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A Radical NotionDung Hoang

A Radical Notion (continued)

NEVER IN HER LIFE had Wang seen such a tiny baby.

Born at 26 weeks—three months early—the preemie’s reluctant first breath required intubation and chest compressions. If, because of the marvels of life-support technology and her colleagues’ considerable skills, this infant survived the week—and even if, in months to come, this fragile being was able to “graduate” from the neonatal intensive care unit and go home (likely with a feeding tube and oxygen)—its translucent skin seemed to Wang to be a window into a future of suffering. Prematurity is a challenge to the brain as well as the lungs. Common, chronic complications of preterm birth include brain bleeds, blindness, hearing loss and lung disease.

As a resident in a hospital that served a low-income minority population, among which almost 20 percent of births are preterm, Wang was keen on learning from the attending physicians how to rescue babies weighing in at just over a pound. But as the preemies kept on coming, she felt responsible, not only for them but also for their disenfranchised parents who were at a loss for how to care for such medically, emotionally and economically demanding newborns. Wang couldn’t imagine how even she, a trained pediatrician, would cope as the mother of such a preemie. Empathy and indignation moved her to tears and moved her to act. There had to be something she could do in addition to saving these lives, here and now. Something preventive.

The first thing she did was to author an elegant analysis that appeared in 1995 in the New England Journal of Medicine, demonstrating the finding that low birth weight and preterm birth repeated from one generation to the next.

The next thing she did was conceive the idea for the Boston Birth Cohort.

She sensed that the complex causes of preterm birth might begin to be teased apart if she could compare a sizable population of mother-preemie pairs against a population of healthy mother-baby pairs, with all coming from similar circumstances. Bleak as the NICU was, Wang recognized it as the ideal place to start to understand why some babies ended up here, connected to tubes and wires, while another group landed safely in the “happy” nursery down the hall. A multitude of risk factors necessitated a large number of cases (preterm births) as well as controls (full-term births). Mothers would need to agree to be interviewed, allow medical records to be scrutinized and contribute samples of maternal blood, cord blood and placental tissue.

With a small seed grant and encourage-ment from her professors Barry Zuckerman and Howard Bauchner, MD (currently editor-in-chief of JAMA), she set out on what now is a massive, 14-year-old project involving 7,600 mother-infant pairs, 60 percent of whom are black and 25 percent Hispanic. To date, analyses of the data have generated more than 30 publications; notably, Wang pioneered the genetic study of preterm birth. With a landmark article in JAMA in 2002, her group demonstrated how smoking mothers with certain genotypes had a 10-fold higher risk of preterm birth over smoking mothers with other genotypes, revealing a synergistic effect between a genetic and an environmental factor. A finding like this paves the way for “biologic hotspotting,” a strategy that identifies genetic vulnerabilities so that individualized interventions can be targeted at a particular behavior or specific biologic variable.

Wang’s Boston Birth Cohort comprises an extensive collection of epidemiological and clinical data as well as biospecimens housed in more than a dozen freezers near her new lab space in the Wolfe Street building. This rare resource allows Wang and her collaborators to investigate environmental, genetic and epigenetic influences on mothers, infants and children. Few, if any, prospective birth cohorts in the nation are so well positioned to answer “why” in the context of a minority, high-risk population bearing a disproportionately high burden of chronic conditions and diseases such as preterm birth, obesity and allergies. Because the study spans decades, researchers may check back with the subjects to ask new questions and look at disease progression.

With that cohort still actively re-cruiting, Wang and colleagues have built two more: The Chicago Family Cohort, focusing on food allergies, involves 4,000 subjects from 1,000 families; and the Chinese Twins cohort involves 2,000 pairs of twins and probes the precursors of obesity and metabolic syndrome. All three studies are churning out data.

“From the Boston Birth Cohort, we have data showing that by age 6, over 45 percent of the children in the study—no kidding!—are overweight/obese,” Wang says. “Fifty percent of the mothers were overweight/obese at the time of conception. Let’s not wait until these kids walk into the doctor’s office as obese adults.”

Statistics like that one are guiding Wang’s latest efforts to corral Johns Hopkins faculty from the schools of Public Health, Medicine and Nursing for investigations into the early life precursors of intergenerational obesity. One NIH grant application involves nutrition expert Laura Caulfield, PhD, and Mei-Cheng Wang, PhD, a biostatistician, both from SPH; Tina Cheng, MD, a professor of pediatrics in the SOM; and mental health expert Deborah Gross, PhD, and Sarah Szanton, PhD, a health disparities researcher, both from the SON. Among Szanton’s contributions is a “society-to-cells” resiliency model that provides a holistic context for understanding health differences and guiding interventions at six different levels. Each one of the levels, Szanton says—society, community, family, individual, physiological and cellular—represents an opportunity to exert positive change. It’s impossible to resist applying this framework to Wang: Given that she was a full-term baby nurtured by family and mentors, her ability to overcome the deleterious effects of the Cultural Revolution begins to make sense.

The average rate of premature births has doubled since 1995 in 65 developed countries. — “Born Too Soon” report

AT A MARCH 21 SYMPOSIUM on the Future of Child Health that marked the occasion of Wang’s assuming her named professorship, a dozen distinguished colleagues (many of them former teachers) gathered from around the country in Sheldon Hall to honor her achievement and give mandate—just as her parents had done a half-century earlier.

Joseph Brain, a professor of environmental physiology at the Harvard School of Public Health who mentored Wang when she was a research fellow there, sought to involve her in a couple of big, important topics: “The first,” he said, “has to do with children who grow up with exposure to toxic metals.”

He described his department’s efforts to develop a birth cohort focusing on early exposure to toxic metals: The group is collecting maternal and cord blood from mother-infant pairs in northeastern Oklahoma where families live next to mountains of mining waste containing lead and zinc. Brain’s related animal studies demonstrate that anemia (iron status) increases lead uptake. The take-home message: Treating anemia could reduce the risk of brain damage by lead poisoning.

“One of the things we’d like to talk to Xiaobin about,” he said, “is how can we use that birth cohort, and apply some of the methods, insights and technology that she has?”

Sitting primly in the front row, wearing a petite white suit and butter yellow top, Wang appeared a genial force of nature, as likely to sweep people up as to be swept up. (“After you talk to her,” asks a colleague, “don’t you feel like your hair has been blown straight back?”)

As is her habit, she smiled easily, often nodding in the affirmative. Hailed by all as an indefatigable researcher and frequently described as a doting mother of her twin teenage sons, Wang was ready to accept their challenge. Her agenda, big and broad, is inclusive, extending beyond one person, institution or discipline.

“We have heaped enormous expectations on her,” Bernie Guyer cautioned the crowd during an affectionate introduction of his former student. “As her colleagues, students and friends, how do we help her to be successful?”

Wang was reflective: “My most challenging and difficult periods turned out to be my most productive and creative periods. I don’t underestimate the challenges before me. With interdisciplinary colleagues down the hall, and collaborators across the street, this is the right place for me now to leverage all the tremendous resources for the best chances of success and for translation.

“That’s my big dream.”

Comments

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  • Graciela Bernardo

    Neuquén- Argentina 05/29/2012 06:54:22 PM

    Congratulations! I´m a midwife and work for the healths of mothers and their babies. I´m very happy with you investigation.. Continue Best wishes!!

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