Parental Mental Illness and the Likelihood of Child Out-of-Home Care: A Cohort Study.

OBJECTIVES: To detail the relationship between parental mental illness and the likelihood of out-of-home care (OHC) among their children, and to identify factors which modify this relationship. METHODS: Using Swedish national registers, children born in 2000 to 2011 (n = 1 249 463) were linked to their parents. Time-dependent parental mental illness (nonaffective and affective psychosis, substance misuse, depression, anxiety and stress, eating disorders, personality disorders, attention deficit hyperactivity disorder, autism, and intellectual disability), was identified through International Classification of Diseases codes. RESULTS: After adjustment for socioeconomic factors, children living with mentally ill parents were 4 times as likely to be placed in OHC than children without (95% confidence interval [CI] 4.24-4.61). The highest hazard ratio (HR) was in the youngest children aged 0 to 1 year (5.77, 95% CI 5.42-6.14), exposed to maternal illness (HR 4.56, 95% CI 4.37-4.76), and parental intellectual disability (HR 4.73, 95% CI 4.09-5.46). Children with parental mental illness with multiple risk factors were at particularly high risk. Compared with children without parental mental illness, and those with university-educated parents, children whose parents had mental illness and only had education to age 16 had a 15 times higher risk of OHC (95% CI 13.75-16.54). CONCLUSIONS: Children with parental mental illness are considerably more likely to be removed from home into care during childhood, particularly during the first year of life and if they are from socially disadvantaged families. Greater knowledge of these risks should lead to increased support for vulnerable new families.

The causal association between maternal depression, anxiety, and infection in pregnancy and neurodevelopmental disorders among 410 461 children: a population study using quasi-negative control cohorts and sibling analysis.

BACKGROUND: To address if the long-standing association between maternal infection, depression/anxiety in pregnancy, and offspring neurodevelopmental disorder (NDD) is causal, we conducted two negative-control studies. METHODS: Four primary care cohorts of UK children (pregnancy, 1 and 2 years prior to pregnancy, and siblings) born between 1 January 1990 and 31 December 2017 were constructed. NDD included autism/autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy. Maternal exposures included depression/anxiety and/or infection. Maternal (age, smoking status, comorbidities, body mass index, NDD); child (gender, ethnicity, birth year); and area-level (region and level of deprivation) confounders were captured. The NDD incidence rate among (1) children exposed during or outside of pregnancy and (2) siblings discordant for exposure in pregnancy was compared using Cox-regression models, unadjusted and adjusted for confounders. RESULTS: The analysis included 410 461 children of 297 426 mothers and 2 793 018 person-years of follow-up with 8900 NDD cases (incidence rate = 3.2/1000 person years). After adjustments, depression and anxiety consistently associated with NDD (pregnancy-adjusted HR = 1.58, 95% CI 1.46-1.72; 1-year adj. HR = 1.49, 95% CI 1.39-1.60; 2-year adj. HR = 1.62, 95% CI 1.50-1.74); and to a lesser extent, of infection (pregnancy adj. HR = 1.16, 95% CI 1.10-1.22; 1-year adj. HR = 1.20, 95% CI 1.14-1.27; 2-year adj. HR = 1.19, 95% CI 1.12-1.25). NDD risk did not differ among siblings discordant for pregnancy exposure to mental illness HR = 0.97, 95% CI 0.77-1.21 or infection HR = 0.99, 95% CI 0.90-1.08. CONCLUSIONS: Maternal risk appears to be unspecific to pregnancy: our study provided no evidence of a specific, and therefore causal, link between in-utero exposure to infection, common mental illness, and later development of NDD.

Representativeness in health research studies: an audit of Greater Manchester Clinical Research Network studies between 2016 and 2021.

BACKGROUND: There are increasing concerns that participants in health research in the UK are not representative of the UK population, risking widening health inequities. However, detailed information on the magnitude of the problem is limited. Therefore, we evaluated if the health research conducted in the Greater Manchester region was broadly representative of its diverse population. METHODS: We conducted an audit of all health  research studies conducted exclusively in Greater Manchester, using data from a national research network. Two researchers selected studies that were (1) an interventional or observational study of a health outcome; (2) 'closed' for recruitment between May 2016 and May 2021 and (3) human research. They extracted study information (dates, contacts, sample recruited, clinical speciality). Participant characteristics were sourced from published and unpublished manuscripts and requested directly from principal investigators and named study contacts. Data were extracted, summarised and compared to the Greater Manchester population for the following metrics: ethnicity, sex, age, deprivation and smoking status. A weighted mean age estimate was calculated to account for variation in age reporting. Too few studies provided patient-level deprivation data so, using the area code of the recruitment site, the area level multiple deprivation, health deprivation and disability index and decile was derived. These data were geo-mapped using QGIS 3.26. RESULTS: Overall, 145/153 (95%) studies met inclusion criteria and participant information was sourced for 85/145 (59%) studies, representing 21,797 participants. Participant information was incomplete for all metrics. Where ethnicity (N = 10,259) data were available and compared to Greater Manchester estimates there was evidence that ethnic minorities were under-represented (6% versus 16%). Most of the recruitment occurred in central Manchester (50%) and with NHS hospital settings (74%). CONCLUSIONS: Greater Manchester health research in 2016-2021 was centralised and under-represented ethnic minorities. We could not report which ethnic minority group was least represented because sourcing detailed participant information was challenging. Recommendations to improve the reporting of key participant characteristics with which to monitor representativeness in health research are discussed.

Maternal mental illness and child atopy: a UK population-based, primary care cohort study.

BACKGROUND: The number of children exposed to maternal mental illness is rapidly increasing and little is known about the effects of maternal mental illness on childhood atopy. AIM: To investigate the association between maternal mental illness and risk of atopy among offspring. DESIGN AND SETTING: Retrospective cohort study using a UK primary care database (674 general practices). METHOD: In total, 590 778 children (born 1 January 1993 to 30 November 2017) were followed until their 18th birthday, with 359 611 linked to their hospital records. Time-varying exposure was captured for common (depression and anxiety), serious (psychosis), addiction (alcohol and substance misuse), and other (eating and personality disorder) maternal mental illness from 6 months before pregnancy. Using Cox regression models, incidence rates of atopy were calculated and compared for the exposed and unexposed children in primary (asthma, eczema, allergic rhinitis, and food allergies) and secondary (asthma and food allergies) care, adjusted for maternal (age, atopy history, smoking, and antibiotic use), child (sex, ethnicity, and birth year/season), and area covariates (deprivation and region). RESULTS: Children exposed to common maternal mental illness were at highest risk of developing asthma (adjusted hazard ratio [aHR] 1.17, 95% confidence interval [CI] = 1.15 to 1.20) and allergic rhinitis (aHR 1.17, 95% CI = 1.13 to 1.21), as well as a hospital admission for asthma (aHR 1.29, 95% CI = 1.20 to 1.38). Children exposed to addiction disorders were 9% less likely to develop eczema (aHR 0.91, 95% CI = 0.85 to 0.97) and 35% less likely to develop food allergies (aHR 0.65, 95% CI = 0.45 to 0.93). CONCLUSION: The finding that risk of atopy varies by type of maternal mental illness prompts important aetiological questions. The link between common mental illness and childhood atopy requires GPs and policymakers to act and support vulnerable women to access preventive (for example, smoking cessation) services earlier.

Prevention of Childhood Adversities and Children's Common Mental Disorders and School Grades.

Importance: Adversity during childhood can limit children's chances of achieving their optimal developmental and psychological outcomes. Well-designed observational studies might help identify adversities that are most implicated in this, thereby helping to identify potential targets for developing interventions. Objective: To compare the association between preventing childhood poverty, parental mental illness and parental separation, and the population rate of offspring common mental disorders (ages 16-21 years) or average school grades (age 16 years). Design, Setting, and Participants: A population-based, longitudinal cohort study using Swedish registries was conducted. A total of 163 529 children born in Sweden between January 1, 1996, and December 31, 1997, were followed up until their 21st birthday. They were linked to registries using Sweden's national personal identification number. Children were linked to birth parents, hospital records, and school data. Parents were linked to registries containing health, income, sociodemographic, and obstetric data. Analyses were conducted between January 10, 2021, and August 26, 2022. Exposures: Childhood adversities of relative poverty (household disposable income <50% of the median), parental inpatient admission for a mental illness, or parental separation. Adversities were categorized into developmental periods: ages 0 to 3, 4 to 7, 8 to 11, and 12 to 16 years. Main Outcomes and Measures: The main outcomes were children's hospital records with a diagnosis of anxiety or depression between ages 16 and 21 years and school grades at the end of compulsory education (age 16 years). The parametric g-formula modeled population changes in outcomes associated with the counterfactual, hypothetical preventing adversity exposures, accounting for fixed and time-varying confounders. Adjustments were made for parental demographic characteristics, obstetric variables, and socioeconomic data at birth. Results: A total of 163 529 children were included in the cohort (51.2% boys, 51.4% born in 1996). Preventing all adversities was associated with an estimated change in the prevalence of offspring common mental disorders from 10.2% to 7.6% and an improvement in school grades with an SD of 0.149 (95% CI, 0.147-0.149). Preventing parental separation provided for the greatest improvement, with an estimated 2.34% (95% CI, 2.23%-2.42%) fewer children with a common mental disorder and an improvement in school grades by 0.127 SDs (0.125-0.129). Greater improvements were shown by hypothetically targeting adolescents (age 12-16 years) and those whose parents had a mental illness when the child was born. Conclusions and Relevance: The results of this cohort modeling study suggest that preventing childhood adversity could provide notable improvements in the rates of common mental disorders and school grades. Many children might achieve better life outcomes if resources are properly allocated to the right adversities (parental separation), the right groups (children with parental mental illness), and at the right time (adolescence).

Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.

INTRODUCTION: Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy. METHODS AND ANALYSIS: Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

Changes to healthcare utilisation and symptoms for common mental health problems over the first 21 months of the COVID-19 pandemic: parallel analyses of electronic health records and survey data in England.

Background: Few studies have investigated the effect of the COVID-19 pandemic on mental health beyond 2020. This study quantifies changes to healthcare utilisation and symptoms for common mental health problems over the pandemic's first 21 months. Methods: Parallel cohort studies using primary care database and survey data for adults (≥16 years) in England from January 2015 to December 2021: 16,551,842 from the Clinical Practice Research Datalink (CPRD) and 40,699 from the UK Household Longitudinal Survey (UKHLS). Interrupted time-series models estimated changes in monthly prevalence of presentations and prescribed medications for anxiety and depression (CPRD); and self-reported psychological distress (UKHLS). The pandemic period was divided into five phases: 1st Wave (April-May 2020); post-1st Wave (June-September 2020); 2nd Wave (October 2020-February 2021); post 2nd Wave (March-May 2021); 3rd Wave (June-December 2021). Findings: Primary care presentations for depression or anxiety dropped during the first wave (4.6 fewer monthly appointments per 1000 patients, 4.4-4.8) and remained lower than expected throughout follow-up. Self-reported psychological distress exceeded expected levels during the first (Prevalence Ratio = 1.378, 95% CI 1.289-1.459) and second waves (PR = 1.285, 1.189-1.377), returning towards expected levels during the third wave (PR = 1.038, 0.929-1.154). Increases in psychological distress and declines in presentations were greater for women. The decrease in primary care presentations for depression and anxiety exceeded that for physical health conditions (rheumatoid arthritis, diabetes, urinary tract infections). Anxiety and depression prescriptions returned to pre-pandemic levels during the second wave due to increased repeat prescriptions. Interpretation: Despite periods of distress during the pandemic, we did not find an enduring effect on common mental health problems. The fall in primary care presentations for anxiety or depression suggests changing healthcare utilisation for mental distress and a potential treatment gap. Funding: National Institute for Health and Care Research (NIHR).

Key outcomes for reporting in studies of pregnant women with multiple long-term conditions: a qualitative study.

BACKGROUND: Maternal multiple long-term conditions are associated with adverse outcomes for mother and child. We conducted a qualitative study to inform a core outcome set for studies of pregnant women with multiple long-term conditions. METHODS: Women with two or more pre-existing long-term physical or mental health conditions, who had been pregnant in the last five years or planning a pregnancy, their partners and health care professionals were eligible. Recruitment was through social media, patients and health care professionals' organisations and personal contacts. Participants who contacted the study team were purposively sampled for maximum variation. Three virtual focus groups were conducted from December 2021 to March 2022 in the United Kingdom: (i) health care professionals (n = 8), (ii) women with multiple long-term conditions (n = 6), and (iii) women with multiple long-term conditions (n = 6) and partners (n = 2). There was representation from women with 20 different physical health conditions and four mental health conditions; health care professionals from obstetrics, obstetric/maternal medicine, midwifery, neonatology, perinatal psychiatry, and general practice. Participants were asked what outcomes should be reported in all studies of pregnant women with multiple long-term conditions. Inductive thematic analysis was conducted. Outcomes identified in the focus groups were mapped to those identified in a systematic literature search in the core outcome set development. RESULTS: The focus groups identified 63 outcomes, including maternal (n = 43), children's (n = 16) and health care utilisation (n = 4) outcomes. Twenty-eight outcomes were new when mapped to the systematic literature search. Outcomes considered important were generally similar across stakeholder groups. Women emphasised outcomes related to care processes, such as information sharing when transitioning between health care teams and stages of pregnancy (continuity of care). Both women and partners wanted to be involved in care decisions and to feel informed of the risks to the pregnancy and baby. Health care professionals additionally prioritised non-clinical outcomes, including quality of life and financial implications for the women; and longer-term outcomes, such as children's developmental outcomes. CONCLUSIONS: The findings will inform the design of a core outcome set. Participants' experiences provided useful insights of how maternity care for pregnant women with multiple long-term conditions can be improved.

The development of a core outcome set for studies of pregnant women with multimorbidity.

BACKGROUND: Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity. METHODS: We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations. RESULTS: Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs. CONCLUSIONS: Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.

Development and validation of a short form psychometric tool assessing the caregiving Challenge of Living with Cystic Fibrosis (CLCF-SF) in a child.

OBJECTIVE: Caring for a child with cystic fibrosis (CF) is a rigorous daily commitment for caregivers and treatment burden is a major concern. We aimed to develop and validate a short form version of a 46-item tool assessing the Challenge of Living with Cystic Fibrosis (CLCF) for clinical or research use. DESIGN: A novel genetic algorithm based on 'evolving' a subset of items from a pre-specified set of criteria, was applied to optimise the tool, using data from 135 families. MAIN OUTCOME MEASURES: Internal reliability and validity were assessed; the latter compared scores to validated tests of parental well-being, markers of treatment burden, and disease severity. RESULTS: The 15-item CLCF-SF demonstrated very good internal consistency [Cronbach's alpha 0.82 (95%CI 0.78-0.87)]. Scores for convergent validity correlated with the Beck Depression Inventory (Rho = 0.48), State Trait Anxiety Inventory (STAI-State, Rho = 0.41; STAI-Trait, Rho = 0.43), Cystic Fibrosis Questionnaire-Revised, lung function (Rho = -0.37), caregiver treatment management (r = 0.48) and child treatment management (r = 0.45), and discriminated between unwell and well children with CF (Mean Difference 5.5, 95%CI 2.5-8.5, p < 0.001), and recent or no hospital admission (MD 3.6, 95%CI 0.25-6.95, p = 0.039). CONCLUSION: The CLCF-SF provides a robust 15-item tool for assessing the challenge of living with a child with CF.

Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.

INTRODUCTION: One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions). METHODS AND ANALYSIS: Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses. ETHICS AND DISSEMINATION: Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.

Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.

BACKGROUND: The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy. METHODS: A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy. RESULTS: During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy. CONCLUSIONS: The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.

Trends in antipsychotic prescribing to children and adolescents in England: cohort study using 2000-19 primary care data.

BACKGROUND: The prescription of antipsychotics to children and adolescents has been increasing worldwide. We described up-to-date trends in antipsychotic prescribing and identified likely indications in a contemporary English cohort. METHODS: We used a large primary care database, the Clinical Practice Research Datalink (CPRD) Aurum database, and we included all children and adolescents aged 3-18 years in the database and registered in England between Jan 1, 2000, and Dec 31, 2019, excluding those whose gender was recorded as indeterminate. Participants were followed up until the earliest of Dec 31, 2019, June 30 of the year they turned 18 years, their death, when they transferred from the primary care practice, or when the practice left the database. Data were not collected on ethnicity. We recorded antipsychotic prescriptions using the date a prescription was issued. As CPRD prescriptions are not linked to indications, we developed an algorithm to ascertain the most likely indication associated with participants' first antipsychotic prescription using clinical codes. We reported prescribing trends as annual period prevalence and the rate of first antipsychotic prescription, and we used joinpoint regression analysis to identify changes in the outcome trend. We stratified prevalence estimates by age group, gender, and Index of Multiple Deprivation quintiles, we reported frequencies of likely indications associated with incident prescriptions, and we explored clinical preference for typical versus atypical antipsychotics within deprivation quintiles. FINDINGS: Between Jan 1, 2000, and Dec 31, 2019, we included 7 216 791 children and adolescents, of whom 3 480 730 (48·2%) were girls and 3 736 061 (51·8%) were boys, with a mean age at the start of follow-up of 7·3 years (SD 4·9; range 3-18). Median follow-up was 4·1 years (IQR 1·5-8·5). 19 496 (0·3%) individuals received 243 529 antipsychotic prescriptions over follow-up, including 225 710 (92·7%) atypical and 17 819 (7·3%) typical antipsychotic prescriptions. The annual period prevalence of antipsychotic prescriptions rose from 0·057% (95% CI 0·052-0·063%) in 2000 to 0·105% (0·100-0·111%) in 2019. From joinpoint analyses, the period prevalence of all antipsychotic prescriptions increased by an average of 3·3% per year (2·2-4·9%) and the rate of first prescriptions increased by 2·2% per year (1·7-2·7%). The most likely indications of the first identified antipsychotic prescriptions were for autism spectrum disorder (2477 [12·7%]), non-affective psychosis (1669 [8·6%]), anxiety disorders (1466 [7·5%]), ADHD (1391 [7·1%]), depression (1256 [6·4%]), and conduct disorders (1181 [6·1%]). INTERPRETATION: The observed increase in antipsychotic prescriptions over 20 years results from the accumulation of repeated prescriptions to the same individuals combined with an increase in new prescriptions. These findings highlight the need for continued monitoring of trends in antipsychotic use and, although this was not examined in this paper, the findings highlights the need for better information about long-term antipsychotic safety. FUNDING: None.

Development and preliminary validation of the challenges of living with cystic fibrosis (CLCF) questionnaire: a 46-item measure of treatment burden for parent/carers of children with CF.

OBJECTIVE: Treatments for cystic fibrosis (CF) are complex, labour-intensive, and perceived as highly burdensome by caregivers of children with CF. An instrument assessing burden of care is needed. DESIGN: A stepwise, qualitative design was used to create the CLCF with caregiver focus groups, participant researchers, a multidisciplinary professional panel, and cognitive interviews. MAIN OUTCOME MEASURES: Preliminary psychometric analyses evaluated the reliability and convergent validity of the CLCF scores. Cronbach's alpha assessed internal consistency and t-tests examined test-retest reliability. Correlations measured convergence between the Treatment Burden scale of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the CLCF. Discriminant validity was assessed by comparing CLCF scores in one vs two-parent families, across ages, and in children with vs without Pseudomonas aeruginosa (PA). RESULTS: Six Challenge subscales emerged from the qualitative data and the professional panel constructed a scoresheet estimating the Time and Effort required for treatments. Internal consistency and test-retest reliability were adequate. Good convergence was found between the Total Challenge score and Treatment Burden on the CFQ-R (r=-0.49, p = 0.02, n = 31). A recent PA infection signalled higher Total Challenge for caregivers (F(23)11.72, p = 0.002). CONCLUSIONS: The CLCF, developed in partnership with parents/caregivers and CF professionals, is a timely, disease-specific burden measure for clinical research.

Association of pregnancy complications/risk factors with the development of future long-term health conditions in women: overarching protocol for umbrella reviews.

INTRODUCTION: With good medical care, most pregnancy complications like pre-eclampsia, gestational diabetes, etc resolve after childbirth. However, pregnancy complications are known to be associated with an increased risk of new long-term health conditions for women later in life, such as cardiovascular disease. These umbrella reviews aim to summarise systematic reviews evaluating the association between pregnancy complications and five groups of long-term health conditions: autoimmune conditions, cancers, functional disorders, mental health conditions and metabolic health conditions (diabetes and hypertension). METHODS AND ANALYSIS: We will conduct searches in Medline, Embase and the Cochrane database of systematic reviews without any language restrictions. We will include systematic reviews with or without meta-analyses that studied the association between pregnancy complications and the future risk of the five groups of long-term health conditions in women. Pregnancy complications were identified from existing core outcome sets for pregnancy and after consultation with experts. Two reviewers will independently screen the articles. Data will be synthesised with both narrative and quantitative methods. Where a meta-analysis has been carried out, we will report the combined effect size from individual studies. For binary data, pooled ORs with 95% CIs will be presented. For continuous data, we will use the mean difference with 95% CIs. The findings will be presented in forest plots to assess heterogeneity. The methodological quality of the studies will be evaluated with the AMSTAR 2 tool or the Cochrane risk of bias tool. The corrected covered area method will be used to assess the impact of overlap in reviews. The findings will be used to inform the design of prediction models, which will predict the risk of women developing these five group of health conditions following a pregnancy complication. ETHICS AND DISSEMINATION: No ethical approvals required. Findings will be disseminated through publications in peer-reviewed journals and conference presentations.

The sexual and reproductive health of women with mental illness: a primary care registry study.

The purpose of this study is to characterise the sexual and reproductive health risks associated with mental illness among women. This was a retrospective cohort study of 2,680,149 women aged 14 to 45 years in the Clinical Practice Research Datalink, a UK primary care register, linked to 1,702,211 pregnancies that ended between the 1st January 1990 and 31st December 2017. Mental illness was identified in primary care and categorised into the following: common mental illness (depression/anxiety); addiction (alcohol/drug misuse); serious mental illness (affective/non-affective psychosis); other mental illness (eating/personality disorders). Logistic regression estimated the association between mental illness and subsequent risk of recurrent miscarriage and termination. Cox proportional hazards estimated the association between mental illness and time to gynaecological diseases, sexually transmitted infections, reproductive cancers, cervical screen, contraception and emergency contraception. Models were adjusted for calendar year, year of birth, smoking status and ethnicity, region and index of socioeconomic status. Compared to women without mental illness, exposed women were more likely to experience recurrent miscarriage (adjOR = 1.50, 95%CI 1.41 to 1.60), termination (adjOR = 1.48, 95%CI 1.45 to 1.50), gynaecological diseases (adjHR = 1.39, 95%CI 1.37 to 1.40), sexually transmitted infections (adjHR = 1.47, 95%CI 1.43 to 1.51), reproductive cancers (adjHR = 1.10, 95%CI 1.02 to 1.19), contraception (adjHR = 1.28 95%CI 1.26 to 1.29) and emergency contraception (adjHR = 2.30, 95%CI 2.26 to 2.34), and less likely to attend for cervical screening (adjHR = 0.91, 95%CI 0.90 to 0.92). Currently, the sexual and reproductive health needs of women with mental illness are unmet representing significant health inequalities. Clinicians must create opportunities to engage with women in primary care and mental health services to address this gap.

Vocal brain development in infants of mothers with serious mental illness (CAPRI-Voc): study protocol.

INTRODUCTION: Improving the lives of children and adolescents with parental mental illness (CAPRI) remains an urgent political and public health concern for the UK and European Union. Recurrent parental mental illness is believed to lead to fractures in the family, academic and social lives of these children, yet interventions are poorly targeted and non-specific. Part of an interdisciplinary programme of work (the CAPRI Programme; grant number: 682741), CAPRI-Voc aims to achieve two goals: first, to test the feasibility of our longitudinal imaging paradigm in mother-infant pairs where the mother has a diagnosis of severe mental illness. Second, to compare development of vocal processing in these infants with infants in the general population. METHODS AND ANALYSIS: Recruitment of 100 infants of mothers with mental illness, alongside 50 infants of healthy mothers. Both cohorts of infants will undergo functional near infrared spectroscopy (fNIRS) brain imaging at three time points: 9, 12 and 18 months to explore differences between cohorts in their neural responses to vocal stimuli in our language paradigm. Mothers will complete an interview and psychological questionnaires. We shall also complete an infant developmental battery and mother-child interaction play session. Data on recruitment, retention and dropout will be recorded. ETHICS AND DISSEMINATION: It will be made clear that fNIRS is a safe, non-invasive technology widely used in infant clinical and psychological research. We shall reassure mothers that no definitive causal link exists between maternal mental illness and language development in infants, and that individual data will only exist as part of the wider dataset. As the study includes both children and vulnerable adults, all research staff will complete National Health Service (NHS) Safeguarding level 3 training. Dissemination will be via direct feedback to stakeholders, patient and advisory groups, and through presentations at conferences, journal publications and university/NHS trust communications. The study was approved through North West-Greater Manchester West Research Ethics Committee (17/NW/0074) and Health Research Authority (212715).

Self-harm risk in pregnancy: recurrent-event survival analysis using UK primary care data.

BACKGROUND: Perinatal self-harm is of concern but poorly understood. AIMS: To determine if women's risk of self-harm changes in pregnancy and the first postpartum year, and if risk varies by mental illness, age and birth outcome. METHOD: This was a retrospective cohort study of 2 666 088 women aged 15-45 years from the 1 January 1990 to 31 December 2017 linked to 1 102 040 pregnancies and their outcomes, utilising the Clinical Practice Research Datalink and Pregnancy Register. We identified self-harm events and mental illness (depression/anxiety/addiction/affective/non-affective psychosis/eating/personality disorders) from clinical records and grouped women's age into 5-year bands. They calculated the rate of self-harm during discrete non-perinatal, pregnant and postpartum periods. We used a gap-time, stratified Cox model to manage multiple self-harm events, and calculated the unadjusted and adjusted hazard ratios (adjHR) of self-harm associated with pregnancy and the postpartum compared with non-perinatal periods. Pre-planned interactions tested if risk varied by mental illness, age and birth outcome. RESULTS: The analysis included 57 791 self-harm events and 14 712 319 person-years of follow-up. The risk of self-harm shrank in pregnancy (2.07 v. 4.01 events/1000 person-years, adjHR = 0.53, 95% CI 0.49-0.58) for all women except for 15- to 19-year-olds (adjHR = 0.95, 95% CI 0.84-1.07) and the risk reduced most for women with mental illness (adjHR = 0.40, 95% CI 0.36-0.44). Postpartum, self-harm risk peaked at 6-12 months (adjHR = 1.08, 95% CI 1.02-1.15), at-risk groups included young women and women with a pregnancy loss or termination. CONCLUSIONS: Maternity and perinatal mental health services are valuable. Family planning services might have psychological benefit, particularly for young women.

Epidemiology of pre-existing multimorbidity in pregnant women in the UK in 2018: a population-based cross-sectional study.

BACKGROUND: Although maternal death is rare in the United Kingdom, 90% of these women had multiple health/social problems. This study aims to estimate the prevalence of pre-existing multimorbidity (two or more long-term physical or mental health conditions) in pregnant women in the United Kingdom (England, Northern Ireland, Wales and Scotland). STUDY DESIGN: Pregnant women aged 15-49 years with a conception date 1/1/2018 to 31/12/2018 were included in this population-based cross-sectional study, using routine healthcare datasets from primary care: Clinical Practice Research Datalink (CPRD, United Kingdom, n = 37,641) and Secure Anonymized Information Linkage databank (SAIL, Wales, n = 27,782), and secondary care: Scottish Morbidity Records with linked community prescribing data (SMR, Tayside and Fife, n = 6099). Pre-existing multimorbidity preconception was defined from 79 long-term health conditions prioritised through a workshop with patient representatives and clinicians. RESULTS: The prevalence of multimorbidity was 44.2% (95% CI 43.7-44.7%), 46.2% (45.6-46.8%) and 19.8% (18.8-20.8%) in CPRD, SAIL and SMR respectively. When limited to health conditions that were active in the year before pregnancy, the prevalence of multimorbidity was still high (24.2% [23.8-24.6%], 23.5% [23.0-24.0%] and 17.0% [16.0 to 17.9%] in the respective datasets). Mental health conditions were highly prevalent and involved 70% of multimorbidity CPRD: multimorbidity with ≥one mental health condition/s 31.3% [30.8-31.8%]). After adjusting for age, ethnicity, gravidity, index of multiple deprivation, body mass index and smoking, logistic regression showed that pregnant women with multimorbidity were more likely to be older (CPRD England, adjusted OR 1.81 [95% CI 1.04-3.17] 45-49 years vs 15-19 years), multigravid (1.68 [1.50-1.89] gravidity ≥ five vs one), have raised body mass index (1.59 [1.44-1.76], body mass index 30+ vs body mass index 18.5-24.9) and smoked preconception (1.61 [1.46-1.77) vs non-smoker). CONCLUSION: Multimorbidity is prevalent in pregnant women in the United Kingdom, they are more likely to be older, multigravid, have raised body mass index and smoked preconception. Secondary care and community prescribing dataset may only capture the severe spectrum of health conditions. Research is needed urgently to quantify the consequences of maternal multimorbidity for both mothers and children.

Association of SARS-CoV-2 Infection With Psychological Distress, Psychotropic Prescribing, Fatigue, and Sleep Problems Among UK Primary Care Patients.

Importance: Infection with SARS-CoV-2 is associated with fatigue and sleep problems long after the acute phase of COVID-19. In addition, there are concerns of SARS-CoV-2 infection causing psychiatric illness; however, evidence of a direct effect is inconclusive. Objective: To assess risk of risk of incident or repeat psychiatric illness, fatigue, or sleep problems following SARS-CoV-2 infection and to analyze changes according to demographic subgroups. Design, Setting, and Participants: This cohort study assembled matched cohorts using the Clinical Practice Research Datalink Aurum, a UK primary care registry of 11 923 499 individuals aged 16 years or older. Patients were followed-up for up to 10 months, from February 1 to December 9, 2020. Individuals with less than 2 years of historical data or less than 1 week follow-up were excluded. Individuals with positive results on a SARS-CoV-2 test without prior mental illness or with anxiety or depression, psychosis, fatigue, or sleep problems were matched with up to 4 controls based on sex, general practice, and year of birth. Controls were individuals who had negative SARS-CoV-2 test results. Data were analyzed from January to July 2021. Exposure: SARS-CoV-2 infection, determined via polymerase chain reaction testing. Main Outcomes and Measures: Cox proportional hazard models estimated the association between a positive SARS-CoV-2 test result and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue, or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking, and body mass index. Results: Of 11 923 105 eligible individuals (6 011 020 [50.4%] women and 5 912 085 [49.6%] men; median [IQR] age, 44 [30-61] years), 232 780 individuals (2.0%) had positive result on a SARS-CoV-2 test. After applying selection criteria, 86 922 individuals were in the matched cohort without prior mental illness, 19 020 individuals had prior anxiety or depression, 1036 individuals had psychosis, 4152 individuals had fatigue, and 4539 individuals had sleep problems. After adjusting for observed confounders, there was an association between positive SARS-CoV-2 test results and psychiatric morbidity (adjusted hazard ratio [aHR], 1.83; 95% CI, 1.66-2.02), fatigue (aHR, 5.98; 95% CI, 5.33-6.71), and sleep problems (aHR, 3.16; 95% CI, 2.64-3.78). However, there was a similar risk of incident psychiatric morbidity for those with a negative SARS-CoV-2 test results (aHR, 1.71; 95% CI, 1.65-1.77) and a larger increase associated with influenza (aHR, 2.98; 95% CI, 1.55-5.75). Conclusions and Relevance: In this cohort study of individuals registered at an English primary care practice during the pandemic, there was consistent evidence that SARS-CoV-2 infection was associated with increased risk of fatigue and sleep problems. However, the results from the negative control analysis suggest that unobserved confounding may be responsible for at least some of the positive association between COVID-19 and psychiatric morbidity.