Paediatrics (RCH) - Research Publications
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ItemNo Preview AvailableAdverse experiences in early intimate relationships and next-generation infant-mother attachment: findings from the ATP Generation 3 Study(WILEY, 2023-12)Abstract Chronic insecurities that emerge from adverse experiences in early intimate partner relationships in adolescence and emerging adulthood can have profound impacts on mental health and well‐being. Less clear is the extent to which these experiences for parents impact subsequent relationships within and across generations. We examine the extent to which secure, dismissing, pre‐occupied, and fearful intimate partner relationships in adolescence and emerging adulthood, well before becoming a parent, are associated with next‐generation patterns of attachment between mothers and infant offspring. Data were drawn from a nested study of infant–mother attachment (n = 220) within the Australian Temperament Project Generation 3 Study (N = 1167, est. 1983). Intimate partner relationships in adolescence and young adulthood were assessed by self‐report at 23–24 years of age. Over a decade later, infant–mother attachment security was assessed at 12 months post‐partum. Young adult intimate partner relationships defined by high levels of fearful, pre‐occupied, and dismissing attachment styles were reported in 11%, 17%, and 38% of young mothers, respectively. Increases in fear of intimacy in relationships were associated with an increase in the odds, by around 50%, of infant–mother insecure attachments (vs secure; OR = 1.56, 95% CI = 1.07, 2.28) and disorganised attachments (vs organised; OR = 1.49, 95% CI = 1.00, 2.22). A mother's self‐reported history of fear of intimacy within young adult relationships predicts later insecure and disorganised mother–infant attachments. Guidance and greater support for young people navigating their earliest intimate relationships may not only prevent adverse relational experiences at the time but also on becoming a parent. Findings have relevance for family and infant mental health therapies. Translating these findings into supported conversations may help prevent infant–mother attachment difficulties, or later repair them, through validation of the lingering effects of early fear of intimacy and empowerment of parents to prevent next‐generation infant experiences of distrust.
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ItemEndophenotyping social cognition in the broader autism phenotype(WILEY, 2023-11-30)Relatives of individuals with autism spectrum disorder (ASD) may display milder social traits of the broader autism phenotype (BAP) providing potential endophenotypic markers of genetic risk for ASD. We performed a case-control comparison to quantify social cognition and pragmatic language difficulties in the BAP (n = 25 cases; n = 33 controls) using the Faux Pas test (FPT) and the Goldman-Eisler Cartoon task. Using deep phenotyping we then examined patterns of inheritance of social cognition in two large multiplex families and the spectrum of performance in 32 additional families (159 members; n = 51 ASD, n = 87 BAP, n = 21 unaffected). BAP individuals showed significantly poorer FPT performance and reduced verbal fluency with the absence of a compression effect in social discourse compared to controls. In multiplex families, we observed reduced FPT performance in 89% of autistic family members, 63% of BAP relatives and 50% of unaffected relatives. Across all affected families, there was a graded spectrum of difficulties, with ASD individuals showing the most severe FPT difficulties, followed by the BAP and unaffected relatives compared to community controls. We conclude that relatives of probands show an inherited pattern of graded difficulties in social cognition with atypical faux pas detection in social discourse providing a novel candidate endophenotype for ASD.
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ItemConfounding-adjustment methods for the causal difference in medians(BMC, 2023-12-07)BACKGROUND: With continuous outcomes, the average causal effect is typically defined using a contrast of expected potential outcomes. However, in the presence of skewed outcome data, the expectation (population mean) may no longer be meaningful. In practice the typical approach is to continue defining the estimand this way or transform the outcome to obtain a more symmetric distribution, although neither approach may be entirely satisfactory. Alternatively the causal effect can be redefined as a contrast of median potential outcomes, yet discussion of confounding-adjustment methods to estimate the causal difference in medians is limited. In this study we described and compared confounding-adjustment methods to address this gap. METHODS: The methods considered were multivariable quantile regression, an inverse probability weighted (IPW) estimator, weighted quantile regression (another form of IPW) and two little-known implementations of g-computation for this problem. Methods were evaluated within a simulation study under varying degrees of skewness in the outcome and applied to an empirical study using data from the Longitudinal Study of Australian Children. RESULTS: Simulation results indicated the IPW estimator, weighted quantile regression and g-computation implementations minimised bias across all settings when the relevant models were correctly specified, with g-computation additionally minimising the variance. Multivariable quantile regression, which relies on a constant-effect assumption, consistently yielded biased results. Application to the empirical study illustrated the practical value of these methods. CONCLUSION: The presented methods provide appealing avenues for estimating the causal difference in medians.
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ItemOn the use of multiple imputation to address data missing by design as well as unintended missing data in case-cohort studies with a binary endpoint(BMC, 2023-12-07)BACKGROUND: Case-cohort studies are conducted within cohort studies, with the defining feature that collection of exposure data is limited to a subset of the cohort, leading to a large proportion of missing data by design. Standard analysis uses inverse probability weighting (IPW) to address this intended missing data, but little research has been conducted into how best to perform analysis when there is also unintended missingness. Multiple imputation (MI) has become a default standard for handling unintended missingness and is typically used in combination with IPW to handle the intended missingness due to the case-control sampling. Alternatively, MI could be used to handle both the intended and unintended missingness. While the performance of an MI-only approach has been investigated in the context of a case-cohort study with a time-to-event outcome, it is unclear how this approach performs with a binary outcome. METHODS: We conducted a simulation study to assess and compare the performance of approaches using only MI, only IPW, and a combination of MI and IPW, for handling intended and unintended missingness in the case-cohort setting. We also applied the approaches to a case study. RESULTS: Our results show that the combined approach is approximately unbiased for estimation of the exposure effect when the sample size is large, and was the least biased with small sample sizes, while MI-only and IPW-only exhibited larger biases in both sample size settings. CONCLUSIONS: These findings suggest that a combined MI/IPW approach should be preferred to handle intended and unintended missing data in case-cohort studies with binary outcomes.
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ItemChanging climates, compounding challenges: a participatory study on how disasters affect the sexual and reproductive health and rights of young people in Fiji.(BMJ, 2023-12-16)Pacific youth are at the forefront of the climate crisis, which has important implications for their health and rights. Youth in Fiji currently bear a disproportionate burden of poor experiences and outcomes related to their sexual and reproductive health and rights (SRHR). There is limited information about how the increasing climate impacts may affect their SRHR, and what the implications may be for climate action and disaster risk reduction. We aimed to explore the experiences of 21 Fijian youth in fulfilling their SRHR when living through multiple natural hazards. We conducted 2 workshops and 18 individual semistructured interviews using visual and storytelling methods. Irrespective of the type of hazard or context of disasters, participants identified limited agency as the main challenge that increased SRHR risks. Through reflexive thematic analysis, we identified four themes centred around 'youth SRHR agency'; (1) information and knowledge, (2) community and belonging, (3) needs and resources, and (4) collective risks. These themes encompassed multiple factors that limited youth agency and increased their SRHR risks. Participants highlighted how existing challenges to their SRHR, such as access to SRHR information being controlled by community gatekeepers, and discrimination of sexual and gender diverse youth, were exacerbated in disasters. In disaster contexts, immediate priorities such as water, food and financial insecurity increased risks of transactional early marriage and transactional sex to access these resources. Daily SRHR risks related to normalisation of sexual and gender-based violence and taboos limited youth agency and influenced their perceptions of disasters and SRHR risks. Findings offer important insights into factors that limited youth SRHR agency before, during and after disasters. We underscore the urgency for addressing existing social and health inequities in climate and disaster governance. We highlight four key implications for reducing youth SRHR risks through whole-of-society approaches at multiple (sociocultural, institutional, governance) levels.
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ItemNo Preview AvailableTrusting relationships and learning together: A rapid review of Indigenous reference groups in Australian Indigenous health research(ELSEVIER SCIENCE INC, 2023-06)OBJECTIVE: This rapid review aims to identify how Indigenous research governance is conceptualised, implemented and documented within Australian Indigenous health research studies. METHODS: We searched for peer-reviewed English-language articles in two databases and for web-based grey literature published from database inception to November 2021. Reference lists were searched to identify additional articles. Data relating to research governance were extracted and analysed thematically. RESULTS: A total of 1120 records were screened, and 27 articles were included. Most articles providing detailed description of Indigenous research governance activities were qualitative studies (n=15, 55.6%). Key themes included members are experts; respectful relationships; flexibility; and key logistic considerations (nuts 'n' bolts). CONCLUSIONS: Although Indigenous research governance is recognised as an essential part of ethical research, activities and contributions made by Indigenous reference group (IRG) members are underreported. This important work needs greater visibility in the published literature to share best practice in Indigenous research governance that foregrounds Indigenous expert knowledge, perspectives, and experiences. IMPLICATIONS FOR PUBLIC HEALTH: The study provides a synthesis of factors to consider when establishing and facilitating an IRG for research with Indigenous communities. This has implications for researchers who can adapt and apply the findings to their practice.
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ItemNo Preview AvailableParental Mental Health and Parenting Behaviors Following Very Preterm Birth: Associations in Mothers and Fathers and Implications for Child Cognitive Outcome.(Oxford University Press (OUP), 2023-03-20)OBJECTIVES: To investigate the longitudinal associations between parental mental health symptoms within 4 weeks of birth, parenting behaviors at 1 year, and child general cognitive ability at 4.5-5 years in a sample of children born very preterm (VP). This study also examined whether these associations differed based on level of family social risk. METHODS: Participants were 143 children born <30 weeks' gestation and their parents. Within 4 weeks of birth, mothers' and fathers' depressive and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale and Hospital Anxiety Depression Scale-Anxiety Subscale. Parents' sensitive and structuring parenting behaviors were assessed at 1 year using the Emotional Availability Scales. Child general cognitive ability was assessed at 4.5-5 years using the Wechsler Preschool & Primary Scale of Intelligence-Fourth Edition. RESULTS: Higher maternal depressive symptoms were associated with lower levels of sensitive and structuring parenting behavior, while higher maternal anxiety symptoms were associated with higher levels of structuring parenting behavior. There was weak evidence for positive associations between mothers' sensitive parenting behavior and fathers' structuring parenting behavior and child general cognitive ability. There was also weak evidence for stronger associations between mothers' mental health symptoms, parenting behaviors, and child general cognitive ability, in families of higher compared with lower social risk. CONCLUSIONS: Depressive and anxiety symptoms experienced by mothers in the initial weeks following VP birth can have long-term effects on their parenting behaviors. Enquiring about parents' mental health during their child's hospitalization in the neonatal intensive care unit is crucial.
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ItemNo Preview AvailableAssociation of maternal air pollution exposure and infant lung function is modified by genetic propensity to oxidative stress.(Cold Spring Harbor Laboratory, 2023-10-13)INTRODUCTION: The association between air pollution and poor respiratory health outcomes is well established, however less is known about the biological mechanisms, especially in early life. Children are particularly at risk from air pollution, especially during the prenatal period as their organs and systems are still undergoing crucial development. Therefore, our study aims to investigate if maternal exposure to air pollution during pregnancy is associated with oxidative stress (OS) and inflammation in pregnancy or infant lung function at 4 weeks of age, and the extent to which the association is modified by an infant's genetic risk of OS. METHODS: The Barwon Infant Study (BIS) is a longitudinal study of Australian children from the region of Geelong, Victoria. A total of 314 infants had available lung function and maternal OS markers. Exposure to annual air pollutants (NO 2 and PM 2.5 ) were estimated using validated, satellite-based, land-use regression models. Infant lung function was measured by multiple-breath washout, and the ratio of peak tidal expiratory flow over expiratory time was calculated at 4 weeks of age. An inflammation biomarker, glycoprotein acetyls (GlycA), was measured in maternal (36 weeks) and cord blood, and oxidative stress (OS) biomarkers, 8-hydroxyguanine (8-OHGua) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in maternal urine at 28 weeks. A genetic pathway score for OS (gPFS ox ) was calculated for each infant participant in the BIS cohort, and high risk defined as score >8. Linear regression was used to explore the association of maternal air pollution exposure with infant lung function, and potential modification by OS genotype was tested through use of interaction terms and other methods. RESULTS: There was no evidence of a relationship between maternal exposure to air pollution and infant lung function in the whole population. We did not find an association between air pollution and GlycA or OS during pregnancy. We found evidence of an association between NO 2 and lower in functional residual capacity (FRC) for children with a high genetic risk of OS (β=-5.3 mls, 95% CI (-9.3, -1.3), p=0.01). We also found that when NO 2 was considered in tertiles, the highest tertile of NO 2 was associated with increase in lung clearance index (LCI) (β=0.46 turnovers, (95% CI 0.10, 0.82), p=0.01) in children with a genetic propensity to OS. CONCLUSION: Our study found that high prenatal levels of exposure to ambient NO 2 levels is associated with lower FRC and higher LCI in infants with a genetic propensity to oxidative stress. There was no relationship between maternal exposure to air pollution with maternal and cord blood inflammation or OS biomarkers.
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ItemNo Preview AvailableStuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40(OXFORD UNIV PRESS, 2023-12-01)Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering. We studied a large four-generation family in which persistent stuttering was inherited in an autosomal dominant manner with disruption of the cortico-basal-ganglia-thalamo-cortical network found on imaging. Exome sequencing of three affected family members revealed the PPID c.808C>T (p.Pro270Ser) variant that segregated with stuttering in the family. We generated a Ppid p.Pro270Ser knock-in mouse model and performed ex vivo imaging to assess for brain changes. Diffusion-weighted MRI in the mouse revealed significant microstructural changes in the left corticospinal tract, as previously implicated in stuttering. Quantitative susceptibility mapping also detected changes in cortico-striatal-thalamo-cortical loop tissue composition, consistent with findings in affected family members. This is the first report to implicate a chaperone protein in the pathogenesis of stuttering. The humanized Ppid murine model recapitulates network findings observed in affected family members.
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ItemNo Preview AvailableYouth Participatory Research Needed to Keep Time Ticking Forward(ELSEVIER SCIENCE INC, 2023-12)