Scientists supported by the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health, report in this week’s New England Journal of Medicine that pregnant women who received non-surgical treatment for their periodontal, or gum, disease did not also significantly lower their risk of delivering a premature or low-birthweight baby. These results come from the largest clinical trial to date to evaluate whether treating periodontal disease during pregnancy reduces a women’s risk of early delivery, an idea that has emerged as a possibility in recent years.

Non-surgical, or standard, periodontal treatment involves thoroughly cleaning the teeth above and below the gums, commonly called scaling and root planing. The study, called the Obstetrics and Periodontal Therapy Trial (OPT), also evaluated the safety of general dental care during pregnancy. It found that dental treatment through the second trimester – both general and periodontal care – did not increase the number of adverse events for women during pregnancy.

Until now, little research had been conducted on the subject, although dentists generally provide limited dental care to women only during the second trimester when the fetus has reached a more stable developmental stage and before treatment becomes too physically cumbersome for the mother. “Dental care during pregnancy has long been an issue dominated by caution more than data,” said NIDCR director Dr. Larry Tabak. “The finding that periodontal treatment during pregnancy did not increase adverse events is important news for women, especially for those who will need to have their periodontal disease treated during pregnancy.”

 In the United States, more than one-half million – or about one in eight – babies are born prematurely, which is defined as a birth that occurs before 37 weeks of pregnancy. Extremely preterm babies can be so small and underdeveloped that they must remain hospitalized for months, and, if they survive, spend years battling chronic health problems. This has spurred scientists to identify several risk factors associated with premature births.

These include smoking, low-income status, hypertension, diabetes, alcohol use, and genitourinary tract infections. However, the list remains incomplete. As many as half of all preterm births occur without any clear explanation, and that has left scientists searching for additional susceptibility factors to help more mothers and ultimately reduce the estimated $26.2 billion annual cost to the nation for preterm births. Over the last two decades, scientists have generated data in observational studies that suggest periodontal disease during pregnancy might be one of those elusive risk factors.

The theory is based on the idea that bacteria associated with periodontal disease may spread to the womb and help to induce preterm births. Results of a previous small-scale clinical trial further supported this idea, but what’s been missing are more definitive data from larger, randomized clinical trials.

To fill this public-health need, the NIDCR funded two large, randomized clinical trials. The first to publish its results is the OPT, which included four participating centers: Hennepin County Medical Center in Minneapolis, University of Kentucky in Lexington, University of Mississippi/Jackson Medical Mall in Jackson, Miss., and Harlem Hospital/Columbia University in New York City. Launched in March 2003, OPT enrolled a total of 823 women with periodontal disease, all of whom were between 13 and 17 weeks pregnant upon entry into the study. Each woman was randomly assigned to receive either: (1) scaling and root planing of the teeth prior to the 21st week of pregnancy, then monthly tooth polishings or (2) scaling and root planing after delivery, meaning women in this group did not have their periodontal disease treated during their pregnancies. All women were 16 years or older to participate, and basic dental care was provided to everyone in the study.

 According to Dr. Bryan Michalowicz, a periodontist at the University of Minnesota and the lead author of the study, one of the OPT’s strengths is its four regional centers generally provide prenatal care to low income, underserved women of all races, who are recognized as being at particularly high risk for early delivery. “When trying to define risk factors for preterm birth, it’s difficult to control for characteristics that may differ between full and preterm mothers, such as socioeconomic status or access to health and dental care,” said Michalowicz. “By randomly assigning women from the same high-risk populations to receive treatment either before or after delivery, we could minimize such differences between groups.”

 As reported this week, the OPT data show: • Birth Outcomes: Forty nine (12.0 percent) women in the treatment group had pregnancies ending before 37 weeks compared to 52 (12.8 percent) of those in the control, or delayed treatment group. Nineteen miscarriages occurred, although the numbers were not indicative of a statistically significant trend in either group. These included: Six spontaneous abortions (two in the treatment group, four in the control group) and 13 stillbirths (three in the treatment arm, 10 in the control group).

A spontaneous abortion was defined as a loss of the baby before 20 weeks, while a stillbirth was considered to occur from 20 weeks to 36 weeks and six days. The researchers also found no significant differences among the two groups in the proportion of infants who were of low birthweight, defined as weighing less than 2500 grams, or about five and half pounds. • Periodontal Disease: Most women had early to moderate periodontal disease.

 The researchers found that the treatment improved all clinical measures of periodontal disease. These included the bleeding of gums when probed, the probing depth between the tooth and gum, and measuring tooth attachment. As additional evidence, the researchers found no difference in risk for preterm birth when they compared treatment and control women who had the most extensive bleeding of the gums, a sign of inflammation, or more advanced periodontal disease at entry.

They also found no differences when they examined a subset of women in the treatment group whose periodontal disease had improved the most during the study. • Safety of Periodontal Therapy: Women in both groups had similar rates of adverse medical events, such as hospitalization of more than 24 hours for labor pains.

 This is an indication that periodontal therapy had no obvious effect on pregnancy. “This study highlights the power of merging disciplines, in this case dentistry and obstetrics, to pursue a public health question,” said Dr. Virginia Lupo, an author on the study and an obstetrician at the Hennepin County Medical Center in Minneapolis. “We literally set up dental practices within our obstetrics clinics, and that was a very unique and needed approach.”

Although OPT is now the largest study to publish on the subject, the NIDCR-supported Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) study is ongoing. “It’s just good science to conduct more than one large clinical trial on any public health question,” said Dr. Jane Atkinson, program director of NIDCR’s Clinical Trials Program. “If periodontal disease plays any role in preterm birth, we want to cast a wide enough investigational net to determine which women are at risk.” Atkinson said the 1,800-patient MOTOR study is designed a little differently than OPT.

It involves a broader socio-economic cross section of women, provides fewer basic dental services, and includes women with slightly less severe periodontal disease. MOTOR will likely report its results within the next two years. The article is titled “Treatment of Periodontal Disease and The Risk of Preterm Birth” and appears in the November 2, 2006 issue of the New England Journal of Medicine.

 The authors are: Bryan S. Michalowicz, James S. Hodges, Anthony J. DiAngelis, Virginia R. Lupo, M. John Novak, James E. Ferguson, William Buchanan, James Bofill, Panos N. Papapanou, Dennis A. Mitchell, Stephen Matseoane, and Pat A. Tschida. The National Institute of Dental and Craniofacial Research is the nation’s leading funder of research on oral, dental, and craniofacial health. The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.