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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.

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 The aim of this study was to examine relationships between internalizing (eg, anxious/depressed, withdrawn) and externalizing (eg, delinquent, aggressive) behavior problems in childhood and age at FSI.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.

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.

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.

Introduction: Neurocognitive 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.Methods: Participants (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).Results: The 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.Conclusions: This 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.

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 intrauteri

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 stress-related 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.

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.

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.

Background: This article investigates whether reading and writing skills among children of equivalent perinatal characteristics differ by neighbourhood socioeconomic status and maternal factors. Methods: Notifications of births for all non-Aboriginal singletons born in 1990-1997 in Western Australia subsequently attending government primary schools were linked to the State literacy tests in grade three and with information on socioeconomic status of the school and the residential area. Using multilevel modelling, the associations between birth characteristics (gestational age, intrauterine growth, birth order and Apgar score at 5 minutes) and literacy attainment in grade three were examined in models that included socioeconomic and demographic factors of the child, mother and community. Results: Higher percentages of optimal head circumference and birth length and term birth were positively and independently associated with literacy scores. A higher percentage of optimal birth weight was associated with higher reading scores especially for children born to mothers residing in educationally advantaged areas. First birth was positively associated with reading and writing attainment: this association was stronger for children born to single mothers and additional advantage in writing was also associated with first birth in children living in disadvantaged areas. Conclusions: These findings suggest that having sub-optimal growth in utero oran older sibling at birth increases vulnerability to poor literacy attainment especially among children born to single mothers or those in disadvantaged neighbourhoods. These data provide evidence for advocating lifestyles compatible with optimum fetal growth and socioeconomic conditions conducive to healthy lifestyles, particularly during pregnancy.

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.

Considerable evidence points to the importance of early development from the time of conception in causalpathways to life-long health and wellbeing. A consistent theme is evolving regarding the interplay betweenpsychological and social factors and biological mechanisms, such as genetic predisposition and stress-relatedneuroendocrine functioning. The focus of interest is the developing child and the emerging capacity for emotional,attentional, and social regulation. Of substantial importance is the possibility that the experience of multiple stressfullife-events within the family, school and community directly and indirectly influences these regulatory processes.Evidence suggests that the experience of life-stress modifies the child?s biology through the central mediator ofstress responsiveness, the hypothalamic-pituitary-adrenal (HPA) axis.Children in both developing and developed countries are at risk of poor health and developmental outcomes acrossthe lifespan. Terrorism, civil unrest, youth crime and violence, high rates of mental health problems in both childrenand adults, high rates of substance abuse, promiscuous sexual behaviour, and high rates of starvation as well asobesity are all symptoms of the underlying problem. While the causes are complex and involve an interplay betweenindividual, family and community characteristics, there is increasing evidence that supportive public policy across arange of portfolios is key to reversing this disturbing situation. Failure to act now, both nationally and globally,poses a dire risk for future human habitation arguably greater than the impact of unabated climate change.

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.

This paper reviews the methods and findings of studies surveying inventors on nationally representative sample of patents or patent applications. These studies show that the most common inventor is a middle-aged man with a postgraduate qualification, with women representing only 0.4% to 3.5% of inventors. They demonstrate that 43% to 68% of granted patents become innovations (52% on average). Despite such findings this body of work has only been cited 61 times in scientific journals. Thus, surveys of inventors provide good insights into the process of commercialising patents and yet are an underutilised method especially within the literature on innovation.

Objectives: To examine the commercial development of Australian medical patents and identify the determinants of their being used in innovations (new or improved products or production processes). Design: Cross-sectional survey with a nested case-control study. Participants and setting: 177 inventors listed as the first Australian on medical patents granted in the United States between 1 January 1984 and 30 December 1994, and surveyed in 1998-1999. Main outcome measure: A series of predictor variables (including characteristics of the patents; characteristics of the inventors; ideas, advice and funding during commercialisation; and the process of commercialisation) for whether or not a patent became an innovation. Results: Half (89/177) of the medical patents became innovations, with 34% generating a total of A $287 million (13% over $1 million) in annual sales a median of 8 years after the patent had been granted. A patent was more likely to become an innovation if the inventor was employed by industry at the time of invention (odds ratio [OR], 3.2; 95% CI, 1.1-9.2), had invested their own finances (OR, 2.8; 95% CI, 1.0-7.4), and if the patent had been licensed (OR, 4.6; 95% CI 1.7-12.7), led to further patents (OR, 3.2; 95% CI, 1.0-10.4) and involved an industry partner in its commercial development (OR, 10.1; 95% CI, 3.6-27.7). It was less likely to become an innovation if finance came from a research funding agency (OR, 0.3; 95% CI, 0.1-0.8) and if interest from Australian industry was judged by inventors as "poor" (OR, 0.6; 95% CI, 0.4-0.9). Conclusions: Medical patents in the US listing Australian inventors are more likely to become innovations if they originate from industry rather than the public sector, and if inventors are willing to invest their own finances.