Sex differences among children, adolescents and young adults for mental health service use within inpatient and outpatient settings, before and during the COVID-19 pandemic: a population-based study in Ontario, Canada

Objectives The pandemic and public health response to contain the virus had impacts on many aspects of young people’s lives including disruptions to daily routines, opportunities for social, academic, recreational engagement and early employment. Consequently, children, adolescents and young adults may have experienced mental health challenges that required use of mental health services. This study compared rates of use for inpatient and outpatient mental health services during the pandemic to pre-pandemic rates. Design Population-based repeated cross-sectional study. Setting Publicly delivered mental healthcare in primary and secondary settings within the province of Ontario, Canada. Participants All children 6–12 years of age (n=2 043 977), adolescents 13–17 years (n=1 708 754) and young adults 18–24 years (n=2 286 544), living in Ontario and eligible for provincial health insurance between March 2016 and November 2021. Primary outcome measures Outpatient mental health visits to family physicians and psychiatrists for: mood and anxiety disorders, alcohol and substance abuse disorders, other non-psychotic mental health disorders and social problems. Inpatient mental health visits to emergency departments and hospitalisations for: substance-related and addictive disorders, anxiety disorders, assault-related injuries, deliberate self-harm and eating disorders. All outcomes were analysed by cohort and sex. Results During the pandemic, observed outpatient visit rates were higher among young adults by 19.01% (95% CI: 15.56% to 22.37%; 209 vs 175 per 1000) and adolescent women 24.17% (95% CI: 18.93% to 29.15%; 131 vs 105 per 1000) for mood and anxiety disorders and remained higher than expected. Female adolescents had higher than expected usage of inpatient care for deliberate self-harm, eating disorders and assault-related injuries. Conclusions Study results raise concerns over prolonged high rates of mental health use during the pandemic, particularly in female adolescents and young women, and highlights the need to better monitor and identify mental health outcomes associated with COVID-19 containment measures and to develop policies to address these concerns

Maternal disability and newborn discharge to child protection in Ontario, Canada

Objectives One in 8 pregnancies are to women with disabilities. These mothers can face additional social, structural, and health-related challenges, and negative health care provider assumptions about their parenting capacity. We aimed to examine rates of newborn discharge to child protection comparing newborns of mothers with and without a disability. Method We are conducting a population-based cohort study in Ontario, Canada using linked administrative health data. The cohort includes all women in Ontario with a live birth between 2003 and 2020. Diagnostic algorithms were applied to health care encounters prior to pregnancy to identify maternal disability. We will use modified Poisson regression to estimate the relative risk of discharge to child protection immediately after the birth hospital stay, comparing newborns of women with physical, sensory, developmental, and multiple disabilities to those without disabilities. Models will be adjusted for socio-demographic factors, antenatal care receipt, and maternal mental illness and substance use disorders. Results The study cohort includes of over 1.4 million newborns delivered to women with physical disabilities (n=120,014), sensory disabilities (n=39,892), developmental disabilities (n=2,182), multiple disabilities (n=8,428), and no known disability (n=1,269,633). Analyses are ongoing and results will be concluded by the conference date. Conclusion Early infancy is a critical period for breastfeeding and maternal-infant bonding. Findings will inform the development of tailored services and resources for supporting women with disabilities in antenatal care and after birth by identifying those most at-risk of child protection intervention, thus potentially reducing maternal-newborn separations

Management of abnormal uterine bleeding by northern, rural and isolated primary care physicians: PART II: What do we need?

BACKGROUND: Abnormal uterine bleeding (AUB) is a common problem that affects one in five women during the pre-menopausal years. It is frequently managed by family physicians, especially in northern, rural and isolated areas where severe shortages of gynecologists exist. METHODS: We surveyed 194 family physicians in northern, rural and isolated areas of Ontario, Canada to determine their educational and resource needs for the management of AUB, with a specific focus on the relevance and feasibility of using clinical practice guidelines (CPGs). RESULTS: Most physicians surveyed did not use CPGs for the management of AUB because they did not know that such guidelines existed. The majority were interested in further education on the management of AUB through mailed CPGs and locally held training courses. A major theme among respondents was the need for more timely and effective gynecological referrals. CONCLUSION: A one-page diagnostic and treatment algorithm for AUB would be easy to use and would place minimal restrictions on physician autonomy. As the majority of physicians had Internet access, we recommend emailing and web posting in addition to mailing this algorithm. Local, hands-on courses including options for endometrial biopsy training would also be helpful for northern, rural and isolated physicians, many of whom cannot readily take time away from their practices

Management of abnormal uterine bleeding by northern, rural and isolated primary care physicians: PART I – How are we doing?

BACKGROUND: Canadian hysterectomy rates have declined in recent years. However, hysterectomy rates for discretionary indications, principally abnormal uterine bleeding (AUB), remain high in some regions. In northern Ontario, hysterectomy rates for women aged 34–45 are almost triple the rates in southern, urban areas. Primary care physicians (family doctors) usually manage AUB initially in these northern areas where a severe shortage of gynecologists exists. METHODS: We surveyed 194 family physicians in northern Ontario with a case scenario of a pre-menopausal woman with heavy vaginal bleeding to characterize management and to gain physicians' perspectives on the factors that affect it. RESULTS: To investigate her heavy vaginal bleeding, only 17% of physicians recommended a pelvic examination for the woman in our case scenario. Most physicians advocated a course of medical therapy before referral to a gynecologist, for whom the average waiting time was seven weeks. However, most physicians recommended referral after only one failed trial of medical treatment. Physicians felt that major deterrents to medical treatments were patient desires for immediate relief and/or permanent solutions, poor patient compliance and the high cost of medication. Only 25% of respondents indicated that they would perform an endometrial biopsy prior to referral. CONCLUSIONS: Family physicians would benefit from further education on appropriate investigations for AUB, primarily training in pelvic examination and endometrial biopsy techniques, as well as appropriate treatment algorithms. Further research into patient perspectives on treatment options is needed

Individual participant data meta analysis to compare EPDS accuracy to detect major depression with and without the self-harm item

Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10, is sometimes used in research due to concern about positive endorsements of item 10 and necessary follow-up. We assessed the equivalence of total score correlations and screening accuracy to detect major depression using the EPDS-9 versus full EPDS among pregnant and postpartum women. We searched Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science from database inception to October 3, 2018 for studies that administered the EPDS and conducted diagnostic classification for major depression based on a validated semi-structured or fully structured interview among women aged 18 or older during pregnancy or within 12 months of giving birth. We conducted an individual participant data meta-analysis. We calculated Pearson correlations with 95% prediction interval (PI) between EPDS-9 and full EPDS total scores using a random effects model. Bivariate random-effects models were fitted to assess screening accuracy. Equivalence tests were done by comparing the confidence intervals (CIs) around the pooled sensitivity and specificity differences to the equivalence margin of δ = 0.05. Individual participant data were obtained from 41 eligible studies (10,906 participants, 1407 major depression cases). The correlation between EPDS-9 and full EPDS scores was 0.998 (95% PI 0.991, 0.999). For sensitivity, the EPDS-9 and full EPDS were equivalent for cut-offs 7-12 (difference range - 0.02, 0.01) and the equivalence was indeterminate for cut-offs 13-15 (all differences - 0.04). For specificity, the EPDS-9 and full EPDS were equivalent for all cut-offs (difference range 0.00, 0.01). The EPDS-9 performs similarly to the full EPDS and can be used when there are concerns about the implications of administering EPDS item 10.This study was funded by the Canadian Institutes of Health Research (CIHR, KRS-140994). Dr. Qiu was supported by a scholarship from the China Scholarship Council. Drs. Wu and Levis were supported by Fonds de recherche du Québec—Santé (FRQ-S) Postdoctoral Training Fellowships. Dr. Benedetti was supported by a Fonds de recherche du Québec – Santé (FRQS) researcher salary award. Dr. Thombs was supported by a Tier 1 Canada Research Chair. Ms. Rice was supported by a Vanier Canada Graduate Scholarship. The primary study by Alvarado et al. was supported by the Ministry of Health of Chile. The primary study by Barnes et al. was supported by a grant from the Health Foundation (1665/608). The primary study by Beck et al. was supported by the Patrick and Catherine Weldon Donaghue Medical Research Foundation and the University of Connecticut Research Foundation. The primary study by Helle et al. was supported by the Werner Otto Foundation, the Kroschke Foundation, and the Feindt Foundation. The primary study by Figueira et al. was supported by the Brazilian Ministry of Health and by the National Counsel of Technological and Scientific Development (CNPq) (Grant no.403433/2004-5). The primary study by Couto et al. was supported by the National Counsel of Technological and Scientific Development (CNPq) (Grant no. 444254/2014-5) and the Minas Gerais State Research Foundation (FAPEMIG) (Grant no. APQ-01954-14). The primary study by Chorwe-Sungani et al. was supported by the University of Malawi through grant QZA-0484 NORHED 2013. The primary study by de Figueiredo et al. was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo. The primary study by Tissot et al. was supported by the Swiss National Science Foundation (grant 32003B 125493). The primary study by Fernandes et al. was supported by grants from the Child: Care Health and Development Trust and the Department of Psychiatry, University of Oxford, Oxford, UK, and by the Ashok Ranganathan Bursary from Exeter College, University of Oxford. Dr. Fernandes is supported by a University of Southampton National Institute for Health Research (NIHR) academic clinical fellowship in Paediatrics. The primary study by van Heyningen et al. was supported by the Medical Research Council of South Africa (fund no. 415865), Cordaid Netherlands (Project 103/10002 G Sub 7) and the Truworths Community Foundation Trust, South Africa. Dr. van Heyningen was supported by the National Research Foundation of South Africa and the Harry Crossley Foundation. VHYTHE001/1232209. The primary study by Tendais et al. was supported under the project POCI/SAU-ESP/56397/2004 by the Operational Program Science and Innovation 2010 (POCI 2010) of the Community Support Board III and by the European Community Fund FEDER. The primary study by Fisher et al. was supported by a grant under the Invest to Grow Scheme from the Australian Government Department of Families, Housing, Community Services and Indigenous Affairs. The primary study by Green et al. was supported by a grant from the Duke Global Health Institute (453-0751). The primary study by Howard et al. was supported by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Numbers RP-PG-1210-12002 and RP-DG-1108-10012) and by the South London Clinical Research Network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The primary study by Kettunen et al. was supported with an Annual EVO Financing (Special government subsidies from the Ministry of Health and Welfare, Finland) by North Karelia Central Hospital and Päijät-Häme Central Hospital. The primary study by Phillips et al. was supported by a scholarship from the National Health and Medical and Research Council (NHMRC). The primary study by Roomruangwong et al. was supported by the Ratchadaphiseksomphot Endowment Fund 2013 of Chulalongkorn University (CU-56-457-HR). The primary study by Martínez et al. was supported by Iniciativa Científica Milenio, Chile, process # IS130005 and by Fondo Nacional de Desarrollo Científico y Tecnológico, Chile, process # 1130230. The primary study by Nakić Radoš et al. was supported by the Croatian Ministry of Science, Education, and Sports (134-0000000-2421). The primary study by Usuda et al. was supported by Grant-in-Aid for Young Scientists (A) from the Japan Society for the Promotion of Science (primary investigator: Daisuke Nishi, MD, PhD), and by an Intramural Research Grant for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry, Japan. The primary study by Pawlby et al. was supported by a Medical Research Council UK Project Grant (number G89292999N). The primary study by Rochat et al. was supported by grants from the University of Oxford (HQ5035), the Tuixen Foundation (9940), the Wellcome Trust (082384/Z/07/Z and 071571), and the American Psychological Association. Dr. Rochat receives salary support from a Wellcome Trust Intermediate Fellowship (211374/Z/18/Z). The primary study by Rowe et al. was supported by the diamond Consortium, beyondblue Victorian Centre of Excellence in Depression and Related Disorders. The primary study by Comasco et al. was supported by funds from the Swedish Research Council (VR: 521-2013-2339, VR:523-2014-2342), the Swedish Council for Working Life and Social Research (FAS: 2011-0627), the Marta Lundqvist Foundation (2013, 2014), and the Swedish Society of Medicine (SLS-331991). The primary study by Smith-Nielsen et al. was supported by a grant from the charitable foundation Tryg Foundation (Grant ID no 107616). The primary study by Prenoveau et al. was supported by The Wellcome Trust (grant number 071571). The primary study by Stewart et al. was supported by Professor Francis Creed’s Journal of Psychosomatic Research Editorship fund (BA00457) administered through University of Manchester. The primary study by Su et al. was supported by grants from the Department of Health (DOH94F044 and DOH95F022) and the China Medical University and Hospital (CMU94-105, DMR-92-92 and DMR94-46). The primary study by Tandon et al. was funded by the Thomas Wilson Sanitarium. The primary study by Tran et al. was supported by the Myer Foundation who funded the study under its Beyond Australia scheme. Dr. Tran was supported by an early career fellowship from the Australian National Health and Medical Research Council. The primary study by Vega-Dienstmaier et al. was supported by Tejada Family Foundation, Inc, and Peruvian-American Endowment, Inc. The primary study by Yonkers et al. was supported by a National Institute of Child Health and Human Development grant (5 R01HD045735). No other authors reported funding for primary studies or for their work on this study

Maternal and infant outcomes associated with lithium use in pregnancy

Background Concerns about teratogenicity and offspring complications limit use of lithium in pregnancy. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations. Methods Meta-analysis of primary data analyzed using a shared protocol. Six study sites participated: Denmark, Canada, Netherlands, Sweden, UK, and US, totaling 727 lithium-exposed pregnancies compared to 21,397 reference pregnancies in mothers with a mood disorder, but unexposed to lithium. Main outcome measures included: (1) pregnancy complications, (2) delivery outcomes, (3) neonatal readmission to hospital within 28 days of birth, and (4) congenital malformations (major malformations and cardiac malformations). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were generated using logistic regression models. Site-specific prevalence rates and ORs were pooled using random-effects meta-analytic models. Findings Lithium exposure was not associated with any of the pre-defined pregnancy complications or delivery outcomes. There was an increased risk for neonatal readmission in lithium exposed (27·5%) versus reference group (14·3%) (Pooled aOR1·62; 95% CI: 1·12–2·33). Lithium exposure during first trimester was associated with increased risk of major malformations (7·4% versus 4·3%; pooled aOR 1·71, 95% CI: 1·07–2·72). Similarly, more lithium exposed children had major cardiac malformations, albeit not stasticially significant (2·1% versus 1·6%; pooled aOR 1·54, 95% CI: 0·64–3·70). Limitations in our study include: Serum lithium 5 levels were not available, hence no analyses related to dose-response effects could be performed, and residual confounding from e.g. substance abuse cannot be ruled out. Interpretation Treatment decisions must weigh the potential for increased risks, considering both effct sizes and the precision of the estimates, in particular associated with first-trimester lithium use against its effectiveness at reducing relapse

Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes

OBJECTIVE: Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring. METHODS: The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018. RESULTS: Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels <0.64 mEq/L and dosages <600 mg/day had more reactive newborns without an increased risk of cardiac malformations. CONCLUSIONS: The risk associated with lithium exposure at any time during pregnancy is low, and the risk is higher for first-trimester or higher-dosage exposure. Ideally, pregnancy should be planned during remission from bipolar disorder and lithium prescribed within the lowest therapeutic range throughout pregnancy, particularly during the first trimester and the days immediately preceding delivery, balancing the safety and efficacy profile for the individual patient

Overestimation of Postpartum Depression Prevalence Based on a 5-item Version of the EPDS:Systematic Review and Individual Participant Data Meta-analysis

Objective:The Maternal Mental Health in Canada, 2018/2019, survey reported that 18% of 7,085 mothers who recently gave birth reported "feelings consistent with postpartum depression" based on scores >= 7 on a 5-item version of the Edinburgh Postpartum Depression Scale (EPDS-5). The EPDS-5 was designed as a screening questionnaire, not to classify disorders or estimate prevalence; the extent to which EPDS-5 results reflect depression prevalence is unknown. We investigated EPDS-5 >= 7 performance relative to major depression prevalence based on a validated diagnostic interview, the Structured Clinical Interview for DSM (SCID).Methods:We searched Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO, and the Web of Science Core Collection through June 2016 for studies with data sets with item response data to calculate EPDS-5 scores and that used the SCID to ascertain depression status. We conducted an individual participant data meta-analysis to estimate pooled percentage of EPDS-5 >= 7, pooled SCID major depression prevalence, and the pooled difference in prevalence.Results:A total of 3,958 participants from 19 primary studies were included. Pooled prevalence of SCID major depression was 9.2% (95% confidence interval [CI] 6.0% to 13.7%), pooled percentage of participants with EPDS-5 >= 7 was 16.2% (95% CI 10.7% to 23.8%), and pooled difference was 8.0% (95% CI 2.9% to 13.2%). In the 19 included studies, mean and median ratios of EPDS-5 to SCID prevalence were 2.1 and 1.4 times.Conclusions:Prevalence estimated based on EPDS-5 >= 7 appears to be substantially higher than the prevalence of major depression. Validated diagnostic interviews should be used to establish prevalence

Overestimation of Postpartum Depression Prevalence Based on a 5-item Version of the EPDS: Systematic Review and Individual Participant Data Meta-analysis

Objective:The Maternal Mental Health in Canada, 2018/2019, survey reported that 18% of 7,085 mothers who recently gave birth reported "feelings consistent with postpartum depression" based on scores >= 7 on a 5-item version of the Edinburgh Postpartum Depression Scale (EPDS-5). The EPDS-5 was designed as a screening questionnaire, not to classify disorders or estimate prevalence; the extent to which EPDS-5 results reflect depression prevalence is unknown. We investigated EPDS-5 >= 7 performance relative to major depression prevalence based on a validated diagnostic interview, the Structured Clinical Interview for DSM (SCID).Methods:We searched Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO, and the Web of Science Core Collection through June 2016 for studies with data sets with item response data to calculate EPDS-5 scores and that used the SCID to ascertain depression status. We conducted an individual participant data meta-analysis to estimate pooled percentage of EPDS-5 >= 7, pooled SCID major depression prevalence, and the pooled difference in prevalence.Results:A total of 3,958 participants from 19 primary studies were included. Pooled prevalence of SCID major depression was 9.2% (95% confidence interval [CI] 6.0% to 13.7%), pooled percentage of participants with EPDS-5 >= 7 was 16.2% (95% CI 10.7% to 23.8%), and pooled difference was 8.0% (95% CI 2.9% to 13.2%). In the 19 included studies, mean and median ratios of EPDS-5 to SCID prevalence were 2.1 and 1.4 times.Conclusions:Prevalence estimated based on EPDS-5 >= 7 appears to be substantially higher than the prevalence of major depression. Validated diagnostic interviews should be used to establish prevalence

Meta-analyses of genome-wide association studies for postpartum depression

Objective: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. Method: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)–based heritability (), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. Results: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. Conclusions: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone)