Eugen Mattes

Pre- and postnatal influences on preschool mental health: a large-scale cohort study.

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Behaviour Checklist (CBCL) was used to measure child mental health with clinical cut-points, including internalising (withdrawn/depressed) and externalising (aggressive/destructive) behaviours (n = 1707).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 childs later environment. Interventions targeting adverse prenatal, perinatal and postnatal influences can be expected to improve mental health outcomes for children in the early years.

Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors.

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), Δ4-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.

Hypertensive diseases of pregnancy and the development of behavioral problems in childhood and adolescence: the Western Australian Pregnancy Cohort Study.

OBJECTIVE To examine whether maternal gestational hypertension and preeclampsia are associated with behavioral problems in offspring throughout childhood and early adolescence. STUDY DESIGN 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. RESULTS 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. CONCLUSIONS The opposing effect on child and adolescent behavior of gestational hypertension and preeclampsia warrants further attention.

Maternal mood scores in mid-pregnancy are related to aspects of neonatal immune function

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 3.7 g/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 > or =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.

Smoking cessation in pregnancy and the risk of child behavioural problems: a longitudinal prospective cohort study

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.

Social determinants of child health and well-being

Strong associations between socioeconomic status, measured by such factors as level of education, income, and occupational status, greater access to resources and political power, and an individuals health and well-being are well established and evident throughout the whole life course. Clearly, social factors are fundamental elements of the causal pathways to ill health and disease (Link and Phelan 1995; Marmot and Wilkinson 1999; CSDH 2008) and indirectly through their impact on early child development. Hence they also influence our current and future wealth (Keating and Hertzman 1999). With the growing evidence of the impact of social inequalities on health, policy makers in all countries are showing an increased interest in understanding them and in seeking ways to create more equitable societies. The importance of this trend is charted in two editions of Social Determinants of Health by Michael Marmot and Richard Wilkinson (1999, 2006), the establishment of the Commission on the Social Determinants of Health (CSDH) by the World Health Organisation (WHO), the CSDH Final Report (CSDH 2008), governmental initiatives to tackle health inequalities (the UK Department of Health 2005; EUROTHINE 2007; the Ministry of Social Affairs and Health - Helsinki Finland 2008; The UN Special Rapporteur 2008) and the proliferation of scholarly publications on social inequity in health in leading journals, such as The Lancet, British Medical Journal, Social Science and Medicine, The New England Journal of Medicine, the International Journal of Epidemiology, American Journal of Public Health and Journal of Epidemiology and Community Health.Research on the social determinants of health has moved beyond the initial stage of simplistic descriptions of diseases and illness patterns by socio-economic status (Townsend and Davidson 1982; Acheson et al 1998; Marmot et al 1991; Marmot and Wilkinson 1999, to cite just a few), to a quest for deeper knowledge of what might be the complex mechanisms that underpin the commonly observed social disparities and gradients in health from both theoretical and empirical approaches (Berkman and Kawachi 2000; Kelly et al 2006; Eckersley et al 2001; Spencer 2006; Thrane 2006). While it is accepted that social gradients and disparity in health are universal and strong, there is less agreement as to what might explain them. Three dominant perspectives offering different explanations exist (Thrane 2006; Turrell 2001; Taylor 2001; Raphael 2002): materialistic explanations, psychosocial perspectives (Marmot and Wilkinson 1999; Marmot 2004; Kawachi et al 1997, 1999) and life style explanations.According to the materialistic explanations, social disparities and gradients in health stem from differential access to economic and social resources that enable healthy living, and to preventive and curative health care, and differential exposures to occupational hazards and unhealthy living environments. The psychosocial explanation emphasises social support, social capital and perceived and relative income inequality as the main causes of health inequality. The life style perspective sees different life style choices individuals make, such as smoking, drinking, diet and exercise, as the primary causes of health inequality (see Raphael 2002; Thrane 2006 for a review). By themselves, none of these explanations can adequately explain the pervasive health inequality so consistently evident cross time and space. The social, economic and behavioural factors highlighted in each of these perspectives may jointly influence, mediate or moderate each other to produce health inequality and there is emerging research that attempts to combine them (Thrane 2006).However, much of the literature on the social determinants of health still lacks a common structural approach to explain universally observed health inequity. Whilst there is some research on the link between childhood social and economic circumstances and adult morbidity and mortality (Davey Smith et al 2001; Osler et al 2003; Pulton et al 2002; Hayward and Gorman 2004), most focus primarily on adult health. …

Maternal and umbilical cord androgen concentrations do not predict digit ratio (2D:4D) in girls: A prospective cohort study

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.

Neurocognitive functioning in adolescents with eating disorders: A population-based study

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.

Severity and persistence of asthma and mental health: a birth cohort study

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.

Perinatal testosterone exposure and autistic-like traits in the general population: a longitudinal pregnancy-cohort study

BackgroundIncreased 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.MethodsUmbilical 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.ResultsThe 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.ConclusionsThese findings indicate that testosterone concentrations from umbilical cord blood are unrelated to autistic-like traits in the general population. However, the findings do not exclude an association between testosterone exposure in early intrauterine life and ASD.