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Open research questions in Prenatal Substance Exposure Effects

100 unresolved questions extracted from the limitations and future-work sections of 1,443 Prenatal Substance Exposure Effects papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Next, Marlow aims to expand on this work with a new study focused on suicide risk and prevention among people with neurodevelopmental disorders, which would be especially relevant for the FASD population and military families. She described a proposed research study that would look at individual, community, and regulatory factors that may influence suicidal behaviors among people with neurodevelopmental disorders, including a granular examination of outcomes among people with different types of disorders. Preliminary data collected to inform this proposal indicate that the prevalence of suicidal behaviors has been rising since before the COVID- 19 pandemic and that the growth has been especially pronounced among people with neurodevelopmental disorders relative to those without such disorders, underscoring the urgency of finding effective interventions to address suicide risk. In the meantime, she emphasized that all programs for the neurodevelopmental disorders community should incorporate strategies to increase access to mental health support and prevent suicide. FASD prevention and clinical guidelines research project updates In the workshop’s second session, researchers shared emerging findings from projects related to the FASD Prevention and Clinical Guidelines Research Initiative (“the FASD Project”). To open the session, Elizabeth H. Lee, DrPH, of USUHS Pediatrics and the USUHS CHSR, and Sarah Brown, MPH, of FASD United, shared outcomes of the first three years of activities within the FASD Project. Then, investigators involved in the ongoing LoEs within the initiative shared emerging findings and insights from their work over the past year. Throughout the session, presenters highlighted cross-cutting issues and themes related to scientific practices and progress on FASD. FASD Project efforts and outcomes to date Lee noted that the FASD Project is supported by Congressionally-directed funding with an overarching goal to increase awareness and response to FASD and its risk factors within the MHS. While its primary focus is on improving care delivery to military children and families affected by FASD, the project also aims to create a model of FASD care delivery that may be replicated among national healthcare systems to benefit the general population. Lee noted that the project applies to children who may or may not have a formal diagnosis of FASD. The FASD Project is overseen by USUHS CHSR and conducted in partnership with FASD United, Boston University, and Madigan Army Medical Center. 2025 marks the end of the project’s third year, and project activities are slated to continue through 2028. Lee described outcomes to date along with ongoing activities across the project’s five LoEs (Fig. 1).

    Fourth annual workshop on fetal alcohol spectrum disorders prevention and clinical guidelines research: co-occurring conditions · 2026 · DOI

  • In this largescale systematic exploration—of four types of exposure in both parents at up to nine timepoints, on 72 child outcomes at up to four ages—we did not find strong evidence for widespread or large magnitude effects of parental health behaviours on child health and wellbeing (although we note that a lack of evidence does not indicate evidence against a causal effect; it may reflect issues such as low power, measurement error, and missing data—see Limitations). To our knowledge, few studies have directly compared the relative contributions of parental behaviours and socioeco- nomic conditions within a DOHaD framework, particularly at this scale.

    Exploring parental prenatal influences on child health: A multicohort study and data visualisation tool · 2026 · DOI

  • Although prenatal alcohol exposure (PAE) has been proposed as an early-life risk factor for Alzheimers disease and related dementias (AD/ADRD), the mechanistic underpinnings are underexplored.

    Prenatal Alcohol Exposure Disrupts γ-Secretase Activity and Impairs Learning and Memory in Wild-Type and 3xTg-AD Mice · 2026 · DOI

  • While few studies have highlighted the lingering effects of prenatal alcohol exposure (PAE) on producing specific immune factors, others suggest a primed neuroimmune state in adulthood, in which a proinflammatory bias is unmasked following subsequent immune activation in later-life.

    Unraveling a comparative landscape of protein-coding genes linked to neuroimmune function during adulthood consequent of prenatal alcohol exposure · 2026 · DOI

  • There are also several limitations. As health administrative datasets are primarily intended for reimbursement rather than research purposes, some important information cannot be captured, including health events for which healthcare was not received, as well as social factors (e.g., socioeconomic status, employment, adverse childhood events). Future research should aim to address these gaps through prospective, participatory, qualitative research. Importantly, the datasets do not contain direct observations of substance use, either through self-report or urine drug testing. This means that individuals without an indication of substance use in their health administrative records may be missing from the cohort. Moreover, our classifications of substance use disorders and administrative loss to follow-up may result in misclassification. We will consider alternative thresholds to assess the robustness of results to these thresholds. Our data are also not linked to data from the BC Ministry of Child and Family Development, meaning we are unable to identify children separated by state apprehensions. There were also 3,102 children who could not be linked to their mothers. These children included twins whose records could not be distinguished from one another, and children with missing linkage information. This limitation will be addressed in a forthcoming data update. With the exception of individuals who are in the broader substance use cohort, our population-based cohort does not currently contain information on fathers or other non-birthing parents. This limitation will also be mitigated in a future data update. There are also limitations within the datasets. The PharmaNet database does not capture medications dispensed in hospital, and is missing costing information for claims paid by the Canadian federal government, as well as antiretroviral PLOS One | https://doi.org/10.1371/journal.pone.0348262 May 26, 2026 9 / 13 Fig 3. Maternal deaths between 2000/04/01–2022/12/31. The increase in the proportion of deaths due to unknown causes since 2019 is due to a lag in data availability. https://doi.org/10.1371/journal.pone.0348262.g003 medications. Similarly, the Medical Services Plan database do not capture billing records under the Alternative Payment Plan, most often associated with community health centres. Lastly, many harm reduction services, which are an important part of the continuum of care for individuals who use substances, do not require individuals to provide identifying information in order to use these services. As a result, these interactions are not captured in provincial databases. Further linkage to community and local services is necessary to characterize health care service utilization, including the use of peer support services.

    Cohort profile: Mothers who use substances and their children in British Columbia, Canada · 2026 · DOI

  • Conclusion The temporal disconnect between early neurodevelopmental dis- ruption and later clinical recognition highlights a structural limitation in current diagnostic approaches, which prioritise observable outcomes over underlying developmental processes. The developmental–diagnos- tic gap offers a framework for understanding this delay by linking early neurobiological change to later behavioural identification. By integrating neurobiological, developmental, and sociocultural perspectives, this framework provides a more comprehensive account of how prenatal alcohol exposure shapes brain development prior to behavioural recognition. The placenta–brain axis further illustrates a potential biological pathway through which early environmental influ- ences may contribute to later neurodevelopmental outcomes. Reliance on behavioural presentation may contribute to delayed recognition, misinterpretation, and the accumulation of secondary developmental consequences. At the same time, advances in biological research highlight emerging opportunities for earlier identification and more developmentally informed approaches to support. The developmental–diagnostic gap provides a clinically relevant and empirically testable framework with implications for research, prac- tice, and public health. Addressing this gap has the potential to improve early identification, reduce secondary harm, and support more effective, developmentally informed intervention across the lifespan.

    The developmental–diagnostic gap: cultural invisibility and delayed recognition of prenatal alcohol exposure · 2026 · DOI

  • Conclusions Supportive housing programs for adults with FASD are sparse, and existing programs often fall short of addressing the holistic needs of these individuals.

    The scope of supportive housing for adults with fetal alcohol spectrum disorder: a rapid review · 2024 · DOI

  • BACKGROUND: While pregnant women in treatment for opioid use disorder (OUD) face considerable challenges, common material hardships- food insecurity and housing instability, known to negatively impact maternal-child health, have been inadequately researched within this population.

    Pregnant women in treatment for opioid use disorder: Material hardships and psychosocial factors · 2019 · DOI

  • BACKGROUND: While studies confirm high prevalence of language disorder among justice-involved young people, little is known about the impact of Fetal Alcohol Spectrum Disorder (FASD) on language among this population.

    Language diversity, language disorder, and fetal alcohol spectrum disorder among youth sentenced to detention in Western Australia · 2018 · DOI

  • The contention that Religion/Spirituality (R/S) influences the development of alcohol dependence (AD) is increasingly supported, but risk factors have not been adequately examined together with protective R/S factors so as to determine the nature and relative strength of these domains at different stages in the development of alcoholism.

    Religion/spirituality, risk, and the development of alcohol dependence in female twins. · 2013 · DOI

  • Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption.

    Safety and Side Effects of Ayahuasca in Humans—An Overview Focusing on Developmental Toxicology · 2013 · DOI

  • The extent to which these deficiencies contribute to future substance abuse remains to be determined, but the data highlight the need to take factors predating alcoholism onset, notably family history, into consideration before making causal assumptions between alcohol abuse and functional measures of brain activity.

    Sleep <scp>EEG</scp> as a Potential Marker of Alcoholism Predisposition—Commentary on “Adolescence and Parental History of Alcoholism: Insights from the Sleep <scp>EEG</scp>” · 2012 · DOI

  • The findings across methodological approaches provide support for a CSA-specific risk for alcohol misuse, despite the significant contribution of family background factors to overall risk, but much work remains to be done before a comprehensive model for this association can be proposed.

    Disentangling the Complex Association Between Childhood Sexual Abuse and Alcohol-Related Problems: A Review of Methodological Issues and Approaches · 2008 · DOI

  • The results from this community sample of low SES, ethnically diverse pregnant women suggest that because of the high levels of child abuse potential among this group, preventative interventions targeted toward child abuse potential are warranted for these women.

    Trauma and Intraveneous Drug Use among Pregnant Alcohol/Other Drug Abusing Women: Factors in Predicting Child Abuse Potential · 2008 · DOI

  • BACKGROUND: Little is known about men's patterns of substance use around their partner's pregnancy, despite evidence from studies of pregnant women that men's substance use may reduce women's ability to desist from substance use during pregnancy, increase the probability that women will return to use postpartum, and increase the risk of adverse child outcomes.

    Men’s and Women’s Patterns of Substance Use Around Pregnancy · 2008 · DOI

  • BACKGROUND: Accurate estimates of the prevalence and characteristics of fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD) in a Western European population are lacking and are of particular interest in settings where the usual pattern of alcohol consumption is thought to be daily drinking with meals.

    Epidemiology of FASD in a Province in Italy: Prevalence and Characteristics of Children in a Random Sample of Schools · 2006 · DOI

  • Prenatal cannabis exposure (PCE) is increasing, yet its effects on early brain development remain incompletely understood.

    Associations of Prenatal Cannabis Exposure and Neonatal Brain Development in the HBCD Cohort · 2026 · DOI

  • The UK has the fourth highest rate of prenatal alcohol use worldwide, but the condition remains stigmatised and under-recognised.

    Perspectives of fetal alcohol spectrum disorder diagnoses in children: The experiences of adoptive parents in Scotland · 2026 · DOI

  • The current gold standard for diagnosing PAE relies on self-reported questionnaires; however, underreporting remains a significant limitation.

    Determination of markers of ethyl alcohol consumption in pregnancy · 2025 · DOI

  • HCPs may recommend low levels of consumption based on other international guidelines, limited evidence to suggest that one unit of alcohol is harmful, and as a harm reduction strategy.

    Reporting on Health Care and Social Service Provider Approaches to Promoting Alcohol Abstinence During Pregnancy · 2024 · DOI

  • The inspiration for this presentation of the problem was a visible gap in the research carried out in the field of social sciences, which would concern directly the parents of harmful drinkers.

    Experience of Mothers of Adult Alcoholics ‒ A Report from Studies. · 2022 · DOI

  • Conclusion: Use of cannabis and cocaine close to pregnancy seems to be closely linked to other risk factors, and further studies on how paternal drug use affects the foetus are warranted.

    Pre conception use of cannabis and cocaine among men with pregnant partners · 2019 · DOI

  • Self-regulation in FASD is poorly defined and interpreted in varying ways, making informed clinical decision making difficult.

    Self-regulation in fetal alcohol spectrum disorder: A concept analysis · 2018 · DOI

  • The objective measurement of the timing and level of prenatal alcohol exposure is key to bridging these gaps; however, there is conflicting or limited evidence to support the use of existing measures.

    The Standardization of Diagnostic Criteria for Fetal Alcohol Spectrum Disorder (FASD): Implications for Research, Clinical Practice and Population Health · 2018 · DOI

  • Although fetal health and development are highly dependent upon the integrity of placentation, little is known about placental morphology following gestational exposure to alcohol in humans.

    Placental Morphology in Fetal Alcohol Spectrum Disorders · 2016 · DOI

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100 open questions have been extracted from the limitations and future-work passages of 1,443 Prenatal Substance Exposure Effects papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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