Determinants of ante-partum depression: a multicenter study

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1 DOI /s z ORIGINAL PAPER Determinants of ante-partum depression: a multicenter study Balestrieri Matteo Isola Miriam Bisoffi Giulia Calò Salvatore Conforti Anita Driul Lorenza Marchesoni Diego Petrosemolo Paola Rossi Michela Zito Adriana Zorzenone Stefania Di Sciascio Guido Leone Roberto Bellantuono Cesario Received: 11 July 2011 / Accepted: 27 March 2012 Ó Springer-Verlag 2012 Abstract Introduction Ante-partum depression (APD) is usually defined as a non-psychotic depressive episode of mild to moderate severity, beginning in or extending into pregnancy. APD has received less attention than postpartum depression. This is a cross-sectional study carried out in the Obstetrics and Gynaecology (OG) departments of four different general hospitals in Italy. Methods Women attending consecutively the OG departments for their first ultrasound examination were asked to fill in the Edinburgh Postnatal Depression Scale (EPDS) in its Italian validated version. We used the total scores of the EPDS as a continuous variable for univariate and linear regression analyses; in accordance with the literature, the item analysis of EPDS was carried out by classifying the sample as women with no depression (scores 0 9), possible depression (scores 10 12), probable depression (scores 13?) and probable APD (scores 15?). Results The number of women recruited was 1,608. The EPDS assessment classified 10.9 % of the women as possibly depressed, 8.3 % as probably depressed and 4.7 % probably affected from an APD. EPDS score distribution was associated with nationality (higher scores for foreigners), cohabitation (higher scores for women living with friends or in a community), occupation (higher scores for housewives), past episodes of depression and use of herbal drugs. Non-depressed women had significantly lower values on all ten items as compared with depressed women, however, the pattern of item distribution on the EPDS scale remained similar across depression severity groups. In all four groups item 4 (anxious depression) attained the highest scores, while item 10 (suicidality) attained the lowest scores. B. Matteo Z. Stefania Section of Psychiatry, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy B. Matteo (&) Clinica Psichiatrica, Azienda Ospedaliero-Universitaria, P.le S. M. Misericordia 15, Udine, Italy matteo.balestrieri@uniud.it I. Miriam Department of Medical and Morphological Sciences, University of Udine, Udine, Italy B. Giulia Biostatistics Office, University Hospital, Verona, Italy C. Anita L. Roberto Clinical Pharmacology Unit, University of Verona, Verona, Italy D. Lorenza M. Diego Clinic of Obstetrics and Gynaecology, University Hospital of Udine, Udine, Italy P. Paola Section of Psychiatry and Clinical Psychology, Department of Medicine and Public Health, University of Verona, Verona, Italy R. Michela B. Cesario Psychiatric Unit, Department of Neuroscience, Polytechnic University of Marche, Ancona, Italy C. Salvatore Z. Adriana D. S. Guido Department of Neurological and Psychiatric Sciences, University Hospital Policlinico Consorziale, University Aldo Moro, Bari, Italy

2 Keywords Ante-partum Depression General hospital Pregnancy EPDS Introduction Ante partum depression (APD) is usually defined as a nonpsychotic depressive episode of mild to moderate severity, beginning in or extending into pregnancy. APD has received less attention than postpartum depression (PPD); nonetheless, it is as common as PPD and is in fact the strongest predictor of post-natal depression itself [1 3]. The prevalence of APD is quite variable. In a Swedish survey, the prevalence of psychiatric disorders in a sample of women in their second trimester of pregnancy was estimated using a two-phase procedure (PRIME-MD system), which included a self-reported questionnaire and a subsequent telephone interview with screen-positive women. About 14 % of the women had one or more PRIME-MD psychiatric diagnoses. Of these, 11.6 % had affective disorders and 6.6 % an anxiety disorder [4]. In Singapore, Chen et al. [5] validated the Centre for Epidemiological Studies-Depression (CES-D) scale amongst pregnant women and found that the rate of depressive disorders was one out of five during antepartum. In Italy, a diagnostic assessment with a structured interview on more than a thousand women at their first ultrasound examination showed that major depression was present in 3 % of cases and minor depression in 4.1 % of cases [6]. A meta-analysis estimated rates of depression, as detected by validated screening instruments and structured interviews, in the order of 7.4, 12.8 and 12.0 % during the first, second and third trimester, respectively [7]. Life stress, lack of social support and domestic violence are associated with a greater likelihood of APD in a few studies [8, 9]. The most widely used instrument for estimating PPD and APD is the Edinburgh Postnatal Depression Scale (EPDS) [10, 11], a questionnaire validated and used in at least 24 countries [12]. The main aims of this study were: a. to estimate the point prevalence of depression in a large Italian sample of pregnant women using the EPDS; b. to correlate the prevalence of depression with some socio-demographic and clinical variables. A secondary aim was the analysis of dimensions of depression across the sample, to identify phenotypical differences in subgroups of depressed women. Methods This is a cross-sectional study carried out in the Obstetrics and Gynaecology (OG) departments of four different general hospitals across different regions of Italy. Specifically, Ascoli (Marche) collected the data of 644 women, Bari (Apulia) of 130 women, Udine (Friuli) of 296 women and Verona (Veneto) of 538 women. The different sample size among these centres was related to the characteristics and dimensions of the OG departments of the general hospitals which participated in this study. Women attending consecutively the OG departments for their first ultrasound examination between weeks 12 and 15 gestational age were asked to fill in the EPDS in its Italian validated version and a form containing relevant information on the socio-demographic and pharmacological data. Women with a cognitive deficit that hindered the reading and comprehension of the questionnaires were excluded. All participants were adequately informed about the aims of the study and gave their written consent to participate in the survey. They were not reimbursed for their participation in the study. The presence and severity of depression were estimated with the EPDS. This instrument is a 10-item scale, typically self-administered. Recently, a systematic review of validation studies of EPDS in ante partum and post-partum women has been performed [11]. Sensitivity and specificity of the cut-off points showed marked heterogeneity between the 37 studies analysed. In the majority of epidemiological studies on PPD, cutoff scores of 10? and 13? have been used as markers of possible minor and major depression, respectively. In APD some data seem to confirm the cut-off score of 13? [13], while Murray and Cox [14], and more recently Matthey et al. [15] and Gibson et al. [11], recommended using 15? as a cut-off score for a probable diagnosable mood disorder. In the studies that adopted an EPDS cut-off score of 13? in postnatal depression, the sensitivity ranged from 34 to 100 % and the specificity from 49 to 100 %. In Italy, EPDS (13? cut-off score) has been validated in 113 women, showing a satisfactory sensitivity (94.4 %), specificity (87.4 %) and positive predictive value (58.6 %). The internal consistency was tested using Chronbach s alpha coefficient (0.79) and Guttman split-half coefficient (0.82) [16]. The three studies validating the EPDS in an antenatal sample selected a cut-off score of 15?; in these studies, the sensitivity for major depression ranged from 57 to 100 % and the specificity from 93 to 99 %. In our study, we used the total scores of EPDS as a continuous variable for univariate and linear regression analyses, while the item analysis of EPDS was carried out by classifying the sample as women with no depression (scores 0 9), possible depression (scores 10 12), probable depression (scores 13?) and probable APD (scores 15?). This was in accordance with the recommendations made by Matthey et al. [15] and Gibson et al. [11].

3 Statistics Table 1 Characteristics of the sample and EPDS scores Characteristics of the study population are described using means and standard deviation (SD) for continuous variables and percentages for categorical variables. v 2 tests were used to analyze categorical values; when assumptions for v 2 test were not verified, Fisher s exact test was used. A univariate regression analysis was carried out to explore the association of demographic and clinical predictors to EPDS scores. Afterwards, we performed a stepwise linear regression analysis including all variables that were significantly associated (p B 0.1). We considered as possible predictors: age (continuous variable), marital status, employment, cohabitation, nation of birth, previous pregnancies, past history of depression, past and present antidepressant treatment, other drug treatments. Finally, an item analysis of EPDS was carried out to investigate the relevance of each dimension of the depressive spectrum. To compare the item distribution across the depression severity groups, we used a nonparametric two-sample test on the equality of medians. A subanalysis was also performed to calculate the clinical and demographic characteristics associated with higher scores on the most represented item (item 4). Analyses were carried out on Stata/SE 11.1 for Windows. Results The overall number of women who refused to participate was negligible (1.1 %). Table 1 shows the general characteristics of the sample of women included in the analyses and the corresponding mean EPDS scores. The EPDS assessment classified 133 women [8.3 %, 95 % CI: ( %)] as probably depressed (scores 13?), 175 [10.9 %, 95 % CI: ( %)] as possibly depressed (scores 10 12) and 1,300 [80.8 %, 95 % CI: ( %)] as not depressed (scores 0 9). When using the 15? cut-off score, only 75 women were found to be probably affected from an APD [4.7 %, 95 % CI: ( %)]. Univariate regression analysis (Table 2) shows that single women reported higher mean EPDS scores than married women, women living with friends or in community arrangements showed higher mean EPDS scores than spouses, both unemployed women and housewives showed a higher mean EPDS scores than employed women, both women with a high school diploma and university degree showed a lower mean EPDS scores than women with primary education and women born in other countries showed higher mean EPDS scores than Italian women. As far as the medical history is concerned, the presence of a previous depression or the report of previous medical Characteristics Whole sample No (100 %) EPDS scores Mean ± SD: 6.0 ± 4.4 Mean age 32.2 ± 4.8 Marital status (No.) Married 1, ± 4.3 Single ± 4.5 Separated/divorced ± 5.0 Cohabitation Spouse ± 4.2 Spouse with children ± 4.5 Alone with/without children ± 2.9 Other ± 4.9 Occupation Employed 1, ± 4.2 Unemployed ± 4.6 Housewife ± 4.8 Education Primary school ± 4.8 High school diploma 1, ± 4.4 University degree ± 4.1 Nationality Italy 1, ± 4.3 Other countries ± 4.5 Previous pregnancies No ± 4.3 Yes, one ± 4.4 Yes, more than one ± 4.6 Previous depression No 1, ± 4.2 Yes ± 4.9 Previous medical contacts for depression No 1, ± 4.2 Yes ± 5.3 Antidepressant drug in the past No 1, ± 4.3 Yes ± 5.4 Actual antidepressant drug use No 1, ± 4.3 Yes ± 5.2 Actual use of other drugs No 1, ± 4.3 Yes ± 4.4 Actual use of herbal drugs No 1, ± 4.3 Yes ± 4.8 contacts for depression was associated with higher mean EPDS scores than the absence of these clinical features. Past and actual use of antidepressant drugs was likewise

4 Table 2 Univariate regression analysis to explore the association between the characteristics of the sample and EPDS scores (continuous variable) Coefficient 95 % CI P Age to Marital status Married Single to Separated/divorced to Cohabitation Spouse Spouse with children to Alone with/without to children Other to 3.97 \ Occupation Employed Unemployed to Housewife to 1.73 \ Education Primary school High school diploma to University degree to Nationality Italy Other countries to Previous pregnancies Yes, one to Yes, more than one to Previous depression Yes to 3.62 \ Previous medical contacts for depression No Yes to 3.33 \ Antidepressant drug in the past No Yes to 4.35 \ Actual antidepressant drug use Yes to Actual use of other drugs Yes to Actual use of herbal drugs Yes to Table 3 Stepwise linear regression model on EPDS scores EPDS Coef. 95 % CI p Nationality (other countries vs. Italy a ) Cohabitation (other vs. spouse a ) Occupation (housewife vs. employed a ) Past depression (yes vs. no a ) Herbal drugs (yes vs. no a ) a Reference category associated with higher mean EPDS scores unlike the absence of using these drugs, while women taking overthe-counter (OTC) herbal drugs (mostly St John s Wort, or Hypericum perforatum) showed higher mean EPDS scores unlike women who did not take any. Table 3 shows the results of the stepwise linear regression model. EPDS score distribution was associated with nationality (higher scores for foreigners, p = 0.012), cohabitation (higher scores for women living with friends or in a community, p = 0.001), occupation (higher scores for housewives, p = 0.001), past episodes of depression (p \ ) and use of herbal drugs (p = 0.003). The proportion of EPDS score variance explained by these covariates was only 7.0 %. A subsequent step was the analysis of the dimensions of depression. Figure 1 shows that the pattern of item distribution (mean ± SD) on the EPDS scale remained similar across depression severity groups. On the other hand, the median equality test showed that non-depressed women had significantly lower values on all ten items as compared with depressed women with both an EPDS score of 13? and of 15? (p \ ). In all four groups, item 4 (anxious depression) attained the highest scores, while item 10 (suicidality) attained the lowest scores. A sub-analysis which focused on item 4 revealed that higher scores were associated with some clinical variables: presence of past depression (v 2 = 30.01, d.f. = 3 p \ ), previous medical contacts for depression (v 2 = 28.06, d.f. = 3, p \ ), past use of antidepressants (v 2 = 15.53, d.f. = 3, p = 0.001) and actual use of herbal drugs (v 2 = 12.11, d.f. = 3, p = 0.007). Discussion In a recent paper, Matthey et al. [15] discussed the possible impact of using an invalidated cut-off score of EPDS, trying to highlight the possible reasons for this error and making recommendations to clinicians and researchers who use this scale. They quoted Murray and Cox [14] in

5 Fig. 1 Mean scores and SD for each EPDS item in four groups of pregnant women saying that pregnancy is a time of emotional, physiological and social change (and) the clinical significance of the (major depression) diagnostic category is not clear. They also observed that women in pregnancy may have various worries (e.g., previous miscarriage gestational age, lack of movement of the foetus; the pain of childbirth and concerns over the current and future health of the baby) that could result in transient heightened anxiety or distress. However, this fails to satisfactorily fulfil the criteria for a defined affective disorder. As a consequence, Matthey et al. [15] supported the recommendations of Murray and Cox [14] to use 15? as a cut-off score for a probable diagnosable mood disorder in pregnancy. In our study, the use of the classic 13? cut-off provided a prevalence of severe depression of 8.3 %, a proportion which is lower than the one (13.2 ± 4.7 %) originally calculated by Murray and Cox [14] with the same cut-off score. On the other hand, in a recent US survey, Rich-Edwards et al. [17] found 9 % of participants with an EPDS score [12 during pregnancy and Bunevicius et al. [13] reported that depression affected 6.1 % of women during their first trimester of pregnancy. Even using the 15? cut-off score, our prevalence of severe depression (4.7 %) was lower than that (6.8 ± 3.5 %) reported by Murray and Cox [14]. When considering these findings, we must be aware that in a recent review on the use of EPDS, Gibson et al. [11] found that only three studies focused on APD, with a sample size of no more than 229 women. These Authors found an

6 extreme heterogeneity among the studies, due to differences in methodology, language and diagnostic interview or criteria used. They concluded that the results of the different studies may not be directly comparable and that the EPDS may not be an equally valid screening tool across all settings and contexts. In this respect, we must take into account that the low prevalence of depression in our multicenter study could be related to the lower prevalence of depression in Italy as compared with English-speaking countries [18 20]. Only five covariates were significantly associated with EPDS scores. When considering these data, we must admit a possible limitation of our study, i.e., the absence of an analysis on the opinion on the quality of the relationship with the spouse/partner or the perception of social support. Such analyses would have required administering a further questionnaire or better carrying out an interview, with the risk of increasing the refusal rate. Among the social variables, we find depression associated with living in the absence of close relatives, being a housewife and a foreigner. Among the clinical variables, we have depression associated with previous episodes of depression and the use of herbal drugs. Some associations (e.g., history of depression, lack of social support) are intuitive and already described [8, 17, 21, 22], but others require further consideration. In our study, in particular, being a housewife was a risk factor for depression. Indeed, we do not know whether these women were housewives because they voluntarily chose to stay at home or following the loss of a temporary job due to pregnancy. Nevertheless, this piece of information is useful to highlight the need to improve obstetrician-gynaecologists diagnostic accuracy for mental health issues in at-risk pregnant women [23]. Equal attention must be paid to the risk of depression in foreign women. Since these women have a lower probability of contacting primary care or mental health services, the detection of depression in these situations is crucial. Perhaps, the most surprising finding is the fact that the use of OTC herbal drugs was associated with depression. To understand this result, we ought to imagine a depressed pregnant woman who is reluctant to use (or refuses being prescribed) an antidepressant drug. As a result depression continues. Since this is a robust finding in our analysis, we must conclude that this is either widespread prescriptive malpractice on the part of physicians or these women prefer to self-medicate themselves with herbal drugs during pregnancy even in moderate-severe cases of depression. Finally, we observed that the pattern of item distribution remained similar across depression severity groups. This may suggest that all items included in the EPDS scale have similar relevance in describing the dimension of depression and both contribute to the rise of the total EPDS score. It should be noted that anxiety in pregnant women (as measured by item 4) is the most represented component in the spectrum of depression. This finding confirms the relevance of anxiety symptoms in ante-partum depression [24, 25]. Higher scores on this item are associated with past episodes of depression, previous medical contacts, past use of antidepressants and the actual use of herbal drugs. This might imply that women with anxiety have a relevant history of disease that required treatment. In conclusion, we can say that in a vast sample of pregnant women living in different parts of Italy depression was most likely present in 5 to 8 % of the sample (depending on a conservative or wider approach). 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