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.

Sex-specific associations between umbilical cord blood testosterone levels and language delay in early childhood.

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.

Associations between anxious-depressed symptoms and cardiovascular risk factors in a longitudinal childhood study.

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 0.6 kg/m(2) 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.

Prenatal stress and risk of behavioral morbidity from age 2 to 14 years: the influence of the number, type, and timing of stressful life events.

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.

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.

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 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.

The umbilical vein in the human fetus has a non-linear growth pattern across gestation.

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.

Childhood behavior problems and age at first sexual intercourse: a prospective birth cohort study.

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.

Umbilical cord blood testosterone and childhood internalizing and externalizing behavior: a prospective study.

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.

The association between perinatal testosterone concentration and early vocabulary development: a prospective cohort study.

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.

Analysis of baseline hypothalamic-pituitary-adrenal activity in late adolescence reveals gender specific sensitivity of the stress axis.

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.

Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis.

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.

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.

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

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

Fetal androgen exposure and pragmatic language ability of girls in middle childhood: implications for the extreme male-brain theory of autism.

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.

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.

Predicting commercial success for Australian medical inventions patented in the United States: a cross sectional survey of Australian inventors.

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.