A 1976 chemical factory explosion near Seveso, Italy exposed residents to high levels of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD or dioxin). Dioxin is a known human carcinogen and potent endocrine disruptor. It is highly lipophilic and has a long half-life in humans. Much of what we know and can learn about the risks of dioxin exposure on human health arose from the tragic circumstances of Seveso. This review aims to describe the Seveso accident, summarize the results of 40 years of research on the health of the Seveso population since the accident, and discuss next-stage research on the health of Seveso residents, their children, and grandchildren.

Purpose of Review Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals with many modern applications, leading to widespread contamination and universal human exposure. PFAS exposure during early life is of particular concern, given susceptibility of the developing fetal and infant brain to toxic exposures. This review aims to synthesize current evidence, discuss methodological challenges, and highlight research gaps to guide future studies on the impact of PFAS on neurodevelopment. Recent Findings Sixty-one studies in total were published from 2008 to March 2024, with 35 in the last five years. Findings primarily link early life PFAS exposure to reduced cognitive, motor, and language development in infancy and increased behavioral issues like hyperactivity in childhood. Large studies have shown mixed results concerning child cognition, executive function, autism, and ADHD, with some indicating no association or unexpected protective findings. Sex-specific associations have been observed, but not consistently. Most research has addressed low-level exposure, suggesting subtle but potentially significant population-wide neurodevelopmental effects. Recent research also highlights concerns about newer, alternative PFAS, suggesting they too might affect neurodevelopment. Summary The effects of early-life PFAS exposure on neurodevelopment merit further study, particularly the cumulative effects of prenatal and postnatal exposures. Research has not fully explored sensitive subgroups or potential mitigating factors such as breastfeeding and nutrient intake, which will require larger, more diverse samples. Future directions include deeper study of PFAS mixtures, interactions with other neurotoxic environmental chemicals, and effects of newer PFAS types. There is also a need to focus on neuropsychological functioning in later childhood, using direct assessments for more reliable evaluations.

Exposures to phthalates, parabens, and other phenols are often correlated due to their ubiquitous use in personal care products and plastics. Examining these compounds as a complex mixture may clarify inconsistent relationships between individual chemicals and childhood adiposity. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal cohort of children in Salinas Valley, California (n = 309), we examined biomarkers of 11 phthalate metabolites and 9 phenols, including several parabens and bisphenol A, measured in maternal urine at two time points during pregnancy. We measured child height and weight at age five to calculate the body mass index (BMI) z-scores and overweight/obesity status. The association between prenatal urinary concentrations of biomarkers with the childhood BMI z-score and overweight/obesity status was analyzed using single-pollutant models and two mixture methods: Bayesian hierarchical modeling (BMH) and Bayesian kernel machine regression (BKMR). Urinary concentrations of monoethyl phthalate, monocarboxy-isononly phthalate (metabolites of diethyl phthalate and di-isodecyl phthalate, respectively), and propylparaben were consistently associated with an increased BMI z-score and overweight/obesity status across all modeling approaches. Higher prenatal exposures to the cumulative biomarker mixture also trended with greater childhood adiposity. These results, robust across two methods that control for co-pollutant confounding, suggest that prenatal exposure to certain phthalates and parabens may increase the risk for obesity in early childhood.

Youth with autism spectrum disorder often have complex medical needs. Disruptions of healthcare during the transition from pediatric to adult healthcare may put youth with autism spectrum disorder at higher risk of medical emergencies and high medical costs. We conducted a study among transition-age youth (14–25 years old) receiving healthcare at Kaiser Permanente Northern California during 2014–2015. We examined the differences in healthcare utilization and costs among youth with autism spectrum disorder ( n = 4123), attention deficit and hyperactivity disorder ( n = 20,6015), diabetes mellitus ( n = 2156), and general population controls ( n = 20,615). Analyses were also stratified by age and sex. Youth with autism spectrum disorder had the highest utilization of outpatient primary care, mental health, and psychotropic medications and the lowest utilization of obstetrics/gynecology and urgent care. Costs for youth with autism spectrum disorder were higher than those for attention deficit and hyperactivity disorder and general population peers and lower than for diabetes mellitus. Utilization patterns varied by age. Transition-age youth with autism spectrum disorder generally utilize healthcare at higher rates relative to attention deficit and hyperactivity disorder and general population peers but at similar or lower rates than diabetes mellitus peers, indicating this group’s complex combination of psychiatric and medical healthcare needs. The relatively high utilization of psychiatric services and low utilization of women’s health services in transition-age youth with autism spectrum disorder may have implications for long-term health and warrants additional research. Lay Youth with autism spectrum disorder often have complex medical needs. Disruptions of healthcare during the transition from pediatric to adult healthcare may put youth with autism spectrum disorder at higher risk of medical emergencies and high medical costs. To understand healthcare utilization during the transition years, we conducted a study among transition-age youth (14–25 years old) receiving healthcare at Kaiser Permanente Northern California during 2014–2015. We examined differences in healthcare utilization and costs among youth with autism spectrum disorder ( n = 4123), attention deficit and hyperactivity disorder ( n = 20,6015), diabetes mellitus ( n = 2156), and general population controls ( n = 20,615). Analyses were also stratified by age and sex. Youth with autism spectrum disorder had the highest utilization of outpatient primary care, mental health, and psychotropic medications and the lowest utilization of obstetrics/gynecology and urgent care. Costs for youth with autism spectrum disorder were higher than those for attention deficit and hyperactivity disorder and general population peers and lower than for diabetes mellitus. Healthcare utilization patterns varied by age. Transition-age youth with autism spectrum disorder generally used healthcare at higher rates relative to attention deficit and hyperactivity disorder and general population peers but at similar or lower rates than diabetes mellitus peers, indicating this group’s complex combination of psychiatric and medical healthcare needs. The relatively high utilization of psychiatric services and low utilization of women’s health services in transition-age youth with autism spectrum disorder may have implications for long-term health and warrants additional research.