BIRTH DEFECTS (pp. 212-219)

As an agent capable of producing meiotic chromosome changes, fluoride also clearly has the potential for transmitting malformations to offspring -- including man. One such birth defect, called mongolism or Down's syndrome, which arises from a trisomy of one of the G-group chromosomes, was the subject of a series of remarkable investigations by the late Ionel Rapaport, a French-trained endocrinologist at the Psychiatric Institute of the University of Wisconsin, Madison. He had no prior interest in fluoride was led to it by his investigations.

In searching for clues to the etiology of Down's syndrome, Rapaport was struck by the high prevalence of cataracts he encountered in mongoloids above age 20 -- an incidence amounting to 70% (67 out of 95) (22). His curiosity was also aroused when he observed that nearly 40% of the mongoloids at one of the Wisconsin State colonies had been born in Green Bay, whereas only 17.5% of the epileptics in that institution had come from that city. He then discovered that the incidence of blindness due to senile cataracts in Green Bay among persons over age 65 was 44% higher (18.6% vs. 12.9%) than in other major cities of the state (22).

Seeking an explanation for these remarkable coincidences, he considered the possibility that an environmental agent might be involved. He recalled that in 1853 Chatin had linked goiter and cretinism, another birth defect, with drinking water and had established a lack of iodine as the culprit. Rapaport also observed that many of the mongoloid children had mottled teeth and, apparently, an unusually low incidence of dental caries (23). All these circumstances directed his attention to the fluoride content of the Green Bay water supply, which indeed turned out to have a comparatively high natural fluoride content: 1.2-2.8 ppm -- much higher than in most other Wisconsin communities.

He then pursued this lead and ascertained the place of birth of all mongoloid children living in institutions as of July 1, 1956, in the four states of Wisconsin, North and South Dakota, and Illinois, and grouped them according to the published fluoride content of the municipal drinking water. In a tabulation of the 687 urban cases he found a statistically significant, two-fold greater prevalence or risk of mongoloid births in communities with 1 ppm or more fluoride than in those with little or none in the water. He presented these findings to the French National Academy of Medicine in Paris in November 1956 (25).

How reliable are these discoveries? An application of Van Valen's formula (26) reveals a combined statistical probability of less than 1 in 125,000 that the entire set of correlations from all four states was due to chance (27). The same parallelism between the prevalence of mongolism and the fluoride content of drinking water at the place of birth subsequently corroborated by data supplied by 46 superintendents of institutions in other areas of the United States (28).

Rapaport also correlated the age of the mothers of mongoloid children in Wisconsin with the fluoride content of the water supply. The mean maternal age was 34.26 years in the low (0.1-0.5 ppm) fluoride areas, whereas in the 1.0-ppm communities it was 33.17 years, and in the high (1.2-2.8 ppm) fluoride areas it was 29.81 years (25,29). In other words, in the high-fluoride areas more mothers gave birth to mongoloid children at an earlier age than in the low-fluoride communities. This same trend can also be seen in a survey reported in 1976 by workers at the USPHS National Center for Disease Control (30). As shown in Table 13-2, distinctly higher age-specific rates of Down's syndrome births occurred among younger mothers in the fluoridated areas. Such an effect is exactly what would be expected from long-term exposure to increased levels of a widespread environmental mutagen.

Shortly after Rapaport's first report appeared, W.T.C. Berry of the British Ministry of Health published a 10-year study of the occurrence of 199 cases of Down's syndrome according to maternal residence in certain selected "high" (0.7-2.0 ppm) and "low" (< 0.2 ppm) fluoride cities of north-central England (31). This survey, like two subsequent unpublished ones cited in a report by the Royal College of Physicians of London (32), apparently contradicts the findings by Rapaport, since it revealed little difference in incidence between the two sets of cities. On the other hand, these studies did not provide maternal age data; without such data the major demographic and other differences between the small number of cities could easily lead to overall incidence findings that are not truly representative. This possibility becomes a reality when we discover that the 5-year pilot study in the county of Essex included by Berry in his paper actually showed a 38% higher incidence of mongolism in the high-fluoride areas than in the low-fluoride ones.

Rapaport also stated that the discrepancy between his findings and those of Berry can be attributed to the 10-fold greater drinking of tea in England, a habit that accounts for a substantial increase in fluoride consumption and therefore erases the narrow difference in fluoride intake between the "high" and "low" fluoride cities (33). Furthermore, tea drinking in Britain has been linked with increased incidence of other birth defects, namely anencephalus (absence of brain) and stillbirths, especially in soft (low calcium) water areas (34).

In a second investigation, Rapaport followed suggestions by Russell, whose unpublished criticisms of Rapaport's original study have been widely cited (35). The new study included all officially recorded cases of mongoloid children in the State of Illinois who were born from 1950 through 1956 to mothers who lived in cities of 10,000 to 100,000 population. The data, reported in 1959 (33) and later in amplified form (36,37), indicated a highly significant association between the frequency of Down's syndrome and the fluoride content of the mother's drinking water (Table 1)

In 1961 Rapaport provided additional experimental evidence supporting fluoride involvement in mongolism. In the previous year the abnormal character of tryptophan metabolism in Down's syndrome had just been announced (38). Rapaport then conducted studies on the previously known formation of melanotic tumors in fruit flies bred in a fluoridated medium and obtained evidence that these lesions were connected with a genetically altered metabolism of tryptophan as in Down's syndrome (39). Other investigators have since confirmed the formation of these melanomas from fluoride in fruit flies (40) as well as the abnormal metabolism of tryptophan in mongoloid children (41).

In connection with his studies on the occurrence of Down's syndrome in Illinois, Rapaport also showed that other known minerals in the water, with the possible exception of calcium, did not affect his results. Although not statistically significant, the incidence of mongolism decreased slightly with a rise in the calcium concentration, in agreement with the well-known antidotal effect of calcium on fluorine (37). Furthermore, in the high-fluoride cities of Wisconsin he observed a significantly higher rate of premature stillbirths, which he attributed to fluoride-linked chromosomal anomalies or malformations incompatible with fetal life (37).

Overall, his data from the second Illinois study indicated a probability of at least 1,000 to 1 that the association of waterborne fluoride with the incidence of mongolism is real and not a statistical illusion. This is the highest figure recognized by the chi-square treatment. Moreover, the combined probability against the results being due to chance in both the first and second series of studies has been calculated (by Van Valen's formula (26)) to be 62,500,000 to 1 (27). No other comparable work on mongolism has achieved such a high degree of statistical reliability.

Despite the impressive statistical significance of his findings, Rapaport himself recognized shortcomings inherent in any such retrospective study. For example, he explicitly stated that probably only 41% of the actual number of cases are recorded at birth (37), an estimate which has since been repeatedly confirmed (42). In his investigations, however, death certificates and institutional records were also consulted, so that the same degree of ascertainment would be expected for both the fluoride and non-fluoride cities. As a matter of fact, his Illinois incidence figures are in the same range as those obtained by similar means in New York (43), and Missouri (44).

In 1974 Rapaport's findings were challenged by a study of Down's syndrome in the state of Massachusetts. This work covered the geographical distribution of 2,469 cases of mongolism born to resident mothers among a total of 1,833,452 live births from 1950 through 1966. These births occurred among residents of 321 non-fluoridated communities (less than 0.3 ppm fluoride in the water supply) and 30 fluoridated communities. In the latter group, nine towns ceased to fluoridate during the 17-year study period. In the nonfluoridating communities there were 1.34 mongoloid births per 1,000 live births and in the fluoridated ones 1.53 during periods of fluoridation (45).

Although the higher rate in the fluoridated cities (14%) was attributed to a slightly higher maternal age in those cities -- reported to be 34.0 years compared to 33.2 in the non-fluoridating ones -- and to "a slight upward trend ['about 1 per cent per year overall'] in the rates of Down's Syndrome" during the study period, no actual data were provided to support this claim; in fact, in none of the years did the overall statewide incidence exceed or even equal that of the fluoridated communities (highest = 1.51 in 1964) (46). Moreover, because the population exposed to fluoridated water was so extremely small, only 4.42% (81,017) of the total births and only 124 of the 2,469 cases of Down's syndrome, this difference of 1.53 versus 1.34 cases per 1,000 births was not formally significant statistically (x2 =1.99; P < 0.12). On the other hand, if the number of cases and total births in the fluoridated towns during this period had been exactly double (keeping the same rate of 1.53 per 1,000 births), the difference in rate between the fluoridated and non-fluoridated communities would then have become statistically significant (x2=3.99; P <0.05)!

In another report claiming "no association" between fluoridated water and Down's syndrome and other birth defects, the overall incidence of mongoloid births in the fluoridated counties of metropolitan Atlanta, Georgia, was actually higher than in the nonfluoridated ones by about the same amount as in Massachusetts (see Table 2) (30). Rapaport, too, had observed only a small increase in the incidence of mongolism after only five to ten years of fluoridation in Wisconsin (25,29). The higher age-specific rate among younger mothers reported in the Atlanta study as well as the National Intelligence Surveillance survey (30), also agrees with Rapaport's findings, although the authors were apparently unaware of the implications of this fact.

Finally, a recent analysis of data for over 2,000 cases of Down's syndrome available from an earlier USPHS investigation in lower Michigan has revealed that the occurrence of mongolism by local maternal residence reflected the same pattern and by about the same amount as in Massachusetts and Atlanta studies. All incorporated cities of 2,500 population and over (1950 Census) were included and grouped according to either the natural or artificial fluoride content of the water supply. Not only were the overall incidence rates higher with fluoridation, but the proportion of mongoloid births among younger mothers in the fluoride communities was also greater (47). The study also emphasized that many of the clinical and biochemical features regularly found in Down's syndrome are similar to various characteristics of the chronic toxic effects of fluoride (48).

In summary, with the exception of the National Intelligence Surveillance survey (30), which was based on admittedly incomplete ascertainment in only five major cities, all large-scale US studies to date have shown higher incidence or prevalence rates of Down's syndrome births in communities with elevated levels of fluoride in the drinking water. Even it the actual increase has been only a conservative 10% with fluoridation, it would still amount to at least 150 extra cases per year among the nearly 100 million people currently supplied with artificially fluoridated water in the United States*. In this situation it is difficult to see how any conceivable dental benefit of fluoridation could outweigh such an increased risk, for the parents of a mongoloid child dental benefits provide little comfort.

* Estimate based on an overall birth rate of 15 per 1,000 persons and the occurrence of one mongoloid birth per thousand live births.

Note: For More Recent Information on Fluoridation and Down's Syndrome, visit: http://www.fluoride-journal.com/98-31-2/31261-73.htm

REFERENCES

22. Rapaport, Y.[I.]: Les opacifications du cristallin mongolisme et cataracte senile (Donillees statistiques recentes). Rev. Anthropol. (Paris), 2(3):133-135, 1957. See also Refs. 29 and 36, below.

23. Orner, G: Dental Caries Experience Among Children With Down's Syndrome and Their Sibs. Arch. Oral. Biol., 20:627-634, 1975.

24. Hodge, H.C., and Smith, F.A.: Chronic Effects of Inorganic Fluorides, in J.H. Simons, Ed.: Fluorine Chemistry, Vol. IV. 1965, pp. 135-136.

25. Rapaport, I.: Contribution a l'etude du mongolisme. Role pathogenique du fluor. Bull. Acad. Natl. Med. (Paris), 140:529-531, 1956.

26. Van Valen, L: Combing the Probabilities from Significance Tests. Nature (Lond.), 201: 642, 1964.

27. Douglas of Barloch, Lord: Mongolism and Fluoride Water. National Pure Water Assoc., Huddersfield, Yorks., England, 1964.

28. Rapaport, I.: Letter to A.L. Russell, D.D.S., Chief, Epidemiology and Biometry Branch, National Institute of Dental Research, Bethesda, Md., May 7, 1957.

29. Rapaport,I: Contribution a l'etude etiologique du mongolisme. Role des inhibiteurs enzymatiques. Encephale, 46: 468-481, 1957. [See copy of paper]

30. Erickson, J.D., Oakley, G.P., Jr., Flint, J.W., Jr,, and Hay, S.: Water Fluoridation and Congenital Malformations: No Association. J. Am. Dent. Assoc., 93: 981-984, 1976; correction of tables, ibid., 95: 476, 1977.

31. Berry, W.T.C.: A Study of the Incidence of Mongolism in Relation to the Fluoride Content of Water. Am. J. Ment. Defic., 62: 634-636, 1958.

32. Report from the Royal College of Physicians of London: Fluoride, Teeth and Health. Pitman Medical, London, 1976, pp. 51-53.

33. Rapaport I: Nouvelles recherches sur le mongolisme. A propos du role pathogenique du fluor. Bull. Acad. Nat. Med. (Paris), 143: 367-370, 1959. See also Refs. 36 and 37 below. [See translated copy of paper| See original paper in french]

34. Fedrick, J: Anencephalus and Maternal tea Drinking: Evidence for a Possible Association. Proc. R. Soc. Med., 67: 356-360, 1974.

35. E.g., Dunning, J.M.: Current Status of Fluoridation. N. Engl. J. Med., 272: 30-34, 84-88, 1965. See also Ref. 24 above.

36. Rapaport, I.: Oligophrenie mongolienne et ectodermoses congenitales. Ann. Dermatol. Syphiligr., 87: 263-278, 1960.

37. Rapaport, I: Oligophrenie mongolienne et caries dentaires. Rev. Stomatol. 64: 207-218, 1963. [See copy of paper]

38. Jerome, H., Lejeune, J., and Turpin, R.: Etude de l'excretion urinaire de certains metabolites du tryptophane chez les enfants mongoliens. C.R. Hebd. Acad. Sci., 251: 474-476, 1960.

39. Rapaport, I.: A propos du mongolisme infantile. Une deviation du metabolisme de tryptophane provoquee par le fluor chez la drosophile. Bull. Acad. Natl. Med. (Paris), 145: 450-453, 1961.

40. Herskowitz, I.H., and Norton, I.L.: Increased Incidence of Melanotic Tumors in Two Strains of Drosophila Melanogaster Following Treatment with Sodium Fluoride. Genetics, 48: 307-310, 1963.

41. Coleman, M., Ed.: Serotonin in Down's Syndrome. North Holland, Amsterdam-London; American Elsevier, New York, 1973.

42. Hook, E.B.: Estimates of Maternal Age-Specific Risks of Down-Syndrome Birth in Women Aged 34-41. Lancet, 2: 33-34, 1976.

43. Gentry, J.T., Pakhurst, E., and Bulin, G.V., Jr.: An Epidemiological Study of Congenital Malformations in New York State. Am. J. Public Health, 49: 497-513, 1959.

44. Silberg, S.L., Marienfeld, C.J., Wright, H., and Arnold, R.C.: Surveillance of Congenital Anomalies in Missouri, 1953-1964. Arch. Envrion. Health, 13: 641-644, 1966.

45. Needleman, H.L., Pueschel, S.M., and Rothman, K.J.: Fluoridation and the Occurrence of Down's Syndrome. N. Engl. J. Med., 291: 821-823, 1974.

46. Fabia, J.J.: Down's Syndrome (Mongolism): A Study of 2421 Cases Born Alive to Massachusetts Residents 1950-1966. D.Sc. Thesis, Harvard School of Public Health, 1970. Table 1.

47: Burgstahler, A.W.: Fluoride in Drinking Water and the Occurrence of Down's Syndrome. Paper presented at the Eighth Conference of the International Society for Fluoride Research, Oxford, England, May 29-31, 1977, and at the 13^th Midwest Regional Meeting of the American Chemical Society, Rolla, Mo., Nov 3-4, 1977.

48. Burgstahler, A.W.: Editorial Review: Fluoride and Down's Syndrome (Mongolism). Fluoride, 8:1-11, 120, 1975.