplasia 1 Arthrogryposis 1 Down's syndrome 24 With congenital heart disease 8
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Vol. 22, No. 3
Congenital Malformations
TABLE 2 (Continued) Major Malformations With congenital heart disease; cataracts With cataracts With cataracts; deformed ear With omphalocele With cleft palate With anal atresia Rubella syndrome Crouzon's syndrome DeLange's syndrome (?) Trisomy 18 Trisomy 13-15 Otomandibular dysostosis Congenital lues Total Multiple malformations—multiple systems Cleft lip and palate; diaphragmatic hernia; microtia; clubhand Cleft lip and palate; inguinal hernia (female) Cleft lip and palate; proptosis right eye Cleft lip and palate; microcephaly; clubfoot Cleft lip and palate; clubfoot, rudimentary finger; syndactyly Cleft palate; clubfoot Cleft palate; clubfoot; tracheoespphageal fistula; hemivertebra; microtia Cleft palate; pseudohermaphroditismj polydactyly Cleft palate; congenital heart disease; anomaly of brain Tracheo-esophageal fistula; aortic stenosis; absent kidney Atresia of esophagus and trachea; aglossia; micrognathia Intestinal obstruction; malformed penis Intestinal obstruction; clubfoot Intestinal obstruction j clubfoot; microphthalmia; micrognathia Omphalocele; absent diaphragm; hypoplastic kidney; clubfoot Imperforate anus; "spine and rib anomalies" Imperf orate anus; dislocated hip; "digital" and vertebral anomalies" . . Cranial dysostosis; branchial cleft cyst; hypertrophy of gingiva Anencephaly; micropenis; clubfoot Cranial meningocele; bilateral cataracts Occipital meningocele; renal agenesis . . Microcephaly; deformed hands and feet Microcephaly; congenital heart disease Microcephaly; tetrology of fallot; micrognathia; deformity of ear Hydrocephaly; cataracts; micrognathia; abnormal genitalia Hydrocephaly; phocomelia; low set ears Hydrocephaly; meningomyelocele; clubfoot; cataract Hydrocephaly; arthrogryposis
No. 1 2 1 1 1 1 2 1 1 2 2 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2
TABLE 2 (Continued) Major Malformations Meninogocele; congenital heart disease Meningomyelocele; clubfoot Meningomyelocele; clubfoot; knee contracture Congenital heart disease With mandibulofacial dysostosis; hypertelorism With microphthalmia With hypoplasia of lung With polydactyly With polydactyly; syndactyly With clubhand; blindness With "lobster claw" deformity of feet With clubfoot With clubfoot; low set ears; malformed chest; CNS malformation . . With dislocated hip; clubfoot; dislocated wrist; corneal opacity . . . . With discolored hip With torticollis With polycystic kidney With anomalous kidney With micropenis Absent arms; syndactyly of toes; patent ductus arteriosus: microphthalmia . . Non-opposable thumbs; choanal atresia "Lobster claw" deformity of feet; deformed hand; choanal atresia Clubfoot; cranial dysostosis Clubfoot; coarctation of aorta Polydactyly; syndactyly; micropenis; micrognathia; low set ears Polydactyly; syndactyly; micrognathia Polydactyly; microtia; "abnormal" fades "Abnormal" toes; facial paralysis . . . . Absent digits; urethral stricture; absent kidney Hypertelorism; low set ears; hand abnormality Undefined multiple abnormalities incompatible with life Total Grand total * Twins concordant.
209
No. 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 60 802
one or more major malformations. This figure compares closely with a frequency of 2.06 per cent found by Woolf and Turner (1969) in the nursery records of liveborn infants at the Latter-Day Saints Hospital in Salt Lake City, Utah. However, it is considerably higher than the 1.02 per cent observed among Japanese by Neel (1958) or the overall frequency of 1.27 per cent recorded by Stevenson et al. (1966) from 24 World Health Organization centers.
Niswander, Barrow, and Bingle
210
Excluding multiple births, there were 43,526 infants recorded in the study. These births represent 33,755 different mothers and 8,874 sibships or half-sibships of two or more infants. A listing of the major malformations occurring within the same sibship is given in Table 3. In only seven cases TABLE 3
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MAJOR MALFORMATIONS OCCURRING IN TWO OR MORE SIBS OR HALF-SIBS AMONG 8,874 SIBSHIPS
1. A. B. 2. A. B. 3. A. B. 4. A. B. 5. A. B. 6. A. B.
7. A. B. C.
Cleft lip and palate Mongolism with congenital heart disease
Albinism Albinism Albinism Albinism Polydactyly Occipital meningocoele Congenital dislocation of hip. Congenital dislocation of hip Clubfoot Arthrogryposis Congenital dislocation of hip Polydactyly of the hand Polydactyly of the hand and feet
was there more than one affected child born to the same mother. Major genes are certainly indicated in the two instances of albinism and possibly for polydactly. The occurrence of this large number of sibs in the sample creates a potential problem for analysis. However, the very low recurrence rates involved suggest that such a factor will have very little effect on the overall results, and therefore it has not been considered in further analyses. Among the 119 stillbirths reported, ten (8.14 per cent) were malformed. Since this small sample of stillbirths is likely to be biased with respect to malformation, we examined fetal death certificates for Indians reported in Arizona for the years under study. During this period, 20,559 Indian births were reported in Arizona with 247 (12.0/1,000) stillbirths recorded. Of these births, 11,466 occurred in IHS hospitals and 126 (10.6/1,000) were stillborn. A
Social Biology
listing of the sixteen (6.5 per cent) malformations recorded among these 247 infants is presented in Table 4. TABLE 4 MAJOR MALFORMATION AMONG 247 ARIZONA STILLBORN AMERICAN INDIANS, J U L Y 1964 TO JULY 1969, FROM FETAL DEATH CERTIFICATES AND INDIAN HEALTH SERVICE NEWBORN RECORDS
Abnormalities Multiple congenital abnormalities Anencephaly Hydrocephaly Cleft lip and cleft palate; congenital heart disease Siamese twins Mongolism Protrusion of forehead Myelomeningocele Phocomelia Corneal opacity Omphalocele
No. 2 1 S 1 1
Mean frequencies for specific malformations among different linguistic groups are given in Table 5. Results of regression analysis for various malformation categories and newborn death are given in Table 6. Although a number of statistically significant effects are noted, the J?2's are all quite low, indicating that, collectively, the variables studied have little predictive value with respect to the individual infant. DISCUSSION MAJOR MALFORMATIONS
The most striking aspect of these data with regard to total major malformation is the variation between the different linguistic groups. The observed frequencies range from 2.6 per cent in the Aleut-Eskimo group t o U per cent in the Uto Aztecans. These difference are highly significant The two-fold differences which we observe between subgroups of Indians, a Mongoloid population, ascertained in a relatively homogeneous hospital system in a single study are difficult to reconcile with Neel's assertion of similar frequencies of
Vol. 22, No. 3
Congenital Malformations O 00
Social Biology Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hsbi19
Congenital Malformations in the American Indian a
a
Jerry D. Niswander , Mark V. Barrow & Glenn J. Bingle
a
a
Genetics and Epidemiology Section, Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research , National Institutes of Health , Bethesda , Maryland Published online: 23 Aug 2010.
To cite this article: Jerry D. Niswander , Mark V. Barrow & Glenn J. Bingle (1975) Congenital Malformations in the American Indian, Social Biology, 22:3, 203-215, DOI: 10.1080/19485565.1975.9988168 To link to this article: http://dx.doi.org/10.1080/19485565.1975.9988168
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sublicensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Congenital Malformations in the American Indian
Jerry D. Niswander, Mark V. Barrow, and Glenn J. Bingle
Downloaded by [UQ Library] at 18:29 13 March 2015
Genetics and Epidemiology Section Laboratory of Developmental Biology and Anomalies National Institute of Dental Research National Institutes of Health Bethesda, Maryland
The relative frequency of congenital malformations in various population groups has received considerable attention in recent years. The problems associated with comparing malformation rates in various groups are well recognized and have been discussed in depth by many authors (Neel, 1958; Stevenson et al., 1966; Morton et al., 1967; Kennedy, 1967; Lilienfeld, 1970). Despite the problems of comparability, a variety of hypotheses and models have been set forth which relate to the etiology of such malformations. Comparison of malformation rates among races and of the effects of interracial crosses has been of particular interest in understanding the genetic basis of birth defects. Thus, in studies of Japanese infants, Neel (1958) observed that the total malformation rate was similar to those reported in other diverse populations, even though rates for specific malformations varied considerably. Subsequently, he proposed that a significant fraction of human congenital defects might be segregants from multilocal homeostatic systems. Morton et al. (1967) in a study of racial crosses in Hawaii obtained similar results in regard to total rate
of malformation among different races. However, their data showed no effect of outcrossing and "therefore no evidence that multiple homozygous 'phenodeviants' are of importance in the etiology of congenital defects" (p. 112). More recently, Carter (1970) suggested that the proposition that the total malformation rate is constant among racial groups may not be true. The purpose of the present report is to document the overall malformation rate as well as frequencies of certain specific malformations in the American Indian. Since the American Indian is considered a migrant population long separated from its parental stock, comparison of these results with those available for other Mongoloid groups is of interest. A further objective of this paper is to examine the effects of admixture on the malformation frequencies from this population. A preliminary report of a part of these data has been published previously (Adams and Niswander, 1968). MATERIALS AND METHODS
From July, 1964, to July, 1969, copies of the birth records of all American Indians and the Alaskan natives born in Indian
203
Downloaded by [UQ Library] at 18:29 13 March 2015
204
Niswander, Barrow, and Bingle
Health Service hospitals were obtained for this study. The Indian Health Service operates a system of 51 hospitals. The inpatient capacities of these facilities range from 6 to 276 beds (Figure 1). All use an identical recording form which includes a newborn physical examination section completed by the attending physician. A discharge summary containing parental tribal affiliation, residence, and other vital statistics, along with a list of coded diagnoses and/or operative procedures relating to the infant was also available. We estimate that approximately one-half of all American Indian births occur within the Indian Health Service (IHS) hospital system. More than 95 per cent of those families residing on federal reservations or within the 51 service unit areas utilize the IHS hospitals. The majority of those births for which we have no record represent families who have migrated to urban centers or areas not served by IHS. Many of these families do receive medical care under contract from local hospitals. However, because of the nommiformity in records and reporting systems and the difficulty in defining the base population served by such hospitals, no attempt was made to include this source of data. The sample reported here represents a nearly complete ascertainment of Indian live births (95 per cent) on major federal reservations and therefore should contain no important ascertainment biases, such as preferential selection by choosing to utilize IHS facilities for delivery. The degree of representativeness of these data compared to that for nonreservation population is difficult to define. VARIABLES REFLECTING OUTCOME OF PREGNANCY
During the period covered by this study, a total of 44,269 infant births was reported from IHS hospitals. These births are sum-
Social Biology TABLE 1
44,269 BIRTHS m INDIAN HEALTH SERVICE HOSPITALS, JULY 1964 TO JUNE 1969 '
Births Total Indian births Normal Single Multiple Stillborn With major malformations Single Multiple Stillborn With minor malformations Single Multiple Stillborn Total Non-Indian births Normal* Major malformed Minor malformed Stillborn
No. 43,830 41,463 40,659 69S 109 813 788 IS 10 1,554 1,526 28 439 402 7 29 1
* Contains 1 twin pair.
marized in Table 1. Newborn records were not routinely completed for stillborn infants. Because of the gross underreporting of stillborns and their importance in evaluating malformation frequencies, an attempt was made to supplement the hospital data. Thus, certificates of all recorded Indian fetal deaths occurring in Arizona between July, 1967, and July, 1969, were reviewed and tabulated. The classification of malformations follows that used in a preliminary report (Adams and Niswander, 1968) and is in accordance with that of Neel (1958), Stevenson et al. (1966), Morton et al. (1967), and Woolf and Turner (1969). The designation of a major versus minor abnormality is arbitrary, but corresponds to these cited studies. Since no information was available after discharge from the hospital, we have no method by which to assess neonatal deaths that occurred after hospitalization. Nevertheless, 398 liveborn infants died before discharge—usually within the first day of life. This group is referred to as "newborn deaths." The data include 348 twin pairs and one
Vol. 22, No. 3
Congenital Malformations
205
U. S . PEPARTMENT OF HEALTH, EPUCATION,'AND WELFARE Public HtaUh Suivicz DIVISION OF IUVIAN HEALTH
Downloaded by [UQ Library] at 18:29 13 March 2015
Area Offices and Hospitals
• Scmbiola Iodiu Rutmtkm Serricef Adminlotici) Fiom the Oklthonu InUu HciUli AIM Offici.
FIG. 1.—Location of Indian Health Service hospitals and area offices.
set of triplets. The twin data will be discussed in detail in another report (Morgan and Niswander, unpublished). VARIABLES RELATING TO EPIDEMIOLOGICAL AND GENETIC CHARACTERISTICS OF THE SAMPLE
The independent variables considered include a variety of indicators and measures of social, medical, demographic, and genetic factors with potential influence on pregnancy outcome. Specifically, we included sex of the infant, year of birth, maternal age, number of previous pregnancies, absence of prenatal care, legitimacy, maternal serology, nonhospital birth, residence (on and off reservation), and endogamy (parents of same or different linguistic group). If no information pertaining to the father appeared on the records, the birth was
considered illegitimate. Infants born outside of IHS hospitals, but admitted within 48 hours received regular newborn records. The newborn record contains space for recording tribal affiliation of both mother and father. If the parents were of different tribes, the child was arbitrarily assigned to the father's tribe. Since 95 different tribal groups were encountered, it was necessary to classify tribes into more discrete groups. The tribes were grouped by major language families following classifications given by Hodge (1912), Swanton (1925), and Wissler (1938). Six specific language groups were delineated: Aleut-Eskimo, Athabascan, Algonquian, Iroquoi-Muskhogean, Hokan-Siouan, and Uto-Aztecan. These six groups encompassed over 90 per cent of the sample with "other" and non-Indians com-
Niswander, Barrow, and Bingle
Downloaded by [UQ Library] at 18:29 13 March 2015
206
Social Biology
prising the remainder. The original geo- blood was recorded in finer fractions, it was graphic distribution of these language arbitrarily rounded down to the nearest groups was modified from Underhill (19S3) one-eighth. Since ABO and Rh blood types and is shown in Figure 2. The eight lan- of the mother are included on the newborn guage groups were coded by use of seven record, it was possible to obtain an overall "dummy" variables indicating deviations appraisal of the reliability of the stated from the Uto-Aztecans (Uto-Aztecan, X i - degree of blood. For each mother's degreeX 7 = 0; Athabascan, Xi = 1, X2-X7 = 0; of-blood category (0-8), frequencies of the Aleut-Eskimo, Xx = 0, X 2 = 1, X3-X7 = B and r alleles were calculated. Assuming that both alleles are absent in pure Indians 0; etc.). and that all intermixture was Caucasian, Information relating to non-Indian adadmixture estimates were calculated for mixture was available from the newborn each "blood" category using 0.074 and record as "degree of Indian blood" and was 0.387 as the respective Caucasian frequenrecorded as a fraction for each parent. For cies of B and r. A high degree of correlaanalytic purposes, the degree of Indian tion was obtained between stated degree blood was coded in eights (0, non-Indian; of blood and admixture estimates based 8, full blood) with the infant scored as the upon blood typing (Figure 3). Although the average of the parents. If the degree of
^ B Eskimo Aleut EZ3 Athabascan E2D Algonquin ESHokan Sioux CED Uto-Azlecan
FIG. 2.—Geographic distribution of major linguistic groups of North American Indians. (Reprinted from Redman's America by Ruth Underhill by permission of the University of Chicago Press. Copyright © 19S4 by The University of Chicago. All rights reserved.)
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87.5 75.0 62.5 50.0 37.5 25.0 12.0 PERCENT CAUCASIAN ADMIXTURE BASED ON REPORTED DEGREE OF BLOOD
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Fie. 3.—Relationship between estimate of Caucasian admixture based on the individual's stated degree of blood (X coordinate) and an estimate based on r and B allele frequencies (Y coordinate within degree of blood categories.
degree of blood clearly underestimates admixture, particularly at the lower levels, it does appear that degree of blood is a justifiable measure of intermixture. In addition to the general descriptive data presented, we have employed stepwise regression to analyze total as well as selected specific malformation rates for effects of (1) linguistic groups, (2) medical-cultural variables, and (3) non-Indian intermixture. Our approach was first to test for differences between linguistic groups using the seven "dummy" variables (as previously mentioned). This procedure considers variation among groups in the regression model. After linguistic group variables were added, the various significant medical-cultural variables were added in stepwise fashion. The next step was to introduce the
child's degree of blood into the regression equation. If the effect of the child's admixture was not significant, the analysis was terminated. If the child's degree of blood was significant, we introduced the square of this term and tested for deviation from additivity; then as a separate procedure, we entered the mother's degree of blood to obtain information regarding maternal effects. This methodology results in a test of genetic admixture which is to an extent free of concomitant environmental variation. RESULTS
A listing of all major malformed infants by organ system is presented in Table 2. Infants with anomalies of more than one system are so classified. Among the 43,711 liveborn infants, 803 or 1.84 per cent had
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208 TABLE 2
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MAJOR MALFORMATIONS AMONG 43,711 LTVEBORN AMERICAN INDIAN INFANTS AS DIAGNOSED IN INDIAN HEALTH SERVICE HOSPITALS ON "NEWBORN MEDICAL RECORDS"
Major Malformations No. Musculo-skeletal system—single malformations Clubfoot 64 Dislocation of hip 27 Diaphragmatic hernia 9 Polydactyly 93 Syndactyly 8 Phocomelia 1 Hemimelus 4 Ectrodactyly 3 Torticollis 2 Craniostenosis 5 Constructive bands of digits 1 Atrophic fingers 4 Absent pectoralis major 1 Rudimentary feet 1 "Buckled" ribs 1 "Claw" feet 1 Clubhand 1 Deformed femur 1 Facial asymmetry 1 Facial cleft 1 Inguinal hernia (female) 3 Total 232 Musculo-skeletal system—Multiple malformations Dislocated fingers; dislocated knees 1 Dislocated hip; subluxation of knee . . . 1 Polydactyly; rudimentary digits 1 "Lobster claw" deformity of hands; lobster claw deformity of feet 2 Clubfoot; "lobster claw" deformity of hand; absent forearm 1 Clubfoot; hand deformity 1 Clubfoot; dislocation of hip 3 Clubfoot; hypoplasia of radius; absent digits 1 Polydactyly; syndactyly 2 Hypoplastic pectoralis major; malformed hand 1 Total 14 Respiratory system Aplasia of lung 1 Choanal atresia 5 Tracheal stenosis 1 Total 7 Cardiovascular system Congenital heart disease (all types incl. undetermined) 121 Hemic and lymphatic system Cystic hygroma 1 Digestive system—single malformations Branchial cleft cyst 4 Cleft lip ± cleft palate 72 Cleft palate 23 Agenesis of mandible 1 Micrognathia 2 Midline cleft of maxillary gingiva . . . . 4 Intestinal obstruction ' 9 Atresia of small intestine (incl. pyloric stenosis) 15
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TABLE 2 (Continued) Major Malformations No. Imperforate anus; recto-vaginal fistula 2 Anal stenosis 2 Omphalocele 6 Atresia of esophagus 1 Tracheo-esophageal fistula 5 Performation of small intestine 1 Total 147 Digestive system—Multiple malformations Imperf orate anus; recto-vaginal fistula Tracheo-esophageal fistula; atresia ani 1 Total 3 Urogenital system Persistent cloaca 1 Polycystic kidney 2 Bladder neck obstruction 3 Hypospadius 30 Extraversion of bladder with patent urachus 1 Pseudohermaphroditisim (incl. adrenogenital syndrome) 8 Bladder, diverticulum 1 Total 46 Nervous system—Single malformations Microcephalus S Hydrocephalus 14 Anencephalus 7 Encephalocele 1 Occipital meningocele 4 Spina bifida Simple 2 With meningocele 9 With meningocyelocele 11 With meningocyelocele; hydrocephalus 2 Bilateral paresis of legs* 2 Total 57 Nervous system—multiple malformations Hydrocephalus; encephalocele 1 Hydrocephalus; agenesis of corpus callosum; meningomyelocele 1 Total 2 Organs of special sense: eye Cataract 3 Corneal opacity 6 Glaucoma 2 Proptosis 1 Total 12 Organs of special sense: ear Microtia/atresia of auditory canal . . . . 21 Integumentary system Albinism 10 Hemangioma 6 Aplasia cutis congenita 2 Ichthyosis congenita 1 Total 19 Endocrine system Congenital goiter 2 Syndromes or recognizable disease entities Achondroplasia 1 Arthrogryposis 1 Down's syndrome 24 With congenital heart disease 8
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Congenital Malformations
TABLE 2 (Continued) Major Malformations With congenital heart disease; cataracts With cataracts With cataracts; deformed ear With omphalocele With cleft palate With anal atresia Rubella syndrome Crouzon's syndrome DeLange's syndrome (?) Trisomy 18 Trisomy 13-15 Otomandibular dysostosis Congenital lues Total Multiple malformations—multiple systems Cleft lip and palate; diaphragmatic hernia; microtia; clubhand Cleft lip and palate; inguinal hernia (female) Cleft lip and palate; proptosis right eye Cleft lip and palate; microcephaly; clubfoot Cleft lip and palate; clubfoot, rudimentary finger; syndactyly Cleft palate; clubfoot Cleft palate; clubfoot; tracheoespphageal fistula; hemivertebra; microtia Cleft palate; pseudohermaphroditismj polydactyly Cleft palate; congenital heart disease; anomaly of brain Tracheo-esophageal fistula; aortic stenosis; absent kidney Atresia of esophagus and trachea; aglossia; micrognathia Intestinal obstruction; malformed penis Intestinal obstruction; clubfoot Intestinal obstruction j clubfoot; microphthalmia; micrognathia Omphalocele; absent diaphragm; hypoplastic kidney; clubfoot Imperforate anus; "spine and rib anomalies" Imperf orate anus; dislocated hip; "digital" and vertebral anomalies" . . Cranial dysostosis; branchial cleft cyst; hypertrophy of gingiva Anencephaly; micropenis; clubfoot Cranial meningocele; bilateral cataracts Occipital meningocele; renal agenesis . . Microcephaly; deformed hands and feet Microcephaly; congenital heart disease Microcephaly; tetrology of fallot; micrognathia; deformity of ear Hydrocephaly; cataracts; micrognathia; abnormal genitalia Hydrocephaly; phocomelia; low set ears Hydrocephaly; meningomyelocele; clubfoot; cataract Hydrocephaly; arthrogryposis
No. 1 2 1 1 1 1 2 1 1 2 2 9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2
TABLE 2 (Continued) Major Malformations Meninogocele; congenital heart disease Meningomyelocele; clubfoot Meningomyelocele; clubfoot; knee contracture Congenital heart disease With mandibulofacial dysostosis; hypertelorism With microphthalmia With hypoplasia of lung With polydactyly With polydactyly; syndactyly With clubhand; blindness With "lobster claw" deformity of feet With clubfoot With clubfoot; low set ears; malformed chest; CNS malformation . . With dislocated hip; clubfoot; dislocated wrist; corneal opacity . . . . With discolored hip With torticollis With polycystic kidney With anomalous kidney With micropenis Absent arms; syndactyly of toes; patent ductus arteriosus: microphthalmia . . Non-opposable thumbs; choanal atresia "Lobster claw" deformity of feet; deformed hand; choanal atresia Clubfoot; cranial dysostosis Clubfoot; coarctation of aorta Polydactyly; syndactyly; micropenis; micrognathia; low set ears Polydactyly; syndactyly; micrognathia Polydactyly; microtia; "abnormal" fades "Abnormal" toes; facial paralysis . . . . Absent digits; urethral stricture; absent kidney Hypertelorism; low set ears; hand abnormality Undefined multiple abnormalities incompatible with life Total Grand total * Twins concordant.
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No. 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 60 802
one or more major malformations. This figure compares closely with a frequency of 2.06 per cent found by Woolf and Turner (1969) in the nursery records of liveborn infants at the Latter-Day Saints Hospital in Salt Lake City, Utah. However, it is considerably higher than the 1.02 per cent observed among Japanese by Neel (1958) or the overall frequency of 1.27 per cent recorded by Stevenson et al. (1966) from 24 World Health Organization centers.
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Excluding multiple births, there were 43,526 infants recorded in the study. These births represent 33,755 different mothers and 8,874 sibships or half-sibships of two or more infants. A listing of the major malformations occurring within the same sibship is given in Table 3. In only seven cases TABLE 3
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MAJOR MALFORMATIONS OCCURRING IN TWO OR MORE SIBS OR HALF-SIBS AMONG 8,874 SIBSHIPS
1. A. B. 2. A. B. 3. A. B. 4. A. B. 5. A. B. 6. A. B.
7. A. B. C.
Cleft lip and palate Mongolism with congenital heart disease
Albinism Albinism Albinism Albinism Polydactyly Occipital meningocoele Congenital dislocation of hip. Congenital dislocation of hip Clubfoot Arthrogryposis Congenital dislocation of hip Polydactyly of the hand Polydactyly of the hand and feet
was there more than one affected child born to the same mother. Major genes are certainly indicated in the two instances of albinism and possibly for polydactly. The occurrence of this large number of sibs in the sample creates a potential problem for analysis. However, the very low recurrence rates involved suggest that such a factor will have very little effect on the overall results, and therefore it has not been considered in further analyses. Among the 119 stillbirths reported, ten (8.14 per cent) were malformed. Since this small sample of stillbirths is likely to be biased with respect to malformation, we examined fetal death certificates for Indians reported in Arizona for the years under study. During this period, 20,559 Indian births were reported in Arizona with 247 (12.0/1,000) stillbirths recorded. Of these births, 11,466 occurred in IHS hospitals and 126 (10.6/1,000) were stillborn. A
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listing of the sixteen (6.5 per cent) malformations recorded among these 247 infants is presented in Table 4. TABLE 4 MAJOR MALFORMATION AMONG 247 ARIZONA STILLBORN AMERICAN INDIANS, J U L Y 1964 TO JULY 1969, FROM FETAL DEATH CERTIFICATES AND INDIAN HEALTH SERVICE NEWBORN RECORDS
Abnormalities Multiple congenital abnormalities Anencephaly Hydrocephaly Cleft lip and cleft palate; congenital heart disease Siamese twins Mongolism Protrusion of forehead Myelomeningocele Phocomelia Corneal opacity Omphalocele
No. 2 1 S 1 1
Mean frequencies for specific malformations among different linguistic groups are given in Table 5. Results of regression analysis for various malformation categories and newborn death are given in Table 6. Although a number of statistically significant effects are noted, the J?2's are all quite low, indicating that, collectively, the variables studied have little predictive value with respect to the individual infant. DISCUSSION MAJOR MALFORMATIONS
The most striking aspect of these data with regard to total major malformation is the variation between the different linguistic groups. The observed frequencies range from 2.6 per cent in the Aleut-Eskimo group t o U per cent in the Uto Aztecans. These difference are highly significant The two-fold differences which we observe between subgroups of Indians, a Mongoloid population, ascertained in a relatively homogeneous hospital system in a single study are difficult to reconcile with Neel's assertion of similar frequencies of
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