ADHD risk factors – Science

IU Researchers Find No Link Between Prenatal Opioid Pain Medication and Increased Autism or ADHD Risk

SCIENMAG — Tue, 16 Sep 2025 18:33:58 +0000

A groundbreaking study conducted by researchers at Indiana University presents a comprehensive analysis that challenges long-held concerns regarding the use of prescribed opioid pain medications during pregnancy and their potential impact on children’s neurodevelopment. Drawing on a vast and meticulously analyzed Swedish population dataset, this extensive research elucidates that mild to moderate prenatal exposure to these opioid analgesics does not directly contribute to heightened risks for autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD). These findings shift the prevailing narrative by suggesting that confounding factors, possibly linked to parental health and environmental influences, may better explain observed correlations rather than opioid exposure itself.

For decades, the clinical community and expectant parents alike have faced a perplexing dilemma—balancing effective pain management with the concern that opioid medications could disrupt fetal brain development. This new study, spearheaded by graduate student Emma Cleary and Professor Brian D’Onofrio from the Department of Psychological and Brain Sciences, offers critical clarity. Their research synthesized epidemiological data from over a million Swedish births, incorporating exhaustive statistical adjustments to parse out the relative contributions of opioid exposure versus familial and environmental confounders in the development of ASD and ADHD.

The study’s methodological rigor is evident in its multi-layered analytical approach. Initially, analyses mimicked prior research by associating higher doses of prescribed opioids during pregnancy with increased neurodevelopmental risks. However, the researchers then implemented sophisticated adjustments for confounding variables including parental psychiatric history, age, socioeconomic status, and prior opioid use patterns. More pivotal were designs incorporating sibling comparisons and timing-based prescription windows which accounted for shared genetic and environmental factors. These strategies collectively eroded the apparent risks attributed solely to opioid exposure, indicating that shared familial traits and underlying conditions were substantial drivers behind the increased incidence of ASD and ADHD.

An innovative aspect of the investigation was the application of text-mining algorithms to the prescription records. This novel technique enabled researchers to parse the dosing instructions with unprecedented precision, capturing variations such as “as needed” ranges versus fixed dosages. Through these algorithmically modeled exposure scenarios, the findings demonstrated robust consistency: even when considering nuanced differences in medication intake patterns, no causal relationship emerged between opioid analgesics administered during pregnancy and heightened risks of neurodevelopmental disorders.

This critical advancement comes at a time when randomized controlled trials examining opioid use during pregnancy remain ethically and logistically untenable. Instead, the interdisciplinary collaboration among epidemiologists, clinicians, and data engineers exemplifies how big data and innovative analytical methods can illuminate complex clinical questions that were previously beyond reach. Professor D’Onofrio highlights that leveraging these population registries and computational tools offers a template for future research tackling similarly intricate prenatal exposures.

The implications for clinical practice and patient counseling are profound. Physicians and pregnant individuals grappling with the management of moderate to severe pain can find reassurance in these results, which indicate that appropriate prescribed opioid use may not inherently elevate risks for ASD or ADHD. Nevertheless, the research team cautions that exposure to high opioid doses, which occurred infrequently in the data, cannot be conclusively exonerated from potential small risk increases. Hence, clinical prudence remains essential, alongside comprehensive psychosocial support for pregnant patients experiencing pain.

Beyond addressing the opioid issue itself, the study raises compelling questions about the underlying etiologies of neurodevelopmental risk in this population. The convergence of genetic predispositions, environmental stressors, mental health conditions, and perhaps the pathophysiological consequences of chronic pain likely contribute more substantially to autism and ADHD prevalence than medication effects per se. Unpacking these multifactorial influences demands further investigation and underscores the necessity for holistic pregnancy care models encompassing mental health and social support services.

As postdoctoral fellow Ayesha Sujan emphasizes, the research spotlights the urgent need for robust, evidence-based pain management alternatives that complement pharmacological treatments. Interdisciplinary efforts toward integrating non-pharmaceutical interventions—including behavioral therapies, physical rehabilitation, and psychosocial resources—could play a transformative role in supporting maternal and fetal health without overreliance on opioids.

In sum, this landmark retrospective study, published in PLOS Medicine, establishes a foundational shift in understanding opioid use in pregnancy. By meticulously disentangling confounders from causal effects, it realigns the clinical discourse and public health policies related to prenatal analgesic strategies. The findings advocate for nuanced decision-making grounded in rigorous data rather than fear-driven avoidance, potentially expanding treatment options for pregnant individuals while safeguarding child neurodevelopment.

While this study proficiently addresses some critical unknowns, it simultaneously opens avenues for future research into the complex biopsychosocial frameworks underpinning neurodevelopmental disorders. Integrating genetic mapping, longitudinal mental health assessments, and detailed pain profiling may yield transformative insights, ultimately guiding personalized interventions that promote healthier maternal and child outcomes.

The collaboration between Indiana University, Karolinska Institutet, University of Oxford, Harvard T.H. Chan School of Public Health, and other leading institutions exemplifies how global scientific partnerships enhance research impact. Supported by the National Institute on Drug Abuse, the work illustrates the potent synergy of population data, computational innovation, and cross-disciplinary expertise in advancing maternal and child health science.

More than a cautionary tale about opioids, this research invites a reexamination of prenatal care paradigms, emphasizing comprehensive support mechanisms over medication stigma. In doing so, it marks a vital step toward unraveling the complex tapestry of factors influencing autism and ADHD, offering hope for informed, compassionate care for generations to come.

Subject of Research: People

Article Title: Prescribed opioid analgesic use in pregnancy and risk of neurodevelopmental disorders in children: A retrospective study in Sweden

News Publication Date: 16-Sep-2025

Web References: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004721

Keywords: Health and medicine

Parental avoidance of toxic exposures could help prevent autism, ADHD in children, new study shows

SCIENMAG — Thu, 28 Mar 2024 01:15:07 +0000

SAN ANTONIO, March 27, 2024 – Autism and attention deficit hyperactivity disorder (ADHD) may be preventable if parents avoid toxic exposures and adopt interventions such as environmental house calls, according to a published study led by researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio). Using a validated, self-administered questionnaire now used worldwide to identify individuals with chemical intolerance – the Quick Environmental Exposure and Sensitivity Inventory (QEESI©) – parents and practitioners can determine the risk for each family and learn which exposures to avoid in their own homes where most people spend most of their day, the researchers said. A population-based survey of nearly 8,000 U.S. adults, using QEESI, found that parents with chemical intolerance scores in the top tenth percentile were 5.7 times as likely to report a child with autism and 2.1 times as likely with ADHD compared with parents in the bottom tenth percentile. The findings build on a 2015 study by UT Health San Antonio that first linked chemical intolerance in patients with the risk of their children developing autism and ADHD. “This is the first-ever article in the medical literature showing that chemical intolerance in parents can predict the risk of autism and ADHD in their children, and suggests that reducing exposures prior to and during pregnancy could help prevention,” said Claudia S. Miller, MD, MS, professor emeritus with the Department of Family and Community Medicine at UT Health San Antonio. “Up to now, most interventions have been behavioral or medical, after a child is diagnosed.” Miller is senior author of the study, titled, “Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children,” published March 1 in the Journal of Xenobiotics, a leading toxicology publication, for its special issue on autism. Co-authors include Raymond F. Palmer, PhD, and Rodolfo Rincon, MD and specialist, both with the Department of Family and Community Medicine at UT Health San Antonio; and David Kattari, a statistician with the Marilyn Brachman Hoffman Foundation in Fort Worth, Texas. The researchers note that the study is observational, and further research is needed using controlled trials to confirm causality and further explore the proposed mechanism behind chemical intolerance. Still, they wrote, “The implications of this study, if confirmed, could be significant for preventive measures and early intervention strategies in families with parental chemical intolerance. We recommend that all prospective parents be assessed for chemical intolerance at an early age.” Mast cells and autism Physician-researcher Miller in 1996 first proposed a two-stage disease process of initiation by exposure and then triggering of symptoms called TILT, for Toxicant-Induced Loss of Tolerance, as the mechanism behind chemical intolerance. She has served as a physician/environmental consultant on exposures. And her published papers have explored the impact of pesticides, the Gulf War, breast and other implants, 9/11, toxic molds, combustion products from fires, and indoor air pollutants in so-called “sick” homes, schools and workplaces, including the EPA’s own headquarters building in Washington, D.C. The new study comes amid a backdrop of a 317% increase in the prevalence of autism since 2000, now occurring in one of every 36 children in the country, the researchers note, citing data originating from the Centers for Disease Control and Prevention. And the prevalence of ADHD has risen to one in eight children, also according to the CDC. Miller and colleagues in 2021 discovered a strong association between chemical intolerance and “mast cells,” considered the immune system’s first responders that originate in the bone marrow and migrate to the interface between tissues and the external environment where they then reside. When exposed to “xenobiotics,” foreign substances like chemicals and viruses, they can release thousands of inflammatory molecules called mediators. This response results in allergic-like reactions, some very severe. These cells can be sensitized by a single acute exposure to xenobiotics, or by repeated lower-level exposures. Thereafter, even low levels of those and other unrelated substances can cause the mast cells to release the mediators that can lead to inflammation and illness. In their latest study, the researchers determined that the high chemical intolerance scores among parents of children with autism, coupled with the 2021 finding of mast-cell activation as a plausible biomechanism for chemical intolerance, suggest that:

The QEESI can identify individuals at increased risk. Environmental counseling, such as personalized environmental house calls to assess risks at home, may reduce personal exposures to possible triggers such as pesticides, fragrances and tobacco smoke, particularly during pregnancy and childhood. The global rise in autism and ADHD may be due to fossil-fuel-derived and biogenic toxicants epigenetically “turning on” or “turning off” critical mast cell genes that can be transmitted trans-generationally.

The researchers conclude that once mast cells are sensitized, diverse xenobiotics that never bothered the person previously and do not bother most people trigger multisystem symptoms that wax and wane over time. And they believe that persistent activation and triggering of mast cells may underlie the brain inflammation in autism. “The potential role of environmental toxicants in influencing epigenetics and mast cell function is a complex and emerging area of research,” they wrote. “Acknowledging the need for further evidence, we hope this study contributes to an improved understanding of the potential role of environmental factors in the global rise of autism and ADHD.” The authors created tools for patients, practitioners and researchers, described in their “TILT Tutorial on Chemical Intolerance, Autism, and ADHD”, available along with other resources at https://TILTresearch.org. Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children Raymond F. Palmer, Rodolfo Rincon, David Kattari, Claudia S. Miller First published: March 1, 2024, Journal of Xenobiotics https://www.mdpi.com/2039-4713/14/1/22 The University of Texas Health Science Center at San Antonio (UT Health San Antonio), a primary driver of San Antonio’s $44.1 billion health care and biosciences sector, is the largest academic research institution in South Texas with an annual research portfolio of $413 million. Driving substantial economic impact with its six professional schools, a diverse workforce of more than 8,500, an annual expense budget of $1.46 billion and clinical practices that provide 2.6 million patient visits each year, UT Health San Antonio plans to add more than 1,500 higher-wage jobs over the next five years to serve San Antonio, Bexar County and South Texas. To learn about the many ways “We make lives better®,” visit UTHealthSA.org. Stay connected with The University of Texas Health Science Center at San Antonio on Facebook, Twitter, LinkedIn, Instagram and YouTube.

Journal

Journal of Xenobiotics

DOI

10.3390/jox14010022

Method of Research

Observational study

Article Title

Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children

Article Publication Date

1-Mar-2024