dietary fluoride; the effect of maternal ingestion on offspring

12
334 Journd of Public ,Health Dentistry DIETARY FLUORIDE; THE EFFECT OF MATERNAL INGESTION ON OFFSPRING" By Brian A. Burt, B.D.Sc.* I t Dr. Burt, with a background of Australian education, was asked to take a "tough," but objective look at the supplementation of the mother's diet with fluoride to prevent dental caries in her ofspring. Not infrequently, expectant mothers in nonfluoridated areas are asking their dentists: "Should I be taking fluoride tablets to protect my baby's teeth against dental decay?" The answers may vary widely. The pharmaceutical industry sug- gests, naturally, that dietary supplements for young children are an efficient substitute for fluoridated water, both pre- and postnatally. The advertisements and sales of these supplements in nonfluoridated areas appear to be extensive. In view of the numbers of mothers in nonfluoride areas who seem to be ingesting dietary supplements of fluoride in the hope that their babies' teeth will become resistant to caries, a close examination of the value of this practice should be particularly appropriate. It is the purpose of this review, therefore, (1). to examine the literature relevant to maternal ingestion of dietary fluorides, per se, (2) to determine the degree of calcification that takes place in the dentition of the fetus prior to birth, (3) to determine the role of the placenta in the regulation of fluoride to the fetus, and, then, (4) to decide whether the mother's ingestion of dietary fluorides as a caries-inhibiting factor for her offspring is justified scientifically. Review of the Literature; 1. Calcification The value of fluoridation of drinking water in the prevention of dental caries has been established.', 4, ': Research on dietary supplements of fluoride, for use where drinking water is deficient in fluoride, has lagged behind that on fluoridation of water. The effectiveness of dietary supplements of fluoride in inhibiting dental caries in young children, however, has been demonstrated,". and supported by others.l", 17, 32, 34 The ingestion of dietary supplements of fluoride, in carefully controlled dosages, now is accepted as a measure to con- trol In an examination of the effectiveness of dietary supplements of fluoride, ingested by the mother before the birth of her child, the amount of dental calci- fication that takes place prenatally has to be considered. Massler and Schour,":' from their research on the development of the human dentition, have conclud- ed that calcification in the fetus begins at four-and-a-half months in utero and begins in the primary central incisors. They stated that, at birth, the crowns of these primary incisors were five-sixths calcified, the crowns of the cuspids were one-half calcified, the cusps of the first primary molars had coinpleted their cal- cification and coalesced, and the cusps of the second primary molars had calci- *An appraisal prepared while a graduate student in the School of Public Health of The Uni- "2, 9, :is, -11 and is being used widely.lS versity of Michigan. His home is 375 Canning Highway, Como, West Australia.

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Page 1: DIETARY FLUORIDE; THE EFFECT OF MATERNAL INGESTION ON OFFSPRING

334 Journd of Public ,Health Dentistry

DIETARY FLUORIDE; THE EFFECT OF MATERNAL INGESTION ON OFFSPRING"

By Brian A. Burt, B.D.Sc.*

I t

Dr. Burt, with a background of Australian education, was asked to take a "tough," but objective look a t the supplementation of the mother's diet with fluoride to prevent dental caries in her ofspring.

Not infrequently, expectant mothers in nonfluoridated areas are asking their dentists: "Should I be taking fluoride tablets to protect my baby's teeth against dental decay?" The answers may vary widely. The pharmaceutical industry sug- gests, naturally, that dietary supplements for young children are an efficient substitute for fluoridated water, both pre- and postnatally. The advertisements and sales of these supplements in nonfluoridated areas appear to be extensive. In view of the numbers of mothers in nonfluoride areas who seem to be ingesting dietary supplements of fluoride in the hope that their babies' teeth will become resistant to caries, a close examination of the value of this practice should be particularly appropriate.

It is the purpose of this review, therefore, (1). to examine the literature relevant to maternal ingestion of dietary fluorides, per se, (2) to determine the degree of calcification that takes place in the dentition of the fetus prior to birth, (3) to determine the role of the placenta in the regulation of fluoride to the fetus, and, then, (4) to decide whether the mother's ingestion of dietary fluorides as a caries-inhibiting factor for her offspring is justified scientifically.

Review of the Literature; 1. Calcification

The value of fluoridation of drinking water in the prevention of dental caries has been established.', 4, ': Research on dietary supplements of fluoride, for use where drinking water is deficient in fluoride, has lagged behind that on fluoridation of water. The effectiveness of dietary supplements of fluoride in inhibiting dental caries in young children, however, has been demonstrated,". and supported by others.l", 17, 3 2 , 34 The ingestion of dietary supplements of fluoride, in carefully controlled dosages, now is accepted as a measure to con- trol

In an examination of the effectiveness of dietary supplements of fluoride, ingested by the mother before the birth of her child, the amount of dental calci- fication that takes place prenatally has to be considered. Massler and Schour,":' from their research on the development of the human dentition, have conclud- ed that calcification in the fetus begins at four-and-a-half months in utero and begins in the primary central incisors. They stated that, at birth, the crowns of these primary incisors were five-sixths calcified, the crowns of the cuspids were one-half calcified, the cusps of the first primary molars had coinpleted their cal- cification and coalesced, and the cusps of the second primary molars had calci-

*An appraisal prepared while a graduate student in the School of Public Health of The Uni-

" 2 , 9, :is, -11 and is being used widely.lS

versity of Michigan. His home is 375 Canning Highway, Como, West Australia.

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Vol. 26, No. 2-Spring Issue, 1966 235

fied but still were isolated. They did not discuss the calcification of first per- manent molars.

In an abstract of a paper to be presented at the 42nd general meeting of the International Association for Dental Research, Christensen and Kraus14 discussed the calcification of the first permanent molar prior to birth. This re- port stated that they extracted the first permanent molars from 73 fetuses and infants, the ages of whom ranged from 19 weeks in utero to six months after birth. The initial calcification was related to the age of the specimens and in every instance calcification was found prior to birth. They claimed, also, their investigation showed that this calcification might begin as early as 28 weeks in utero, or as late as 32 weeks, and that as many as four cuspal tips might be present before birth. They reported the conclusion that the time, location, and degree of calcification of the first permanent molar was quite consistent, and fell within the range cited.

Gilster, Smith, and Wallace‘!’ used radiographs of 249 children to study the degree of calcification of the mandibular second primary molar in relation to age. They concluded that the previously established norms for ages of calci- fication of this tooth might be somewhat earlier than the averages obtained through radiographic evidence alone. They found at birth that this tooth was about eight percent calcified.

In his exhaustive research in Tokyo, Nomata:’!’ found that the primary molars of Japanese children began calcifying at five to six months in utero. Consider- ing the degree of calcification of the primary molars at birth, Nomata stated that maturation of enamel only was completed in two cusps of the first primary molar. Nomata studied the 140 fetuses and infants, belonging to the Tokyo Medical and Dental School. He used microscopic scanning of serial sections and viewed crowns after they were dissected.

During the research for his thesis, Bollerl” utilized about 200 fetuses to study the morphogenesis of the human dentition. He used dissection in his study as well as radiographs, and claimed that the results of his work confirmed the findings of Massler and Schour.23 Boller found that the pattern of the oc- clusal surface of the first primary molar had been outlined by birth, and that a certain amount of matiration of the enamel had taken place. His finding in this respect was similar to that of Nomata. Boller stated that evidence of calci- fication of the first permanent molar could be found at seven months in utero, and he stated further: “One should note that the first permanent molar (at birth) is well on its way to maturity . . . ” Boller considers the first permanent molar to be a primary tooth in its developmental pattern. His statement concern- ing the beginning of calcification in the first permanent molar was similar to that of Christensen and Kra11s.l~

2. Role of Placenta

The degree to which the placenta will allow passage of fluoride to the fetus has been the subject of considerable research. The investigation carried out with rats and dogs during the 1930s showed that the placenta, to some degree,’i1. ’$ was permeable to fluoride, although the concentration of fluoride at which this permeability occurred was not established. In Arizona, in 1935, Smith and Smith4? claimed to have found mottled enamel of primary teeth in some areas, and accepted this mottling as evidence of placental transfer of fluoride. The areas where they noted this mottling had levels of fluoride in the drinking water of 12 to 16 ppm.

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236 Journal of Public Health Dentistry

Gardner and his associates,L4 in 1952, examined and compared placentas from Rochester and Newburgh, New York. Rochester, at the time, had muni- cipal water containing 0.06 ppm of fluoride, while Newburgh's water contained 1.0-1.2 ppm. Gardner and his group found a consistently higher storage of fluoride in the placentas of the Newburgh group, and they concluded that the placenta may act as a concentrating organ or as a barrier. Buttner and Muhlerl? studied seven groups of rats who were receiving different concentrations of fluoride in their drinking water during pregnancy, and then determined the skeletal concentration of fluoride in the offspring at birth. The seven groups were drinking water containing'no fluoride, one ppm, three ppm, five ppm, 10 ppm, 25 ppm, and 50 ppm of fluoride, respectively. Buttner and Muhler concluded that the level of fluoride in drinking water needed to be at least 10 ppm during pregnancy before any appreciable increase in the concentration of fluoride was found in the offspring. In a later publication, Muhler?? stated:

Recently, sodium fluoride has been added to prenatal products as a suggested means of providing fluoride to the embryo. Undoubt- edly, this is the greatest abuse of fluoride therapy, because a consensus suggests that fluoride does not pass the placenta in sufficient amounts to afford any significant benefits to the embryonic tooth unless the concen- tration is more than 6-8 ppm.

In answer to a physician's question, Bibbf said that the placenta allowed passage of fluoride to the fetus, but did not cause mottling of the primary teeth. He stated further that it has not been established clearly that prenatal ingestion of fluoride reduces the activity of dental caries in the offspring. A differing view was expressed by Blayney and Hillg from their study of fluoridation in Evan- ston. They grouped their children so that they could compare the prevalence of carious lesions found in the primary dentition of children whose mothers used fluoridated water during preganancy, and those who did not. All used the same Evanston water postnatally. They concluded that the use of water con- taining one ppm of fluoride during the prenatal period, followed by its post- natal use, contributed added protection to the primary teeth over that provided by postnatal use only. A study, similar to that of Blayney and Hill, was carried out by Carlos and his group1? in Newburgh, New York. Carlos studied one group of children before fluoridation began in May, 1945, and additional groups afterward. In contrast to the findings of Blayney and Hill, Carlos and his asso- ciates found no statistical difference in the caries-experience of primary teeth between groups. They drew no conclusions regarding the role of the placenta in transference of fluoride to the fetus.

Investigating in the area of Jerusalem, where the drinking water had a level of fluoride of 0.55 ppm, Brzezinski and his associateT'l examined fetuses, whose ages ranged from three months to nine months, and determined the levels of fluoride in the femurs of these fetuses. They found that there was little demand for fluoride during the early months of preganancy, but that the demand in- creased greatly in the last three to four months. They did not relate this storage of fluoride to the maternal intake.

GedaIia and his group2" reached a quite similar conclusion in their studies of levels of fluoride in the urine of 117 pregnant women from the same area of Jerusalem used in Brzezinski's study. Gedalia studied the women from the fourth month through the ninth month of pregnancy, and found, at the fourth

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month, that the level of fluoride was the same as in the drinking water. It began to drop from this point and reached its lowest concentration in the eighth month of pregnancy. Gedalia used this evidence to suggest that fluoride was stored in the fetus and placenta. In a further study of 115 fetuses from the same area, Gedalia and his groupzii confirmed the finding that the mean level of fluoride in the fetus increased as the fetus approached full term, but they did not find such a marked increase in a study of 88 fetuses from an area where the level of fluor- ide in the drinking water was low, 0.05 to 0.1 ppm. The ages of the fetuses in this study ranged from four months to nine months.

A comparison of the two groups of fetuses, the 88 from the area of the low level of fluoride in the drinking water and the 115 from the area of medium level (0.55 ppm), detected no significant difference in the deposits of fluoride at the age of four months. With increasing age, however, the fetuses from the area of medium fluoride showed an ever-increasing mean level of deposition of fluoride. Gedalia and his associates used femurs, mandibles, and teeth to determine the level of fluoride deposited in the fetuses.

In still another study, Gedalia and his groupLi showed, when the maternal intake of fluoride was low, that fluoride passed freely through the placenta, and when the intake was high, the placenta played a regulatory role which pro- tected the fetus from the excess of fluoride. In this study Gedalia used two groups of pregnant women, a “low” group, ingesting water with a level of fluor- ide of 0.06-0.15 ppm, during pregnancy, and a “h igh group, which ingested water with a level of 0.6-0.9 ppm during pregnancy. There actually was a third group participating in this study; which ingested water with a level of fluoride of 0.5-0.6 ppin during pregnancy and with a dietary supplement of fluoride during the second half of pregnancy. This supplement was ingested daily in the form of a tablet that contained 0.5 ing. of sodium fluoride. The results ob- tained from this third group were the same as from the “h igh group, so Gedalia included them in the “high” group in his tabulations. At parturition, he found the level of fluoride in the blood from the cords was very little different for each group, but the levels of fluoride in the placentas of the “high” group, as well as the maternal blood-levels of fluoride in that group, were considerably higher. Gedalia gained his conclusion concerning the regulatory role of the placenta on the basis of these findings. He presented no specific conclusions about the group that ingested the dietary supplement of fluoride during preg- nancy.

In the most recent publication from this group, Gedalia, Zukerman and Le\.enthal”” found that the deposition of fluoride in bones and teeth for areas served by drinking water containing one ppm of fluoride was little different from the deposition found in areas served by water containing 0.5 ppm. For this investigation, Gedalia and his associates studied 71 fetuses, the ages of which ranged from five months to full term. Gedalia thought that this finding might indicate a maximum level of fluoride metabolized from drinking water, and he suggested that the fetus might take only the quantity of fluoride that it needs. Gedalia’s suggestion, that the placenta provided a partial barrier to the passage of larger quantities of fluoride, was similar to that suggested by Gard- n e P in 1952. The results of this latest study by Gedalia and his group were in accord with their previous findings.

At the completion of a 14-year study, Feltman and Kosel”’.“ concluded that fluoride did cross the placenta to enter the fetal blood and that this action took place both when the pregnant mother ingested fluoridated water and when

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238 J ournal of Public Health Dentistry

she used dietary supplements of fluoride. Feltman and Kosel based their conclu- sions on their studies of four large groups of women, one group ingested fluor- idated water throughout pregnancy, a control group which did not, a third group which ingested a tablet daily of calcium or sodium fluoride, and a control group which did not.

In an interesting study which took advantage of a Swedish law that legal- ized abortion, Ericsson and Malmnas'!' were able to observe the passage of fluoride across the human placenta. Their technic was to inject the isotope F'" intravenously into the maternal circulation just prior to the abortion, and then to examine the blood level of the isotope in both the maternal and fetal circula- tions, as well as the concentration of F'" in the placenta. Because of the short half-life of the isotope, the examinations had to be carried out during a period of not more than 10 minutes after the injection. The investigators found, in this time, that the concentration of F1& in the fetal circulation never exceeded one quarter of the simultaneous concentration of F" in the maternal circulation. The concentration of F1> in the placenta a t any one time was found to be somewhere between the other two concentrations, which would indicate passage of the iso- tope through the placenta into the fetal circulation. Ericsson and Malmnas carried out a similar investigation with rabbits and obtained similar results, except for a slightly higher mean level of the isotope in the fetal circulation.

The isotope F" was used again in the research of Bawden and his asso- ciates"7 at the University of North Carolina. Experimenting with sheep, Baw- den developed a technic which allowed him to determine the levels of the iso- tope in the fetal blood while the fetus was still in utero. He would inject the pregnant ewe with FlS, and then observe the level of the isotope in the fetal circulation over a two-hour period. The highest concentration of FIh recovered in the fetal circulation was 0.005 percent of the amount injected into the mother, which figure, interestingjy enough, was the same as that which Ericsson and Malmnas found in their human subjects. Bawden concluded that this low level resulted from a limited placental transfer, rather than from rapid clearance in the fetal plasma. In addition to these measurements, Bawden also ashed the carcasses of the fetuses to determine their total deposition of P. Of the original dose injected into the mother 0.42 percent was the highest concentration that he found in the fetuses. In a discussion of his research, together with an extensive review of the literature, Bawden stated:

It is not possible to state, on the basis of scientific evidence, that prenatal administration of fluorides will result in a beneficial effect in reduction of dental decay in the offspring. Likewise, the possibility of such results cannot be eliminiated. Physiologic evidence indicating rapid clearance of fluorides from the maternal blood, and relatively low fetal blood levels cast serious doubts on probable effectiveness of the once- a-day-administration of oral fluoride preparations. Clinical data are conflicting in nature and minimal in amount. Finally, commercial prod- ucts available have not been subjected to clinical trial in their mar- keted form.

Bawden then concluded by stating that ". . . patients should not be given the impression that clinical effectiveness in reducing dental decay in their off - spring is an established fact."

Montgomery,"'; in her review of the literature concerning dietary supple- ments of fluorides, stated that cariostatic effects possibly might be obtained

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Vol. 26, No. %--Spring Issue, 1966 239

from fluoride tablets, but that much more needed to be known before their value could be stated. She stated no conclusions regarding the value of dietary sup- plements of fluoride by the mother during the prenatal development of her infant .

Hodge,”’ in answer to questions put to him from physicians, stated that limited data on human beings, who drink water with a level of fluoride at one ppm, have failed to show any benefit from drinking this water during preg- nancy. He stated that there was no endorsement for therapy by fluoride other than through fluoridation of water, and that fluoride tablets should not be given to a mother during pregnancy. Hodge continued:

Fluoride does cross the placental barrier so that maternal and fetal blood levels are comparable . . . there is no worthwhile evidence that this fluoride is effective in reducing any dental caries which may de- velop ultimately in the deciduous or permanent teeth.

Hodge based this conclusion on his statement that those portions of the enamel in primary teeth, which usually become carious, are mineralized largely after birth.

Appraisal of the Literature Reported

The findings of Massler and Schour,”:’ on the development of the human dentition, have been accepted by the dental profession sufficiently to be used for teaching purposes in a number of dental schools. The conclusion of Gilster, Smith, and Wallace,’!’ that previously established norms for the age of calcifica- tion of the mandibular second primary molar may be somewhat earlier than averages obtained through their study, was based on radiographic evidence. Because of the limited nature of their study, their results probably cannot be regarded as conclusive. The “somewhat earlier,” to which they refer probably is a short space of time that would make for little clinical difference in effect. The claim of Christensen and Kraus,’4 that the first permanent molar began calcifying before birth was reported in their abstract, only. The abstract al- lowed insufficient space to state the experimental method used. Their research, though interesting, would have to be appraised on the basis of the limited ab- stract, since no full report has been published to date.

Nomata’s study in Tokyo”“ was performed thoroughly. His findings did not differ markedly from those of Massler and Schour, although his subjects were Japanese, but his detailed experimental method permitted detailed conclu- sions. Nomata’s conclusion that the maturation of enamel was complete in only two cusps of the first primary molars, and completed in most of the primary anterior teeth at birth, was quite compatible with the findings of Massler and Schour. He did not discuss the first permanent molar. Boller’s research also was extremely thorough,’” and his findings agreed with those of both Massler and Schour and Nomata. Boller assigned credibility to the findings of Christensen and Kraus, and it appeared from his study that the first permanent molar may be calcified to a considerable extent at birth.

Because of the important role that they play in the eruption of the per- manent dentition, the primary molars might be considered as the most import- ant teeth in the primary dentition, hence, most of the discussion of prenatal calcification was centered on them. All of the investigations cited were in agreement, within quite narrow limits, concerning the amount of prenatal cal-

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cification of the primary dentition. The findings of Christensen and Kraus ap- pear acceptable, in view of Boller’s studies, and should possess some clinical significance, insofar as the dietary supplements with fluoride by the expectant mother are concerned.

The research of Gardner and his associates,g4 in their Rochester-Newburgh study of 1952, constituted a well-conducted investigation. Gardner and his asso- ciates stated rather cautious conclusions, and their statement that the placenta may act as a concentrating organ or as a barrier appeared to be justified. It served as a starting point for some later research. Buttner and Muhler,l? work- ing with rats, were able to come to more definite conclusions, which apparently were justified in the rat. They found that the maternal ingestion of fluoride pre- natally needed to be at least 10 ppm before any appreciable increase in skeletal deposition of fluoride was found. They were careful to state that this finding could not be applied necessarily to human beings and they were unable to come to any conclusion about resistance to caries by the teeth of the offspring. Their conclusions, however, may serve as a guide to the study of the process in human beings.

The report of Smith and Smith,42 which claimed that they observed mottled enamel of primary dentitions in Arizona in 1935, has not been supported by other researchers. Bibby” agreed that the placenta does allow passage of fluoride to the fetus, but he stated that mottled enamel in the primary dentition did not occur. It is possible that the condition reported by the Smiths was not mottled enamel although Bibby’s statement did not state his evidence for absence of mottling.

Carlos and his associates,’” working in Newburgh, found that the maternal ingestion of fluoridated water prenatally made no statistical difference in the caries-experience of the offspring. Carlos and his group, conceded that the sta- tistical methods used were not entirely satisfactory. In their analysis, a child with one carious first primary molar was counted in the same w i y a s a child who had a carious lesion in all four first primary molars. This group claimed that the customary comparisons of the average number of carious teeth per person, or carious surfaces per person, could be misleading. The claim was made because of the stronger correlation that existed between the condition of the teeth within individual mouths, than the correlation between the condition of the teeth between different individuals. This group stated that lack of inde- pendence between observations of this type made statements about the statistical significance of any observed differences hazardous. Some basis for this reason- ing may exist, but their admission that the statistical methods which were used were unsatisfactory, together with the lack of evidence of random sampling, leave these conclusions open to question.

Blayney and Hill,!) in their study of fluoridation in Evanston, also provided no evidence of random sampling. Their actual statistical tabulations, however, appeared sound, and they did use much larger samples than Carlos and his group. Both followed the same methods of research, but their conclusion, that maternal ingestion of fluoridated water prenatally did reduce the extent of caries-activity in the dentition of the offspring, was quite different. Because of a possible deficiency in the technic of sampling, some question of the conclu- sion by Blayney and Hill also should be raised. It was interesting to find in the literature, soon after Blayney and Hill published their research, that Carlos and his group criticized it.!) They made no claim that the conclusions were faulty, ,but expressed the opinion that the data presented did not support the

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conclusions. Carlos and group based their criticism on two points: (1) there was no examination of the relative prevalence of carious lesions in children, exposed to fluoride from birth, with that of children exposed throughout gestation; and (2) time cannot be disregarded as a possible factor of variability, since serial examinations, separated by the passage of some years, cannot be regarded legit- imately as independent of time. In reply to this criticism, Blayney and Hill'' stated their opinion that the data presented did support the conclusions, and that the use of serial examinations had not introduced another variable in the study.,

One point not raised in this discussion of the findings of Blayney and Hill was the clinical significance, They did not state which teeth were utilized in their study. Since the anterior teeth are five-sixths calcified at birth, it must be reasonable to assume that the reduction in carious lesions of the primary teeth, reported by them applied principally to the anterior teeth. It would be impor- tant to know how far their results applied to the primary molars. If it is ac- cepted that the molars are the most important teeth in the primary dentition then the results obtained by Blayney and Hill would not be as important clinic- ally as they might seem statistically.

The work of Gedalia, Rrzezinski, and their associates in Jerusalem,','. "-" lias maintained a consistently high standard, and appears to have advanced the knowledge of the prenatal physiology of fluoride considerably. The conclusion of this group that the demand for fluoride by the fetus increased greatly dur- ing the last three to four months of preganancy appeared to be valid, and their analyses of the urine of pregnant women2: provided documentation for this conclusion. Their studies were simple in nature and quite conclusive. The num- ber of women studied was 117 and sufficient, hence, for a sound statistical re- sult. The technic of sampling was not reported apart from that only healthly women were studied, Obviously, the group was limited to an investigation with available women and fetuses. Disregarding sampling, the thorough nature of the group's research should encourage acceptance of the conclusions.

The storage of fluoride in the fetus was confirmed by Gedalia and his group at a later date,"; and his conclusion that fluoride was stored in the fetus and in the placenta was in harmony with the earlier finding of Gardner," and ac- tually carried Gardner's conclusion a step further. In their later study, they demonstrated the regulatory role of the placenta in governing the passage of fluoride to the fetus,"'. and supported another of Gardner's suggestions. In the study during which the group made use of dietary fluoride as a supple- ment,?? this supplement was not studied and discussed carefully. Inferences might be drawn concerning this supplement, but the group rightly drew none. The impression was left that the group used the supplement with one group of women, almost as an afterthought. The hope might be expressed that this excel- lent group of researchers will carry out a more detailed and specific study with prenatal dietary supplements of fluoride.

but errors in investigative methodology render their conclusions quite unacceptable. No evidence of random sampling was cited, and the numbers of women examined for their first report'n were too small to demonstrate statistical significance. Some of the results on which conclusions were based appeared somewhat odd in retro- spect. For example, the mean placental concentration of fluoride for one of the controI-groups of women, supposedly receiving negligible fluoride, was

The investigation of Feltman and Kosel covered 14 years,2o,

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242 Journal of Public Health Dentistry

higher than the mean placental concentration of fluoride for a group ingest- ing fluoridated water. The finding of some fluoride, though not marked in amount, in one of the pharmaceutical preparations taken by the control-group, raised a question about how much ‘‘stray’’ fluoride was entering the investiga- tion. For their studies of the seven-year-old offspring of mothers, in the experi- mental group while pregnant, no accounting of diet and socioeconomic status was made, although the investigators admitted that all of the credit for the im- munity to caries, or relative immunity, could not be attributed to the fluoride alone. Feltman and Kosel Stated that supplements of dietary fluoride must be ingested during the first or second trimester of pregnancy in order to be effec- tive, rather than the third, but provided no evidence to support this statement. They disregarded time of calcification in their report. They presented no basis for the statements: “From the fetal blood supply, it (fluoride) enters into the enamel complex of the forming teeth . . .” and “Fluoride passes through the placenta to enter the fetal blood supply.” Neither statement was supported by their investigation. Feltman and Kosel claimed to have detected undesirable side-effects from the fluoride tablets used in the study, inasmuch as they stated that one percent of the group of women that received calcium fluoride or SO-

dium fluoride tablets exhibited gastrointestinal illness, nausea and vomiting. These symptoms, the researchers stated, were caused by the fluoride tablets - a claim which was poorly documented. It is possible, of course, that other fac- tors unrelated to the research might have produced such symptoms. Feltman and Kosel appeared not to have investigated this issue sufficiently to support their claim of undesirable side-effects produced by the dietary supplements of fluoride, since no other similar effects have been described in the scientific literature available. Unfortunately th? conclusions of Feltman and Kosel, be- cause of the faults in methodology, could not be utilized.

Ericsson and Malmnas were able to utilize but four human patients in their study with the radioactive tracer, F“. They have stated, because of the very small concentrations of the isotope measured, that errors could have occurred in their measurements, Since they obtained all of their samples within 10 minutes after injection of the isotope, it appeared possible that haste may have con- tributed some error. Rapid clearance of Flh from the maternal circulation seem to be more of a reason for haste than the half-life of the tracer, which they stated to be 110 minutes. Despite these drawbacks, the conduct of their investi- gation appeared sound enough for limited conclusions to be accepted. Other researchers, notably Bawden, have used their findings as a starting point for continuing studies.

Bawden’s investigation at the University of North Carolina was thorough.‘-’ His experiments with FIX were carried out in two pregnant ewes, and his re- sults were similar to those obtained with the four women by Ericsson and Malmnas. The curves obtained by Bawden, from plotting the clearance of F“ from the maternal blood against time, were similar to those obtained by Ericsson and Malmnas. His figure of 0.005 percent, representing the highest concentra- tion of the injected dose recovered from the fetal circulation, also was similar to the figure obtained by the Swedish investigators.

Bawden was the first researcher found in the literature who used the tech- nic of testing fetal blood-levels while the fetus was still in utero. He described his technic at length, and presented a method that appeared to be a sound ap- proach. It would appear of course, that he would encounter the same problem that Ericsson and Malmnas encountered in the possibility of error with such

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minute measurements. Bawden did not discuss this possibility, but the figures submitted for the total recovery of fluoride from the ashed carcasses of the fe- tuses showed a wide range. For example, the first fetus had stored 0.16 percent of the original dose injected into the mother, and the second had stored 0.42 percent. >Bawden agreed that definite conclusions could not be defended on the basis of the results from but two lambs and their mothers. He also cited the difference between sheep and human placentas as a further reason why his findings could not be used as a base for definite conclusions regarding human beings. Further development and use of his technics, it would appear, could provide valuable information in the future.

The statements of Hodge"' were cited in a context where the citing of references probably was inconvenient, but an assessment leaves the reader with the lack of evidence to document his statements. His contention that there was no endorsement for therapy with fluoride other than with fluoridation of water, has to be questioned, in light of the investigations reported with fluoride tab- lets.''. "' His statement, that fluoride tablets should not be given to a mother dur- ing pregnancy, also might find trouble in documentation.

A Summary

Literature relevant to the ingestion of dietary supplements of fluoride by expectant mothers has been reviewed. In seeking to determine the effectiveness of these dietary supplements, research has been examined that pertains to the pre- natal calcification of teeth and to the role of the placenta in regulating the amount of fluoride going to the fetus. From a critical examination of the methodology of the research repprted, it appeared that certain recommendations were justified re- garding (1) the average extent of calcification to be anticipated in the teeth at birth, (2) the factual basis for the regulatory mechanism of the placenta, in- sofar as fluoride was concerned, and (3) the justification for the ingestion of dietary supplements of fluoride by the mother to gain caries-resistant teeth in her offspring. Conclusions from this appraisal of the scientific literature now can he stated.

Some Conclusions

1. The use of the following average extent of calcification of the crowns of the primary dentition at birth appears justified by the research reviewed: (1) five-sixths of the anterior teeth, (2) one-half of the cuspids, (3) the cusps co- alesced of the first molars, (4) the cusps still isolated of the second molars, and (5) evidence seems to be increasing that substantially more of the crown of the first permanent molar is calcified at birth than was accepted earlier in the lit- erature;

2. The human placenta appears to exert a regulatory mechanism that limits the passage of fluoride to the fetus and probably protects against an ex- cess of fluoride in the mother's blood:

3. At the level of ingestion of one ppm in drinking water, clinical evidence is insufficient or too conflicting to conclude that the amount deposited in the fetal portion of the teeth will protect them against dental caries;

4. For those areas that have drinking water deficient in fluoride, published evidence is not sufficiently conclusive to support prescription of dietary fluorides to expectant mothers in order to increase the resistance of the primary dentition

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to caries, and, conversely there is insufficient evidence to contraindicate the in- gestion of such supplements;

5. The need exists, hence, to engage in further research to determine the effectiveness or ineffectiveness of dietary supplementation with fluoride during pregnancy to obtain protection of the offspring’s primary teeth against caries.

Bibliography

1.

2.

3.

4.

5.

6.

7.

8. 9.

10.

11.

12.

13.

14.

15.

16.

17. 18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

American Dental Association, Council on Dental Therapeutics. of dietary fluorides. Am. Dent. A. J., 56:589-91, Apr. 1958. Arnold, F. A., Jr., et al. prevalence; 10th year of the Grand Rapids-Muskegon studv. July 1956. Arnold, F. A., Jr., McClure, F. J., and White, C. L. Dent. Progress, 1:8-12, Oct. 1960. Ast, D. B., and Fitzgerald, Bern:dette.

Bawden, J. W. 1964. Bawden, J. W., Wolkoff, A. S., and Flowers, C . E., Jr. following intravenous injection into the ewe.

Oct. 1964. Bibby, B. G. Blayney, J. R., and Hill, I. N. Evanston dental caries study. XXIV. Prenatal fluorides- value of waterborne fluorides during pregnancy. Am. Dent. A. J., 69:291-4, Sept. 1964. Comment and reply, 69:808-9, Dec. 1964. Boller, R. J. J. Dent. Child., 31:67-97, 2nd Quar. 1964. Brzezinski, Aron, et. al. Fluorine in the human fetus. J. Obstet. ancl Gynecol., 15:329-31, Mar. 1960. Buttner, G., and Muhler, J. C. J. Dent. Res., 37:326-9, Mar.-Apr. 1958. Carlos, J. P., Cittelsohn, A. M., and Haddon, William, Jr. Caries in deciduous teeth in relation to maternal ingestion of fluoride. Christensen, G. J., and Kraus, B. S. Initial calcification of the human first permanent molar. Dean, H. T., et al. Studies on mass control of dental caries through fluoridation of the public water supply.

Prescribing supplements

Effect of fluoridated public water supplies on dental caries Pub. Health Rep., 71:652-8,

Sodium fluoride tablets for children.

Effectiveness of water fluoridation. Am. Dent.

N. C. Dent. So?. J.. 47:10-6, Jan,

17” recovery from fetal lambs J. Dent. Res., 44: 1013-4, Sept.-Oct. 1965.

Placental transfer of F“ in sheep. J. Dent. Rrs., 43:678-83, Sept-

A. J., 65:581-7, NOV. 1962. Prenatal +dministration of fluorides.

Prenatal exposure to fluoride. Am. hled. A. J., 176:831, June 3, 1961.

Fetal morphogenesis of the human dentition.

Fluoridle placental transfer in the rat.

Pub. Health Rep., 77:658-60, Aug. 1962.

Abstr. J. Dent. Res., 43:897, Sept.-Oct. 1964.

Pub. Health Rep., 65:1403-8, Oct. 27, 1950. Dietz, H. V. Dent. A. J., 33:7-9, Dec. 1953.

Sodium fluoride tablets in the precision control of dental caries. Mo. S.

- _ - _ _ _ - _ - _ _ _ - ~ . Dudenbostel, R. E., Grissoni, D. K., and Steinberg, S. S. by Anierican dentists. Ericsson, Y., and Malmnas, C. L. in man and rabbit. Acta Obstet. Gynecol. Scanclinav., 41: 144-58, 1962. Feltman, Ruben, and Kosel, George. to the fetus. - _ _ - - - - _ _ ~ __-_. gation-final report. J. Dent. Med., 16: 190-9, Oct. 1961.

Sodium fluoride tablets. Dent. Surv., 34: 180-1, Feb. 1958. The use of svsteinic fluorides

Placental transfer of fluorine investigated with F’*

Prenatal ingestion of fluorides and their transfer

Prenatal and postnatal ingestion of fluorides-fourteen Years of investi-

Pub. Health Dent., 20: 13-6, Summer 1960.

Science, 122:560-1, Sept. 23, 1955.

Fluoride supplements for the prevention of dental caries. Edit. Canacl. Dent. A. J., 29:410, June 1963. Fluoride with vitamins rejected by Council on Dental Therapeutics, American Dental Association. Gardner, D. E., et. al. The fluoride content of placental tissue as related to the fluoride content of drinking water. Gedalia, Itzhak, Brzezinski, Aron, and Bercovici, Bruno. Uninary fluoride levels in women during pregnancy and after delivery. Gedalia, Itzhak, et al. Fluoride content of teeth and bones of human fetuses. Arch. Oral Biol., 9:331-40, May-June 1964. _____-___-____. Placental transfer of fluoride in the human fetus at low and high F- intake. J. Dent. Res., 43:669-71, Sept.-Oct. 1964.

Am. Dent. A. J., 62:466, Apr. 1981.

Science, 115:208-9, Feb. 22, 1952.

J. Dent. Res., 38:548-51, May-June 1959.

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28.

29.

30. 31.

32.

33.

34. 35.

36.

37.

38. 39.

4u.

41.

42.

Gedalia, I., Zukerman, H., and Leventhal, H. Fluoride content of human bones and fetuses: in areas with about 1 ppm of fluoride in drinking water. Am. Dent. A. J., 71:1121-3, Nov. 1965. Gilster, J. E., Smith, F. H., and Wallace, G. K. Calcification of mandibular second primary molars in relation to age. J. Dent. Child., 31:284-8, 3rd Quar. 1964. Hodge, H. C. J. Pediat., 63:454-8, Sept. 1963. Knouff, R. A,, et. al. J. Dent. Res., 15:291-4, SeDt. 1936.

Fluoride tablets: questions and answers. Permeability of the placenta to fluoride.

Martin, N. D. Role of fluorides in preventing dental caries. Dent. Mag. and Oral Topics, 80:37-9, Mar. 1963. Massler, Maury, and Schour, Isaac. Dent. A. J., 28:1153-60, July 1941. Menczer, L. F. Fluoride tablets. Am. Dent. A. J., 59:542-3, Sept. 1959. hlichigan Department of Health, Division of Public Health Dentistry, and University of Michigan, School of Public Health. Prescribed supplements of dietary fluorides. Mich. S. Dent. A. J., 45:231, May 1963. Montgomery, Adele. Utilizing dietary fluorides; an appraisal of their effectiveness, practicality and safety. Pub. Health Dent., 23: 199-207, Winter 1964. Muhler, J. C. Current evaluation of fluoride therapy. Am. Pharm. A. J., 3:133-5, Mar. 1963. Murray, Margaret. J. Physiol., 87: 388-93, Sept. 1936. Nomata, Nobukazu. Chronological study on the crown formation of the human deciduous dentition. Tokyo Med. and Dent. Univ. Bul., 11:55-76, Mar. 1964. Pollak, H. Caries prevention bv administration of mulgatum F tablets. Deutsche Zahuarzleblatt, 14: 363-5, June 22, 1960. Public Health Association defines use of fluoride supplements. Am. Dent. A. J., 68:96-7. Jan. 1964. Smith, Margaret C., and Smith, H. B. Science, 81:77-9, Jan. 18, 1935.

The development of the human dentition. Am.

Maternal transferance of fluorine.

Mottled enamel of deciduous teeth.

Women In Science; Why So Few?

In Science for May 32, 1965, Alice S. Rossi, an associate in research at the University of Chicago, published an article, under the title indicated, which stated that mothers could achieve scientific careers too. In the issue of Science for July 30, the same year, Marjorie Dorman of Media, Pennsylvania, submitted a lullaby that had been stimulated by Alice Rossi’s contemplation of a ‘brave new scientific world” for women. Said Miss Dorman, edited slightly:

Hush m y little baby and brush away that tear, Your hlonz needs science for completing her career.

Please don’t fret and whimper, that an affective quirk; Mother’s just out looking for more meaningful work,

You’ll love the child-care center, so cunningly contrived To cope with all the ills when maternally deprived.

So what if meals are tardy and the cleaning inefectual; Take comfort in the fact that your Mom’s an intellectual.