A groundbreaking new study published in BMC Psychiatry sheds fresh light on the enduring impact of prenatal alcohol exposure (PAE) on the physiological stress mechanisms of offspring, charting a developmental course from childhood into adolescence. This research delves into the complex interplay between maternal behaviors during pregnancy—specifically alcohol consumption and prenatal depressive symptoms—and their long-term influence on the hypothalamic-pituitary-adrenal (HPA) axis functioning in children.
The HPA axis is a central component of the body’s response to stress, coordinating the release of glucocorticoids like cortisol, which regulate a myriad of physiological processes from immune function to metabolism. Dysregulation of this axis during critical developmental windows has been implicated in various neuropsychiatric and behavioral disorders, making the investigation of prenatal influences on HPA axis activity especially urgent.
Researchers employed hair cortisol concentration (HCC) as a biomarker to evaluate HPA axis function in the children studied. Hair cortisol offers a cumulative measure of cortisol secretion over extended periods, providing a more stable and integrated picture of chronic stress exposure, in contrast to snapshot assessments via blood or saliva. This longitudinal study involved 94 children whose HCC was measured both at approximately 7.7 years of age and again during early adolescence, at around 13.3 years, enabling the investigators to observe developmental trajectories of stress hormone regulation.
Critically, the determination of prenatal alcohol exposure was triangulated using maternal self-reports alongside quantification of ethyl glucuronide (EtG) in neonatal meconium. EtG, a direct metabolite of ethanol, serves as a reliable and objective biomarker indicating in utero exposure to alcohol. Two EtG cut-off points were utilized: a lower threshold at 10 ng/g, and a higher risk threshold at 154 ng/g, which demarcated subgroups with varying degrees of exposure intensity.
The data revealed a pronounced and statistically significant reduction in hair cortisol levels in children whose EtG levels exceeded the higher cut-off during pregnancy. This suggests a blunted or hypoactive HPA axis response in these offspring during early childhood, a finding with profound implications for understanding how prenatal alcohol exposure alters neuroendocrine development. Interestingly, this suppressed cortisol signature appeared to diminish as the children entered adolescence, indicating a potential developmental recalibration or compensation of the HPA axis over time.
Contrary to expectations, maternal prenatal depressive symptoms—assessed via the Edinburgh Postnatal Depression Scale—did not correspond with significant differences in the children’s HCC at either time point. This null finding challenges assumptions about prenatal maternal mood disorders and their direct association with offspring HPA activity in this cohort, inviting further nuanced exploration into maternal-foetal stress transmission pathways.
Perhaps most compellingly, the researchers correlated these biomarker findings with the children’s behavioral profiles using the Strengths and Difficulties Questionnaire (SDQ). While the study primarily implicated prenatal alcohol exposure rather than maternal depressive symptoms in modulating HPA axis development, the extent to which these physiological alterations translated into emotional or behavioral problems remains an open question, as the report detailed but did not specify the strength of these correlations.
The methodological robustness of combining biochemical markers with psychological screening instruments in a longitudinal framework heightens the study’s contribution to perinatal mental health and developmental psychobiology. These findings underscore the critical importance of maternal health behaviors during pregnancy—not merely in terms of immediate birth outcomes but in shaping the physiological substrate that governs stress resilience or vulnerability across critical developmental windows.
This research cuts through long-standing clinical ambiguities by providing objective evidence that prenatal alcohol exposure can leave persistent molecular traces in offspring, manifesting as altered HPA axis functioning visible through hair cortisol assessments. This biological imprinting could underpin increased susceptibility to stress-related disorders, cognitive impairments, and emotional dysregulation in later life.
Furthermore, the attenuation of cortisol differences from childhood to adolescence suggests dynamic neuroendocrine adaptations that future studies might investigate for potential interventions aimed at recalibrating stress system function in populations at risk. It raises pivotal questions about developmental plasticity and the windows of opportunity to mitigate adverse prenatal exposures.
The lack of association with prenatal depressive symptoms provokes a re-examination of how maternal mood disorders exert influence on foetal programming. It invites researchers to consider genetic factors, the timing and severity of depressive episodes, and other psychosocial variables that might mediate or moderate HPA axis development in offspring.
Overall, this study adds a critical dimension to our understanding of prenatal influences on child and adolescent health, linking biochemical evidence with developmental outcomes. It reveals the invisible, enduring traces that early alcohol exposure can imprint on the stress regulatory systems of the body, with potential cascading effects on mental health trajectories.
As public health frameworks increasingly emphasize early prevention, these insights reinforce the imperative for heightened awareness and intervention around alcohol use during pregnancy. They also act as a catalyst for developing screening protocols that integrate biological markers with psychosocial assessments to identify children who may benefit most from targeted support.
In future research, expanding sample sizes, incorporating detailed neuropsychological assessments, and exploring epigenetic mechanisms will be essential to unravel the complex mechanisms by which prenatal environments scaffold individual differences in HPA axis function and stress responsivity.
This landmark study hence positions hair cortisol analysis as a promising tool in perinatal research and clinical practice, bridging prenatal exposures with long-term physiological and potentially psychological outcomes. It serves as a clarion call for interdisciplinary approaches to safeguarding neurodevelopment through maternal health optimization.
With mounting evidence of the ripple effects of prenatal alcohol consumption on offspring’s biological systems, efforts to translate these findings into policy and clinical guidelines could profoundly impact the prevention and management of stress-related disorders across the lifespan.
Subject of Research: Prenatal alcohol exposure and prenatal maternal depressive symptoms’ effect on offspring’s hypothalamic-pituitary-adrenal (HPA) axis function as measured by hair cortisol concentration during childhood and adolescence.
Article Title: Association of prenatal alcohol exposure and prenatal depressive symptoms with offspring hair cortisol in childhood and adolescence.
Article References:
Plank, AC., Panaseth-Gehle, K., Gerlach, J. et al. Association of prenatal alcohol exposure and prenatal depressive symptoms with offspring hair cortisol in childhood and adolescence.
BMC Psychiatry 25, 1060 (2025). https://doi.org/10.1186/s12888-025-07559-9
Image Credits: AI Generated
DOI: 10.1186/s12888-025-07559-9 (Published 05 November 2025)
Keywords: Prenatal Alcohol Exposure, Hair Cortisol Concentration, Hypothalamic-Pituitary-Adrenal Axis, Prenatal Depressive Symptoms, Early Adolescence, Biomarkers, Ethyl Glucuronide, Neuroendocrine Development, Child Stress Physiology
