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 randomized controlled experiments and from other observational designs. We conceptualise natural experiments in the context of public health evaluations and align the study design to the Target Trial Framework.Methods: A literature search was conducted, and key methodological papers were used to develop this work. Peer-reviewed papers were supplemented by grey literature.Results: Natural experiment studies (NES) combine features of experiments and non-experiments. They differ from planned experiments, such as randomized controlled trials, in that exposure allocation is not controlled by researchers. They differ from other observational designs in that they evaluate the impact of events or process that leads to differences in exposure. As a result they are, in theory, less susceptible to bias than other observational study designs. Importantly, causal inference relies heavily on the assumption that exposure allocation can be considered ‘as-if randomized’. The target trial framework provides a systematic basis for evaluating this assumption and the other design elements that underpin the causal claims that can be made from NES.Conclusions: NES should be considered a type of study design rather than a set of tools for analyses of non-randomized interventions. Alignment of NES to the Target Trial framework will clarify the strength of evidence underpinning claims about the effectiveness of public health interventions.

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. 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. 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. 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.

Fetal alcohol spectrum disorders (FASDs) are lifelong disabilities caused by prenatal alcohol exposure. Prenatal alcohol use is common in the UK, but FASD prevalence was unknown. Prevalence estimates are essential for informing FASD prevention, identification and support. We applied novel screening algorithms to existing data to estimate the screening prevalence of FASD. Data were from a population-based cohort study (ALSPAC), which recruited pregnant women with expected delivery dates between 1991 and 1992 from the Bristol area of the UK. We evaluated different missing data strategies by comparing results from complete case, single imputation (which assumed that missing data indicated no exposure and no impairment), and multiple imputation methods. 6.0% of children screened positive for FASD in the analysis that used the single imputation method (total N = 13,495), 7.2% in complete case analysis (total N = 223) and 17.0% in the analysis with multiply imputed data (total N = 13,495). A positive FASD screen was more common among children of lower socioeconomic status and children from unplanned pregnancies. Our analyses showed that the complete case and single imputation methods that are commonly used in FASD prevalence studies are likely to underestimate FASD prevalence. Although not equivalent to a formal diagnosis, these screening prevalence estimates suggest that FASD is likely to be a significant public health concern in the UK. Given current patterns of alcohol consumption and recent changes in prenatal guidance, active case ascertainment studies are urgently needed to further clarify the current epidemiology of FASD in the general population of the UK.

Foetal alcohol spectrum disorders (FASDs) are a leading cause of developmental disability. Prenatal alcohol use is the sole necessary cause of FASD, but it is not always sufficient. Multiple factors influence a child’s susceptibility to FASD following prenatal alcohol exposure. Much of the FASD risk factor literature has been limited to discussions of association, rather than causation. While knowledge of predictor variables is important for identifying who is most at risk of FASD and for targeting interventions, causal knowledge is important for identifying effective mechanisms for prevention and intervention programmes. We conducted a systematic search and narrative synthesis of the evidence and used this to create a causal diagram (directed acyclic graph; DAG) to describe the causal pathways to FASD. Our results show that the aetiology of FASD is multifaceted and complex. FASD risk is determined by a range of lifestyle, sociodemographic, maternal, social, gestational, and genetic factors. The causal diagram that we present in this review provides a comprehensive summary of causal risk factors for FASD and can be used as a tool to inform data collection and statistical modelling strategies to minimise bias in future studies of FASD.

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.

Background and Aims: Given the costs of alcohol to society, it is important to evaluate whether local alcohol licensing decisions can mitigate the effects of alcohol misuse. Robust natural experiment evaluations of the impact of individual licensing decisions could potentially inform and improve local decision‐making. We aimed to assess whether alcohol licensing decisions could be evaluated at small spatial scale by using a causal inference framework.Design: Three natural experiments.Setting and participants: Three English local areas of 1000–15 000 people each.Intervention and comparator: The case study interventions were (i) the closure of a nightclub following reviews; (ii) closure of a restaurant/nightclub following reviews and (iii) implementation of new local licensing guidance (LLG). Trends in outcomes were compared with synthetic counterfactuals created using Bayesian structural time–series.Measurements: Time–series data were obtained on emergency department admissions, ambulance call‐outs and alcohol‐related crime at the Lower or Middle Super Output geographical aggregation level.Findings: Closure of the nightclub led to temporary 4‐month reductions in antisocial behaviour (−18%; 95% credible interval − 37%, −4%), with no change in other outcomes. Closure of the restaurant/nightclub did not lead to measurable changes in outcomes. The new licensing guidance led to small reductions in drunk and disorderly behaviour (nine of a predicted 21 events averted), and the unplanned end of the LLG coincided with an increase in domestic violence of two incidents per month.Conclusions: The impact of local alcohol policy, even at the level of individual premises, can be evaluated using a causal inference framework. Local government actions such as closure or restriction of alcohol venues and alcohol licensing may have a positive impact on health and crime in the immediate surrounding area.