Lauter Bach

8/13/2019 Lauter Bach

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2008;139;138-145 J Am Dent Assoc

Woods and Timothy DeRouenBrenda Townes, Gail Rosenbaum, James S.Helena Amaral, Jorge Leitão, Michael D. Martin,Castro-Caldas, Mario Bernardo, Henrique Luis,Martin Lauterbach, Isabel P. Martins, Alexandre

randomized trialSeven years of longitudinal observations in awithout amalgam-related mercury exposure:Neurological outcomes in children with and

jada.ada.org ( this information is current as of December 14, 2009 ):The following resources related to this article are available online at

http://jada.ada.org/cgi/content/full/139/2/138

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C O V E R S T O R Y

138 JADA, Vol. 139 http://jada.ada.org February 2008

Background. Although large-scale, randomized trials involving chil-dren have been completed and their results demonstrate an absence of

neurobehavioral effects from clinical exposure to mercury amalgam, neuro-

logical findings from such studies have not been reported.

Methods. The authors conducted a randomized, prospective trial exam-

ining the safety of dental amalgam in which 507 children aged 8 through

12 years were assigned to treatment with either amalgam or resin-based

composite. During seven years of follow-up, the authors performed annual

clinical neurological examinations, including an evaluation of neurological

hard signs (NHSs), presence of tremor and neurological soft signs (NSSs).

Results. The authors found no significant differences between treatment

groups in any of the neurological measures. Groups did not differ with

respect to the presence or absence of NHSs or tremor, nor the presence or

absence or severity of NSSs at any point. As expected, NSS severity scores

diminished with increasing age.

Conclusions. Even at the levels of amalgam exposure in this study (a

mean of 7.7-10.7 amalgam surfaces per subject across the seven years of

follow-up), the authors conclude that exposure to mercury from dental

amalgam does not adversely affect neurological status.

Clinical Implications. The current evidence is that potential

neurobehavioral or neurological effects from dental amalgam mercury

exposure in children are inconsequential.

Key Words. Mercury; amalgam; neurological; children.

JADA 2008;139(2):138-45.

For the past 150 yearsdental amalgam, formu-

lated from approximately

50 percent elemental mer-cury, has been used in

dental restorations. Controversyexists, however, as to whether detri-

mental effects on brain develop-ment in children occur as a function

of low-level exposures to mercuryfrom amalgam.1,2 In two recent long-

term, randomized, controlled clin-ical trials of elementary school chil-

dren, investigators found nosignificant differences in neuro-

behavioral performance betweenchildren who received amalgamrestorations and those who received

only resin-based compositerestorations.3,4

The nervous system and thekidney are the two main sites in

which any toxic effects of mercurymight be expected to occur, accord-

ing to results from studies of high-level mercury exposure.1,5 The neu-

rological examination provides one

ABSTRACT

Dr. Lauterbach is a neurologist/researcher, Laboratorio de Estudios de Linguagem, Faculty of Medicine, University of Lisbon, Portugal.Dr. Martins is a neurologist and the director, Laboratorio de Estudios de Linguagem, Faculty of Medicine, University of Lisbon, Portugal.Dr. Castro-Caldas is a professor, Department of Neurology, Faculty of Medicine, University of Lisbon, Portugal.Dr. Bernardo is an associate professor and the chairperson, Department of Preventive Dentistry, Faculty of Dental Medicine, University of Lisbon, Portugal.Mr. Luis is an assistant professor, Dental Hygiene Program, Faculty of Dental Medicine, University of Lisbon, Portugal.Ms. Amaral is a patient care coordinator, Faculty of Dental Medicine, University of Lisbon, Portugal.Dr. Leitão is a cathedratical professor, Institute of Health Sciences, Portuguese Catholic University, Lisbon, Portugal.Dr. Martin is an associate professor, Department of Oral Medicine, School of Dentistry, University of Washington, UW Health Sciences Building, 1958 PacificNortheast, Room B316, Seattle, Wash. 98195-6370, e-mail “[email protected]”. Address reprint requests to Dr. Martin.Dr. Townes is a professor emeritus, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle.Ms. Rosenbaum is a psychometrist supervisor, Neuropsychology Laboratory, University of Washington, Seattle.Dr. Woods is a research professor, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle.Dr. DeRouen is the executive associate dean for academic affairs and research, School of Dentistry, and a professor, Department of Dental Public Health Sciences,School of Dentistry, University of Washington, Seattle.

Neurological outcomes in children with andwithout amalgam-related mercury exposureSeven years of longitudinal observations in a randomized trial

Martin Lauterbach, MD; Isabel P. Martins, MD, PhD; Alexandre Castro-Caldas, MD, PhD;Mario Bernardo, DMD, PhD; Henrique Luis, MS; Helena Amaral, BS; Jorge Leitão, MD;Michael D. Martin, DMD, MPH, MA, MSD, PhD; Brenda Townes, PhD; Gail Rosenbaum, MS;James S. Woods, PhD; Timothy DeRouen, PhD

Copyright ©2008 American Dental Association. All rights reserved.

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JADA, Vol. 139 http://jada.ada.org February 2008 139

method of assessing the integrity of the central

nervous system. In children, it includes observa-tions of neurological hard signs (NHSs) and neu-

rological soft signs (NSSs). NHSs indicatedamage to specific neural structures and, in clin-

ical practice, are used to localize the site of lesionor dysfunction—for example, right homonymoushemianopsia as a sign for left occipital lobe lesion.

Screening for NHSs, consists of a brief neurolog-ical examination, including the evaluation of

mental status, cranial nerves, gross motor andsensory function.6,7

NSSs, on the other hand, are subtle signs of cen-tral nervous system dysfunction that have no local-

izing value—that is, they may merely point toimmature sensory-motor skills and not to any

structural damage or localization in the brain,

such as showing clumsiness in rapid sequences of fine finger movements. In healthy children, theirfrequency and severity tend to decrease with age,along with central nervous system maturation.8-10

In addition, their prevalence is increased in anumber of conditions, such as low birth weight,

mental or cognitive disturbances, emotional distur-bances, low IQ, attention-deficit/hyperactivity dis-

order, obsessive-compulsive disorders and schizo-phrenia.11-16 Although the physiopathology of NSSs

is not fully understood, the fact that they are asso-ciated with or might be predictive of certain disor-

ders makes them useful as nonspecific probes fordisturbances of neurological development.

In previously reported findings, our research

team found no significant differences in neuro-behavioral performance or nerve conduction

velocity (the primary study endpoints) betweenchildren who received only amalgam restorations

and children who received only resin-based com-posite restorations.4,17 This article reports additional

findings on secondary endpoints from systematicneurological examinations of the same cohort of 507

children, randomly assigned to receive dental treat-

ment with either amalgam or resin-based com-posite for posterior restorations (and composite for

all anterior restorations) and studied across aseven-year follow-up period. The aim of the neuro-

logical examination was to identify evidence of focallesions or diffuse dysfunction of the nervous system

to determine whether dental restoration withamalgam has a deleterious effect on neurological

development. The presence of tremor was specifi-cally recorded, in addition to the results of the rou-

tine neurological examination, because it is one of the common manifestations of mercury toxicity.2,3,5

PARTICIPANTS, METHODS ANDMATERIALS

Participants. The study participants were 507children from the Casa Pia school system in

Lisbon, Portugal, who were 8 to 12 years old at thetime of enrollment in the study, which began inJanuary 1997. Inclusion criteria for the study

were having at baseline at least one carious lesionin a permanent tooth, no previous exposure to

amalgam treatments, urinary mercury level lessthan 10 micrograms per liter, blood lead level less

than 15 µg per deciliter, IQ equal to or greaterthan 67 as obtained with the Comprehensive Test

of Nonverbal Intelligence18 and no interfering health condition, such as progressive neurological

disease or renal insufficiency. Participants were

randomly assigned to receive either dentalamalgam for posterior restorations (and resin-based composite restorations elsewhere) or resin-based composite restorations only. The study

design has been described in detail previously.4,17,19

Institutional review board (IRB) approval was

obtained at both the University of Washington,Seattle, and the University of Lisbon, Portugal.

( Author’s note: Please see a note at the end of this article regarding this IRB approval.) We

obtained parental or guardian consent, as well asassent from each child (although assent was not

required). Neurological examinations were ob-tained before the beginning of dental treatmentat baseline and at yearly follow-up examinations

for seven subsequent years.The table shows the number of participants in

each of the randomly assigned groups who under-went neurological examinations at baseline

(before receiving dental treatment) and at follow-up years 1 through 7, together with their sex, eth-

nicity and age. Similar to what was reported pre-viously for the neurobehavioral endpoints,4

among those with neurological examinations

there were no significant differences between thetwo randomized groups in sex, ethnicity or mean

age at the study’s inception.The number of participants who received a

neurological examination in a given year some-times is less than the number for whom we had

data at primary endpoints because the neurolog-

ABBREVIATION KEY. IRB: Institutional review

board. NHS: Neurological hard sign. NSS: Neurologi-cal soft sign.


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TABLE

Demographic data for subjects who received neurologicalexaminations.CHARACTERISTIC SUBJECTS’ DATA AT EACH MEASUREMENT POINT, ACCORDING TO RESTORATION TYPE

Baseline Year 1

Amalgam

Resin-Based Composite

Year 2 Year 3 Year 4 Year 5 Year 6 Year 7

No. of Children

Sex Male

Female

Ethnicity (No. [%])White

Nonwhite

Age (Years)Mean

Standard deviation (SD)

Amalgam SurfacesPresent (Mean No.)

No. of Children

Sex Male

Female

Ethnicity (No. [%])WhiteNonwhite

Age (Years)Mean

SD

Amalgam SurfacesPresent (Mean No.)

253

137

116

178 (70)

75 (30)

10.2

0.98

0.0

253*

141

112

180 (71)

73 (29)

10.1

0.94

0.0

235

129

106

164 (70)

71 (30)

11.3

1.01

8.3

231

131

100

164 (71)

67 (29)

11.1

0.99

0.0

230

126

104

163 (71)

67 (29)

12.3

1.03

8.1

222

130

92

155 (70)

67 (30)

12.2

1.00

0.0

197

109

88

137 (70)

60 (30)

13.3

1.06

7.7

185

102

83

134 (72)

51 (28)

13.2

1.02

0.0

197

111

86

137 (70)

60 (30)

14.3

1.07

8.0

193

104

89

132 (68)

61 (32)

14.1

1.05

0.0

194

101

93

145 (75)

49 (25)

15.3

0.99

8.9

200

111

89

141 (71)

59 (29)

15.1

0.99

0.0

146

78

68

98 (67)

48 (33)

16.2

0.94

9.7

144

79

65

96 (67)

48 (33)

16.0

0.93

0.0

136

69

67

95 (70)

41 (30)

17.2

0.98

10.7

142

80

62

99 (70)

43 (30)

16.9

1.03

0.0

* Data from the neurological examination are missing for one subject in the resin-based composite group.

ical examinations took place in schools and thechildren sometimes could not leave their class-

rooms at the time the neurological evaluationswere scheduled. The number of participants was

not uniform across study years because of dropouts and missed appointments.

The table also shows the average numbers of

surfaces filled with amalgam that were present atthe time of each neurological examination for

those in the amalgam group. The overall averagenumber of amalgam surfaces filled during the

study was previously reported,4 but the numberspresented here are specific to those who under-

went neurological examinations at each year. Asis shown, those in the amalgam group had a rela-

tively large number of surfaces treated withamalgam in the first year and maintained during

follow-up, so that those in the amalgam groupwho had neurological examinations averaged

between 7.7 and 10.7 surfaces of amalgam presentduring the seven years of follow-up neurological

examinations. The resin-based composite group,on the other hand, did not have any exposure to

amalgam. (Technically, two participants in thecomposite group received amalgam restorations

through inadvertent protocol violations. Although

those two participants originally were included inthe composite group as called for in intent-to-treat

analyses, the results presented here, for purposesof clarity, do not include any outcomes from those

two participants after they received the erroneousamalgam restorations. Their inclusion or exclu-

sion did not change the results of the analysis.)

Methods. One of two neurologists (either

I.P.M. or M.L.) performed neurological exami-nations for NHSs at baseline and annually for the

seven years of follow-up. A category for recording adventitious movements (including tremor) was


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added to the examination midway through year 1

of follow-up. We introduced screening for NSSs infollow-up year 2 and continued it throughout the

remaining five years of the study. NSS severityscores were added starting in follow-up year 3.

The neurologists performed the complete neuro-logical examination at one visit, and all exami-nations took place at the participants’ school.

At any point in the study, the difference betweenthe youngest and the oldest children of the sample

was four years. The children were examined onceper year, with an interval of approximately one

year between the follow-ups. During the course of the study, the sample became smaller because of

dropouts and because not all subjects were able toundergo every follow-up examination owing to

incompatibility with their school schedules. The

loss of participants throughout the seven-yearperiod, however, was in the acceptable range forsufficient statistical power.

The neurological examination was performed

according to standard practice.7 It included a brief evaluation of mental status (consciousness; lan-

guage; and orientation to person, time and place),observation of the function of the 12 cranial

nerves, gross motor function (muscle strength andtone and deep tendon reflexes), plantar responses,

cerebellar functions (including limb and gait coor-dination), touch, joint position and vibration

senses and recording of involuntary movements(such as athetosis or chorea). The neurologistsscored NHSs in eight different categories. They

evaluated the presence of tremor separately fromthe other NHSs. For analysis purposes, they

denoted NHSs (including tremor) as present if any were present or absent if none were present.

Because of the relationship of positional or kinetictremor to mercury toxicity, its presence or

absence also was reported separately.We introduced screening for NSSs in follow-up

year 2. We adapted the NSS evaluation from the

examination described by Peters and colleagues.

20

Six items of that examination have shown a high

correlation with cognitive performance and schoolachievement10; therefore, we selected them for our

study. All of these items were motor signs thathad a better interrater and test-retest reliability

than did sensory tasks21: the presence of mirrormovements, synkinesias, clumsiness of fine finger

movements, clumsiness of heel-to-toe walking (tandem gait), motor impersistence and restless-

ness or hyperactivity. The neurologists scoredeach item from 0 (absent) to 3 (maximum devia-

tion) points, depending on the degree of deviation

observed. There were two scores: one for the pres-ence or absence of any NSSs and an overall NSS

score calculated by summing the score of the sixindividual items. The latter ranged from 0 to 18

points, with higher scores corresponding to thepresence of more, or more evident, NSSs thanlower scores. (A detailed description of NSS

scoring is reported in the supplemental data sec-tion of the online version of this article, available

at “http://jada.ada.org”.)

Statistical analyses. We recorded for each

year the proportions of patients in the two treat-ment groups who exhibited NHSs, tremor or any

NSSs. We also computed means and standarddeviations of the NSS severity scores within each

treatment group for follow-up years 3 through 7.

We made comparisons between treatment groupsusing the Fisher exact test for proportions and thetwo-sample Student t test for mean severityscores (using SPSS, Version 15, SPSS, Chicago).

We report P values for each univariate test,without adjustment for multiple comparisons.

RESULTS

As is demonstrated in Figure 1, the percentage of participants exhibiting any NHSs before receiving

dental treatment was 2.4 percent in the resin-based composite group and 3.6 percent in the

amalgam group. Across time, there were slightdifferences between the two treatment groups inthe percentages exhibiting any NHSs, but the

directions of the differences were not consistentfrom year to year, and the differences were not

statistically significant in any of the years. Therewas an overall slight increase in the percentage of

participants exhibiting NHSs in both of thegroups during the last three years, as high as 8.9

percent to 14.1 percent.We report every NHS registered in follow-up

year 7 to illustrate the above-mentioned increase

in NHSs. Among the 31 children with NHSs, 13showed either kinetic tremor in the finger-nose

test or postural tremor in the outstretched-armtest. Two children had congenital decreased

auditory acuity, two had congenital nystagmus,and one child was blind in the right eye as a

result of surgery at the age of 7 months. Theneurologists observed one case of decreased level

of tendon reflexes of the lower limb (present onlyin follow-up year 7) and four cases of loss of

olfactory discrimination because of sinus disease.Two children showed an abnormal mental status


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with elevated affect, two children showed

decreases in visual acuity, and in two other chil-dren, the motor examination finding was not

normal owing to an acute trauma or surgicalintervention. In the remaining two cases, the

neurologists observed unilateral alteration of coordination and, in one child, a sensory loss in

the right thumb and second finger. At the end of the study, we still were investigating the eti-

ology of the latter two cases.

As is demonstrated inFigure 2, the percentage of

participants exhibiting posi-tional hand tremor started

low (0-2 percent) in the firstfour years of follow-up andincreased over the seven

years of follow-up to a levelbetween 4.4 percent and 4.9

percent. However, theincrease was uniform in both

groups, group differenceswere not consistently in one

direction, and there were nosignificant differences

between the amalgam and

composite groups in any of the years.

Observation of NSSsbegan in follow-up year 2. As

shown in Figure 3, in year 2,68.0 percent of participants

in the amalgam group and78.4 percent of participants

in the composite group exhib-ited one or more NSSs. That

difference is marginally sig-nificant ( P = .02), but in a sit-

uation in which one is testing differences across multiple(in this case, six) years, an

appropriate adjustment forthe multiple comparisons

would be to multiply the P

value by the number of com-

parisons, which wouldincrease the P value to a non-

significant .12. Regardless,the direction of the difference

in year 2 (10 percent higher

in the composite group) wasopposite the direction one

would expect if the mercuryfrom amalgam was having a deleterious effect.

For the remaining years, differences were smalland in varying directions, and none was near sta-

tistical significance. There was a clear trend of decreasing percentages across time in both

groups.For follow-up years 3 through 7, when the NSS

severity scores were recorded, Figure 4 showsmean NSS severity scores for the amalgam and

15

12

9

6

3

1 2 3 4 5 6 7

253

9

253

6

235

10

231

11

230

12

222

12

197

4

185

7

197

7

193

4

194

12

200

15

146

13

144

11

136

11

142

20

.60 .83 > .99 .37 .54 .69 .83 .13

3.6

2.4

4.34.8

5.2 5.4

2.0

3.83.6

2.1

6.2

7.5

8.9

7.68.1

14.1

Baseline Year of Follow-Up

No. of Patients Examined

No. With Any NHSs

Fisher Exact Test ( Value)

P E R C E N T A G E O F P A T I E N T S

Amalgam Group

Composite Group

Figure 1. Presence of neurological hard signs (NHSs), according to treatment group (amalgamor resin-based composite).

15

12

9

6

3

1 2 3 4 5 6 7

100

2

105

1

230

4

222

2

197

0

185

1

197

0

193

0

194

5

200

5

146

5

144

5

135

6

142

7

.61 .69 .48 > .99 > .99 > .99 > .99

2.0

1.0 1.7

0.9

0 0.5

0 0

2.6 2.5

3.4 3.5 4.4

4.9



No. With Any Tremor

Fisher Exact Test ( Value)

P E R C E N T A G E O F P A T I E N T S

Amalgam Group

Composite Group

Figure 2. Presence of positional tremor, according to treatment group (amalgam or resin-basedcomposite).


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C O V E R S T O R Y


composite groups. In a trend

similar to that of the NSSpercentages presented in

Figure 3, the average NSSseverity scores for the two

treatment groups differedonly slightly from year toyear, in varying directions,

with none of the differencessignificant in any of the five

years of follow-up for whichthe scores were recorded.

And, similar to what is seenin the data on percentages of

children exhibiting NSSs inFigure 3, there was a general

trend in both groups for the

average NSS severity score todecrease progressively acrosstime (with age), as isexpected in normally devel-

oping children.

DISCUSSION

This study’s results show

clearly that children exposedto elemental mercury from

dental amalgam, a substancepotentially toxic to the ner-

vous system,1,2

do not differfrom similar childrenwithout amalgam exposure

in terms of gross and fineneurological development, as

assessed in routine clinicalneurological examinations.

Thus, these data indicate theabsence of a generalized neg-

ative effect on children’s ner-vous system functions stem-

ming from the presence of

dental amalgam, and whilewe cannot rule out potential

adverse reactions in indi-vidual children, we found no indications of any.

An unexpected finding is the increased fre-quency of NHSs in both groups across the course

of the study. These signs usually indicate struc-tural damage to or dysfunction of either the cen-

tral or the peripheral nervous system. They usu-ally begin with adverse life or health events and

may occur at any point during life, and they maypersist (adding up in consecutive evaluations) or

disappear. The 31 NHSs observed in follow-up

year 7 appear to stem from from differing causative backgrounds. With 13 cases, almost

one-half of the NHSs in follow-up year 7 isexplained by the presence of tremor. In our

sample, the prevalence of tremor in follow-upyear 7 is 4.7 percent. Throughout the whole

study, tremor accounts for 24 percent of all NHSs.The prevalence of essential tremor in the general

100

80

60

40

20

1 2 3 4 5 6 7

228

155

222

174

197

139

185

130

197

119

193

113

194

97

200

113

146

65

144

59

135

43

142

53.02 > .99 .76 .23 .56 .38

68.0

78.470.6 70.3

60.458.5

50.056.5

44.541.0

31.9

37.3



No. With Any NSSsFisher Exact Test ( Value)

P E R C E N T A G E O F P A T I E

N T S

Amalgam Group

Composite Group

2.0

1.6

1.2

0.8

0.4

1 2 3 4 5 6 7

175

1.68

168

1.65

197

1.48

193

1.32

194

1.52

200

1.59

146

1.31

144

1.25

135

0.81

142

0.94

.33 .97 .31 .51 .29

1.61

1.79

1.20 1.20

0.99 1.16

0.85

0.75

0.46

0.57



Standard Deviation

Two-Sample t Test ( Value)

P E R C E N T A G E O F

P A T I E N T S

Amalgam Group

Composite Group

Figure 3. Presence of neurological soft signs (NSSs), according to treatment group (amalgam orresin-based composite).

Figure 4. Mean neurological soft sign score, according to treatment group (amalgam or resin-based composite).


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C O V E R S T O R Y


population ranges between 2 and 5 percent. The

prevalence of essential tremor shows a bimodaldistribution, with a peak in the second and sixth

decades.22-25 Although not all of the children in thesample will develop essential tremor, the remark-

able increase of tremor seems to be related toessential tremor. Furthermore, the severity of

physiological tremor is influenced by emotionaltension or stress and may increase during a med-

ical examination, becoming more obvious to the

observer. Another 13 incidences of NHSs were first

observations or reflected transient pathologicalconditions, such as decrease of olfactory discrimi-

nation owing to constipation or occasionally lowtendon reflex level caused by insufficient relax-ation or low environmental temperature. The

eight first observations of a NHS in follow-up year7 were related to adverse life events such as

traumas or surgical interventions, changes of visual acuity or changes of mood as a symptom of

a possible first manifestation of a psychiatric ill-ness. At baseline, approximately 3 percent of the

children demonstrated NHSs that were scoredcontinuously throughout the study. As children

became older, the probability of their showing

manifestations of chronic diseases increased. Fur-thermore, teenagers are more inclined to demon-strate risky behavior, thus increasing their risk of injury.

The incidence of NSSs decreased across thecourse of the study. This is consistent with matu-

ration of the nervous system and the fact thatNSSs tend to diminish or disappear with

increasing age.9,10 In addition, the severity of NSSs decreased steadily across time in the whole

group of participants and within each treatmentgroup, reflecting progressive neural development

and maturation with time. A large 2005 study of 1,663 adults examined

the relationship of mercury from dental amalgam

exposure to neurological function and found thatthere were no associations between amalgam

exposure and neurological signs (including tremor) or clinically evident peripheral neu-

ropathy.26 These findings are consistent withthose among the children in our study.

Because ours was a large-scale, randomizedtrial, the exposure to mercury from all sources

besides dental amalgam should have been equiva-

lent between the two treatment groups. The pri-mary outside source would be dietary, so we per-

formed a dietary survey and analyses of seafoodsamples eaten by the children to examine the con-

tribution of dietary mercury27 to total mercuryexposure and found that dietary mercury was not

a significant source of mercury exposure in thestudy population. A second source of mercury

exposure in children is vaccines. All children inthe study received the routine series of vaccines

used in Portugal, which is similar to that used inthe United States, so there was no difference

Amalgam ban reported in Norway

Norway has acted to discontinue the use of

dental amalgam, the American Dental Associa-tion reported in an eGram sent Jan. 4 to more

than 75,000 members who have provided theire-mail addresses to the Association.

The eGram noted that Norway acted on

amalgam shortly after the new year as part of asweeping effort to restrict the use of mercury—

action reportedly taken chiefly for environ-mental reasons and with some limited excep-

tions that still allow amalgam to be used.It is possible, the eGram also stated, that

Sweden may have taken similar action,although this could not be verified at the time

the eGram was prepared.

The ADA noted, too, that no new scientificstudies or other new data have been cited ascalling for this action, which is not likely tohave an economic impact in these countries

because of their national health care systems.

INFORMATION ON AMALGAM

For information about amalgam, dentists can

visit the ADA’s Web site, ADA.org, at “www.ada.org/prof/resources/topics/amalgam.asp”.

Patients seeking credible information onamalgam can visit the public side of ADA.org at

“www.ada.org/public/topics/fillings.asp”.

NEW PATIENT BROCHURE

The ADA also has posted a new, free-of-chargepatient education brochure on dental restora-

tive materials that dentists may wish to down-load and have available for patients. Visit

Dental Fillings Facts (abstract) at “www.ada.org/prof/resources//topics/materials/dental_

fillings_facts_abstract.pdf” or Dental Filling Facts (full) at “www.ada.org/prof/resources/

topics/materials/dental_fillings_facts_full.pdf”.

—James H. Berry, associate publisher


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C O V E R S T O R Y


between groups for this source either.

Studies of neurological parameters in dentalpersonnel exposed to mercury from both occupa-

tional sources and amalgam restorations in theirmouths have been performed as well, and investi-

gators have not found that clinically evident neu-rological findings (including those examined inour study) have been present.28,29

CONCLUSION

Because there are concerns that both develop-mental and psychiatric disorders may result from

environmental toxic exposures (such as to mer-cury), it is important to understand the possible

effect of such exposures on NSSs. This study failsto show that exposure to mercury in childhood as

a consequence of treatment with amalgam resto-

rations is associated with a higher frequency of NSSs in childhood and adolescence.

From a prognostic point of view, the decrease of the NSS scores observed in this study group could

serve as a baseline for comparison with singlesubjects in a clinical arena. The persistence of

NSSs may correlate with diverse negative neu-robehavioral and emotional outcomes, but in our

large longitudinal randomized trial, we found noindication that it is associated with exposure to

mercury from dental amalgam. ■

This project was funded by the National Institute of Dental and

Craniofacial Research Cooperative Agreement grant U01 DE11894. Additional funding was provided by Center grant P30ES07033 and bySuperfund Program Project grant P42ES04696 to the University of Washington from the National Institute of Environmental HealthSciences.

Clarification: In a 2006 review, the Office of Human Research Protec-tion of the U.S. Department of Health and Human Services said thatthe University of Washington institutional review board (IRB) shouldhave required more discussion of the risk associated with both dentalmaterials being studied in the consent forms that were approved at thebeginning of the study in 1996 (P.J. McNeilly, PhD, Office for HumanResearch Protections, U.S. Department of Health and Human Services,written communication, Dec. 13, 2006). The University of Washington’sresponse was that its IRB exercised due diligence at the time in con-cluding that the consent form satisfied federal requirements for pro-cedures that were standard of care and in routine use, but that it wouldimplement a new IRB process for explicitly addressing risks associated

with all procedures for future studies comparing two or more standard-of-care protocols (J.M. Cheek, PhD, Office of Research, University of Washington, written communication, March 8, 2007).

The authors wish to acknowledge the assistance of Peter Slade, PhD,of Expert Data Analysis for Doctors & Others, West Kirby, Wirral,England, and Tessa Rue, MS, of the University of Washington, Seattle,with the statistical analyses.

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