5-year mental health outcomes for children and adolescents presenting with psychiatric symptoms to general practitioners in England: a retrospective cohort study.

BACKGROUND: Little information is available on the clinical trajectories of children and adolescents who attend general practice (GP) with psychiatric symptoms. We aimed to examine 5-year service use in English primary care for children and adolescents with neurodevelopmental or mental health symptoms or diagnoses. METHODS: In this retrospective cohort study, we used anonymised primary care health records from the Clinical Practice Research Datalink Aurum database (CPRD-Aurum). We identified children and adolescents (aged 3-18 years) presenting to primary care in England between Jan 1, 2000, and May 9, 2016, with a symptom or diagnosis of a mental health, behavioural, or neurodevelopmental condition. Participants were excluded if they had less than 1 year of follow-up. We followed up participants from their index date until either death, transfer out of the practice, or the end of data collection on May 5, 2021, and for trajectory analysis we limited follow-up to 5 years. We used group-based multi-trajectory models to identify clusters with similar trajectories over 5 years of follow-up for three primary outcomes: mental health-related GP contacts, psychotropic medication prescriptions, and specialist mental health-care contact. We did survival analysis to examine the associations between trajectory-group membership and hospital admission for self-harm or death by suicide, as indicators of severe psychiatric distress. FINDINGS: We included 369 340 children and adolescents, of whom 180 863 (49·0%) were girls, 188 438 (51·0%) were boys, 39 (<0·1%) were of indeterminate gender, 290 125 (78·6%) were White, 9161 (2·5%) were South Asian, 10 418 (2·8%) were Black, 8115 (2·2%) were of mixed ethnicity, and 8587 (2·3%) were other ethnicities, and the median age at index presentation was 13·6 years (IQR 8·4-16·7). In the best-fitting, seven-group, group-based multi-trajectory model, over a 5-year period, the largest group (low contact; 207 985 [51·2%]) had low rates of additional service contact or psychotropic prescriptions. The other trajectory groups were moderate, non-pharmacological contact (43 836 [13·0%]); declining contact (25 469 [8·7%]); year-4 escalating contact (18 277 [6·9%]); year-5 escalating contact (18 139; 5·2%); prolonged GP contact (32 147 [8·6%]); and prolonged specialist contact (23 487 [6·5%]). Non-White ethnicity and presentation in earlier study years (eg, 2000-2004) were associated with low-contact group membership. The prolonged specialist-contact group had the highest risk of hospital admission for self-harm (hazard ratio vs low-contact group 2·19 [95% CI 2·03-2·36]) and suicide (2·67 [1·72-4·14]). INTERPRETATION: Most children and adolescents presenting to primary care with psychiatric symptoms or diagnoses have low or declining rates of ongoing contact. If these trajectories reflect symptomatic improvement, these findings provide reassurance for children and adolescents and their caregivers. However, these trajectories might reflect an unmet need for some children and adolescents. FUNDING: National Institute for Health and Care Research and the Wellcome Trust.

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.

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).

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).

Substantially more children receiving antidepressants see a specialist than reported by Jack et al.

We would like to draw attention to evidence of substantial bias in the article published in this journal by Jack et al. (BMC Med 18:1-12, 2020). They provide an analysis of antidepressant prescribing to children and young people (CYP; ages 5 to 17) in primary care in England and reported that only 24.7% of CYP prescribed SSRIs for the first time were seen by a child and adolescent psychiatrist-contrary to national guidelines. We believe that their analysis is based on incomplete data that misses a large proportion of specialist mental health contacts. This is because the dataset Jack et al. used to capture specialist mental health contact-The Hospital Episode Statistics (HES) dataset-has poor coverage, as most CYP mental health services do not submit data. We demonstrate the level of underreporting with an analysis of events in a large primary care dataset where there has been a record of definite contact with CYP mental health services. We report that as many as three quarters of specialist CYP contacts with mental health specialists are missed in the HES dataset, indicating that the figure presented by Jack et al. is substantially wrong.

Fertility Trends and Adverse Pregnancy Outcomes in Female Patients With Psoriasis in the UK.

Importance: Evidence regarding fertility trends and obstetric outcomes among patients with psoriasis is limited by studies of small sample sizes, noninclusion of comparators, and the lack of accurate pregnancy records. Objective: To investigate fertility rates and obstetric outcomes of pregnancies in female patients with psoriasis compared with age- and general practice-matched comparators without psoriasis. Design, Setting, and Participants: This population-based cohort study used data from 887 primary care practices that contributed to the UK Clinical Practice Research Datalink GOLD database between 1998 and 2019, linked to a pregnancy register and Hospital Episode Statistics. There were 6 223 298 patients of common childbearing ages (15-44 years), and 63 681 patients with psoriasis had at least 1 year of follow-up data prior to the diagnosis of psoriasis. For each patient with psoriasis, 5 patients were matched by age from the same general practice. The median follow-up duration was 4.1 years. Data analysis was performed in 2021. Exposures: Patients with psoriasis were identified using clinical diagnostic codes from consultations. Main Outcomes and Measures: Fertility rates were calculated as the number of pregnancies per 100 patient-years. The outcomes of each pregnancy recorded in the pregnancy register or Hospital Episode Statistics were screened to identify obstetric outcomes. A negative binomial model was used to examine the association between psoriasis and the fertility rate. Logistic regression was applied to compare the association between psoriasis and obstetric outcomes. Results: A total of 63 681 patients with psoriasis and 318 405 matched comparators were included in the analysis (median [IQR] age, 30 [22-37] years). Lower fertility rates (rate ratio, 0.75; 95% CI, 0.69-0.83) were found in patients with moderate to severe psoriasis. Compared with matched comparators without psoriasis, pregnancies in patients with psoriasis had a higher risk of loss (odds ratio, 1.06; 95% CI, 1.03-1.10); however, there was no increase in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes. Conclusion and Relevance: In this cohort study, patients with moderate to severe psoriasis had a lower fertility rate, and the risk of pregnancy loss was higher than in matched comparators without psoriasis. Future research should identify the mechanism of increased risk of pregnancy loss among patients with psoriasis.

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.

Hospital inpatient admissions of children of mothers with severe mental illness: A Western Australian cohort study.

BACKGROUND: Children of parents with mental illness face a number of adversities, potentially contributing to poor health. AIM: The aim of this study was to quantify the association between maternal severe mental illness and children's hospital admissions. METHOD: Record linkage cohort study of 467,945 children born in Western Australia between 1 January 1980 and 31 December 2001. Follow-up was from age 28 days until fifth birthday. Linked registers captured information on potential confounders. Rate ratios and adjusted rate ratios measured relative change in the numbers of admissions and total days of stay, while rate differences measured absolute change in outcomes. Cause-specific increases were calculated for ICD-9 chapters and for 'potentially preventable' conditions. RESULTS: After adjusting for potential confounders, children of mothers with severe mental illness had a 46% relative increased rate in hospital admissions (95% confidence interval = [38%, 54%]) and an absolute increase in 0.69 extra days in hospital per child, per year (95% confidence interval = [0.67, 0.70]). The relative increase in admissions was greatest in the child's first year of life (adjusted rate ratio = 1.76, 95% confidence interval = [1.64, 1.88]; rate difference = 0.32, 95% confidence interval = [0.30, 0.34]). Rates of admissions were increased for a range of causes, particularly injuries, infections and respiratory disease, and for conditions classified as 'potentially preventable'. CONCLUSION: Children of mothers with severe mental illness have a substantial excess in hospital use compared to children of well mothers. This vulnerable group should be targeted with interventions to avert preventable morbidity and premature mortality in later life.

Psychological distress, depression, anxiety, and life satisfaction following COVID-19 infection: evidence from 11 UK longitudinal population studies.

BACKGROUND: Evidence on associations between COVID-19 illness and mental health is mixed. We aimed to examine whether COVID-19 is associated with deterioration in mental health while considering pre-pandemic mental health, time since infection, subgroup differences, and confirmation of infection via self-reported test and serology data. METHODS: We obtained data from 11 UK longitudinal studies with repeated measures of mental health (psychological distress, depression, anxiety, and life satisfaction; mental health scales were standardised within each study across time) and COVID-19 status between April, 2020, and April, 2021. We included participants with information available on at least one mental health outcome measure and self-reported COVID-19 status (suspected or test-confirmed) during the pandemic, and a subset with serology-confirmed COVID-19. Furthermore, only participants who had available data on a minimum set of covariates, including age, sex, and pre-pandemic mental health were included. We investigated associations between having ever had COVID-19 and mental health outcomes using generalised estimating equations. We examined whether associations varied by age, sex, ethnicity, education, and pre-pandemic mental health, whether the strength of the association varied according to time since infection, and whether associations differed between self-reported versus confirmed (by test or serology) infection. FINDINGS: Between 21 Dec, 2021, and July 11, 2022, we analysed data from 54 442 participants (ranging from a minimum age of 16 years in one study to a maximum category of 90 years and older in another; including 33 200 [61·0%] women and 21 242 [39·0%] men) from 11 longitudinal UK studies. Of 40 819 participants with available ethnicity data, 36 802 (90·2%) were White. Pooled estimates of standardised differences in outcomes suggested associations between COVID-19 and subsequent psychological distress (0·10 [95% CI 0·06 to 0·13], I2=42·8%), depression (0·08 [0·05 to 0·10], I2=20·8%), anxiety (0·08 [0·05 to 0·10], I2=0·0%), and lower life satisfaction (-0·06 [-0·08 to -0·04], I2=29·2%). We found no evidence of interactions between COVID-19 and sex, education, ethnicity, or pre-pandemic mental health. Associations did not vary substantially between time since infection of less than 4 weeks, 4-12 weeks, and more than 12 weeks, and were present in all age groups, with some evidence of stronger effects in those aged 50 years and older. Participants who self-reported COVID-19 but had negative serology had worse mental health outcomes for all measures than those without COVID-19 based on serology and self-report. Participants who had positive serology but did not self-report COVID-19 did not show association with mental health outcomes. INTERPRETATION: Self-reporting COVID-19 was longitudinally associated with deterioration in mental health and life satisfaction. Our findings emphasise the need for greater post-infection mental health service provision, given the substantial prevalence of COVID-19 in the UK and worldwide. FUNDING: UK Medical Research Council and UK National Institute for Health and Care Research.

Association between parental mental illness and autoimmune diseases in the offspring - A nationwide register-based cohort study in Sweden.

Mental illness has been previously linked with autoimmune diseases, yet the associations between parental mental illness and offspring's risk of autoimmune diseases is largely unknown. We conducted a population-based cohort study of 2,192,490 Swedish children born between 1991 and 2011 and their parents to determine the associations between parental mental illness and risk of autoimmune diseases among the offspring. Time-dependent diagnoses of parental mental illness (psychosis, alcohol/drug misuse, depression, anxiety, eating disorders, personality disorders, attention deficit hyperactivity disorder, autism spectrum disorder) and offspring autoimmune diseases (type 1 diabetes (T1D), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus, psoriasis, multiple sclerosis, inflammatory bowel disease (IBD), coeliac disease) were identified from inpatient/outpatient healthcare visits. Associations were measured by hazard ratios (HRs) adjusted for potential confounders. Overall, parental mental illness was associated with a small increase in risk of offspring's autoimmune diseases (HR 1.05, 95% CI 1.02-1.08). However, parental common mental disorder (anxiety/depression) was associated with higher risk of JIA, psoriasis, and T1D (HR T1D 1.11, 95% CI 1.01-1.22), while maternal psychosis with reduced risk of coeliac disease (HR 0.68, 95% CI 0.49-0.95) and paternal alcohol/drug misuse with reduced risk of IBD (HR 0.80, 95% CI 0.64-0.99). Maternal eating disorders were associated with a markedly increased risk for T1D (HR 1.41, 95% CI 1.05-1.89). Further studies are needed to confirm these findings and to understand underlying mechanisms. There is a need for greater clinical awareness about potential risk of JIA, psoriasis, and T1D among children of parents with common psychiatric morbidity.

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.

Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation, and region in England and Wales during 2020: A registry-based study.

BACKGROUND: Deaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups. METHODS AND FINDINGS: We used national mortality registers in England and Wales, from 27 December 2014 until 25 December 2020, covering 3,265,937 deaths. YLLs (main outcome) were calculated using 2019 single year sex-specific life tables for England and Wales. Interrupted time-series analyses, with panel time-series models, were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7 March 2020 and 25 December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease and diabetes, cancer, and other indirect deaths (all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group. Between 7 March 2020 and 25 December 2020, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England and Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from 916 (95% CI: 820 to 1,012) for the least deprived quintile to 1,645 (95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, a mean of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, a mean of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were much higher in younger age groups, but similar for those aged 85 or over. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in the North West. Limitations include the quasi-experimental nature of the research design and the requirement for accurate and timely recording. CONCLUSIONS: In this study, we observed strong socioeconomic and geographical health inequalities in YLL, during the first calendar year of the COVID-19 pandemic. These were in line with long-standing existing inequalities in England and Wales, with the most deprived areas reporting the largest numbers in potential YLL.

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.

Excess deaths from COVID-19 and other causes by region, neighbourhood deprivation level and place of death during the first 30 weeks of the pandemic in England and Wales: A retrospective registry study.

BACKGROUND: Excess deaths during the COVID-19 pandemic compared with those expected from historical trends have been unequally distributed, both geographically and socioeconomically. Not all excess deaths have been directly related to COVID-19 infection. We investigated geographical and socioeconomic patterns in excess deaths for major groups of underlying causes during the pandemic. METHODS: Weekly mortality data from 27/12/2014 to 2/10/2020 for England and Wales were obtained from the Office of National Statistics. Negative binomial regressions were used to model death counts based on pre-pandemic trends for deaths caused directly by COVID-19 (and other respiratory causes) and those caused indirectly by it (cardiovascular disease or diabetes, cancers, and all other indirect causes) over the first 30 weeks of the pandemic (7/3/2020-2/10/2020). FINDINGS: There were 62,321 (95% CI: 58,849 to 65,793) excess deaths in England and Wales in the first 30 weeks of the pandemic. Of these, 46,221 (95% CI: 45,439 to 47,003) were attributable to respiratory causes, including COVID-19, and 16,100 (95% CI: 13,410 to 18,790) to other causes. Rates of all-cause excess mortality ranged from 78 per 100,000 in the South West of England and in Wales to 130 per 100,000 in the West Midlands; and from 93 per 100,000 in the most affluent fifth of areas to 124 per 100,000 in the most deprived. The most deprived areas had the highest rates of death attributable to COVID-19 and other indirect deaths, but there was no socioeconomic gradient for excess deaths from cardiovascular disease/diabetes and cancer. INTERPRETATION: During the first 30 weeks of the COVID-19 pandemic there was significant geographic and socioeconomic variation in excess deaths for respiratory causes, but not for cardiovascular disease, diabetes and cancer. Pandemic recovery plans, including vaccination programmes, should take account of individual characteristics including health, socioeconomic status and place of residence. FUNDING: None.