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Background Antidepressants are commonly prescribed during pregnancy, despite a lack of evidence from randomised trials on the benefits or risks. Some studies have reported associations of antidepressants during pregnancy with adverse offspring neurodevelopment, but whether or not such associations are causal is unclear. Objectives To study the associations of antidepressants for depression in pregnancy with outcomes using multiple methods to strengthen causal inference. Design This was an observational cohort design using multiple methods to strengthen causal inference, including multivariable regression, propensity score matching, instrumental variable analysis, negative control exposures, comparison across indications and exposure discordant pregnancies analysis. Setting This took place in UK general practice. Participants Participants were pregnant women with depression. Interventions The interventions were initiation of antidepressants in pregnancy compared with no initiation, and continuation of antidepressants in pregnancy compared with discontinuation. Main outcome measures The maternal outcome measures were the use of primary care and secondary mental health services during pregnancy, and during four 6-month follow-up periods up to 24 months after pregnancy, and antidepressant prescription status 24 months following pregnancy. The child outcome measures were diagnosis of autism, diagnosis of attention deficit hyperactivity disorder and intellectual disability. Data sources UK Clinical Practice Research Datalink. Results Data on 80,103 pregnancies were used to study maternal primary care outcomes and were linked to 34,274 children with at least 4-year follow-up for neurodevelopmental outcomes. Women who initiated or continued antidepressants during pregnancy were more likely to have contact with primary and secondary health-care services during and after pregnancy and more likely to be prescribed an antidepressant 2 years following the end of pregnancy than women who did not initiate or continue antidepressants during pregnancy (odds ratioinitiation 2.16, 95% confidence interval 1.95 to 2.39; odds ratiocontinuation 2.40, 95% confidence interval 2.27 to 2.53). There was little evidence for any substantial association with autism (odds ratiomultivariableregression 1.10, 95% confidence interval 0.90 to 1.35; odds ratiopropensityscore 1.06, 95% confidence interval 0.84 to 1.32), attention deficit hyperactivity disorder (odds ratiomultivariableregression 1.02, 95% confidence interval 0.80 to 1.29; odds ratiopropensityscore 0.97, 95% confidence interval 0.75 to 1.25) or intellectual disability (odds ratiomultivariableregression 0.81, 95% confidence interval 0.55 to 1.19; odds ratiopropensityscore 0.89, 95% confidence interval 0.61 to 1.31) in children of women who continued antidepressants compared with those who discontinued antidepressants. There was inconsistent evidence of an association between initiation of antidepressants in pregnancy and diagnosis of autism in offspring (odds ratiomultivariableregression 1.23, 95% confidence interval 0.85 to 1.78; odds ratiopropensityscore 1.64, 95% confidence interval 1.01 to 2.66) but not attention deficit hyperactivity disorder or intellectual disability; however, but results were imprecise owing to smaller numbers. Limitations Several causal-inference analyses lacked precision owing to limited numbers. In addition, adherence to the prescribed treatment was not measured. Conclusions Women prescribed antidepressants during pregnancy had greater service use during and after pregnancy than those not prescribed antidepressants. The evidence against any substantial association with autism, attention deficit hyperactivity disorder or intellectual disability in the children of women who continued compared with those who discontinued antidepressants in pregnancy is reassuring. Potential association of initiation of antidepressants during pregnancy with offspring autism needs further investigation. Future work Further research on larger samples could increase the robustness and precision of these findings. These methods applied could be a template for future pharmaco-epidemiological investigation of other pregnancy-related prescribing safety concerns. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/80/19) and will be published in full in Health Technology Assessment; Vol. 27, No. 15. See the NIHR Journals Library website for further project information. Plain language summary About one in seven women experience depression during pregnancy. Left untreated, this may harm them and their unborn babies. However, the decision to take antidepressants during pregnancy is difficult because women often worry about the risks to their unborn baby. Research findings have been inconsistent, so women often do not have clear information to enable them to make informed decisions. We studied women’s and children’s outcomes after starting (compared with not starting) or continuing (compared with stopping) antidepressants in pregnancy. We used a large UK primary care database and several novel methods of analysis. We tracked 80,103 pregnancies of women with depression for up to 2 years after pregnancy. We also tracked 34,274 children from these pregnancies for at least 4 years to check for developmental outcomes. Women prescribed antidepressants were more likely than women not prescribed antidepressants to use general practice and mental health services during and after pregnancy, and to be prescribed antidepressants 2 years after pregnancy. This suggests that antidepressants were being prescribed to women with greater clinical need. Women who continued antidepressants in pregnancy had no higher likelihood than those who discontinued antidepressants of autism, attention deficit hyperactivity disorder or intellectual disability in their children. This should reassure women making the decision to continue taking their medications in pregnancy. Women who started antidepressants in pregnancy may possibly have had a slightly higher likelihood of autism in their children than those who did not start them. These findings were not seen in all analyses and were based on smaller numbers; therefore, they should be viewed with caution. Importantly, over 98 in every 100 children of women who initiated or continued antidepressants in pregnancy did not receive an autism diagnosis. The findings may help women and clinicians make informed decisions on treatment with antidepressants in pregnancy. Scientific summary Background Depression is common in women of childbearing age and up to one in seven women experience depression during pregnancy. Untreated depression may have serious consequences, such as distress, self-neglect and suicidal behaviour, in affected women and birth complications in their babies. Many women with depression may, therefore, encounter a situation in which they need to decide whether to start or continue an antidepressant during their pregnancy; however, the potential for resulting harm to the neurodevelopment of their offspring is a common concern. In the absence of randomised controlled trials, the information available to guide these decisions is based on observational data, which are subject to confounding. Given that maternal depression may itself lead to adverse outcomes, isolating any effect of antidepressants from the underlying depression is particularly difficult: a problem known as confounding by indication. In the absence of randomised trials, studies designed to emulate such trials and using methods to account for confounding may help triangulate results and strengthen causal inference. Objectives This research aimed to simulate two scenarios that could be tested in pregnant women with depression in a hypothetical target randomised controlled trial asking the following research questions: Does the initiation of antidepressants for depression during pregnancy affect maternal service use outcomes and childhood neurodevelopmental outcomes? Does the continuation of antidepressant use during pregnancy for depression affect maternal service use outcomes and childhood neurodevelopmental outcomes? The data were interrogated using several methods of causal inference, and assessed in relation to dose response, timing of exposure and type of antidepressants according to class and their serotonin-receptor affinity. Methods Design: This was an observational cohort design, with use of multiple methods to strengthen causal inference. Setting and participants: This took place in UK general practice. Participants were UK primary care patients, specifically pregnant women with depression. Data sources: This study used data from the Clinical Practice Research Datalink (CPRD), a large ongoing database of anonymised primary care medical records in the UK. The CPRD’s pregnancy register was used to identify the dates and stages of pregnancy, and the CPRD mother–baby link allowed for the linkage of the records of pregnant women with their live born offspring. For consenting CPRD practices in England, the primary care records were linked to Hospital Episode Statistics, which include registers for inpatient admissions, outpatient care and accident and emergency (A&E) attendance in England, and with mortality data from the Office for National Statistics and Census small-area socioeconomic data. Eligible patients: The data extract covered dates between 1 January 1995 and 31 December 2017. Within this time frame, we identified 344,720 pregnancies in the pregnancy register for which there was evidence of depressive symptoms, or prescription of an antidepressant up to 1 year before or during pregnancy. From this sample, we constructed two cohorts: (1) the pregnant women’s cohort, which contained all pregnancies for which women could be followed up for at least 2 years beyond the pregnancy end date, regardless of the pregnancy outcome or ability to link to the child; (2) the mother and child cohort, which consisted of pregnancies followed up at least until delivery that could be linked with the patient records of the children arising from these pregnancies. The pregnant women’s cohort: The exclusion criteria were (1) records for which the general practice was not yet up to standard, as defined by CPRD (n = 61,704); (2) where the patient had not yet registered with her current general practice 1 year prior to conception (n = 93,638); (3) records suggesting that the woman had transferred out of the general practice while still pregnant (n = 15,627); (4) records with

Background: Emotional dysregulation may be a risk factor for disordered eating and self‐harm in young people, but few prospective studies have assessed these associations long‐term, or considered potential mediators. We examined prospective relationships between childhood emotional dysregulation and disordered eating and self‐harm in adolescence; and social cognition, emotional recognition, and being bullied as mediators. Methods: We analysed Avon Longitudinal Study of Parents and Children data on 3,453 males and 3,481 females. We examined associations between emotional dysregulation at 7 years and any disordered eating and any self‐harm at 16 years with probit regression models. We also assessed whether social cognition (7 years), emotional recognition (8 years) and bullying victimisation (11 years) mediated these relationships. Results: Emotional dysregulation at age 7 years was associated with disordered eating [fully adjusted probit B (95% CI) = 0.082 (0.029, 0.134)] and self‐harm [fully adjusted probit B (95% CI) = 0.093 (0.036, 0.150)] at age 16 years. There was no evidence of sex interactions or difference in effects between self‐harm and disordered eating. Mediation models found social cognition was a key pathway to disordered eating (females 51.2%; males 27.0% of total effect) and self‐harm (females 15.7%; males 10.8% of total effect). Bullying victimisation was an important pathway to disordered eating (females 17.1%; males 10.0% of total effect), but only to self‐harm in females (15.7% of total effect). Indirect effects were stronger for disordered eating than self‐harm. Conclusions: In males and females, emotional dysregulation in early childhood is associated with disordered eating and self‐harm in adolescence and may be a useful target for prevention and treatment. Mediating pathways appeared to differ by sex and outcome, but social cognition was a key mediating pathway for both disordered eating and self‐harm. [ABSTRACT FROM AUTHOR]

Objective: We investigated recent trends in youth suicide and their associations with societal and psychological factors in Taiwan. Methods: Suicide data (1971–2019) for 10–24 year olds were extracted from Taiwan's national cause-of-death data files. We investigated changes in trends in youth suicide rates, societal factors (gross domestic product per capita, Gini index, overall and youth unemployment rates, divorce rates in people aged 40–59 years [i.e. the age of most 15–24 year olds' parents] and Internet use rates) and psychological distress indicators (youth self-harm rates and the prevalence of worry-related insomnia, and suicide ideation, plan and attempt) using joinpoint regression and graphic examinations. The associations of these factors with youth suicide rates were examined using Prais–Winsten regression. Results: Suicide rates in Taiwan's 10–24 year olds changed from a downward trend (2005–2014) to an upward trend in 2014 and increased 11.5% (95% confidence interval = [5.2%, 18.1%]) annually between 2014 and 2019. There was also an upturn in divorce rates among females aged 40–59 years in 2014 and self-harm rates among 15- to 24-year-old youth in 2013. The prevalence of self-reported insomnia and suicide ideation, plan and attempt in youth started to increase from 2013 to 2016. In the regression analysis, Internet use, female divorce rates and youth self-harm rates were positively associated with youth suicide rates. Conclusion: Suicide rates and the prevalence of suicidal behaviors began to increase in Taiwanese youth in the 2010s. These increases may be associated with concurrent rises in parental divorce rates, Internet use and poor sleep. Further research is needed to examine the mechanisms underlying recent increases in youth suicide risk. [ABSTRACT FROM AUTHOR]

Background: The occurrence of early childhood adversity is strongly linked to later self-harm, but there is poor understanding of how this distal risk factor might influence later behaviours. One possible mechanism is through an earlier onset of puberty in children exposed to adversity, since early puberty is associated with an increased risk of adolescent self-harm. We investigated whether early pubertal timing mediates the association between childhood adversity and later self-harm. Methods: Participants were 6698 young people from a UK population-based birth cohort (ALSPAC). We measured exposure to nine types of adversity from 0 to 9 years old, and self-harm when participants were aged 16 and 21 years. Pubertal timing measures were age at peak height velocity (aPHV – males and females) and age at menarche (AAM). We used generalised structural equation modelling for analyses. Results: For every additional type of adversity; participants had an average 12–14% increased risk of self-harm by 16. Relative risk (RR) estimates were stronger for direct effects when outcomes were self-harm with suicidal intent. There was no evidence that earlier pubertal timing mediated the association between adversity and self-harm [indirect effect RR 1.00, 95% confidence interval (CI) 1.00–1.00 for aPHV and RR 1.00, 95% CI 1.00–1.01 for AAM]. Conclusions: A cumulative measure of exposure to multiple types of adversity does not confer an increased risk of self-harm via early pubertal timing, however both childhood adversity and early puberty are risk factors for later self-harm. Research identifying mechanisms underlying the link between childhood adversity and later self-harm is needed to inform interventions. [ABSTRACT FROM AUTHOR]

Background: We aimed to identify groups of children presenting distinct perinatal adversity profiles and test the association between profiles and later risk of suicide attempt. Methods: Data were from the Québec Longitudinal Study of Child Development (QLSCD, N = 1623), and the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5734). Exposures to 32 perinatal adversities (e.g. fetal, obstetric, psychosocial, and parental psychopathology) were modeled using latent class analysis, and associations with a self-reported suicide attempt by age 20 were investigated with logistic regression. We investigated to what extent childhood emotional and behavioral problems, victimization, and cognition explained the associations. Results: In both cohorts, we identified five profiles: No perinatal risk, Poor fetal growth, Socioeconomic adversity, Delivery complications, Parental mental health problems (ALSPAC only). Compared to children with No perinatal risk, children in the Poor fetal growth (pooled estimate QLSCD-ALSPAC, OR 1.89, 95% CI 1.04–3.44), Socioeconomic adversity (pooled-OR 1.42, 95% CI 1.08–1.85), and Parental mental health problems (OR 1.74, 95% CI 1.27–2.40), but not Delivery complications, profiles were more likely to attempt suicide. The proportion of this effect mediated by the putative mediators was larger for the Socioeconomic adversity profile compared to the others. Conclusions: Perinatal adversities associated with suicide attempt cluster in distinct profiles. Suicide prevention may begin early in life and requires a multidisciplinary approach targeting a constellation of factors from different domains (psychiatric, obstetric, socioeconomic), rather than a single factor, to effectively reduce suicide vulnerability. The way these factors cluster together also determined the pathways leading to a suicide attempt, which can guide decision-making on personalized suicide prevention strategies. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that domestic violence (DV) is an important risk factor for suicidal behaviour. The level of risk and its contribution to the overall burden of suicidal behaviour among men and women has not been quantified in South Asia. We carried out a large case-control study to examine the association between DV and self-poisoning in Sri Lanka. Methods: Cases (N = 291) were patients aged ⩾18 years, admitted to a tertiary hospital in Kandy Sri Lanka for self-poisoning. Sex and age frequency matched controls were recruited from the hospital's outpatient department (N = 490) and local population (N = 450). Exposure to DV was collected through the Humiliation, Afraid, Rape, Kick questionnaire. Multivariable logistic regression models were conducted to estimate the association between DV and self-poisoning, and population attributable fractions were calculated. Results: Exposure to at least one type of DV within the previous 12 months was strongly associated with self-poisoning for women [adjusted OR (AOR) 4.08, 95% CI 1.60–4.78] and men (AOR 2.52, 95% CI 1.51–4.21), compared to those reporting no abuse. Among women, the association was strongest for physical violence (AOR 14.07, 95% CI 5.87–33.72), whereas among men, emotional abuse showed the highest risk (AOR 2.75, 95% CI 1.57–4.82). PAF% for exposure to at least one type of DV was 38% (95% CI 32–43) in women and 22% (95% CI 14–29) in men. Conclusions: Multi-sectoral interventions to address DV including enhanced identification in health care settings, community-based strategies, and integration of DV support and psychological services may substantially reduce suicidal behaviour in Sri Lanka. [ABSTRACT FROM AUTHOR]