In the winter of 1944, at the tail end of World War II, Nazi troops cut off food supplies to the western provinces of the Netherlands, creating a widespread famine that killed nearly 20,000 people. Conditions improved dramatically when the war ended a year later, but the health implications of the humanitarian crisis would be felt for generations. In what is considered one of the most startling paradoxes in medicine, children born to women who survived on meager rations during the Dutch Hunger Winter, as the period is now known, tended to be the same weight at birth as those born to unaffected mothers, but they became heavier as adults. They were also more prone to heart disease, obesity, diabetes, and early death.
The phenomenon raised a profound and perplexing question: How could the environment in the womb leave such a dramatic and lasting mark on human health and longevity? Studies of the Dutch children, as well as other major investigations from Japan, Scandinavia, and elsewhere have since begun to tease out the answers. Harsh conditions during a critical early window of human development, evidence suggests, may trigger a survival mechanism called a thrifty phenotype. The hypothesis posits that hormonal changes in the developing fetus can help it adapt to unfavorable conditions, such as by converting calories into fat instead of protein or sugar to maximize energy when food is scarce. Later in life, though, the adaptation can become a threat: continuing to readily convert calories into fat, even when food is abundant, can predispose someone to obesity and diabetes.
As it turns out, starvation isn’t the only condition that can reconfigure the body’s metabolic and hormonal wiring early in life. Leonardo Trasande, MD, MPP, vice chair for research in the Department of Pediatrics at NYU Langone Health, is among a growing cadre of scientists who believe that chronic exposure to the chemicals found in numerous everyday sources, such as plastics, flame retardants, pesticides, and air pollution, can trigger the same phenomenon and may be fueling the rising rates of diseases like obesity and diabetes. “We suspect the thrifty phenotype can occur in a subtler fashion and impact children through early chemical exposures,” says Dr. Trasande, director of the Division of Environmental Pediatrics, and professor of pediatrics, environmental medicine, and population health.
Equal parts physician, researcher, and policy expert, Dr. Trasande has spent the past two decades painstakingly documenting the threat and burden of environmental toxins on human health, and the economic cost of failing to prevent related diseases, all while advocating for reforms to mitigate their damage. His concerns about the health hazards of hormone-disrupting chemicals have been echoed by the World Health Organization, the International Federation of Gynecology and Obstetrics, the Endocrine Society, and the American Academy of Pediatrics.
Even as the evidence mounts, however, the challenge of protecting society from a pervasive threat hiding in plain sight can seem insurmountable. Synthetic chemicals lurk just about everywhere: in our soil and food supply, in cosmetics and hygiene products, in furniture and clothing, and even in medical equipment (think IV bags, tubing, and pill bottles). Since 2004, the world has produced more than 4 billion metric tons of plastic alone.
Dr. Trasande, for his part, is undaunted by the scope and scale of the task before him. Supported by more than $40 million in federal funding, he and his colleagues at NYU School of Medicine are leading some of the most ambitious clinical studies yet to clarify the link between chemical exposure and childhood development. Beyond more research, his antidote turns on a public awareness campaign whose message is as persistent as the chemicals it seeks to oust. Dr. Trasande recently published a book to alert the public to the hazards of hormone-disrupting chemicals, which he considers an environmental challenge second only to climate change. “We can do a lot to protect everyone from ‘lifestyle’ diseases caused by things other than lifestyle,” he says. “Our choices and habits matter.”
In the relatively young field of pediatric environmental health, Dr. Trasande has rapidly earned an international reputation for his expertise and leadership. In 2014, he organized the Endocrine Disrupting Chemical Disease Burden Working Group, a cohort of nearly 30 international scientists who advise policymakers about the economic burden of medical conditions linked to these chemicals. Earlier this year, he was appointed director of NYU Langone’s new Center for the Investigation of Environmental Hazards. The center, which complements the clinical care provided by Hassenfeld Children’s Hospital at NYU Langone, advances tools and technologies to help measure the effects of environmental exposure and translates research findings for the public. “I think he’s a towering intellect—and a practical person,” says Catherine S. Manno, MD, the Pat and John Rosenwald Professor of Pediatrics and chair of the Department of Pediatrics. “And those things together augur for a great contribution to public health.”
The Case for More Vigilance
Dr. Trasande was first drawn to health policy during medical school at Harvard University in the 1990s. After completing his pediatric residency at Boston Children’s Hospital and Boston Medical Center, he completed a legislative fellowship in then-Senator Hillary Rodham Clinton’s office. Working on both child and environmental health policy, he realized that formulating sound medical guidance could fundamentally impact the health of not only individuals but entire populations. Since then, Dr. Trasande has increasingly focused on building the public health case against a group of chemicals known as endocrine disruptors, which interfere with the function of hormones such as estrogen, androgen, and thyroid. “We know that hormones, in addition to performing important physiological functions, are crucial for shaping body mass,” he says.
Dr. Trasande’s work has been driven by the central hypothesis that early-life exposure to environmental chemicals, especially endocrine disruptors, alters our hormones in harmful ways, contributing to birth defects, developmental delays, obesity, diabetes, infertility, and cardiovascular and immunological diseases. He notes that while these chemicals have been shown to have long-lasting health implications for everyone, babies and young children are particularly vulnerable. “Pound for pound,” says Dr. Trasande, “children are breathing more air, eating more food, and drinking more water, so they have greater exposure, and their organ systems are still developing.”
For much of their research, Dr. Trasande and his investigators have zeroed in on four kinds of chemicals for which there is the strongest evidence of health effects: bisphenols, phthalates, organophosphate pesticides, and polycyclic aromatic hydrocarbons (PAHs). Bisphenols make plastics hard, and because they are used to prevent corrosion in aluminum cans, they are often present in canned foods. Phthalates increase the flexibility and durability of plastics and are often added to lotions, cosmetics, soaps, fragrances, food packaging, and other consumer products. Organophosphate pesticides are widely used to kill insect pests in agricultural fields and homes. PAHs are air pollutants found in everything from vehicle exhaust to charred meat.
Research in humans and lab animals has linked these endocrine disruptors to other potential consequences, as well. Bisphenol A (BPA), for example, makes fat cells bigger and disrupts the function of a protein that protects against heart disease, potentially contributing to cardiovascular risks. Phthalates can alter the function of protein receptors involved in sugar and fat metabolism, meaning that—like the thrifty phenotype—they may fundamentally reset the body’s response to calories in food.
Given the pervasiveness of these chemicals, they often end up in household air and dust. Our reliance on products made from them could be coming at a steep cost. Evidence of the harm they pose has accrued primarily through epidemiological studies of hormone-deficient mothers or children and through toxicology studies of lab animals.
Epidemiological studies are notoriously challenging due to the near-impossibility of finding control populations that haven’t been exposed to the ubiquitous chemicals and the sheer variety of other contributing factors that must be considered. Uncertainty remains over the cumulative effects of exposure to intermingling chemicals and over how best to assess the risks from chronic low-level exposures. Some skeptics have likewise questioned the validity of extending the results of toxicology experiments on animals to people, particularly as the scientific basis for new policies.
Although correlations between exposures and impairments don’t prove that such chemicals are toxic, Dr. Trasande argues that most human and lab animal studies have consistently pointed in the same direction, strengthening the case for causation. In a 2015 study that measured children’s and adolescents’ exposure to phthalates found in processed foods, Dr. Trasande and his colleagues discovered that higher concentrations of phthalate in urine samples were associated with higher blood pressure. In a related study, his group linked some of the same chemicals to increased insulin resistance, which causes sugar to build up in the blood and can lead to diabetes.
Among multiple studies that have sought to estimate the public health burden of endocrine-disrupting chemicals, Dr. Trasande and his colleagues have suggested that reproductive disorders account for billions of dollars in expenditures. In men, these chemicals were associated with major costs for disorders such as infertility, testicular cancer, and undescended testicles, while in women, they were linked to reproductive disorders such as fibroids and endometriosis.
In a major 2016 study, Dr. Trasande and his team conservatively estimated that exposure to endocrine disruptors accounted for total annual healthcare costs of $340 billion in the United States (2.3 percent of the nation’s gross domestic product) and $217 billion in Europe. They linked the lion’s share of these costs to the effects of organophosphates on children’s brain development. Even these huge expenditures are likely to be underestimated, Dr. Trasande explains, given that the researchers focused on only a small fraction of the chemicals sold commercially and their associated medical conditions. There are more than 85,000 such chemicals on the market, but limited screening efforts have identified about 1,000 as endocrine disruptors. “That’s why we need to keep doing research,” says Dr. Trasande. “There are substantial gaps.”
What Can We Learn from 50,000 Children?
It’s one thing to study chemical exposures in mice or to comb existing data sets for associations. But how do we really know what’s happening in humans? A few reviews of observational studies have yielded contradictory results, and experts agree that the field may never find a true “smoking gun” because of the impossibility of ethically testing the effects of potential toxins on people. “Causation is never certain,” Dr. Trasande acknowledges. “The best we can do as scientists is to lay out the information, along with all the uncertainties, and interpret the probability of a scientific phenomenon.”
To drill deeper, Dr. Trasande is spearheading some of the largest clinical investigations of endocrine disruptors to date. In 2016, he and his colleagues began tracking chemical exposures in women early in their pregnancy through a clinical study called CHES, for NYU Children’s Health and Environment Study. CHES has since received substantial funding through a larger National Institutes of Health (NIH) program called Environmental influences on Child Health Outcomes, or ECHO. This research initiative is examining how maternal and pediatric exposure to a wide range of environmental factors prior to conception through early childhood can affect the health and development of children and adolescents. ECHO aims to enroll more than 50,000 children from dozens of study sites nationwide, providing a scale that Dr. Trasande says will represent the best opportunity yet to understand the effects of endocrine disruptors and other environmental exposures.
By the end of last year, Dr. Trasande’s team had recruited more than 2,000 women and 1,100 infants from Tisch Hospital, NYC Health + Hospitals/Bellevue, and NYU Langone Hospital—Brooklyn. Based on their success, they subsequently received a $40 million 5-year NIH grant to ramp up their efforts. Some of that funding has gone toward amplifying existing collaborations with other institutions in the United States and the Netherlands that are examining the effects of chemicals on infant development. Another portion of the grant has allowed Dr. Trasande and his colleagues to extend their CHES study window to include childhood exposures through age two and track some maternal exposures prior to pregnancy. Dr. Trasande and his colleagues are calling the new preconception phase Factors Influencing Reproductive Success and Time to pregnancy, or FIRST.
“While pregnancy matters, it may be exposures even before pregnancy that impact how the baby does,” Dr. Trasande explains. The first phase enrolls women who come in for regular gynecologic or well visits. If they become pregnant, they move on to the second phase, CHES prenatal. Researchers follow the women through their prenatal care and collect samples at 18 weeks or less, at 18 to 25 weeks, and again in the third trimester. The combined FIRST–CHES data bank will be one of only three in the world to contain prospective data from preconception through early childhood, and the only one to contain preconception semen samples from male partners.
The Power of Personal Choice
One of Dr. Trasande’s overarching goals is to establish the threats posed by certain chemicals with enough evidence to guide people on how to better protect themselves and their children. But he acknowledges that personal choices can only go so far, given the pervasiveness of these chemicals in consumer products and the environment. Even if you can control what’s in your home, you can’t necessarily control what’s in your school, workplace, or surrounding environment. For this reason, he and other researchers stress that change must also take place at the institutional level. “We have much more power as a society through our pocketbooks and wallets,” Dr. Trasande says. “The ban on BPA in sippy cups and baby bottles occurred because consumers cried out to companies asking whether BPA was in these products.”
Dr. Trasande hopes that his studies will help drive broader changes in public policy, as well, by characterizing and confirming the risks of specific chemicals and by identifying the most vulnerable populations, notably children. The key, he says, is to imagine childhood health and disease as a three-legged stool supported by environment, behavior, and genetics: any leg can affect another, and all three must be examined together. “If we incorporate better information about these influences into our studies,” says Dr. Trasande, “we can unlock diseases and their origins.”
As the lessons of the Dutch Hunger Winter suggest, revealing the true agents of disease and devising early ways to overcome them may help prevent a lifetime of avoidable illness.