The relationship between abdominal pain and emotional wellbeing in children and adolescents in the Raine Study

Abdominal pain is a common reason for medical visits. We examined the prevalence, gastrointestinal, and emotional significance of abdominal pain in a population-based cohort serially followed up from birth to 17 years. Children and adolescents from Generation 2 of the Raine Study participated in comprehensive cross-sectional assessments at ages 2, 5, 8, 10, 14 and 17 years. At 17 years, medical history, general health, gastrointestinal symptoms, medications, health practitioner attendance, and self-rated unhappiness were recorded. Longitudinal data regarding abdominal pain or unhappiness, from serial questionnaires, were analysed to identify factors associated with abdominal pain and adverse emotional health at age 17 years. Females experienced more abdominal pain than males at all ages (p \u3c 0.05). Seventeen-year-old adolescents with abdominal pain reported a higher prevalence of depression, anxiety, being bullied at school, and poorer health status than those without abdominal pain (p \u3c 0.05 for all). Abdominal pain and unhappiness during childhood and mid-adolescence were prospectively associated with recurrent abdominal pain, anxiety, depression and unhappiness during late adolescence (p \u3c 0.05 for all). In conclusion, abdominal pain in children and adolescents associates with depression, anxiety, being bullied, unhappiness and reduced overall health-rating during adolescence. Awareness of these factors may guide management decisions

The relationship between abdominal pain and emotional wellbeing in children and adolescents in the Raine Study

Abdominal pain is a common reason for medical visits. We examined the prevalence, gastrointestinal, and emotional significance of abdominal pain in a population-based cohort serially followed up from birth to 17 years. Children and adolescents from Generation 2 of the Raine Study participated in comprehensive cross-sectional assessments at ages 2, 5, 8, 10, 14 and 17 years. At 17 years, medical history, general health, gastrointestinal symptoms, medications, health practitioner attendance, and self-rated unhappiness were recorded. Longitudinal data regarding abdominal pain or unhappiness, from serial questionnaires, were analysed to identify factors associated with abdominal pain and adverse emotional health at age 17 years. Females experienced more abdominal pain than males at all ages (p \u3c 0.05). Seventeen-year-old adolescents with abdominal pain reported a higher prevalence of depression, anxiety, being bullied at school, and poorer health status than those without abdominal pain (p \u3c 0.05 for all). Abdominal pain and unhappiness during childhood and mid-adolescence were prospectively associated with recurrent abdominal pain, anxiety, depression and unhappiness during late adolescence (p \u3c 0.05 for all). In conclusion, abdominal pain in children and adolescents associates with depression, anxiety, being bullied, unhappiness and reduced overall health-rating during adolescence. Awareness of these factors may guide management decisions

Utility of hepatic or total body iron burden in the assessment of advanced hepatic fibrosis in HFE hemochromatosis

Development of advanced hepatic fibrosis in HFE Hemochromatosis (HH) is influenced by hepatic iron concentration (HIC) and age. In patients with HH, it is important to assess the likelihood of cirrhosis and thus the need for confirmatory liver biopsy. Therapeutic phlebotomy also provides an estimate of mobilisable iron stores. We determined whether mobilisable iron stores may predict the presence of advanced fibrosis. Retrospective analysis of 137 male and 65 female HH subjects was undertaken. Biochemical, histological and phlebotomy data were available on all subjects. The mean values of HIC, HIC × [age], mobilisable iron, mobilisable iron × [age] and serum ferritin in the cohort were higher in the group with advanced fibrosis. HIC had an optimum sensitivity and specificity of 73% for the diagnosis of advanced liver fibrosis, with a cut-off HIC level of 200 µmol/g (AUROC 0.83, p \u3c 0.0001). AUROC for HIC was greater in females (0.93) than males (0.79). Mobilisable iron had an optimum sensitivity and specificity both of 83% at a cut-off of 9.6 g for the prediction of advanced fibrosis in all subjects (AUROC 0.92, p \u3c 0.0001). Mobilisable iron stores provide a simple, clinically useful indication of the risk of advanced fibrosis and should routinely be considered

Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents

Background & Aims: Remnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors. Methods: Adolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed. Results: NAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR. Conclusions: There is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk. Lay summary: Remnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease

Prospective dietary polyunsaturated fatty acid intake is associated with trajectories of fatty liver disease: An 8 year follow-up study from adolescence to young adulthood

Background and aim: Dietary fat intake has long been associated with fatty liver. Our study aimed to determine the effect of dietary fats on longitudinal fatty liver index (FLI) trajectories from adolescence to young adulthood. Methods: Nine hundred eighty-five participants in the Raine Study, Perth, Western Australia, Australia, had cross-sectional assessments at ages 14, 17, 20 and 22 years, during which anthropometric measurements and blood tests were obtained. FLI trajectories were derived from the longitudinal FLI results. Dietary fat intake was measured with a semi-quantitative food frequency questionnaire at 14 years and log multinominal regression analyses were used to estimate relative risks. Results: Three FLI trajectories were identified and labelled as stable-low (79.1%, N = 782), low-to-high (13.9%, N = 132), and stable-high (7%, N = 71). The low-to-high group associated with an increased intake of the long-chain polyunsaturated fatty acids EPA, DPA and DHA (RR 1.27, 95% CI 1.10–1.48) relative to the stable-low group. Compared to the stable-low group, omega-6 and the ratio of omega-6 to omega-3 in the stable-high group were associated with an increased relative risk of 1.34 (95% CI 1.02–1.76) and 1.10 (95% CI 1.03–1.16), respectively. Conclusion: For those at high risk of fatty liver in early adolescence, high omega-6 fatty acid intake and a high ratio of omega-6 to omega-3 fatty acids are associated with increased risk of fatty liver. There should be caution in assuming these associations are causal due to possible undetected and underestimated confounding factors

Insights about Cannabis and Psychosis Using Video Games for Young People with a First Episode of Psychosis, Particularly Those from Black Racialized Communities: Protocol for a Mixed Methods Study

Background: Cannabis use disorder among young people with a first episode of psychosis contributes to relapse, hospitalization, and impaired functioning. However, few studies have examined what young people with early phase psychosis, particularly those from Black racialized communities, understand or appreciate about this relationship, even though they may be at risk. There are no formally tested knowledge translation strategies that disseminate these research findings for young people with emerging psychosis from Black racialized communities. Objective: This study aims to conceptualize what young people with early phase psychosis/cannabis use disorder understand about the relationship between cannabis and psychosis, focusing on people from racialized backgrounds. This study also aims to assess whether the knowledge translation product, the “Back to Reality Series,” increases awareness of the impact of cannabis use on psychosis from the perspectives of young people with emerging psychosis and cannabis use disorder from Black African and Caribbean communities. Methods: Qualitative analysis will reveal themes from qualitative interviews about cannabis and psychosis from the perspectives of young people with emerging psychosis and cannabis use disorder from Black African and Caribbean communities. Perceptions before and after exposure to the Back to Reality Series will be qualitatively analyzed. A control game will be used for comparison, and scores on a quiz after playing the Back to Reality Series will be quantitatively analyzed to establish whether the Back to Reality Series raises awareness of the effects of cannabis on psychosis. An advisory council involving young people from Black communities, family members, and clinicians will bring community perspectives to this research. Results: We began recruiting participants for this study in September 2021. We will complete data collection on demographic and clinical factors, qualitative interviews, and quantitative assessments of the Back to Reality Series. Conclusions: The voices of young people from racialized backgrounds will generate preliminary data to inform early psychosis programs, addressing cannabis use in this population. The findings may advance the use of a new knowledge translation product that deals with gaps in knowledge about cannabis use for people experiencing early phase psychosis, particularly those from racialized communities

Comparison of the cardiometabolic profiles of adolescents conceived through ART with those of a non-ART cohort

STUDY QUESTION Is the cardiometabolic health of adolescents conceived through ART worse than that of their counterparts conceived without ART? SUMMARY ANSWER The majority of cardiometabolic and vascular health parameters of adolescents conceived through ART are similar or more favourable, than those of their counterparts of similar age and conceived without ART. WHAT IS KNOWN ALREADY It has been proposed that the cardiometabolic health of offspring conceived with ART may be unfavourable compared to that of their counterparts conceived without ART. The literature pertaining to cardiometabolic health of offspring conceived after ART is contradictory, but generally suggests unfavourable cardiometabolic health parameters, such as an increase in blood pressure (BP), vascular dysfunction and adiposity, as well as unfavourable glucose and lipid profiles. With over 8 million children and adults born through ART worldwide, it is important to investigate whether these early signs of adverse cardiometabolic differences persist into adolescence and beyond. STUDY DESIGN, SIZE, DURATION The Growing Up Healthy Study (GUHS) is a prospective cohort study that recruited 303 adolescents and young adults conceived after ART (aged 13–21 years) and born between 1991 and 2001 in Western Australia. Their health parameters, including cardiometabolic factors, were assessed and compared with counterparts from the Raine Study Generation 2 (Gen2). The 2868 Gen2 participants were born 1989–1992 and are representative of the Western Australian adolescent population. At ∼17 years of age (2013–2017), 163 GUHS participants replicated assessments previously completed by Gen2 at a similar age. PARTICIPANTS/MATERIALS, SETTING, METHODS Cardiometabolic parameters were compared between a total of 163 GUHS and 1457 Gen2 adolescents. Separate male (GUHS n = 81, Gen2 n = 735) and female (GUHS n = 82, Gen2 n = 722) analyses were conducted. Assessments consisted of a detailed questionnaire including health, lifestyle and demographic parameters, anthropometric assessments (height, weight, BMI, waist circumference and skinfold thickness), fasting serum biochemistry, arterial stiffness and BP (assessed using applanation tonometry). Abdominal ultrasonography was used to assess the presence and severity of hepatic steatosis, and thickness of abdominal fat compartments. Non-alcoholic fatty liver disease (NAFLD) was diagnosed if there was sonographic fatty liver in the absence of significant alcohol consumption. Chi2, Fisher’s exact and Mann–Whitney U tests, performed in SPSS V25, examined cohort differences and generalized estimating equations adjusted for the following covariates: singleton vs non-singleton pregnancy, birthweight (z-score), gestational age, BMI, smoking, alcohol consumption in the past 6 months and parent cardiovascular status. Arterial stiffness measures and waist circumference were additionally adjusted for height, and female analyses were additionally adjusted for use of oral contraceptives in the preceding 6 months. MAIN RESULTS AND THE ROLE OF CHANCE In adjusted analyses, GUHS females had a lower BMI (22.1 vs 23.3 kg/m2, P = 0.014), and thinner skinfolds (triceps, subscapular, mid-abdominal; 16.9 vs 18.7 mm, P = 0.021, 13.4 vs 15.0 mm, P = 0.027, 19.7 vs 23.2 mm, P < 0.001, respectively), whereas males were not significantly different. Waist circumference was lower in GUHS adolescents (males: 78.1 vs 81.3 cm, P = 0.008, females: 76.7 vs 83.3 cm, P = 0.007). There were no significant differences between the two groups in glucose, insulin, homeostatic model assessment for insulin resistance, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), alanine aminotransferase and high-sensitivity C-reactive protein in both sexes. In females, serum triglycerides were lower in GUHS adolescents (1.0 vs 1.2 mmol/l, P = 0.029). GUHS males had higher serum HDL-C (1.1 vs 1.0 mmol/l, P = 0.004) and a lower TC/HDL-C ratio (3.2 vs 3.6, P = 0.036). There were no significant differences in the prevalence of NAFLD or steatosis severity scores between the cohorts in males and females. GUHS females had less subcutaneous adipose tissue (9.4 vs 17.9 mm, P < 0.001), whereas GUHS males had greater visceral adipose thickness (44.7 vs 36.3 mm, P < 0.001). There was no significant difference in pre-peritoneal adipose thickness. Pulse wave velocity was lower in GUHS males (5.8 vs 6.3 m/s, P < 0.001) and heart rate corrected augmentation index was lower in GUHS females (−8.4 vs −2.7%, P = 0.048). There were no significant differences in BP or heart rate in males or females between the two groups. LIMITATIONS, REASONS FOR CAUTION Despite the substantial study size and the unique study design of the ART cohort, we were unable to differentiate between different types of ART, due to the low number of ICSI cycles (e.g. IVF vs ICSI), draw definite conclusions, or relate the outcomes to the cause of infertility. Considering the differences in time points when both cohorts were studied, external factors could have changed, which could not be accounted for. Given the observational nature of this study, causation cannot be proven. WIDER IMPLICATIONS OF THE FINDINGS Contrary to our hypothesis and previous findings focussing mainly on childhood, this study reports mostly similar or favourable cardiometabolic markers in adolescents conceived with ART compared to those conceived without ART. The greater visceral adipose thickness, particularly present in males, requires further investigation. While these findings are generally reassuring, future well-designed and appropriately powered studies are required to definitively address the issue of cardiometabolic health in ART adults. STUDY FUNDING/COMPETING INTEREST(S) This project was supported by NHMRC project grant number 1042269 and R.J.H. received education grant funding support from Ferring Pharmaceuticals. R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director of PIVET Medical Centre, Perth, Western Australia

Associations between prenatal exposure to phthalates and features of the metabolic syndrome in males from childhood into adulthood

Phthalate metabolites are detectable within the majority of the population. Evidence suggests that a prenatal exposure to phthalates may be associated with the subsequent risks of obesity and elevated blood pressure. We hypothesised that a prenatal exposure to phthalates would lead to an increase in adverse cardiometabolic parameters through childhood and adulthood. The maternal serum phthalate measurements from the stored samples taken from Gen1 mothers at 18 and 34 weeks gestation were examined in relation to the cardiometabolic measures in 387 male offspring from the Raine Study. Data from the Gen2 follow-ups between 3 and 27 years were used. The primary outcomes were analysed longitudinally using linear mixed models for the repeated measures. Non-alcoholic fatty liver disease (NAFLD) was assessed at 17 years using logistic regression. A consistent positive relationship was observed between a prenatal exposure to mono-carboxy-iso-octyl phthalate (MCiOP) through adolescence into adulthood with systolic blood pressure. There were no other consistent cardiovascular associations. Mid-levels of prenatal exposures to Mono-n-butyl phthalate (MnBP) were associated with a greater incidence of NAFLD. Detectable Mono-3-carboxypropyl phthalate (MCPP) was associated with a lower serum HDL-C through late childhood into adulthood, while a higher prenatal exposure to mono-iso-butyl phthalate (MiBP), was associated with a higher LDL-C at 22 years of age. A mid-level prenatal exposure to mono-2-ethylhexyl phthalate (MEHP) metabolites was associated with higher insulin in adulthood, while a higher prenatal exposure to the sum of the Di-(2-ethyl-hexyl) phthalate (DEHP) and Di-iso-nonyl phthalate (DiNP) metabolites was associated with higher fasting serum glucose in adulthood. In conclusion, our study demonstrated that higher prenatal phthalate exposures to some phthalate metabolites was associated with some adverse metabolic profiles through adolescence into adulthood, although the consistent themes were limited to a few metabolites and the outcomes of systolic blood pressure, fasting insulin and glucose