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Background/Objectives: Little is currently known about the relationship between the parental diet during pregnancy and the growth of the child from early childhood until early adulthood. This study was designed to examine whether the dietary patterns of the parents during a pregnancy and of the respective child at 3 years are associated with the length/height-for-age z-score of child at birth, 3 years of age and at 19 years of age. Subjects/Methods: Dietary patterns of pregnant women and their partners, and offspring at 3 years that were enroled in the 1990-1991 period in the Czech part of the European Longitudinal Study of Pregnancy and Childhood. Multivariable linear regression models were used to estimate the relationship between the dietary patterns of parents (835 child-mother-father trios) during pregnancy and the length/height-for-age z-score of their offspring at birth, 3 years and 19 years. Results: The maternal health-conscious food pattern was found to predict lower child height at 3 years, but not at birth nor at 19 years of age. An increase in the health-conscious pattern score of the maternal diet was associated with significantly lower height-for-age z-score at 3 years; however, the observed effect lost its significance after the adjustment for diet of the child at 3 years. Conclusions: After full adjustment, the only significant predictors of the height-for-age z-score of the child at 3 years were the heights of both parents and maternal education. More research into the association of maternal diet in pregnancy and height of child is necessary., Author(s): J Bienertová-Vasku [sup.1] [sup.2] , F Zlámal [sup.1] [sup.2] , T Prusa [sup.1] , J Novák [sup.2] , O Mikes [sup.1] , P Cupr [sup.1] , A Pohoralá [sup.1] [...]

Intrapartum antibiotic prophylaxis (IAP) is commonly used during C-section delivery and in Group B Streptococcus-positive women before vaginal delivery. Here, we primarily aimed to investigate the effect of IAP on the neonatal oral and fecal bacteriomes in the first week of life. In this preliminary study, maternal and neonatal oral swabs and neonatal fecal (meconium and transitional stool) swabs were selected from a pool of samples from healthy mother-neonate pairs participating in the pilot phase of CELSPAC: TNG during their hospital stay. The DNA was extracted and bacteriome profiles were determined by 16S rRNA amplicon sequencing (Illumina). In the final dataset, 33 mother-neonate pairs were exposed to antibiotics during C-section or vaginal delivery (cases; +IAP) and the vaginal delivery without IAP (controls, -IAP) took place in 33 mother-neonate pairs. Differences in alpha diversity (Shannon index, p=0.01) and bacterial composition (PERMANOVA, p<0.05) between the +IAP and -IAP groups were detected only in neonatal oral samples collected ≤48 h after birth. No significant differences between meconium bacteriomes of the +IAP and -IAP groups were observed (p>0.05). However, the IAP was associated with decreased alpha diversity (number of amplicon sequence variants, p<0.001), decreased relative abundances of the genera Bacteroides and Bifidobacterium, and increased relative abundances of genera Enterococcus and Rothia (q<0.01 for all of them) in transitional stool samples. The findings of this study suggest that exposure to IAP may significantly influence the early development of the neonatal oral and gut microbiomes. IAP affected the neonatal oral bacteriome in the first two days after birth as well as the neonatal fecal bacteriome in transitional stool samples. In addition, it highlights the necessity for further investigation into the potential long-term health impacts on children., (© 2024. The Author(s).)

Heavy maternal alcohol drinking during pregnancy has been associated with altered neurodevelopment in the child but the effects of low-dose alcohol drinking are less clear and any potential safe level of alcohol use during pregnancy is not known. We evaluated the effects of prenatal alcohol on reward-related behavior and substance use in young adulthood and the potential sex differences therein. Participants were members of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort who participated in its neuroimaging follow-up in young adulthood. A total of 191 participants (28-30 years; 51% men) had complete data on prenatal exposure to alcohol, current substance use, and fMRI data from young adulthood. Maternal alcohol drinking was assessed during mid-pregnancy and pre-conception. Brain response to reward anticipation and reward feedback was measured using the Monetary Incentive Delay task and substance use in young adulthood was assessed using a self-report questionnaire. We showed that even a moderate exposure to alcohol in mid-pregnancy but not pre-conception was associated with robust effects on brain response to reward feedback (six frontal, one parietal, one temporal, and one occipital cluster) and with greater cannabis use in both men and women 30 years later. Moreover, mid-pregnancy but not pre-conception exposure to alcohol was associated with greater cannabis use in young adulthood and these effects were independent of maternal education and maternal depression during pregnancy. Further, the extent of cannabis use in the late 20 s was predicted by the brain response to reward feedback in three out of the nine prenatal alcohol-related clusters and these effects were independent of current alcohol use. Sex differences in the brain response to reward outcome emerged only during the no loss vs. loss contrast. Young adult men exposed to alcohol prenatally had significantly larger brain response to no loss vs. loss in the putamen and occipital region than women exposed to prenatal alcohol. Therefore, we conclude that even moderate exposure to alcohol prenatally has long-lasting effects on brain function during reward processing and risk of cannabis use in young adulthood., (© 2024. The Author(s).)

Phthalates are mainly used as plasticizers for polyvinyl chloride (PVC). Exposure to several phthalates is associated with different adverse effects most prominently on the development of reproductive functions. The HBM4EU Aligned Studies (2014-2021) have investigated current European exposure to ten phthalates (DEP, BBzP, DiBP, DnBP, DCHP, DnPeP, DEHP, DiNP, DiDP, DnOP) and the substitute DINCH to answer the open policy relevant questions which were defined by HBM4EU partner countries and EU institutions as the starting point of the programme. The exposure dataset includes ∼5,600 children (6-11 years) and adolescents (12-18 years) from up to 12 countries per age group and covering the North, East, South and West European regions. Study data from participating studies were harmonised with respect to sample size and selection of participants, selection of biomarkers, and quality and comparability of analytical results to provide a comparable perspective of European exposure. Phthalate and DINCH exposure were deduced from urinary excretions of metabolites, where concentrations were expressed as their key descriptor geometric mean (GM) and 95th percentile (P95). This study aims at reporting current exposure levels and differences in these between European studies and regions, as well as comparisons to human biomonitoring guidance values (HBM-GVs). GMs for children were highest for ∑DEHP metabolites (33.6 μg/L), MiBP (26.6 μg/L), and MEP (24.4 μg/L) and lowest for∑DiDP metabolites (1.91 μg/L) and ∑DINCH metabolites (3.57 μg/L). In adolescents highest GMs were found for MEP (43.3 μg/L), ∑DEHP metabolites (28.8 μg/L), and MiBP (25.6 μg/L) and lowest for ∑DiDP metabolites (= 2.02 μg/L) and ∑DINCH metabolites (2.51 μg/L). In addition, GMs and P95 stratified by European region, sex, household education level, and degree of urbanization are presented. Differences in average biomarker concentrations between sampling sites (data collections) ranged from factor 2 to 9. Compared to the European average, children in the sampling sites OCC (Denmark), InAirQ (Hungary), and SPECIMEn (The Netherlands) had the lowest concentrations across all metabolites and ESTEBAN (France), NAC II (Italy), and CROME (Greece) the highest. For adolescents, comparably higher metabolite concentrations were found in NEB II (Norway), PCB cohort (Slovakia), and ESTEBAN (France), and lower concentrations in POLAES (Poland), FLEHS IV (Belgium), and GerES V-sub (Germany). Multivariate analyses (Survey Generalized Linear Models) indicate compound-specific differences in average metabolite concentrations between the four European regions. Comparison of individual levels with HBM-GVs revealed highest rates of exceedances for DnBP and DiBP, with up to 3 and 5%, respectively, in children and adolescents. No exceedances were observed for DEP and DINCH. With our results we provide current, detailed, and comparable data on exposure to phthalates in children and - for the first time - in adolescents, and - for the first time - on DINCH in children and adolescents of all four regions of Europe which are particularly suited to inform exposure and risk assessment and answer open policy relevant questions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest related to this work., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures., Competing Interests: Declarations of competing interest The authors declare no conflict of interest. José V. Tarazona is employed by the European Food Safety Authority (EFSA). The views expressed in this publication are those of the authors and should not be interpreted as representing the official position of EFSA., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Importance: Maternal mental health problems during pregnancy are associated with altered neurodevelopment in offspring, but the long-term relationship between these prenatal risk factors and offspring brain structure in adulthood remains incompletely understood due to a paucity of longitudinal studies., Objective: To evaluate the association between exposure to maternal depression in utero and offspring brain age in the third decade of life, and to evaluate recent stressful life events as potential moderators of this association., Design, Setting, and Participants: This cohort study examined the 30-year follow-up of a Czech prenatal birth cohort with a within-participant design neuroimaging component in young adulthood conducted from 1991 to 2022. Participants from the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort were recruited for 2 magnetic resonance imaging (MRI) follow-ups, one between ages 23 and 24 years (early 20s) and another between ages 28 and 30 years (late 20s)., Exposures: Maternal depression during pregnancy; stressful life events in the past year experienced by the young adult offspring., Main Outcomes and Measures: Gap between estimated neuroanatomical vs chronological age at MRI scan (brain age gap estimation [BrainAGE]) calculated once in participants' early 20s and once in their late 20s, and pace of aging calculated as the differences between BrainAGE at the 2 MRI sessions in young adulthood., Results: A total of 260 individuals participated in the second neuroimaging follow-up (mean [SD] age, 29.5 [0.6] years; 135 [52%] male); MRI data for both time points and a history of maternal depression were available for 110 participants (mean [SD] age, 29.3 [0.6] years; 56 [51%] male). BrainAGE in participants' early 20s was correlated with BrainAGE in their late 20s (r = 0.7, P < .001), and a previously observed association between maternal depression during pregnancy and BrainAGE in their early 20s persisted in their late 20s (adjusted R2 = 0.04; P = .04). However, no association emerged between maternal depression during pregnancy and the pace of aging between the 2 MRI sessions. The stability of the associations between maternal depression during pregnancy and BrainAGE was also supported by the lack of interactions with recent stress. In contrast, more recent stress was associated with greater pace of aging between the 2 MRI sessions, independent of maternal depression (adjusted R2 = 0.09; P = .01)., Conclusions and Relevance: The findings of this cohort study suggest that maternal depression and recent stress may have independent associations with brain age and the pace of aging, respectively, in young adulthood. Prevention and treatment of depression in pregnant mothers may have long-term implications for offspring brain development.

The objectives of the study were to estimate the current exposure to cadmium (Cd) in Europe, potential differences between the countries and geographic regions, determinants of exposure and to derive European exposure levels. The basis for this work was provided by the European Human Biomonitoring Initiative (HBM4EU) which established a framework for alignment of national or regional HBM studies. For the purpose of Cd exposure assessment, studies from 9 European countries (Iceland, Denmark, Poland, Czech Republic, Croatia, Portugal, Germany, France, Luxembourg) were included and urine of 20-39 years old adults sampled in the years 2014-2021 (n = 2510). The measurements in urine were quality assured by the HBM4EU quality assurance/quality control scheme, study participants' questionnaire data were post-harmonized. Spatially resolved external data, namely Cd concentrations in soil, agricultural areas, phosphate fertilizer application, traffic density and point source Cd release were collected for the respective statistical territorial unit (NUTS). There were no distinct geographic patterns observed in Cd levels in urine, although the data revealed some differences between the specific study sites. The levels of exposure were otherwise similar between two time periods within the last decade (DEMOCOPHES - 2011-2012 vs. HBM4EU Aligned Studies, 2014-2020). The age-dependent alert values for Cd in urine were exceeded by 16% of the study participants. Exceedances in the different studies and locations ranged from 1.4% up to 42%. The studies with largest extent of exceedance were from France and Poland. Association analysis with individual food consumption data available from participants' questionnaires showed an important contribution of vegetarian diet to the overall exposure, with 35% higher levels in vegetarians as opposed to non-vegetarians. For comparison, increase in Cd levels due to smoking was 25%. Using NUTS2-level external data, positive associations between HBM data and percentage of cropland and consumption of Cd-containing mineral phosphate fertilizer were revealed, which indicates a significant contribution of mineral phosphate fertilizers to human Cd exposure through diet. In addition to diet, traffic and point source release were identified as significant sources of exposure in the study population. The findings of the study support the recommendation by EFSA to reduce Cd exposure as also the estimated mean dietary exposure of adults in the EU is close or slightly exceeding the tolerable weekly intake. It also indicates that regulations are not protecting the population sufficiently., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Exposure to maternal stress in utero has long-term implications for the developing brain and has been linked with a higher risk of depression. The amygdala, which develops during the early embryonic stage and is critical for emotion processing, might be particularly sensitive., Methods: Using data from a neuroimaging follow-up of the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort (n = 129, 47% men, 23-24 years old), we studied the impact of prenatal stress during the first and second halves of pregnancy on the volume of the amygdala and its nuclei in young adult offspring. We further evaluated the relationship between amygdala anatomy and offspring depressive symptomatology. Amygdala nuclei were parcellated using FreeSurfer's automated segmentation pipeline. Depressive symptoms were measured via self-report using the Beck Depression Inventory., Results: Exposure to stress during the first half of pregnancy was associated with smaller accessory basal (Cohen's f 2  = 0.27, false discovery rate [FDR]-corrected p [p FDR ] = .03) and cortical (Cohen's f 2  = 0.29, p FDR  = .03) nuclei volumes. This effect remained significant after correcting for sex, stress during the second half of pregnancy, maternal age at birth, birth weight, maternal education, and offspring's age at magnetic resonance imaging. These two nuclei showed a quadratic relationship with Beck Depression Inventory scores in young adulthood, where both smaller and larger volumes were associated with more depressive symptoms (accessory basal nucleus: adj. R 2  = 0.05, p FDR  = .015; cortical nucleus: adj. R 2  = 0.04, p FDR  = .015)., Conclusions: We conclude that exposure to stress during the first half of pregnancy might have long-term implications for amygdala anatomy, which may in turn predict the experience of depressive symptoms in young adulthood., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)

Background: Prenatal stress influences brain development and mood disorder vulnerability. Brain structural covariance network (SCN) properties based on inter-regional volumetric correlations may reflect developmentally-mediated shared plasticity among regions. Childhood trauma is associated with amygdala-centric SCN reorganization patterns, however, the impact of prenatal stress on SCN properties remains unknown., Methods: The study included participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) with archival prenatal stress data and structural MRI acquired in young adulthood (age 23-24). SCNs were constructed based on Freesurfer-extracted volumes of 7 subcortical and 34 cortical regions. We compared amygdala degree centrality, a measure of hubness, between those exposed to high vs. low (median split) prenatal stress, defined by maternal reports of stressful life events during the first (n = 93, 57% female) and second (n = 125, 54% female) half of pregnancy. Group differences were tested across network density thresholds (5-40%) using 10,000 permutations, with sex and intracranial volume as covariates, followed by sex-specific analyses. Finally, we sought to replicate our results in an independent all-male sample (n = 450, age 18-20) from the Avon Longitudinal Study of Parents and Children (ALSPAC)., Results: The high-stress during the first half of pregnancy ELSPAC group showed lower amygdala degree particularly in men, who demonstrated this difference at 10 consecutive thresholds, with no significant differences in global network properties. At the lowest significant density threshold, amygdala volume was positively correlated with hippocampus, putamen, rostral anterior and posterior cingulate, transverse temporal, and pericalcarine cortex in the low-stress (p(FDR) < 0.027), but not the high-stress (p(FDR) > 0.882) group. Although amygdala degree was nominally lower across thresholds in the high-stress ALSPAC group, these results were not significant., Conclusion: Unlike childhood trauma, prenatal stress may shift SCN towards a less amygdala-centric SCN pattern, particularly in men. These findings did not replicate in an all-male ALSPAC sample, possibly due to the sample's younger age and lower prenatal stress exposure., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Maternal stress during pregnancy and shortly thereafter is associated with altered offspring brain development that may increase risk of mood and anxiety disorders. Cortical gyrification is established during the prenatal period and the first 2 years of life and is altered in psychiatric disorders. Here, we sought to characterize the effects of perinatal stress exposure on offspring gyrification patterns and mood dysregulation in young adulthood. Participants included 85 young adults (56.5% women; 23-24 years) from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) with perinatal stress data across four distinct timepoints and structural MRI data from young adulthood. Perinatal stress exposure was measured as maternal stress during first and second half of pregnancy, first 6 months, and 6-18 months after birth. Cortical gyrification and mood dysregulation were quantified using local gyrification index (LGI), computed with Freesurfer, and the Profile of Mood States questionnaire, respectively. Perinatal stress predicted cortical gyrification in young adulthood, and its timing influenced location, direction, and sex-specificity of effects. In particular, whereas early prenatal stress was associated with sex-dependent medium-to-large effects in large temporal, parietal, and occipital regions (f 2 = 0.19-0.38, p < .001), later perinatal stress was associated with sex-independent small-to-medium effects in smaller, more anterior regions (f 2 = 0.10-0.19, p < .003). Moreover, in females, early prenatal stress predicted higher LGI in a large temporal region, which was further associated with mood disturbance in adulthood (r = 0.399, p = .006). These findings point out the long-term implications of perinatal stress exposure for cortical morphology and mood dysregulation., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Maternal depression during pregnancy is associated with elevated risk of anxiety and depression in offspring, but the mechanisms are incompletely understood. Here we conducted a neuroimaging follow-up of a prenatal birth cohort from the European Longitudinal Study of Pregnancy and Childhood (n = 131; 53% women, age 23-24) to test whether deviations from age-normative structural brain development in young adulthood may partially underlie this link. Structural brain age was calculated based on previously published neuroanatomical age prediction models using cortical thickness maps from healthy controls aged 6-89. Brain age gap was computed as the difference between chronological and structural brain age. Participants also completed self-report measures of anxiety and mood dysregulation. Further, mothers of a subset of participants (n = 103, 54% women) answered a self-report questionnaire in 1990-1992 about depressive symptoms during pregnancy. Higher exposure to maternal depressive symptoms in utero showed a linear relationship with elevated brain age gap, which showed a quadratic relationship with anxiety and mood dysregulation in the young adult offspring. Our findings suggest that exposure to maternal depressive symptoms in utero may be associated with accelerated brain maturation and that deviations from age-normative structural brain development in either direction predict more anxiety and dysregulated mood in young adulthood., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)