Council on Environmental Health
Article Review

Prepared by: Joel A. Forman, MD
March 2008

TITLE
Renal Effects of Dental Amalgam in Children: The New England Children’s Amalgam Trial

AUTHORS
Barregard, L., et al.

REFERENCE
Environmental Health Perspectives, vol 116, num 3, March 2008, pgs 394 – 399

STUDY TYPE
Prospective Cohort

BACKGROUND
Mercury is a toxic metal whose primary targets are the nervous system and the kidney. Humans are exposed to mercury primarily from fish consumption (organic mercury) and from off-gassed mercury vapor from dental amalgams (inorganic mercury). Inorganic Mercury has been shown to impact renal tubular function in adults in the occupational settings at urinary mercury levels of 10 – 20 mcg/gm creatinine. Glomular impact has also been demonstrated in the occupational setting but at even higher levels of exposure, greater than 100 mcg/gm creatinine. Children have been less well studied for the renal effects of inorganic mercury exposure. Of interest, the other major prospective cohort study of dental amalgams in Portugal (DeRouen at al JAMA 2006) did not identify any renal effects. A recent European study (de Burbure et al. EHP 2006) unexpectedly found evidence of increased excretion of N-acetyl-β-D-glucosaminidase (NAD), a marker of subtle tubular damage, in the setting of very low levels of urinary mercury, less than 1 mcg/gm creatinine. Glomerular impact has not been demonstrated in children at low-level inorganic mercury exposure.

METHODS
The New England Children’s Amalgam Trial (NECAT) is one of two large prospective cohorts designed to assess the potential toxicity of mercury exposure in young children with dental amalgams. This study included 534 children without any prior dental amalgam recruited at ages 6 to 10 years and followed prospectively for 5 years. The primary outcome of interest was IQ and no adverse effect was found (Bellinger et al. JAMA 2006 and EHP 2007).  This manuscript reports on the secondary outcome of renal effects examining both tubular and glomerular markers of renal injury.           

598 children between the ages of 6 and 10 years presenting with at least 2 dental carries at two sites (one in Massachusetts and the other in Maine) were recruited and determined to be eligible to participate in the study. Patients with evidence of prior psychological, behavioral, neurologic, immunosuppressive, or renal disorders were excluded. Participants were randomized to receive either traditional mercury dental amalgam repairs or alternative (composite) materials. The children were followed for 5 years with bi-annual dental exams and any necessary repairs and annual medical evaluations that included IQ testing and urine collections for markers of tubular and glomerular injury. The authors looked for three markers of proximal tubular injury: Alpha-1-microglobulin that is reabsorbed less efficiently when the proximal tubule is damaged; N-acetyl-β-D-glucosaminidase (NAD), which is excreted in greater quantities in the setting of proximal tubular damage, and g-glutamyl transpeptidase, a brush border cell enzyme also excreted in greater amounts in the setting of proximal tubular damage. Urinary albumin was measured as a marker of glomerular injury and a level greater than 30 mg/gm creatinie was defined as microalbuminuria (MA). The patients, their families, and the dentists could not be blinded to the assigned group but all others, including those performing the laboratory analyses, were blinded.

RESULTS
The study did not find any association between the amalgam group and markers of tubular function. The mean albumin level was also not different between the two groups. The authors did identify a statistically significant increase in the prevalence of MA in the amalgam group (48 vs. 38 cases) with an odds ratio of 1.8 (CI 1.1 – 2.9, p=0.03). 10 children in the amalgam group had MA at both the 3 and 5 year exams as opposed to 2 in the control group. There was, however, no relationship between the number of amalgams or urine mercury level and this finding.

DISCUSSION
Pediatricians in practice are frequently asked questions about the use of mercury amalgams in pediatric dentistry. The results of the NECAT and the DeRouen Portuguese cohort demonstrate the absence of adverse neurocognitive toxicity from the very small exposure to mercury vapor from dental amalgams.  This report focusing on the secondary outcome of nephrotoxicity demonstrated no evidence of tubular effects. The finding of possible glomerular impact (increased MA) was unexpected. The authors felt that although this could reflect a real mercury effect, it was also possible that the finding was due to chance or might reflect other causes of MA such as exercise or orthostatic proteinuria. They noted that their evaluation for renal effects was not detailed enough to clearly resolve this. In addition, many urine measurements were from spot urine samples instead of 24-hour collections, reducing the reliability of the finding. Finally, the clinical significance of the MA is unclear, although the fact that 10 children had MA on both the 3 and 5 year measurement raises the possibility that the result could be real. Overall, the study findings are reassuring and suggest strongly that the level of mercury exposure from dental amalgams in children does not pose a significant risk of renal toxicity in young children with dental amalgams. Additional, more thorough studies of renal effects in a similar cohort might more definitively resolve any lingering concerns.

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