Newborn babies' immature immune systems make them highly vulnerable to infections, and to make matters worse, most vaccines don't work in them. Ofer Levy, MD, PhD, and colleagues in Children's Hospital Boston's Division of Infectious Diseases, now believe they've found a way to boost immunity in these tiny infants, possibly making infections like respiratory syncytial virus, pneumococcus, pertussis, HIV and rotavirus much less of a threat. The ability to immunize babies at birth would also provide global health benefits, since birth may be a child's only contact with a health care system in developing countries.
Since the 1990s, Levy has uncovered a series of differences between newborn and adult immune systems. His latest study, in the April 25 online edition of the journal Blood, focuses on Toll-like receptors (TLRs), molecules on the surface of certain white blood cells. Like an early radar system, TLRs detect invading microbes and trigger the production of cytokines—biochemical "danger signals" that prompt other immune cells to mount a defense. People have 10 different kinds of TLRs, and Levy's team, which included Eugenie Suter, MA, BA, and Michael Wessels, MD, found that TLRs trigger very weak immune responses in newborns. But there was one important exception: the TLR8 receptor triggered a robust response, prompting white blood cells to produce normal, adult levels of two key cytokines—TNF-alpha and IL-12—and another immune-system stimulant, CD40. Levy speculates that drugs that stimulate TLR8 could possibly be used to enhance immune responses in human newborns, perhaps as adjuvants given along with vaccines.
Levy will soon publish two related studies that suggest additional targets for boosting newborns' immunity. He believes nature may suppress babies' production of TNF-alpha and IL-12 before birth because these inflammatory compounds can trigger preterm labor. But once babies are born, fooling Mother Nature may help save their lives.
Each year, more than 70 million Americans receive tooth fillings with dental amalgam. But these "silver" fillings have become controversial because they contain mercury, known to be toxic in large doses. However, it's unknown what level of mercury exposure poses a health threat, or how much mercury exposure people actually get from dental fillings. Researchers, led by Children's David Bellinger, PhD, conducted one of the first two clinical trials to address the safety of dental amalgam in children, and found no effect of dental amalgam on children's cognitive or behavioral function.
Bellinger and colleagues recruited 534 children, aged 6 to 10, from dental clinics in the Boston area (including Children's) and in Farmington, Maine. None of the children had received amalgam in the past, and all had at least two back molars with cavities. They were randomly assigned to receive either amalgam or composite fillings (a mixture of plastic resin and powdered glass). Both groups were offered free dental care for the duration of the study; on average, children in each group had 9.5 cavities filled.
The health of each child was then tracked for five years. On average, the amalgam group had higher urine mercury levels, but levels in both groups were no higher than those in the general population. The amalgam and composite groups showed no significant differences in scores for IQ, memory, visual-motor function, kidney function or in reported health problems. A concurrent randomized trial, at the University of Washington, had similar findings.
Bellinger cautions that the studies did not include children under age 6, who could be more vulnerable to mercury's effects. Both studies appear in the April 19 Journal of the American Medical Association.