Effects of prenatal alcohol consumption on cognitive development and <scp>ADHD</scp>‐related behaviour in primary‐school age: a multilevel study based on meconium ethyl glucuronide

Eichler, Anna; Hudler, Linda; Grunitz, Juliane; Grimm, Jennifer; Raabe, E; Goecke, Tamme W.; Fasching, Peter A.; Beckmann, Matthias W.; Kratz, Oliver; Moll, Gunther H.; Kornhuber, Johannes; Heinrich, Hartmut

doi:10.1111/jcpp.12794

Cited by 28 publications

(42 citation statements)

References 35 publications

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“…Moreover, the observed differences in the Go-P3 ( Eichler et al, 2018 ) as reported recently were also stable using the threshold of EtG ≥ 30 ng/g ( Table 1 ). The differences between the EtG+ group ( n = 31) and controls ( n = 117) were analyzed by t -test ( t = 2.43, p = 0.004, d = 0.49).…”

Section: Resultssupporting

confidence: 78%

“…Using the FRANCES cohort, Eichler et al (2018) showed IQ differences in children with an EtG concentration in meconium above the 50th percentile. Here, we report this effect to be also persistent in the group of the EtG positive children with a threshold set at ≥30 ng/g.…”

Section: Resultsmentioning

confidence: 98%

“…In the FRANCES cohort, we could previously demonstrate the negative impact of PAE on child’s cognitive development and ADHD-related behavior on the basis of the ethanol metabolite EtG in newborn’s meconium ( Eichler et al, 2018 ). In this study, we present a comprehensive genome-wide analysis of DNA methylation in buccal cells of children of the same FRANCES cohort both positive and negative for meconium EtG.…”

Section: Discussionmentioning

confidence: 96%

“…As Go-P3 effects of EtG-positive vs. EtG-negative children did not depend on the reward condition as described in Eichler et al (2018) , the Go-P3 averaged over blocks with and without incentives was used for the analysis in the present manuscript.…”

Section: Methodsmentioning

confidence: 99%

“…As a part of our FRANCES ( Hein et al, 2014 ; Schneider et al, 2014 ; Eichler et al, 2016 ), we have studied attention and cognitive development of the 6- to 9-year-old children who were positive for EtG in meconium at birth, a child-related biomarker of intrauterine alcohol exposure ( Eichler et al, 2018 ). Children with a positive meconium EtG, were found to have a 6-point lower IQ and a positive correlation between EtG value and ADHD symptoms (predominantly inattention) ( Eichler et al, 2018 ). Considering ERPs in the EEG, which capture different aspects of attention and response control, EtG positive children (≥10 ng/g) were found to have a smaller P3 amplitude in go trials (Go-P3) indicating a reduced capacity of attentional resources.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children

Frey

Eichler

Stonawski

et al. 2018

Front. Behav. Neurosci.

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Prenatal alcohol exposure (PAE) is known to elicit a broad range of systemic effects, including neurophysiological alterations that result in adverse behavioral and cognitive outcomes. However, molecular pathways underlying these long-term intrauterine effects remain to be investigated. Here, we tested a hypothesis that PAE may lead to epigenetic alterations to the DNA resulting in attentional and cognitive alterations of the children. We report the results of the study that included 156 primary school children of the Franconian Cognition and Emotion Studies (FRANCES) cohort which were tested for an objective marker of PAE, ethyl glucuronide (EtG) in meconium at birth. Thirty-two newborns were found to be exposed to alcohol with EtG values above 30 ng/g (EtG+). Previously we described PAE being associated with lower IQ and smaller amplitude of the event-related potential component P3 in go trials (Go-P3), which indicates a reduced capacity of attentional resources. Whole-genome methylation analysis of the buccal cell DNA revealed 193 differentially methylated genes in children with positive meconium EtG, that were clustered into groups involved in epigenetic modifications, neurodegeneration, neurodevelopment, axon guidance and neuronal excitability. Furthermore, we detected mediation effects of the methylation changes in DPP10 and SLC16A9 genes on the EtG related cognitive and attention-related deficits. Our results suggest that system-wide epigenetic changes are involved in long-term effects of PAE. In particular, we show an epigenetic mediation of PAE effects on cognition and attention-related processes.

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Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children

Frey

Eichler

Stonawski

et al. 2018

Front. Behav. Neurosci.

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The association between prenatal alcohol consumption and preschool child stress system disturbance

Grimm

Stemmler

Golub

et al. 2020

Developmental Psychobiology

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Background Drinking alcohol during pregnancy is considered a risk factor for child development; however, child biomarkers of prenatal alcohol exposure have been rarely studied. We examined whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with child cortisol concentrations at primary school age. Methods For 137 children, prenatal alcohol exposure was operationalized by the meconium biomarker EtG and by maternal self‐reports during pregnancy. Two EtG cut‐offs (EtG ≥10 ng/g and EtG ≥112 ng/g) were applied. Cortisol concentrations were measured in saliva and hair samples. Results Children with EtG ≥10 ng/g showed significantly reduced hair cortisol concentrations (HCCs) (p = .050, ηp2 = 0.042). For children with EtG ≥112 ng/g, the cortisol awakening response (CAR) was significantly decreased (p = .025, ηp2 = 0.070). These effects were also present in correlational analyses with continuous EtG data, speaking for partly dose‐dependent effects. Especially, within the EtG ≥112 ng/g group, the basal (CAR: rp = −.642, p = .120) and cumulative (HCC: rp = −.660, p = .107) cortisol parameters were associated with child emotional symptoms at medium effect size. Conclusions The present study showed both the biological association of intrauterine alcohol exposure with the cortisol stress system, partly dose‐dependent, and the functional association with emotional and behavioral symptoms.

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Effects of prenatal alcohol exposition on cognitive outcomes in childhood and youth: a longitudinal analysis based on meconium ethyl glucuronide

Roetner

Doren

Maschke

et al. 2023

Eur Arch Psychiatry Clin Neurosci

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Background Prenatal alcohol exposure (PAE) has been linked to severe, adverse child outcomes. However, little is known regarding subclinical outcomes of low/moderate PAE and its longitudinal consequences, especially regarding neurophysiological and neurocognitive development. A newborn biomarker of PAE, meconium ethyl glucuronide (EtG), has been shown to predict cognitive impairments in primary-school-aged children. The current study investigated the ongoing effects of subclinical PAE in adolescence. Methods A sample of n = 96 mother–child dyads of the FRAMES/FRANCES cohort were classified into PAE/no PAE using EtG with a 10 ng/g cutoff. Mothers were recruited during pregnancy and children were assessed during primary-school age (M = 7.57, SD = 0.65, range: 6.00–9.92 years) and adolescence (M = 13.26, SD = 0.31, range: 12.79–14.20 years) on three levels: clinical (ADHD rating), neuropsychological (IQ score and performance in a go/nogo task), and neurophysiological (analysis of P3 event-related potentials (ERP) during said go/nogo task). Developmental outcomes and courses following PAE were assessed using rmANCOVAs, controlling for relevant confounders (socioeconomic status (SES), birth weight, and maternal psychopathology). Results Neurophysiological impairments emerged for exposed children in the form of diminished attentional resource recruiting in childhood and adolescence (reduced go-P3 amplitudes) with no differences in performance. Neuropsychological testing showed a reduced IQ score for both time points with dose-dependent effects in childhood. Clinical ADHD symptoms were not significantly affected. Conclusion Subclinical PAE, as determined by meconium EtG, has negative developmental consequences on cognitive function that persist from childhood to adolescence. These findings suggest that there is no safe limit for alcohol consumption during pregnancy and that more thorough screening of alcohol consumption during pregnancy is necessary for early identification and treatment of at-risk children.

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Effects of prenatal alcohol consumption on cognitive development and ADHD‐related behaviour in primary‐school age: a multilevel study based on meconium ethyl glucuronide

Cited by 28 publications

References 35 publications

Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children

Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children

The association between prenatal alcohol consumption and preschool child stress system disturbance

Effects of prenatal alcohol exposition on cognitive outcomes in childhood and youth: a longitudinal analysis based on meconium ethyl glucuronide

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