The concept of the exposome, the cumulative measure of environmental exposures an organism experiences across its lifespan, has gained traction in adult epidemiology, but its application to the newborn period carries a particular urgency. Very preterm birth fundamentally reshapes the developmental exposome by relocating a substantial portion of gestation outside the body. The fetus that would have been bathed in amniotic fluid, nourished continuously through the placenta, and shielded from most external chemicals instead receives parenteral nutrition through central lines, undergoes repeated blood transfusions, rests on plasticized medical devices, and breathes filtered, conditioned air. Each of these interventions is essential, and each introduces its own chemical signature. The commentary emphasizes that because survival has improved so dramatically, understanding how this prolonged hospital-based developmental setting influences long-term neurodevelopmental, respiratory, and cardiometabolic health has become a central question for children’s environmental health.

The central methodological obstacle has always been measurement. Collecting repeated biospecimens from medically fragile infants weighing sometimes less than a kilogram presents formidable practical and ethical challenges, and blood draws are limited by volume and clinical necessity. Bauer and Romano-Keeler highlight an elegant alternative that has been quietly maturing over the past decade: naturally shed deciduous teeth. Children lose their baby teeth in mid-childhood, and those teeth, it turns out, are meticulous biological recorders. As dentin mineralizes, elements circulating in the bloodstream are incorporated into the growing crystalline matrix in temporal sequence, layer by layer, much like tree rings. A distinctive microstructural feature called the neonatal line marks the moment of birth, giving researchers an exact chronological anchor from which to reconstruct week-by-week exposure histories stretching from fetal life through the entire NICU stay.

This approach offers something maternal biomarkers cannot. Measurements in maternal blood or hair primarily reflect maternal dose and may fail to capture placental transfer or fetal uptake, whereas prenatal tooth measurements derive from tissues formed in utero and therefore provide a more direct indicator of the fetal internal chemical environment. Postnatal metal exposure measured in teeth is increasingly investigated in cohort studies, but the exposures unique to the NICU have remained poorly characterized. The commentary accompanies a study in the same issue by Lieberman-Cribbin and colleagues that applies the technique to precisely this question, reconstructing weekly metal exposure histories using shed teeth collected from children across the United States who were born preterm.

The study drew participants from the Developmental Impact of NICU Exposures, or DINE, study, which enrolled children from multiple preterm cohorts participating in the Environmental influences on Child Health Outcomes, or ECHO, program. These infants spent a median of 85 days in the NICU, an extended hospitalization that allowed the researchers to examine metal exposure across a substantial portion of early development that would otherwise have occurred in utero. The findings were striking in their asymmetry. Several metals were higher on average during the prenatal period, while estimated average levels of lithium, rubidium, and strontium were higher postnatally, with the clearest difference observed for strontium. In other words, the chemical profile of development measurably shifts when the environment shifts from placenta to intensive care, and those shifts are written permanently into the mineralized tissue.

What could explain a postnatal rise in elements like strontium? The commentary lays out a set of plausible exposure pathways that the findings generate as hypotheses for future investigation. Infant feeding is an obvious candidate, since both human milk and formula carry distinct elemental profiles. Parenteral nutrition, the intravenous feeding that sustains the smallest infants for weeks, has a documented history of delivering trace metals, with earlier research identifying increased manganese deposition in the brains of infants receiving it and, in a landmark 1997 study, aluminum neurotoxicity in preterm infants fed intravenous solutions. Blood transfusions represent another under-recognized route, as red cell transfusions can carry toxic metals into a newborn circulation. Medical devices, including plasticized tubing and equipment, and other ambient features of the NICU environment round out the list. These pathways are especially relevant for extremely and very low birthweight infants, who receive the most prolonged and intensive nutritional and medical support precisely during a period of heightened developmental susceptibility.

Interpreting tooth biomarker data, however, demands careful attention to developmental biology, and the commentary is refreshingly candid about this complication. Temporal changes in elemental concentrations in dentin may reflect not only external exposures but also tissue growth, mineralization dynamics, shifts in nutrient requirements, and the maturation of metabolic and homeostatic pathways. A developing infant’s physiology is itself changing week by week, and those internal changes can alter which elements circulate and how they are deposited in mineralizing tissue. Distinguishing exposures arising from the external environment from endogenous developmental processes is therefore central to the enterprise. At the same time, the authors argue, the real value of these measurements lies in their ability to place both processes on a common developmental timescale, clarifying how the external environment and internal physiology jointly shape the chemical milieu of the developing child rather than pretending one can be isolated from the other.

The roadmap that emerges from the commentary is both practical and ambitious. Future studies that integrate tooth biomarkers with detailed clinical, nutritional, and environmental records will be essential for identifying the origins of NICU exposures: information on enteral and parenteral nutrition, medications, transfusions, respiratory support, medical devices, and treatment duration could help separate the chemical contributions of neonatal care from those of endogenous development. The authors also propose a structural innovation with lasting value: incorporating permission for future recontact and deciduous teeth collection into existing neonatal biorepositories, creating a resource that would enable longitudinal investigations of how early-life exposures influence health and disease for decades to come. Extending tooth-based methods beyond metals to plastic-associated chemicals and persistent organic pollutants, with potential applications to pharmaceuticals and other metabolites, would round out the picture of the NICU environment, building on emerging work that has already detected organic pollutants in primary teeth and linked fetal exposures to later outcomes.

The ultimate prize is causal clarity about long-term consequences. Preterm birth is associated with elevated risks of neurodevelopmental impairment, respiratory disease, and cardiometabolic dysfunction in adulthood, but the contribution of hospital-based exposures during the NICU course to those outcomes remains largely unmapped. Longitudinal follow-up of children whose teeth have been analyzed will be essential for determining whether exposures occurring during specific windows of the NICU stay are associated with later cognition, growth, respiratory health, or cardiometabolic function. If specific periods or specific care practices turn out to carry disproportionate chemical burden, the exposome map becomes a clinical instrument, pointing toward modifiable aspects of neonatal care, from nutritional formulations to device materials, that could be adjusted without compromising the lifesaving function of the unit itself.

What makes this research paradigm resonate beyond neonatology is its simplicity and its reversibility. Baby teeth that most families discard, or tuck into keepsake boxes, contain a week-by-week archive of one of the most chemically complex periods of human development, retrievable years later without a single invasive procedure. The NICU sustains life outside the intrauterine environment, and it does so brilliantly, but it is also a distinct setting in which clinical care, nutrition, environmental chemicals, and developmental physiology converge during a period of heightened vulnerability. Defining the developmental exposome of that setting, as Bauer and Romano-Keeler argue, may ultimately help design developmental environments that better support health across the entire life course, turning an underutilized biological resource into a bridge between the intensive care that saves infants and the lifelong health those survivors deserve.

Subject of Research: Reconstructing prenatal and NICU metal exposures in preterm infants using deciduous tooth biomarkers

Article Title: Defining the developmental exposome of the neonatal intensive care unit in preterm infants

Article References: Bauer, J. A., & Romano-Keeler, J. (2026). Defining the developmental exposome of the neonatal intensive care unit in preterm infants. Journal of Exposure Science & Environmental Epidemiology. https://doi.org/10.1038/s41370-026-00981-5

Image Credits: AI Generated

DOI: 10.1038/s41370-026-00981-5

Keywords: exposome, neonatal intensive care unit, preterm infants, deciduous teeth, metal exposure, biomonitoring, ECHO program, DINE study, parenteral nutrition, child environmental health, dentin biomarkers, strontium

The challenge at the heart of this research is deceptively simple to state and notoriously hard to solve. Radioactive wastewater typically contains a cocktail of radionuclides, including cesium, strontium, and lanthanum species, whose ionic properties overlap to a remarkable degree. Cesium exists in solution as a monovalent cation, Cs+, while strontium and lanthanum appear as divalent Sr2+ and trivalent La3+ ions. Conventional separation technologies, ranging from chemical precipitation to adsorption and forward osmosis, struggle to discriminate between these species because differences in hydrated radius and charge are subtle. Yet precise separation matters enormously: safely disposing of nuclear waste, recycling nuclear resources, and minimizing environmental contamination all depend on isolating specific ions from complex mixtures.

The team, led by Ziwen Dai and Shushan Yuan of Huazhong University of Science and Technology in Wuhan, together with Pengrui Jin of KU Leuven and the University of Bath and collaborators in France and Korea, took their design cue from biology. Natural ion channels, such as the potassium channels found in cell membranes, achieve exquisite selectivity not through brute-force size exclusion alone but through precisely arranged binding sites that impose tuned energetic penalties on unwanted ions. Translating that principle to a synthetic membrane, the researchers constructed vertically aligned two-dimensional subnanochannels within graphene oxide lamellae and functionalized them with ethylenediaminetetraacetic acid, better known as EDTA. This chelating agent is famous in chemistry for its strong grip on metal ions, and here it serves as the molecular machinery that dictates which ions pass and which are held back.

The resulting GO-EDTA membrane contains stable, ordered channels whose internal functional groups exhibit strong, affinity-driven binding interactions with Sr2+ and La3+. In practical terms, the chemistry of the channel walls raises the diffusion energy barrier for multivalent ions far above that faced by monovalent Cs+. An ion crossing the membrane effectively must climb an energetic mountain, and the height of that mountain differs depending on the ion’s charge and its interaction with the EDTA groups. Because ion permeation rates depend exponentially on the barrier height according to transition-state theory, even modest differences in barrier energy translate into enormous differences in transport rates. This is precisely how the membrane achieves its headline performance: measured mono/multivalent ion selectivity reaches 485 for Cs+/Sr2+ and an extraordinary 1300 for Cs+/La3+.

What distinguishes this study from earlier work on graphene oxide membranes is the depth of the mechanistic analysis. Rather than reporting selectivity numbers alone, the researchers used a quartz crystal microbalance to dissect the overall energy barrier for salt transport into its two constituent contributions: partitioning at the pore mouth, where an ion must shed part of its hydration shell and enter the confined channel, and intrapore diffusion, where the ion migrates through the channel interior. The measurements revealed that the diffusion energy barrier is the dominant obstacle governing transmembrane ion transport, meaning that selectivity can be engineered by deliberately manipulating the energetic landscape inside the channels rather than merely adjusting their physical width. This insight reframes membrane design: instead of thinking of nanofiltration as a sieve, researchers can treat it as a tunable energetic landscape, much as enzyme chemists think about activation energies.

A crucial concern for any material destined for nuclear applications is resilience to radiation. Harsh irradiation environments degrade most organic polymers and many inorganic structures, causing swelling, embrittlement, or loss of functional groups. The GO-EDTA membrane passed this test: the channels maintained stable separation performance under irradiation conditions, a property the authors attribute to the inherent robustness of the graphene oxide scaffold and the stability of the aligned two-dimensional subnanochannel architecture. This radiation resistance is what moves the material from an elegant laboratory curiosity toward genuine deployment potential inside nuclear reprocessing facilities and wastewater treatment plants, where background radiation would rapidly compromise conventional polymeric membranes.

The practical payoff of the technology was demonstrated through electrodialysis experiments in which the membrane recovered cesium in the form of a purified CsCl product reaching a purity of 99.5 percent. That figure is significant beyond the laboratory. Cesium-137 is one of the most problematic fission products in nuclear waste, with a half-life of about thirty years and a chemistry that closely mimics potassium, allowing it to infiltrate biological systems. Capturing it selectively, in high purity, opens the possibility of converting a liability into a resource, since recovered cesium has applications in radiation sources and industrial gauges, while the decontaminated effluent becomes far easier and safer to manage. The same principle extends to strontium-90 and various actinide and lanthanide species that populate legacy waste tanks at sites such as Hanford and Sellafield.

The work also fits into a broader and rapidly accelerating scientific movement centered on confined ion transport in two-dimensional materials. Over the past decade, graphene oxide laminates have been shown to sieve ions through capillaries just a few angstroms wide, and related efforts have exploited metal-organic frameworks, MXenes, and covalent organic frameworks to create subnanometer transport pathways. Each of these platforms controls selectivity through some combination of steric exclusion, electrostatic repulsion, and dehydration penalties. The EDTA-functionalized graphene oxide membrane adds a powerful new lever to that toolbox: strong, chemically specific coordination interactions embedded within the channel walls, coupled with an explicit, experimentally validated understanding of how the diffusion energy barrier, rather than the partitioning barrier, dominates the separation.

The implications ripple outward beyond nuclear waste. Energy barrier engineering, as the authors describe it, offers a general design principle for any membrane application demanding high ion-ion selectivity: lithium extraction from magnesium-rich brines, where Li+ and Mg2+ share similar hydrated radii; the recovery of cobalt and nickel from battery recycling streams; and the removal of toxic heavy metals from industrial effluents. In each case, anchoring tailored chelating chemistry inside robust two-dimensional channels could deliver selectivity levels that conventional charge-based or size-based membranes cannot approach. The traceability of the mechanism, made possible by the quartz crystal microbalance measurements, means that future membrane designers can compute in advance how a given functional group will shift the transport energetics for a target ion pair.

Challenges remain before the technology reaches industrial scale. Fabricating large-area, defect-free GO-EDTA membranes with uniformly aligned channels will require process engineering that laboratory-scale methods do not yet provide, and long-term fouling behavior in genuinely complex waste matrices, which contain organic molecules, suspended solids, and competing ions in far greater variety than the model solutions tested here, must be established. Nevertheless, the combination of ultrahigh selectivity, radiation tolerance, demonstrated product recovery at 99.5 percent purity, and a clear mechanistic framework represents a milestone in membrane science. As the authors conclude, their work provides both a mechanism for designing membranes with high ion-ion selectivity and a concrete demonstration of the application potential of nuclear resource recycling, a message likely to resonate across environmental engineering, radiochemistry, and materials science in the years ahead.

The study was supported by the National Natural Science Foundation of China, the Innovation and Self-Development Research Fund of Huazhong University of Science and Technology, and the Hubei Provincial Science and Technology Research Project. The full article is available open access under a Creative Commons Attribution 4.0 license.