Andersson, Liselott MD*†; Sundström-Poromaa, Inger MD, PhD‡; Wulff, Marianne MD, PhD*; Åström, Monica MD, PhD§; Bixo, Marie MD, PhD*
Depression and anxiety disorders are common health problems that affect women more often than men.1 The World Health Organization's Global Burden of Disease Study2 has estimated unipolar major depression to be the leading cause of disease-related disability among women in the world today. Reproductive events have been suggested to be involved in the onset and course of depression and anxiety,3,4 in which context, postpartum depression5 is probably the most studied. Prior research has found associations between antenatal depression and/or anxiety and deteriorated neonatal outcome in terms of preterm delivery and small-for-gestational-age births.6,7 Although a number of studies have assessed the prevalence of antenatal depression and anxiety,8,9 few studies have investigated the impact of these disorders on obstetric outcome. Perkins and colleagues10 found a weak relationship between anxiety and use of analgesia/anesthesia in the second stage of labor, but no other obstetric complications. Likewise, a recent study of Chung and coworkers11 indicated an increased risk for use of epidural analgesia and operative deliveries in women with antenatal depressive symptoms. On the other hand, Wu and colleagues12 did not reveal any associations between antenatal depressive symptoms and mode of delivery. Validation and comparison of results between studies is, however, difficult, because most studies have used different rating scales and/or criteria for diagnosing depression and anxiety. For example, none of the 3 last-mentioned studies has used modern psychiatric criteria that adhere to Diagnostic and Statistical Manual of Mental Disorders-4th edition guidelines. Another more general problem when addressing the impact of antenatal depression and/or anxiety on obstetric outcome is that few studies have been performed in population-based samples.
The aim of this study was to investigate obstetric outcome and health care consumption during pregnancy, delivery, and the early postpartum period in an unselected population-based sample of pregnant women diagnosed with antenatal depressive and/or anxiety disorders, compared with healthy subjects.
MATERIALS AND METHODS
All women attending the second trimester routine ultrasound screening at Umeå University Hospital and at Sunderby Central Hospital were approached for study participation. The inclusion period was from October 2, 2000, to October 1, 2001. The Swedish antenatal health care system includes almost 100% of the Swedish pregnant population.13 Furthermore, approximately 97% of the Swedish pregnant population participate in the ultrasound examination, which is performed at 16–18 weeks of gestation, mainly for estimation of the expected date of delivery and detection of multiples.14 During the study period, Umeå University Hospital served a population of 134,428 people, of which 27,063 were women of reproductive age. The corresponding figures for Sunderby Central Hospital were 115,600 and 19,277, respectively. Most importantly, there were no other available ultrasound screening facilities or delivery units in these 2 cities.
Exclusion criteria for the study were 1) detection of malformation or missed abortion at the ultrasound examination, 2) inability to read and understand the questionnaire because of language difficulties, and 3) not providing informed consent. Moreover, only cases with complete medical records for the entire pregnancy and delivery were included in the study.
The Primary Care Evaluation of Mental Disorders system was used for screening of depressive and anxiety disorders. It has been validated for use in primary care settings15 and conforms to the criteria of Diagnostic and Statistical Manual of Mental Disorders-4th edition. The agreement between diagnoses of the Primary Care Evaluation of Mental Disorders and those of independent mental health professionals is excellent, with an overall accuracy of 88%. Primary Care Evaluation of Mental Disorders was considered to be a suitable tool for assessing the prevalence of psychiatric disorders in an obstetric outpatient setting because of its utility and ease of use. Furthermore, a self-administered version of Primary Care Evaluation of Mental Disorders, the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, has been validated for use in obstetric–gynecologic patients.16 The Primary Care Evaluation of Mental Disorders system consists of 2 components: a 1-page patient questionnaire and a 12-page clinician evaluation guide, which is a structured interview for the clinician to follow when evaluating the responses on the patient questionnaire. The instrument estimates the presence of 20 possible mental disorders, among which this study focused on 13 diagnoses. Among these 13 diagnoses of interest, 8 correspond to the specific requirements of Diagnostic and Statistical Manual of Mental Disorders-4th edition (major depressive disorder, dysthymia, partial remission of major depressive disorder, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social phobia, and bulimia nervosa). Additionally, 4 subthreshold diagnoses are included (minor depressive disorder, anxiety not otherwise specified, eating disorder not otherwise specified, and binge-eating disorder). Because fewer symptoms are required than for a specific diagnosis from Diagnostic and Statistical Manual of Mental Disorders-4th edition, these diagnoses are called “subthreshold.” However, they are included because they are associated with considerable impairment in function.17 Finally, a rule-out diagnosis of bipolar disorder was included. For the present study, a modified form of the patient questionnaire was used, which contained 25 questions evaluating somatoform disorder, mood disorders, anxiety disorders (including social phobia and obsessive-compulsive disorder), and eating disorders. Somatoform disorders and rule-out diagnoses of mood and/or anxiety related to a physical disorder, medication, or drugs were not assessed.
Before attending the ultrasound examination, the women completed the patient questionnaire. In doing so, they were also asked to provide name, date of birth, telephone number, and an informed consent allowing for a telephone interview. If any key question for mental disorders was indicated, the woman was considered to be screen-positive, and a telephone interview was conducted within 1–2 weeks after the ultrasound examination using a computerized version of the clinician evaluation guide. Those who were asking for help and/or had thoughts about committing suicide were immediately referred to psychiatric specialist care. One research nurse and 4 obstetricians performed the telephone interviews.
The results, fully described elsewhere,9 were as follows: A total of 2,263 women were examined by ultrasound screening during the inclusion period. After exclusion for refusal to participate (10 women), language difficulties (82 women), too intense patient flow (362 women), and other reasons (14 women), 1,795 women received the patient questionnaire. Sixty-four women did not answer the questionnaire, and 105 women did not sign the informed consent. Furthermore, 22 women were excluded because of missed abortion or malformation, and 49 women were not reached within the stipulated 14 days. Incomplete medical records were present in 60 women. Thus, the study population consisted of 1,495 women.
Three months after delivery, the medical records of the women were thoroughly reviewed. Demographic and behavioral characteristics, such as maternal age, parity, body mass index (BMI) in the first trimester, marital status, socioeconomic status, smoking and tobacco habits, alcohol consumption, prevalence of chronic disease, and history of psychiatric disorders, were extracted from the medical records. Furthermore, data on previous miscarriage and infertility treatment (ovulation stimulation and in vitro fertilization) in the actual pregnancy were assessed. Data on drug abuse other than tobacco and alcohol were not assessed because no routine screening is made for these drugs in the antenatal health care program since the prevalence during pregnancy generally is considered to be very low in Sweden.
Pregnancy data obtained from the medical charts included number of midwife visits, nausea and vomiting (defined as doctors visits and/or disability days because of nausea and vomiting), incidence of sick leave during first trimester, total amount of sick leave before 36 weeks of gestation, number of ultrasound examinations, total number of visits to the obstetrician, and specific visits for amniocentesis or chorion villi sampling, pain, fear of childbirth, and premature contractions. Pregnancy complications assessed were hypertensive disorder, including preeclampsia, postterm labor, oligohydramnios, bleeding in late gestation (including placenta previa and abruption placenta), intrauterine growth restriction, fetal hypoxia, and preterm delivery.
Delivery data were obtained on induced labor, planned or acute cesarean delivery, instrumental delivery, use of oxytocin and epidural analgesia during labor, time from self-experienced start of labor to delivery, and time from arrival in the delivery unit to delivery. Data on poor progress in labor, postpartum bleeding, fetal distress, and rupture of the anal sphincter were recorded for assessment of delivery complications. Finally, data were recorded on early postpartum complications, such as postpartum infection, postpartum readmission, mastitis, other postpartum complications, and stay at the maternity ward.
The study was approved by the Ethics Committee, Umeå University, Sweden.
The study population and the group of eligible, but not included, women were compared with regard to age, parity, marital status, socioeconomic status, smoking, snuff taking, and history of psychiatric disorder.
Hospital-to-hospital variation was evaluated regarding the distribution of diagnoses from the Primary Care Evaluation of Mental Disorders. Continuous variables were compared with the t test and are displayed as mean ± standard deviation. Frequencies were compared between groups by χ2 test.
Multiple logistic regression analysis was used to calculate adjusted odds ratios for obstetric outcome. For adjustment, the following maternal factors were included: maternal age as completed years at the time of the psychiatric investigation, parity as primipara or not, marital status as married/cohabiting with a partner and single parents, and socioeconomic status according to Swedish socioeconomic indices as professional employees or laborers. Smoking, recorded at the first visit to antenatal care, was categorized into nonsmoking (not daily smoking) and smoking (one or more cigarettes per day). Likewise, snuff taking was classified into no snuff taking and snuff taking. The first trimester BMI, kg/m2, was categorized according to recommendation by the World Health Organization: underweight (BMI < 18.5), normal (BMI 18.5–24.9), overweight (BMI 25.0–29.9), and obese (BMI ≥ 30). A history of heart disease, diabetes mellitus, hypertension, or renal disease was used to indicate chronic disease. Data on previous miscarriage and infertility treatment in the actual pregnancy were also categorized.
Pregnancy and delivery data were categorized according to group means as follows: number of midwife visits, duration of sick leave, number of ultrasound examinations, visits to the obstetrician, time from start of labor to delivery, and time from arrival in the delivery unit to delivery. Preterm delivery was defined as less than 37 weeks of completed gestation. The gestational age was estimated according to the result of the second-trimester ultrasound screening. No other methods were used in spontaneous pregnancies. The gestational age in pregnancies resulting from in vitro fertilization was estimated according to the day of embryo transfer. Stay at the maternity ward postpartum was categorized to fit the Swedish definition of early discharge, which is less than 72 hours. Women who delivered by planned cesarean delivery were excluded in the statistical analyses on variables concerning only spontaneous and induced labor, such as use of oxytocin, epidural analgesia, time from start of labor to delivery, time from arrival in delivery department to delivery, poor progress in labor, and rupture of the anal sphincter.
A 2-sided P value < .05 was considered significant.
All statistical analyses, with one exception, were performed using SPSS 10.0 (SPSS Inc, Chicago, IL). Confidence intervals for proportions were calculated using EpiCalc 2000 (Brixton Health, www.brixtonhealth.com).
In the study population of 1,495 women, 211 (14.1%; 95% confidence interval [CI] 12.40–15.99%) had one or more psychiatric diagnoses. Depressive disorders were most common, with a prevalence of 174 (11.6%; 95% CI 10.04–13.36%) subjects. Major depression was present in 48 (3.2%; 95% CI 2.39–4.26%) women, and 106 (7.1%; 95% CI 5.87–8.55%) had a minor depressive disorder. Anxiety disorders were present in 92 (6.2%; 95% CI 5.06–7.57%) women, and anxiety not otherwise specified was most common, found in 63 (4.2%; 95% CI 3.27–5.38%) subjects. A total number of 11 (5.2%; 95% CI 2.75–9.37%) of the 211 women with a psychiatric diagnosis had some sort of treatment for their psychiatric condition. Only one of them used any antidepressant therapy at the time for second-trimester ultrasound screening. One additional woman was prescribed antidepressant therapy later in pregnancy. In both of these cases, the drug was a selective serotonin reuptake inhibitor. None of the women without any psychiatric diagnosis were noted to use psychoactive medication.
Comparisons between the original study group and the group of women not included in the study are given in Table 1. The excluded subjects had a significantly lower socioeconomic status than the study population and were more seldom snuff taking.
Multiple pregnancies were exclusively twins, and the distribution of twins between women with a psychiatric diagnosis and those without did not differ significantly (17 [1.3%] in healthy subjects and 4 [1.9%] among women with a psychiatric diagnosis). Also, the distribution of stillbirths was not significantly different between groups (4 [0.3%] stillbirths in women without a psychiatric diagnosis and 2 [0.9%] in women with antenatal depressive and/or anxiety disorders).
Regarding the distribution of psychiatric diagnoses, there was no significant difference between the 2 hospitals (not in table).
Maternal factors associated with depressive and/or anxiety disorders are presented in Table 2. Not being married or cohabiting with a partner, low socioeconomic status, smoking, multiparity, and BMI more than 30 kg/m2 were significantly and independently associated with the presence of a diagnosis of depression and/or anxiety in the second trimester of pregnancy.
Women with antenatal depressive and/or anxiety disorder more often suffered from nausea and vomiting (Table 3). They more often had their first sick leave already during the first trimester, and they had a significantly higher number of disability days throughout the entire pregnancy, compared with the group without a diagnosis (Table 3). Thirty-seven percent of all women had disability days at some time during pregnancy (not presented in table). Furthermore, women with an antenatal psychiatric diagnosis visited their obstetrician more often than healthy subjects, and specifically, they more frequently attended the obstetrics–gynecology clinic because of fear of childbirth and premature contractions (Table 3). Also, they were more commonly delivered by planned cesarean, had an increased use of epidural analgesia, and reported a longer self-experienced time of labor (Table 4). Severe complications of pregnancy, delivery, and the early postpartum period were not affected by antenatal depression and/or anxiety (Tables 5 and 6).
The results of the present study suggest that antenatal depressive and anxiety disorders are associated with more negative events during pregnancy and delivery. Severe obstetric complications, on the other hand, were not affected by antenatal depression and/or anxiety.
Our finding that more women with a psychiatric diagnosis suffered from nausea and vomiting is supported in a study of Chou and colleagues,18 who noticed an association between depression and nausea, vomiting, and fatigue in early pregnancy. Whether depression preceded or resulted from the symptoms was considered unclear, both in their study and in other investigations.19,20 However, in a study by Rodriguez and coworkers,21 frequent nausea was found to decrease from 51% in gestational weeks 10–12 to 9% in week 20, suggesting that the risk for overestimating psychiatric disorders ought to be a minor problem at the later time point. Furthermore, as previously mentioned, a self-administered version of Primary Care Evaluation of Mental Disorders, the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, has been validated for use in obstetric–gynecologic patients.16 Depressive symptoms are not often recognized in clinical gynecological practice, most likely because psychiatric disorders in women often are disguised by somatic complaints, such as headache, chronic fatigue, pain, and bleeding irregularities.22 Among patients with major depression seeking help at their general practitioner, the majority presented with other symptoms or causes for their consultation.22 Presumably, nausea and vomiting could represent one such symptom of discomfort.
Our study suggests that women with antenatal depressive and/or anxiety disorder were on sick leave earlier in the pregnancy and for a longer time period throughout pregnancy than women without any diagnosis. Although not specifically concerned with a pregnant population, similar results were obtained in DEPRES (Depression Research in European Society), which was the first pan-European study on depression in the community, performed by Lépine and coworkers.17 DEPRES was performed on a large population (78,463 adults) in 6 countries and was not performed exclusively on pregnant women. The results of the DEPRES study revealed more lost days of productivity in depressed subjects and also a strong correlation between the severity of depression and number of sick-leave days. Those who suffered from major depression lost 4 times as many working days over a 6-month period as nonsufferers (13 versus 3 days). In our study, 37% of women, at some time point during pregnancy, had a sick-leave period. Although missing data on disability days was prevalent in 207 subjects, thus opening up the possibility of some degree of uncertainty in the results, the frequency is similar to what previously has been reported from Swedish register data. In 2002, 39% of pregnant Swedish women were on sick leave during the last trimester of pregnancy.23
Another finding in the DEPRES17 study was that sufferers from major depression imposed the greatest demand on healthcare resources, making almost 3 times as many visits to their general practitioner or family doctor as nonsufferers. In our study we also found more doctor visits among women with a diagnosis than among women without.
Furthermore, consultation related to fear of childbirth was significantly associated with a psychiatric diagnosis. Supporting data are presented in a study by Sjogren and Thomassen,24 who found a higher frequency of psychological problems in women with severe anxiety over childbirth compared with controls, and likewise, significant associations between antenatal depressive and/or anxiety disorders and pronounced fear of childbirth have been reported.9
Finally, we noted significant associations between antenatal depression and/or anxiety and consultations related to premature contractions, planned cesarean delivery, use of epidural analgesia during labor, and a self-experienced longer time of labor. The higher incidence of cesarean deliveries might be explained by a covariation between depression and/or anxiety and fear of childbirth, as already mentioned. Sjogren and Thomassen24 noted in their study that 68% of the women with severe anxiety over childbirth initially requested cesarean delivery. In Sweden, the cesarean delivery rate has increased from 10.6% in 1990 to 16.0% in 2001.13 Because there are no firm somatic explanations for this increase, psychological factors have been suggested to be involved. The increased use of epidural analgesia found among patients with depressive and/or anxiety disorders in our study was also supported by Chung and colleagues.11 This finding, together with the experienced longer time of labor, might be associated with more sensations of pain. As previously mentioned,22 somatic complaints seem to be associated with depressive and/or anxiety disorder, and pain especially has been noted to complicate the diagnosing of depression.25 Likewise, McWilliams and colleagues26 found associations between chronic pain and mood and anxiety disorders. In their study, anxiety disorders were more strongly associated with pain than were mood disorders.
Other studies have noted associations between antenatal depressive symptoms and adverse events in pregnancy and/or delivery,6,11,27 including increased frequency of operative deliveries, preterm delivery, and preeclampsia. The study on preeclampsia, performed by Kurki and coworkers,27 revealed significant associations between the disease and antenatal depressive and/or anxiety symptoms. One suggested explanation was that depression and anxiety might alter excretion of vasoactive hormones or other neuroendocrine transmitters, leading to an increased risk for hypertension. Our study did not reveal any correlations between antenatal depression and/or anxiety and complications of pregnancy and delivery, such as hypertensive disorder including preeclampsia, fetal growth restriction/hypoxia, and preterm delivery. Operative vaginal deliveries and acute cesarean deliveries were also similarly distributed between women with a psychiatric diagnosis and healthy subjects.
A limitation of the present investigation is the sample size, which presumably is too small to detect adverse events that normally are rare. For that reason, only a limited number of relatively frequent obstetric complications have been studied. Another limitation is that the assessment of psychiatric diagnoses were made at one time point only during pregnancy, raising questions as to whether symptoms remained unchanged, were transitory, or might have developed after the time of screening. For example, Evans and coworkers28 have noted a significant increase in depression scores between 18 and 32 weeks of pregnancy. Finally, a third limitation is that the excluded women, in fact, did differ from the study population in that they had a lower socioeconomic status. Because low socioeconomic status was associated with the presence of a psychiatric diagnosis, it can be assumed that a number of women with antenatal depression and/or anxiety have been excluded from the study group and that the prevalence of psychiatric disorder during pregnancy would have been higher if these subjects had been included.
In conclusion, this study has pointed out that there is an association between depressive and anxiety disorders during pregnancy and lost productivity and increased health care use. Besides the individual suffering, this also generates increased costs for society.
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