Women who have amalgam dental fillings placed during the first trimester of pregnancy are more likely to give birth to infants with isolated cleft palate, a Scandinavian study found.

In a case-control study involving 1,336 infants born in Norway during a 7-year period, women who had fillings placed in the first or second month of pregnancy had roughly quadrupled odds of giving birth to an infant with cleft palate. The odds were even higher among women who had fillings placed during multiple months of the first trimester.

Placement of fillings during these periods was rare, and the study had other limitations, cautioned lead investigator Lisa A. DeRoo, Ph.D. Still, the findings raise the possibility that fetal exposure to mercury from maternal fillings during a critical period in orofacial development may increase the risk of cleft palate.

"Since this is the first study we know of that has examined this, it is probably a little premature to answer some of the questions [about the mechanism]," she commented. "But we do think it warrants further study."

The American Dental Association declined to comment.

Two-thirds of infants with facial clefts do not have any family history of the condition, and research has implicated a variety of environmental exposures, according to Dr. DeRoo, an epidemiologist with the National Institute of Environmental Health Sciences in Research Triangle Park, N.C.

Amalgam fillings continuously give off small amounts of vaporized elemental mercury, which is inhaled and can cross the placenta and accumulate in the fetus, she explained. "Among mothers who have amalgam fillings, the number of fillings they have correlates with mercury measured in cord blood and breast milk."

Using data from the Norway Facial Clefts Study (NCL), a population-based case-control study, the investigators assessed associations between maternal amalgam fillings and two categories of facial clefts that appear to have different etiologies: cleft lip with or without cleft palate, and isolated cleft palate.

The study involved 573 infants with facial clefts (66% with cleft lip with or without cleft palate, and 34% with isolated cleft palate) identified shortly after birth and 763 randomly selected control infants, all born between 1996 and 2001.

Within 4 months after birth, the infants' mothers completed questionnaires asking if they had amalgam fillings placed during the first trimester of pregnancy and, if so, in which month(s).

This exposure window was chosen in light of what is known about the timing of both fetal development and mercury release after filling placement, Dr. DeRoo said.

Specifically, the fetal lip and palate close between weeks 5 and 10 of pregnancy, she explained. And "new placement of fillings leads to a transient higher mercury concentration that peaks at about eight- to ninefold normal levels about 1-2 weeks after the filling has been placed."

Study results showed that very few of the women overall, merely 44 (3%), had fillings placed during the first trimester of pregnancy, Dr. DeRoo reported. About 27 had fillings placed in the first or second month, and 19 did so in the third month. Just 6 had fillings placed in multiple months of the first trimester, used as a measure of higher level of exposure.

In adjusted analyses, women who had fillings placed in the first or second month of pregnancy had a significant near quadrupling of the odds of giving birth to an infant with isolated cleft palate relative to their counterparts who did not have any fillings placed during those months (odds ratio, 3.6).

In addition, women who had fillings placed in multiple months of the first trimester had a significant, even greater increase in the likelihood of this outcome relative to their peers who did not have fillings placed in any of those months (OR, 17), albeit with very wide confidence intervals because of the small number with this much exposure.

"I want to point out, though, that all five women who reported having placements in both months 1 and 2 had infants with cleft palate," Dr. DeRoo noted. "Four of them had infants with cleft palate only, and one of them had an infant with cleft lip with cleft palate."

Placement of fillings in month 3 was not associated with an increased risk of isolated cleft palate. And placement of fillings during any of the intervals studied was not associated with a significantly elevated risk of cleft lip with or without cleft palate.

Recall bias was a potential limitation, acknowledged Dr. DeRoo. "However, we did see increased risk for only one of the cleft groups and for a specific time period," she noted. "We might expect, if recall bias was important here, you'd see it sort of broadly across all of these categories."

Lack of information on the number of fillings women had before or during pregnancy, and on removal of fillings--which also leads to a transient increase in mercury exposure--was also a shortcoming, according to Dr. DeRoo.

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Major Finding: Women's odds of giving birth to an infant with isolated cleft palate were increased about fourfold if they had fillings placed in the first or second month of pregnancy and 17-fold if they had fillings placed in multiple months during the first trimester.

Data Source: Population-based case-control study involving 573 infants with facial clefts and 763 randomly selected control infants born between 1996 and 2001.

Disclosures: Dr. DeRoo reported that she had no relevant conflicts of interest.

Originally published in OB/GYN News / Oct, 2010 by Susan London

THIS INFORMATION WAS PRESENTED TO THE FDA IN 2010, BY JIM LOVE OF THE INTERNATIONAL ACADEMY OF ORAL MEDICINE AND TOXICOLOGY ( www.iaomt.org ).