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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.

Zusammenfassung. Schlafstörungen sind im Erwachsenen- wie auch im Kindes- und Jugendalter weit verbreitet. Kinder und Jugendliche in kinder- und jugendpsychiatrischer (KJP) Behandlung sind insbesondere davon betroffen. Die kognitive Verhaltenstherapie ist die Behandlung der ersten Wahl bei Schlafstörungen, der eine standardisierte Schlafdiagnostik vorangehen sollte. Im deutschsprachigen Raum fehlen bislang systematische Untersuchungen zur Schlafdiagnostik im teilstationären (TK) KJP-Setting. Für N = 46 Kinder/Jugendliche in TK-KJP-Behandlung wurde ein Schlafprotokoll (7 Tage), ein Schlafanamneseschema (Eltern & Kind/Jugendlicher) sowie ein klinisches Urteil zum Schlafverhalten (Diagnostiker_in) erhoben. Zudem wurde die Eltern-, Selbst- und klinische Beurteilung der psychischen Störung erfasst. Bei 52 % der Kinder/Jugendlichen wurden Schlafauffälligkeiten (= Schlafstörungssymptome im Rahmen komorbider Störungen) oder Schlafstörungen festgestellt, insbesondere Einschlafstörungen oder Ein- und Durchschlafstörungen (26 %). Zudem berichteten 33 % Albträume. Das Schlafverhalten korrelierte signifikant mit externalen Auffälligkeiten (r = .38 bis .61, p = 02 bis .04), auch beeinflussten Geschlecht (weiblich: p = .01 bis ≤ .001, |d| = 1.57 bis 2.50) und Alter (Ältere: p = .05, |d| = 0.78) das Schlafverhalten signifikant. Es scheinen insbesondere externale Auffälligkeiten einen Zusammenhang zu Schlafstörungen in der teilstationären Population aufzuweisen. Für die systematische Diagnostik der im TK-KJP-Setting vielfach vorliegenden Schlafauffälligkeiten, empfiehlt sich zusammenfassend ein Multi-Informant-Multi-Method-Vorgehen mit einer anschließenden individualisierten kognitiven Verhaltenstherapie der Schlafstörungen – gehäuft bei externalen Auffälligkeiten. Abstract. Sleep disorders are common in adults as well as children and adolescents. Children and adolescents in psychiatric treatment (CAP) are especially affected by sleep problems. Cognitive behavioral therapy represents the first-line treatment, preceded by a standardized procedure for sleep diagnostics. To date, no study has investigated sleep behavior in CAP day clinics in Germany. In this study, N = 46 children/adolescents receiving CAP treatment in a day clinic completed a sleep diary (7 days) and a sleep anamnesis scheme with the help of their parents, and their sleep behavior was assessed by a clinician. Furthermore, a parent- and a self-report questionnaire plus a clinical assessment of the mental disorders in the children/adolescents were collected. 52 % of the children/ adolescents exhibited sleep disorders or sleep abnormalities (= sleep disorder symptoms in the context of comorbid disorders), in particular problems falling asleep or to falling asleep and sleeping through the night (26 %). In addition, 33 % reported having nightmares. Their sleep behavior correlated significantly with their external behavior problems (r = .38 .61, p = .02-.04); their sex (female: p = .01–≤ .001, |d| = 1.57–2.50) and their age (older: p = .05, |d| = .78) also significantly influenced sleep behavior. Particularly external behavior problems were associated with sleep problems in this day-care population. In summary, a multi-method-multi-informant procedure should be established for the systematic diagnostics of sleep abnormalities, together with individualized cognitive-behavioral therapy of sleep problems, especially in patients with external behavior problems.

BACKGROUND As a marker of cumulative cortisol activity, hair cortisol has received attention in clinical and methodological research. Currently, it is a common practice to relate the hair cortisol concentration (HCC) to hair weight. This article explores the hair protein concentration (HPC) as another possible reference value for HCC. METHODS For n = 18 hair samples cut from the posterior vertex, the HCC, HPC, and hair sample weight were determined, and the cortisol-to-weight and cortisol-to-protein ratios were calculated. Correlations were analyzed between the HCC, HPC, and hair sample weight as well as between the cortisol-to-weight and cortisol-to-protein ratios. Hair sample weight and HPC were included as independent variables in a stepwise linear regression model to predict HCC. RESULTS The HCC and HPC did not correlate significantly (r = 0.393, P = 0.106); however, the correlation between HCC and hair sample weight was significant (r = 0.520, P = 0.027). The HPC and hair sample weight (r = 0.605, P = 0.008) as well as the cortisol-to-weight and cortisol-to-protein ratios (r = 0.858, P < 0.000) showed a high correlation. The hair sample weight was the better predictor of the HCC (β = 0.520, P = 0.027) than HPC (β = 0.125, P = 0.657). CONCLUSIONS The results indicate that the hair sample weight is the more suitable reference value for the HCC. Thus, the standard cortisol-to-weight ratio should be used as the preferred expression for the cumulative cortisol activity measured in the scalp hair. However, calculating the cortisol-to-protein ratio can be considered as an alternative if the hair sample weight is not available.

Unfavourable intrauterine environmental factors increase the risk of delivery complications as well as postpartum developmental and behavioural problems in children and adolescents with ongoing effects into older age. Biomarker studies show that maternal stress and the use of alcohol and tobacco during pregnancy are associated with a higher intrauterine testosterone exposure of the child. The antenatal testosterone load, in turn, is a risk factor for lasting adverse health effects which extend into adulthood. A 15-week, mindfulness-oriented, app-based programme for the reduction of stress as well as for the reduction of alcohol and tobacco use in pregnant women is established. In the monocentre, prospective, controlled, and investigator-blinded MINDFUL/PMI (Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention) study, pregnant women carry out the programme. Its effect on antenatal testosterone exposure of the child is examined by assessing the index/ring finger length ratio and other biomarkers in the 1-year-old children. In addition, the programme's effects on self-regulation, the developmental status and the mental health of the children at the age of one year will be investigated. Additional aspects of the course of the pregnancy and delivery represent exploratory study objectives. This longitudinal study project is intended to improve the understanding of the impact of intrauterine environmental factors on early childhood development and health. Maternal stress as well as alcohol and tobacco use during pregnancy are modifiable factors and represent potential preventive targets.Ungünstige intrauterine Umweltfaktoren erhöhen das Risiko für Geburtskomplikationen sowie postpartale Entwicklungs- und Verhaltensauffälligkeiten bei den Kindern und Jugendlichen mit permanenten Auswirkungen bis ins höhere Alter. Biomarkerstudien zeigen, dass mütterlicher Stress und Konsum von Alkohol und Tabak während der Schwangerschaft mit höherer intrauteriner Testosteronexposition des Kindes assoziiert sind. Die pränatale Testosteronlast ist wiederum ein Risikofaktor für anhaltende und bis ins Erwachsenenalter reichende Gesundheitsbeeinträchtigungen. Es wird ein 15-wöchiges, achtsamkeitsorientiertes, App-basiertes Programm zur Reduktion von Stress sowie zur Verminderung von Alkohol- und Tabakkonsum bei schwangeren Frauen etabliert. In der monozentrischen, prospektiven, kontrollierten und untersucherverblindeten MINDFUL/PMI (Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention)-Studie führen schwangere Frauen das Programm durch. Dabei wird der Effekt auf die pränatale Testosteronexposition des Kindes untersucht, die mit dem Zeige-/Ringfingerlängenverhältnis und weiteren Biomarkern bei den 1-jährigen Kindern erhoben wird. Außerdem soll beforscht werden, wie sich das Programm auf die Selbstregulation, den Entwicklungstand und die psychische Gesundheit der Kinder im Alter von einem Jahr auswirkt. Weitere Aspekte des Schwangerschafts- und Geburtsverlaufs stellen explorative Studienziele dar. Dieses longitudinale Studienprojekt soll das Verständnis der Bedeutung intrauteriner Umweltfaktoren für die frühe kindliche Entwicklung und Gesundheit verbessern. Mütterlicher Stress sowie Alkohol- und Tabakkonsum während der Schwangerschaft sind modifizierbare Faktoren und stellen potenzielle präventive Ansatzpunkte dar.

The second-to-forth digit length ratio (2D:4D) is considered to be a biomarker for intrauterine androgen levels. It is associated with adult and child mental health problems, primarily with behavioral symptoms and predominantly in males. Using a cross-sectional design, we examined whether 2D:4D was associated with conduct disorder (CD) symptoms in 138 primary-school aged children (54% boys, Mage = 7.70 years) and considered child sex as a moderating factor. Children's digit lengths were measured from hand scans and mothers rated the behavioral/emotional symptoms of their child. The regression analyses revealed that 2D:4D ratios were associated with behavioral symptoms in boys (β = −0.260, p = 0.026), but not in girls (β = −0.040, p = 0.762). Child emotional symptoms, analyzed as a control, were not significantly correlated with 2D:4D. In conclusion, prenatal brain hyperandrogenization - operationalized by the 2D:4D biomarker - could result in behavioral symptoms in boys at early school age, reflecting one predictor for early onset CD. Our data support the use of 2D:4D as a marker of prenatal androgen exposure.

Zusammenfassung. Die Schwangerschaft stellt einen Lebensabschnitt der Frau dar, der mit körperlichen und hormonellen Veränderungen sowie einer erhöhten emotionalen und psychischen Beanspruchung einhergeht. Für das Kind gilt die Zeit im Mutterleib dabei als besonders sensible Phase, in der ungünstige intrauterine Bedingungen sowohl die fetale als auch die postnatale Entwicklung und Gesundheit langfristig beeinflussen können. So haben sich Depression, Angst und Stress in der Schwangerschaft als Risikofaktoren für Entwicklungsverzögerungen sowie emotionale und Verhaltensauffälligkeiten erwiesen. Epigenetische Veränderungen, insbesondere die DNA-Methylierung, werden als Wirkmechanismus für den Einfluss pränataler affektiver Belastungen auf das Kind diskutiert. Diese Arbeit soll einen Überblick geben, welche Veränderungen in der kindlichen DNA-Methylierung mit affektiven Belastungen in der Schwangerschaft assoziiert sind. Dabei werden Ergebnisse aus genspezifischen und epigenomweiten Studien vorgestellt, Problemfelder diskutiert und Anregungen für zukünftige Fragestellungen gegeben.

Zusammenfassung. Eltern-Kind-Interaktionen erfolgen natürlicherweise bidirektional. In der Folge sollte kinder- und jugendpsychiatrische / -psychotherapeutische (KJP–) Behandlung individuums- und kontextzentrierte Interventionen berücksichtigen. Dafür wurde eine dimensionale Erhebung elterlicher Belastung, wie sie mittels des Eltern-Belastungs-Inventars (EBI; Tröster, 2011 ) möglich ist, untersucht. Für N = 166 zu einem KJP-Erstkontakt vorstellige Kinder und Jugendliche (11 – 18 Jahre) wurden KJP-relevante Merkmale (inkl. kritischer Lebensereignisse), die elterliche Belastung (EBI) und drei Messungen der kindseitigen Symptomatik betrachtet (1. Elternurteil, 2. Selbsturteil, 3. klinisches Urteil). Zusätzlich wurde die Elternsicht auf die KJP-Behandlung als Be- oder Entlastung analysiert. Die Ergebnisse zeigen eine auffällig hohe elterliche Belastung. Diese Belastung korrelierte signifikant mit kritischen Lebensereignissen sowie mit dem Elternurteil. Verglichen mit dem Selbst- und dem klinischen Urteil erwies sich nur das Elternurteil als hoch signifikanter Prädiktor elterlicher Belastung, die für verschiedene KJP-Merkmale variierte. Die Inanspruchnahme der KJP-Behandlung wurde seitens der Eltern zumeist als Entlastung erlebt. Das EBI erlaubt folglich die Beschreibung eltern- bzw. familienbezogener Belastungen aus dimensionaler Perspektive, die eine fundierte kontextzentrierte Behandlungsplanung unterstützt.

Objective Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. Method We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013–2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005–2007) and measured the 2D : 4D of their children (2013–2016). Results The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients’ liver transaminase activities (P

The aim of the present work is to investigate the association of salivary and cumulative cortisol levels with emotional and behavioral symptoms in a Franconian Cognition and Emotion Studies (FRANCES) general population cohort of 158 6- to 9 year old children. Salivary cortisol values were measured by one-day diurnal cortisol profile, whereas cumulative cortisol was estimated via one-month hair cortisol concentrations (rHCC). Nearly all significant associations of clinical symptoms with child cortisol indices were age dependent: We report emotional symptoms being associated with lower rHCC in younger children (6.06–7.54 years). In older children (7.55–9.41 years) behavioral problems were further associated with higher rHCC and lower salivary cortisol awakening responses. In summary, child clinical symptoms were stronger associated with markers of hair cortisol compared to salivary cortisol. To picture developmental mechanisms, we suggest longitudinal designs for cortisol measures of stress systems in children and adolescents.

(1) This longitudinal study aimed to investigate the link between prenatal alcohol exposure and prenatal maternal depression with the offspring’s low-grade inflammatory status. (2) Prenatal alcohol exposure was determined via maternal self-report during the 3rd trimester of pregnancy (self-report+: n = 29) and the meconium alcohol metabolite Ethyl Glucuronide (EtG), collected at birth (≥30 ng/g: n = 23). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for prenatal maternal depressive symptoms during the 3rd trimester (≥10: n = 35). Fifteen years later, 122 adolescents (M = 13.32 years, 48.4% female) provided blood samples for the analysis of high sensitivity C-reactive protein (hsCRP, M = 0.91, SD = 1.28). (3) Higher hsCRP levels were found in EtG positive adolescents (p = 0.036, ηp2 = 0.04) and an inverse non-significant dose–response relation with hsCRP (r = −0.35, p = 0.113). For maternal self-reported prenatal alcohol consumption (p = 0.780, ηp2 = 0.00) and prenatal depressive symptoms (p = 0.360, ηp2 = 0.01) no differences for hsCRP levels between the affected and unaffected groups were found. (4) Adolescents with prenatal alcohol exposure are at risk for low-grade systemic inflammation. The EtG biomarker may be more accurate compared to self-reports. The findings suggest that prenatal maternal depression does not evoke low-grade systemic inflammation.

Aim This case-control study examined the long-term consequences of surgical correction for ventricular septal defect (VSD; the most common congenital heart defect) in infancy. It assessed children who had undergone VSD surgery and the factors related to maternal conditions, surgery, and hospital stay. Method Thirty-nine children (23 females, 16 males; age range 6y 1mo-9y 7mo [mean 7y 4mo, SD 1y]) with repaired isolated, non-syndromic, non-genetic VSD were compared with 39 typically developing children (22 females, 17 males; age range 6y-9y 2mo [mean 7y 3mo, SD 10mo]). The children completed behavioural tests of neurodevelopment and a quality of life (QoL) questionnaire. Mothers rated children's emotional/behavioural symptoms and QoL. Measures of maternal parenting behaviour and psychopathology were treated as moderators. Results Affected children showed reduced language skills (p=0.002) unless mothers reported high parenting behaviour subscale scores (p=0.04). Children's anxiety symptoms were elevated when mothers had anxiety symptoms (p=0.01). Longer hospital stay was associated with lower intelligence (p=0.003) and psychomotor scores (p=0.006). Longer scars predicted elevated child anxiety (p=0.008), and age at surgery and QoL were inversely related (p=0.01). Interpretation Impairments could be mitigated if VSD repair was performed early in life with a relatively small scar and uncomplicated hospital stay. This outcome depends on maternal parenting behaviour and anxiety symptoms. What this paper adds Children's cognitive and psychomotor development after surgical ventricular septal defect repair was unimpaired. Children showed no mental health restrictions when their mothers reported few anxiety symptoms themselves. Language impairments might be preventable by pro-active parenting. The outcome also depends on variables related to surgery and hospital stay.

Epigenetic DNA modifications in genes related to the hypothalamic–pituitary–adrenal (HPA) axis are discussed as a mechanism underlying the association between prenatal depression and altered child HPA activity. In a longitudinal study, DNA methylation changes related to prenatal depressive symptoms were investigated in 167 children aged 6 to 9 years. At six candidate genes, 126 cytosine–guanine dinucleotides were considered without correcting for multiple testing due to the exploratory nature of the study. Further associations with the basal child HPA activity were examined. Children exposed to prenatal depressive symptoms exhibited lower bedtime cortisol (p = .003, ηp2 = 0.07) and a steeper diurnal slope (p = .023, ηp2 = 0.06). For total cortisol release, prenatal exposure was related to lower cortisol release in boys, and higher release in girls. Furthermore, prenatal depressive symptoms were associated with altered methylation in the glucocorticoid receptor gene (NR3C1), the mineralocorticoid receptor gene (NR3C2), and the serotonin receptor gene (SLC6A4), with some sex-specific effects (p = .012–.040, ηp2 = 0.03–0.04). In boys, prenatal depressive symptoms predicted bedtime cortisol mediated by NR3C2 methylation, indirect effect = –0.07, 95% confidence interval [–0.16, –0.02]. Results indicate relations of prenatal depressive symptoms to both child basal HPA activity and DNA methylation, partially fitting a mediation model, with exposed boys and girls being affected differently.

The aim of this study was to evaluate maternal, prenatal, perinatal, and postpartum parameters as risk factors for the later development of an attention deficit hyperactivity disorder (ADHD) in the child. Women who had given birth at Erlangen University Hospital between 1996 and 1999 were sent a questionnaire in 2009. The results of the questionnaire were correlated with the prospectively collected data for the births in 1996–1999. A total of 573 mother and child pairs were analyzed. Forty-four of the mothers reported that their child had ADHD (7.7%). No significant associations were found for the following parameters: mother’s age; mother’s educational level; number of the pregnancy; maternal weight before and at the end of pregnancy; mother’s height; alcohol consumption during pregnancy; mode of delivery; gestational week; birthweight; umbilical artery blood values; Apgar score at 5 and 10 min; or breastfeeding. The parameters of smoking in pregnancy and an Apgar score lower than 7 after 1 min were significantly associated with a risk for later development of ADHD. This analysis of maternal, prenatal, perinatal, and postnatal parameters found that smoking in pregnancy and a low Apgar score 1 min after birth are associated with a significantly greater risk for the development of ADHD. Beyond the question of the causal mechanism involved, this is a relevant finding, since smoking during pregnancy is a preventable risk factor.

Consuming alcohol during pregnancy is one of the most verified prenatal risk factors for impaired child development. Information about the amount of alcohol consumed prenatally is needed to anticipate negative effects and to offer timely support. Women's self-reports are not reliable, often influenced by social stigmas and retrospective recall bias, causing biomarkers of intrauterine ethanol exposure to become more and more relevant. The present study compares both women's gestational and retrospective self-reports of prenatal alcohol consumption with levels of ethyl glucuronide (EtG) in meconium. Women (n = 180) gave self-reports of prenatal alcohol consumption both during their 3rd trimester (gestational self-report) and when their children were 6–8 years old (retrospective self-report). Child meconium was collected after birth and analyzed for EtG. No individual feedback of children's EtG level was given to the women. All analyses were run separately for two cut-offs: 10 ng/g (limit of detection) and 120 ng/g (established by Goecke et al., 2014). Mothers of children with EtG values above 10 ng/g (n = 42) tended to report prenatal alcohol consumption more frequently. There was no trend or significance for the EtG cut-off of 120 ng/g (n = 26) or for retrospective self-report. When focusing on women who retrospectively reported alcohol consumption during pregnancy, a claim to five or more consumed glasses per month made an EtG over the 10 ng/g and the 120 ng/g cut-off more probable. Women whose children were over the 10 ng/g EtG cut-off were the most inconsistent in their self-report behavior, whereas the consistency in the above 120 ng/g EtG group was higher than in any other group. The next step to establish EtG as a biomarker for intrauterine alcohol exposure is to correlate EtG values in meconium with child developmental impairments.