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The present study investigated the relations among fetal testosterone, child socio-emotional engagement and language development in a sample of 467 children (235 boys) from the Western Australian Pregnancy Cohort (Raine) Study. Bioavailable testosterone concentration measured in umbilical cord blood taken at birth was found to be significantly negatively correlated with socio-emotional engagement and vocabulary development for boys but not for girls. Socio-emotional engagement mediated the effect of boys' fetal testosterone levels on their vocabulary development. However, the size of the effects was small, and fetal testosterone and socio-emotional engagement were no longer significant predictors of boys' vocabulary scores after accounting for the effects of other predictors including maternal age and education, parity, and parent-child book reading. It is concluded that further research into these associations is warranted in both typical and atypical development and that this research would profit from including a broader focus on the role that proximal processes such as socio-emotional engagement, joint attention and imitation have in mediating the developmental effects of prenatal factors such as fetal testosterone exposure.

Background: Preliminary evidence suggests that prenatal testosterone exposure may be associated with language delay. However, no study has examined a large sample of children at multiple time-points. Methods: Umbilical cord blood samples were obtained at 861 births and analysed for bioavailable testosterone (BioT) concentrations. When participating offspring were 1, 2 and 3 years of age, parents of 767 children (males = 395; females = 372) completed the Infant Monitoring Questionnaire (IMQ), which measures Communication, Gross Motor, Fine Motor, Adaptive and Personal-Social development. Cut-off scores are available for each scale at each age to identify children with "clinically significant" developmental delays. Chi-square analyses and generalized estimating equations examined longitudinal associations between sex-specific quartiles of BioT concentrations and the rate of developmental delay. Results: Significantly more males than females had language delay (Communication scale) at age 1, 2 and 3 years (p-values less than or equal to 0.01). Males were also more likely to be classified as delayed on the Fine-Motor (p = 0.04) and Personal-Social (p less than 0.01) scales at age 3 years. Chi-square analyses found a significant difference between BioT quartiles in the rate of language delay (but not Fine-Motor and Personal-Social delay) for males (age 3) and females (age 1 and 3). Generalized estimating equations, incorporating a range of sociodemographic and obstetric variables, found that males in the highest BioT quartile were at increased risk for a clinically significant language delay during the first 3 years of life, with an odds ratio (OR) of 2.47 (95% CI: 1.12, 5.47). By contrast, increasing levels of BioT reduced the risk of language delay among females (Quartile 2: OR = 0.23, 95% CI: 0.09, 0.59; Quartile 4: 0.46, 95% CI: 0.21, 0.99). Conclusion: These data suggest that high prenatal testosterone levels are a risk factor for language delay in males, but may be a protective factor for females.

Background: Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western Australian children. Methods: The Raine Study is a prospective cohort study of 2,868 live born children involving 2,979 pregnant women recruited at 18 weeks gestation. Children were followed up at age two and five years. The Child Behaviour Checklist (CBCL) was used to measure child mental health with clinical cut-points, including internalising (withdrawn/depressed) and externalising (aggressive/destructive) behaviours (n = 1707). Results: Multinomial logistic regression analysis showed that the significant risk factors for behaviour problems at age two were the maternal experience of multiple stress events in pregnancy (OR = 1.20, 95% CI = 1.06, 1.37), smoking during pregnancy (OR = 1.30, 95% CI = 1.06, 1.59) and maternal ethnicity (OR = 3.34, 95% CI = 1.61, 6.96). At age five the experience of multiple stress events (OR = 1.17, 95% CI = 1.08, 1.27), cigarette smoking (OR = 1.19, 95% CI = 1.03, 1.37), male gender (OR = 1.43, 95% CI = 1.02, 2.00), breastfeeding for a shorter time (OR = 0.97, 95% CI = 0.94, 0.99) and multiple baby blues symptoms (OR = 1.08, 95% CI = 1.02, 1.14) were significant predictors of mental health problems. Conclusions: Early childhood mental health is significantly affected by prenatal events in addition to the child's later environment. Interventions targeting adverse prenatal, perinatal and postnatal influences can be expected to improve mental health outcomes for children in the early years.

Abstract Background Increased prenatal testosterone exposure has been hypothesized as a mechanism underlying autism spectrum disorders (ASD). However, no studies have prospectively measured prenatal testosterone exposure and ASD. The current study sought to determine whether testosterone concentrations in umbilical cord blood are associated with a clinical diagnosis of ASD in a small number of children and with autistic-like traits in the general population. Methods Umbilical cord blood was collected from 707 children. Samples were analyzed for total (TT) and bioavailable (BioT) testosterone concentrations. Parent report indicated that five individuals had a clinical diagnosis of ASD. Those participants without a diagnosis were approached in early adulthood to complete the Autism-Spectrum Quotient (AQ), a self-report measure of autistic-like traits, with 184 males (M = 20.10 years; SD= 0.65 years) and 190 females (M = 19.92 years; SD=0.68 years) providing data. Results The BioT and TT concentrations of the five children diagnosed with ASD were within one standard-deviation of the sex-specific means. Spearman’s rank-order coefficients revealed no significant correlations between TT levels and scores on any AQ scale among males (rho range: -.01 to .06) or females (rho value range: -.07 to .01). There was also no significant association between BioT or TT concentrations and AQ scores among males (rho value range: -.07 to .08) or females (rho value range: -.06 to .12). Males were more likely than females to have ‘high’ scores (upper decile) on the AQ scale relating pattern and detail processing. However, the likelihood of a high score on this scale was unrelated to BioT and TT concentrations in both males and females. Conclusions These findings indicate that testosterone concentrations from umbilical cord blood are unrelated to autistic-like traits in the general population. However, the findings do not exclude an association between testosterone exposure in early intrauterine life and ASD.

The authors of this commentary concur with the viewpoint presented by Mareschal et al. (2007a; 2007b) concerning the relevance of neurological data when theorizing about cognitive development. However, we argue here that Mareschal et al. fail to consider adequately the relevance of reorganizational brain events occurring through adolescence and early adulthood, especially regarding the prefrontal cortex and the ontogeny of executive functioning. In addition, evidence from the lifespan neurodevelopmental literature indicates that increased activity of neural networks may signify less efficient processing. This observation is of potential relevance when considering the neurological changes associated with cognitive development during childhood and adolescence.

Introduction and Objectives Estimation of the umbilical venous blood flow volume relies on the diameter of the vein, which has been reported to be reduced in severely growth restricted fetuses. However, there is only limited information on the growth pattern of this vessel in the normal human fetus. The aim of this study is to examine the growth pattern of the umbilical vein across gestation in low-risk human pregnancies. Methods In a prospective, longitudinal ultrasound study of 136 low-risk pregnancies, the internal diameter of the intra-amniotic portion of the umbilical vein was measured at 18, 26 and 34 weeks of gestation. To investigate the growth pattern of the venous diameter, the ratios of diameters at 26 weeks to diameters at 18 weeks (ratio 1) and the ratios at 34 to 26 weeks (ratio 2) were also calculated. A paired-sample t-test was performed to compare the means of the two ratios. Results The mean diameter of the umbilical vein at 18 weeks was 2.8 mm (SD 0.40), 5.8 mm (SD 0.67) at 26 weeks and 7.6 mm (SD 0.98) at 34 weeks. The mean of ratio 1 was 2.06 (95% CI 2.01-2.14), which was significantly higher than ratio 2 (mean 1.33, 95% CI 1.29-1.36), P < 0.001. Conclusion The umbilical venous diameter demonstrates a non-linear growth pattern between 18 and 34 weeks of gestation. The diameter doubled in size between 18 and 26 weeks but grew at a slower rate between 26 and 34 weeks of gestation. This study provides new data on the normal growth pattern of the umbilical vein by identifying a period of gestation where its growth is accelerated. [ABSTRACT FROM AUTHOR]

IntroductionNeurocognitive deficits have been identified in eating disorders, including anorexia nervosa and bulimia nervosa. However, current data do not allow for firm conclusions regarding the nature or extent of these deficits. The current study aimed to evaluate neurocognitive functioning in a population-based sample of adolescents with and without eating disorders. MethodsParticipants (N=669) were drawn from the Western Australian Pregnancy Cohort (Raine) Study. Cognitive testing was conducted using the computerised CogState assessment battery. Eating disorder symptoms were assessed using questions adapted from the Child Eating Disorder Examination and Eating Disorder Examination–Questionnaire. Adolescents who met full or partial criteria for a DSM-IV eating disorder (n=58) were compared to adolescents with no significant eating pathology (n=592). ResultsThe eating disorder sample showed impaired performance on measures of executive functioning, including global processing and set shifting, but performed better than control participants on measures of visual attention and vigilance. ConclusionsThis is the first study to evaluate neurocognitive functioning in a population-based sample of adolescents with eating disorders. Support is provided for weak central coherence and set-shifting difficulties early in the course of eating disorders. Research is needed to determine if these deficits precede and predict eating disorder onset. [ABSTRACT FROM PUBLISHER]

Antenatal testosterone exposure influences fetal neurodevelopment and gender-role behavior in postnatal life and may contribute to differences in developmental psychopathology during childhood. We prospectively measured the associations between umbilical cord blood testosterone levels at birth and childhood behavioral development in both males and females from a large population based sample. The study comprised 430 females and 429 males from the Western Australian Pregnancy Cohort (Raine) Study where umbilical cord blood had been collected. Total testosterone concentrations were determined by mass spectrometry and bioavailable testosterone (BioT) levels were calculated. At two, five, eight and ten years of age, the participants completed the Child Behavior Checklist (CBCL). Linear regression models were used to analyse the relationship between BioT concentrations (in quartiles) and CBCL scores (total, internalizing, externalizing and selected syndrome). Boys had higher mean CBCL T-scores than girls across all ages of follow-up. There was no significant relationship between cord blood BioT quartiles and CBCL total, internalizing and externalizing T-scores at age two or five to ten combined. In the syndrome score analyses, higher BioT quartiles were associated with significantly lower scores for attention problems for boys at age five, eight and ten, and greater withdrawal symptoms in pre-school girls (age five). We did not identify a consistent relationship between antenatal testosterone exposure and total, internalizing or externalizing behavioral difficulties in childhood. Higher umbilical cord BioT levels were associated with lower scores for attention problems in boys up to 10 years and more withdrawn behavior in 5-year-old girls; however, these findings were not consistent across ages and require further investigation in a larger sample. [ABSTRACT FROM AUTHOR]

The present study investigated the relations among fetal testosterone, child socio-emotional engagement and language development in a sample of 467 children (235 boys) from the Western Australian Pregnancy Cohort (Raine) Study. Bioavailable testosterone concentration measured in umbilical cord blood taken at birth was found to be significantly negatively correlated with socio-emotional engagement and vocabulary development for boys but not for girls. Socio-emotional engagement mediated the effect of boys' fetal testosterone levels on their vocabulary development. However, the size of the effects was small, and fetal testosterone and socio-emotional engagement were no longer significant predictors of boys' vocabulary scores after accounting for the effects of other predictors including maternal age and education, parity, and parent-child book reading. It is concluded that further research into these associations is warranted in both typical and atypical development and that this research would profit from including a broader focus on the role that proximal processes such as socio-emotional engagement, joint attention and imitation have in mediating the developmental effects of prenatal factors such as fetal testosterone exposure. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The aim of this study was to measure umbilical blood androgen concentrations in a birth cohort using a highly specific liquid chromatography- tandem mass spectrometry (LC-MS/MS) assay and assesses the effects of sex, labor, and gestational age on fetal androgen levels at birth. We performed a prospective cohort study of androgen concentrations in mixed arterial and venous umbilical cord serum from 803 unselected singleton pregnancies from a general obstetric population in Western Australia. Total testosterone (TT), D4- androstenedione, and dehydroepiandrosterone were extracted from archived cord serum samples and measured using LC-MS/MS. SHBG was measured by ELISA; free testosterone (FT) and bioavailable testosterone (BioT) values were also calculated. Median values for all three androgens were generally lower than previously published values. Levels of TT, FT, BioT, and SHBG were significantly higher in male verses female neonates (P<0.0001), while dehydroepiandrosterone levels were higher in females (P<0.0001). Labor was associated with a significant (~15-26%) decrease in median cord blood TT and FT levels (both sexes combined), but a modest (~16-31%) increase in SHBG, Δ4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, Δ4- androstenedione, and dehydroepiandrosterone were positively correlated. Antenatal glucocorticoid administration also had a significant effect in the multiple regression models. This is the first study to report umbilical cord androgen levels in a large unselected population of neonates using LC-MS/MS. Our findings suggest that previous studies have over-estimated cord androgen levels, and that fetal, maternal, and obstetric factors influence cord androgen levels differentially. Caution should be exercised when interpreting previously- published data that have not taken all of these factors into account. [ABSTRACT FROM AUTHOR]

Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response. Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stressrelated behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders. [ABSTRACT FROM AUTHOR]

This Editorial provides a critical review of the progress in social determinants of health research over the last two decades, suggesting new perspectives which may further our understanding of persistent social inequalities in health. It highlights the global significance of the Special Issue setting it in the context of the recently released WHO Commission on Social Determinants of Health Final Report (CSDH 2008). The Editorial introduces individual papers in the Special Issue and discusses how they are in line with, complement or provide feedback to, the WHO CSDH Final Report and its call for actions to close the health gap in a generation. Finally, based on the articles in this Special Issue and emerging themes of the global research and policy literature, it outlines a number of significant directions for future research and actions, from both methodological and theoretical points of view. [ABSTRACT FROM AUTHOR]

The maternal experience of stressful events during pregnancy has been associated with a number of adverse consequences for behavioral development in offspring, but the measurement and interpretation of prenatal stress varies among reported studies. The Raine Study recruited 2900 pregnancies and recorded life stress events experienced by 18 and 34 weeks' gestation along with numerous sociodemographic data. The mother's exposure to life stress events was further documented when the children were followed-up in conjunction with behavioral assessments at ages 2, 5, 8, 10, and 14 years using the Child Behavior Checklist. The maternal experience of multiple stressful events during pregnancy was associated with subsequent behavioral problems for offspring. Independent (e.g., death of a relative, job loss) and dependent stress events (e.g., financial problems, marital problems) were both significantly associated with a greater incidence of mental health morbidity between age 2 and 14 years. Exposure to stressful events in the first 18 weeks of pregnancy showed similar associations with subsequent total and externalizing morbidity to events reported at 34 weeks of gestation. These results were independent of postnatal stress exposure. Improved support for women with chronic stress exposure during pregnancy may improve the mental health of their offspring in later life.