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Women with anxiety disorders during pregnancy are at increased risk of intense postnatal depressive symptoms: a prospective survey of the MATQUID cohort
European Psychiatry 19 (2004) 459–463 http://france.elsevier.com/direct/EURPSY/
Original article
Women with anxiety disorders during pregnancy are at increased risk of intense postnatal depressive symptoms: a prospective survey of the MATQUID cohort A.L. Sutter-Dallay, V. Giaconne-Marcesche, E. Glatigny-Dallay, H. Verdoux * EA 3676, IFR 99 of Public Health, Department of Psychiatry, University Victor Segalen Bordeaux 2, Bordeaux, France Available online 18 November 2004
Abstract Objective. – Studies have suggested that women with pregnancy anxiety may be at greater risk of postnatal depression (PND). However, due to the high comorbidity between anxiety and depressive disorders, this finding may be confounded by the association between prenatal depression and postnatal depression. The aim of the present prospective study was to assess whether anxiety disorder (AD) during pregnancy is an independent predictor of intensity of postnatal depressive symptoms. Method. – The MATQUID cohort survey was conducted on pregnant women (n = 497) attending a state maternity hospital. Psychiatric status during pregnancy was assessed during the third trimester using a structured diagnostic interview. Intense postnatal depressive symptoms at 6 weeks post-partum were defined by a score >12 on the Edinburgh Postnatal Depression Scale (EPDS). Results. – Nearly one out of four women (24.1%) presented with at least one pregnancy AD, and 29 (5.8%) presented with a score >12 on the EPDS. After adjustment for presence of major depression during pregnancy and other confounding factors, women with pregnancy AD were nearly three times more likely to present with intense postnatal depressive symptoms (OR = 2.7, 95%CI 1.1–6.3, P = 0.03). Conclusion. – Promoting the recognition and management of AD in pregnant women may be of interest for the prevention of postnatal depression. © 2004 Elsevier SAS. All rights reserved. Keywords: Post-partum depression; Risk factors; Anxiety disorders; Pregnancy
1. Introduction In recent decades, a large number of psychiatric, psychosocial and obstetrical risk factors for postnatal depression (PND) have been identified [13,18,24]. Among psychiatric risk factors, the best documented to date is a personal or family history of mood disorder, with an increased risk especially marked in women with pregnancy depression [18]. The impact of other pregnancy psychiatric disorders on the risk of PND is less well-known. In particular, the links between anxiety during pregnancy and PND require further exploration due to the high prevalence of anxiety disorders (AD) in the general population and their high comorbidity with depressive disorders. When anxiety is considered as a dimensional characteristic clinically assessed or measured by a score on a rating * Corresponding author. Hôpital Charles Perrens, 121, rue de la Béchade, 33076 Bordeaux cedex, France. E-mail address: [email protected] (H. Verdoux). 0924-9338/$ - see front matter © 2004 Elsevier SAS. All rights reserved. doi:10.1016/j.eurpsy.2004.09.025
scale, the findings in the literature are discrepant. Precursor studies suggested that anxiety during pregnancy increased the risk of PND [6,22], while others did not confirm this association [19]. More recent prospective studies on larger samples of women did not find a link between dimensional anxiety and PND [3,13], though a meta-analysis of five studies carried out between 1968 and 1985 found that dimensional anxiety during pregnancy was a strong predictor of PND [18]. Few studies have explored the link between AD defined as diagnostic categories and PND. A historical prospective study of 22 women suggested that a diagnosis of panic disorder before pregnancy did not markedly increase the risk of PND [26]. A retrospective study of 25 patients found that 37% of women with pre-existing obsessive–compulsive disorder developed a PND [25]. A study on a cohort of 66 women showed that severity of a post-traumatic stress disorder after stillbirth predicted the occurrence of PND
460
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during a consecutive pregnancy [23]. To our knowledge, no study has explored the links between generalized AD and PND. Although these findings suggest that dimensionally or categorically defined anxiety may be a risk factor for PND, their interpretation is hampered by methodological limitations such as their small sample sizes and the lack of adjustment for confounding factors. In particular, most studies did not take into account the strong comorbidity between mood and AD, and thus did not explore whether pregnancy AD increases the risk of PND independently of the existence of pregnancy depression. Therefore, the aim of the present prospective study was to assess in a large sample of women whether pregnancy AD is an independent risk factor for the occurrence of intense postnatal depressive symptoms 6 weeks after delivery.
2. Method 2.1. Subjects The present study was based upon data collected in the MATQUID prospective survey designed to explore the impact of PND on the emotional and psychomotor development of the child. The method of this study has been previously presented [21,24]. Briefly, consecutive pregnant women attending antenatal clinics at the maternity units of the University Hospital of Bordeaux were screened by obstetricians or midwives during prenatal visits, or by research psychologists during prenatal educational meetings. Inclusion criteria were designed to include a homogeneous sample of women with regard to gestational age and delivery conditions. Women were included if they fulfilled the following criteria: (1) written informed consent to participate in the study; (2) fluent in French; (3) living in the catchment area of the hospital (Bordeaux and neighboring suburbs); (4) no personal history of psychotic illness; (5) no multiple pregnancy or in vitro fertilization for the current pregnancy; (6) less than 1 week of hospitalization due to pregnancy complications; (7) no planned Cesarean section delivery. Women fulfilling these baseline inclusion criteria were subsequently excluded after delivery in the case of premature birth or unplanned Cesarean delivery. Of the 945 screened women fulfilling the inclusion criteria, 347 women (37%) did not participate in the survey: 272 refused to participate, mostly because the survey was considered as too time-consuming, 64 women could not be contacted by phone, and 11 women who initially agreed to attend the baseline interview did not come. 2.2. Assessment The baseline interview (T1) carried out by research psychologists took place during the third trimester of pregnancy (beginning of eighth month) at the maternity hospital. This
included collection of socio-demographic information and a structured diagnostic interview with the Mini International Neuropsychiatric Interview (MINI) [14] giving DSM-IV diagnoses of AD (generalized anxiety, social phobia, obsessive–compulsive disorder, agoraphobia, panic disorder, posttraumatic stress disorder) and of Major Depressive Disorder (MDD). The follow-up interview (T2) took place at home 6 weeks after delivery. A self-report questionnaire was then given to the mothers. If it was not possible to complete it during the psychologist’s visit, mothers were asked to return it by mail. This questionnaire included the Edinburgh Postnatal Depression Scale (EPDS), a 10-item self-report questionnaire specifically aimed at screening for depressive mood symptoms in the postnatal period [4]. We considered a woman as presenting with intense postnatal depressive symptoms when the EPDS score was higher than 12. This threshold was defined according to previous studies using the EPDS French version which demonstrated its validity for research purposes, with a high specificity (0.98) for detecting PND [9,11]. The self-report questionnaire also included the dyadic adjustment scale (DAS, Spanier, 1979; French translation by Baillargeon et al. [1], a 32-item self-report questionnaire designed to assess marital adjustment. Of the 598 women assessed at T1, 561 were assessed at T2 and 497 completed the self-report questionnaire (83% of the baseline sample). 2.3. Statistical analyses Statistical analyses were carried out using STATA 7 [20]. The characteristics of women with and without missing data for the variable of interest (EPDS score) were compared using univariate analyses (chi square test for categorical variables and Student’s t-test for continuous variables). Logistic regressions yielding odds ratios (ORs) and 95% CI were used to explore the associations between pregnancy disorders and high postnatal EPDS score (>12). The selection strategy of variables included in the multivariate regression models was based upon a priori selection of potentially confounding variables that were forced in all the models [2]. All the associations were adjusted for maternal age, educational level (categorized according to the distribution in the sample as <12 vs. ≥12 years), mean income (categorized into <1500 Euro vs. ≥1500 Euro), parity (primiparity vs. multiparity), and marital adjustment (measured by the DAS summary score). Pregnancy AD was defined as the existence of at least one MINI AD during pregnancy (generalized anxiety, social phobia, obsessive–compulsive disorder, agoraphobia, panic disorder, post-traumatic stress disorder). We examined (i) the main effect of pregnancy AD on the risk of high vs. low postnatal EPDS score; (ii) the main effect of pregnancy MDD on the risk of high vs. low postnatal EPDS score; (iii) the independent effects of pregnancy AD and MDD on the risk of high vs. low postnatal EPDS score, by entering pregnancy AD and MMD into the same model; (iv) the interaction between pregnancy AD and MDD on the risk of high vs. low EPDS postnatal score using the Wald test.
A.L. Sutter-Dallay et al. / European Psychiatry 19 (2004) 459–463
We conducted sensitivity analyses to examine whether missing data could have biased any findings. This was done by substituting missing data in the mothers who had missed EPDS data in such a way that the extremes of any bias could be quantified. In the first sensitivity analysis, all missing mothers for EPDS were assigned to the high postnatal EPDS score group. In the second analysis, all missing mothers for the EPDS were assigned to the low postnatal EPDS score group.
3. Results 3.1. Characteristics of the sample
461
presenting with at least one AD were four times more likely to present also with MDD than those without (adjusted OR = 4, 95%CI 1.8–8.9, P = 0.001). At T2, the mean EPDS score was 4.1 (S.D. 4.1, median 3; range 0–17) and 29 (5.8%) women presented with high postnatal EPDS score (>12). Women presenting with pregnancy AD were 2.6 times more likely to present with high postnatal EPDS score (Table 2). Although women with MDD at T1 more frequently presented with high postnatal EPDS score, the association was not significant. The association between pregnancy AD and postnatal EPDS score was unchanged after further adjustment for MDD, indicating that presenting with pregnancy AD increased the risk of high postnatal EPDS score independently of the existence of a pregnancy MDD.
The characteristics of the women without missing data included in the present study are shown in Table 1. Women with missing data were more likely than those without to be younger, to have a lower income, a lower educational level, to live alone, and to present with AD at T1.
No interaction was found between pregnancy AD and MMD on the risk of high postnatal EPDS score (chi2 = 0.88, df = 1, P = 0.35). This finding indicates that the existence of a pregnancy depression does not modify the risk of high postnatal EPDS score in women presenting pregnancy AD.
3.2. Associations between pregnancy AD and PND
The results of the sensitivity analyses regarding the association between AD at T1 and postnatal EPDS score were as follows: (i) assuming all missing mothers were in the high postnatal EPDS score group: adjusted OR = 1.9, 95%CI 1.2–2.9, P = 0.005; (ii) assuming all missing mothers were in the low postnatal EPDS score group: adjusted OR = 1.9, 95%CI 0.9–4.4, P = 0.11. The strength of the association was slightly decreased for both extreme biases, but the direction of the association was unchanged.
Nearly one out of four women (n = 119, 24%) presented with at least one pregnancy AD [agoraphobia (n = 70, 14%), generalized AD (n = 51, 8.5%); panic disorder (n = 7, 1.4%); obsessive–compulsive disorder (n = 6, 1.2%); social phobia: n = 10, 2%; post-traumatic stress disorder: none]. Pregnancy MDD was identified in 28 (5.7%) women. There was a strong comorbidity between the two types of disorders, women Table 1 Baseline characteristics of women with and without missing data for EPDS
Age Primiparity Income ≥1500 Euro Educational level ≥12 years Married Pregnancy AD a Pregnancy major depression a
No missing EPDS data (N = 497) Mean (S.D.), N (%) 29.6 (4.2) 317 (64%) 368 (74%) 362 (72.8%) 476 (95.9%) 120 (24.1%) 28 (5.6%)
Missing EPDS data (N = 101) Mean (S.D.), N (%) 28.6 (4.8) 67 (66.3%) 59 (58.4%) 53 (53%) 89 (88%) 37 (36.6%) 2 (2%)
Statistical test t = 2.1 df = 596 P = 0.04 Chi2 = 0.20, df = 1, P = 0.66 Chi2 = 10, df =1, P = 0.002 Chi2 = 15.5, df = 1, P = 0.0001 Chi2 = 10.2, df = 1, P = 0.001 Chi2 = 6.8, df = 1, P = 0.009 Chi2 = 2.4, df = 1, P = 0.12
At least one of the MINI diagnoses: generalized anxiety, social phobia, obsessive–compulsive disorder, agoraphobia, panic disorder.
Table 2 Effects of anxiety and depressive disorder during pregnancy on the risk of intense postnatal depressive symptoms EPDS a >12, N = 29 (5.8%) 13 (10.8%) 16 (4.2%) 3 (10.3%) 25 (5.4%)
d
AD No AD Major depression No major depression Independent effects of AD Major depression a
Adjusted b OR, 95%CI c 2.6 (1.1–6.1) P = 0.02 1.6 (0.4–6.4) P = 0.5
e
2.7 (1.1–6.3) P = 0.03 1.1 (0.3–4.7) P = 0.86
EPDS. Adjusted for maternal age, parity, income, educational level, dyadic adjustment. c OR, 95% confidence interval. d At least one of the MINI diagnoses: generalized anxiety, social phobia, obsessive–compulsive disorder, agoraphobia, panic disorder. e AD and major depression in the same model. b
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4. Discussion This cohort study carried out on 497 women prospectively assessed during pregnancy and 6 weeks after delivery shows that presence of AD during pregnancy predicts the occurrence of intense postnatal depressive symptoms, independently of the existence of a prenatal maternal depression and other confounding factors. 4.1. Methodological limitations As women participated on a voluntary basis, the study was not carried out on an epidemiological sample. This may have favored the inclusion of women of middle–high socioeconomic status and education level, hence at lower risk of PND. This hypothesis is also suggested by the low (5.8%) frequency of women presenting with high postnatal EPDS score in our sample compared to that usually reported in the literature (between 10% and 20%) [5,13,18]. However, this selection is unlikely to have induced spurious findings, as it may have decreased rather than increased the strength of the association between pregnancy AD and postnatal depressive symptoms. Missing data on EPDS were in part favored by the fact that mothers were asked to send back the self-report questionnaires by mail, but women with missing EPDS data had more risk factors for PND. As previously demonstrated, this may have attenuated but not increased the strength of the association between AD and postnatal depressive symptoms. Furthermore, sensitivity analyses showed that missing EPDS data did not modify the direction and only slightly decreased the strength of the association between pregnancy AD and intensity of postnatal depressive symptoms. As postnatal depressive symptoms were measured using a self-report questionnaire, the validity of this measure compared to those obtained using observer-rated scales or a structured diagnostic interview may be questioned. However, a large number of studies have now demonstrated the validity of the EPDS as a screening tool for postnatal depressive symptoms [8,17]. We considered pregnancy AD as a single diagnostic category because of the relatively low prevalence of each specific AD disorder, and in order to limit the number of statistical tests. We cannot exclude that the association between AD and postnatal depressive symptoms is especially marked for or restricted to specific AD, and further studies are required to explore this issue. Lastly, we did not assess the onset of AD, so the present findings do not discriminate between AD pre-existing the current pregnancy or with pregnancy onset.
later depression in subjects suffering from AD, and the therapeutic overlap have generated considerable debate regarding the boundaries, if any, between the two disorders [10,12]. In accordance with previous findings, the present study suggests that a continuum of risk may exist between pregnant women and subjects from the general population with regard to the comorbid association between anxiety and depressive disorders. The specificity of the postnatal period compared to other periods of the life cycle may be related to a possible acceleration of the risk of transition from AD to depression under the influence of the various psychosocial and biological stressors prevalent in the perinatal period. In other words, the link between anxiety and depression may be quantitatively, but not qualitatively, different in perinatal periods compared to other stages of the life. Beyond the nosographic and pathophysiological questions raised by the increased risk of intense postnatal depressive symptoms in women with pregnancy AD, the present findings have potential clinical implications. Anxiety symptoms are frequently reported by pregnant women and are often considered by midwives and obstetricians as part of the normal psychic experiences of pregnancy, especially if they are focused on the baby’s health or on maternal competencies. The present findings suggest that these symptoms should not be too hastily considered as a normal adaptive process to pregnancy, but should be further investigated to identify possible AD. As valid screening tests and efficient psychotherapeutic treatments of limited duration are available for AD, further studies are required to investigate whether detection and treatment of pregnancy AD may prevent the occurrence of PND.
Acknowledgments This study was financially supported by a grant from the French Ministry of Health (“Programme Hospitalier de Recherche Clinique-1995”) and by a grant from SmithKlineBeecham Laboratories. We acknowledge M. Bourgeois, J.F. Dartigues, L. Dequae-Merchadoux, B. Dubroca and A. Cantagrel who assisted in the organization of the survey and in data collection. We are most grateful to the obstetricians and midwives who helped in the recruitment, especially D. Roux, D. Dallay, J.J. Leng, and J. Horovitz. We also thank Ray Cooke who kindly supervised the English of this paper.
References [1]
4.2. Interpretation of findings The complex relationships between anxiety and depression have been widely explored in clinical and epidemiological samples [7,15,16]. The frequent co-occurrence of anxiety and depressive symptoms and disorders, the increased risk of
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Original article
Women with anxiety disorders during pregnancy are at increased risk of intense postnatal depressive symptoms: a prospective survey of the MATQUID cohort A.L. Sutter-Dallay, V. Giaconne-Marcesche, E. Glatigny-Dallay, H. Verdoux * EA 3676, IFR 99 of Public Health, Department of Psychiatry, University Victor Segalen Bordeaux 2, Bordeaux, France Available online 18 November 2004
Abstract Objective. – Studies have suggested that women with pregnancy anxiety may be at greater risk of postnatal depression (PND). However, due to the high comorbidity between anxiety and depressive disorders, this finding may be confounded by the association between prenatal depression and postnatal depression. The aim of the present prospective study was to assess whether anxiety disorder (AD) during pregnancy is an independent predictor of intensity of postnatal depressive symptoms. Method. – The MATQUID cohort survey was conducted on pregnant women (n = 497) attending a state maternity hospital. Psychiatric status during pregnancy was assessed during the third trimester using a structured diagnostic interview. Intense postnatal depressive symptoms at 6 weeks post-partum were defined by a score >12 on the Edinburgh Postnatal Depression Scale (EPDS). Results. – Nearly one out of four women (24.1%) presented with at least one pregnancy AD, and 29 (5.8%) presented with a score >12 on the EPDS. After adjustment for presence of major depression during pregnancy and other confounding factors, women with pregnancy AD were nearly three times more likely to present with intense postnatal depressive symptoms (OR = 2.7, 95%CI 1.1–6.3, P = 0.03). Conclusion. – Promoting the recognition and management of AD in pregnant women may be of interest for the prevention of postnatal depression. © 2004 Elsevier SAS. All rights reserved. Keywords: Post-partum depression; Risk factors; Anxiety disorders; Pregnancy
1. Introduction In recent decades, a large number of psychiatric, psychosocial and obstetrical risk factors for postnatal depression (PND) have been identified [13,18,24]. Among psychiatric risk factors, the best documented to date is a personal or family history of mood disorder, with an increased risk especially marked in women with pregnancy depression [18]. The impact of other pregnancy psychiatric disorders on the risk of PND is less well-known. In particular, the links between anxiety during pregnancy and PND require further exploration due to the high prevalence of anxiety disorders (AD) in the general population and their high comorbidity with depressive disorders. When anxiety is considered as a dimensional characteristic clinically assessed or measured by a score on a rating * Corresponding author. Hôpital Charles Perrens, 121, rue de la Béchade, 33076 Bordeaux cedex, France. E-mail address: [email protected] (H. Verdoux). 0924-9338/$ - see front matter © 2004 Elsevier SAS. All rights reserved. doi:10.1016/j.eurpsy.2004.09.025
scale, the findings in the literature are discrepant. Precursor studies suggested that anxiety during pregnancy increased the risk of PND [6,22], while others did not confirm this association [19]. More recent prospective studies on larger samples of women did not find a link between dimensional anxiety and PND [3,13], though a meta-analysis of five studies carried out between 1968 and 1985 found that dimensional anxiety during pregnancy was a strong predictor of PND [18]. Few studies have explored the link between AD defined as diagnostic categories and PND. A historical prospective study of 22 women suggested that a diagnosis of panic disorder before pregnancy did not markedly increase the risk of PND [26]. A retrospective study of 25 patients found that 37% of women with pre-existing obsessive–compulsive disorder developed a PND [25]. A study on a cohort of 66 women showed that severity of a post-traumatic stress disorder after stillbirth predicted the occurrence of PND
460
A.L. Sutter-Dallay et al. / European Psychiatry 19 (2004) 459–463
during a consecutive pregnancy [23]. To our knowledge, no study has explored the links between generalized AD and PND. Although these findings suggest that dimensionally or categorically defined anxiety may be a risk factor for PND, their interpretation is hampered by methodological limitations such as their small sample sizes and the lack of adjustment for confounding factors. In particular, most studies did not take into account the strong comorbidity between mood and AD, and thus did not explore whether pregnancy AD increases the risk of PND independently of the existence of pregnancy depression. Therefore, the aim of the present prospective study was to assess in a large sample of women whether pregnancy AD is an independent risk factor for the occurrence of intense postnatal depressive symptoms 6 weeks after delivery.
2. Method 2.1. Subjects The present study was based upon data collected in the MATQUID prospective survey designed to explore the impact of PND on the emotional and psychomotor development of the child. The method of this study has been previously presented [21,24]. Briefly, consecutive pregnant women attending antenatal clinics at the maternity units of the University Hospital of Bordeaux were screened by obstetricians or midwives during prenatal visits, or by research psychologists during prenatal educational meetings. Inclusion criteria were designed to include a homogeneous sample of women with regard to gestational age and delivery conditions. Women were included if they fulfilled the following criteria: (1) written informed consent to participate in the study; (2) fluent in French; (3) living in the catchment area of the hospital (Bordeaux and neighboring suburbs); (4) no personal history of psychotic illness; (5) no multiple pregnancy or in vitro fertilization for the current pregnancy; (6) less than 1 week of hospitalization due to pregnancy complications; (7) no planned Cesarean section delivery. Women fulfilling these baseline inclusion criteria were subsequently excluded after delivery in the case of premature birth or unplanned Cesarean delivery. Of the 945 screened women fulfilling the inclusion criteria, 347 women (37%) did not participate in the survey: 272 refused to participate, mostly because the survey was considered as too time-consuming, 64 women could not be contacted by phone, and 11 women who initially agreed to attend the baseline interview did not come. 2.2. Assessment The baseline interview (T1) carried out by research psychologists took place during the third trimester of pregnancy (beginning of eighth month) at the maternity hospital. This
included collection of socio-demographic information and a structured diagnostic interview with the Mini International Neuropsychiatric Interview (MINI) [14] giving DSM-IV diagnoses of AD (generalized anxiety, social phobia, obsessive–compulsive disorder, agoraphobia, panic disorder, posttraumatic stress disorder) and of Major Depressive Disorder (MDD). The follow-up interview (T2) took place at home 6 weeks after delivery. A self-report questionnaire was then given to the mothers. If it was not possible to complete it during the psychologist’s visit, mothers were asked to return it by mail. This questionnaire included the Edinburgh Postnatal Depression Scale (EPDS), a 10-item self-report questionnaire specifically aimed at screening for depressive mood symptoms in the postnatal period [4]. We considered a woman as presenting with intense postnatal depressive symptoms when the EPDS score was higher than 12. This threshold was defined according to previous studies using the EPDS French version which demonstrated its validity for research purposes, with a high specificity (0.98) for detecting PND [9,11]. The self-report questionnaire also included the dyadic adjustment scale (DAS, Spanier, 1979; French translation by Baillargeon et al. [1], a 32-item self-report questionnaire designed to assess marital adjustment. Of the 598 women assessed at T1, 561 were assessed at T2 and 497 completed the self-report questionnaire (83% of the baseline sample). 2.3. Statistical analyses Statistical analyses were carried out using STATA 7 [20]. The characteristics of women with and without missing data for the variable of interest (EPDS score) were compared using univariate analyses (chi square test for categorical variables and Student’s t-test for continuous variables). Logistic regressions yielding odds ratios (ORs) and 95% CI were used to explore the associations between pregnancy disorders and high postnatal EPDS score (>12). The selection strategy of variables included in the multivariate regression models was based upon a priori selection of potentially confounding variables that were forced in all the models [2]. All the associations were adjusted for maternal age, educational level (categorized according to the distribution in the sample as <12 vs. ≥12 years), mean income (categorized into <1500 Euro vs. ≥1500 Euro), parity (primiparity vs. multiparity), and marital adjustment (measured by the DAS summary score). Pregnancy AD was defined as the existence of at least one MINI AD during pregnancy (generalized anxiety, social phobia, obsessive–compulsive disorder, agoraphobia, panic disorder, post-traumatic stress disorder). We examined (i) the main effect of pregnancy AD on the risk of high vs. low postnatal EPDS score; (ii) the main effect of pregnancy MDD on the risk of high vs. low postnatal EPDS score; (iii) the independent effects of pregnancy AD and MDD on the risk of high vs. low postnatal EPDS score, by entering pregnancy AD and MMD into the same model; (iv) the interaction between pregnancy AD and MDD on the risk of high vs. low EPDS postnatal score using the Wald test.
A.L. Sutter-Dallay et al. / European Psychiatry 19 (2004) 459–463
We conducted sensitivity analyses to examine whether missing data could have biased any findings. This was done by substituting missing data in the mothers who had missed EPDS data in such a way that the extremes of any bias could be quantified. In the first sensitivity analysis, all missing mothers for EPDS were assigned to the high postnatal EPDS score group. In the second analysis, all missing mothers for the EPDS were assigned to the low postnatal EPDS score group.
3. Results 3.1. Characteristics of the sample
461
presenting with at least one AD were four times more likely to present also with MDD than those without (adjusted OR = 4, 95%CI 1.8–8.9, P = 0.001). At T2, the mean EPDS score was 4.1 (S.D. 4.1, median 3; range 0–17) and 29 (5.8%) women presented with high postnatal EPDS score (>12). Women presenting with pregnancy AD were 2.6 times more likely to present with high postnatal EPDS score (Table 2). Although women with MDD at T1 more frequently presented with high postnatal EPDS score, the association was not significant. The association between pregnancy AD and postnatal EPDS score was unchanged after further adjustment for MDD, indicating that presenting with pregnancy AD increased the risk of high postnatal EPDS score independently of the existence of a pregnancy MDD.
The characteristics of the women without missing data included in the present study are shown in Table 1. Women with missing data were more likely than those without to be younger, to have a lower income, a lower educational level, to live alone, and to present with AD at T1.
No interaction was found between pregnancy AD and MMD on the risk of high postnatal EPDS score (chi2 = 0.88, df = 1, P = 0.35). This finding indicates that the existence of a pregnancy depression does not modify the risk of high postnatal EPDS score in women presenting pregnancy AD.
3.2. Associations between pregnancy AD and PND
The results of the sensitivity analyses regarding the association between AD at T1 and postnatal EPDS score were as follows: (i) assuming all missing mothers were in the high postnatal EPDS score group: adjusted OR = 1.9, 95%CI 1.2–2.9, P = 0.005; (ii) assuming all missing mothers were in the low postnatal EPDS score group: adjusted OR = 1.9, 95%CI 0.9–4.4, P = 0.11. The strength of the association was slightly decreased for both extreme biases, but the direction of the association was unchanged.
Nearly one out of four women (n = 119, 24%) presented with at least one pregnancy AD [agoraphobia (n = 70, 14%), generalized AD (n = 51, 8.5%); panic disorder (n = 7, 1.4%); obsessive–compulsive disorder (n = 6, 1.2%); social phobia: n = 10, 2%; post-traumatic stress disorder: none]. Pregnancy MDD was identified in 28 (5.7%) women. There was a strong comorbidity between the two types of disorders, women Table 1 Baseline characteristics of women with and without missing data for EPDS
Age Primiparity Income ≥1500 Euro Educational level ≥12 years Married Pregnancy AD a Pregnancy major depression a
No missing EPDS data (N = 497) Mean (S.D.), N (%) 29.6 (4.2) 317 (64%) 368 (74%) 362 (72.8%) 476 (95.9%) 120 (24.1%) 28 (5.6%)
Missing EPDS data (N = 101) Mean (S.D.), N (%) 28.6 (4.8) 67 (66.3%) 59 (58.4%) 53 (53%) 89 (88%) 37 (36.6%) 2 (2%)
Statistical test t = 2.1 df = 596 P = 0.04 Chi2 = 0.20, df = 1, P = 0.66 Chi2 = 10, df =1, P = 0.002 Chi2 = 15.5, df = 1, P = 0.0001 Chi2 = 10.2, df = 1, P = 0.001 Chi2 = 6.8, df = 1, P = 0.009 Chi2 = 2.4, df = 1, P = 0.12
At least one of the MINI diagnoses: generalized anxiety, social phobia, obsessive–compulsive disorder, agoraphobia, panic disorder.
Table 2 Effects of anxiety and depressive disorder during pregnancy on the risk of intense postnatal depressive symptoms EPDS a >12, N = 29 (5.8%) 13 (10.8%) 16 (4.2%) 3 (10.3%) 25 (5.4%)
d
AD No AD Major depression No major depression Independent effects of AD Major depression a
Adjusted b OR, 95%CI c 2.6 (1.1–6.1) P = 0.02 1.6 (0.4–6.4) P = 0.5
e
2.7 (1.1–6.3) P = 0.03 1.1 (0.3–4.7) P = 0.86
EPDS. Adjusted for maternal age, parity, income, educational level, dyadic adjustment. c OR, 95% confidence interval. d At least one of the MINI diagnoses: generalized anxiety, social phobia, obsessive–compulsive disorder, agoraphobia, panic disorder. e AD and major depression in the same model. b
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4. Discussion This cohort study carried out on 497 women prospectively assessed during pregnancy and 6 weeks after delivery shows that presence of AD during pregnancy predicts the occurrence of intense postnatal depressive symptoms, independently of the existence of a prenatal maternal depression and other confounding factors. 4.1. Methodological limitations As women participated on a voluntary basis, the study was not carried out on an epidemiological sample. This may have favored the inclusion of women of middle–high socioeconomic status and education level, hence at lower risk of PND. This hypothesis is also suggested by the low (5.8%) frequency of women presenting with high postnatal EPDS score in our sample compared to that usually reported in the literature (between 10% and 20%) [5,13,18]. However, this selection is unlikely to have induced spurious findings, as it may have decreased rather than increased the strength of the association between pregnancy AD and postnatal depressive symptoms. Missing data on EPDS were in part favored by the fact that mothers were asked to send back the self-report questionnaires by mail, but women with missing EPDS data had more risk factors for PND. As previously demonstrated, this may have attenuated but not increased the strength of the association between AD and postnatal depressive symptoms. Furthermore, sensitivity analyses showed that missing EPDS data did not modify the direction and only slightly decreased the strength of the association between pregnancy AD and intensity of postnatal depressive symptoms. As postnatal depressive symptoms were measured using a self-report questionnaire, the validity of this measure compared to those obtained using observer-rated scales or a structured diagnostic interview may be questioned. However, a large number of studies have now demonstrated the validity of the EPDS as a screening tool for postnatal depressive symptoms [8,17]. We considered pregnancy AD as a single diagnostic category because of the relatively low prevalence of each specific AD disorder, and in order to limit the number of statistical tests. We cannot exclude that the association between AD and postnatal depressive symptoms is especially marked for or restricted to specific AD, and further studies are required to explore this issue. Lastly, we did not assess the onset of AD, so the present findings do not discriminate between AD pre-existing the current pregnancy or with pregnancy onset.
later depression in subjects suffering from AD, and the therapeutic overlap have generated considerable debate regarding the boundaries, if any, between the two disorders [10,12]. In accordance with previous findings, the present study suggests that a continuum of risk may exist between pregnant women and subjects from the general population with regard to the comorbid association between anxiety and depressive disorders. The specificity of the postnatal period compared to other periods of the life cycle may be related to a possible acceleration of the risk of transition from AD to depression under the influence of the various psychosocial and biological stressors prevalent in the perinatal period. In other words, the link between anxiety and depression may be quantitatively, but not qualitatively, different in perinatal periods compared to other stages of the life. Beyond the nosographic and pathophysiological questions raised by the increased risk of intense postnatal depressive symptoms in women with pregnancy AD, the present findings have potential clinical implications. Anxiety symptoms are frequently reported by pregnant women and are often considered by midwives and obstetricians as part of the normal psychic experiences of pregnancy, especially if they are focused on the baby’s health or on maternal competencies. The present findings suggest that these symptoms should not be too hastily considered as a normal adaptive process to pregnancy, but should be further investigated to identify possible AD. As valid screening tests and efficient psychotherapeutic treatments of limited duration are available for AD, further studies are required to investigate whether detection and treatment of pregnancy AD may prevent the occurrence of PND.
Acknowledgments This study was financially supported by a grant from the French Ministry of Health (“Programme Hospitalier de Recherche Clinique-1995”) and by a grant from SmithKlineBeecham Laboratories. We acknowledge M. Bourgeois, J.F. Dartigues, L. Dequae-Merchadoux, B. Dubroca and A. Cantagrel who assisted in the organization of the survey and in data collection. We are most grateful to the obstetricians and midwives who helped in the recruitment, especially D. Roux, D. Dallay, J.J. Leng, and J. Horovitz. We also thank Ray Cooke who kindly supervised the English of this paper.
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