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Nigel Paneth, M.D., '70: Snow job

By Jennifer Durgin

When a pediatric researcher claims to be interested in aging, the apparent oxymoron turns heads. Perhaps that's why Dr. Nigel Paneth, a neonatal epidemiologist, is so fond of stating exactly that.

"I study the aging placenta," he declares. When a baby reaches 40 weeks' gestation—a full-term pregnancy—the infant has no further need for the placenta. So at that point, posits Paneth, "it's an aging organ," whereas "at 28 weeks or 32 weeks, the placenta is still very functional."

This intriguing observation is characteristic of Paneth's unconventional approach to research. For more than 30 years, he has combined the disciplines of pediatrics and epidemiology to study what can go wrong during pregnancy, birth, and early infancy—and what can be done to solve problems when they do occur. Recently, Paneth, a professor at Michigan State University (MSU), has been investigating the association between cerebral palsy and low thyroid hormone levels in premature infants.

To explain this research, Paneth first poses a very broad question: How do premature babies' brains get damaged? "The first thought," he says, is that "they're born so immature and so little and so unable to withstand everything that's going on that they get into trouble—respiratory and brain and so forth. They lack oxygen, they lack this, they lack that." That's the conventional theory.

But Paneth has another hypothesis. Maybe what goes awry, he suggests, is that preemies are separated too early from the placenta and the support that it pipes in from the mother's body. For example, the thyroid hormone thyroxine is essential for proper brain development. In the womb, fetuses draw on their mother's stores of thyroxine, transmitted through the placenta. Once they're born, babies must produce their own thyroxine to develop properly. Twelve hours after birth,

Alumnus Nigel Paneth is one of the leaders of the massive NIH-funded National Children's Study, which will follow 100,000 children from before they are born to age 21.

healthy, full-term babies double or triple their production of thyroid-stimulating hormone, says Paneth. That surge, he notes, is a "wakeup call: 'Hey, wake up. You're out in the real world by yourself.'"

But in preemies, that surge often doesn't occur. Instead, their thyroid hormone levels plummet and can stay low for weeks. Paneth coauthored a 1996 paper in the New England Journal of Medicine which showed that preemies with very low levels of thyroxine were much more likely to develop cerebral palsy and other cognitive and motor problems than preemies who had more normal thyroxine levels. Infants with the lowest levels seemed to have the most severe, long-term developmental problems.

These findings beg the question whether giving these infants thyroid hormone supplements would improve their outcomes. Paneth and other researchers just completed Phase I of an international trial testing just that question; the results were in but not yet available at press time for this article.

However, Paneth is careful not to get too enthusiastic about the idea until it has been fully tested. If supplementation is shown to work, he says, he'll be able to look back on that 1996 paper "and sound proud of it." But if supplementation does not improve babies' developmental outcomes, then "that paper really didn't lead us anywhere. . . . It could be that the thyroid hormone simply correlates with something else."

In Paneth's field, "one needs a skeptical mind and a good deal of education on epidemiology and statistics," notes Dr. Alan Leviton, a pediatric neuropathologist and neuroepidemiologist at Boston Children's Hospital. Leviton and Paneth have been working together for almost a decade on a study to identify protein biomarkers that can predict early brain damage and later developmental disabilities. The collaborators frequently consult each other for feedback and advice on other projects, too. "We always challenge each other with, 'Might you be wrong?'" says Leviton.

Most recently, Paneth put his experience and skepticism to use as one of the designers of a massive project funded by the National Institutes of Health (NIH). Called the National Children's Study, it will follow 100,000 U.S. children from before they're born until they're 21 years old to examine the effects of various environmental influences. "Environment" is being defined broadly to include social, familial, and cultural influences, as well as physical, biological, chemical, and genetic factors. Paneth is also the study's principal investigator forWayne County (which includes Detroit), one of 26 counties nationwide in the first wave of the study.

Paneth has lots of experience with big, long-range observational studies. In the 1980s, he got NIH funding for a project called the Neonatal Brain Hemorrhage Study, which has followed more than 1,000 low-birth-weight infants for more

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Jennifer Durgin is Dartmouth Medicine magazine's senior writer.

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