http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2014; 27(13): 1339–1342 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2013.858242
ORIGINAL ARTICLE
Obstetric and neonatal outcome in patients with anxiety disorders Michael Pavlov1*, Naama Steiner2*, Roy Kessous2, Adi Y. Weintraub2, and Eyal Sheiner2 1
Department of Psychiatry and 2Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract
Keywords
Objective: To investigate whether a diagnosis of anxiety disorder is a risk factor for adverse obstetric and neonatal outcome. Methods: A retrospective population-based study was conducted comparing obstetric and neonatal complications in patients with and without a diagnosis of anxiety. Multivariable analysis was performed to control for confounders. Results: During the study period 256 312 singleton deliveries have occurred, out of which 224 (0.09%) were in patients with a diagnosis of an anxiety disorder. Patients with anxiety disorders were older (32.17 5.1 versus 28.56 5.9), were more likely to be smokers (7.1% versus 1.1%) and had a higher rate of preterm deliveries (PTD; 15.2% versus 7.9%), as compared with the comparison group. Using a multiple logistic regression model, anxiety disorders were independently associated with advanced maternal age (OR 1.087; 95% CI 1.06–1.11; p ¼ 0.001), smoking (OR 4.51; 95% CI 2.6–7.29; p ¼ 0.001) and preterm labor (OR 1.92; 95% CI 1.32-–2.8; p ¼ 0.001). In addition, having a diagnosis of an anxiety disorder was found to be an independent risk factor for cesarean section (adjusted OR 2.5; 95% CI 1.82–3.46; p50.001), using another multivariable model. No association was noted between anxiety disorders and adverse neonatal outcomes including small for gestational age, low Apgar scores and perinatal mortality. Conclusion: Anxiety disorders are independent risk factors for spontaneous preterm delivery and cesarean section, but in our population it is not associated with adverse perinatal outcome.
Anxiety disorders, neonatal outcome, obstetric complication
Introduction Anxiety disorders have been distinctly defined according to DSM-IV diagnostic criteria: They include panic disorder, agoraphobia, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder and phobias [1]. Anxiety disorders are characterized by prominent symptoms of anxiety and worrying that are unproportional to circumstances and persist in a patient for the majority of at least six months prior to diagnosis. Controversy and difficulty exists regarding its distinction from mood disorders such as major depression [2]. Data regarding the prevalence of anxiety disorders is inconclusive. Different definitions of anxiety disorders account for a wide variability in the reported prevalence that ranges from as low as 1.6% to as high as 28.8%. In a large population-based study (the National Institute of Mental Health Epidemiologic Catchment Area study), anxiety disorders were more prevalent than any other mental disorder (8.3% of the population). Also, Kim et al.
*Authors Pavlov and Steiner are equal contributors. Address for correspondence: Eyal Sheiner, MD, PhD, Department of Obstetrics and Gynecology, Soroka University Medical Center, POB 151, Beer Sheva 84101, Israel. E-mail: [email protected]
History Received 27 July 2013 Revised 7 October 2013 Accepted 19 October 2013 Published online 26 November 2013
have reported a prevalence of anxiety of 10% during pregnancy in patients from Minnesota [2–5]. Few studies found an association between anxiety disorders in women of childbearing age and some adverse obstetrical complications and fetal and neonatal outcomes [6–15]. Alder et al [6], in a review of 35 studies that were published between the years 1990–2005 have reported that depression and anxiety were associated with adverse obstetric outcomes and had implications for fetal and neonatal wellbeing and behavior. However, the authors declared that conclusions regarding the impact of anxiety and mood disorders are limited due to methodological problems [6]. Studies of the relationship between anxiety disorders and obstetrical and neonatal complications are inconclusive and sometimes contradictive. However, the most common obstetrical complications reported are preterm labor, hypertensive disorders, cesarean mode of delivery and an increased perception of pain during labor [6–15]. In terms of neonatal complications small for gestational age and low Apgar scores were the most studied complications related to anxiety disorders [16–20]. In an attempt to add to the current data regarding these common and important diagnoses, the aim of the present study was to examine whether patients with a diagnosis of an anxiety disorder are exposed to a higher risk for adverse obstetrical and neonatal complications.
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Materials and methods Setting The study was conducted at the Soroka University Medical Center, the sole tertiary hospital in the Negev, the southern region of Israel, serving the entire obstetrical population. Thus, the study represents non-selective population-based data. The Institutional Review Board (in accordance with the Helsinki declaration) approved the study. Study population The study population was composed of all patients who delivered between the years 1989–2010. Patients with multiple pregnancies and those lacking prenatal care were excluded from the analysis. Study design A retrospective study was conducted, comparing pregnancy outcome of patients with and without a diagnosis of an anxiety disorder. Data regarding the diagnosis of anxiety disorder were recorded by the admitting physician from the referral information. The diagnosis was made according to the charts, by a psychiatrist or a family physician. All current anxiety disorders diagnoses were included. Pregnancy complications and adverse outcomes were available from the perinatal database of the center. Data were reported by an obstetrician immediately after delivery. Skilled medical secretaries routinely reviewed the information prior to entering it into the database. Coding was performed after assessing the medical prenatal care records together with the routine hospital documents. The following demographic and clinical characteristics were evaluated: maternal age, ethnicity (Jewish or Bedouin), gravidity, parity, smoking, gestational age at delivery. Obstetrical complications that were examined included: recurrent abortions, hypertensive disorders, diabetes mellitus, previous cesarean section, anemia, polyhydramnios, oligohydramnios, intrauterine growth restriction, placenta previa. Data that were recorded regarding labor included preterm labor, preterm premature rupture of membranes (PROM), placental abruption, induction of labor, use of epidural, cesarean section and postpartum hemorrhage (PPH). The following perinatal outcomes were assessed: birth weight and fetal gender, low Apgar scores at 1 and 5 min (57) and perinatal mortality. Statistical analysis Statistical analysis was performed using the SPSS package (SPSS, Chicago, IL). Statistical significance was calculated using the chi square test for differences in qualitative variables and the Student’s t-test for differences in continuous variables. A multiple logistic regression model was used to investigate the independent association between anxiety disorders and maternal age, ethnicity, smoking, induction of labor, preterm labor, cesarean section, hypertensive disorders, diabetes mellitus and PROM (controlling for confounders that were found statistically and clinically significant in the univariate analysis).
J Matern Fetal Neonatal Med, 2014; 27(13): 1339–1342
Odds ratio (OR) and their 95% confidence intervals (CI) were computed. A value of p50.05 was considered statistically significant.
Results During the study period 256 312 singleton deliveries have occurred in our hospital, out of which 224 (0.09%) have occurred in patients with a recorded diagnosis of an anxiety disorder. Table 1 presents a comparison of clinical and demographic characteristics of patients with and without a diagnosis of an anxiety disorder. Patients with anxiety were older than the comparison group and had a tendency to smoke. In addition, a significantly higher rate of patients were of Jewish ethnicity. Table 2 presents a comparison of the prevalence of obstetric complications between patients with and without anxiety disorders. Patients with a diagnosis of an anxiety disorder had a significantly higher incidence of hypertensive disorders, diabetes mellitus, anemia and previous cesarean sections. Labor complications and outcomes of patients with and without anxiety disorders are presented in Table 3. Patients with a diagnosis of anxiety had a significantly higher prevalence of labor complications such as premature rupture of membranes, preterm delivery, induction of labor, PPH and cesarean section. In addition, patients with anxiety used more epidural analgesia. Neonatal outcomes such as birth weight, low Apgar scores (57) at 1 and 5 min or perinatal mortality did not differ between the groups (Table 4). Table 1. Clinical characteristics of women with and without anxiety disorders.
Characteristics Maternal age in years (mean) Parity 1 2–4 5þ Ethnicity Bedouins Jewish Smoking
Anxiety N ¼ 224
No Anxiety N ¼ 256 088
32.17 5.15
28.56 5.9
18.3% (41) 57.6% (129) 24.1% (54)
23.5% (60 223) 50.9% (130 226) 25.6% (65 608)
21.0% (47) 79% (177) 7.1% (16)
50.5% (129 246) 49.5% (126 842) 1.1% (2717)
OR
p value 50.001
0.091
3.837
50.001
7.173
50.001
Table 2. Obstetric complications of patients with and without anxiety disorders.
Characteristics Previous cesarean delivery Recurrent abortions Hypertensive disorders Diabetes mellitus Anemia (Hb510 mg/dL) Polyhydramnios Oligohydramnios Intra uterine growth restriction
Anxiety N ¼ 224 16.5% 6.7% 9.8% 9.8% 42% 4.5% 1.8% 2.2%
(37) (15) (22) (22) (94) (10) (4) (5)
No Anxiety N ¼ 256 088 12.2% 5.2% 5.5% 5.7% 28.2% 3.5% 2.3% 2.1%
(31 282) (13 409) (14 009) (14 480) (72 266) (9075) (5933) (5283)
OR
p value
1.422 0.049 1.299 0.327 1.882 0.004 1.817 0.007 1.839 50.001 1.272 0.456 0.767 0.597 1.084 0.859
Pregnancy in women with anxiety disorders
DOI: 10.3109/14767058.2013.858242
Table 3. Labor complications and outcomes of patients with and without anxiety disorders. Anxiety N ¼ 224
No Anxiety N ¼ 256 088
OR
11.2% (25)
6.4% (16 282)
1.850
0.003
14.3% (32)
8% (20 511)
1.316
0.001
2.539 2.95 2.083 4.616
50.001 50.001 50.001 50.001
Characteristics Mechanical induction of labor Premature rupture of membranes Epidural anesthesia Caesarian section Preterm labor below 37 w Post-partum hemorrhage
29.5% 31.7% 15.2% 2.7%
(66) (71) (34) (6)
14.1 13.6% 7.9% 0.6%
(36 185) (34 807) (20 256) (1518)
p value
Table 4. Neonatal outcome of patients with and without anxiety disorders.
Characteristics Birth weight (g) 52500 2500–4000 44000 Apgar 1 minute 57 Apgar 5 minute 57 Perinatal mortality
Anxiety N ¼ 224 11.2% 84.4% 4.5% 6.7% 2.2% 0.9%
(25) (189) (10) (15) (5) (2)
No Anxiety N ¼ 256 088 8.0% 87.2% 4.8% 6.5% 3% 1.3%
(20 487) (223 298) (12 303) (16 655) (7667) (3452)
OR
p value 0.217
1.032 0.74 0.659
0.907 0.504 0.555
Table 5. Factors associated with anxiety disorders: results from a multiple logistic regression model. Characteristics Maternal age Ethnicity (Jewish versus Bedouins) Smoking Induction of labor Preterm labor 537w Hypertensive disorders Diabetes mellitus PROM
OR
95% CI
p value
1.087 3.04 4.51 1.13 1.92 1.42 1.08 1.627
1.06–1.11 2.12–4.22 2.6–7.29 0.84–1.51 1.32–2.80 0.89–2.3 0.69–1.70 1.11–2.38
50.001 50.001 50.001 0.428 0.001 0.133 0.724 0.012
Table 5 shows a multiple logistic regression model that was constructed in order to identify factors that are independently associated with anxiety disorders. Anxiety disorders remained independently associated with advanced maternal age, Jewish ethnicity, smoking and preterm labor. The association between anxiety disorders and hypertensive disorders and diabetes mellitus lost its significance. Another multivariable logistic regression model was constructed, with cesarean section as the outcome variable. The model included anxiety disorders in addition to other confounders that are known to be related to a higher risk for cesarean section such as maternal age, placental abruption, induction of labor, gestational age, previous cesarean section, hypertensive disorders, ethnicity and diabetes mellitus. Having a diagnosis of an anxiety disorder was found to be an independent risk factor for cesarean section (adjusted odds ratio 2.5; 95% CI 1.82–3.46; p50.001).
Discussion The current population-based study was aimed to examine the effect of anxiety disorders on adverse pregnancy and perinatal
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outcomes. Anxiety disorder was found to be independently related to common obstetric and labor complications such as preterm birth, premature rupture of membranes and delivery by cesarean section. In general, current literature regarding the effects of anxiety disorders on obstetric and neonatal complications is rather confusing and inconclusive. In our study even after controlling for confounders, higher rates of preterm deliveries were recorded in patients that were diagnosed with anxiety disorders. Our results correlate with several previous studies [7–9]. Sanchez et al. [7] performed a case-control study that included 480 patients with preterm labor and 479 controls. They found a correlation between the severity of the anxiety disorder and the risk for preterm delivery [7]. The same positive correlation was also found by Martini et al. [8] who studied obstetric complications of 992 patients following an assessment for presence of anxiety disorder and self predictive distress [8]. Nevertheless, in a study performed by Maina et al. [10] a relatively small group of 178 patients was studied; out of which only 20 patients had psychiatric disorders (13 defined as anxiety). In their study, no correlation was found between anxiety disorders and preterm labor, but the numbers were probably too small for conclusive results [10]. Controversy exists regarding the association between anxiety disorders and the mode of delivery. While several studies found higher rates of cesarean delivery (either elective or emergency) in patients with a diagnosis of anxiety disorders [8,11,12], other studies did not demonstrate this correlation [13,14]. In our study anxiety disorder was noted as an independent risk factor for delivering by cesarean section, even after careful analysis controlling for major important confounders. There is general agreement regarding the extended use of epidural analgesia by patients with anxiety disorders [6,11,12]. Our data is in agreement with previous studies. Andersson et al. [11] studied 1495 patients with a diagnosis of depressive and anxiety disorders and did not demonstrate a correlation between anxiety disorders and the development of preeclampsia latter in pregnancy [11]. Nevertheless, Kurki et al. [15] studied 623 patients out of which 99 were diagnosed with anxiety disorders (19%) early in pregnancy. The authors found anxiety disorders to be associated with the development of preeclampsia in pregnancy. In this study, detection rate of depression and anxiety disorders were relatively high and based on a single questioner [15]. Interestingly, while using multivariable analysis, the association between anxiety disorders and hypertensive disorders lost its significance in the current analysis. Few studies have reported the neonatal outcomes of patients with anxiety disorders and showed contradicting results: While some studies reported no correlation between anxiety disorders and small for gestational age infants [16–19], others reported a positive correlation [20]. In our study, we did not find a significant association between anxiety disorders and small for gestational age fetuses. Regarding Apgar scores, our results support previous studies reporting no association between low Apgar scores and anxiety disorders [18,19]. Perinatal mortality was not found to be increased in patients with anxiety disorders, thus a
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diagnosis of an anxiety disorder in a patient is not associated with higher rates of neonatal complications. Our study offers several strengths; the relatively large sample size allowed us to add significant data to current knowledge regarding these complications. In addition, data for the study were based on a computerized database collected by physicians and based on patient’s evaluation. Nevertheless, our study suffers from several weaknesses; one is that we do not have data regarding the criteria used for the diagnosis of the different anxiety disorders. Potential differences may exist between different definitions and criteria used for the diagnosis of anxiety disorder. Another potential weakness is that some undiagnosed women with anxiety disorders are included in the general population group, an assumption which is reinforced by the fact that the prevalence of diagnosed anxiety disorders is smaller than described in the literature. Cases were located from the computerized database of our center, where data were recorded by the admitting physician based on the patient’s referral information. Perhaps only the most severe cases received a diagnosis of an anxiety disorder and a proportion of patients with milder disease on the one hand or with untreated anxiety disorders on the other hand were missed. Finally, a weakness inherent to retrospective cohort studies is the potential for missing data. However, the data were reported by an obstetrician directly after delivery. Skilled medical secretaries routinely reviewed the information prior to entering it into the database. Coding was done after assessing the medical prenatal care records together with the routine hospital documents. Women lacking prenatal care were excluded from the study analysis. This makes this potential source of selection bias less likely. In conclusion, according to the results of our study, anxiety disorders are independently related to preterm labor, premature rupture of membranes and the risk for cesarean delivery. However, the patient can be reassured that the perinatal outcomes are comparable to the general population. When assessing a patient with anxiety disorder physicians should consider these complications and consult the patient accordingly. Further studies are needed in order to assess the rate of complications associated with the different type of anxiety disorders and the effects of treatment for anxiety on these adverse outcomes.
References 1. American Psychiatric Association. Diagnostic and statistical manual for psychiatric disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000 (Text Revision). 2. Kessler RC, Gruber M, Hettema JM, et al. Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up. Psychol Med 2008;38:365–74.
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3. Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62: 593–602. 4. Wittchen HU, Zhao S, Kessler RC, Eaton WW. DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:355–64. 5. Kim HG, Mandell M, Crandall C, et al. Antenatal psychiatric illness and adequacy of prenatal care in an ethnically diverse innercity obstetric population. Arch Womens Ment Health 2006;9: 103–7. 6. Alder J, Fink N, Bitzer J, et al. Depression and anxiety during pregnancy: a risk factor for obstetric, fetal and neonatal outcome? A critical review of the literature. J Matern Fetal Neonatal Med 2007;20:189–209. 7. Sanchez SE, Puente GC, Atencio G, et al. Risk of spontaneous preterm birth in relation to maternal depressive, anxiety, and stress symptoms. J Reprod Med 2013;58:25–33. 8. Martini J, Knappe S, Beesdo-Baum K, et al. Anxiety disorders before birth and self-perceived distress during pregnancy: associations with maternal depression and obstetric, neonatal and early childhood outcomes. Early Hum Dev 2010;86:305–10. 9. Ibanez G, Charles MA, Forhan A, et al.; EDEN Mother–Child Cohort Study Group. Depression and anxiety in women during pregnancy and neonatal outcome: data from the EDEN motherchild cohort. Early Hum Dev 2012;88:643–9. 10. Maina G, Saracco P, Giolito MR, et al. Impact of maternal psychological distress on fetal weight, prematurity and intrauterine growth retardation. J Affect Disord 2008;111:214–20. 11. Andersson L, Sundstro¨m-Poromaa I, Wulff M, et al. Implications of antenatal depression and anxiety for obstetric outcome. Obstet Gynecol 2004;104:467–76. 12. Chung TK, Lau TK, Yip AS, et al. Antepartum depressive symptomatology is associated with adverse obstetric and neonatal outcomes. Psychosom Med 2001;63:830–4. 13. Wu J, Viguera A, Riley L, et al. Mood disturbance in pregnancy and the mode of delivery. Am J Obstet Gynecol 2002;187: 864–7. 14. Perkin MR, Bland JM, Peacock JL, Anderson HR. The effect of anxiety and depression during pregnancy on obstetric complications. Br J Obstet Gynaecol 1993;100:629–34. 15. Kurki T, Hiilesmaa V, Raitasalo R, et al. Depression and anxiety in early pregnancy and risk for preeclampsia. Obstet Gynecol 2000; 95:487–90. 16. Hoffman S, Hatch MC. Depressive symptomatology during pregnancy: evidence for an association with decreased fetal growth in pregnancies of lower social class women. Health Psychol 2000;19: 535–43. 17. Orr ST, James SA, Blackmore Prince C. Maternal prenatal depressive symptoms and spontaneous preterm births among African-American women in Baltimore, Maryland. Am J Epidemiol 2002;156:797–802. 18. Andersson L, Sundstro¨m-Poromaa I, Wulff M, et al. Neonatal outcome following maternal antenatal depression and anxiety: a population-based study. Am J Epidemiol 2004;159:872–81. 19. Berle JØ, Mykletun A, Daltveit AK, et al. Neonatal outcomes in offspring of women with anxiety and depression during pregnancy. A linkage study from The Nord-Trøndelag Health Study (HUNT) and Medical Birth Registry of Norway. Arch Womens Ment Health 2005;8:181–9. 20. Field T, Diego M, Hernandez-Reif M, et al. Pregnancy anxiety and comorbid depression and anger: effects on the fetus and neonate. Depress Anxiety 2003;17:140–51.
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ORIGINAL ARTICLE
Obstetric and neonatal outcome in patients with anxiety disorders Michael Pavlov1*, Naama Steiner2*, Roy Kessous2, Adi Y. Weintraub2, and Eyal Sheiner2 1
Department of Psychiatry and 2Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract
Keywords
Objective: To investigate whether a diagnosis of anxiety disorder is a risk factor for adverse obstetric and neonatal outcome. Methods: A retrospective population-based study was conducted comparing obstetric and neonatal complications in patients with and without a diagnosis of anxiety. Multivariable analysis was performed to control for confounders. Results: During the study period 256 312 singleton deliveries have occurred, out of which 224 (0.09%) were in patients with a diagnosis of an anxiety disorder. Patients with anxiety disorders were older (32.17 5.1 versus 28.56 5.9), were more likely to be smokers (7.1% versus 1.1%) and had a higher rate of preterm deliveries (PTD; 15.2% versus 7.9%), as compared with the comparison group. Using a multiple logistic regression model, anxiety disorders were independently associated with advanced maternal age (OR 1.087; 95% CI 1.06–1.11; p ¼ 0.001), smoking (OR 4.51; 95% CI 2.6–7.29; p ¼ 0.001) and preterm labor (OR 1.92; 95% CI 1.32-–2.8; p ¼ 0.001). In addition, having a diagnosis of an anxiety disorder was found to be an independent risk factor for cesarean section (adjusted OR 2.5; 95% CI 1.82–3.46; p50.001), using another multivariable model. No association was noted between anxiety disorders and adverse neonatal outcomes including small for gestational age, low Apgar scores and perinatal mortality. Conclusion: Anxiety disorders are independent risk factors for spontaneous preterm delivery and cesarean section, but in our population it is not associated with adverse perinatal outcome.
Anxiety disorders, neonatal outcome, obstetric complication
Introduction Anxiety disorders have been distinctly defined according to DSM-IV diagnostic criteria: They include panic disorder, agoraphobia, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder and phobias [1]. Anxiety disorders are characterized by prominent symptoms of anxiety and worrying that are unproportional to circumstances and persist in a patient for the majority of at least six months prior to diagnosis. Controversy and difficulty exists regarding its distinction from mood disorders such as major depression [2]. Data regarding the prevalence of anxiety disorders is inconclusive. Different definitions of anxiety disorders account for a wide variability in the reported prevalence that ranges from as low as 1.6% to as high as 28.8%. In a large population-based study (the National Institute of Mental Health Epidemiologic Catchment Area study), anxiety disorders were more prevalent than any other mental disorder (8.3% of the population). Also, Kim et al.
*Authors Pavlov and Steiner are equal contributors. Address for correspondence: Eyal Sheiner, MD, PhD, Department of Obstetrics and Gynecology, Soroka University Medical Center, POB 151, Beer Sheva 84101, Israel. E-mail: [email protected]
History Received 27 July 2013 Revised 7 October 2013 Accepted 19 October 2013 Published online 26 November 2013
have reported a prevalence of anxiety of 10% during pregnancy in patients from Minnesota [2–5]. Few studies found an association between anxiety disorders in women of childbearing age and some adverse obstetrical complications and fetal and neonatal outcomes [6–15]. Alder et al [6], in a review of 35 studies that were published between the years 1990–2005 have reported that depression and anxiety were associated with adverse obstetric outcomes and had implications for fetal and neonatal wellbeing and behavior. However, the authors declared that conclusions regarding the impact of anxiety and mood disorders are limited due to methodological problems [6]. Studies of the relationship between anxiety disorders and obstetrical and neonatal complications are inconclusive and sometimes contradictive. However, the most common obstetrical complications reported are preterm labor, hypertensive disorders, cesarean mode of delivery and an increased perception of pain during labor [6–15]. In terms of neonatal complications small for gestational age and low Apgar scores were the most studied complications related to anxiety disorders [16–20]. In an attempt to add to the current data regarding these common and important diagnoses, the aim of the present study was to examine whether patients with a diagnosis of an anxiety disorder are exposed to a higher risk for adverse obstetrical and neonatal complications.
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Materials and methods Setting The study was conducted at the Soroka University Medical Center, the sole tertiary hospital in the Negev, the southern region of Israel, serving the entire obstetrical population. Thus, the study represents non-selective population-based data. The Institutional Review Board (in accordance with the Helsinki declaration) approved the study. Study population The study population was composed of all patients who delivered between the years 1989–2010. Patients with multiple pregnancies and those lacking prenatal care were excluded from the analysis. Study design A retrospective study was conducted, comparing pregnancy outcome of patients with and without a diagnosis of an anxiety disorder. Data regarding the diagnosis of anxiety disorder were recorded by the admitting physician from the referral information. The diagnosis was made according to the charts, by a psychiatrist or a family physician. All current anxiety disorders diagnoses were included. Pregnancy complications and adverse outcomes were available from the perinatal database of the center. Data were reported by an obstetrician immediately after delivery. Skilled medical secretaries routinely reviewed the information prior to entering it into the database. Coding was performed after assessing the medical prenatal care records together with the routine hospital documents. The following demographic and clinical characteristics were evaluated: maternal age, ethnicity (Jewish or Bedouin), gravidity, parity, smoking, gestational age at delivery. Obstetrical complications that were examined included: recurrent abortions, hypertensive disorders, diabetes mellitus, previous cesarean section, anemia, polyhydramnios, oligohydramnios, intrauterine growth restriction, placenta previa. Data that were recorded regarding labor included preterm labor, preterm premature rupture of membranes (PROM), placental abruption, induction of labor, use of epidural, cesarean section and postpartum hemorrhage (PPH). The following perinatal outcomes were assessed: birth weight and fetal gender, low Apgar scores at 1 and 5 min (57) and perinatal mortality. Statistical analysis Statistical analysis was performed using the SPSS package (SPSS, Chicago, IL). Statistical significance was calculated using the chi square test for differences in qualitative variables and the Student’s t-test for differences in continuous variables. A multiple logistic regression model was used to investigate the independent association between anxiety disorders and maternal age, ethnicity, smoking, induction of labor, preterm labor, cesarean section, hypertensive disorders, diabetes mellitus and PROM (controlling for confounders that were found statistically and clinically significant in the univariate analysis).
J Matern Fetal Neonatal Med, 2014; 27(13): 1339–1342
Odds ratio (OR) and their 95% confidence intervals (CI) were computed. A value of p50.05 was considered statistically significant.
Results During the study period 256 312 singleton deliveries have occurred in our hospital, out of which 224 (0.09%) have occurred in patients with a recorded diagnosis of an anxiety disorder. Table 1 presents a comparison of clinical and demographic characteristics of patients with and without a diagnosis of an anxiety disorder. Patients with anxiety were older than the comparison group and had a tendency to smoke. In addition, a significantly higher rate of patients were of Jewish ethnicity. Table 2 presents a comparison of the prevalence of obstetric complications between patients with and without anxiety disorders. Patients with a diagnosis of an anxiety disorder had a significantly higher incidence of hypertensive disorders, diabetes mellitus, anemia and previous cesarean sections. Labor complications and outcomes of patients with and without anxiety disorders are presented in Table 3. Patients with a diagnosis of anxiety had a significantly higher prevalence of labor complications such as premature rupture of membranes, preterm delivery, induction of labor, PPH and cesarean section. In addition, patients with anxiety used more epidural analgesia. Neonatal outcomes such as birth weight, low Apgar scores (57) at 1 and 5 min or perinatal mortality did not differ between the groups (Table 4). Table 1. Clinical characteristics of women with and without anxiety disorders.
Characteristics Maternal age in years (mean) Parity 1 2–4 5þ Ethnicity Bedouins Jewish Smoking
Anxiety N ¼ 224
No Anxiety N ¼ 256 088
32.17 5.15
28.56 5.9
18.3% (41) 57.6% (129) 24.1% (54)
23.5% (60 223) 50.9% (130 226) 25.6% (65 608)
21.0% (47) 79% (177) 7.1% (16)
50.5% (129 246) 49.5% (126 842) 1.1% (2717)
OR
p value 50.001
0.091
3.837
50.001
7.173
50.001
Table 2. Obstetric complications of patients with and without anxiety disorders.
Characteristics Previous cesarean delivery Recurrent abortions Hypertensive disorders Diabetes mellitus Anemia (Hb510 mg/dL) Polyhydramnios Oligohydramnios Intra uterine growth restriction
Anxiety N ¼ 224 16.5% 6.7% 9.8% 9.8% 42% 4.5% 1.8% 2.2%
(37) (15) (22) (22) (94) (10) (4) (5)
No Anxiety N ¼ 256 088 12.2% 5.2% 5.5% 5.7% 28.2% 3.5% 2.3% 2.1%
(31 282) (13 409) (14 009) (14 480) (72 266) (9075) (5933) (5283)
OR
p value
1.422 0.049 1.299 0.327 1.882 0.004 1.817 0.007 1.839 50.001 1.272 0.456 0.767 0.597 1.084 0.859
Pregnancy in women with anxiety disorders
DOI: 10.3109/14767058.2013.858242
Table 3. Labor complications and outcomes of patients with and without anxiety disorders. Anxiety N ¼ 224
No Anxiety N ¼ 256 088
OR
11.2% (25)
6.4% (16 282)
1.850
0.003
14.3% (32)
8% (20 511)
1.316
0.001
2.539 2.95 2.083 4.616
50.001 50.001 50.001 50.001
Characteristics Mechanical induction of labor Premature rupture of membranes Epidural anesthesia Caesarian section Preterm labor below 37 w Post-partum hemorrhage
29.5% 31.7% 15.2% 2.7%
(66) (71) (34) (6)
14.1 13.6% 7.9% 0.6%
(36 185) (34 807) (20 256) (1518)
p value
Table 4. Neonatal outcome of patients with and without anxiety disorders.
Characteristics Birth weight (g) 52500 2500–4000 44000 Apgar 1 minute 57 Apgar 5 minute 57 Perinatal mortality
Anxiety N ¼ 224 11.2% 84.4% 4.5% 6.7% 2.2% 0.9%
(25) (189) (10) (15) (5) (2)
No Anxiety N ¼ 256 088 8.0% 87.2% 4.8% 6.5% 3% 1.3%
(20 487) (223 298) (12 303) (16 655) (7667) (3452)
OR
p value 0.217
1.032 0.74 0.659
0.907 0.504 0.555
Table 5. Factors associated with anxiety disorders: results from a multiple logistic regression model. Characteristics Maternal age Ethnicity (Jewish versus Bedouins) Smoking Induction of labor Preterm labor 537w Hypertensive disorders Diabetes mellitus PROM
OR
95% CI
p value
1.087 3.04 4.51 1.13 1.92 1.42 1.08 1.627
1.06–1.11 2.12–4.22 2.6–7.29 0.84–1.51 1.32–2.80 0.89–2.3 0.69–1.70 1.11–2.38
50.001 50.001 50.001 0.428 0.001 0.133 0.724 0.012
Table 5 shows a multiple logistic regression model that was constructed in order to identify factors that are independently associated with anxiety disorders. Anxiety disorders remained independently associated with advanced maternal age, Jewish ethnicity, smoking and preterm labor. The association between anxiety disorders and hypertensive disorders and diabetes mellitus lost its significance. Another multivariable logistic regression model was constructed, with cesarean section as the outcome variable. The model included anxiety disorders in addition to other confounders that are known to be related to a higher risk for cesarean section such as maternal age, placental abruption, induction of labor, gestational age, previous cesarean section, hypertensive disorders, ethnicity and diabetes mellitus. Having a diagnosis of an anxiety disorder was found to be an independent risk factor for cesarean section (adjusted odds ratio 2.5; 95% CI 1.82–3.46; p50.001).
Discussion The current population-based study was aimed to examine the effect of anxiety disorders on adverse pregnancy and perinatal
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outcomes. Anxiety disorder was found to be independently related to common obstetric and labor complications such as preterm birth, premature rupture of membranes and delivery by cesarean section. In general, current literature regarding the effects of anxiety disorders on obstetric and neonatal complications is rather confusing and inconclusive. In our study even after controlling for confounders, higher rates of preterm deliveries were recorded in patients that were diagnosed with anxiety disorders. Our results correlate with several previous studies [7–9]. Sanchez et al. [7] performed a case-control study that included 480 patients with preterm labor and 479 controls. They found a correlation between the severity of the anxiety disorder and the risk for preterm delivery [7]. The same positive correlation was also found by Martini et al. [8] who studied obstetric complications of 992 patients following an assessment for presence of anxiety disorder and self predictive distress [8]. Nevertheless, in a study performed by Maina et al. [10] a relatively small group of 178 patients was studied; out of which only 20 patients had psychiatric disorders (13 defined as anxiety). In their study, no correlation was found between anxiety disorders and preterm labor, but the numbers were probably too small for conclusive results [10]. Controversy exists regarding the association between anxiety disorders and the mode of delivery. While several studies found higher rates of cesarean delivery (either elective or emergency) in patients with a diagnosis of anxiety disorders [8,11,12], other studies did not demonstrate this correlation [13,14]. In our study anxiety disorder was noted as an independent risk factor for delivering by cesarean section, even after careful analysis controlling for major important confounders. There is general agreement regarding the extended use of epidural analgesia by patients with anxiety disorders [6,11,12]. Our data is in agreement with previous studies. Andersson et al. [11] studied 1495 patients with a diagnosis of depressive and anxiety disorders and did not demonstrate a correlation between anxiety disorders and the development of preeclampsia latter in pregnancy [11]. Nevertheless, Kurki et al. [15] studied 623 patients out of which 99 were diagnosed with anxiety disorders (19%) early in pregnancy. The authors found anxiety disorders to be associated with the development of preeclampsia in pregnancy. In this study, detection rate of depression and anxiety disorders were relatively high and based on a single questioner [15]. Interestingly, while using multivariable analysis, the association between anxiety disorders and hypertensive disorders lost its significance in the current analysis. Few studies have reported the neonatal outcomes of patients with anxiety disorders and showed contradicting results: While some studies reported no correlation between anxiety disorders and small for gestational age infants [16–19], others reported a positive correlation [20]. In our study, we did not find a significant association between anxiety disorders and small for gestational age fetuses. Regarding Apgar scores, our results support previous studies reporting no association between low Apgar scores and anxiety disorders [18,19]. Perinatal mortality was not found to be increased in patients with anxiety disorders, thus a
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diagnosis of an anxiety disorder in a patient is not associated with higher rates of neonatal complications. Our study offers several strengths; the relatively large sample size allowed us to add significant data to current knowledge regarding these complications. In addition, data for the study were based on a computerized database collected by physicians and based on patient’s evaluation. Nevertheless, our study suffers from several weaknesses; one is that we do not have data regarding the criteria used for the diagnosis of the different anxiety disorders. Potential differences may exist between different definitions and criteria used for the diagnosis of anxiety disorder. Another potential weakness is that some undiagnosed women with anxiety disorders are included in the general population group, an assumption which is reinforced by the fact that the prevalence of diagnosed anxiety disorders is smaller than described in the literature. Cases were located from the computerized database of our center, where data were recorded by the admitting physician based on the patient’s referral information. Perhaps only the most severe cases received a diagnosis of an anxiety disorder and a proportion of patients with milder disease on the one hand or with untreated anxiety disorders on the other hand were missed. Finally, a weakness inherent to retrospective cohort studies is the potential for missing data. However, the data were reported by an obstetrician directly after delivery. Skilled medical secretaries routinely reviewed the information prior to entering it into the database. Coding was done after assessing the medical prenatal care records together with the routine hospital documents. Women lacking prenatal care were excluded from the study analysis. This makes this potential source of selection bias less likely. In conclusion, according to the results of our study, anxiety disorders are independently related to preterm labor, premature rupture of membranes and the risk for cesarean delivery. However, the patient can be reassured that the perinatal outcomes are comparable to the general population. When assessing a patient with anxiety disorder physicians should consider these complications and consult the patient accordingly. Further studies are needed in order to assess the rate of complications associated with the different type of anxiety disorders and the effects of treatment for anxiety on these adverse outcomes.
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