Contraceptive use in women of childbearing age with bipolar disorder

Contraceptive use in women of childbearing age with bipolar disorder | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Contraceptive use in women of childbearing age with bipolar disorder Elisa Rodríguez-Toscano, Ingrid de Chazeron, Raoul Belzeaux, Pierre Michel Llorca, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4654126/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 4 You are reading this latest preprint version Abstract Introduction Unplanned pregnancies are frequent in women with bipolar disorder (BD) while perinatal period is associated with a higher risk of relapse. Effective contraception during childbearing age in BD could reduce the risk of unplanned pregnancy and its consequences. The present study studied the prevalence of contraceptive use and which sociodemographic and clinical variables affect its use in women with BD. Methods 796 women (18-50 years old) with BD were recruited and evaluated by the MONTRA survey in France among hospital and consultant psychiatrists. Sociodemographic, clinical and treatment variables were compared between patients with and without contraception use. A logistic regression estimated which variables had a predictive effect on the use of contraception. Results A 61.2% reported the use of effective contraception. Women who use contraception were in 26-35 (OR=2.40,p<0.001) and 36-45 (OR=1.92,p<0.001) range age, displayed higher levels of education (OR= 5.07,p=0.003), were more active (OR=1.63,p=0.006), did not live alone (OR=1.41,p=0.033) and had fewer manic or mixed episodes (OR=0.50,p=0.007).No association was found with the nature of pharmacological treatment. Conclusion Sociodemographic variables were mainly associated with contraception use among BD women. As preventive measures for risk of relapse in BD, contraceptive counseling, including reduction of unplanned pregnancies, should be systematically ensured. Bipolar disorder Childbearing age Contraceptive use Women Figures Figure 1 1. Introduction Bipolar Disorder (BD) is a chronic severe psychiatric disorder characterized by the course of alternating manic, hypomanic, and depressive episodes (Grande, et. al., 2016 ). BD, like other severe mental illnesses, is correlated of sexual risk behavior (Meade and Sikkema, 2005 ). In comparison to people with no psychiatric conditions, BD has been associated with more casual partners, less rates of monogamous sexual partnerships, more rates of HIV condition (Marengo, et al., 2015a ), increased risk of early pregnancy (Yang, et. al., 2022 ) and lower level of planning of pregnancies or unplanned pregnancy (Marengo, et al., 2015b ). During pregnancy and in the postpartum period, withholding or stopping pharmacotherapeutic treatment constitutes a risk for the recurrence of the illness (Dinc, et al., 2019 ; Harlow et al. 2007 ; Miller, et al., 2015 ). Contraception during childbearing age in BD could reduce the risk of unplanned pregnancy and its consequences. Long-term use of both mood stabilizers and second-generation antipsychotics was associated with a reduced risk of early pregnancy (Yang, et. al., 2022 ). Previous reviews on pharmacotherapy for the peripartum management of BD have displayed that management of the pharmacological treatment for BD patients during the perinatal period is challenging and consideration of risks, benefits, and alternative therapies is needed before initiating therapy (Kameg, 2021 ; Epstein, et al., 2015 ). Treatment usually entails use of medications that not only interfere with the clearance of oral contraceptives, but may also be teratogenic or unsafe, such as the anticonvulsant mood stabilizers or lithium (Cohen, 2007 ). Although treatment guidelines may be of significant help, high heterogeneity exists across them. Shared decision-making represents a useful patient-centered approach during the perinatal period (Belzeaux,R. et al., 2019). It exists scarce literature about the prevalence of contraceptive use in BD women of childbearing age (Magalhães, et al., 2009 ; Posada-Correa, et al., 2020 ; Dinc, et al., 2019 ). These studies either found a lower or similar rate of contraception use compared to healthy controls, but it appears to be sub-optimal use, mainly using the least efficient methods and leading to a higher rate of unplanned pregnancies (Magalhães, et al., 2009 ; Posada-Correa, et al., 2020 ; Dinc, et al., 2019 ). However, it is not clear which sociodemographic and clinical variables are associated to a higher use of contraception in BD women of childbearing age. In the present study, we studied the prevalence of contraceptive use in BD women of childbearing age and which variables affect its use. Therefore, we aimed to make a sociodemographic, clinical and pharmacological treatment characterizations of a large representative sample of BD women of childbearing age, and analyzed which variables were associated to the use of a contraceptive method. 2. Methods 2.1. Project The present study was supported by the MONTRA survey carried out in France between 2010 and 2011 among hospital and consultant psychiatrists. Its aim was to describe the conditions of care for BD patients using real-life data collection. 439 psychiatrists participated in the study recruiting the patients and evaluating them. These psychiatrists were randomly chosen from a national file of 12,000 psychiatrists (CEGEDIM file) in order to ensure the representativeness of the population, particularly in terms of clinical practice (consultants, day hospital, hospital practice). During 4 consecutive days, they completed a questionnaire including sociodemographic, environmental, clinical and therapeutic characteristics of patients with BP diagnosis according to DSM-IV criteria. The variables of interest for this study were extracted from the MONTRA database, which will be explained in the next sub-sections. The investigation was declared to the French Data Protection Agency (CNIL-France) and the patient data remained anonymous. The procedures followed in this study were approved by the ethics committe (CPP Sud-Est, IRB 00008526). Informed consent to participate in the study was obtained from participants. More details of the project can be found elsewhere (Llorca, et al., 2013 ). 2.2. Participants The MONTRA survey defined as inclusion criteria the following: Patients between 18 and 60 years old; Having a diagnosis of BD according to DSM-IV criteria and based on the judgment of the clinician. On the other hand, the exclusion criteria were as follows: Minors or patients over the age of 60; Specifically, for the present study we selected only women of childbearing age (up to 50 years old regarding consensus literature (Paton, et al., 2018 ; Samalin, et al., 2020 ). The subject’s eligibility can be seen in the flowchart in Fig. 1 . 2.3. Measures Socio-demographic characteristics : In this section it was described the age of the participants, level of education, working situation, living situation and the presence of care givers. The categorization of data of these variables were performed as follows: Age in years. Following the study of Paton (2018), the age of the participants was categorized into four groups (from 18 to 25, from 26 to 35, from 36 to 45 and from 46 to 50). The highest education level achieved. This variable was registered considering the following categories: professional training, primary education, secondary education (which include both secondary and bachelor) and superior education. Working situation. It was included as active all the subjects that were working or studying at the moment of the evaluation. We categorized as Inactive all the subjects that respond as disability, pensioner or other. Living situation. It was considered in one group if the participant lives alone and another group named as other , which included the subjects that live with the spouse, the parents, in a therapeutic apartment, in an institution or other. Caring. The present variable contains whether there exists a care giver that takes care of the participant or not. Effective contraception : Participants reported whether they were using contraceptive methods and, in case they were, the type of contraceptive method that they were using. For the present study, it was considered as effective contraception method the ones that have proved a high effectivity at preventing pregnancies. The following methods were considered effective: combined pill, progestogen-only pill, contraceptive patch, vaginal ring, contraceptive implant, intrauterine system, intrauterine device, female sterilisation, condoms or diaphragm. Withdrawal method was not considered by the clinicians as an effective contraception method in the study. Clinical features : In this section we took into consideration the specific characteristics of the BD including the type of BD (type I, type II or other type), the presence of rapid cycles (defined as 4 mood episodes per year or more) and the phase of BD (euthymic phase, manic and mixed episode and depressive episode). Moreover, other clinical variables were assessed such as the history of suicide attempt, the illness duration (calculated from the diagnosis to the moment of the inclusion in the study), the previous hospitalization, and the presence of comorbidities including anxiety disorders and substance use disorders. Regarding the psychosocial functioning, autonomy in disease management and autonomy in the treatment management variables were selected. Treatment modalities (Treatment prescribed during the consultation) : The pharmacological treatment (lithium, antipsychotics, anticonvulsants and antidepressants) was recorded. Moreover, pharmacological treatment with high (valproate) or intermediate risk (lithium, carbamazepine, clozapine, haloperidol, milnacipran) for teratogenic effect were considered. 2.4. Statistical analysis The sample of our cohort was characterized using the variables of interest and comparing them between two groups of patients: “with contraception” and “without contraception”. Statistical analyzes were performed with SPSS statistics 27.0 and all statistical tests will be performed for a 5% risk of type I error. Continuous variables with normal distribution were presented as mean (standard deviation (SD). Categorical variables are expressed as counts and percentages. For univariate analyses, the Student test or Mann-Whitney test was used for the quantitative variables (homoscedasticity studied by the Fisher-Snedecor test) and the Chi 2 test or Fisher's exact test for the categorical parameters. The results can be expressed in terms with 95% confidence intervals. Finally, in order to find out which variables had a predictive effect on the use of contraception, it was run a logistic regression test. Candidate variable selection was based on statistical significance (p < 0.05) from previous univariate screening and retained age bands, level of education, working situation, living situation, illness duration, illness management, treatment management and current phase of BD. 3. Results 3.1. Sociodemographic, clinical and treatment characteristics of women of childbearing age with BD A total sample of 796 BD women of childbearing age was analyzed in the present study (Table 1 ). Within this sample, 487 (61.2%) reported contraception use. They were in majority between 36 and 45 years old (42.5%), followed by the groups of subjects from 26 to 35 years old and from 46 to 50 years old, with more than 20%. The majority group of subjects had studied either secondary or superior education, more than half of the participants were active and do not live alone. Table 1 Sociodemographic, clinical and treatment characteristics of childbearing age women with BD (n = 796) Sociodemographic variables Age bands 18–25, n (%) 61 (7.7) 26–35, n (%) 220 (27.6) 36–45, n (%) 338 (42.5) 46–50, n (%) 177 (22.2) Level of education Professional training, n (%) 178 (22.4) Primary education, n (%) 28 (3.5) Secondary education, n (%) 287 (36.1) Superior education, n (%) 303 (38.1) Working situation: active, n (%) 515 (64.7) Living situation: alone, n (%) 272 (34.2) Has a caregiver, n (%) 225 (28.3) Contraception use , n (%) 487 (61.2) Clinical characteristics Type of BD Type I, n (%) 418 (52.5) Type II, n (%) 350 (44.0) Other type, n (%) 28 (3.5) Rapid cycle, Yes, n (%) 75 (9.4) Current phase of BD Euthymic phase, n (%) 605 (76.0) Manic and mixed episode, n (%) 74 (9.3) Depressive episode, n (%) 113 (14.2) History of at least one suicide attempt, n (%) 309 (38.8) Illness duration, years mean (SD) 6.92 (5.8) Hospitalization, ever, n (%) 587 (73.7) Autonomous in illness management, n (%) 588 (73.9) Autonomous in treatment management, n (%) 705 (88.6) Psychiatric comorbidities Anxiety disorders, n (%) 406 (51.0) Substance use disorder, n (%) 121 (15.2) Pharmacologic treatment Types of pharmacological treatment Lithium, n (%) 148 (18.6) Second-generation antipsychotic (SGA), n (%) 404 (50.8) Anticonvulsant (AC), n (%) 204 (25.6) Antidepressant (AD), n (%) 58 (7.3) According to teratogenic effect Pharmacologic treatment with high or intermediate risk*, n (%) 224 (28.1) Valproate, n (%) 25 (3.1) Abb : BD, Bipolar Disorder; SD, Standard Deviation. Note : Mean and standard deviation for quantitative variables, and number and proportion for categorical variables. * Pharmacological treatment with high (valproate) or intermediate risk (lithium, carbamazepine, clozapine, haloperidol, milnacipran) for teratogenic effect. Considering the clinical characteristics, half of the subjects were diagnosed with BD type I, and the average of illness duration was almost seven years. Most of the subjects with BD were hospitalized at least once in their lifetime. Almost 80% of the subjects was in a euthymic phase, around 10% in manic and mixed episode and other 15% in a major depressive episode. In regard to psychosocial functioning, around 70% of BD women displayed a self-management of their illness and more than 80% in the management of their treatment. Half of the BD women of childbearing age were treated with SGA, and around 20% either with lithium or AC. When the teratogenic effect was taken into consideration, data showed that 28% of the BD women of childbearing age were treated with a high or intermediate risk of teratogenic pharmacologic treatment and only 3% were taking valproate. 3.2 Comparison of sociodemographic and clinical characteristics of women of childbearing age with BD that use and do not use contraception methods In relation to the sociodemographic characteristics, there were a significant difference in age and level of education (Table 2). The group of age between 46 and 50 years old had a lower rate of women using contraception than the other age bands. The group of women with only primary education had a lower rate of contraception use than the other educational groups. Also, women that used a contraceptive method had a significantly higher percentage of active women and women not living alone in comparison to women that do not use a method of contraception. Table 2. Comparison of Sociodemographic, clinical and treatment characteristics of childbearing age BD women with and without contraception With contraception method (n = 487) Without contraception method (n = 309) Statistical test Post hoc analysis Sociodemographic variables Age bands 18–25, n (%) 39 (8.0) 22 (7.1) 30.55, p 46–50, p = 0.009 26–35 > 36–45, p = 0.035 26–35 > 46–50, p 46–50, p < 0.001 26–35, n (%) 157 (31.8) 63 (20.4) 36–45, n (%) 212 (43.5) 126 (40.8) 46–50, n (%) 79 (16.2) 98 (31.7) Level of education Primary education (PE), n (%) 6 (1.2) 22 (7.1) 24.55, p < 0.001 PE < SE, p < 0.001 PE < SuE, p < 0.001 SE PE, p < 0.001 PF = SE, p = 0.128 PF = SuE, p = 0.700 Secondary education (SE), n (%) 165 (33.9) 122 (39.5) Professional training (PF), n (%) 115 (23.6) 63 (20.4) Superior education (SuE), n (%) 201 (41.3) 102 (33.0) Working situation: active, n (%) 346 (71.0) 169 (54.7) 22.14, p < 0.001 Living situation: alone, n (%) 149 (30.6) 123 (39.8) 7.13, p = 0.008 Has a caregiver, n (%) 141 (29.0) 84 (27.2) 0.292, p = 0.589 Clinical characteristics Type of BD Type I, n (%) 253 (52.0) 165 (53.4) 1.043, p = 0.594 Type II, n (%) 219 (45.0) 131 (42.4) Other type, n (%) 15 (3.1) 13 (4.2) Rapid cycle, Yes, n (%) 44 (9.0) 31 (10.0) 1.136, p = 0.567 Current phase of BD Euthymic phase, n (%) 386 (79.4) 219 (71.6) 8.27, p = 0.016 Manic and mixed episode, n (%) 44 (9.1) 30 (9.8) Depressive episode, n (%) 56 (11.5) 57 (18.6) History of at least one suicide attempt, n (%) 193 (39.6) 116 (37.5) 1.277, p = 0.528 Illness duration, years mean (SD) 6.33 (5.0) 7.84 (6.7) 3.59, p < 0.001 Hospitalization, ever, n (%) 134 (27.5) 75 (24.3) 1.027, p = 0.311 Autonomous in illness management, n (%) 372 (76.4) 216 (69.9) 4.117, p = 0.042 Autonomous in treatment management, n (%) 443 (91.0) 262 (84.8) 7.120, p = 0.008 Psychiatric comorbidities Anxiety disorders, n (%) 250 (51.3) 156 (50.5) 2.893, p = 0.235 Substance use disorder, n (%) 73 (15) 48 (15.5) 0.153, p = 0.926 Pharmacologic treatment Types of pharmacological treatment Lithium, n (%) 92 (18.9) 56 (18.1) 0.074, p = 0.786 Second generation antipsychotic (SGA), n (%) 247 (50.7) 157 (50.8) 0.001, p = 0.980 Anticonvulsant (AC), n (%) 124 (25.5) 80 (25.9) 0.018, p = 0.893 Antidepressant (ATD), n (%) 34 (7.0) 24 (7.8) 0.173, p = 0.678 According to teratogenic effect Pharmacologic treatment with high or intermediate risk*, n (%) 139 (28.5) 85 (27.5) 0.100, p = 0.752 Valproate, n (%) 15 (3.1) 10 (3.2) 0.015, p = 0.902 Abb : BD, Bipolar disorder. Note : Chi square for categorical variables and t test for quantitative variables. Regarding the clinical characteristics, no differences were found in proportion of type of BD, rates of hospitalizations, history of suicide attempts or presence of rapid cycles between the groups of women with and without use of contraception. Women with contraception displayed a significantly shorter duration of the illness, higher rates of patients in euthymic phase and lower rates of patients in depressive phase than the women without use of contraception. Considering the psychosocial functioning of the participants, the contraception use was significantly higher for autonomous women in illness management and treatment management. In regard to the pharmacological treatment, no differences were found between the women using and not using contraception. 3.3. Predictive variables of contraception use in BD women of childbearing age We performed a logistic regression test for predicting the odds of using contraception with the following explanatory variables: age bands, level of education, working situation, living situation, illness duration, autonomy in illness management, treatment management and current phase of BD (Table 3 ). Table 3 Logistic regression model for sociodemographic, clinical and funcional variables associated with the use of contraception in BD women at childbearing age. Exp(B) 95% C.I. p. Variable Inferior Superior Age bands, years 46–50 < 0.001 18–25 1.510 0.781 2.921 0.220 26–35 2.404 1.538 3.760 < 0.001 36–45 1.919 1.303 2.827 < 0.001 Level of education Primary education 0.024 Secondary education 4.267 1.507 12. 079 0.006 Professional training 5.125 1.745 15.050 0.003 Superior education 5.070 1.753 14.666 0.003 Working situation (active) 1.626 1.151 2.299 0.006 Living situation (not living alone) 1.414 1.028 1.944 0.033 Illness duration 0.974 0.947 1.002 0.068 Autonomy in illness management 1.153 0.754 1.765 0.511 Autonomy in treatment management 1.504 0.852 2.655 0.160 Current phase of BD Euthymic phase 0.007 Manic and mixed episode 0.501 0.326 0.771 0.002 Depressive episode 0.871 0.506 1.501 0.619 Note : 46–50 years old and superior education have been selected as baseline or constant dummy variable Abb : C.I, Confidence Interval; SD, Standard Deviation; Sig., Significance According to Nagelkerke Rsquare in our model the 13.1% of the variance of the outcome, so whether the participants use contraception or not, can be explained by our predictors. The model has predicted overall a percentage of 66.2%. The model found no significant effect of the dependent variables of years of illness duration, autonomy in illness management and treatment management. The variables significantly associated with an effect on contraception use were age, level of education, working, living situation and current phase of BD. 4. Discussion The use of contraceptive methods can reduce the unplanned pregnancies in BD. Its use during childbearing age is associated with high level of education and capacity to planned pregnancy and avoid unplanned pregnancy in BD women. Therefore, it is important to find out which variables are associated with a less adherence to contraceptive methods. Interestingly, the present study found out that the strongest predictive effect are the sociodemographic factors rather than the clinical or treatment characteristics. The analyzed sample displayed a 61.2% rate of BD women of childbearing age that use contraception. According to the French Health Report in 2016, the use of a contraceptive method in general population in France is around 70% in women of childbearing age (Rahib, et al., 2016 ). Previous literature with BD women were similar to the present study. They reported rates of contraception use in BD women of 52.1% (Posada-Correa, et al., 2020 ), 59% (Magalhães, et al., 2009 ) and 73% (Dinc, et al., 2019 ), being systematically slightly lower in the group of BD patients in comparison to general population. This could be at least partially explained by variables related to education level, economic status, social barriers and some attitudes of professionals in which the sexuality of people with mental health disorders is not always considered (Santé publique France, 2013 ). A systematic review of pregnancy in BD described that adverse pregnancy outcomes such as gestational hypertension and antepartum haemorrhage, induction of labor and caesarean section occur more frequently in BD women. BD Women also have an increased risk of relapse in the postnatal period and are more likely to have babies that are severely small for gestational age (Rusner et al., 2016 ). In relation to the demographic characteristics associate to contraception use in BD, the present study found that the age, level of education, active working situation, not living alone are positively associated to higher rates of use of contraception. This is consistent with the only study that described demographic variables related to the use of contraception in BD. They displayed that being married, pertaining to the older age group and having had one or two pregnancies and more than two were associated with using contraception (Magalhães, 2019). Similar results with an association with low level of education and no working were found in a study among immigrant and second-generation immigrant women (Poncet et al 2013 ). It might suggest that the increase age and level of education can be associated to a higher understanding of contraception and sexual education. Interestingly, in light of the present results and the ones published previously (Magalhães, 2019) there are other demographic variables that do not seem to be related to the use of contraceptive methods, such as income or having a care giver. Regarding the clinical characteristics, no differences were found in BD type, hospitalization rates, history of suicide attempts or presence of rapid cycling between the groups of women with and without use of contraception. These findings were again consistent with previous research which found no association between use of contraception and symptoms or illness severity (Magalhães, 2019). Data nevertheless highlighted that women using contraception displayed a significantly shorter duration of the illness than the women without use of contraception. In relation to comorbid disorders, it is interesting to report that, although no differences were found between subjects with and without contraception, half of the patients had an anxiety disorder and more that 15% a substance use disorder. These high rates of comorbidities have been previously described in BD (Icick, et al., 2017 ). Considering the level of functioning of the participants, the already described functional impairment of BD patients (Burdick, et al., 2022 ) was observed in the present study. Over 25% of the analyzed sample displayed a lack of autonomy in the illness management and over 10% a lack of autonomy in their treatment management. Moreover, the percentage of autonomous women using contraception was significantly higher than the percentage of autonomous women not using contraception both for the illness management and the treatment management. This novel finding can suggest that the use of contraception in BD is related to the level of autonomy of the patient and the ability to cope and manage their illness. Regarding the pharmacological treatment, around 28% of the women received treatment with high or intermediate risk for teratogenic effect. A previous study found that the use of lithium and anticonvulsant mood stabilizers was unrelated to use of contraception (Magalhães, et al., 2019). In the present study, although no differences were found between the women using and not using contraception, only 3% of the women were taking valproate medication. This highlights the avoidance of pharmacological treatment with high risk of teratogenic effect in BD women of childbearing age. In summary, the present study found out that the most important variables associated with the use of contraception were age, level of education, working and living conditions. These demographic variables are similar to the ones influencing the contraception use in general population (Bentley et al., 2009 ; Oddens, 1997 ). However, as BD has an increased risk of unplanned pregnancies, intervention protocols might take this into consideration. Therefore, a collaboration between the psychiatric and gynecologic specialties could be implemented in the protocol assistance for adolescent girls with BD, with a focus on the plan of pregnancy and contraceptive methods, so as to reduce the risk of unplanned pregnancy. A study reported that 32.2% of women with mental health illness had never received information on sexual education and family planning. Authors indicated that evaluation and education on the topic in psychiatry consultations is limited, due to factors such as: lack of knowledge of the psychiatrist on the use of contraceptives, the perception that this evaluation does not correspond to the mental health consultation, avoidance of the topic (Posada-correa et al., 2020 ). Our findings need to be appraised in the context of limitations. Firstly, the present study did not use standardized scales with an adequate methodological validation. However, the recruitment of participants followed a systematic procedure and the high level of raters was guaranteed by the involvement of active clinician psychiatrists. Moreover, longitudinal data were not analyzed. Large cohort studies with follow up visits are needed to better identify risk associated to treatment discontinuation or treatment exposure. Furthermore, the data presented was collected ten years ago and therefore the results should be interpreted cautiously taking into consideration potential variations. Finally, in this study, women until 50 years old, who may already be in menopause, were included. In conclusion, our findings confirm previous evidence of the similar rates of contraception use in BD women of childbearing age. We add to previous studies that it was mainly sociodemographic variables that were associated with contraception use among BD women. As preventive measures for risk of relapse in BD, contraceptive counseling, including reduction of the risk of unwanted pregnancies, should be systematically ensured. Declarations Competing Interests Conflict of interest:Ludovic Samalin has received personal fees and/or non-financial support from Janssen, Lundbeck, Sanofi, Otsuka, Rovi. Raoul Belzeaux has received personal fees and/or non-financial support from Janssen, Lundbeck, Sanofi. The other authors have no conflicts of interest to declare.Role of the funding source:The funders had no role in the design, analysis, write-up or decision to submit for publication. Funding: None Author Contribution E.R.-T: Conceptualization, data analysis, literature search, original draft preparation; L.dC : Conceptualization, writing—review and editing; RB : writing—review and editing ; PM.L : Conceptualization, writing—review and editing; LS. Conceptualization, literature search, assessment, writing—review and editing, supervision. All authors have read and agreed to the published version of the manuscript. Acknowledgement None The content of the article has never been published before and is not under consideration for publication elsewhere. We confirm that the relevant codes of ethics and research ethics were upheld through the conduct of the research, including the assignment of authorship (i.e., based on meritorious scientific contribution). All authors have contributed significantly to the paper and are in total agreement with the content of the manuscript. References Belzeaux R., Sanguinetti, C., Murru, A., Verdolini, N., Pacchiarotti, I., Hidalgo-Mazzei, D., Cohen, L., Anmell, G., Barbuti, M., Vieta, E., Llorca, P-M., and Samalin, L. 2019. Pharmacotherapy for the peripartum management of bipolar disorder. EXPERT OPINION ON PHARMACOTHERAPY. https://doi.org/10.1080/14656566.2019.1626826. Bentley R , Kavanagh A , Smith A . 2009. Area disadvantage, socioeconomic position and women ’ s contraception use: A multilevel study in the UK . J Fam Plann Reprod Health Care; 35 : 221 – 6 . Burdick KE, Millett CE, Yocum AK, et al. Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative. Bipolar Disord. 2022;24:709-719. doi: 10.1111/bdi.13208 Cohen LS. 2007. Treatment of bipolar disorder during pregnancy. J Clin Psychiatry 68(Suppl 9):4–9 C Magalhães PV, Kapczinski F, Kauer-Sant’Anna M. 2009. Use of contraceptive methods among women treated for bipolar disorder. Arch Womens Ment Health.;12(3):183. doi:10.1007/s00737-009-0060-y Dinc H, Boyacioglu NE, Ozcan NK, Enginkaya S. Reproductive and sexual health in women with bipolar disorder: a comparative study. Dusunen Adam. 2019;32(1):23–32 Epstein RA., Moore KM., Bobo WV. Treatment of bipolar disorders during pregnancy: maternal and fetal safety and challenges. Drug Healthc Patient Saf. 2015; 7: 7–29. Grande, I., Berk, M., Birmaher, B., Vieta, E., 2016. Bipolar disorder. Lancet 387, 1561–1572. https://doi.org/10.1016/S0140-6736(15)00241-X Harlow BL, Vitonis AF, Sparen P, Cnattingius S, Joffe H, Hultman CM (2007) Incidence of hospitalization for postpartum psychotic and bipolar episodes in women with and without prior prepregnancy or prenatal psychiatric hospitalizations. Arch Gen Psychiatry 64(1):42–48 Icick R, Gard S, Barde M, et al. 2017. Physical and mental health burden in cases of bipolar disorder classified as current, former, or non‐ tobacco smokers. J Affect Disord.;208:406‐413 Kameg BN PMHNP‐BC, CARN, CNE. 2021. Bipolar disorder: Treatment strategies for women of childbearing age. Perspect Psychiatr Care; 57:1244–1249 Llorca,P-M; Camus, V., Courtet, P., Gourion, D., Lukasiewicz, M., Coulomb, S. 2013. Caractéristiques et modalités de prise en charge des patients présentant un trouble bipolaire en France: enquête MONTRA. L’Encéphale, 39, 212—223 Marengo E., Martino D.J., Igoa A., Scápola M., Fassi G., Urtueta M., Baamonde, Strejilevich, S. 2015a. Unplanned pregnancies and reproductive health among women with bipolar disorder. Journal of Affective Disorders 178, 201-205. Marengo E., Martino D.J., Igoa A., Scápola M., Fassi G., Baamonde M.U., Strejilevich, S. 2015b. Sexual risk behaviors among women with bipolar disorder. Psychiatry Research, 230, 835-838. Meade, C.S. and Sikkema, K.J. 2005. HIV risk behavior among adults with severe mental illness: a systematic review. Clin. Psychol. Rev., 25, pp. 433-457 Miller LJ, Ghadiali NY, Larusso EM, et al. 2015. Bipolar disorder in women. Health Care Women Int. 2015;36(4):475–498. doi:10.1080/07399332. Oddens B . 1997. Determinants of contraception use among women of reproductive age in Great Britain and Germany: II Psychological factors . J Biosoc Sci; 29 : 437 – 70 Paton C, Cookson J, Ferrier IN, et al. A UK clinical audit addressing the quality of prescribing of sodium valproate for bipolar disorder in women of childbearing age. BMJ Open 2018;8:e020450. doi:10.1136/bmjopen-2017-020450 Poncet, LC; Huang, N; Rei, W., Lin, YC & Chen, YC. 2013. Contraceptive use and method among immigrant women in France: Relationship with socioeconomic status. The European Journal of Contraception and Reproductive Health Care, 2013; 18: 468–479 Posada-Correa, AM., Andrade-Carrillo, RA., Suarez-Vega, D.C., Gómez-Cano, S.,Agudelo-Arango, LG.,Tabares-Builes, LF.,Agudelo-García, AM.,Uribe-Villa, E., CamiloAguirre-Acevedo, DC.,López-Jaramillo, C. 2020. Sexual and reproductive Health in patients with Schizophrenia and Bipolar Disorder.Revista Colombiana de Psiquiatría.Volume 49, Issue 1, January–March, Pages 15-22 Rusner, M., Berg, M., and Begley, C., 2016. Bipolar disorder in pregnancy and childbirth: a systematic review of outcomes. BMC Pregnancy and Childbirth 16:331 DOI 10.1186/s12884-016-1127-1 Samalin, L., Godin, O., et al. Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort. Journal of Affective Disorders 276 (2020) 963–969 Rahib D, Le Guen M, Lydié N. Baromètre santé 2016. Contraception. Quatre ans après la crise de la pilule, les évolutions se poursuivent. Saint-Maurice : Santé publique France, 2017. 8 p. Santé publique France. 2013. État des lieux des pratiques contraceptives et des freins à l’accès et au choix d’une contraception adaptée. Yang, HS., Hsu, JW., Huang, KL., Tsai, SJ., Bai, YM., Su, TP., Chen, TJ., Chen, MH. 2022. Risk of teenage pregnancy among adolescents with bipolar disorder: a cohort study of 35,398 adolescent girls. European Child & Adolescent Psychiatry https://doi.org/10.1007/s00787-022-02029-z Additional Declarations Competing interest reported. Conflict of interest: Ludovic Samalin has received personal fees and/or non-financial support from Janssen, Lundbeck, Sanofi, Otsuka, Rovi. Raoul Belzeaux has received personal fees and/or non-financial support from Janssen, Lundbeck, Sanofi. The other authors have no conflicts of interest to declare. Role of the funding source: The funders had no role in the design, analysis, write-up or decision to submit for publication. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 22 Jul, 2024 Editor assigned by journal 19 Jul, 2024 Submission checks completed at journal 19 Jul, 2024 First submitted to journal 28 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4654126","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":330231486,"identity":"1f295abb-82ad-448e-86b7-42646688bf90","order_by":0,"name":"Elisa Rodríguez-Toscano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYDACdsYGCOMAjMHeQEALM7oWHp4DhLTAGDCFPBIJ+HXwMzM3f/jBcE+O7/bh5tc8FXUM9pJvDD/dYLCxx6VFspmxTbKHodhY8lximzXPGTYGHukcY+kchrTEBhxaDA4ztjHwMCQkbjjD2GbM28YD0mLGnMNwGKfz7A8zNn/8A9fyT4KBR/IMSMt/nA4zAIaYNNSW5se8DQZA7/OAtMDDHANIAB0mLWOQYCwJtIVxzrEEHp4zacXSOQbJOP3C397++OObigQ5vjPsjz+8qamTY28/vPFzToUdTodBnQcm2SSABA+yCEHA/IE4daNgFIyCUTDSAABLRUs77z9cyQAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Experimental Psychology, Cognitive Processes and Speech Therapy, Universidad Complutense de Madrid (UCM)","correspondingAuthor":true,"prefix":"","firstName":"Elisa","middleName":"","lastName":"Rodríguez-Toscano","suffix":""},{"id":330231487,"identity":"389be664-b875-47da-8cb8-873bacaea5da","order_by":1,"name":"Ingrid de Chazeron","email":"","orcid":"","institution":"Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal (UMR 6602)","correspondingAuthor":false,"prefix":"","firstName":"Ingrid","middleName":"","lastName":"de Chazeron","suffix":""},{"id":330231488,"identity":"b15a9bb8-840a-4c72-bd40-8dc091276adf","order_by":2,"name":"Raoul Belzeaux","email":"","orcid":"","institution":"Pôle Universitaire de Psychiatrie, CHU de Montpellier","correspondingAuthor":false,"prefix":"","firstName":"Raoul","middleName":"","lastName":"Belzeaux","suffix":""},{"id":330231489,"identity":"cba5eb58-50a1-463e-be00-e0aebf75506e","order_by":3,"name":"Pierre Michel Llorca","email":"","orcid":"","institution":"Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal (UMR 6602)","correspondingAuthor":false,"prefix":"","firstName":"Pierre","middleName":"Michel","lastName":"Llorca","suffix":""},{"id":330231490,"identity":"b64357bf-d296-442b-9db4-3af6525c6d13","order_by":4,"name":"Ludovic Samalin","email":"","orcid":"","institution":"Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal (UMR 6602)","correspondingAuthor":false,"prefix":"","firstName":"Ludovic","middleName":"","lastName":"Samalin","suffix":""}],"badges":[],"createdAt":"2024-06-28 10:36:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4654126/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4654126/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62661387,"identity":"6b1404fd-2996-49e6-a42d-705f43569c25","added_by":"auto","created_at":"2024-08-17 02:40:27","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36453,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart for subject eligibility\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4654126/v1/eb0389eb64f889faa8222d1d.jpg"},{"id":62661761,"identity":"01d2481c-03d2-4bd9-a527-6cdd04cc7109","added_by":"auto","created_at":"2024-08-17 02:48:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1202241,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4654126/v1/f59a083c-933f-4893-a12c-62108a136e70.pdf"}],"financialInterests":"Competing interest reported. Conflict of interest:\nLudovic Samalin has received personal fees and/or non-financial support from Janssen, Lundbeck, Sanofi, Otsuka, Rovi. Raoul Belzeaux has received personal fees and/or non-financial support from Janssen, Lundbeck, Sanofi. The other authors have no conflicts of interest to declare.\n\n\nRole of the funding source:\nThe funders had no role in the design, analysis, write-up or decision to submit for publication.","formattedTitle":"Contraceptive use in women of childbearing age with bipolar disorder","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eBipolar Disorder (BD) is a chronic severe psychiatric disorder characterized by the course of alternating manic, hypomanic, and depressive episodes (Grande, et. al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eBD, like other severe mental illnesses, is correlated of sexual risk behavior (Meade and Sikkema, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). In comparison to people with no psychiatric conditions, BD has been associated with more casual partners, less rates of monogamous sexual partnerships, more rates of HIV condition (Marengo, et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2015a\u003c/span\u003e), increased risk of early pregnancy (Yang, et. al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) and lower level of planning of pregnancies or unplanned pregnancy (Marengo, et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2015b\u003c/span\u003e). During pregnancy and in the postpartum period, withholding or stopping pharmacotherapeutic treatment constitutes a risk for the recurrence of the illness (Dinc, et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Harlow et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Miller, et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2015\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eContraception during childbearing age in BD could reduce the risk of unplanned pregnancy and its consequences. Long-term use of both mood stabilizers and second-generation antipsychotics was associated with a reduced risk of early pregnancy (Yang, et. al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003ePrevious reviews on pharmacotherapy for the peripartum management of BD have displayed that management of the pharmacological treatment for BD patients during the perinatal period is challenging and consideration of risks, benefits, and alternative therapies is needed before initiating therapy (Kameg, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Epstein, et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Treatment usually entails use of medications that not only interfere with the clearance of oral contraceptives, but may also be teratogenic or unsafe, such as the anticonvulsant mood stabilizers or lithium (Cohen, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). Although treatment guidelines may be of significant help, high heterogeneity exists across them. Shared decision-making represents a useful patient-centered approach during the perinatal period (Belzeaux,R. et al., 2019).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eIt exists scarce literature about the prevalence of contraceptive use in BD women of childbearing age (Magalh\u0026atilde;es, et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Posada-Correa, et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Dinc, et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). These studies either found a lower or similar rate of contraception use compared to healthy controls, but it appears to be sub-optimal use, mainly using the least efficient methods and leading to a higher rate of unplanned pregnancies (Magalh\u0026atilde;es, et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Posada-Correa, et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Dinc, et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). However, it is not clear which sociodemographic and clinical variables are associated to a higher use of contraception in BD women of childbearing age.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn the present study, we studied the prevalence of contraceptive use in BD women of childbearing age and which variables affect its use. Therefore, we aimed to make a sociodemographic, clinical and pharmacological treatment characterizations of a large representative sample of BD women of childbearing age, and analyzed which variables were associated to the use of a contraceptive method.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Project\u003c/h2\u003e \u003cp\u003eThe present study was supported by the MONTRA survey carried out in France between 2010 and 2011 among hospital and consultant psychiatrists. Its aim was to describe the conditions of care for BD patients using real-life data collection.\u003c/p\u003e \u003cp\u003e439 psychiatrists participated in the study recruiting the patients and evaluating them. These psychiatrists were randomly chosen from a national file of 12,000 psychiatrists (CEGEDIM file) in order to ensure the representativeness of the population, particularly in terms of clinical practice (consultants, day hospital, hospital practice).\u003c/p\u003e \u003cp\u003eDuring 4 consecutive days, they completed a questionnaire including sociodemographic, environmental, clinical and therapeutic characteristics of patients with BP diagnosis according to DSM-IV criteria.\u003c/p\u003e \u003cp\u003eThe variables of interest for this study were extracted from the MONTRA database, which will be explained in the next sub-sections.\u003c/p\u003e \u003cp\u003eThe investigation was declared to the French Data Protection Agency (CNIL-France) and the patient data remained anonymous. The procedures followed in this study were approved by the ethics committe (CPP Sud-Est, IRB 00008526). Informed consent to participate in the study was obtained from participants.\u003c/p\u003e \u003cp\u003eMore details of the project can be found elsewhere (Llorca, et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2013\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Participants\u003c/h2\u003e \u003cp\u003eThe MONTRA survey defined as inclusion criteria the following: Patients between 18 and 60 years old; Having a diagnosis of BD according to DSM-IV criteria and based on the judgment of the clinician. On the other hand, the exclusion criteria were as follows: Minors or patients over the age of 60;\u003c/p\u003e \u003cp\u003eSpecifically, for the present study we selected only women of childbearing age (up to 50 years old regarding consensus literature (Paton, et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Samalin, et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The subject\u0026rsquo;s eligibility can be seen in the flowchart in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Measures\u003c/h2\u003e \u003cp\u003e \u003cem\u003eSocio-demographic characteristics\u003c/em\u003e:\u003c/p\u003e \u003cp\u003eIn this section it was described the age of the participants, level of education, working situation, living situation and the presence of care givers. The categorization of data of these variables were performed as follows:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAge in years. Following the study of Paton (2018), the age of the participants was categorized into four groups (from 18 to 25, from 26 to 35, from 36 to 45 and from 46 to 50).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eThe highest education level achieved. This variable was registered considering the following categories: professional training, primary education, secondary education (which include both secondary and bachelor) and superior education.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eWorking situation. It was included as \u003cem\u003eactive\u003c/em\u003e all the subjects that were working or studying at the moment of the evaluation. We categorized as \u003cem\u003eInactive\u003c/em\u003e all the subjects that respond as disability, pensioner or other.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eLiving situation. It was considered in one group if the participant lives \u003cem\u003ealone\u003c/em\u003e and another group named as \u003cem\u003eother\u003c/em\u003e, which included the subjects that live with the spouse, the parents, in a therapeutic apartment, in an institution or other.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCaring. The present variable contains whether there exists a care giver that takes care of the participant or not.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eEffective contraception\u003c/em\u003e:\u003c/p\u003e \u003cp\u003eParticipants reported whether they were using contraceptive methods and, in case they were, the type of contraceptive method that they were using.\u003c/p\u003e \u003cp\u003eFor the present study, it was considered as effective contraception method the ones that have proved a high effectivity at preventing pregnancies. The following methods were considered effective: combined pill, progestogen-only pill, contraceptive patch, vaginal ring, contraceptive implant, intrauterine system, intrauterine device, female sterilisation, condoms or diaphragm. Withdrawal method was not considered by the clinicians as an effective contraception method in the study.\u003c/p\u003e \u003cp\u003e \u003cem\u003eClinical features\u003c/em\u003e:\u003c/p\u003e \u003cp\u003eIn this section we took into consideration the specific characteristics of the BD including the type of BD (type I, type II or other type), the presence of rapid cycles (defined as 4 mood episodes per year or more) and the phase of BD (euthymic phase, manic and mixed episode and depressive episode). Moreover, other clinical variables were assessed such as the history of suicide attempt, the illness duration (calculated from the diagnosis to the moment of the inclusion in the study), the previous hospitalization, and the presence of comorbidities including anxiety disorders and substance use disorders.\u003c/p\u003e \u003cp\u003eRegarding the psychosocial functioning, autonomy in disease management and autonomy in the treatment management variables were selected.\u003c/p\u003e \u003cp\u003e \u003cem\u003eTreatment modalities (Treatment prescribed during the consultation)\u003c/em\u003e:\u003c/p\u003e \u003cp\u003eThe pharmacological treatment (lithium, antipsychotics, anticonvulsants and antidepressants) was recorded.\u003c/p\u003e \u003cp\u003eMoreover, pharmacological treatment with high (valproate) or intermediate risk (lithium, carbamazepine, clozapine, haloperidol, milnacipran) for teratogenic effect were considered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Statistical analysis\u003c/h2\u003e \u003cp\u003eThe sample of our cohort was characterized using the variables of interest and comparing them between two groups of patients: \u0026ldquo;with contraception\u0026rdquo; and \u0026ldquo;without contraception\u0026rdquo;. Statistical analyzes were performed with SPSS statistics 27.0 and all statistical tests will be performed for a 5% risk of type I error.\u003c/p\u003e \u003cp\u003eContinuous variables with normal distribution were presented as mean (standard deviation (SD). Categorical variables are expressed as counts and percentages.\u003c/p\u003e \u003cp\u003eFor univariate analyses, the Student test or Mann-Whitney test was used for the quantitative variables (homoscedasticity studied by the Fisher-Snedecor test) and the Chi\u003csup\u003e2\u003c/sup\u003e test or Fisher's exact test for the categorical parameters. The results can be expressed in terms with 95% confidence intervals.\u003c/p\u003e \u003cp\u003eFinally, in order to find out which variables had a predictive effect on the use of contraception, it was run a logistic regression test. Candidate variable selection was based on statistical significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) from previous univariate screening and retained age bands, level of education, working situation, living situation, illness duration, illness management, treatment management and current phase of BD.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Sociodemographic, clinical and treatment characteristics of women of childbearing age with BD\u003c/h2\u003e \u003cp\u003eA total sample of 796 BD women of childbearing age was analyzed in the present study (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Within this sample, 487 (61.2%) reported contraception use. They were in majority between 36 and 45 years old (42.5%), followed by the groups of subjects from 26 to 35 years old and from 46 to 50 years old, with more than 20%. The majority group of subjects had studied either secondary or superior education, more than half of the participants were active and do not live alone.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSociodemographic, clinical and treatment characteristics of childbearing age women with BD (n\u0026thinsp;=\u0026thinsp;796)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSociodemographic variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge bands\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;25, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26\u0026ndash;35, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e220 (27.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36\u0026ndash;45, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e338 (42.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e46\u0026ndash;50, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e177 (22.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLevel of education\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProfessional training, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e178 (22.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary education, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (3.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary education, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e287 (36.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuperior education, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e303 (38.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWorking situation: active, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e515 (64.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLiving situation: alone, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e272 (34.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHas a caregiver, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e225 (28.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eContraception use\u003c/b\u003e, \u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e487 (61.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical characteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of BD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType I, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e418 (52.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType II, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e350 (44.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther type, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (3.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRapid cycle, Yes, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (9.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent phase of BD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEuthymic phase, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e605 (76.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eManic and mixed episode, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (9.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepressive episode, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e113 (14.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of at least one suicide attempt, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e309 (38.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIllness duration, years mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.92 (5.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHospitalization, ever, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e587 (73.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutonomous in illness management, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e588 (73.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutonomous in treatment management, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e705 (88.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePsychiatric comorbidities\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnxiety disorders, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e406 (51.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubstance use disorder, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e121 (15.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacologic treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTypes of pharmacological treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLithium, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148 (18.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond-generation antipsychotic (SGA), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e404 (50.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnticonvulsant (AC), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e204 (25.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntidepressant (AD), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAccording to teratogenic effect\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacologic treatment with high or intermediate risk*, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e224 (28.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eValproate, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbb\u003c/b\u003e: BD, Bipolar Disorder; SD, Standard Deviation.\u003c/p\u003e \u003cp\u003e\u003cb\u003eNote\u003c/b\u003e: Mean and standard deviation for quantitative variables, and number and proportion for categorical variables.\u003c/p\u003e \u003cp\u003e* Pharmacological treatment with high (valproate) or intermediate risk (lithium, carbamazepine, clozapine, haloperidol, milnacipran) for teratogenic effect.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eConsidering the clinical characteristics, half of the subjects were diagnosed with BD type I, and the average of illness duration was almost seven years. Most of the subjects with BD were hospitalized at least once in their lifetime. Almost 80% of the subjects was in a euthymic phase, around 10% in manic and mixed episode and other 15% in a major depressive episode.\u003c/p\u003e \u003cp\u003eIn regard to psychosocial functioning, around 70% of BD women displayed a self-management of their illness and more than 80% in the management of their treatment.\u003c/p\u003e \u003cp\u003eHalf of the BD women of childbearing age were treated with SGA, and around 20% either with lithium or AC. When the teratogenic effect was taken into consideration, data showed that 28% of the BD women of childbearing age were treated with a high or intermediate risk of teratogenic pharmacologic treatment and only 3% were taking valproate.\u003c/p\u003e \u003cp\u003e \u003cb\u003e3.2 Comparison of sociodemographic and clinical characteristics of women of childbearing age with BD that use and do not use contraception methods\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIn relation to the sociodemographic characteristics, there were a significant difference in age and level of education (Table\u0026nbsp;2). The group of age between 46 and 50 years old had a lower rate of women using contraception than the other age bands. The group of women with only primary education had a lower rate of contraception use than the other educational groups. Also, women that used a contraceptive method had a significantly higher percentage of active women and women not living alone in comparison to women that do not use a method of contraception.\u003c/p\u003e\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003e\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;2. Comparison of Sociodemographic, clinical and treatment characteristics of childbearing age BD women with and without contraception\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith contraception method (n\u0026thinsp;=\u0026thinsp;487)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWithout contraception method (n\u0026thinsp;=\u0026thinsp;309)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStatistical test\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePost hoc analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSociodemographic variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge bands\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;25, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e30.55, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e18\u0026ndash;25\u0026thinsp;=\u0026thinsp;26\u0026ndash;35, p\u0026thinsp;=\u0026thinsp;0.264\u003c/p\u003e \u003cp\u003e18\u0026ndash;25\u0026thinsp;=\u0026thinsp;36\u0026ndash;45, p\u0026thinsp;=\u0026thinsp;0.857\u003c/p\u003e \u003cp\u003e18\u0026ndash;25\u0026thinsp;\u0026gt;\u0026thinsp;46\u0026ndash;50, \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.009\u003c/b\u003e\u003c/p\u003e \u003cp\u003e26\u0026ndash;35\u0026thinsp;\u0026gt;\u0026thinsp;36\u0026ndash;45, \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.035\u003c/b\u003e\u003c/p\u003e \u003cp\u003e26\u0026ndash;35\u0026thinsp;\u0026gt;\u0026thinsp;46\u0026ndash;50, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e36\u0026ndash;45\u0026thinsp;\u0026gt;\u0026thinsp;46\u0026ndash;50, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26\u0026ndash;35, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e157 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (20.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36\u0026ndash;45, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e212 (43.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e126 (40.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e46\u0026ndash;50, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (31.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLevel of education\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary education (PE), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e24.55, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003ePE\u0026thinsp;\u0026lt;\u0026thinsp;SE, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePE\u0026thinsp;\u0026lt;\u0026thinsp;SuE, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSE\u0026thinsp;\u0026lt;\u0026thinsp;SuE, \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.027\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePF\u0026thinsp;\u0026gt;\u0026thinsp;PE, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePF\u0026thinsp;=\u0026thinsp;SE, p\u0026thinsp;=\u0026thinsp;0.128\u003c/p\u003e \u003cp\u003ePF\u0026thinsp;=\u0026thinsp;SuE, p\u0026thinsp;=\u0026thinsp;0.700\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary education (SE), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e165 (33.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e122 (39.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProfessional training (PF), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115 (23.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (20.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuperior education (SuE), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e201 (41.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102 (33.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWorking situation: active, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e346 (71.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169 (54.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.14, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLiving situation: alone, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e149 (30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123 (39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.13, \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHas a caregiver, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141 (29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (27.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.292, p\u0026thinsp;=\u0026thinsp;0.589\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical characteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of BD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType I, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e253 (52.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e165 (53.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1.043, p\u0026thinsp;=\u0026thinsp;0.594\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType II, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e219 (45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e131 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther type, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRapid cycle, Yes, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (9.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.136, p\u0026thinsp;=\u0026thinsp;0.567\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent phase of BD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEuthymic phase, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e386 (79.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e219 (71.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e8.27, \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eManic and mixed episode, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepressive episode, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of at least one suicide attempt, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e193 (39.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.277, p\u0026thinsp;=\u0026thinsp;0.528\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIllness duration, years mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.33 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.84 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.59, \u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHospitalization, ever, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134 (27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (24.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.027, p\u0026thinsp;=\u0026thinsp;0.311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutonomous in illness management, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e372 (76.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e216 (69.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.117, \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.042\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutonomous in treatment management, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e443 (91.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e262 (84.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.120, \u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePsychiatric comorbidities\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnxiety disorders, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e250 (51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e156 (50.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.893, p\u0026thinsp;=\u0026thinsp;0.235\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubstance use disorder, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.153, p\u0026thinsp;=\u0026thinsp;0.926\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacologic treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTypes of pharmacological treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLithium, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.074, p\u0026thinsp;=\u0026thinsp;0.786\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond generation antipsychotic (SGA), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e247 (50.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e157 (50.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001, p\u0026thinsp;=\u0026thinsp;0.980\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnticonvulsant (AC), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (25.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.018, p\u0026thinsp;=\u0026thinsp;0.893\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntidepressant (ATD), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.173, p\u0026thinsp;=\u0026thinsp;0.678\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAccording to teratogenic effect\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacologic treatment with high or intermediate risk*, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139 (28.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.100, p\u0026thinsp;=\u0026thinsp;0.752\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eValproate, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015, p\u0026thinsp;=\u0026thinsp;0.902\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbb\u003c/b\u003e: BD, Bipolar disorder.\u003c/p\u003e \u003cp\u003e\u003cb\u003eNote\u003c/b\u003e: Chi square for categorical variables and t test for quantitative variables.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRegarding the clinical characteristics, no differences were found in proportion of type of BD, rates of hospitalizations, history of suicide attempts or presence of rapid cycles between the groups of women with and without use of contraception. Women with contraception displayed a significantly shorter duration of the illness, higher rates of patients in euthymic phase and lower rates of patients in depressive phase than the women without use of contraception.\u003c/p\u003e \u003cp\u003eConsidering the psychosocial functioning of the participants, the contraception use was significantly higher for autonomous women in illness management and treatment management.\u003c/p\u003e \u003cp\u003eIn regard to the pharmacological treatment, no differences were found between the women using and not using contraception.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Predictive variables of contraception use in BD women of childbearing age\u003c/h2\u003e \u003cp\u003eWe performed a logistic regression test for predicting the odds of using contraception with the following explanatory variables: age bands, level of education, working situation, living situation, illness duration, autonomy in illness management, treatment management and current phase of BD (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTable 3 Logistic regression model for sociodemographic, clinical and funcional variables associated with the use of contraception in BD women at childbearing age.\u003c/p\u003e\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExp(B)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e95% C.I.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInferior\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge bands, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e46\u0026ndash;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.510\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.781\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.921\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.220\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26\u0026ndash;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.404\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.538\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.760\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36\u0026ndash;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.919\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.827\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLevel of education\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.507\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12. 079\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProfessional training\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.745\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuperior education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.666\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWorking situation (active)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.626\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLiving situation (not living alone)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.414\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.944\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIllness duration\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.947\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutonomy in illness management\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.754\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.765\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.511\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutonomy in treatment management\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.504\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.160\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent phase of BD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEuthymic phase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eManic and mixed episode\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.501\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.326\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.771\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepressive episode\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.501\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNote\u003c/b\u003e: 46\u0026ndash;50 years old and superior education have been selected as baseline or constant dummy variable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbb\u003c/b\u003e: C.I, Confidence Interval; SD, Standard Deviation; Sig., Significance\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAccording to Nagelkerke Rsquare in our model the 13.1% of the variance of the outcome, so whether the participants use contraception or not, can be explained by our predictors. The model has predicted overall a percentage of 66.2%.\u003c/p\u003e \u003cp\u003eThe model found no significant effect of the dependent variables of years of illness duration, autonomy in illness management and treatment management.\u003c/p\u003e \u003cp\u003eThe variables significantly associated with an effect on contraception use were age, level of education, working, living situation and current phase of BD.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe use of contraceptive methods can reduce the unplanned pregnancies in BD. Its use during childbearing age is associated with high level of education and capacity to planned pregnancy and avoid unplanned pregnancy in BD women. Therefore, it is important to find out which variables are associated with a less adherence to contraceptive methods. Interestingly, the present study found out that the strongest predictive effect are the sociodemographic factors rather than the clinical or treatment characteristics.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe analyzed sample displayed a 61.2% rate of BD women of childbearing age that use contraception. According to the French Health Report in 2016, the use of a contraceptive method in general population in France is around 70% in women of childbearing age (Rahib, et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Previous literature with BD women were similar to the present study. They reported rates of contraception use in BD women of 52.1% (Posada-Correa, et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2020\u003c/span\u003e), 59% (Magalh\u0026atilde;es, et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2009\u003c/span\u003e) and 73% (Dinc, et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), being systematically slightly lower in the group of BD patients in comparison to general population. This could be at least partially explained by variables related to education level, economic status, social barriers and some attitudes of professionals in which the sexuality of people with mental health disorders is not always considered (Sant\u0026eacute; publique France, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). A systematic review of pregnancy in BD described that adverse pregnancy outcomes such as gestational hypertension and antepartum haemorrhage, induction of labor and caesarean section occur more frequently in BD women. BD Women also have an increased risk of relapse in the postnatal period and are more likely to have babies that are severely small for gestational age (Rusner et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn relation to the demographic characteristics associate to contraception use in BD, the present study found that the age, level of education, active working situation, not living alone are positively associated to higher rates of use of contraception. This is consistent with the only study that described demographic variables related to the use of contraception in BD. They displayed that being married, pertaining to the older age group and having had one or two pregnancies and more than two were associated with using contraception (Magalh\u0026atilde;es, 2019). Similar results with an association with low level of education and no working were found in a study among immigrant and second-generation immigrant women (Poncet et al \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). It might suggest that the increase age and level of education can be associated to a higher understanding of contraception and sexual education.\u003c/p\u003e\u003cp\u003eInterestingly, in light of the present results and the ones published previously (Magalh\u0026atilde;es, 2019) there are other demographic variables that do not seem to be related to the use of contraceptive methods, such as income or having a care giver.\u003c/p\u003e\u003cp\u003eRegarding the clinical characteristics, no differences were found in BD type, hospitalization rates, history of suicide attempts or presence of rapid cycling between the groups of women with and without use of contraception. These findings were again consistent with previous research which found no association between use of contraception and symptoms or illness severity (Magalh\u0026atilde;es, 2019). Data nevertheless highlighted that women using contraception displayed a significantly shorter duration of the illness than the women without use of contraception.\u003c/p\u003e\u003cp\u003eIn relation to comorbid disorders, it is interesting to report that, although no differences were found between subjects with and without contraception, half of the patients had an anxiety disorder and more that 15% a substance use disorder. These high rates of comorbidities have been previously described in BD (Icick, et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eConsidering the level of functioning of the participants, the already described functional impairment of BD patients (Burdick, et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) was observed in the present study. Over 25% of the analyzed sample displayed a lack of autonomy in the illness management and over 10% a lack of autonomy in their treatment management. Moreover, the percentage of autonomous women using contraception was significantly higher than the percentage of autonomous women not using contraception both for the illness management and the treatment management. This novel finding can suggest that the use of contraception in BD is related to the level of autonomy of the patient and the ability to cope and manage their illness.\u003c/p\u003e\u003cp\u003eRegarding the pharmacological treatment, around 28% of the women received treatment with high or intermediate risk for teratogenic effect. A previous study found that the use of lithium and anticonvulsant mood stabilizers was unrelated to use of contraception (Magalh\u0026atilde;es, et al., 2019). In the present study, although no differences were found between the women using and not using contraception, only 3% of the women were taking valproate medication. This highlights the avoidance of pharmacological treatment with high risk of teratogenic effect in BD women of childbearing age.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eIn summary, the present study found out that the most important variables associated with the use of contraception were age, level of education, working and living conditions. These demographic variables are similar to the ones influencing the contraception use in general population (Bentley et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Oddens, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e1997\u003c/span\u003e). However, as BD has an increased risk of unplanned pregnancies, intervention protocols might take this into consideration. Therefore, a collaboration between the psychiatric and gynecologic specialties could be implemented in the protocol assistance for adolescent girls with BD, with a focus on the plan of pregnancy and contraceptive methods, so as to reduce the risk of unplanned pregnancy. A study reported that 32.2% of women with mental health illness had never received information on sexual education and family planning. Authors indicated that evaluation and education on the topic in psychiatry consultations is limited, due to factors such as: lack of knowledge of the psychiatrist on the use of contraceptives, the perception that this evaluation does not correspond to the mental health consultation, avoidance of the topic (Posada-correa et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eOur findings need to be appraised in the context of limitations. Firstly, the present study did not use standardized scales with an adequate methodological validation. However, the recruitment of participants followed a systematic procedure and the high level of raters was guaranteed by the involvement of active clinician psychiatrists. Moreover, longitudinal data were not analyzed. Large cohort studies with follow up visits are needed to better identify risk associated to treatment discontinuation or treatment exposure. Furthermore, the data presented was collected ten years ago and therefore the results should be interpreted cautiously taking into consideration potential variations. Finally, in this study, women until 50 years old, who may already be in menopause, were included.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eIn conclusion, our findings confirm previous evidence of the similar rates of contraception use in BD women of childbearing age. We add to previous studies that it was mainly sociodemographic variables that were associated with contraception use among BD women. As preventive measures for risk of relapse in BD, contraceptive counseling, including reduction of the risk of unwanted pregnancies, should be systematically ensured.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003cp\u003eConflict of interest:Ludovic Samalin has received personal fees and/or non-financial support from Janssen, Lundbeck, Sanofi, Otsuka, Rovi. Raoul Belzeaux has received personal fees and/or non-financial support from Janssen, Lundbeck, Sanofi. The other authors have no conflicts of interest to declare.Role of the funding source:The funders had no role in the design, analysis, write-up or decision to submit for publication.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eE.R.-T: Conceptualization, data analysis, literature search, original draft preparation; L.dC : Conceptualization, writing\u0026mdash;review and editing; RB : writing\u0026mdash;review and editing ; PM.L : Conceptualization, writing\u0026mdash;review and editing; LS. Conceptualization, literature search, assessment, writing\u0026mdash;review and editing, supervision. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eNone\u003c/p\u003e\nThe content of the article has never been published before and is not under consideration for publication elsewhere. We confirm that the relevant codes of ethics and research ethics were upheld through the conduct of the research, including the assignment of authorship (i.e., based on meritorious scientific contribution). All authors have contributed significantly to the paper and are in total agreement with the content of the manuscript."},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBelzeaux R., Sanguinetti, C., Murru, A., Verdolini, N., Pacchiarotti, I., Hidalgo-Mazzei, D., Cohen, L., Anmell, G., Barbuti, M., Vieta, E., Llorca, P-M., and Samalin, L. 2019. Pharmacotherapy for the peripartum management of bipolar disorder. EXPERT OPINION ON PHARMACOTHERAPY. https://doi.org/10.1080/14656566.2019.1626826.\u003c/li\u003e\n\u003cli\u003eBentley R , Kavanagh A , Smith A . 2009. Area disadvantage, socioeconomic position and women \u0026rsquo; s contraception use: A multilevel study in the UK . J Fam Plann Reprod Health Care; 35 : 221 \u0026ndash; 6 .\u003c/li\u003e\n\u003cli\u003eBurdick KE, Millett CE, Yocum AK, et al. Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative. Bipolar Disord. 2022;24:709-719. doi: 10.1111/bdi.13208\u003c/li\u003e\n\u003cli\u003eCohen LS. 2007. Treatment of bipolar disorder during pregnancy. J Clin Psychiatry 68(Suppl 9):4\u0026ndash;9 C\u003c/li\u003e\n\u003cli\u003eMagalh\u0026atilde;es PV, Kapczinski F, Kauer-Sant\u0026rsquo;Anna M. 2009. Use of contraceptive methods among women treated for bipolar disorder. Arch Womens Ment Health.;12(3):183. doi:10.1007/s00737-009-0060-y\u003c/li\u003e\n\u003cli\u003eDinc H, Boyacioglu NE, Ozcan NK, Enginkaya S. Reproductive and sexual health in women with bipolar disorder: a comparative study. Dusunen Adam. 2019;32(1):23\u0026ndash;32\u003c/li\u003e\n\u003cli\u003eEpstein RA., Moore KM., Bobo WV. Treatment of bipolar disorders during pregnancy: maternal and fetal safety and challenges. Drug Healthc Patient Saf. 2015; 7: 7\u0026ndash;29.\u003c/li\u003e\n\u003cli\u003eGrande, I., Berk, M., Birmaher, B., Vieta, E., 2016. Bipolar disorder. Lancet 387, 1561\u0026ndash;1572. https://doi.org/10.1016/S0140-6736(15)00241-X\u003c/li\u003e\n\u003cli\u003eHarlow BL, Vitonis AF, Sparen P, Cnattingius S, Joffe H, Hultman CM (2007) Incidence of hospitalization for postpartum psychotic and bipolar episodes in women with and without prior prepregnancy or prenatal psychiatric hospitalizations. Arch Gen Psychiatry 64(1):42\u0026ndash;48\u003c/li\u003e\n\u003cli\u003eIcick R, Gard S, Barde M, et al. 2017. Physical and mental health burden in cases of bipolar disorder classified as current, former, or non‐ tobacco smokers. J Affect Disord.;208:406‐413\u003c/li\u003e\n\u003cli\u003eKameg BN PMHNP‐BC, CARN, CNE. 2021. Bipolar disorder: Treatment strategies for women of childbearing age. Perspect Psychiatr Care; 57:1244\u0026ndash;1249\u003c/li\u003e\n\u003cli\u003eLlorca,P-M; Camus, V., Courtet, P., Gourion, D., Lukasiewicz, M., Coulomb, S. 2013. Caract\u0026eacute;ristiques et modalit\u0026eacute;s de prise en charge des patients pr\u0026eacute;sentant un trouble bipolaire en France: enqu\u0026ecirc;te MONTRA. L\u0026rsquo;Enc\u0026eacute;phale, 39, 212\u0026mdash;223\u003c/li\u003e\n\u003cli\u003eMarengo E., Martino D.J., Igoa A., Sc\u0026aacute;pola M., Fassi G., Urtueta M., Baamonde, Strejilevich, S. 2015a. Unplanned pregnancies and reproductive health among women with bipolar disorder. Journal of Affective Disorders 178, 201-205.\u003c/li\u003e\n\u003cli\u003eMarengo E., Martino D.J., Igoa A., Sc\u0026aacute;pola M., Fassi G., Baamonde M.U., Strejilevich, S. 2015b. Sexual risk behaviors among women with bipolar disorder. Psychiatry Research, 230, 835-838.\u003c/li\u003e\n\u003cli\u003eMeade, C.S. and Sikkema, K.J. 2005. HIV risk behavior among adults with severe mental illness: a systematic review. Clin. Psychol. Rev., 25, pp. 433-457\u003c/li\u003e\n\u003cli\u003eMiller LJ, Ghadiali NY, Larusso EM, et al. 2015. Bipolar disorder in women. Health Care Women Int. 2015;36(4):475\u0026ndash;498. doi:10.1080/07399332. \u003c/li\u003e\n\u003cli\u003eOddens B . 1997. Determinants of contraception use among women of reproductive age in Great Britain and Germany: II Psychological factors . J Biosoc Sci; 29 : 437 \u0026ndash; 70\u003c/li\u003e\n\u003cli\u003ePaton C, Cookson J, Ferrier IN, et al. A UK clinical audit addressing the quality of prescribing of sodium valproate for bipolar disorder in women of childbearing age. BMJ Open 2018;8:e020450. doi:10.1136/bmjopen-2017-020450\u003c/li\u003e\n\u003cli\u003ePoncet, LC; Huang, N; Rei, W., Lin, YC \u0026amp; Chen, YC. 2013. Contraceptive use and method among immigrant women in France: Relationship with socioeconomic status. The European Journal of Contraception and Reproductive Health Care, 2013; 18: 468\u0026ndash;479\u003c/li\u003e\n\u003cli\u003ePosada-Correa, AM., Andrade-Carrillo, RA., Suarez-Vega, D.C., G\u0026oacute;mez-Cano, S.,Agudelo-Arango, LG.,Tabares-Builes, LF.,Agudelo-Garc\u0026iacute;a, AM.,Uribe-Villa, E., CamiloAguirre-Acevedo, DC.,L\u0026oacute;pez-Jaramillo, C. 2020. Sexual and reproductive Health in patients with Schizophrenia and Bipolar Disorder.Revista Colombiana de Psiquiatr\u0026iacute;a.Volume 49, Issue 1, January\u0026ndash;March, Pages 15-22\u003c/li\u003e\n\u003cli\u003eRusner, M., Berg, M., and Begley, C., 2016. Bipolar disorder in pregnancy and childbirth: a systematic review of outcomes. BMC Pregnancy and Childbirth 16:331 DOI 10.1186/s12884-016-1127-1\u003c/li\u003e\n\u003cli\u003eSamalin, L., Godin, O., et al. Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort. Journal of Affective Disorders 276 (2020) 963\u0026ndash;969\u003c/li\u003e\n\u003cli\u003eRahib D, Le Guen M, Lydi\u0026eacute; N. Barom\u0026egrave;tre sant\u0026eacute; 2016. Contraception. Quatre ans apr\u0026egrave;s la crise de la pilule, les \u0026eacute;volutions se poursuivent. Saint-Maurice : Sant\u0026eacute; publique France, 2017. 8 p.\u003c/li\u003e\n\u003cli\u003eSant\u0026eacute; publique France. 2013. \u0026Eacute;tat des lieux des pratiques contraceptives et des freins \u0026agrave; l\u0026rsquo;acc\u0026egrave;s et au choix d\u0026rsquo;une contraception adapt\u0026eacute;e.\u003c/li\u003e\n\u003cli\u003eYang, HS., Hsu, JW., Huang, KL., Tsai, SJ., Bai, YM., Su, TP., Chen, TJ., Chen, MH. 2022. Risk of teenage pregnancy among adolescents with bipolar disorder: a cohort study of 35,398 adolescent girls. European Child \u0026amp; Adolescent Psychiatry https://doi.org/10.1007/s00787-022-02029-z\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bipolar disorder, Childbearing age, Contraceptive use, Women","lastPublishedDoi":"10.21203/rs.3.rs-4654126/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4654126/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnplanned pregnancies are frequent in women with bipolar disorder (BD) while perinatal period is associated with a higher risk of relapse. Effective contraception during childbearing age in BD could reduce the risk of unplanned pregnancy and its consequences. The present study studied the prevalence of contraceptive use and which sociodemographic and clinical variables affect its use in women with BD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e796 women (18-50 years old) with BD were recruited and evaluated by the MONTRA survey in France among hospital and consultant psychiatrists. Sociodemographic, clinical and treatment variables were compared between patients with and without contraception use. A logistic regression estimated which variables had a predictive effect on the use of contraception.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA 61.2% reported the use of effective contraception. Women who use contraception were in 26-35 (OR=2.40,p\u0026lt;0.001) and 36-45 (OR=1.92,p\u0026lt;0.001) range age, displayed higher levels of education (OR= 5.07,p=0.003), were more active (OR=1.63,p=0.006), did not live alone (OR=1.41,p=0.033) and had fewer manic or mixed episodes (OR=0.50,p=0.007).No association was found with the nature of pharmacological treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusion\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSociodemographic variables were mainly associated with contraception use among BD women. As preventive measures for risk of relapse in BD, contraceptive counseling, including reduction of unplanned pregnancies, should be systematically ensured.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Contraceptive use in women of childbearing age with bipolar disorder","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-17 02:40:23","doi":"10.21203/rs.3.rs-4654126/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-22T14:10:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-19T10:37:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-19T10:37:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2024-06-28T10:35:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5a003f5c-b5ac-48d2-8d75-71d5bcea53d3","owner":[],"postedDate":"August 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T02:39:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-17 02:40:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4654126","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4654126","identity":"rs-4654126","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}