Sex differences in the teratogenic effects of alcohol: Findings from animal models.

Otero, Nicha K. H.; Kelly, Sandra J.

doi:10.1037/13092-008

Cited by 5 publications

(5 citation statements)

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“…Sex differences were not detected in the present study in the fluid reasoning and executive functioning or learning and memory domains, but females performed worse on a measure of visual spatial ability (AW), and on 1 measure in the language domain (WD) across exposure history. While investigations of sexually dimorphic behavior using human subjects with FASD have been limited and we are hesitant to over interpret the current findings, our results are consistent with animal studies that found sexually dimorphic behaviors and abilities in rats with prenatal alcohol exposure follow a pattern similar to those of control rats (Otero and Kelly, ). Furthermore, many of the sexually dimorphic secondary disabilities in FASD, reviewed by Streissguth (), such as rates of confinement and school suspensions/expulsions, are also sexually dimorphic in the general population (Golinelli and Minton, ), which may help to explain why we did not see any interactions between exposure history and sex in the present study.…”

Section: Discussionsupporting

confidence: 87%

“…It is possible that environmental factors outside of prenatal alcohol exposure may contribute to these differences and in general, most studies investigating neuropsychological performance and behavior in humans with prenatal alcohol exposure have not explored sex effects, perhaps due to limitations of sample size. While animal studies have addressed sex effects after prenatal exposure to alcohol more extensively than human studies have, many of these studies lack sufficient power to detect interactive effects, decreasing reliability of the results (see Otero and Kelly, ). One replicated effect is that prenatal alcohol exposure lowers testosterone levels in male rodent fetuses, reducing the differentiation of the male brain, ultimately causing the brains of males with prenatal alcohol exposure to be feminized (Otero and Kelly, ).…”

mentioning

confidence: 99%

“…While animal studies have addressed sex effects after prenatal exposure to alcohol more extensively than human studies have, many of these studies lack sufficient power to detect interactive effects, decreasing reliability of the results (see Otero and Kelly, ). One replicated effect is that prenatal alcohol exposure lowers testosterone levels in male rodent fetuses, reducing the differentiation of the male brain, ultimately causing the brains of males with prenatal alcohol exposure to be feminized (Otero and Kelly, ). Such an effect may result in the absence of typical sexual dimorphism in behavior or cognitive ability among those with prenatal exposure to alcohol, but insufficient research with humans limits this conclusion.…”

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confidence: 99%

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Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure

Panczakiewicz

Glass

Coles

et al. 2016

Alcoholism Clin & Exp Res

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Background Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented, however the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods Subjects were 407 youth with prenatal alcohol exposure (n=192) and controls (n=215). Two age groups [child (5–7y) or adolescent (10–16y)] and both sexes were included. All subjects completed standardized neuropsychological testing and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) MANOVAs. Significant effects were followed by univariate analyses. Results No three-way or two-way interactions were significant. The main effect of group was significant in all three MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on three measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual-spatial scores and fewer somatic complaints than females. Conclusion Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for non-exposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the two age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains.

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Section: Discussionsupporting

confidence: 87%

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confidence: 99%

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confidence: 99%

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Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure

Panczakiewicz

Glass

Coles

et al. 2016

Alcoholism Clin & Exp Res

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“…In addition only 2 symptoms significantly differed for females at the 1.0 level and 1 at the 1.5 level. Sex differences are not frequently studied in FASD [26,27] and the results from this study suggest that more attention should be given to how alcohol-related neurobehavioral deficits may manifest as a function of biological sex. This should not be unexpected for this disorder given that other psychiatric conditions also have variable expression as a function of biological sex [28][29][30].…”

Section: Discussionmentioning

confidence: 77%

Characteristics of the Symptoms of the Proposed ND-PAE Disorder in First Grade Children in a Community Sample

Kable

Coles

Holton

et al. 2022

Child Psychiatry Hum Dev

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The proposed symptoms for Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) were evaluated in children who participated in the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study. Children "at-risk" for ND-PAE (n = 204) were contrasted to children with no prenatal alcohol exposure, alcohol-related dysmorphia or growth deficits (n = 908). Symptoms were defined based on neuropsychological testing using two diagnostic threshold levels (1.0 and 1.5 STD). Individuals at risk for ND-PAE had higher endorsement rates of the self-regulation and adaptive impairments at the 1.0 threshold and of the neurocognitive and self-regulation impairments at the 1.5 threshold. Endorsement of the disorder significantly differed at the 1.0 threshold. Receiver operating characteristic curve analysis indicated that having an IQ below 70 was not predictive of the diagnosis but modifications of the IQ criterion improved predictive validity. Discrimination validity was poor without documentation of PAE which continues to be a necessity for a diagnosis of ND-PAE.

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“…Individuals with FASD experience significant neurocognitive and behavioral difficulties (Cook et al, 2016) and many also navigate complex physical and mental health challenges and environmental adversity across the lifespan (Flannigan et al, 2021; McLachlan et al, 2020). Most data on sex‐based differences in PAE/FASD come from the animal literature (Otero & Kelly, 2012), where researchers have identified differential impacts on fetal growth (Kwan et al, 2020), metabolic and immune function (Bake et al, 2021; Ieraci & Herrera, 2020), neurotransmitter systems (Converse et al, 2014), DNA methylation (Lussier et al, 2021), brain volume, memory (Zimmerberg et al, 1991), behavior, and social interaction (Bake et al, 2021). Across these studies, male animals tended to be more susceptible than females to the damaging impacts of PAE.…”

Section: Introductionmentioning

confidence: 99%

Sex‐related differences among individuals assessed for fetal alcohol spectrum disorder in Canada

Flannigan¹,

Poole

Cook

et al. 2023

Alcohol: Clinical and Experimental Research

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Background Consideration of sex‐ and gender‐related factors is critical for understanding and supporting health and wellbeing. Although both sex and gender influence people with developmental disabilities, there is relatively little research on these factors and their influences among individuals with fetal alcohol spectrum disorder (FASD), a complex neurodevelopmental disability impacting an estimated 4%–5% of the population. Understanding sex‐ and gender‐related differences in FASD is needed to facilitate evidence‐informed assessment, treatment planning, and advocacy. To begin unpacking these factors, we investigated sex‐based differences in clinical presentation and experiences among individuals assessed for FASD across the lifespan. Methods We analyzed 2574 clinical records from 29 FASD diagnostic centers in Canada. Participants ranged in age from 1 to 61 years (mean 15.2 years), and more than half (58.3%) were male at birth. Study variables included participant demographics, physical indicators of prenatal alcohol exposure (PAE), neurodevelopmental impairment, FASD diagnosis, co‐occurring physical and mental health diagnoses, and environmental adversity. Results There were no significant differences between males and females with respect to FASD diagnostic outcome or physical indicators of PAE. However, males experienced significantly more neurodevelopmental impairment. Females experienced higher rates of endocrine problems, anxiety, and depressive/mood disorders, whereas males had higher rates of attention deficit‐hyperactivity disorder, conduct disorder, and oppositional defiant disorder. Adversity also differed by sex, with females experiencing higher rates of trauma and legal problems with victimization/custody, and males having more difficulties with school and offending/incarceration. Sex‐based differences were most apparent in adolescents (13–17 years) and adults (≥25 years). Conclusions Individuals with PAE/FASD experience notable sex‐related differences in clinical presentation and experiences across the lifespan. Findings from this study should help to guide researchers, service providers, and policy makers to improve FASD screening, diagnosis, and intervention and better address the needs of individuals with PAE/FASD of all genders.

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Sex differences in the teratogenic effects of alcohol: Findings from animal models.

Cited by 5 publications

References 73 publications

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure

Characteristics of the Symptoms of the Proposed ND-PAE Disorder in First Grade Children in a Community Sample

Sex‐related differences among individuals assessed for fetal alcohol spectrum disorder in Canada

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