Epidemiology of prenatal alcohol use and fetal alcohol spectrum disorder

Prenatal alcohol exposure (PAE) can lead to fetal alcohol spectrum disorder (FASD). FASD refers to a range of lifelong conditions caused by PAE, characterised by a distinctive facial phenotype, growth deficiencies and/or neurobehavioural impairments. This thesis presents four studies that I conducted to address knowledge gaps relevant to the epidemiology of PAE and FASD. First, objective measures of PAE are essential for identifying children at risk of adverse outcomes. Biomarkers have been advocated for use in universal PAE screening programs but their validity had not been comprehensively evaluated. I conducted a systematic review and found that biomarker test performance varied widely across studies. The quality of published studies was low, resulting in insufficient evidence to support the use of objective measures of PAE in practice. Second, the prevalence of FASD in the UK was unknown. Active case ascertainment studies have not been possible due to funding and ethical issues. To overcome these issues, I developed an algorithm to estimate FASD prevalence using existing data from a population-based birth cohort in England (ALSPAC). Up to 17% of children met criteria for FASD, indicating that it is a significant public health concern. Third, although PAE is the sole necessary cause of FASD, it is not always sufficient. Understanding risk factors for FASD is important for informing prevention strategies. However, existing studies have mostly been limited to discussion of association, rather than causation. I produced a causal diagram to depict hypothesised causal pathways to FASD. I used this diagram to guide analyses in a FASD risk factor study, reported below. Finally, I investigated FASD risk factors using multivariable logistic regression within the ALSPAC cohort. Prenatal stress, smoking and mental health problems increased the odds of FASD. Social support and folic acid supplementation were protective. These results indicate novel potential targets for FASD intervention

Pharmacological interventions for challenging behaviour in children with intellectual disabilities: a systematic review and meta-analysis

Background Psychotropic medications are frequently used to treat challenging behaviour in children with intellectual disabilities, despite a lack of evidence for their efficacy. This systematic review and meta-analysis aimed to determine the safety and efficacy of pharmacological interventions for challenging behaviour among children with intellectual disabilities. Methods Electronic databases were searched and supplemented with a hand search of reference lists and trial registries. Randomised controlled trials of pharmacological interventions for challenging behaviour among children with intellectual disabilities were included. Data were analysed using meta-analysis or described narratively if meta-analysis was not possible. For quality assessment, the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were used. Results Fourteen studies including 912 participants met inclusion criteria. Antipsychotic medication reduced challenging behaviour among children with intellectual disabilities in the short-term (SMD = −1.09, p < 0.001 for risperidone; SMD = −0.64, p <0.001 for aripiprazole). However, there were significant side-effects including elevated prolactin levels (SMD = 3.22, p < 0.001) and weight gain (SMD = 0.82, p < 0.001). Evidence was inconclusive regarding the effectiveness of anticonvulsants and antioxidants for reducing challenging behaviour. The quality of all evidence was low and there were no long term follow up studies. Conclusions Antipsychotic medications appear to be effective for reducing challenging behaviour in the short-term among children with intellectual disabilities, but they carry a risk of significant side effects. Findings from this review must be interpreted with caution as studies were typically of low quality and most outcomes were based on a small number of studies. Further long-term, high-quality research is needed to determine the effectiveness and safety of psychotropic medication for reducing challenging behaviour

The causal web of foetal alcohol spectrum disorders : a review and causal diagram

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Objective measures of prenatal alcohol exposure: a systematic review

CONTEXT: Objective measurement of prenatal alcohol exposure (PAE) is essential for identifying children at risk for adverse outcomes, including fetal alcohol spectrum disorders. Biomarkers have been advocated for use in universal screening programs, but their validity has not been comprehensively evaluated. OBJECTIVE: To systematically review the validity of objective measures of PAE. DATA SOURCES: Thirteen electronic databases and supplementary sources were searched for studies published between January 1990 and October 2015. STUDY SELECTION: Eligible studies were those that evaluated the diagnostic accuracy of objective measures of PAE. DATA EXTRACTION: Three reviewers independently verified study inclusion, quality assessments, and extracted data. RESULTS: Twelve studies met inclusion criteria. Test performance varied widely across studies of maternal blood (4 studies; sensitivity 0%–100%, specificity 79%–100%), maternal hair (2 studies; sensitivity 19%–87%, specificity 56%–86%) maternal urine (2 studies; sensitivity 5%–15%, specificity 97%–100%), and biomarker test batteries (3 studies; sensitivity 22%–50%, specificity 56%–97%). Tests of the total concentration of 4 fatty acid ethyl esters (in meconium: 2 studies; in placenta: 1 study) demonstrated high sensitivity (82%–100%); however, specificity was variable (13%–98%). LIMITATIONS: Risk of bias was high due to self-report reference standards and selective outcome reporting. CONCLUSIONS: Current evidence is insufficient to support the use of objective measures of prenatal alcohol exposure in practice. Biomarkers in meconium and placenta tissue may be the most promising candidates for further large-scale population-based research

Conceptualising natural and quasi experiments in public health

Background: Natural or quasi experiments are appealing for public health research because they enable the evaluation of events or interventions that are difficult or impossible to manipulate experimentally, such as many policy and health system reforms. However, there remains ambiguity in the literature about their definition and how they differ from randomised controlled experiments and from other observational designs. Methods: We conceptualise natural experiments in in the context of public health evaluations, align the study design to the Target Trial Framework, and provide recommendation for improvement of their design and reporting. Results: Natural experiment studies combine features of experiments and non-experiments. They differ from RCTs in that exposure allocation is not controlled by researchers while they differ from other observational designs in that they evaluate the impact of event or exposure changes. As a result they are, in theory, less susceptible to bias than other observational study designs. Importantly, the strength of causal inferences relies on the plausibility that the exposure allocation can be considered "as-if randomised". The target trial framework provides a systematic basis for assessing the plausibility of such claims, and enables a structured method for assessing other design elements. Conclusions: Natural experiment studies should be considered a distinct study design rather than a set of tools for analyses of non-randomised interventions. Alignment of natural experiments to the Target Trial framework will clarify the strength of evidence underpinning claims about the effectiveness of public health interventions.Comment: 28 pages, 1 figure, 1 table, 1 supplementary tabl

Association between cigarette smoking status and voting intentions:Cross sectional surveys in England 2015-2020

Background and aims: Cigarette smoking takes place within a cultural and social context. Political views and practices are an important part of that context. To gain a better understanding of smoking, it may be helpful to understand its association with voting patterns as an expression of the political views and practices of the population who smoke. This study aimed to assess the association between cigarette smoking and voting intentions and to examine how far any association can be explained by sociodemographic factors and alcohol use. Methods: Pooled monthly representative repeat cross-sectional household surveys of adults (16+) in England (N = 55,482) between 2015 and 2020 were used to assess the association between cigarette smoking status and voting intentions, and whether this was accounted for by age, occupational grade, gender, region and alcohol use. Voting intention was measured by asking ‘How would you vote if there were a General Election tomorrow?’ Respondents chose from a list of the major English political parties or indicated their intention not to vote. Results: In adjusted multinomial regression, compared with intending to vote Conservative (majority party of government during the period), being undecided (aOR1.22 [1.13-1.33] <0.001), intending to vote Labour (aOR1.27 [1.16-1.36] <0.001), to vote “Other” (aOR1.54 [1.37-1.72] <0.001), or not to vote (aOR1.93 [1.77-2.11] <0.001) was associated with higher odds of current relative to never smoking rates. Intending to vote for the Liberal Democrats was associated with a significant lower odds of current smoking prevalence (aOR0.80 [0.70-0.91] <0.001) compared with intending to vote Conservative. Conclusions: Controlling for a range of other factors, current as compared with never-smokers appear more likely to intend not to vote, to be undecided, to vote for Labour or a non-mainstream party, and less likely to vote for the Liberal Democrats, compared with the Conservative party

Screening prevalence of fetal alcohol spectrum disorders in a region of the United Kingdom: a population-based birth-cohort study

We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. This study was funded by a doctoral studentship from Cardiff University (awarded to CM). The UK Medical Research Council and Wellcome Trust (Grant ref.: 102215/2/13/2) and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). Funding for the facial scan data was provided by Cardiff University.Peer reviewedPublisher PD