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Earlier puberty, especially in girls, is associated with physical and mental disorders. Prenatal glucocorticoid exposure influences the timing of puberty in animal models, but the human relevance of those findings is unknown. We studied whether voluntary consumption of licorice, which contains glycyrrhizin (a potent inhibitor of placental 11β-hydroxysteroid dehydrogenase type 2, the "barrier" to maternal glucocorticoids), by pregnant women was associated with pubertal maturation (height, weight, body mass index for age, difference between current and expected adult height, Tanner staging, score on the Pubertal Development Scale), neuroendocrine function (diurnal salivary cortisol, dexamethasone suppression), cognition (neuropsychological tests), and psychiatric problems (as measured by the Child Behavior Checklist) in their offspring. The children were born in 1998 in Helsinki, Finland, and examined during 2009-2011 (mean age = 12.5 (standard deviation (SD), 0.4) years; n = 378). Girls exposed to high maternal glycyrrhizin consumption (≥500 mg/week) were taller (mean difference (MD) = 0.4 SD, 95% confidence interval (CI): 0.1, 0.8), were heavier (MD = 0.6 SD, 95% CI: 0.2, 1.9), and had higher body mass index for age (MD = 0.6 SD, 95% CI: 0.2, 0.9). They were also 0.5 standard deviations (95% CI: 0.2, 0.8) closer to adult height and reported more advanced pubertal development (P < 0.04). Girls and boys exposed to high maternal glycyrrhizin consumption scored 7 (95% CI: 3.1, 11.2) points lower on tests of intelligence quotient, had poorer memory (P < 0.04), and had 3.3-fold (95% CI: 1.4, 7.7) higher odds of attention deficit/hyperactivity disorder problems compared with children whose mothers consumed little to no glycyrrhizin (≤249 mg/week). No differences in cortisol levels were found. Licorice consumption during pregnancy may be associated with harm for the developing offspring., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits., Methods: We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Consortium. 10,554 children of European ancestry were included in the discovery, and 1,250 children in the replication phase., Results: We found evidence of significant but modest SNP heritability of sleep duration in children (SNP h 2 0.14, 95% CI [0.05, 0.23]) using the LD score regression method. A novel region at chromosome 11q13.4 (top SNP: rs74506765, P = 2.27e-08) was associated with sleep duration in children, but this was not replicated in independent studies. Nominally significant genetic overlap was only found ( rG = 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism., Conclusions: The significant SNP heritability of sleep duration in children and the suggestive genetic overlap with type 2 diabetes support the search for genetic mechanisms linking sleep duration in children to multiple outcomes in health and disease., (© 2016 Associated Professional Sleep Societies, LLC.)

Study Objectives: We examined associations between pubertal maturation and sleep in early adolescence, at age 12 y, and continuity and change in actigraphy-based sleep and parent-reported sleep disorders from age 8 to 12 y. We also explored longitudinal associations between actigraph estimates of sleep and sleep disorders., Design: A cohort study of children born in 1998 and tested at ages 8 y (standard deviation [SD] = 0.3) and 12 y (SD = 0.5)., Participants: A total of 348 children participated in cross-sectional analyses. We had longitudinal actigraphy data for 188 children and repeated parent reports of sleep disorders for 229 children., Measurements and Results: At age 8 y, participants wore actigraphs for 7.1 nights (SD = 1.2, range 3-14) on average and at age 12 y for 8.4 nights (SD = 1.7, range 3-11). Sleep disorders were parent-rated based on the Sleep Disturbance Scale for Children. Pubertal maturity was self-reported at age 12 y using the continuous Pubertal Development Scale and the picture-assisted categorical Tanner scales., Results: Significant mean-level changes toward shorter but higher quality sleep occurred over time. Sleep variables had low to high rank-order stability over time. Sleep disorders were highly stable from age 8 to 12 y. Actigraphy-based sleep and parent-rated sleep disorders showed no association either in cross-section or longitudinally. Pubertal maturation was not associated with worse sleep., Conclusions: Sleep in early adolescence can be anticipated from childhood sleep patterns and disorders, but is not associated with pubertal maturity. Although sleep duration becomes shorter, sleep quality may improve during early adolescence. Parent-rated sleep disorders are distinct from actigraph estimates of sleep.

Context: Children who undertake more physical activity (PA) not only have more optimal physical health but also enjoy better mental health. However, the pathways by which PA affects well-being remain unclear., Objective: To address this question, we examined whether objectively measured daytime PA was associated with diurnal hypothalamic-pituitary-adrenocortical axis (HPAA) activity and HPAA responses to psychosocial stress., Design and Setting: We conducted a cross-sectional study in a birth cohort in Helsinki, Finland., Participants: We studied 258 8-year-old children., Main Outcome Measures: PA was assessed with wrist-worn accelerometers. Overall PA and percentage of time spent in vigorous PA (VPA) were categorized by sex into thirds. Salivary cortisol was measured diurnally and in response to the Trier Social Stress Test for Children., Results: The children in different PA groups did not show differences in diurnal salivary cortisol (P > .10 for overall PA and VPA). Children with the highest levels of overall PA or VPA showed no, or only small, increases over time in salivary cortisol after stress (P = .10 and P =.03 for time in analyses of PA and VPA, respectively), whereas children belonging to the lowest and intermediate thirds showed significant increases over time in salivary cortisol after stress (P ≤ .002 for time in the analyses of overall PA and VPA)., Conclusions: These results suggest that children with lower levels of daytime PA have higher HPAA activity in response to stress. These findings may offer insight into the pathways of PA on physical and mental well-being.

Personality traits are basic dimensions of behavioral variation, and twin, family, and adoption studies show that around 30% of the between-individual variation is due to genetic variation. There is rapidly growing interest in understanding the evolutionary basis of this genetic variation. Several evolutionary mechanisms could explain how genetic variation is maintained in traits, and each of these makes predictions in terms of the relative contribution of rare and common genetic variants to personality variation, the magnitude of nonadditive genetic influences, and whether personality is affected by inbreeding. Using genome-wide single nucleotide polymorphism (SNP) data from > 8000 individuals, we estimated that little variation in the Cloninger personality dimensions (7.2% on average) is due to the combined effect of common, additive genetic variants across the genome, suggesting that most heritable variation in personality is due to rare variant effects and/or a combination of dominance and epistasis. Furthermore, higher levels of inbreeding were associated with less socially desirable personality trait levels in three of the four personality dimensions. These findings are consistent with genetic variation in personality traits having been maintained by mutation-selection balance., (© 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.)

Context: Neuroendocrine alterations, with well-known links with health, may offer insight into why poor sleep is associated with poor health. Yet, studies testing associations between sleep and neuroendocrine activity in children are scarce., Objective: The aim of this study was to determine whether actigraphy-based sleep pattern is associated with hypothalamic-pituitary-adrenocortical axis and sympatho-adrenal-medullary system activity in children., Design and Setting: We conducted a cross-sectional study in a birth cohort in Helsinki, Finland., Participants: We studied 282 8-yr-old children., Main Outcome Measures: We measured diurnal salivary cortisol and salivary cortisol and alpha-amylase (a sympatho-adrenal-medullary system marker) responses to the Trier Social Stress Test for Children (TSST-C)., Results: Children with short (77.4%) displayed higher diurnal cortisol levels across the entire day (P < 0.03), higher cortisol levels after the TSST-C stressor (P < 0.04), and higher overall alpha-amylase levels across the entire TSST-C protocol (P < 0.05). The effects were not confounded by factors that may alter sleep or hormonal patterns., Conclusions: Poor sleep may signal altered neuroendocrine functioning in children. The findings may offer insight into the pathways linking poor sleep with poor health.

Overexposure to glucocorticoids may link prenatal adversity with detrimental outcomes in later life. Glycyrrhiza, a natural constituent of licorice, inhibits placental 11-beta-hydroxysteroid dehydrogenase type 2, the feto-placental "barrier" to higher maternal levels of cortisol. The authors studied whether prenatal exposure to glycyrrhiza in licorice exerts detrimental effects on cognitive performance (subtests of the Wechsler Intelligence Scale for Children III as well as the Children's Developmental Neuropsychological Assessment and the Beery Developmental Test of Visual-Motor Integration) and psychiatric symptoms (Child Behavior Checklist) in 321 Finnish children 8.1 years of age born in 1998 as healthy singletons at 35-42 weeks of gestation. In comparison to the group with zero-low glycyrrhiza exposure (0-249 mg/week), those with high exposure (>or=500 mg/week) had significant decrements in verbal and visuospatial abilities and in narrative memory (range of mean differences in standard deviation units, -0.31 to -0.41; P < 0.05) and significant increases in externalizing symptoms and in attention, rule-breaking, and aggression problems (range of odds ratios, 2.15 to 3.43; P < 0.05). The effects on cognitive performance appeared dose related. Data are compatible with adverse fetal "programming" by overexposure to glucocorticoids and caution against excessive intake of licorice-containing foodstuffs during pregnancy.

Slow childhood growth is associated with poorer intellectual ability. The critical periods of growth remain uncertain. Among 2,786 Finnish male military conscripts (1952-1972) born in 1934-1944, the authors tested how specific growth periods from birth to age 20 years predicted verbal, visuospatial, and arithmetic abilities at age 20. Small head circumference at birth predicted poorer verbal, visuospatial, and arithmetic abilities. The latter 2 measures were also associated with lower weight and body mass index (weight (kg)/height (m)(2)) at birth (for a 1-standard-deviation (SD) decrease in test score per SD decrease in body size > or = 0.05, P's < 0.04). Slow linear growth and weight gain between birth and age 6 months, between ages 6 months and 2 years, or both predicted poorer performance on all 3 tests (for a 1-SD decrease in test score per SD decrease in growth > or = 0.05, P's < 0.03). Reduced linear growth between ages 2 and 7 years predicted worse verbal ability, and between age 11 years and conscription it predicted worse performance on all 3 tests. Prenatal brain growth and linear growth up to 2 years after birth form a first critical period for intellectual development. There is a second critical period, specific for verbal development, between ages 2 and 7 years and a third critical period for all 3 tested outcomes during adolescence.

Study Objectives: We examined whether small body size at birth and prenatal tobacco or alcohol exposure predict poor sleep and more sleep disturbances in children., Design: An epidemiologic cohort study of 289 eight-year-old children born at term., Measurements and Results: Sleep duration and efficiency were measured by actigraphy for 7 consecutive nights (mean = 7.1, SD = 1.2). We used both continuous measures of poor sleep and binary variables of short sleep and low sleep efficiency ( < or = 10th percentiles). Parents completed the Sleep Disturbance Scale for Children. Lower birth weight and shorter length at birth were associated with lower sleep efficiency. For every 1-SD decrease in weight and length at birth, the odds for low sleep efficiency increased by 1.7 fold (95% confidence interval [CI]: 1.1 to 2.7) and 2.2 fold (95% CI: 1.3 to 3.7), respectively. For every 1-SD decrease in ponderal index at birth, the risk of parent-reported sleep disorders increased by 1.4 fold (95% CI: 1.0 to 2.0). Moreover, children exposed prenatally to alcohol had a 2.9-fold (95% CI: 1.1 to 7.6) and 3.6-fold (95% CI: 1.3 to 10.0) increased risk for having short sleep and low sleep efficiency, respectively. The associations were not confounded by sex, gestational length, prenatal and perinatal complications, body mass index at 8 years, asthma, allergies, or parental socioeconomic status., Conclusions: Poor sleep in children may have prenatal origins. Possible mechanisms include alcohol consumption during pregnancy and other conditions associated with small body size at birth.

Objective: To assess the relationship between very low birth weight (VLBW; <1,500 g) and quality and amount of sleep in young adults., Methods: We compared 89 VLBW and 78 term-born 19- to 26-year-old adults, by actigraphy and the Basic Nordic Sleep Questionnaire., Results: There were no group differences in sleep quality or amount (p's >.15), although VLBW adults went to bed on average 36 min earlier (95% confidence interval 6-66 min). Shorter gestational age was related to longer sleep latency both within VLBW (standardized regression coefficient beta = -.36, p =.040) and term-born adults (beta = -.25, p =.029)., Conclusion: Adults with VLBW had similar quality and amount of sleep as those born at term, although VLBW adults went to bed earlier, suggesting an advanced sleep phase. Within each group, a lower gestational age was related to a longer sleep onset.

Despite the significance of childhood trauma for later life, there is little evidence on the long-term consequences of parent-child separation. World War II created a unique natural experiment that allowed the authors to test whether 1) evacuation to temporary foster care unaccompanied by either parent and 2) separation from the father because of his military service predicted depressive symptoms later on. Members of the Helsinki 1934-1944 Birth Cohort (n = 1,658) filled out the Beck Depression Inventory (BDI) at the ages of 61.6 (standard deviation: 2.9) and 63.4 (standard deviation: 2.9) years. The mean of the two BDI scores was used as the dependent variable. The data on separation experiences were extracted from the Finnish National Archives and from a survey among the participants. Former evacuees (n = 410) reported 20% (95% confidence interval: 8.7, 33.1) more severe depressive symptoms, and the odds ratio was 1.7 (95% confidence interval: 1.1, 2.6) for having at least mild (BDI score: > or =10) symptoms over time compared with those who were not separated. Those separated from their father because of the father's military assignment (n = 744) did not differ from those who were not separated.

Background: Studies in humans and animals have suggested intrauterine programming of hypothalamic-pituitary-adrenal axis (HPAA) function as an important mechanism in linking fetal life conditions with adult disease., Objective: Our aim was to assess how body size at birth, a marker of intrauterine conditions, is associated with hypothalamic-pituitary-adrenal axis response to psychosocial stress in late adulthood., Design and Setting: We conducted a clinical study in the Helsinki Birth Cohort., Participants: Two hundred eighty-seven men and women born between 1934 and 1944 whose birth measurements and gestational age came from hospital records participated in the study., Measurements: We measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations in conjunction with a standardized psychosocial stressor (Trier Social Stress Test)., Results: There was a linear relationship between low birth weight and low plasma ACTH but no linear relationship with cortisol. There were, however, quadratic relationships between birth weight and salivary (mixed model P = 0.001) and plasma cortisol (P = 0.005) but not with plasma ACTH (P = 0.1). The lowest peak salivary cortisol concentrations were seen in the lowest third of birth weights (adjusted for gestational age and sex): 12.9 nmol/liter (95% confidence interval of mean 11.2-15.0), compared with 17.1 nmol/liter (14.8-19.8) in the middle and 14.1 nmol/liter (12.6-15.7) in the highest third of birth weights. Corresponding figures for plasma cortisol were 418 nmol/liter (380-459), 498 nmol/liter (455-545), and 454 nmol/liter (428-482), and for plasma ACTH 8.17 pmol/liter (6.98-9.57), 12.42 pmol/liter (10.64-14.51), and 11.50 (10.06-13.14), respectively. Results for areas under the curve were similar., Conclusions: We found an inverse U-shaped relationship between birth weight and cortisol concentrations during psychosocial stress. The lowest cortisol and ACTH concentrations were seen in subjects with the lowest birth weights. These results support the hypothesis that both hyper- and hypocortisolism may be programmed during the fetal period.

Objective: To study whether infant weight for gestational age, and gestational age predict mother- and father-rated infant temperament (IBQ) at 6 months., Methods: The sample comprised of family units with both biological parents and infants born at term (n = 152). Data on weight and gestational age were collected form obstetric database., Results: Infants born small for gestational age (SGA) (weight < 10th percentile for gestational age) were rated by both parents as significantly more fearful and negatively reactive compared to infants born appropriate for gestational age (AGA). Infants born SGA defined by using the lowest 15th or 20th percentile groups did not differ from AGA group in temperament. The weekly continuum of gestational age predicted differences in parental ratings of infant temperamental attentiveness., Conclusions: The predictive significance of infant weight for gestational age and gestational age for behavioral outcomes appear true also for infants born at term. Concordance in parental perceptions of an infant born SGA emphasizes the clinical significance of the findings.