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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. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Prenatal exposure to testosterone is known to affect fetal brain maturation and later neurocognitive function. However, research on the effects of prenatal testosterone exposure has been limited by indirect measures of testosterone and small unrepresentative samples. This study investigated whether bioavailable testosterone (BioT) concentrations in umbilical cord blood are associated with expressive vocabulary development, in a large birth cohort. Cord blood samples were taken immediately after delivery and expressive vocabulary was measured at two years of age using the language development survey (LDS). BioT concentration significantly predicted vocabulary size in males (n =197), such that higher concentrations were associated with lower LDS scores, indicating smaller vocabulary. This relationship between BioT concentrations and vocabulary at aged 2 years was not observed in girls (n =176). Higher circulating prenatal testosterone concentrations at birth may be associated with reduced vocabulary in early childhood among boys. [Copyright &y& Elsevier]

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]

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 ≤. 01). Males were also more likely to be classified as delayed on the Fine-Motor ( p = .04) and Personal-Social ( p < .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. [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]

Abstract: Background: Although there are recognised associations between psychological and immune function, the effects of maternal depressive symptoms on fetal immune development have not been investigated. Methods: This study examined the relationship between maternal depression scores as assessed by the Beck Depression Inventory (BDI) in the second trimester and measure of neonatal immune function measured in cord blood. This study was conducted in a cohort of women (n =83) who had received either fish oil containing 3.7g/day n-3 polyunsaturated fatty acid (n-3PUFA) or a placebo from 20 weeks gestation as part of a randomised controlled trial. Results: At 20 weeks gestation, prior to the intervention, 22% of women in the study manifested mild to moderate depressive symptoms (BDI ⩾10). Neonates of these women had higher lymphoproliferative responses to a range of stimuli (including egg ovalbumin and cat allergen) compared with neonates of women with normal BDI scores (<10). These neonates also showed higher spontaneous cytokine production including (IL-6 and IL-10) and higher stimulated cytokine responses to both bacterial antigens and allergens. These patterns were evident after allowing for maternal age and education, parity, gestation, infant gender, delivery method and neonatal n-3/n-6 PUFA status. Conclusion: This exploratory study supports the notion that maternal mood in pregnancy may have the potential to influence fetal immune development. Further studies are needed to determine the significance of this. [Copyright &y& Elsevier]

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]

Summary: We investigated the causal effects of female empowerment (female educational attainment, female labor force participation, and total fertility rates) on democratic development for 97 countries from 1980 to 2005. Using Polity IV as an indicator of levels of democracy, our results show that female empowerment was strongly associated with democratic development over this period. The effect of female education increased with lags of 5 and 10years, suggesting that democracy is more likely to occur in nations with a history of educating girls and a longer experience of the social and economic conditions that have occurred because of this investment. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Early first sexual intercourse (FSI) is a risk factor for unplanned teenage pregnancy sexually transmitted infection, and adverse social, emotional, and physical health outcomes in adolescence and into adulthood. The aim of this study was to examine relationships between internalizing (eg, anxious/depressed, withdrawn) and externalizing (eg, delinquent, aggressive) behavior problems in childhood and age at FSI. METHODS: We used a large, population-based birth cohort (The Western Australian Pregnancy Cohort [Raine] Study) to address this question. Child behavior was measured by using the Child Behavior Checklist collected from parents at ages 2, 5, 8, 10, and 14 and scores calculated for total, internalizing, and externalizing behavior problems. At age 17, 1200 participants reported sexual behavior. RESULTS: Participants with clinically significant Child Behavior Checklist scores (T ≥60) were at increased risk for earlier first sexual intercourse [FSI] [<16 years). Adjusted odds ratios revealed that total and externalizing behavior problems from age 5 years onward significantly increased the risk of earlier FSI for boys. In girls, externalizing problems from age 10 years increased the risk for earlier FSI. Internalizing problems at ages 8 and 10 were significantly associated with early FSI for boys but not girls. CONCLUSIONS: Externalizing behavior from as early as 5 in boys and 10 in girls is a significant risk factor for earlier age at FSI. Adolescent sexual health promotion should consider early intervention in children with behavior problems, particularly boys. [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]

Summary: Dysfunctional regulation of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an important biological mechanism underlying stress-related diseases; however, a better understanding of the interlinked neuroendocrine events driving the release of cortisol by this stress axis is essential for progress in preventing or halting irreversible development of adverse HPA-function. We aimed to investigate basal HPA-activity in a normal population in late adolescence, the time of life believed to overlap with HPA-axis maturation and establishment of a lasting set point level of HPA function. A total of 1258 participants (mean age 16.6 years) recruited from the Western Australian Pregnancy (Raine) Cohort provided fasting morning blood and saliva samples for basal HPA activity assessment. Irrespective of gender, linear regression modelling identified a positive correlation between the main components of the HPA-cascade of events, ACTH, total cortisol and free cortisol in saliva. Corticosteroid binding globulin (CBG) was inversely associated with free cortisol in saliva, an effect most clearly observed in boys. ACTH levels were lower, but cortisol levels were higher in girls than in boys. Girls may also be exposed to more bioactive cortisol, based on higher average free cortisol measured in saliva at awakening. These relatively higher female free cortisol levels were significantly reduced by oral contraceptive use, eliminating the gender specific difference in salivary cortisol. Free plasma cortisol, calculated from total circulating cortisol and CBG concentrations, was also significantly reduced in girls using oral contraceptives, possibly via an enhancing effect of oral contraceptives on blood CBG content. This study highlights a clear gender difference in HPA activity under non-stressful natural conditions. This finding may be relevant for research into sex-specific stress-related diseases with a typical onset in late adolescence. [ABSTRACT FROM AUTHOR]

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]

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]

Abstract: Objective: To examine the influence of anxious/depressed scores on cardiovascular risk factors throughout childhood. Methods: Data from the Western Australian Pregnancy Cohort (Raine) Study, a study of 2900 pregnancies recruited between 1989 and 1991, were used. Anxious-depressed scores (derived from the Childhood Behavior Checklist), body mass index (BMI) and blood pressure were measured at 5 (n=1681), 8 (n=1697), 10 (n=1575) and 14 (n=1386) years. At age 14 depressive symptom scores (Beck Depression Inventory for Youth), anxious-depressed scores (Youth Self-Report (YSR) and Teacher Report Form (TRF)) and fasting lipid, glucose and insulin were also available. Cross sectional and longitudinal analyses were conducted. Results: At age 14, girls with higher anxious-depressed scores had higher BMI (p≤0.005) and homeostasis model assessment-estimated insulin resistance (p≤0.0001). This equated to a difference of 0.6kg/m2 and 0.3 units in predicted BMI and HOMA-IR respectively (top 5% vs. score of zero). Boys with higher anxious-depressed scores had lower systolic blood pressure trajectories (p=0.024). Conclusion: Depressive scores appear to have differing influences on BMI, homeostasis model assessment-estimated insulin resistance and systolic blood pressure in boys and girls. Paradoxically boys with higher anxious-depressed scores had lower blood pressure throughout childhood. [Copyright &y& Elsevier]

Summary: Prenatal exposure to testosterone has been shown to affect fetal brain maturation as well as postnatal cognition and behavior in animal studies. Although there are well-established sex-differences in the use of social communication (or ‘pragmatic language’) in humans, there has been limited investigation of the association between fetal testosterone exposure and postnatal pragmatic language ability. In this prospective study, pragmatic language skills, assessed using a pragmatic language score (PLS), were measured in 78 girls aged 10 years and correlated with testosterone levels in umbilical cord blood. A measure of the biologically active, ‘free’ fraction of testosterone, the free androgen index (FAI), was positively correlated with the PLS (R =.3). Regression analyses showed that the FAI was a significant, positive predictor of pragmatic language difficulties in girls after controlling for maternal and infant-health variables (B =0.02, 95% confidence interval=0.01–0.04, p =0.02). This is the first prospective study to identify an association between early life testosterone exposure and pragmatic language difficulties in girls. These novel findings are discussed with reference to the ‘extreme male-brain’ theory of autism. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to examine the influence of smoking in pregnancy on child and adolescent behavioural development, in comparison with mothers who ceased smoking in the first 18 weeks of pregnancy and with those who never smoked, in a large prospective pregnancy cohort. Methods The Western Australian Pregnancy Cohort (Raine) Study provided comprehensive data from 2900 pregnancies. Smoking was assessed at 18 weeks gestation, and children were followed up at ages 1, 2, 3, 5, 8, 10 and 14 years. The Child Behaviour Checklist (CBCL) was used to measure problem child behaviour with continuous z-scores and clinical cut points at ages 2, 5, 8, 10 and 14 years. Potential confounders included maternal and family sociodemographic characteristics and alcohol exposure. Results After adjusting for confounders, children of light smokers who quit smoking by 18 weeks gestation had significantly lower CBCL total z-scores, indicative of better behaviour, than children of women who never smoked, children of heavy smokers who quit and continuing smokers. Maternal smoking during pregnancy resulted in higher CBCL total, internalising and externalising scores and a higher risk of clinically meaningful behaviour problems in children from ages 2 to 14. Conclusion The maternal decision not to quit smoking, or the inability to quit smoking, during pregnancy appears to be a particularly strong marker for poor behavioural outcomes in children. There is a need for a greater understanding of the psychosocial characteristics associated with the decision and ability to quit smoking in pregnancy. [ABSTRACT FROM AUTHOR]

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 = .97, 95% CI = .94, .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 FROM AUTHOR]