To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk fact... more To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk factors throughout childhood. This study utilized cross-sectional and longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study (n = 2900). Aggressive behaviour scores were derived from the Child Behavior Checklist/4-18(CBCL), Youth Self-Report/11-18 (YSR) and Teacher Report Form/6-18 (TRF). CVD risk factors included body mass index (BMI), blood pressure, fasting lipids and homeostasis model of insulin resistance (HOMA-IR). Girls with higher aggressive behaviour scores had higher BMI from 10 years of age (P ≤ 0.001), higher BMI trajectories throughout childhood (P = 0.0003) and at 14 years higher HOMA-IR (P = 0.008). At the 14-year survey, this equated to a difference of 1.7 kg/m2 in the predicted BMI between the extreme CBCL scores in girls (top 5% (CBCL ≥ 17) vs. CBCL score = 0). Boys with higher aggressive behaviour scores had higher BMI at 5 years (P = 0.002), lower diastolic pressure at 14 years (P = 0.002) and lower systolic blood pressure trajectories throughout childhood (P = 0.016). Aggressive behaviour influences BMI from early childhood in girls but not boys. If this association is causal, childhood offers the opportunity for early behavioural intervention for obesity prevention.
Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a hi... more 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.
Antenatal testosterone exposure influences fetal neurodevelopment and gender-role behavior in pos... more 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.
Background: Increased prenatal testosterone exposure has been hypothesized as a mechanism underly... more 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.
To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk fact... more To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk factors throughout childhood. This study utilized cross-sectional and longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study (n = 2900). Aggressive behaviour scores were derived from the Child Behavior Checklist/4-18(CBCL), Youth Self-Report/11-18 (YSR) and Teacher Report Form/6-18 (TRF). CVD risk factors included body mass index (BMI), blood pressure, fasting lipids and homeostasis model of insulin resistance (HOMA-IR). Girls with higher aggressive behaviour scores had higher BMI from 10 years of age (P ≤ 0.001), higher BMI trajectories throughout childhood (P = 0.0003) and at 14 years higher HOMA-IR (P = 0.008). At the 14-year survey, this equated to a difference of 1.7 kg/m2 in the predicted BMI between the extreme CBCL scores in girls (top 5% (CBCL ≥ 17) vs. CBCL score = 0). Boys with higher aggressive behaviour scores had higher BMI at 5 years (P = 0.002), lower diastolic pressure at 14 years (P = 0.002) and lower systolic blood pressure trajectories throughout childhood (P = 0.016). Aggressive behaviour influences BMI from early childhood in girls but not boys. If this association is causal, childhood offers the opportunity for early behavioural intervention for obesity prevention.
Early first sexual intercourse (FSI) is a risk factor for unplanned teenage pregnancy, sexually t... more 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. 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. 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 th...
Digit ratio (2D:4D) is widely used as a marker of prenatal androgen exposure. However, there are ... more Digit ratio (2D:4D) is widely used as a marker of prenatal androgen exposure. However, there are no published prospective studies where prenatal androgen exposure has been measured and correlated with digit ratio in adult life. We aimed to establish the prospective relationship between prenatal androgen exposure in the second and third trimesters of pregnancy (as measured by maternal circulating androgen concentrations and umbilical cord androgen concentrations) and digit ratio in adolescent girls. Androgen concentrations (testosterone, free androgen index, androstenedione, DHEAS) and sex hormone binding globulin (SHBG) were measured in stored plasma samples from pregnant mothers at 18 (n=118) and 34/36 (n=114) weeks of gestation and in cord blood (n=82) from the Western Australian Pregnancy (Raine) Cohort Study (www.rainestudy.org.au). Digit ratio was measured in 244 female offspring from this cohort at age 14-16 years. Only one borderline statistically significant correlation between maternal circulating androstenedione levels at 18 weeks of gestation and left hand digit ratio was seen. No other statistically significant relationship between maternal androgen concentrations or umbilical cord androgen concentrations and digit ratio in adolescence were observed. These findings suggest that variation in 2D:4D in girls is not established as a result of testosterone concentrations in the second and third trimesters. We conclude that prenatal androgen exposure as measured by maternal circulating androgen concentrations at 18 and 34/36 weeks of gestation or in the umbilical cord at birth may not predict digit ratio in girls.
Prenatal exposure to testosterone has been shown to affect fetal brain maturation as well as post... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;pragmatic language&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;) 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, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;free&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;extreme male-brain&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; theory of autism.
ABSTRACT BACKGROUND: The goal of the current study was to investigate asthma and mental health am... more ABSTRACT BACKGROUND: The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link. Method Data were drawn from the Raine Study, a population-based birth cohort study in Western Australia. Logistic regression models and generalized estimating equations were used to examine the relationship between asthma at age 5 years and the range of internalizing and externalizing mental health problems at ages 5-17 years. Analyses were stratified by asthma severity and persistence, and adjusted for a range of potential confounders. RESULTS: More severe and persistent asthma at age 5 was associated with significantly increased odds of affective, anxiety, somatic, oppositional defiant and conduct problems at ages 5-17. Mild asthma and remitted asthma were not associated with heightened vulnerability to mental disorders. CONCLUSIONS: Our results suggest that youth with symptomatic asthma are more likely to suffer from a wide range of mental health problems, and that the likelihood of mental health problems appears to increase as a function of asthma severity. Youth with poorly controlled and/or more severe and persistent asthma may be considered a vulnerable group who might benefit from mental health screening in clinical, school and community settings.
To examine whether maternal gestational hypertension and preeclampsia are associated with behavio... more To examine whether maternal gestational hypertension and preeclampsia are associated with behavioral problems in offspring throughout childhood and early adolescence. We conducted a prospective cohort study of 2804 women in the Western Australian Pregnancy Cohort Study and their children observed at age 2, 5, 8, 10, and 14 years. The Child Behavior Checklist (CBCL) was used to measure problem child behavior with continuous z-scores and clinical cutoff points. Control variables included known biomedical, sociodemographic, and psychological factors. After adjustment, with general linear model analyses children of women with gestational hypertension were shown to be more likely to have higher CBCL z-scores, indicative of poorer behavior, from 8 years on, with the largest difference seen at 14 years. Children of mothers with preeclampsia were more likely to have lower CBCL z-scores, indicative of pro-social behaviors. The multivariable logistic regression analysis showed that gestational hypertension was predictive of clinically significant CBCL T-scores from age 8 to 14 years. This association was significant for externalizing behavior, such as delinquent and aggressive behavior, and for internalizing behavior at age 14 years. Unexpectedly, preeclampsia reduced internalizing morbidity at ages 5 and 8 years. The opposing effect on child and adolescent behavior of gestational hypertension and preeclampsia warrants further attention.
This article investigates whether reading and writing skills among children of equivalent perinat... more This article investigates whether reading and writing skills among children of equivalent perinatal characteristics differ by neighbourhood socioeconomic status and maternal factors. Notifications of births for all non-Aboriginal singletons born in 1990-7 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. 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. These findings suggest that having suboptimal growth in utero or an 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.
Background: Methodological challenges such as confounding have made the study of the early determ... more 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.
Background: Preliminary evidence suggests that prenatal testosterone exposure may be associated w... more 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 timepoints. 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.
adolescents highlighted the complexities by condemning and supporting the idea of young parenthoo... more adolescents highlighted the complexities by condemning and supporting the idea of young parenthood. They also exemplified their unique developmental stage, specifically the abstract nature of future plans, with only one individual acknowledging the long-term impact and "close[d] opportunities" of adolescent parenthood. The discussions of peer pressure and advice suggest that adolescents may be useful partners in changing the environment to be supportive of delayed childbearing. However, structural changes need to occur to support this change, for instance improving youth friendly clinical services and providing more opportunities for adult-youth interaction to nourish growth and development for Baltimore's youth.
To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk fact... more To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk factors throughout childhood. This study utilized cross-sectional and longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study (n = 2900). Aggressive behaviour scores were derived from the Child Behavior Checklist/4-18(CBCL), Youth Self-Report/11-18 (YSR) and Teacher Report Form/6-18 (TRF). CVD risk factors included body mass index (BMI), blood pressure, fasting lipids and homeostasis model of insulin resistance (HOMA-IR). Girls with higher aggressive behaviour scores had higher BMI from 10 years of age (P ≤ 0.001), higher BMI trajectories throughout childhood (P = 0.0003) and at 14 years higher HOMA-IR (P = 0.008). At the 14-year survey, this equated to a difference of 1.7 kg/m2 in the predicted BMI between the extreme CBCL scores in girls (top 5% (CBCL ≥ 17) vs. CBCL score = 0). Boys with higher aggressive behaviour scores had higher BMI at 5 years (P = 0.002), lower diastolic pressure at 14 years (P = 0.002) and lower systolic blood pressure trajectories throughout childhood (P = 0.016). Aggressive behaviour influences BMI from early childhood in girls but not boys. If this association is causal, childhood offers the opportunity for early behavioural intervention for obesity prevention.
Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a hi... more 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.
Antenatal testosterone exposure influences fetal neurodevelopment and gender-role behavior in pos... more 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.
Background: Increased prenatal testosterone exposure has been hypothesized as a mechanism underly... more 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.
To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk fact... more To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk factors throughout childhood. This study utilized cross-sectional and longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study (n = 2900). Aggressive behaviour scores were derived from the Child Behavior Checklist/4-18(CBCL), Youth Self-Report/11-18 (YSR) and Teacher Report Form/6-18 (TRF). CVD risk factors included body mass index (BMI), blood pressure, fasting lipids and homeostasis model of insulin resistance (HOMA-IR). Girls with higher aggressive behaviour scores had higher BMI from 10 years of age (P ≤ 0.001), higher BMI trajectories throughout childhood (P = 0.0003) and at 14 years higher HOMA-IR (P = 0.008). At the 14-year survey, this equated to a difference of 1.7 kg/m2 in the predicted BMI between the extreme CBCL scores in girls (top 5% (CBCL ≥ 17) vs. CBCL score = 0). Boys with higher aggressive behaviour scores had higher BMI at 5 years (P = 0.002), lower diastolic pressure at 14 years (P = 0.002) and lower systolic blood pressure trajectories throughout childhood (P = 0.016). Aggressive behaviour influences BMI from early childhood in girls but not boys. If this association is causal, childhood offers the opportunity for early behavioural intervention for obesity prevention.
Early first sexual intercourse (FSI) is a risk factor for unplanned teenage pregnancy, sexually t... more 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. 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. 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 th...
Digit ratio (2D:4D) is widely used as a marker of prenatal androgen exposure. However, there are ... more Digit ratio (2D:4D) is widely used as a marker of prenatal androgen exposure. However, there are no published prospective studies where prenatal androgen exposure has been measured and correlated with digit ratio in adult life. We aimed to establish the prospective relationship between prenatal androgen exposure in the second and third trimesters of pregnancy (as measured by maternal circulating androgen concentrations and umbilical cord androgen concentrations) and digit ratio in adolescent girls. Androgen concentrations (testosterone, free androgen index, androstenedione, DHEAS) and sex hormone binding globulin (SHBG) were measured in stored plasma samples from pregnant mothers at 18 (n=118) and 34/36 (n=114) weeks of gestation and in cord blood (n=82) from the Western Australian Pregnancy (Raine) Cohort Study (www.rainestudy.org.au). Digit ratio was measured in 244 female offspring from this cohort at age 14-16 years. Only one borderline statistically significant correlation between maternal circulating androstenedione levels at 18 weeks of gestation and left hand digit ratio was seen. No other statistically significant relationship between maternal androgen concentrations or umbilical cord androgen concentrations and digit ratio in adolescence were observed. These findings suggest that variation in 2D:4D in girls is not established as a result of testosterone concentrations in the second and third trimesters. We conclude that prenatal androgen exposure as measured by maternal circulating androgen concentrations at 18 and 34/36 weeks of gestation or in the umbilical cord at birth may not predict digit ratio in girls.
Prenatal exposure to testosterone has been shown to affect fetal brain maturation as well as post... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;pragmatic language&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;) 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, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;free&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;extreme male-brain&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; theory of autism.
ABSTRACT BACKGROUND: The goal of the current study was to investigate asthma and mental health am... more ABSTRACT BACKGROUND: The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link. Method Data were drawn from the Raine Study, a population-based birth cohort study in Western Australia. Logistic regression models and generalized estimating equations were used to examine the relationship between asthma at age 5 years and the range of internalizing and externalizing mental health problems at ages 5-17 years. Analyses were stratified by asthma severity and persistence, and adjusted for a range of potential confounders. RESULTS: More severe and persistent asthma at age 5 was associated with significantly increased odds of affective, anxiety, somatic, oppositional defiant and conduct problems at ages 5-17. Mild asthma and remitted asthma were not associated with heightened vulnerability to mental disorders. CONCLUSIONS: Our results suggest that youth with symptomatic asthma are more likely to suffer from a wide range of mental health problems, and that the likelihood of mental health problems appears to increase as a function of asthma severity. Youth with poorly controlled and/or more severe and persistent asthma may be considered a vulnerable group who might benefit from mental health screening in clinical, school and community settings.
To examine whether maternal gestational hypertension and preeclampsia are associated with behavio... more To examine whether maternal gestational hypertension and preeclampsia are associated with behavioral problems in offspring throughout childhood and early adolescence. We conducted a prospective cohort study of 2804 women in the Western Australian Pregnancy Cohort Study and their children observed at age 2, 5, 8, 10, and 14 years. The Child Behavior Checklist (CBCL) was used to measure problem child behavior with continuous z-scores and clinical cutoff points. Control variables included known biomedical, sociodemographic, and psychological factors. After adjustment, with general linear model analyses children of women with gestational hypertension were shown to be more likely to have higher CBCL z-scores, indicative of poorer behavior, from 8 years on, with the largest difference seen at 14 years. Children of mothers with preeclampsia were more likely to have lower CBCL z-scores, indicative of pro-social behaviors. The multivariable logistic regression analysis showed that gestational hypertension was predictive of clinically significant CBCL T-scores from age 8 to 14 years. This association was significant for externalizing behavior, such as delinquent and aggressive behavior, and for internalizing behavior at age 14 years. Unexpectedly, preeclampsia reduced internalizing morbidity at ages 5 and 8 years. The opposing effect on child and adolescent behavior of gestational hypertension and preeclampsia warrants further attention.
This article investigates whether reading and writing skills among children of equivalent perinat... more This article investigates whether reading and writing skills among children of equivalent perinatal characteristics differ by neighbourhood socioeconomic status and maternal factors. Notifications of births for all non-Aboriginal singletons born in 1990-7 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. 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. These findings suggest that having suboptimal growth in utero or an 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.
Background: Methodological challenges such as confounding have made the study of the early determ... more 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.
Background: Preliminary evidence suggests that prenatal testosterone exposure may be associated w... more 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 timepoints. 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.
adolescents highlighted the complexities by condemning and supporting the idea of young parenthoo... more adolescents highlighted the complexities by condemning and supporting the idea of young parenthood. They also exemplified their unique developmental stage, specifically the abstract nature of future plans, with only one individual acknowledging the long-term impact and "close[d] opportunities" of adolescent parenthood. The discussions of peer pressure and advice suggest that adolescents may be useful partners in changing the environment to be supportive of delayed childbearing. However, structural changes need to occur to support this change, for instance improving youth friendly clinical services and providing more opportunities for adult-youth interaction to nourish growth and development for Baltimore's youth.
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Papers by E. Mattes