Trajectories of antidepressant drugs during pregnancy: A cohort study from a community-based sample
The authors confirm that the Principal Investigator for this paper is Catherine Laporte and that she had direct clinical responsibility for data.
Abstract
Aims
The aim of this study was to monitor the trajectories of antidepressant use during pregnancy and the postpartum period among women chronically treated with antidepressants before their pregnancy, and to assess characteristics associated with each trajectory.
Methods
This cohort study included all pregnant women whose data were included in the General Sample of Beneficiaries (EGB) database affiliated with the French Health Insurance System, from 2009 to 2014. Women were followed up until 6 months after childbirth. Chronic treatment was defined as exposure over the 6-month period preceding pregnancy. A group-based trajectory model (GBMT) was estimated to identify distinctive longitudinal profiles of antidepressant use.
Results
Among 760 women chronically treated with antidepressants before their pregnancy, 55.8% stopped their treatment permanently in the first trimester, 20.4% discontinued it for a minimum of 3 months and resumed it postpartum, and 23.8% maintained it throughout pregnancy and postpartum. No sociodemographic or medical characteristics were associated with any trajectory group. Women who maintained treatment presented more frequent obstetric complications and postpartum psychiatric disorders. Among women who interrupted treatment, prescription of benzodiazepines and anxiolytics decreased initially but rose postpartum to a higher level than before pregnancy.
Conclusions
Pregnant women treated with antidepressant require a re-evaluation of psychiatric treatment. It is necessary to pay attention to obstetric complications for severely depressed women. Additionally, as relapse was associated with increased benzodiazepine use, it is important to carefully monitor all women who stop antidepressant treatment during pregnancy.
What is already known about this subject
- There is no absolute contraindication to taking antidepressants during pregnancy.
- The majority of pregnant women treated with antidepressants stop treatment abruptly.
- Seventy per cent of pregnant women treated with antidepressants who stop them abruptly may experience a relapse.
What this study adds
- Half of the participating women stopped their antidepressant treatment without complications.
- Women undergoing antidepressant treatment who stopped during pregnancy and resumed in the following weeks had a rebound effect of increased prescription of benzodiazepines and anxiolytics.
1 INTRODUCTION
In France, the use of psychotropic drugs was of particular concern in women of childbearing age, with a prevalence of 23% versus 13% in men of the same age, and 3.2% of women started pregnancy when exposed to antidepressants1 in 2010. The main indication for antidepressants is depression,2 and women of childbearing age are indeed twice as likely as men to develop depression.3 Pregnancy is also a risk period, with a prevalence of depression during pregnancy in France between 5 and 15%.4
Untreated maternal depression has deleterious consequences for the expectant mother and the fetus.5 In the mother, psychic relapse can lead to suicidal risk, puerperal psychoses and an unstable emotional connection between the mother and the child.4, 6 Although there are fewer deaths and suicide attempts during pregnancy and the postnatal period than in the general female population, deaths by suicide account for 20% of all deaths in the postnatal period.7-9 Additionally, severe depressive state may increase the risk of intrauterine growth retardation and prematurity in the fetus and delayed psychomotor development in children may be due to increased amounts of maternal cortisol released into the bloodstream.10, 11
As all antidepressants pass the placental barrier,12 about 30% of newborns exposed in utero suffer from neonatal withdrawal syndrome, which is usually benign, treatable and resolves under surveillance.13
Selective serotonin reuptake inhibitors (SSRIs) are the antidepressants most commonly prescribed during pregnancy. Despite contrasting evidence, they appear to be safe in pregnant women,14-18 so they are recommended by the National Agency for Health and Medicines (ANSM)19 and the 2018 International Cochrane Review International Publications.20 As there is no absolute contraindication to taking antidepressant medications during pregnancy, they should not be stopped abruptly, which would increase the risk of depression relapse with a rebound effect.21, 22
In France in 2016, 5% of women were exposed to at least one anxiolytic–hypnotic drug during pregnancy.23 Benzodiazepines are often prescribed for anxiety and depression,24 with substantial heterogeneity across countries, and across the different periods of pregnancy (e.g., increase from preconception to pregnancy, with a subsequent decrease to postpartum).25 When used during pregnancy, benzodiazepines and benzodiazepine-related drugs pass readily through the placenta, and are associated with adverse birth outcomes (spontaneous abortion, preterm birth, and when used in the third semester loppy infant syndrome or respiratory problems).25
Many studies have shown that the use of antidepressants decreases during the first 3 months of pregnancy.26-30 A recent population-based study from Denmark, observed that the prescription of antidepressants was less common during pregnancy than before and after it in the period 1997 to 2016.31 To our knowledge, only few previous studies have investigated trajectories of medication use during pregnancy. Hurault et al. were the first researchers to study psychotropic drugs during pregnancy with longitudinal methods23 and to describe use of anxiolytics.24 They encouraged longitudinal methods over this period which evolves over 9 months, and which is studied over 3-months periods. Hurault et al. compared the use of cross-sectional and longitudinal methods during pregnancy: transverse methods will be better suited to looking for a specific effect of a drug during a given time. Longitudinal studies are needed to compare women who discontinue antidepressant treatment with those who did not, with respect to relapse of depression during pregnancy and the postnatal period and to consequences for newborn infants.24 Bandoli et al. studied the prescription trajectories of antidepressants during pregnancy and during the postpartum period but without linking the two periods, and on a small sample (166 women).32
The prevalence of depressive disorders in women and their consequences for the mother and child during and after pregnancy, as well as the high prevalence of use of antidepressants in France, necessitates monitoring the trajectories of antidepressant treatment during and after pregnancy in women who were treated before their pregnancy. Our study is the first to study antidepressant use over the entire pre-intra-post pregnancy period, with a large sample of women chronically treated with antidepressants before their pregnancy. This allows us to (1) assess the prevalence of antidepressant discontinuation, (2) compare women's characteristics and consequences associated with antidepressant treatment maintenance vs discontinuation, and (3) to inform preventive interventions in this vulnerable population.
2 OBJECTIVES
The primary aim of the study was to monitor the time trends of antidepressant treatment during pregnancy and the postpartum 6-month period among women chronically treated with antidepressants before their pregnancy, using trajectory models that help in identifying treatment changes. The secondary objectives were: (i) to identify factors associated with stopping antidepressant treatment during pregnancy; (ii) to investigate complications associated with each trajectory of treatment use; and (iii) to assess the parallel evolution of co-treatment with benzodiazepines.
3 METHODS
3.1 Design and data sources
This cohort study was conducted using data from the General Sample of Beneficiaries database (EGB) during the period from January 1, 2009 to December 31, 2014.33 We used a group-based trajectory model (GBMT) to identify distinctive longitudinal profiles of reimbursement for antidepressant use.34
The EGB database contains a representative 1/97th random sample of the population (600,000 beneficiaries) and is affiliated with the French national health insurance system (approximately 98% of the French population).33 The EGB is updated quarterly and counts entries (births, new affiliations) and exits (deaths, regime changes). Since 2005, the EGB database has included anonymous information on the sociodemographic characteristics of the beneficiaries (age, sex, date of death, affiliation fund, and welfare benefit for low-income people) and some medical information. The sample contains detailed codes for biologicals, medical devices and medical technical procedures according to the Common Classification of Medical Acts (CCAM). It includes information about health professionals who met beneficiaries (specialty, nature of practice) and care facilities. The database is linked to the national hospitalization database of the Medical Information Systems Program (PMSI) with information on the diagnoses (main, connected, associated) according to the 10th version of the International Classification of Diseases (ICD-10), for each hospital stay of the beneficiary (except psychiatric hospitalization). Diagnoses are also available through the long-term condition status (ALD), which gives access to care free of charge for the given disease (collected according to their ICD-10). Finally, the EGB database includes all drug reimbursements, classified according to their Anatomical Therapeutic Chemical (ATC) code, with the exception of drugs retroceded by the hospital. The collected data are kept for 20 years beyond the current year. The EGB database has been widely used for public health and pharmaco-epidemiological purposes for over 5 years.35, 36
Time trends in the reimbursement for antidepressants were monitored for 6 months before conception date, during pregnancy and up to 6 months after childbirth, divided into 3-month periods. The pregnancy trimesters were calculated in 90-day increments, thus following the definition of the World Health Organization (WHO) by indicating gestational age in weeks of gestation (WG) (1–15 WG inclusive for 1st trimester – T1; 16–28 WG inclusive for 2nd trimester – T2; and 29–41 WG inclusive for 3rd trimester –_T3). We chose to analyse postpartum treatment for 6 months.37
3.2 Study sample
The study was conducted on all women chronically treated with antidepressants prior to pregnancy and who gave birth between 2009 and 2014 (see Appendix 1). We selected women who had: (i) a pregnancy ending with birth from January 1, 2009 to December 31, 2014; (ii) a refund for three boxes or more of antidepressant over the 6 months preceding the beginning of pregnancy; and (iii) available data from 6 months before pregnancy to 6 months after childbirth. The conception date was based on the gestational age at delivery (based on early ultrasound) subtracted from the date of birth. We excluded women for whom the term at delivery was unknown, women who had a pregnancy ending in an abortion or miscarriage before 22 weeks, and women without antidepressant treatment before pregnancy.
3.3 Measures and outcomes
3.3.1 Drug exposure
Drug exposure was identified through the reimbursement for antidepressants. Non-selective monoamine reuptake inhibitors (INSRMs), selective serotonin reuptake inhibitors (SSRI), non-selective monoamine inhibitors (IMONSs), monoamine oxidase inhibitors (MAOIs), and serotonin–norepinephrine reuptake inhibitors (SNRIs) were identified in the EGB database via their ATC code (Appendix 2). In France, antidepressants are only available on doctor's prescription and are therefore all reimbursed (the database therefore gives access to the entirety of antidepressants delivered to patients), and the majority of antidepressants are sold in boxes of 7, 14, 28 or 30 tablets (the prescription can be from 1/2 to several tablets per day). Considering at least one reimbursement over 3 months allows us to take into account the participants who had a prescription during this period and not to miss a patient under treatment. For each 3-month time unit, there was at least one antidepressant reimbursement for the patient in the EGB database (1) or there was none (0).
3.3.2 Collected data
Data were extracted from the EGB database using the CCAM, ICD-10 or ALD codes (Appendix 3). The collected data concerned sociodemographic information, pregnancy outcomes and obstetric or non-obstetric history of the patient: age at delivery (a three-category variable: <20 years, 20–35 years, or >35 years), welfare beneficiary, nulliparous or parous, history of complicated pregnancy, sterility or pathway of assisted reproduction, anorexia, diabetes, substance use, ALD status or psychiatric comorbidities, psychiatric disorders or suicide attempt.
Context of ongoing pregnancy: single or multiple pregnancy, substance use, or obesity.
Pregnancy tracking: number of obstetric ultrasounds (usually three per pregnancy) (Appendix 3), number of general practice or psychiatric consultations and number of hospitalizations during the pregnancy, length of maternity stay.
Complications of pregnancy and childbirth: excessive weight gain, preeclampsia/eclampsia, threatened preterm labour (PAD), gestational diabetes, haemorrhage during pregnancy and delivery, Non-reassuring fetal heart rate, Caesarean delivery but also ALD status or psychiatric comorbidities during a hospitalization, psychiatric disorders or suicide attempt during pregnancy (Appendix 3).
Psychiatrics events or complications before, during and after pregnancy: ALD status or psychiatric comorbidities during a hospitalization, psychiatric disorders or suicide attempt (Appendix 3).
Reimbursement for benzodiazepines before, during and after pregnancy, identified in the EGB database via their ATC code (Appendix 2). For each 3-month time unit, there was at least one benzodiazepine reimbursement for the patient in the EGB database (1) or there was none (0).
3.4 Statistical analysis
3.4.1 Trajectories of antidepressant reimbursement
To identify distinctive longitudinal patterns of reimbursement for antidepressant use, we used a semi-parametric mixture model group-based trajectory model (GBTM).34 GBTM is an empirical procedure that uses multinomial modelling with maximum likelihood to identify clusters of individuals who follow similar treatment trajectories. Models with one to five trajectories and different shapes (i.e., constant, linear, quadratic or cubic evolution over time) were estimated and compared using the Bayesian information criterion (BIC). We used Mplus to model the trajectories, so the best-fitting model is the one minimizing the BIC. Participants were assigned to the trajectory with the highest posterior probability. The average posterior probability was used as a criterion of the quality of the classification operated by the model (good if >0.70); because it is a binary variable (0 = no treatment, 1 = treatment), we used a logit model to answer the research questions.38
3.4.2 Analysis
The population was described using numbers and percentages for categorical data and means ± standard deviations (or median and interquartile range when data are not normal) for continuous data. Comparisons among the three groups created by the GBTM were carried out using the chi-squared test (or Fisher's exact test when appropriate), followed by the Marascuilo procedure39 when significance was reached (omnibus p < 0.05) for categorical data. For categorical outcomes such as low birth weight, preeclampsia and premature delivery, results are shown as odds ratios (ORs) with their 95% confidence intervals for each two-group comparisons. Following this, a multivariable logistic regression model was fitted using obstetric and psychiatric complications as dependent variable and GBTM groups and two demographic variables (age and CMU) as independent variables. Results are shown as adjusted ORs and their 95% confidence intervals (95% CIs). Comparisons of means between groups were carried out using analysis of variance (or by the Kruskal–Wallis test when data were not normal), followed by a post hoc Tukey–Kramer test (or Dunn's test when data were not normal). Normality was assessed graphically and using Shapiro–Wilk's test. All tests were two-sided and a p-value of <5% was considered significant. Statistics were computed using STATA v15 (Stata Corp., College Station, TX, USA) and Mplus.
3.5 Ethics approval and consent to participate
The EGB database guarantees the confidentiality of all data and anonymity (agreement of the National Commission for Computing and Freedoms (CNIL) on June 14, 2005).
4 RESULTS
4.1 Trajectories of antidepressant treatment
Among women who gave birth from 2009 to 2014 (n = 41,722), we identified 760 treated with antidepressants for at least 6 months prior to pregnancy (Appendix 4). SSRIs were the most widely reported class of antidepressants (62%, n = 471), followed by SNRIs (19.3%, n = 147) and INSRMs (6.3%, n = 48).
The GBTM showed that three models had a very close BIC: 3-, 4- and 5-trajectory model (see Appendix 5). Even if the BIC was slightly lower in the 4- and 5-trajectories models, we selected the 3-trajectory model as the most clinically pertinent (BIC = +4666.42). Specifically, the fourth and fifth trajectories were obtained by splitting one of the trajectories obtained in the 3-trajectory model, but clinically all these groups would not be treated differently. The three selected trajectories of antidepressant reimbursement (Figure 1) were: the “Stopped” trajectory, which included 424 women (55.8%) who stopped their treatment during the first trimester of their pregnancy without resuming over the study period; the “Interrupted” trajectory, which comprised 155 (20.4%) who discontinued treatment for at least 3 months during pregnancy but resumed it postpartum; and the “Maintained” trajectory, which included 181 (23.8%) who maintained their treatment throughout pregnancy. The average posterior probability was 0.87.
4.2 Factors associated with treatment change during pregnancy
Table 1 describes the characteristics of the study population and the comparison of the three groups. The maternal age at delivery was slightly higher in the Maintained group (33.3 ± 5.2 years) than in the Stopped group (31.8 ± 5.5 years; p = 0.02. The proportion of patients receiving welfare benefit was the same in the three trajectories, as was a history of pregnancy or complications during pregnancy. Fewer than 2% of the participants used medical assisted procreation (PMA) and it was not associated with the time trends of the treatment. Difference in history of anorexia or obesity, or of substance use (alcohol or tobacco), was not related to any trajectory. Drug use was more common in the Interrupted group than in the Stopped group (p < 0.001).
Variable | All sample (n = 760) | Stopped (n = 424) | Interrupted (n = 155) | Maintained (n = 181) | p-value |
---|---|---|---|---|---|
Sociodemographic characteristics | |||||
Age at delivery | 32.3 (5.5) | 31.8 (5.5) | 32.5 (5.3) | 33.3 (5.2) | 0.02b |
<20 | 6 (0.8) | 5 (1.2) | 1 (0.7) | 0 (0.0) | 0.2 |
20–35 | 522 (68.7) | 302 (71.3) | 103 (66.5) | 117 (64.6) () | |
>35 | 232 (30.5) | 117 (27.6) | 51 (32.9) | 64 (35.4) | |
CMU | 156 (20.5) | 89 (21.0) | 38 (24.5) | 29 (16.0) | 0.15 |
Multiparous | 385 (50.7) | 226 (53.3) | 79 (51.0) | 0.12 | |
History of complicated pregnancy | 13 (1.7) | 6 (1.4) | 2 (1.3) | 5 (2.8) | 0.48 |
Medical assisted procreation | 14 (1.8) | 8 (1.9) | 3 (1.9) | 3 (1.7) | 1 |
Multiple pregnancy | 12 (1.6) | 5 (1.2) | 5 (3.2) | 2 (1.10) | 0.23 |
History before pregnancy | |||||
Anorexia | 14 (1.8) | 6 (1.4) | 4 (2.6) | 4 (2.2) | 0.54 |
Diabetes | 11 (1.5) | 8 (1.9) | 1 (0.7) | 2 (1.1) | 0.65 |
Alcohol | 25 (3.3) | 9 (2.1) | 9 (5.8) | 7 (3.9) | 0.08 |
Tobacco | 61 (8.0) | 28 (6.6) | 14 (9.0) | 19 (10.5) | 0.24 |
Drugs | 24 (3.2) | 6 (1.4) | 13 (8.4) | 5 (2.8) | <0.001a |
Obesity | 41 (5.4) | 16 (3.8) | 11 (7.1) | 14 (7.7) | 0.08 |
Current pregnancy | |||||
Pregnancy tracking | |||||
No. of obstetric consultations | 3 [1;6] | 3 [0.5;6] | 4 [1;7] | 3 [0;6] | 0.64 |
No. of ultrasounds | 2 [0;4] | 2 [0;4] | 2 [0;4] | 2 [0;4] | 0.51 |
No. of general practice cs (med) | 5 [2;9] | 5 [2;8] | 6 [3;1] | 5 [2;8] | 0.05a,c |
No. of psychiatric cs (med) | 0 [0;0] | 0 [0;0] | 0 [0;0] | 0 [0;2] | 0.005a,b,c |
Length of hospital stay for childbirth | 5.5 (3.5) | 5.7 (4.0) | 5.0 (2.2) | 5.7 (3.2) | 0.03a,b,c |
No. of hospitalizations during pregnancy | 0 [0;1] | 0 [0;0] | 0 [0;1] | 0 [0;1] | 0.52 |
Complications of pregnancy | |||||
Excessive weight gain | 30 (4.0) | 17 (4.0) | 6 (3.9) | 7 (3.9) | 1 |
Pregnancy-induced hypertension | 23 (3.0) | 12(2.8) | 3 (1.9) | 8 (4.4) | 0.41 |
Preeclampsia | 27 (3.6) | 13 (3.1) | 2 (1.3) | 12 (6.6) | 0.02c |
Eclampsia | 0 | 0 | 0 | 0 | |
Gestational diabetes | 83 (10.9) | 44 (10.4) | 14 (9.0) | 25 (13.8) | 0.32 |
Early haemorrhage during pregnancy | 6 (0.8) | 3 (0.7) | 0 (0.0) | 3 (1.7) | 0.23 |
Haemorrhage before childbirth | 5 (0.7) | 1 (0.2) | 2 (1.3) | 2 (1.1) | 0.15 |
Complications of childbirth | |||||
Gestational age childbirth | 38.7 (2.3) | 38.9 (2.0) | 38.5 (3.0) | 38.5 (2.1) | 0.03a,c |
Threat of premature delivery | 40 (5.3) | 20 (4.7) | 12 (7.7) | 8 (4.4) | 0.3 |
Premature delivery | 64 (8.4) | 26 (6.1) | 18 (11.6) | 20 (11.1) | 0.04 |
Premature rupture of membranes | 66 (8.7) | 32 (7.6) | 16 (10.3) | 18 (9.9) | 0.45 |
Fetal distress | 177 (23.3) | 85 (20.1) | 36 (23.2) | 56 (30.9) | 0.02a |
Non-reassuring fetal heart rate | 126 (16.6) | 59 (13.9) | 27 (17.4) | 40 (22.1) | 0.04 |
Fetal dystocia | 58 (7.6) | 33 (7.8) | 14 (9.0) | 11 (6.1) | 0.59 |
Haemorrhage during childbirth | 4 (0.5) | 3 (0.7) | 0 (0.0) | 1 (0.6) | 0.82 |
Caesarean delivery | 196 (25.8) | 103 (24.3) | 42 (27.1) | 51 (28.2) | 0.56 |
Low birth weight | 32 (4.2) | 15 (3.5) | 6 (3.9) | 11 (6.1) | 0.35 |
Post partum | |||||
Postpartum haemorrhage | 47 (6.2) | 22 (5.2) | 6 (3.9) | 19 (10.5) | 0.02 |
- Data are presented as frequencies (associated percentages).
- Abbreviations: CMU, Universal health insurance; cs, Consultation.
- a p < 0.05 between Traj1 and Traj2;
- b p < 0.05 between Traj1 and Traj3;
- c p < 0.05 between Traj2 and Traj3.
4.3 Obstetric factors associated with treatment trajectory
During pregnancy, univariate analysis showed fetal distress more frequently in the Maintained group (30.9%, n = 56) than in the Stopped group (20.1%; n = 85; p = 0.02) (Table 1). This result was confirmed by the multivariable analysis (OR, 95% CI: 1.77 [1.19–2.63]), which also showed a higher risk for non-reassuring fetal heart rate (OR, 95% CI: 1.74 [1.11–2.73]) without difference between the Maintained and Interrupted groups (Table 2). Premature delivery was less frequently observed in the Stopped than in the Maintained (OR, 95% CI: 1.84 [0.99–3.41]) and Interrupted (OR, 95% CI: 1.93 [1.02–3.64]) groups. Postpartum haemorrhage were more frequent in the Maintained than in the Interrupted (OR, 95% CI: 2.54 [1.31–4.91]) and Stopped (OR, 95% CI: 3.33 [1.28;8.66]) groups, as it was for preeclampsia (respectively OR, 95% CI: 5.51 [1.21–25.2] and to a lesser extent OR, 95% CI: 2.15 [0.95–4.85]).
Low birth weight | Preeclampsia | Premature delivery | Fetal distress | Postpartum haemorrhage | Non-reassuring fetal heart rate | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Obstetric complications | OR [CI 95%] | p | OR [CI 95%] | p | OR [CI 95%] | p | OR [CI 95%] | p | OR [CI 95%] | p | OR [CI 95%] | p |
Interrupted/Stopped | 0.99 [0.37–2.62] | 0.981 | 0.39 [0.09–1.75] | 0.220 | 1.93 [1.02–3.64] | 0.042 | 1.20 [0.77–1.87] | 0.418 | 0.76 [0.30–1.94] | 0.571 | 1.30 [0.79–2.14] | 0.305 |
Maintained/Stopped | 1.65 [0.73–3.72] | 0.225 | 2.15 [0.95–4.85] | 0.065 | 1.84 [0.99–3.41] | 0.052 | 1.77 [1.19–2.63] | 0.005 | 2.54 [1.31–4.91] | 0.006 | 1.74 [1.11–2.73] | 0.016 |
Maintained/Interrupted | 1.67 [0.59–4.70] | 0.330 | 5.51 [1.21–25.2] | 0.028 | 0.95 [0.48–1.89] | 0.893 | 1.47 [0.90–2.40] | 0.123 | 3.33 [1.28–8.66] | 0.014 | 1.34 [0.78–2.31] | 0.293 |
Postpartum depression | Puerperal psychiatric disorder | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Post-partum psychiatric complications | OR [CI 95%] | p | OR [CI 95%] | p | ||||||||
Interrupted/Stopped | 6.46 [1.64–25.4] | 0.008 | 2.13 [1.07–4.25] | 0.032 | ||||||||
Maintained/Stopped | 4.89 [1.20–20.0] | 0.027 | 6.88 [3.87–12.2] | <0.001 | ||||||||
Maintained/Interrupted | 0.76 [0.25–2.32] | 0.627 | 3.23 [1.70–6.13] | <0.001 |
- OR [CI 95%] odds ratio, [95% confidence interval]. Adjusted on age and CMU.
4.4 Monitoring of pregnancy according to treatment trajectory
Women in the Interrupted group consulted their GP more frequently during pregnancy (8 ± 9.4 consultations vs 6.1 ± 5.1 for the Maintained group and 5.8 ± 4.4 for the Stopped group), and consulted a private psychiatrist more often than women in the Stopped group did (1.7 ± 5.0 vs 0.9 ± 3.4, p < 0.05). Women in the Maintained group consulted a private psychiatrist more often than others did (2.3 ± 6 consultations vs 1.7 ± 5.0 for the Interrupted group and 0.9 ± 3.4 for the Stopped group, p < 0.05) (Table 1).
4.5 Psychiatric factors associated with treatment trajectory
Compared to the Stopped group, women in the Maintained group were more likely to have psychiatric comorbidities during hospitalization or had long-term condition status (ALD) for depression-anxiety (30.9%, n = 56 vs 18.2%, n = 77, p = 0.002), and other psychiatric disorders (17.1%, n = 37 vs 6.6%, n = 28, p = 0.002) in the lifespan (Table 3). However, there was no difference in rates of psychiatric comorbidities during hospitalization or ALD according to psychiatric history (depression, anxiety, psychotic disorders or suicide attempt) in the 6 months preceding pregnancy. During pregnancy, women in the Maintained group, had more frequent psychiatric comorbidities during hospitalization or ALD for depression-anxiety than those in the Stopped group (15.5%, n = 28 vs 2.4%, n = 10, p < 0.001), and those in the Interrupted group (6.5%, n = 10, p < 0.001), and more often suffered from other psychiatric disorders than those in Stopped group (5.5%, n = 10 vs 0.9%, n = 4, p = 0.003). During the postpartum period, the rate of psychiatric comorbidities during hospitalization or ALD for psychiatric disorders related to the puerperium was higher in the Maintained group (24.3%, n = 44) than in the others (Interrupted: 10.3%, n = 16 and Stopped 5.0%, n = 21, p < 0.001 for all). This result was confirmed by the multivariable analysis (Maintained/Interrupted OR, 95% CI: 3.23 [1.70–6.13] and Maintained/Stopped OR, 95% CI: 6.88 [3.87–12.2]).
Variable | All sample | Stopped (Traj 1) | Interrupted (Traj 2) | Maintained (Traj 3) | p-value |
---|---|---|---|---|---|
Psychiatric comorbidities during hospitalization or long-term affection before pregnancy | |||||
Depression/anxiety | 165 (21.7) | 77 (18.2) | 32 (20.7) | 56 (30.9) | 0.002b |
Psychiatric disorder | 80 (10.5) | 28 (6.6) | 21 (13.6) | 37 (17.1) | <0.001b |
Suicide attempt | 62 (8.2) | 28 (6.6) | 17 (11.0) | 17 (9.4) | 0.19 |
Psychiatric comorbidities during hospitalization or long-term affection 6 months before pregnancy | |||||
Depression/anxiety | 39 (5.1) | 23 (5.4) | 7 (4.5) | 9 (5.0) | 0.9 |
Psychiatric disorder | 7 (0.9) | 3 (0.7) | 1 (0.7) | 3 (1.7) | 0.58 |
Suicide attempt | 21 (2.8) | 12 (2.8) | 5 (3.2) | 4 (2.2) | 0.87 |
Psychiatric comorbidities during hospitalization or long-term affection during pregnancy and childbirth | |||||
Depression/anxiety | 48 (6.3) | 10 (2.4) | 10 (6.5) | 28 (15.5) | <0.001b,c |
Psychiatric disorder | 18 (2.4) | 4 (0.9) | 4 (2.6) | 10 (5.5) | 0.003b |
Suicide attempt | 2 (0.3) | 1 (0.2) | 0 (0.0) | 1 (0.6) | 0.69 |
Psychiatric comorbidities during hospitalization or long-term-affection post partum (6 month after childbirth) | |||||
Depression/anxiety | 15 (2.0) | 2 (0.5) | 7 (4.5) | 6 (3.3) | 0.001 |
Psychiatric disorder | 0 | 0 | 0 | 0 | n.a. |
Suicide attempt | 5 (0.7) | 1 (0.2) | 3 (1.9) | 1 (0.6) | 0.05 |
Psychiatric comorbidities during hospitalization or long-term affection during childbirth and post partum | |||||
Psychiatric disorder related to the puerperium | 81 (10.7) | 21 (5.0) | 16 (10.3) | 44 (24.3) | <0.001b,c |
- Data are presented as frequencies (associated percentages).
- a p < 0.05 between Traj1 and Traj2;
- b p < 0.05 between Traj1 and Traj3;
- c p < 0.05 between Traj2 and Traj3.
4.6 Evolution of benzodiazepine treatments
Benzodiazepine reimbursement was not different in the three groups over the 6 months preceding pregnancy: Stopped = 42.0% (181), Interrupted = 40.7% (63) and Maintained = 46.4% (84), p = 0.9 (Figure 2). Over the 6 months following delivery, women had lower benzodiazepine prescriptions than before pregnancy in the Stopped group (8.5%, n = 36 vs 42%, n = 181, p < 0.001) and in the Maintained group (30.4%, n = 55 vs 46.6%, n = 84, p < 0.001). In the Interrupted group, the benzodiazepines dispensed decreased to T3 (13.6%) but then rose to a higher level than before pregnancy (54.2%, n = 84 vs 40.7%, n = 63, p = 0.005). The same time trend was observed for other anxiolytics.
5 DISCUSSION
Among women who started pregnancy when exposed to antidepressant treatment, we identified three trajectories of antidepressant dispensing during pregnancy: more than half stopped their treatment; a quarter maintained their treatment throughout pregnancy; and one out of five discontinued it for a minimum of 3 months and then resumed it during the postpartum period. Before pregnancy, only lifetime history of psychiatric disorders was associated with maintenance versus stopping of treatment. There was no sociodemographic or medical characteristic associated with the trajectories of antidepressant treatment during pregnancy. There were more obstetric complications in the Maintained group than in the Stopped (premature delivery, non-reassuring fetal heart rate, postpartum haemorrhage and rhythm disorder) and Interrupted group (preeclampsia and postpartum haemorrhage) groups. The frequency of psychiatric comorbidities during hospitalization over the postpartum period was higher for the Maintained and Interrupted groups than for the Stopped group. The dispensing of benzodiazepines and other anxiolytics differed in the Interrupted group: it initially decreased with the decrease in antidepressants, then rose to a higher level in the postpartum period than before pregnancy.
The women who maintained their antidepressant treatment presented with the most severe depression profile: they more often had ALD status for depression, anxiety or other psychiatric disorders and more frequently consulted a psychiatrist and/or a GP than women in the Stopped group did. In terms of obstetric complications, there were more obstetric complications in the Maintained group than in the Stopped (premature delivery, non-reassuring fetal heart rate, postpartum haemorrhage and rhythm disorder) and Interrupted (preeclampsia and postpartum haemorrhage) groups. Consistent with this finding, a prior study showed that women exposed to antidepressant and/or anxiolytic medication before the 16th week of pregnancy have a 3-fold increased risk for preeclampsia.40 A meta-analysis showed that exposure to antidepressants in late gestation was associated with a significantly increased risk of postpartum haemorrhage.41 Therefore, when a woman is treated with antidepressants in late pregnancy, health professionals should be especially vigilant, and ask the woman about a possible interruption of treatment during pregnancy: if the antidepressant was maintained throughout the pregnancy, the woman is even more at risk of complications than if there was an interruption. Moreover, women who maintained their antidepressant treatment probably had the most severe depression, which in turn is associated with obstetric complications due to increased amounts of maternal cortisol released into the bloodstream during severe depressive states.10, 11
Half of the women stopped their treatment and did not return to their treatment; they did not relapse. It is therefore essential to re-evaluate antidepressant treatment in early pregnancy and to discontinue unnecessary treatments. In France, the prevalence of individuals taking antidepressant drugs is 6%. Their use is higher among women.42
The women in the Interrupted group showed intermediate levels of pre-pregnancy psychiatric events and had fewer depression or anxiety events during pregnancy and the postpartum period than women in the Maintained group. It is possible that women in the Interrupted group had less severe depression than those in the Maintained group, which would explain the interruption of their treatment, and their less frequent follow-up with a psychiatrist. However, they consulted a GP more often; this is a sign of mood disorders, which explains the resumption of their treatment. Finally, their prescription of benzodiazepines and anxiolytics, after a decreasing that paralleled that of the antidepressants, rose to a higher level postpartum than before pregnancy. A first hypothesis is that stopping the antidepressant may have resulted in a relapse of depression21 with resumption of treatment and the prescription of benzodiazepine. A second hypothesis is that the profile of these pregnant women was perhaps different before their pregnancy. Specifically, those women may have been more anxious than depressed, so that their management would have been different. An implication of this finding is that if antidepressants are stopped at the beginning of pregnancy, patients must be reassessed to identify those who will either relapse or will present with an increase in anxiety. These women would require a different management compared to those who stop without psychiatric complications. The drop in benzodiazepines associated with stopping antidepressants is also observed in a study on health insurance data in the Netherlands (from 33% in the 1st trimester to 2.8% in the 3rd trimester),43 but the originality of our study is the observation of this rebound during the postpartum period. Prescribed during pregnancy, treatment with benzodiazepine may be harmful if combined with treatment with antidepressants,44 and prescribed after pregnancy, it carries the known risks of dependence on treatment.
Our study did not identify any somatic, psychological or obstetric risk factors that predict appropriate cessation of the treatment. The evaluation of psychiatric events related to depression over the 6 months preceding pregnancy is therefore not indicative of the evolution of antidepressant use, as no differences among the three groups were identified. To reassess disease severity and therefore obtain an indication of whether to maintain or stop treatment, we should question the whole history of antidepressant treatment in the patient and not just that in the last 6 months. These findings also should encourage an enhancement of maternal follow-up during the postpartum period.
The strength of this study was the use of the French EGB database, which allows an effective supply of patients. The data were reimbursement data; therefore, there was no declarative bias. Trajectory modelling made it possible to follow the purchase of the treatment as closely as possible to the evolution of the pregnancy. Some limitations of this study should be considered in interpreting the results.. The EGB database provides information on the drugs prescribed and purchased by the patient. Therefore, there is the possibility that the were not actually taken. The lack of compliance, which can be 50% in high-income countries45 and especially relevant for psychotropic drugs, was not taken into account in this study. Therefore, there is a risk of having overestimated the actual treatment intake.
However, as the women went to the pharmacy to buy their treatment regularly, this bias seems very limited, and the Maintained group does not seem to be concerned. Additionally, to avoid an overestimation of treatment intake, we observed the 6 months preceding pregnancy as an inclusion criterion. Another limitation is that previous events of depression were identified in our study by measuring psychiatric comorbidities during hospitalization or ALD declarations for depression; however, a large number of cases of depression do not lead to hospitalization or ALD, and this proportion could therefore have been underestimated. Finally, despite the longitudinal design, caution is needed in interpreting our results as causal association; it is possible that several confounders were unmeasured.
In conclusion, an announcement of pregnancy in an antidepressant-treated woman requires re-evaluation of psychiatric treatment, not only assessing the events of the 6 months preceding the pregnancy, but more generally, her history of depression. Women requiring continued treatment, and therefore those with more severe depression, demonstrated a higher rate of perinatal complications. Half of the women treated before pregnancy stop their antidepressant use in early pregnancy and do not resume the treatment postpartum, without this having any consequences on the events of depression during pregnancy or the postpartum period. However, when antidepressants are stopped at the beginning of pregnancy, patients must be reassessed to identify those who will relapse their psychiatric disorder, and manage them differently to prevent an over-prescription of benzodiazepines.
COMPETING INTERESTS
There are no competing interests to declare. The study did not receive any funding.
CONTRIBUTORS
C.L., A.B., J.D., M.C.Z., C.C. and N.A. conceived the presented idea. C.C., J.D. and A.M. verified the analytical methods. A.M. and M.O. performed the analysis of the data. A.C., A.M., M.V.O., M.T., D.G., C.C., N.A. and C.L. contributed to the interpretation of the results. A.C. took the lead in writing the manuscript. A.C., M.V.O., M.T., D.G., N.A. and C.L. discussed the results and contributed to the final manuscript. C.L. supervised the findings of this work.
APPENDIX 1
APPENDIX 2
Anatomical Therapeutic Chemical codes for study antidepressants and anxiolytics
ATC codes of antidepressants
Non-selective monoamine reuptake inhibitor | NO6AA |
---|---|
Selective serotonin reuptake inhibitor | NO6AB |
Non-selective monoamine inhibitors | NO6AF |
Monoamine oxidase inhibitors | N06AG |
Others | N06AX, NO6CA |
ATC codes of benzodiazepines, anxiolytics and hynotics
Benzodiazepines and derivatives | N05BA |
---|---|
Diphenylmethane | N05BB |
Azaspirodecandedione | N05BE |
Other anxiolytics | N05BX |
Benzodiazepines derivatives | N05CD |
Benzodiazepine-related drugs | N05CF |
Other hypnotics and sedatives | N05CM |
Associated hypnotics and sedatives, other than barbiturates | N05CX |
APPENDIX 3
CCAM, ICD-10 or ALD codes of Measures and outcomes
Eligibility criteria
Medical termination of pregnancy and late miscarriages
CODES | INTITULE |
---|---|
O049 | Avortement médical complet ou sans précision, sans complication = IMG |
O039 | Avortement spontané complet ou sans précision, sans complication (fausse couche tardive) |
O036 | Avortement spontané complet ou sans précision, compliqué d'une hémorragie retardée ou sévère (fausse couche hémorragique) |
Obstetric or non-obstetrical history before pregnancy
Nulliparous
CODE | INTITULE |
---|---|
JQGD013 | Accouchement unique par le siège par voie naturelle avec grande extraction, chez Une primipare |
JQGD010 | Accouchement céphalique unique par voie naturelle, chez Une primipare |
JQGD004 | Accouchement unique par le siège par voie naturelle, chez Une primipare |
JQGD003 | Accouchement unique par le siège par voie naturelle avec petite extraction, chez Une primipare |
JQGD002 | Accouchement multiple par voie naturelle, chez Une primipare |
Z355 | Surveillance d'une primipare âgée |
Z356 | Surveillance d'une primipare très jeune |
Parous
CODE | INTITULE |
---|---|
JQGD012 | Accouchement céphalique unique par voie naturelle, chez Une multipare |
JQGD008 | Accouchement unique par le siège par voie naturelle avec petite extraction, chez Une multipare |
JQGD007 | Accouchement multiple par voie naturelle, chez Une multipare |
JQGD005 | Accouchement unique par le siège par voie naturelle avec grande extraction, chez Une multipare |
JQGD001 | Accouchement unique par le siège par voie naturelle, chez Une multipare |
Z354 | Surveillance d'une grossesse avec multiparité élevée |
Z641 | Difficultés liées à Une multiparité |
History of complicated pregnancies
CODE | INTITULE |
---|---|
Z875 | Antécédents personnels de complications de la grossesse, de l'accouchement et de la puerpéralité |
Sterility or pathway of assisted reproduction
CODE | INTITULE |
---|---|
N97 | Stérilité de la femme |
N974 | Stérilité de la femme associée à des facteurs relevant de l'homme |
N989 | Complication de la fécondation artificielle, sans précision |
Z31.1 | Insémination artificielle |
Z31.2 | Fécondation in vitro |
Z31.3 | Autres méthodes de fécondation assistée |
JHFB001 | Prélèvement de spermatozoïdes au niveau du testicule, de l'épididyme ou du conduit déférent, par voie transcutanée |
JJFC011 | Prélèvement d'ovocytes Sur un ou deux ovaires, par coelioscopie |
JJFJ001 | Prélèvement d'ovocytes Sur un ou deux ovaires, par voie transvaginale avec guidage échographique |
JKHD002 | Prélèvement et examen de la glaire cervicale, sans examen de la mobilité des spermatozoïdes |
JKHD003 | Prélèvement et examen de la glaire cervicale, avec examen de la mobilité des spermatozoïdes [test postcoïtal de Huhner] |
JSEC001 | Transfert intratubaire d'embryon, par coelioscopie |
JSED001 | Transfert intra-utérin d'embryon, par voie vaginale |
JSLD002 | Insémination artificielle intracervicale |
Long-term condition status for depression or anxiety
CODE | INTITULE |
---|---|
F40 | Troubles anxieux phobiques |
F41 | Autres troubles anxieux |
F410 | Trouble panique [anxiété épisodique paroxystique] |
F411 | Anxiété généralisée |
F412 | Trouble anxieux et dépressif mixte |
F419 | Trouble anxieux, sans précision |
F32 | Épisodes dépressifs |
F320 | Épisode dépressif léger |
F321 | Épisode dépressif moyen |
F322 | Épisode dépressif sévère sans symptômes psychotiques |
F323 | Épisode dépressif sévère avec symptômes psychotiques |
F328 | Autres épisodes dépressifs |
F329 | Épisode dépressif, sans précision |
F33 | Trouble dépressif récurrent |
F920 | Troubles des conduites avec dépression |
Long-term condition status for psychiatric issues other than depression and anxiety
CODE | INTITULE |
---|---|
F20 | Schizophrénie |
F21 | Trouble schizotypique |
F22 | Troubles délirants persistants |
F220 | Trouble délirant |
F23 | Troubles psychotiques aigus et transitoires |
F25 | Troubles schizo-affectifs |
F28 | Autres troubles psychotiques non organiques |
F29 | Psychose non organique, sans précision |
F31 | Trouble affectif bipolaire |
F310 | Trouble affectif bipolaire, épisode actuel hypomaniaque |
F312 | Trouble affectif bipolaire, épisode actuel maniaque avec symptômes psychotiques |
F319 | Trouble affectif bipolaire, sans précision |
F34 | Troubles de l'humeur [affectifs] persistants |
F348 | Autres troubles de l'humeur [affectifs] persistants |
F39 | Trouble de l'humeur [affectif], sans précision |
F42 | Trouble obsessionnel-compulsif |
F44 | Troubles dissociatifs [de conversion) |
F60 | Troubles spécifiques de la personnalité |
F608 | Autres troubles spécifiques de la personnalité |
F68 | Autres troubles de la personnalité et du comportement chez l'adulte |
F69 | Trouble de la personnalité et du comportement chez l'adulte, sans précision |
F98 | Autres troubles du comportement et troubles émotionnels apparaissant habituellement Durant l'enfance et l'adolescence |
F989 | Trouble du comportement et trouble émotionnel apparaissant habituellement Durant l'enfance et l'adolescence, sans précision |
Substance use
CODE | INTITULE |
---|---|
Z720 | Usage du tabac |
F17 | Troubles mentaux et du comportement liés à l'utilisation du tabac |
Z71.6 | Conseil pour tabagisme |
Z721 | Consommation d'alcool |
F10 | Troubles mentaux et du comportement liés à l'utilisation de l'alcool |
Z714 | Conseil et surveillance pour alcoolisme |
Z50.2 | Sevrage d'alcool |
Y90 | Preuves du rôle de l'alcool confirmé par le taux d'alcoolémie |
Y91 | Preuves du rôle de l'alcool confirmé par le degré d'intoxication |
X65 | Auto-intoxication par l'alcool et exposition à l'alcool |
Y15 | Intoxication par l'alcool et exposition à l'alcool, intention non déterminée |
O354 | Soins maternels pour lésions fœtales (présumées) dues à l'alcoolisme maternel |
Z722 | Utilisation de drogues |
F12 | Troubles mentaux et du comportement liés à l'utilisation de dérivés du cannabis |
F13 | Troubles mentaux et du comportement liés à l'utilisation de sédatifs ou d'hypnotiques |
F14 | Troubles mentaux et du comportement liés à l'utilisation de cocaïne |
F15 | Troubles mentaux et du comportement liés à l'utilisation d'autres stimulants, y compris la caféine |
F16 | Troubles mentaux et du comportement liés à l'utilisation d'hallucinogènes |
F18 | Troubles mentaux et du comportement liés à l'utilisation de solvants volatils |
F19 | Troubles mentaux et du comportement liés à l'utilisation de drogues multiples et troubles liés à l'utilisation d'autres substances psychoactives. |
Z71.5 | Conseil et surveillance pour toxicomanie et pharmaco dépendance |
Pregnancy tracking
Obstetric ultrasound
CODE | INTITULE |
---|---|
JQQM019 | Échographie biométrique et morphologique d'une grossesse multifoetale au 2ème trimestre |
JNQM001 | Échographie non morphologique de la grossesse avant 11 semaines d'aménorrhée |
JQQJ037 | Mesure de la longueur du canal cervical du col de l'utérus, par échographie par voie vaginale |
JQQM001 | Échographie de surveillance de la croissance foetale |
JQQM002 | Échographie d'une grossesse unifoetale à partir du 2ème trimestre avec échographie-doppler des artères utérines de la mère et des vaisseaux du foetus, pour souffrance foetale |
JQQM003 | Échographie de surveillance de la croissance foetale avec échographie-doppler des artères utérines de la mère et des vaisseaux du foetus |
JQQM007 | Échographie d'une grossesse multifoetale à partir du 2ème trimestre avec échographie-doppler des artères utérines de la mère et des vaisseaux des foetus, pour souffrance foetale |
JQQM008 | Échographie et hémodynamique doppler du coeur et des vaisseaux intrathoraciques du foetus |
JQQM010 | Échographie biométrique et morphologique d'une grossesse uniembryonnaire au 1er trimestre |
JQQM015 | Échographie biométrique et morphologique d'une grossesse multiembryonnaire au 1er trimestre |
JQQM016 | Échographie biométrique et morphologique d'une grossesse unifoetale au 3ème trimestre |
JQQM017 | Échographie biométrique et morphologique d'une grossesse multifoetale au 3ème trimestre |
JQQM018 | Échographie biométrique et morphologique d'une grossesse unifoetale au 2ème trimestre |
Complications of pregnancy
Monofetal pregnancy
CODE | INTITULE |
---|---|
O800 | Accouchement spontané par présentation du sommet |
O801 | Accouchement spontané par présentation du siège |
O808 | Autres accouchements uniques et spontanés |
O809 | Accouchement spontané, sans précision |
Z370 | Naissance unique, enfant vivant |
Z371 | Naissance unique, enfant mort- né |
Z3710 | Naissance unique, enfant mort-né, hors interruption de la grossesse pour motif médical |
Z3711 | Naissance unique, enfant mort-né, à la suite d'une interruption de la grossesse pour motif médical |
Multiple pregnancy
CODE | INTITULE |
---|---|
Z374 | Naissance gémellaire, jumeaux morts-nés |
Z3740 | Naissance gémellaire, jumeaux morts-nés, hors interruption de la grossesse pour motif médical |
Z3741 | Naissance gémellaire, jumeaux morts-nés, à la suite d'une interruption de la grossesse pour motif médical |
Z373 | Naissance gémellaire, l'un des jumeaux né vivant, l'autre mort-né |
Z3730 | Naissance gémellaire, l'un des jumeaux né vivant, l'autre mort-né, hors interruption de la grossesse pour motif médical |
Z3731 | Naissance gémellaire, l'un des jumeaux né vivant, l'autre mort-né, à la suite d'une interruption de la grossesse pour motif médical |
Z372 | Naissance gémellaire, jumeaux nés vivants |
O840 | Accouchements multiples, Tous spontanés |
O841 | Accouchements multiples, Tous avec forceps et ventouse |
O842 | Accouchements multiples, Tous par césarienne |
Z3771 | Autres naissances multiples, Tous morts-nés, à la suite d'une interruption de la grossesse pour motif médical |
Z3770 | Autres naissances multiples, Tous morts-nés, hors interruption de la grossesse pour motif médical |
Z377 | Autres naissances multiples, Tous morts-nés |
Z3761 | Autres naissances multiples, certains enfants nés vivants, à la suite d'une interruption de la grossesse pour motif médical |
Z3760 | Autres naissances multiples, certains enfants nés vivants, hors interruption de la grossesse pour motif médical |
Z376 | Autres naissances multiples, certains enfants nés vivants |
Z375 | Autres naissances multiples, Tous nés vivants |
Z372 | Naissance gémellaire, jumeaux nés vivants |
O849 | Accouchements multiples, sans précision |
O848 | Autres accouchements multiples |
O300 | Grossesse multiple: Jumeaux |
O301 | Grossesse multiple: triplés |
O302 | Grossesse multiple: quadruplés |
O308 | Autres grossesses multiples |
O309 | Grossesse multiple, sans précision |
O310 | Foetus papyracé |
O311 | Poursuite de la grossesse après avortement d'un ou plusieurs foetus |
O312 | Poursuite de la grossesse après mort intra-utérine d'un ou plusieurs foetus |
O318 | Autres complications spécifiques à Une grossesse multiple |
Pregnancy-induced hypertension/preeclampsia/eclampsia
CODE | INTITULE |
---|---|
O14 | Prééclampsie |
O140 | Prééclampsie modérée |
O141 | Prééclampsie sévère |
O142 | Syndrome HELLP |
O149 | Prééclampsie, sans précision |
ECLAMPSIE | |
O150 | Éclampsie au cours de la grossesse |
O151 | Éclampsie au cours du travail |
O152 | Éclampsie au cours de la puerpéralité |
O159 | Éclampsie, sans précision quant à la période |
O13 | Hypertension gestationnelle |
O100 | Hypertension essentielle préexistante compliquant la grossesse, l'accouchement et la puerpéralité |
O101 | Cardiopathie hypertensive préexistante compliquant la grossesse, l'accouchement et la puerpéralité |
O102 | Néphropathie hypertensive préexistante compliquant la grossesse, l'accouchement et la puerpéralité |
O103 | Cardionéphropathie hypertensive préexistante compliquant la grossesse, l'accouchement et la puerpéralité |
O104 | Hypertension secondaire préexistante compliquant la grossesse, l'accouchement et la puerpéralité |
O109 | Hypertension préexistante compliquant la grossesse, l'accouchement et la puerpéralité, sans précision |
O16 | Hypertension de la mère, sans précision |
Threat of premature delivery
CODE | INTITULE |
---|---|
O470 | Faux travail avant 37 semaines entières de gestation [menace d'accouchement prématuré] |
Premature membrane rupture
CODE | INTITULE |
---|---|
O420 | Rupture prématurée des membranes, avec début du travail dans les 24 heures |
O421 | Rupture prématurée des membranes, avec début du travail au-delà des 24 heures |
O422 | Rupture prématurée des membranes, travail retardé par traitement |
O429 | Rupture prématurée des membranes, sans précision |
Obesity/excessive weight gain
CODE | INTITULE |
---|---|
E66 | Obésité |
E660 | Obésité due à un excès calorique |
E6600 | Obésité due à un excès calorique de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 30 kg/m2 et inférieur à 40 kg/m2, ou obésité due à un excès calorique de l'enfant |
E6601 | Obésité due à un excès calorique de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 40 kg/m2 et inférieur à 50 kg/m2 |
E6602 | Obésité due à un excès calorique de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 50 kg/m2 |
E6609 | Obésité due à un excès calorique de l'adulte, indice de masse corporelle [IMC] non précisé |
E661 | Obésité médicamenteuse |
E6610 | Obésité médicamenteuse de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 30 kg/m2 et inférieur à 40 kg/m2, ou obésité médicamenteuse de l'enfant |
E6611 | Obésité médicamenteuse de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 40 kg/m2 et inférieur à 50 kg/m2 |
E6612 | Obésité médicamenteuse de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 50 kg/m2 |
E6619 | Obésité médicamenteuse de l'adulte, indice de masse corporelle [IMC] non précisé |
E662 | Obésité extrême avec hypoventilation alvéolaire |
E6620 | Obésité extrême avec hypoventilation alvéolaire, avec indice de masse corporelle égal ou supérieur à 30 kg/m2 et inférieur à 40 kg/m2 |
E6621 | Obésité extrême avec hypoventilation alvéolaire, avec indice de masse corporelle égal ou supérieur à 40 kg/m2 et inférieur à 50 kg/m2 |
E6622 | Obésité extrême avec hypoventilation alvéolaire, avec indice de masse corporelle égal ou supérieur à 50 kg/m2 |
E6629 | Obésité extrême avec hypoventilation alvéolaire, avec indice de masse corporelle inconnu |
E668 | Autres obésités |
E6680 | Autres obésités de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 30 kg/m2 et inférieur à 40 kg/m2, ou autres obésités de l'enfant |
E6681 | Autres obésités de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 40 kg/m2 et inférieur à 50 kg/m2 |
E6682 | Autres obésités de l'adulte avec indice de masse corporelle égal [IMC] ou supérieur à 50 kg/m2 |
E6689 | Autres obésités de l'adulte, indice de masse corporelle [IMC] non précisé |
E669 | Obésité, sans précision |
E6690 | Obésité sans précision de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 30 kg/m2 et inférieur à 40 kg/m2, ou obésité sans précision de l'enfant |
E6691 | Obésité sans précision de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 40 kg/m2 et inférieur à 50 kg/m2 |
E6692 | Obésité sans précision de l'adulte avec indice de masse corporelle [IMC] égal ou supérieur à 50 kg/m2 |
E6699 | Obésité sans précision de l'adulte, indice de masse corporelle [IMC] non précisé |
0260 | Prise de poids excessive pendant la grossesse |
Gestational diabetes
CODE | INTITULE |
---|---|
O244 | Diabète sucré survenant au cours de la grossesse |
O249 | Diabète sucré au cours de la grossesse, sans précision |
Haemorrhage during pregnancy and delivery
Long-term condition status for depression or anxiety during pregnancy
CODE | INTITULE |
---|---|
F0632 | Troubles dépressif organique |
F320 | Episode dépressif léger |
F3200 | Episode dépressif léger, sans syndrome somatique |
F3201 | Episode dépressif léger, avec syndrome somatique |
F321 | Episode dépressif moyen |
F3210 | Episode dépressif moyen, sans syndrome somatique |
F3211 | Episode dépressif moyen, avec syndrome somatique |
F322 | Episode dépressif sévère sans symptômes psychotiques |
F323 | Episode dépressif sévère avec symptômes psychotiques |
F3230 | Episode dépressif sévère avec symptômes psychotiques congruents à l'humeur |
F328 | Autres épisodes dépressifs |
F329 | Episode dépressif, sans précision |
F330 | Troubles dépressif récurrent, épisode actuel léger |
F3300 | Troubles dépressif récurrent, épisode actuel léger, sans syndrome somatique |
F3301 | Troubles dépressif récurrent, épisode actuel léger, avec syndrome somatique |
F331 | Troubles dépressif récurrent, épisode actuel moyen |
F3310 | Troubles dépressif récurrent, épisode actuel moyen, sans syndrome somatique |
F3311 | Troubles dépressif récurrent, épisode actuel moyen, avec syndrome somatique |
F332 | Troubles dépressif récurrent, épisode actuel sévère sans symptômes psychotiques |
F333 | Troubles dépressif récurrent, épisode actuel sévère avec symptômes psychotiques |
F3330 | Troubles dépressif récurrent, épisode actuel sévère avec symptômes psychotiques congruents à l'humeur |
F412 | Troubles anxieux et dépressif mixte |
F4322 | Réaction mixte, anxieuse et dépressive |
F920 | Troubles des conduites avec dépression |
F53 | Troubles mentaux et du comportement associés à la puerpéralité, non classés ailleurs |
F530 | Troubles mentaux et du comportement légers associés à la puerpéralité, non classés ailleurs |
F531 | Troubles mentaux et du comportement sévères associés à la puerpéralité, non classés ailleurs |
F538 | Autres troubles mentaux et du comportement associés à la puerpéralité, non classés ailleurs |
F539 | Trouble mental de la puerpéralité, sans précision |
0993 | Troubles mentaux et maladies du système nerveux compliquant la grossesse, l'accouchement et la puerpéralité |
Prematurity (childbirth before 37 weeks of gestation)
CODE | INTITULE |
---|---|
O60 | Travail et accouchement prématurés [avant Terme] |
Low birth weight
CODE | INTITULE |
---|---|
O365 | Soins maternels pour croissance insuffisante du foetus |
Suicide attempt/suicide
CODE | INTITULE |
---|---|
X60 JUSQU A X84 | Lésions auto-infligées |
Z03.6 | Mise en observation pour suspicion d'effet toxique de substances ingérées |
Z91.5X-003 | Tentative de suicide |
Complications of childbirth
Caesarean delivery
CODE | INTITULE |
---|---|
JQGA005 | Accouchement par césarienne, par abord vaginal |
JQGA002 | Accouchement par césarienne programmée, par laparotomie |
JQGA003 | Accouchement par césarienne au cours du travail, par laparotomie |
JQGA004 | Accouchement par césarienne en urgence en dehors du travail, par laparotomie |
YYYY069 | Supplément pour accouchement multiple par césarienne |
O820 | Accouchement par césarienne programmée |
O821 | Accouchement par césarienne d'urgence |
O822 | Accouchement par césarienne avec hystérectomie |
O828 | Autres accouchements uniques par césarienne |
O829 | Accouchement par césarienne, sans précision |
O842 | Accouchements multiples, Tous par césarienne |
Delivery with instruments/assistance
CODE | INTITULE |
---|---|
O830 | Accouchement avec extraction par le siège |
O831 | Autres accouchements par le siège |
O832 | Autres accouchements avec l'aide de manipulations |
O833 | Accouchement d'un foetus viable après grossesse abdominale |
O834 | Intervention destructrice lors d'un accouchement |
O838 | Autres accouchements précisés, avec assistance |
O839 | Accouchement avec assistance, sans précision |
O810 | Accouchement par forceps bas |
O811 | Accouchement par forceps à la partie moyenne de l'excavation |
O812 | Accouchement par forceps à la partie moyenne de l'excavation, avec rotation |
O813 | Accouchements par forceps, autres et sans précision |
O814 | Accouchement par extraction pneumatique |
O815 | Accouchement par association d'un forceps et d'une ventouse |
JQGD011 | Extraction instrumentale Sur tête dernière, au cours d'un accouchement par le siège |
Haemorrhage during delivery
CODE | Hémorragie précédent l'accouchement |
---|---|
O460 | Hémorragie précédant l'accouchement avec anomalie de la coagulation |
O468 | Autres hémorragies précédant l'accouchement |
O469 | Hémorragie précédant l'accouchement, sans précision |
Fetal distress
CODE | INTITULE |
---|---|
O680 | Travail et accouchement compliqués d'une anomalie du rythme cardiaque du foetus |
O681 | Travail et accouchement compliqués de la présence de méconium dans le liquide amniotique |
O682 | Travail et accouchement compliqués d'une anomalie du rythme cardiaque du foetus avec présence de méconium dans le liquide amniotique |
O683 | Travail et accouchement compliqués de signes biochimiques de détresse foetale |
O688 |
Travail et accouchement compliqués d'autres signes de détresse foetale |
O689 | Travail et accouchement compliqués d'une détresse foetale, sans précision |
Post partum
Psychiatric disorder related to the puerperium
CODES | INTITULES |
---|---|
O993 | Troubles mentaux et maladies du système nerveux compliquant la grossesse, l'accouchement et la puerpéralité |
F53 | Troubles mentaux et du comportement associés à la puerpéralité, non classés ailleurs |
APPENDIX 4
Comparison of patients included in the study versus those not included
Non included patients n = 41,722 | Included patients n = 760 | p-value | |
---|---|---|---|
Age at delivery | 29.6 ± 5.4 | 32.3 ± 5.5 | <0.001 |
<20 years | 1,071 (2.6) | 6 (0.8) | <0.001 |
20–35 years | 3,595 (82.9) | 522 (68.7) | |
>35 years | 6,056 (14.5) | 232 (30.5) | |
Gestational age | 39.0+/−2.1 | 38.7+/−2.3 | 0.001 |
CMU | 7,423 (17.8) | 153 (20.1) | 0.10 |
Multiparous | 21,889 (52.5) | 385 (50.7) | 0.32 |
Medical assisted procreation | 955 (2.3) | 14 (1.8) | 0.41 |
Psychiatric comorbidities during hospitalization or long-term affection | |||
Depression/anxiety | |||
|
854 (2.1) | 165 (21.7) | <0.001 |
|
69 (0.2) | 39 (5.1) | <0.001 |
Psychiatric disorder | |||
|
311 (0.8) | 80 (10.5) | <0.001 |
|
18 (0) | 7 (0.9) | <0.001 |
Suicide attempt | |||
|
373 (0.9) | 62 (8.2) | <0.001 |
|
46 (0.1) | 21 (2.8) | <0.001 |
History of complicated pregnancy | 188 (0.5) | 13 (1.7) | <0.001 |
History before pregnancy | |||
Alcohol | 134 (0.3) | 25 (3.3) | <0.001 |
Tobacco | 1,291 (3.1) | 61 (8.0) | <0.001 |
Drugs | 115 (0.3) | 24 (3.2) | <0.001 |
Obesity | 939 (2.3) | 41 (5.4) | <0.001 |
- CMU, Universal health insurance.
APPENDIX 5
Model selection criteria
Model | LogLikelihood | AIC | BIC | Entropy | % smaller class |
---|---|---|---|---|---|
1-class | −2,941,261 | 5,892,522 | 5,915,689 | ||
2-class | −2,341,353 | 4,704,707 | 4,755,673 | 0.886 | 30.9 |
3-class | −2,219,131 | 4,472,261 | 4,551,028 | 0.934 | 9.9 |
4-class | −2,167,099 | 4,380,198 | 4,486,765 | 0.947 | 10.1 |
5-class | −2,134,851 | 4,327,703 | 4,462,069 | 0.945 | 5.5 |
- Abbreviations: AIC, Akaike information criterion; BIC, Bayesian information criterion.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.