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Background Antidepressants have been proposed to act via their influence on emotional processing. We investigated the effect of discontinuing maintenance antidepressant treatment on positive and negative self-referential recall and the association between self-referential recall and risk of relapse. Methods The ANTLER trial was a large (N = 478) pragmatic double-blind trial investigating the clinical effectiveness of long-term antidepressant treatment for preventing relapse in primary care patients. Participants were randomised to continue their maintenance antidepressants or discontinue via a taper to placebo. We analysed memory for positive and negative personality descriptors, assessed at baseline, 12- and 52-week follow-up. Results The recall task was completed by 437 participants. There was no evidence of an effect of discontinuation on self-referential recall at 12 [positive recall ratio 1.00, 95% CI (0.90–1.11), p = 0.93; negative recall ratio 1.00 (0.87–1.14), p = 0.87] or 52 weeks [positive recall ratio 1.03 (0.91–1.17), p = 0.62; negative recall ratio 1.00 (0.86–1.15), p = 0.96; ratios larger than one indicate higher recall in the discontinuation group], and no evidence of an association between recall at baseline or 12 weeks and later relapse [baseline, positive hazard ratio (HR) 1.02 (0.93–1.12), p = 0.74; negative HR 1.01 (0.90–1.13), p = 0.87; 12 weeks, positive HR 0.99 (0.89–1.09), p = 0.81; negative HR 0.98 (0.84–1.14), p = 0.78; ratios larger than one indicate a higher frequency of relapse in those with higher recall]. Conclusions We found no evidence that discontinuing long-term antidepressants altered self-referential recall or that self-referential recall was associated with risk of relapse. These findings suggest that self-referential recall is not a neuropsychological marker of antidepressant action.

Catatonia is a debilitating psychomotor disorder. Previous neuroimaging studies have used small samples with inconsistent results. The authors aimed to describe the structural neuroradiological abnormalities in clinical magnetic resonance imaging (MRI) brain scans of patients with catatonia, comparing them with scans of psychiatric inpatients without catatonia. They report the largest study of catatonia neuroimaging to date.In this retrospective case-control study, neuroradiological reports of psychiatric inpatients who had undergone MRI brain scans for clinical reasons were examined. Abnormalities were classified by lateralization, localization, and pathology. The primary analysis was prediction of catatonia by presence of an abnormal MRI scan, adjusted for age, sex, Black race-ethnicity, and psychiatric diagnosis.Scan reports from 79 patients with catatonia and 711 other psychiatric inpatients were obtained. Mean age was 36.4 (SD=17.3) for the cases and 44.5 (SD=19.9) for the comparison group. Radiological abnormalities were reported in 27 of 79 cases (34.2%) and in 338 of 711 in the comparison group (47.5%) (odds ratio [OR]=0.57, 95% confidence interval [CI]=0.35, 0.93; adjusted OR=1.11, 95% CI=0.58, 2.14). Among the cases, most abnormal scans had bilateral abnormalities (N=23, 29.1%) and involved the forebrain (N=25, 31.6%) and atrophy (N=17, 21.5%).Patients with catatonia were commonly reported to have brain MRI abnormalities, which largely consisted of diffuse cerebral atrophy rather than focal lesions. No evidence was found that these abnormalities were more common than in other psychiatric inpatients undergoing neuroimaging, after adjustment for demographic variables. Study limitations included a heterogeneous control group and selection bias in requesting scans.

BackgroundEating disorders are stigmatised. Little is known about whether stigma has decreased over time and which groups hold more stigmatising beliefs.AimsTo explore whether stigma towards eating disorders has changed between 1998 and 2008 and whether it varies by sociodemographic characteristics.MethodWe used the Office for National Statistics Omnibus surveys 1998 and 2008. As outcomes, we selected four questions eliciting participants’ views on issues of blame and ability to recover, and compared their mean scores across eating disorders, depression and alcohol dependence in both years. We used multivariable linear regressions to investigate associations between sociodemographic characteristics and each stigma domain.ResultsIn total, 2720 participants had data on all variables of interest. Compared with 1998, in 2008 stigmatising views towards eating disorders improved. In both years, participants believed it was easier to recover from eating disorders than depression or alcohol dependence. Respondents believed people with eating disorders were more to blame for their condition than those with depression, but less than those with alcohol dependence. Men, those with less formal education, and those from ethnic minority backgrounds were more likely to place greater blame on individuals for their mental illness. Men were more likely than women to think it was possible to recover from an eating disorder.ConclusionsStigmatising attitudes towards people with eating disorders have improved over time, but are still greater than those observed for other mental illnesses. Improving eating disorder mental health literacy could help to reduce these negative views and lead to improved quality of life, greater help-seeking and better prognosis.

BackgroundEmotional 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.MethodsWe analysed Avon Longitudinal Study of Parents and Children data on 3453 males and 3481 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.ResultsEmotional 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.ConclusionsIn 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.

Objective: Individuals with bulimia nervosa and binge eating disorder have greater cardiovascular morbidity than the general population. Longitudinal re search on the association between binge eating and metabolic syndrome is lim ited. We tested the longitudinal association between binge eating and metabolic syndrome and its components in a large population sample of Brazilian adults. Methods: We used data from Brazilian Longitudinal Study of Adult Health (ELSA-Brasil, N = 15,105). To test for the association between binge eating at baseline (2008–2010) and metabolic syndrome at follow-up (2012–2014), we used univariable and multivariable logistic regression models progressively adjusting for potential socio-demographic confounders, number of metabolic syndrome components, and body mass index (BMI) at baseline. Results: In total, 13,388 participants (54.8% female; 52.2% white) had complete data on all variables of interest. Binge eating was associated with increased odds of metabolic syndrome at follow-up (odds ratio (OR):1.66, 95% confidence inter vals (CI): 1.44, 1.75). However, the size of this association was attenuated after in cluding number of metabolic syndrome components at baseline (OR:1.19, 95% CI: 1.05, 1.35) and was no longer present after adjusting for baseline BMI (OR:1.09, 95% CI: 0.96, 1.25). Binge eating was also associated with higher odds of hyper tension (OR:1.14, 95% CI: 0.99, 1.37) and hypertriglyceridemia (OR:1.21, 95% CI: 1.06, 1.37) at the follow-up assessment after adjustment for all confounders. Conclusions: Individuals who binge eat are at increased risk of metabolic syndrome via increased BMI, and of hypertriglyceridemia and hypertension independently of BMI. If these are causal associations, effective interventions for binge eating could also have beneficial effects on metabolic health outcomes..

Summary Background Loneliness is experienced by a third of older adults in the UK and is a modifiable potential risk factor for depressive symptoms. It is unclear how the association between loneliness and depressive symptoms persists over time, and whether it is independent of related social constructs and genetic confounders. We aimed to investigate the association between loneliness and depressive symptoms, assessed on multiple occasions during 12 years of follow-up, in a large, nationally representative cohort of adults aged 50 years and older in England. Methods We did a longitudinal study using seven waves of data that were collected once every 2 years between 2004 and 2017, from adults aged 50 years and older in the English Longitudinal Study of Ageing (ELSA). The exposure was loneliness at baseline (wave two), measured with the short 1980 revision of the University of California, Los Angeles Loneliness Scale (R-UCLA). The primary outcome was a score indicating severity of depression measured at six subsequent timepoints (waves three to eight), using the eight-item version of the Centre for Epidemiologic Studies Depression Scale (CES-D). Analyses were linear multilevel regressions, before and after adjusting for social isolation, social support, polygenic risk scores, and other sociodemographic and health-related confounders. The secondary outcome was depression diagnosis, measured using a binary version of the CES-D. Findings 4211 (46%) of 9171 eligible participants had complete data on exposure, outcome, and confounders, and were included in our complete case sample. After all adjustments, a 1-point increase in loneliness score was associated with a 0·16 (95% CI 0·13–0·19) increase in depressive symptom severity score (averaged across all follow-ups). We estimated a population attributable fraction for depression associated with loneliness of 18% (95% CI 12–24) at 1 year of follow-up and 11% (3–19) at the final follow-up (wave eight), suggesting that 11–18% of cases of depression could potentially be prevented if loneliness were eliminated. Associations between loneliness and depressive symptoms remained after 12 years of follow-up, although effect sizes were smaller with longer follow-up. Interpretation Irrespective of other social experiences, higher loneliness scores at baseline were associated with higher depression symptom severity scores during 12 years of follow-up among adults aged 50 years and older. Interventions that reduce loneliness could prevent or reduce depression in older adults, which presents a growing public health problem worldwide. Funding National Institute on Aging and a consortium of UK Government departments coordinated by the National Institute for Health Research.

Highlights • Levels of IL6 at 9 years were not associated with eating disorders at 14, 16, and 18. • Lower CRP levels at 9 were associated with greater disordered eating in adolescence. • The associations we observed were weak and residual confounding cannot be excluded., Objective Few studies have explored the association between inflammation and eating disorders and none used a longitudinal design. We investigated the association between serum-levels of interleukin 6 (IL-6) and C-reactive protein (CRP) measured in childhood and eating disorders and related behaviours and cognitions in adolescence in a large general population sample. Methods We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Our exposures were thirds of IL6 and CRP derived from serum measurements taken at age nine years, and outcomes were eating disorder diagnoses and self-reported disordered eating behaviours at ages 14, 16, and 18 years. We used univariable and multivariable multilevel logistic regression models adjusting for a number of potential confounders, including sex, fat mass, and pre-existing mental health difficulties. Results Our sample included 3480 children. Those in the top third of CRP had lower odds of binge eating (odds ratio(OR):0.62, 95% confidence interval (CI):0.39,1.00,p “equals” 0.05) and fasting (OR:0.63, 95% CI:0.38,1.07,p “equals” 0.09) after adjustment for confounders. We also observed weak associations of comparable magnitude for purging, anorexia nervosa, and bulimia nervosa. We did not find any associations between levels of IL6 and any of the outcomes under study. Conclusions There was little evidence of an association between CRP and IL-6 and adolescent eating disorder outcomes. The inverse association observed between CRP and binge eating was unexpected, so caution is needed when interpreting it. One possible explanation is that higher CRP levels could have a protective role for disordered eating by affecting appetitive traits.

Purpose: To identify potential determinants of the Total/ionized Ca ratio (T/iCa), a marker of citrate acctimulation. Materials and methods: Single-center retrospective observational study evaluating citrate dose, citrate target, albumin, phosphate, pH, lactate, and APACHE II score as potential determinants. Linear mixed models (LMM) using citrate dose and citrate target were developed describing associations with T/iCa. Results: From a dataset of 471 samples in 103 patients, an LMM in 379 complete samples (95 patients) sets revealed that citrate dose, pH, phosphate, albumin and APACHE were interactively related to T/iCa. A rising citrate dose was associated with a higher increase in T/iCa when phosphate was high, and less when phosphate was low. A rising albumin was associated with a higher increase in T/iCa when APACHE was high and phosphate was low and less when APACHE was low and phosphate high. In case of acidosis, a rising lactate was associated with a higher increase in T/iCa. In the LMM using citrate target, citrate target and pH were the main independent predictors of T/iCa with albumin, phosphate and APACHE score as modifiers. Conclusions: Besides citrate dose, a high pH and high phosphate, albumin and APACHE are also associated with a rising T/iCa. (C) 2020 Elsevier Inc. All rights reserved. Boer, W (corresponding author), Ziekenhuis Oost Limburg ZOL, Dept Anesthesiol Intens Care Med Emergency Med &, Schiepsehos 6, B-3600 Genk, Belgium. willem.boer@zol.be

SUMMARYBackgroundVaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles displaying the receptor-binding domain (RBD) in a highly immunogenic array.MethodsWe conducted a randomized, placebo-controlled, observer-blinded, phase 1/2 trial to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19–85 years. The main outcomes included solicited and unsolicited adverse events; anti-SARS-CoV-2 RBD IgG antibody and neutralizing antibody responses; T-cell immune responses.FindingsOf 328 participants who underwent randomization, 327 participants received at least 1 dose of vaccine. Each received either 10 μg GBP510 adjuvanted with AS03 (n = 101), 10 μg unadjuvanted GBP510 (n = 10), 25 μg GBP510 adjuvanted with AS03 (n = 104), 25 μg unadjuvanted GBP510 (n = 51), or placebo (n = 61). Most solicited adverse events were mild-to-moderate in severity and transient. Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic adverse events. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163.6/2599.2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 μg/25 μg) by 14 days after the second dose. Two-dose vaccination with 10 μg or 25 μg GBP510 adjuvanted with AS03 induced high titers of neutralizing antibody via pseudovirus (1369.0/1431.5 IU/mL) and wild-type virus (949.8/861.0 IU/mL) assays.InterpretationGBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3.FundingCoalition for Epidemic Preparedness InnovationsRESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for research articles published by December 31, 2021, using the terms “COVID-19” or “SARS-CoV-2,” “vaccine,” and “clinical trial.” In previously reported randomized clinical trials, we found that mRNA vaccines were more immunogenic than adenovirus-vectored vaccines. Solicited adverse events were more frequent and more severe in intensity after the first dose compared to the second dose for adenovirus-vectored vaccines, whereas they increased after the second dose of mRNA or recombinant spike-protein nanoparticle vaccines.Added value of this studyThis is the first human study evaluating the immunogenicity and safety of recombinant SARS-CoV-2 protein nanoparticle with and without adjuvant AS03, designed to elicit functional cross-protective responses via receptor-binding domain (RBD). Both 10 and 25 μg of GBP510 with AS03 formulations were well tolerated with an acceptable safety profile. Potent humoral immune responses against the SARS-CoV-2 RBD were induced and peaked by day 42 (14 days after the second dose). In addition, GBP510 adjuvanted with AS03 elicited a noticeable Th1 response, with production of IFN-γ, TNF-α, and IL-2. IL-4 was inconsistent and IL-5 nearly inexistent response across all groups.Implications of the available evidenceThe results from this phase 1/2 trial indicate that GBP510 adjuvanted with AS03 has an acceptable safety profile with no vaccine-related serious adverse events. Two-dose immunization with GBP510 adjuvanted with AS03 induced potent humoral and cellular immune responses against SARS-CoV-2.

Purpose Previous research suggests that eating disorders may be associated with certain personality profiles; however, there is limited research investigating associations with night eating syndrome (NES). This research suggests harm avoidance personality trait is higher in NES individuals than in the general population, however, evidence of associations with other personality traits is inconsistent. To understand which personality traits are associated with NES symptoms, the current study aimed to improve understanding of the relationship between NES symptoms and a range of personality traits, addressing limitations in the earlier literature in this area by controlling for common confounders. Methods Baseline data were analysed from an outpatient psychotherapy trial for 111 women with bulimia nervosa or binge eating disorder. Pre-treatment measures of personality traits (measured with the Temperament and character inventory—revised) and NES symptoms (measured with the Night eating questionnaire) were used. Regression analyses tested associations between these variables, adjusting for potential confounders, including age and ethnicity. Results Low cooperativeness scores were associated with greater NES symptoms in the multivariable model (mean difference: − 0.10, 95% confidence intervals: − 0.20 to − 0.01, p = 0.033). There was weak evidence of associations between both high harm avoidance and low self-directedness personality traits and greater NES symptoms. Conclusions This study adds to the limited research measuring associations between a range of personality traits and NES, addressing limitations of previous research. Weak evidence for an association between high harm avoidance and low self-directedness and increased NES symptoms was found. A novel association was found between low cooperativeness and greater NES symptoms. Further research is needed to validate its presence in those with and without comorbid eating disorders and to examine the relative change in NES, eating disorder symptoms and personality scores in treatments focusing on cooperativeness. Level of evidence Level IV (cross-sectional data from a randomised controlled trial, CTB/04/08/139).

Importance People with anorexia nervosa often experience difficulties regulating their emotions. There is no longitudinal evidence as to whether these differences are already present in childhood or when they begin to emerge.Objective To investigate the association between emotion regulation trajectories from 3 to 7 years of age and symptoms of anorexia nervosa and atypical anorexia nervosa in adolescence.Design, Setting, and Participants This cohort study included all children with complete exposure data in the Millennium Cohort Study, a UK general population birth cohort. Data were acquired from June 2001 to March 2016 and analyzed from June to November 2020.Exposures Mothers reported on their children’s emotion regulation skills at 3, 5, and 7 years of age using the Children’s Social Behavior Questionnaire. Multilevel models were used to derive early childhood emotion regulation scores (ie, predicted intercept) and within-child changes in emotion regulation scores from 3 to 7 years of age (ie, predicted slope).Main Outcome and Measures Symptoms consistent with a DSM-5 diagnosis of anorexia nervosa or atypical anorexia nervosa at 14 years of age, defined using a range of questions relative to body image, weight perception, and dieting behaviors (hereinafter referred to as broad anorexia nervosa). Univariable and multivariable logistic regression models tested the association between exposures and outcome. Regression models were adjusted for child and family sociodemographic and socioeconomic characteristics and mental health difficulties, prenatal and perinatal factors, child’s cognitive development, and maternal attachment.Results A total of 15 896 participants (85.7% of total sample; 51.0% boys; 84.5% White individuals) had complete data on the exposure and were included in the main analyses. Among those with complete exposure and outcome data (9912 of the analytical sample [62.4%]), 97 participants (1.0%; 86 [88.7%] girls and 85 [87.6%] White individuals) had symptoms consistent with a diagnosis of broad anorexia nervosa at 14 years of age. No evidence suggested that children with lower emotion regulation ability at 3 years of age had greater odds of later reporting symptoms of broad anorexia nervosa (odds ratio [OR], 1.21; 95% CI, 0.91-1.63). However, children whose emotion regulation skills did not improve over childhood and who had greater problems regulating emotions at 7 years of age had higher odds of having broad anorexia nervosa at 14 years of age (OR, 1.45; 95% CI, 1.16-1.83).Conclusions and Relevance These findings suggest that difficulties in developing age-appropriate emotion regulation skills in childhood are associated with experiencing broad anorexia nervosa in adolescence. Interventions to support the development of emotion regulation skills across childhood may help reduce the incidence of anorexia nervosa.

Purpose Loneliness is an important issue for mental health service users. However, it has not been a particularly prominent focus of recent mental health research. This paper aimed to explore the severity of loneliness among people leaving mental health community crisis services, and to identify factors associated with loneliness. Methods A total of 399 participants experiencing mental health crises recruited for a research trial from community crisis services were included in this cross-sectional study. They completed the eight-item measure of the University of California at Los Angeles Loneliness Scale and a set of instruments assessing socio-demographic, psychosocial, and psychiatric variables. Results Severity of loneliness was high among people leaving community crisis services. Longer years since first contact with mental health services (2–10 years, coefficient = 1.83, 95% CI 0.49–3.16; more than 10 years, coefficient = 1.91, 95% CI 0.46–3.36) and more severe affective symptoms (coefficient = 0.32, 95% CI 0.23–0.40) were associated with greater loneliness, whereas bigger social network size (coefficient = − 0.56, 95% CI − 0.76 to − 0.36) and greater social capital (coefficient = − 0.16, 95% CI − 0.31 to − 0.003) were associated with less severe loneliness. Conclusions This paper supports a view that people experiencing mental health crises often report relatively severe loneliness, and that loneliness tends to become more severe during the course of illness. A greater awareness of loneliness among mental health professionals may be beneficial. Loneliness is a potential focus of the development of interventions to improve the lives and outcomes of people with significant mental health problems.

Background Urban birth is associated with risk of non-affective psychoses, but the association with subclinical positive and negative symptoms is less clear, despite emerging evidence. Further the extent to which these findings are confounded by polygenic risk scores (PRS) for schizophrenia is also unknown. Methods Using data from the Avon Longitudinal Study of Parents and Children, linked to census geographical indicators, we examined whether various indices of urbanicity at birth were associated with negative and positive psychotic symptoms at age 16 and 18 years, respectively. We used logistic regression models, controlling for child’s ethnicity, maternal age, education, marital status, social class, depressive symptoms, other neighborhood exposures, and, in a subsample of children of white ethnicity (N = 10 283), PRS for schizophrenia. Results Amongst 11 879 adolescents, those born in the most densely populated tertile had greater odds of reporting positive psychotic experiences, after multivariable adjustment (odds ratio [OR]: 1.57, 95% confidence intervals (CIs): 1.14–2.17). Adolescents born in the most socially fragmented neighborhoods had greater odds of negative symptoms, after multivariable adjustment (OR: 1.43, 95% CI: 1.06–1.85). Although we found that greater schizophrenia PRS were associated with an increased risk of being born in more deprived and fragmented (bot not more densely populated areas), these associations were not confounded by PRS. Interpretation Birth into more densely populated and socially fragmented environments increased risk of positive and negative psychotic phenomena in adolescence, respectively, suggesting that different forms of neighborhood social adversity may impinge on different psychopathophysiologies associated with the clinical expression of psychosis.

Background: The effect of the Colombian armed conflict on the mental health of adolescents is still poorly understood. Aims: Given social interventions are most likely to inform policy, we tested whether two potential intervention targets, family functioning and social capital, were associated with mental health in Colombian adolescents, and whether this was moderated by experience of violence and displacement. Methods: We examined the cross-sectional association between family functioning, cognitive social capital, structural social capital and 12-month prevalence of Composite International Diagnostic Interview (CIDI) diagnosed psychiatric disorder, using data on 12 to 17-year-old adolescents ( N = 1,754) from the 2015 National Mental Health Survey of Colombia, a nationally representative epidemiological study. We tested whether associations survived cumulative adjustment for demographic confounders, experience of non-specific violence and harm and displacement by armed conflict. Results: Neither structural nor cognitive social capital were associated with better mental health. Better family functioning was associated with reduced risk of poor mental health in an unadjusted analysis (OR 0.90 [0.85–0.96]), and after cumulative adjustments for demographic confounders (OR 0.91 [0.86–0.97]), non-specific violence and harm (OR 0.91 [0.86–0.97]) and social capital variables (OR 0.91 [0.85–0.97]). In the final model, each additional point on the family APGAR scale was associated with a 9% reduced odds of any CIDI diagnosed disorder in the last 12 months. Conclusions: Better family functioning was associated with better mental health outcomes for all adolescents. This effect remained present in those affected by the armed conflict even after accounting for potential confounders.

Background Young adults and especially those with pre-existing mental health conditions, such as disordered eating and self-harm, appear to be at greater risk of developing metal health problems during the COVID-19 pandemic. However, it is unclear whether this increased risk is affected by any changes in lockdown restrictions, and whether any lifestyle changes could moderate this increased risk. Methods In a longitudinal UK-based birth cohort (The Avon Longitudinal Study of Parents and Children, ALSPAC) we assessed the relationship between pre-pandemic measures of disordered eating and self-harm and mental health during the COVID-19 pandemic in 2657 young adults. Regression models examined the relationship between self-reported disordered eating, self-harm, and both disordered eating and self-harm at age 25 years and depressive symptoms, anxiety symptoms and mental wellbeing during a period of eased restrictions in the COVID-19 pandemic (May–July 2020) when participants were aged 27–29 years. Analyses were adjusted for sex, questionnaire completion date, pre-pandemic socioeconomic disadvantage and pre-pandemic mental health and wellbeing. We also examined whether lifestyle changes (sleep, exercise, alcohol, visiting green space, eating, talking with family/friends, hobbies, relaxation) in the initial UK lockdown (April–May 2020) moderated these associations. Results Pre-existing disordered eating, self-harm and comorbid disordered eating and self-harm were all associated with the reporting of a higher frequency of depressive symptoms and anxiety symptoms, and poorer mental wellbeing during the pandemic compared to individuals without disordered eating and self-harm. Associations remained when adjusting for pre-pandemic mental health measures. There was little evidence that interactions between disordered eating and self-harm exposures and lifestyle change moderators affected pandemic mental health and wellbeing. Conclusions Young adults with pre-pandemic disordered eating, self-harm and comorbid disordered eating and self-harm were at increased risk for developing symptoms of depression, anxiety and poor mental wellbeing during the COVID-19 pandemic, even when accounting for pre-pandemic mental health. Lifestyle changes during the pandemic do not appear to alter this risk. A greater focus on rapid and responsive service provision is essential to reduce the impact of the pandemic on the mental health of these already vulnerable individuals. Plain English summary The aim of this project was to explore the mental health of young adults with disordered eating behaviours (such as fasting, vomiting/taking laxatives, binge-eating and excessive exercise) and self-harm during the COVID-19 pandemic. We analysed data from an established study that has followed children from birth (in 1991 and 1992) up to present day, including during the pandemic when participants were 28 years old. We looked at the relationship between disordered eating and/or self-harm behaviours from before the pandemic and mental health problems (symptoms of depression and anxiety) and mental wellbeing during the pandemic. We also explored whether there were any lifestyle changes (such as changes in sleep, exercise, visiting green space) that might be linked to better mental health and wellbeing in young adults with disordered eating and self-harm. We found that young adults with prior disordered eating and/or self-harm had more symptoms of depression and anxiety, and worse mental wellbeing than individuals without prior disordered eating or self-harm. However, lifestyle changes did not appear to affect mental health and wellbeing in these young adults. Our findings suggest that people with a history of disordered eating and/or self-harm were at high risk for developing mental health problems during the pandemic, and they will need help from mental health services.

This cohort study uses data from 3 cohort studies in the UK to investigate the changes in prevalence of adolescent weight-loss and weight-perception behaviors and their association with depressive symptoms., Key Points Question Has the prevalence of behaviors aimed at weight loss and weight perception in adolescents and their association with depressive symptoms changed over 30 years? Findings This study, which used data from a total of 22 503 adolescents in 3 UK cohorts spanning 30 years, found that the prevalence of behaviors aimed at achieving weight loss increased in 2015 compared with both 2005 and 1986 and that this change was not explained by known changes in body mass index alone. Weight-control behaviors increased more in boys than in girls, but among the latter, these behaviors were associated with greater depressive symptoms in 2015 compared with 2005 and 1986. Meaning These findings suggest that an increased societal and public health focus on obesity could have had unintended consequences related to weight-control behaviors and poor mental health; thus, public health campaigns around the prevention of obesity should include prevention of disordered eating behaviors and be sensitive to adverse outcomes such as poor mental health., Importance In the context of the growing prevalence of childhood obesity, behaviors aimed at weight loss and their psychological burden might be increasing. Objective To investigate whether the prevalence of weight-control behaviors and weight perception, including their association with depressive symptoms, has changed in the 3 decades between 1986 and 2015. Design, Setting, and Participants This study used data from repeated cross-sections from successive longitudinal birth cohort studies. These included general population samples of UK adolescents aged 14 to 16 years from 3 ongoing birth cohorts: the British Cohort Study 1970 (children born between April 5 and 11, 1970; data collected in 1986), the Avon Longitudinal Study of Parents and Children (mothers with expected delivery between April 1, 1991, and December 21, 1992; data collected in 2005), and the Millennium Cohort Study (children born between September 1, 2000, and January 11, 2002; data collected in 2015). A total of 22 503 adolescents with data available on at least 1 weight-control or weight-perception variable in midadolescence were included in the study. Data were analyzed from August 1, 2019, to January 15, 2020. Main Outcomes and Measures Self-reported lifetime dieting and exercise for weight loss, current intentions about weight (doing nothing, lose weight, stay the same, gain weight), and weight perception (underweight, about the right weight, overweight) adjusted for body mass index. The secondary outcome was depressive symptoms. Exposures The main exposure was time (ie, cohort); secondary exposures were weight-change behaviors and weight perception. Results The study cohort included 22 503 adolescents (mean [SD] age, 14.8 [0.3] years; 12 061 girls [53.6%]; and 19 942 White individuals [89.9%]). A total of 5878 participants were from the British Cohort Study, 5832 were from the Avon Longitudinal Study of Parents and Children, and 10 793 were from the Millennium Cohort Study. In 2015, 4809 participants (44.4%) had dieted and 6514 (60.5%) had exercised to lose weight compared with 1952 (37.7%) and 344 (6.8%) in 1986. Furthermore, 4539 (42.2%) were trying to lose weight in 2015 compared with 1767 (28.6%) in 2005. Although girls were more likely to report these behaviors in all years, their prevalence increased more in boys over time (lifetime dieting in boys: odds ratio [OR], 1.79; 95% CI, 1.24-2.59; in girls: OR, 1.23; 95% CI, 0.91-1.66; currently trying to lose weight in boys: OR, 2.75; 95% CI, 2.38-3.19; in girls: OR, 1.70; 95% CI, 1.50-1.92). Adolescents also became more likely to overestimate their weight (boys describing themselves as overweight adjusting for body mass index, 2005 vs 1985 OR, 1.60; 95% CI, 1.17-2.19; 2015 vs 1985 OR, 1.36; 95% CI, 1.04-1.80; girls describing themselves as underweight, after adjusting for body mass index, 2015 vs 1986 OR, 0.51; 95% CI, 0.28-0.91). Girls who described themselves as overweight experienced increasingly greater depressive symptoms over time compared to girls who described their weight as about right (mean difference 1986, 0.32; 95% CI, 0.22-0.41; mean difference 2005, 0.33; 95% CI, 0.24-0.42; mean difference 2015, 0.56; 95% CI, 0.49-0.62). Conclusions and Relevance These findings suggest that the growing focus on obesity prevention might have had unintended consequences related to weight-control behaviors and poor mental health. Public health campaigns addressing obesity should include prevention of disordered eating behaviors and be sensitive to negative impact on mental health.

Background: Some people with eating disorders have difficulties with social communication. However, no longitudinal evidence regarding the direction of this association exists. We investigated trajectories of autistic social traits across childhood and adolescence in adolescents with and without disordered eating behaviours in early adolescence.Methods: We used data from the Avon Longitudinal Study of Parents and Children. Our disordered eating measure indicated presence of any, monthly, and weekly disordered eating (fasting, purging, dieting, binge-eating) at age 14 years. Autistic social traits were reported by mothers using the Social Communication Disorders Checklist (SCDC) at age seven, 11, 14, and 16 years. We modelled SCDC score trajectories using multilevel negative binomial models adjusting for a number of child- and maternal-level confounders.Results: Of the 5,381 adolescents included in our sample, 421 (7.8%) experienced one or more disordered eating behaviours, and 148 (2.8%) weekly episodes. Adolescents with disordered eating had a 20% increase in SCDC scores (relative risk (RR) 1.23, 95% Confidence Interval (CI):1.14, 1.32) compared to those without disordered eating. This association was particularly apparent for those reporting weekly (RR 1.43, 95%CI: 1.27, 1.61) as opposed to monthly disordered eating (RR 1.12, 95%CI: 1.01, 1.22).Conclusions: Greater autistic social traits in childhood could represent a risk factor for the development of disordered eating in adolescence. Although mechanisms of this association need to be elucidated, clinicians should be aware that autistic social traits could have predated the eating disorder when managing people with these conditions.

Do cities cause psychosis? Over 50% of the world’s population now live in cities, a figure set to rise to two-thirds by 2050. This unprecedented change in the organization of human populations will have both positive and negative consequences on a wide variety of social, political, economic, and health-related domains for individuals and society. In this chapter, we focus on one potentially negative consequence of city living; namely, raised risks of non-affective psychotic disorders in urban populations. We review the possible drivers of this phenomenon, which range from a causal role for exposure to deleterious factors in our urban environments through to non-causal factors, such as reverse causation—or social drift—potentially spanning several generations. We conclude by linking current epidemiological evidence with the latest findings from genetics and social neuroscience on this important public mental health issue.

BackgroundPrenatal infections have been proposed as a putative risk factor for a number of psychiatric outcomes across a continuum of severity. Evidence on eating disorders is scarce. We investigated whether exposure to prenatal maternal infections is associated with an increased risk of disordered eating and weight and shape concerns in adolescence in a large UK birth cohort.MethodsWe used data from the Avon Longitudinal Study of Parents and Children. The primary exposure was maternal experience of infections at any time in pregnancy. Study outcomes were presence of any, monthly or weekly disordered eating at 14 and 16 years of age, and weight and shape concerns at 14 years. We defined the causal effect of the exposure on these outcomes using a counterfactual framework adjusting our analyses for a number of hypothesised confounders, and imputing missing confounder data using multiple imputation.ResultsIn total, 4884 children had complete exposure and outcome data at age 14 years, and 4124 at 16 years. Exposed children had a greater risk of reporting weekly disordered eating at both age 14 [risk difference (RD) 0.9%, 95% confidence interval (CI) −0.01 to 1.9, p = 0.08] and 16 (RD 2.3%, 95% CI 0.6–3.9, p < 0.01), though evidence of an association was weak at age 14 years. Exposed children also had greater weight and shape concerns at age 14 years (mean difference 0.15, 95% CI 0.05–0.26, p < 0.01).ConclusionsExposure to prenatal maternal infection is associated with greater risk of disordered eating in adolescence. This association could be explained by in utero processes leading to impaired neurodevelopment or altered immunological profiles. Residual confounding cannot be excluded.

Despite great advances, experiments concerning the response of ecosystems to climate change still face considerable challenges, including the high complexity of climate change in terms of environmental variables, constraints in the number and amplitude of climate treatment levels, and the limited scope of responses and interactions covered. Drawing on the expertise of researchers from a variety of disciplines, this Perspective outlines how computational and technological advances can help in designing experiments that can contribute to overcoming these challenges, and also outlines a first application of such an experimental design. We thank the Flemish government (through Hercules Stichting big infrastructure and the Fund for Scientific Research Flanders project G0H4117N) and LSM (Limburg Sterk Merk, project 271) for providing funds to build the UHasselt Ecotron; Hasselt University for both funding and policy support (project BOF12BR01 and Methusalem project 08M03VGRJ); and the ecotron research committee for comments on the experimental design. We also thank Regional Landscape Kempen and Maasland for its collaboration and support. N.W., S.L., A.N. and I.V. are funded by Research Foundation-Flanders (FWO).

Background There are few population-based cohort studies of the emergence, development, and persistence of mental health problems in sexual minorities compared with heterosexuals. We compared trajectories of depressive symptoms in sexual-minority adolescents and heterosexual adolescents from when they were aged 10 to 21 years, and examined self-harm at ages 16 and 21 years. Methods The study included 4828 adolescents born between April 1, 1991, and Dec 31, 1992, from the Avon Longitudinal Study of Parents and Children birth cohort (Bristol, UK) who reported their sexual orientation when aged 16 years. Depressive symptoms were assessed with the short Mood and Feelings Questionnaire at seven timepoints between ages 10 and 21 years. A self-harm questionnaire was completed at ages 16 and 21 years. Analyses were linear multilevel models with growth curves (depressive symptoms), logistic multilevel models (self-harm in the previous year at ages 16 and 21 years), and multinomial regression (lifetime self-harm with and without suicidal intent at age 21 years). Findings At age 10, depressive symptoms were higher in sexual minorities than in heterosexuals and increased with age to a larger extent. Depressive symptoms increased at each timepoint by 0·31 points in hetereosexuals, and by 0·49 points in sexual minorities. Sexual-minority adolescents were more likely than heterosexual adolescents to report self-harm in the previous year at ages 16 and 21 years, with no evidence that this estimate decreased with age. At aged 21, sexual minorities were more likely to report lifetime self-harm (ie, on at least one previous occasion) with suicidal intent than heterosexuals. Interpretation Mental health disparities between heterosexuals and sexual minorities are present early in adolescence and increase throughout the school years, persisting to young adulthood. Prevention of these mental health problems and early intervention must be a priority.

Background The effectiveness of Early Intervention in Psychosis (EIP) services for individuals with a first episode of psychosis (FEP) could be thwarted by high rates of early disengagement. Aims To investigate which factors predict disengagement with EIP services. Method Using data from a naturalistic cohort of 786 EIP clients in East Anglia (UK), we investigated the association between sociodemographic and clinical predictors and disengagement using univariable and multivariable Cox proportional hazards models. Results Over half (54.3%) of our sample were discharged before receiving 3 years of EIP care, with 92 (11.7%) participants discharged due to disengagement. Milder negative symptoms, more severe hallucinations, not receiving an FEP diagnosis, polysubstance use and being employed were associated with greater disengagement. Conclusions Our findings highlight heterogeneous reasons for disengagement with EIP services. For some patients, early disengagement may hinder efforts to sustain positive long-term EIP outcomes. Efforts to identify true FEP cases and target patients with substance use problems and more severe positive symptoms may increase engagement. Declaration of interest None.

No studies have investigated the prevalence of eating disorders (ED) according to DSM-5 criteria and few have explored their comorbidity and service use in the general population in the UK. We aimed to estimate the prevalence, comorbidity, and service use in individuals with ED in a multi-ethnic inner city sample. A total of 1698 individuals (age 16/90) were screened for ED in the first phase of the South East London Community Health Study and 145 were followed up with a diagnostic interview. Data was weighed for survey design and Chi Square tests were used to investigate socio-demographic distribution, comorbidity and service use in participants with ED. The point prevalence of ED was 4.4 % (Binge Eating Disorder (BED) 3.6 %; Bulimia Nervosa (BN) 0.8 %) and 7.4 % when including sub-threshold diagnoses (Purging Disorder (PD) 0.6 %; Other Specified Feeding and Eating Disorders (OSFED) 2.4 %). No cases of AN were identified. Purging Disorder was the ED with the highest proportion of comorbid disorders. A minority of participants with ED had accessed specialist care services. ED are common, the comorbidity of ED was in line with previous studies and no ethnic differences were identified. Although PD is not a full diagnosis in DSM-5, we found some evidence of high comorbidity with other disorders, that needs to be replicated using larger samples. Service use was low across ED diagnoses, despite high levels of comorbidity.

BackgroundIdentifying childhood predictors of binge eating and understanding risk mechanisms could help improve prevention and detection efforts. The aim of this study was to examine whether features of attention-deficit/hyperactivity disorder (ADHD), as well as childhood eating disturbances, predicted binge eating later in adolescence.MethodWe studied specific risk factors for the development of binge eating during mid-adolescence among 7120 males and females from the Avon Longitudinal Study of Parents and Children (ALSPAC), a cohort study of children in the UK, using data from multiple informants to develop structural equation models. Repeated assessment of eating disturbances during childhood (mid-childhood overeating, late-childhood overeating and early-adolescent strong desire for food), as well as teacher- and parent-reported hyperactivity/inattention during mid- and late childhood, were considered as possible predictors of mid-adolescent binge eating.ResultsPrevalence of binge eating during mid-adolescence in our sample was 11.6%. The final model of predictors of binge eating during mid-adolescence included direct effects of late-childhood overeating [standardized estimate 0.145, 95% confidence interval (CI) 0.038–0.259,p= 0.009] and early-adolescent strong desire for food (standardized estimate 0.088, 95% CI −0.002 to 0.169,p= 0.05). Hyperactivity/inattention during late childhood indirectly predicted binge eating during mid-adolescence (standardized estimate 0.085, 95% CI 0.007–0.128,p= 0.03) via late-childhood overeating and early-adolescent strong desire for food.ConclusionsOur findings indicate that early ADHD symptoms, in addition to an overeating phenotype, contribute to risk for adolescent binge eating. These findings lend support to the potential role of hyperactivity/inattention in the development of overeating and binge eating.

Background: Finding innovative and cost-efficient care strategies that induce long-term health benefits in cardiac patients constitutes a big challenge today. The aim of this Telerehab III follow-up study was to assess whether a 6-month additional cardiac telerehabilitation programme could induce long-term health benefits and remain cost-efficient after the tele-intervention ended. Methods and results: A total of 126 cardiac patients first completed the multicentre, randomised controlled telerehabilitation trial (Telerehab III, time points t(0) to t(1)). They consequently entered the follow-up study (t(1)) with evaluations 2 years later (t(2)). A quantitative analysis of peak aerobic capacity (VO2 peak, primary endpoint), international physical activity questionnaire self-reported physical activity and HeartQoL quality of life (secondary endpoints) was performed. The incremental cost-effectiveness ratio was calculated. Even though a decline in VO2 peak (248ml/[min*kg] at t(1) and 226ml/[min*kg] at t(2); P

This study aims to investigate longitudinal patterns of psychopathology during the antenatal and postnatal periods among women with current (C-ED) and past (P-ED) eating disorders. Women were recruited to a prospective longitudinal study: C-ED (n = 31), P-ED (n = 29) and healthy control (HC; n = 57). Anxiety, depression and ED symptoms were measured at four time points: first/second trimester, third trimester, 8 weeks and 6 months postpartum. Linear mixed effects models were used to test for group differences. Women with C-ED and P-ED, in all diagnostic categories, had significantly higher levels of psychopathology at all time points. ED symptoms decreased in the C-ED group, compared with an overall increase in the other two groups but subsequently increased after pregnancy. Overall, depression and state and trait anxiety scores decreased in the C-ED group compared with the HC group throughout the antenatal and postnatal periods. High levels of psychopathology are common throughout the antenatal and postnatal periods among women with current and past ED, and despite some overall reductions, symptoms remain clinically significant. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd.

Diagnostic criteria for eating disorders (ED) remain largely based on clinical presentations, but do not capture the full range of behaviours in the population. We aimed to derive an empirically based ED behaviour classification using behavioural and body mass index (BMI) indicators at three time-points in adolescence, and to validate classes investigating prospective associations with adverse outcomes. Adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) provided data on ED at age 14 (n = 6615), 16 (n = 5888), and 18 years (n = 5100), and had weight and height measured. Psychological and behavioural outcomes were assessed at 15.5/16 and 17.5/18 years. We fit gender- and age-stratified latent class models, and employed logistic regression to investigate associations between classes and later outcomes. One asymptomatic and two symptomatic (largely representing higher and lower frequency ED behaviours) classes were observed at each time-point, although their relative prevalence varied by age and gender. The majority of girls in symptomatic classes remained symptomatic at subsequent assessments. Girls in symptomatic classes had higher odds of subsequent anxiety and depressive disorders, binge drinking, drug use, and deliberate self-harm. Data analyses were underpowered amongst boys. The presence of two symptomatic classes (characterised by different ED behaviour frequency) and their prospective association with adverse outcomes suggest a need to refine diagnostic thresholds based on empirical data. Despite some instability of classes, particularly in mid-adolescence, evidence that half of girls in symptomatic classes remained symptomatic suggests persistence of ED behaviours in adolescence, and highlights a need for early identification to reduce chronicity.

Background: The NHS Bowel Cancer Screening Programme in England offers biennial guaiac faecal occult blood testing (gFOBt). There is a socioeconomic gradient in participation and socioeconomically disadvantaged groups have worse colorectal cancer survival than more advantaged groups. We compared the effectiveness and cost of an enhanced reminder letter with the usual reminder letter on overall uptake of gFOBt and the socioeconomic gradient in uptake. Methods: We enhanced the usual reminder by including a heading ‘A reminder to you’ and a short paragraph restating the offer of screening in simple language. We undertook a cluster-randomised trial of all 168 480 individuals who were due to receive a reminder over 20 days in 2013. Randomisation was based on the day of invitation. Blinding of individuals was not possible, but the possibility of bias was minimal owing to the lack of direct contact with participants. The enhanced reminder was sent to 78 067 individuals and 90 413 received the usual reminder. The primary outcome was the proportion of people adequately screened and its variation by quintile of Index of Multiple Deprivation. Data were analysed by logistic regression with conservative variance estimates to take account of cluster randomisation. Results: There was a small but statistically significant ( P ¼ 0.001) increase in participation with the enhanced reminder (25.8% vs 25.1%). There was significant ( P ¼ 0.005) heterogeneity of the effect by socioeconomic status with an 11% increase in the odds of participation in the most deprived quintile (from 13.3 to 14.1%) and no increase in the least deprived. We estimated that implementing the enhanced reminder nationally could result in up to 80 more people with high or intermediate risk colorectal adenomas and up to 30 more cancers detected each year if it were implemented nationally. The intervention incurred a small one- off cost of d 78 000 to modify the reminder letter. Conclusions: The enhanced reminder increases overall uptake and reduces the socioeconomic gradient in bowel cancer screening participation at little additional cost.

The objective of disability policy is to create a society where people with disabilities and their families enjoy an equal standard of living to those without disabilities, though evidence to underpin policy is sparse. We defined the compensating variation (CV) of child disability as the amount of additional income a family with a disabled child would require to achieve the same living standards as a similar family without a disabled child. The aims of this study were to estimate the CV for child disability and to explore how this varied for different levels of disability and reference levels of living standards. Using data on 54,641 families from the Family Resources Survey (2004–2012), we matched families with (cases) and without (controls) a disabled child on family and child characteristics plus living standards and calculated the income difference inclusive of disability benefits. Our findings suggest that across families with the most disabled children, a compensating variation equal to an extra £56–£79 a week was required to achieve the same living standards as matched families without a disabled child compared with the mean level of state disability benefit £47–£71 a week in this group.

BackgroundThere is a large body of evidence indicating that eating disorders (EDs) are characterized by particular neuropsychological profiles. We aimed to further explore whether impairments in neuropsychological functioning previously found in ED groups are present prior to onset, or are secondary to the disorder.MethodThis is the first study to explore neuropsychological functioning in children born to a mother with a lifetime ED, who are therefore at high risk of developing an ED, in a large cohort sample. We investigated intelligence and attention at age 8 years (n = 6201) and working memory (WM) and inhibition at age 10 years (6192) in children who are at high risk of developing an ED, compared to children who are not.ResultsThe children of women with lifetime anorexia nervosa (AN) showed high full-scale and performance IQ, increased WM capacity, better visuo-spatial functioning, and decreased attentional control. The children of women with lifetime bulimia nervosa (BN) showed comparatively poor visuo-spatial functioning.ConclusionsOur findings suggest that high intelligence, increased WM capacity and impaired attentional control might be intermediate phenotypes on the pathway between genetic vulnerability and the development of an ED.

Background Women who have an overweight or obese BMI are more likely to experience pregnancy complications. However, little is known on the cost of childbirth in this group and no studies have been undertaken in England to date. The aim of this paper is therefore to investigate whether women with overweight and obese pre-pregnancy body mass index (BMI) incur higher average hospital costs of childbirth. Methods We employed data from 7564 women in the first wave of data collection of the Millennium Cohort Study. Using interval regression, we investigated the association between hospital costs of childbirth and pre-pregnancy BMI, fitting four models, progressively adjusting for additional potential confounders and mediators. Model 1 was a univariate model; model 2 adjusted for maternal age, education, marital status, ethnicity, income, and region; model 3 additionally included number of previous children, number of babies delivered, whether birth was at term, and type of delivery; model 4 also included length of hospital stay. Results Childbirth costs incurred by women who were overweight, obese class I and obese class II and III were £22, £82 and £126 higher than those incurred by women whose BMI was in the normal range (p ≤ 0.05). Delivery method, pre-term delivery, and length of hospital stay accounted for the observed difference. Conclusions Women with elevated pre-pregnancy BMI make greater use of services resulting in higher hospital costs. Interventions promoting healthy BMI in pre-pregnancy among women of child-bearing age have the potential to reduce pregnancy complications and be cost-effective. Electronic supplementary material The online version of this article (10.1186/s12884-018-1893-z) contains supplementary material, which is available to authorized users.