1 Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA
2 Department of Dental Public Health Sciences, School of Dentistry, University of Washington, Seattle, WA
3 Department of Family and Child Nursing, School of Nursing, University of Washington, Seattle, WA
4 Department of Orthodontics, School of Dentistry, University of Washington, Seattle, WA
5 Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA
6 Department of Restorative Dentistry, School of Dentistry, University of Washington, Seattle, WA
7 Washington Dental Service, Seattle, WA
Reprint requests to Dr. Philippe Hujoel, University of Washington Department of Dental Public Health Sciences, Health Sciences Center, B-509, Seattle, WA 98195-7475 (e-mail: hujoel{at}u.washington.edu).
Received for publication July 19, 2004. Accepted for publication December 10, 2004.
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ABSTRACT |
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birth weight; case-control studies; dentistry; estrogens; infant, low birth weight; mercury; pregnancy; risk
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INTRODUCTION |
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The rationale for these advisories is based in part on the precautionary principle that dental amalgam contains and releases mercury, a naturally occurring metal which at higher levels can be an environmental pollutant, and which has been associated in an animal model with fetal growth retardation (6). In humans, mercury exposure has been associated with delayed neurodevelopment (7
9
) and low birth weight (10
12
). Upon the placement of dental amalgam, the urinary mercury concentrations increase approximately ninefold within the first week, reaching a peak concentration of approximately 8 µg of mercury for a 24-hour urine sample. Recommendation to abandon mercury-containing amalgam fillings during pregnancy is not without potential risks. Resin-based dental filling materials, the most common alternative to mercury-containing dental amalgams, can leach estrogen-like molecules that in animal models have been associated with an abnormal number of chromosomes in eggs, fetal loss, and other adverse pregnancy outcomes (13
, 14
). Several countries have expressed the need for better epidemiologic research to establish evidence-based guidelines on the use of dental filling materials during pregnancy. The goal of this study was to determine the potential associations between mercury-containing dental fillings placed during pregnancy and risk of low-birth-weight infants. A secondary aim was to evaluate whether resin-based materials affected birth weight.
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MATERIALS AND METHODS |
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The combination of the mother's exact birth date along with the mother's first name and either the father's last name or mother's maiden name gave a conclusive match for 94.1 percent of the matched sample of women. The exact date of mother's birth, along with a partial name match, accounted for a further 2.7 percent of matches. Partial name matches and either an address match (0.5 percent) or a transposed date of mother's birth year, month, or day segment (2.7 percent) accounted for the remaining matches. During this matching process, the Washington Dental Service data manager received infants' birth dates only from the birth certificate data manager, and the birth certificate data manager did not receive dental utilization data from Washington Dental Service. All successful matches combined with infants' birth dates (n = 29,215) were sent back to Washington Dental Service, where it was determined whether eligibility for dental services existed during a period 40 weeks prior to birth and for how many months eligibility existed. Prior to 1995, eligibility for dental services could be determined only for those women who had at least one dental visit, whereas subsequent to 1995 eligibility could be determined regardless of whether a dental visit occurred. This change in method of determining eligibility did not impact the reported findings.
The unique identifiers of those women eligible for dental services during pregnancy were sent to the birth certificate data manager, who then selected the case-control study population. The case group consisted of all pregnancies resulting in low-birth-weight infants. Four normal birth weight infants (2,5005,414 g) were randomly selected for each case without matching. Both the Washington Dental Service and birth certificate data managers stripped the data files of personal identifiers and sent them to the University of Washington, where linking occurred using the patient unique identifier. Human subject approval was obtained from the Human Research Review Board of the Washington State Department of Health.
Outcome and exposure data
Low birth weight was defined as any liveborn infant weighing less than 2,500 g. Dentists submit information on both the type of restorative material used and the date the restoration was inserted intraorally to Washington Dental Service, a not-for-profit dental insurance company, where it is archived in an electronic database. The information was stored using American Dental Association codes, where code 1351 represents a sealant; codes 23302337, 23802382, and 23852388 represent resin-based fillings; codes 2140, 2150, and 21602161 represent amalgams; and codes 27102799 represent crowns. For all analyses, the number of restorative procedures women received since the last menstrual period was calculated and summarized using three statistics: the insertion of at least one filling during pregnancy (yes/no), the number of teeth filled per woman (possible range: 032 teeth), and the number of surfaces filled per woman (possible range: 0128 surfaces).
Confounding variables
Together, the birth certificate records and the dental utilization data provided information on the following potential confounding variables: dental radiation doses (0, 0.10.4, >0.4 mGy); maternal age at the time of delivery (categorized into <20, 2024, 2529, 3034, 3539, 40 years); ethnicity (Caucasian, African American, Asian, and other ethnicities); the duration of eligibility for dental insurance during pregnancy (continuous); marital status (yes/no); parity (0, 12,
3 prior pregnancies); self-reported maternal smoking during pregnancy (yes/no); the presence of gestational or established diabetes (yes/no); the Kessner Index of adequacy of prenatal care (15
) (adequate, intermediate, inadequate); educational level of mother (less than high school, more than high school, unknown); self-reported consumption of one or more alcoholic drinks per week during pregnancy (yes/no); weight gain during pregnancy (continuous variable); prepregnancy weight (continuous variable); preeclampsia (yes/no); chronic hypertension (yes/no); and the eight different nonrestorative types of dental care procedures performed during pregnancy (continuous).
Statistical analysis
Between 1993 and 2000, a total of 5,179 women had one singleton birth, 197 women had two singleton births, and four women had three singleton births. To take into account that the pregnancy outcomes for women with more than one birth are correlated events, generalized estimating equation models with independence correlation structures were used for all analyses. Risk factors for low birth weight were evaluated using generalized linear models with an independence correlation structure, a logit link, and a binomial error distribution. To evaluate whether restorative materials are associated with an increased birth weight, we limited the analyses to infants with a birth weight greater than 2,500 g, and generalized linear models were used with an independence correlation structure, an identity link, and a normal error distribution.
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RESULTS |
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Significant associations were not observed either when the odds for term low birth weight associated with having at least one mercury-containing amalgam filling were evaluated (odds ratio = 1.07, 95 percent confidence interval: 0.59, 1.94). When a dose-response relation was evaluated, the odds ratio associated with 14 amalgam fillings was 1.05 (95 percent confidence interval: 0.57, 1.95), and the odds ratio associated with 511 amalgam fillings was 1.36 (95 percent confidence interval: 0.16, 11.23).
Resin-based fillings and birth weight
A secondary aim of the study was to evaluate the association among resin-based filling materials, sealants, and birth weight. Before or after adjustment for sociodemographic, medical, or dental potential confounders, there was no association between the use of resin-based materials and low birth weight (table 3) (odds ratio = 0.83, 95 percent confidence interval: 0.55, 1.25). There also was no association identified between the number of teeth or surfaces filled with resins and the odds for low birth weight (table 4). When the analyses were limited to women who did not receive amalgam fillings or sealants, similar associations were observed between resin-based restorations and low birth weight (table 4).
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When the analyses were limited to women with infants of normal birth weight (2,500 g), there was no association between the number of amalgam fillings, resin-based fillings, or sealants and birth weight. For every additional sealant, the birth weight increased by 3 g (95 percent confidence interval: 41 to 47; p = 0.89); for every tooth with a resin-based filling, the birth weight increased by 5 g (95 percent confidence interval: 12 to 22; p = 0.59); and for every amalgam filling, the birth weight decreased by 9 g (95 percent confidence interval: 32 to 15; p = 0.48). These analyses were adjusted for all the potential confounding variables listed in table 2.
Restorative materials, regardless of chemical composition, and low birth weight
The odds for a low-birth-weight infant were not associated with the number of restorative procedures performed during pregnancy (odds ratio = 0.95, 95 percent confidence interval: 0.88, 1.02). Adjustment for the potential sociodemographic, medical, and dental risk factors for low birth weight did not alter this finding of no association between birth weight and restorative procedures (odds ratio = 0.96, 95 percent confidence interval: 0.88, 1.05).
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DISCUSSION |
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Because the mercury in dental amalgam was thought to exist in a metallic crystalline form, it was long believed that no mercury escaped from the completed dental restoration. In recent years, however, the development of highly sensitive methods for the detection and examination of the fate of mercury in dental amalgams has shown that mercury is released from dental amalgam fillings in the form of mercury vapor, and that the rate of this release is dependent upon several factors. For instance, nicotine gum chewing can increase the exposure to mercury to levels close to occupational health limits (16). The dose of elemental mercury absorbed from dental amalgam restorations has been reported to range from approximately 2.9 to 17.5 µg/day (17
21
). Estimates of absorbed elemental mercury from ambient sources are one to two orders of magnitude less, ranging from 32 to 96 ng/day. Placement of new dental amalgams leads to eightfold increases in mercury intake and, when combined with preexisting amalgams, may lead to a peak intake of 100200 µg of mercury per week (22
). Clarkson et al. (23
) have estimated that, for the general US population, the dominant exposure for elemental mercury is to mercury vapor from dental amalgam fillings.
An important consideration in the interpretation of these values is the chemical form of the mercury exposure. Mercury vapor readily crosses the placenta and accumulates in the fetus as a result of mercury's high lipid solubility. It is not clear if elemental mercury released by dental amalgams remains entirely in the inorganic form after exposure. It has been shown that three common intraoral strains can transform elemental mercury to methylmercury (7), raising the possibility that similar transformations may occur in vivo, possibly in the oral cavity or in the gut. This is an important consideration, since organic mercury can be toxic at very low doses (<1 mg/day) and, at high doses, has been associated with severe toxicity effects (24
, 25
). Some countries have guidelines to limit the intake of organic mercury. For instance, the US Food and Drug Administration reports that pregnant women should not consume more than 0.01 µg of methylmercury per kilogram per day (approximately two cans of tuna).
Our ability to estimate actual mercury exposure subsequent to amalgam placement in this population of pregnant women is limited by several factors. First, the type of material removed prior to the placement of the dental amalgam was not known. If the insertion of a mercury-containing dental filling was preceded by the removal of a prior amalgam filling, higher levels of mercury exposure are to be expected than if carious tooth material or non-mercury-containing dental materials are removed. This weakness was somewhat attenuated by the knowledge that restorative procedures of any type were not associated with an increased risk for low birth weight. Second, we did not have information on the number of existing amalgam fillings prior to pregnancy. The chronic long-term, low-level release of mercury from these fillings may have confounded the acute higher-level exposure associated with placement of a dental amalgam. Third, because the increased mercury exposure associated with amalgam placement is short term and because the estimate of the last menstrual period is inaccurate, there may be some misclassification with respect to the determination of mercury exposure during pregnancy. Inaccuracies in the birth certificate records may have further diluted our ability to detect associations.
While this is the first study evaluating the effects of dental filling materials on low birth weight, some important questions remain unanswered. This study was not designed to evaluate the effect of mercury on chromosomal alterations, neurobehavioral characteristics, or other possible adverse pregnancy outcomes such as spontaneous abortions. In addition, this study was not designed to evaluate the effects of resin-based filling materials on pregnancy outcomes. The safety profile of resin-based filling materials is considerably more difficult to establish because of significant product variability and analytical complexity. Composite-based filling materials are of concern because of the presence of estrogen-like molecules, which are an environmental pollutant and which have been associated with chromosomal abnormalities in mice, fetal loss, and an increased birth weight soon after birth (4), as well as with underdevelopment of the brain, kidney, and testes in mice (26
).
Because our study was specifically designed to evaluate risks for low birth weight, we were limited in our ability to assess whether resin-based filling materials increase birth weight. Analysis limited to those women with an infant weighing 2,500 g or more could not identify an association between resin-based, tooth-filling materials and increased birth weight. Case-control studies specifically designed to detect macrosomia (>4,000 g) will be more sensitive to detect any potential association between plastic filling materials and increased birth weight.
In summary, the present study could not identify an increased risk for a low-birth-weight infant among those women receiving mercury-containing dental amalgam fillings. Further evaluations of the safety profiles of dental amalgams, resin-based fillings, and other types of dental materials used intraorally are required to establish evidence-based guidelines for usage of dental materials during pregnancy.
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References |
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