General Hospital Psychiatry 35 (2013) 492–496

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General Hospital Psychiatry

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Do psychiatric disorders continue during pregnancy in women with hyperemesisgravidarum: a prospective study

Bilge Burçak Annagür, M.D. a,⁎, Aybike Tazegül, M.D. b, Sule Gündüz, M.D. a

a Department of Psychiatry, Faculty of Medicine, Selcuk University, Konya 42131, Turkeyb Department of Obstetrics and Gynecology, Faculty of Medicine, Selcuk University, Konya 42131, Turkey

a b s t r a c ta r t i c l e i n f o

⁎ Corresponding author. Selçuk Üniversitesi, Tıp FakKonya, Turkey. Tel.: +90 332 2244019.

E-mail addresses: bilgeannagur@yahoo.com (B.B. Anaybiketzgl@hotmail.com (A. Tazegül), dr.sule.gunduz@h

0163-8343/$ – see front matter. Crown Copyright © 20http://dx.doi.org/10.1016/j.genhosppsych.2013.05.008

Article history:

Received 18 March 2013Revised 23 May 2013Accepted 28 May 2013

Keywords:Hyperemesis gravidarumDepressionAnxietyPsychiatric etiology

Objective: We aimed to determine Axis I psychiatric disorders in women with hyperemesis gravidarum(HG) and to follow up the course of psychiatric disorder and its association with nausea and vomiting (NV)during pregnancy.Methods: The study sample was composed of 47 patients with HG. Psychiatric interviews were conductedusing the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition(SCID-I). Other psychiatric interviews were performed in the second and third trimesters. On each visit, thesubjects completed the Beck Depression Inventory and the Beck Anxiety Inventory.Results: The prevalence of any anxiety disorder was 25.5%, and the prevalence of anymood disorder was 14.9%in women with HG in the first trimester. Psychiatric disorders continued throughout the pregnancy in two

thirds of the women who had HG and a psychiatric diagnosis. Any SCID diagnosis in the first trimester washigher in women whose NV had partially resolved than in women whose NV had fully resolved (Pb .05).Conclusion: The present studies suggest that psychiatric disorders may play a significant role in the etiologyof HG. Our findings presented a potential connection between HG and anxiety disorders and majordepressive disorder. Additionally, the NV symptoms in women with HG and a psychiatric disorder maypersist during pregnancy.

Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved.

1. Introduction

Hyperemesis gravidarum (HG) affects 0.5–2% of pregnant women,and 10% of those diagnosed will require at least one inpatienthospitalization [1]. HG, characterized by intractable nausea andvomiting (NV), begins in the first trimester and causes weight lossduring pregnancy, dehydration, electrolyte disturbance and nutritiondeficiency [2,3]. HG is differentiated from the NV common duringpregnancy that affect approximately 75% of pregnant women by theneed for hospitalization [2].

The pathogenesis of HG has not yet been clearly identified. Someendocrine factors (such as human chorionic gonadotropin, estro-gens, progesterone and thyroid hormone), gastrointestinal dysfunc-tion, hepatic abnormalities, autonomic nervous dysfunction andpsychosomatic causes may play a role in this medical condition [4].Despite the common psychiatric symptoms observed in womenwith HG, in these subjects, the psychiatric etiology is unclear. Manystudies have evaluated the relationship between HG and psychiatricdisturbances; however, most studies evaluated psychiatric symp-

ültesi, Psikiyatri AD, Selçuklu-

nagür),otmail.com (S. Gündüz).

13 Published by Elsevier Inc. All rig

toms based on self-report measures and had many limitations [5–10]. Mazzotta et al. suggested that depressive symptoms inpregnant women were associated with more severe NV [5]. Tan etal. showed that anxiety and depressive symptomatology is commonin HG and that risk factors can be identified [10]. However,psychiatric symptom scales were used in these studies, and thesescales have low clinical value. A retrospective study reported thatwomen with HG had more frequent psychiatric diagnoses precedingthe pregnancy compared to the control subjects [8]. In a clinic-based study, Uguz et al. [11] reported that the prevalence of anymood disorder and any anxiety disorder in women with HG was15.4% and 36.5%, respectively. Moreover, the researchers deter-mined that 36.5% of the patients with HG had at least onepersonality disorder [11]. However, the recent study was cross-sectional and did not show prospective features of psychiatricdisorders in women with HG.

Despite the frequency of Axis I psychiatric disorders, data on theeffect of these disorders in women with HG are limited [8,11]. Inaddition, few studies have been based on a structured clinicalinterview. To our knowledge, no prospective study based onpsychiatric interviews from the first trimester to the third trimesterof pregnancy has been published in the literature. Consequently, weaimed to determine Axis I psychiatric disorders in women with HGand to follow up the course of psychiatric disorder and its associationwith NV during pregnancy.

hts reserved.

Table 1The prevalence rates of psychiatric disorders in women with HG (n=47) in the firstrimester

Psychiatric disorders, n (%) Women with HG (n=47)

Any mood disorders 7 (14.9)Major depression 7 (14.9)Bipolar disorder 0 (0)Dysthymia 0 (0)

Any anxiety disorders 12 (25.5)GAD 6 (12.8)Social phobia 1 (2.1)PD 4 (8.5)Specific phobia 2 (4.3)Obsessive compulsive disorder 0 (0)Posttraumatic stress disorder 0 (0)

Any eating disorders 0 (0)

493B.B. Annagür et al. / General Hospital Psychiatry 35 (2013) 492–496

2. Methods

2.1. Setting and sample

The study was a prospective follow-up study of the course ofpsychiatric disorder in pregnant women with HG. The number of thestudy group was determined with the patients hospitalized to ourclinic with a 1-year period. Data were collected from April 2011 toDecember 2012, the period during which 49 pregnant women withHG were invited to follow up in each trimester. The patients wereselected among women with HG hospitalized at the ObstetricInpatient Clinic of Selcuk University Hospital. The study was approvedby the Selçuk University Medical Faculty's Ethics Committee. Thestudy's objectives and procedures were explained, and writteninformed consent was given in accordance with the Declaration ofHelsinki.

The criteria for inclusion were age 20–40 years and the ability tocommunicate and to read and write Turkish. The exclusion criteriawere severe medical illnesses (e.g., uncontrolled endocrine abnor-malities, cardiovascular and pulmonary system diseases); gestationalproblems (e.g., imminent abortion, trophoblastic disease and ectopicpregnancy); cognitive incompetence, which can make a psychiatricinterview difficult; and a history of schizophrenia or related psychoticdisorders.

Initially, 49 women with HG were screened in the obstetric clinic.Patients who did notmeet the study's criteria (n=1) and did not wantto participate (n=1) were excluded. Thus, 47 consecutive patientswere included in the study. After the participants' sociodemographicand clinical characteristics were recorded at the obstetric clinic, thepatients were referred to the psychiatry department. Gestationalweek was detected with ultrasound screening based on the date oflast menstruation. Psychiatric interviews were conducted using theStructured Clinical Interview for Diagnostic and Statistical Manual ofMental Disorders, Fourth Edition (DSM-IV) (SCID-I) at the first visit. Apsychiatrist performed the psychiatric diagnoses. Then two psychiat-ric interviewswere conducted during the second and third trimesters.All of the psychiatric interviews were conducted by one psychiatristwith at least 4 years of experience (Dr. B.B.A.). The first interviewslasted approximately 1–1.5 h. Other two interviews took 30–40 min.On each visit, the subjects completed a Beck Depression Inventory(BDI) and a Beck Anxiety Inventory (BAI) and were evaluated by thesame psychiatrist. Partial resolution of NV was evaluated by theobstetrician (Dr. A.T.) according to the patients' reports and clinicalfeatures such as urine ketone negativity and adequate weight gain.

2.2. Measures

SCID-I is a semistructured interview instrument used to establishAxis I psychiatric disorders according to DSM-IV criteria [12]. Thisinstrument is widely used in clinical practice and for researchpurposes all over the world. The instrument has six modules. Theinterview instruments have been standardized for Turkish popula-tions [13].

2.2.1. Beck Depression InventoryThe BDI, a 21-item self-report questionnaire, assesses the severity

of depression. Individuals are asked to rate themselves on a 0–3spectrum (0=“least” and 3=“most”) with a score range of 0–63. Thetotal score is the sum of all items [14]. The Turkish version of the BDIused in this study has been validated in Turkish populations [15].

2.2.2. Beck Anxiety InventoryThe BAI is a 21-item self-report questionnaire. Each item is rated

on a 4-point Likert scale ranging from 0 (“not at all”) to 3 (“severely”).The total score ranges from 0 to 63 [16]. The Turkish version of the BAIused in this study has been validated in Turkish populations [17].

2.3. Statistical analysis

Statistical analysis of the data was performed with SPSS version15.0. Descriptive statistical analyses were also performed. The datawere checked with the Kolmogorov-Smirnov test and normallydistributed. Categorical variables among the study groups werecompared using the χ2 test. For comparisons of continuous variablesamong the study groups, a t test was used.

3. Results

The mean age of the sample (n=47) was 27.38±5.27 years. Allparticipants were married. Most of the participants were unemployed(n= 45, 93.8%) and primary school graduates (n=29, 61.7%). Themean duration of pregnancy was 8.4±1.62 weeks, the mean numberof pregnancies was 2.3±1.43 (1–7) and the mean number of childrenwas 1.0±0.99. All the women were in the first trimester of gestation,17 (36.2%) women were primigravidae, 24 (51.1%) women had HGhistory in their prior pregnancy and 10 (21.3%) women had a historyof abortion. Most of the women were pregnant with singletons (n=44, 93.6%).

Of the women with HG, 15 (31.9%) met the criteria for at least onemood or anxiety disorder; 5 (10.6%) met the criteria for at least twodisorders according to SCID-I. Among thewomenwith HG, the currentprevalence of any anxiety disorder and any mood disorder was 25.5%(n=12) and 14.9% (n=7), respectively. The most common specificpsychiatric diagnoses were major depressive disorder (MDD; n=7,14.9%), generalized anxiety disorder (GAD; n=6, 12.8%) and panicdisorder (PD; n=4, 8.5%). None of the participants had a diagnosis ofbipolar disorder, cyclothymia, obsessive compulsive disorder, post-traumatic stress disorder, eating disorder or alcohol and othersubstance use. Table 1 shows the prevalence rates of mood andanxiety disorders in women with HG.

Among the patients with HG and a psychiatric diagnosis, 11(73.3%) described that the onset of psychiatric disorders occurredbefore pregnancy. One woman was excluded from follow-up becauseshe miscarried in the second trimester. This woman had nopsychiatric disorder in her first trimester. After the patients dischargefrom the hospital, we applied monthly supportive psychotherapy andbehavior modification (e.g., no caffeine, sleep hygiene, daily walks) tothe women with HG and comorbid depression/anxiety articulated.Three out of seven women diagnosed with depression agreed to usean antidepressant. These patients were given a selective serotonin re-uptake inhibitor (SSRI) after 20 weeks. One patient did not tolerateantidepressant therapy and stopped on the 5th day. Two otherpatients diagnosed with depression benefited from antidepressanttherapy, and clinical improvement was observed. The treatment planincluded monthly supportive psychotherapy and behavioral modifi-cations for women who did not agree to use SSRIs. None of thepatients with anxiety disorder agreed to use an SSRI. A similar therapy

t

05

101520253035404550

Women withoutpsychiatricdisorders

Women withpsychiatricdisorders

Fig. 1. The number of women whose NV had partially resolved and the number of thewomen who received a psychiatric diagnosis during the pregnancy.

494 B.B. Annagür et al. / General Hospital Psychiatry 35 (2013) 492–496

plan was also recommended for these patients. The follow-up resultsfor the women with HG and a psychiatric diagnosis are presented inTable 2.

Initially, we found that 15 women had at least one psychiatricdiagnosis. We observed that psychiatric disorders continued in 9 outof 15 patients in the third trimester. These 9 patients' psychiatricconditions began prior to pregnancy. NV continued in 22 (46.8%)women out of all in the second trimester, which was not as severe asin the initial trimester. Among the women with HG and a psychiatricdiagnosis, 10 (66.6% of women with HG and a psychiatric diagnosis)observed that NV had continued in the second trimester. In the thirdtrimester, 37 women with HG fully recovered; 9 patients with HG(19.1%) described partial resolution of NV. Among these women, 6had at least one psychiatric diagnosis; 2 patients had MDD andcomorbid GAD, 1 patient had GAD, 2 patients had PD and 1 patient hadspecific phobia. All of the patients were followed up as outpatients.During follow-up, the patients were not hospitalized for psychiatric ormedical purpose. The follow-up results for the women with HG and apsychiatric diagnosis are shown in Table 2. The number of womenwhose NV had partially resolved and the number of the women whoreceived a psychiatric diagnosis is shown in Fig. 1.

The mean BDI scores for the first, second and third trimester in allwomen were 15.38±9.18, 11.32±6.51 and 10.26±5.98, respectively.The mean BAI scores for the first, second and third trimester in allwomenwere 17.38±12.58, 14.64±9.58 and 13.02±9.07, respectively.The mean depression and anxiety scores in women with HG for eachtrimester are shown in Fig. 2. The women were divided into twogroups. The first group included women whose NV had partiallyresolved (n=9), and the second group included women whose NVhad fully resolved (n=37) at the end of the follow-up period. Therewas no significant difference between the two groups regardingsociodemographic and obstetric characteristics. A significant differ-ence among the two groups was found for the Beck Depression scorein the first trimester (BDI-1; Pb .05) and the Beck Anxiety score(Pb .05) in the third trimester (BAI-3). We found no significantdifference between the two groups for BAI-1 and BDI-3. Additionally,any SCID diagnosis in the first trimester was higher in the first groupthan in the second group (77.8% versus 21.6%; Pb .05). The BDI and

Table 2The follow-up results for the women with HG and a psychiatric diagnosis

Diagnoses I. Trimester II. Trimester (NV) III. Trimester (NV)

Major depressionCase 12a + + –

Case 16 + + (NV±) + (NV±)Case 23a + + –

Case 24 + + (NV±) + (NV±)Case 27 + − (NV±) –

Case 36 + – –

Case 46 + − (NV±) –

Generalized anxiety disorderCase 16 + + (NV±) + (NV±)Case 19 + + (NV±) +Case 22 + + (NV±) + (NV±)Case 23a + + +Case 24 + + (NV±) − (NV±)Case 32 + – –

PDCase 2 + + (NV±) + (NV±)Case 12a + + –

Case 25 + − (NV±) –

Case 29 + + (NV±) + (NV±)Specific phobiaCase 2 + + (NV±) + (NV±)Case 33 + + (NV±) + (NV±)Social phobiaCase 21 + + +

+, exist of disorder; −, no exist of disorder; NV±, partial resolution of NV.a Patients used an SSRI.

BAI scores for the women whose NV had partially resolved and fullyresolved at the end of the follow-up period are shown in Table 3.

4. Discussion

The main finding of this study is that one third of the women withHG had at least one psychiatric diagnosis, and the prevalence rateswere higher than the rates for women in the general population [18–21]. Psychiatric disorders continued throughout the pregnancy in twothirds of the women with HG and a psychiatric diagnosis. Similarly,two thirds of the women with NV throughout their pregnancy had apsychiatric diagnosis. Our findings suggested that psychiatric disor-ders may play a significant role in the etiology of HG.

Although psychiatric disorders were observed in women with HG,the causal relationship between HG and psychiatric disorders isunclear. Tan et al. [10] noted that the psychological distress observedin women with HG was secondary to the physical illness rather thanthe driver in the pathogenesis of HG. Simpson et al. [22] suggestedthat, compared to women without HG, women with HG havesignificantly higher psychological symptom levels during pregnancy,but there were no significant differences between the subjects withHG and the controls after pregnancy. Bozzo et al. [23] examinedwhether pregnant women, diagnosed with depression pre-concep-tionally, treated with an antidepressant, reported a higher incidenceof NV when compared with pregnant women without depression.They reported that depression and treatment with antidepressantsprior to and in early pregnancy does not appear to affect the incidenceof NV. Uguz et al. [11] reported that mood and anxiety disorders andpersonality disturbances are frequently observed among womenwithHG and that there is a potential relationship between thesepsychiatric disorders and HG during pregnancy. However, theavailable studies on the topic have deficient methodological designs

15.38

11.3210.26

17.38

14.64

13.02

0

2

4

6

8

10

12

14

16

18

20

I.Trimester II.Trimester III.Trimester

BDI

BAI

Fig. 2. The mean BDI and BAI scores in women with HG for each trimester.

Table 3Beck Depression (BDI) and Beck Anxiety (BAI) scores for the women whose NV hadpartially resolved and fully resolved at the end of the follow-up period

Women had partiallyresolved (n=9)

Women had fullyresolved (n=37)

P value

BAI-1 28.0±19.89 14.62±8.78 0.081a

BDI-1 23.11±11.0 13.64±7.87 0.005a

BAI-2 21.77±15.39 12.75±6.88 0.121a

BDI-2 15.77±9.39 10.32±5.31 0.127a

BAI-3 21.55±13.22 10.94±6.44 0.044a

BDI-3 15.11±9.15 9.08±4.33 0.087a

Any SCID, n (%) 7 (77.8) 8 (21.6) 0.001b

BAI-1, Beck Anxiety score in the first trimester.BDI-1, Beck Depression score in the first trimester.BAI-2, Beck Anxiety score in the second trimester.BDI-2, Beck Depression score in the second trimester.BAI-3, Beck Anxiety score in the third trimester.BAI-3, Beck Anxiety score in the third trimester.Any SCID, any psychiatric diagnose in the first trimester.

a t test.b χ2 test.

495B.B. Annagür et al. / General Hospital Psychiatry 35 (2013) 492–496

such as cross-sectional studies or self-questionnaires [9–11,22]. Toour knowledge, this is the first prospective study based on psychiatricinterviews from the first trimester to the third trimester of pregnancy.We determined that one third of the women with HG had at least onepsychiatric disorder in the first trimester. In the second trimester andin the third trimester, the rates of psychiatric disorders in womenwhose NV partially recovered were one half and two thirds,respectively. A high percentage of our sample with psychiatricdiagnoses and NV continued to report both conditions in the thirdtrimester. These findings suggest that the NV symptoms in womenwith HG and a psychiatric disorder may persist during pregnancy.

In a previous study, Seng et al. [8] reported that, whileapproximately 12% of women with HG had a psychiatric diagnosispreceding pregnancy, this rate was 5.4% in the control subjectswithout HG. In contrast, Uguz et al. [11] indicated that, according toreports by women with HG, most current psychiatric diagnosesoccurred before pregnancy (70.5%). Similarly, in our sample, most ofthe current psychiatric diagnoses occurred before pregnancy (73.3%).Furthermore, the women who continued to have HG and depression/anxiety into the third trimester were from this group. Additionally,only 26.7% of women with HG and a psychiatric diagnosis describedan onset of the psychiatric disorder after hyperemesis. Moreover,most of the womenwhose NV had partially resolved had a psychiatricdiagnosis in the third trimester. These findings suggest thatpsychiatric disorders may be associated with the occurrence or thecontinuation of HG in pregnant women. However, we did not use anyvalid and reliable tools for NV. Partial resolution of NV was evaluatedaccording to the patients' reports in this study [24,25]. It should bestated that our sample may not be representative of all HG patientsbecause we have included only the patients requiring hospitalization.The relatively small sample size is another limitation of the study.However, we did not evaluate women with a psychiatric disorder inthe postpartum period. To consider the complex effects of thepostpartum period, women with a psychiatric diagnosis may requirelong-term follow-up. These conditions are some limitations in theinterpretation of our results regarding a possible causal relationshipbetween HG and psychiatric disorders. Another limitation is that wedid not include a control group of pregnant women without HG.

In symptom-based studies, anxiety and depressive symptomswere frequently observed in women with HG [7,10]. Although themost common specific psychiatric diagnosis was MDD, anxietydisorders were more common than mood disorders in our study.The rate of anxiety disorders was 25.5% and the rate of mood disorderwas 14.9% in the study samples. The depression and anxiety scoreswere consistent with these findings. The most common anxiety

disorders were GAD and PD in the study. Uguz et al. found that therate of anxiety disorders was higher than mood disorders in womenwith HG [11]. The authors reported that the most common anxietydisorders were GAD and obsessive compulsive disorder. In our study,the rate of GAD was similar to that in the study of Uguz et al., but therates of other anxiety disorders were not consistent with the findingsof that study. Patients with HG experience intense physical symptomsand this condition may be confused with an anxiety disorder. Patientswith PD or GAD are more sensitive to bodily changes [26]. Physicalsymptoms can also trigger the onset of a specific anxiety disorder suchas PD and GAD. Findings of this prospective study support theexistence of a two-way relationship between HG and psychiatricdisorders. However, distinguishing the primary etiology of thediseases is difficult.

In conclusion, HG is a medical condition that has a psychiatricetiology as much as a genetic and hormonal etiology [11,27]. Ourfindings show that psychiatric disorders may play a significant role inthe etiology of HG. Therefore, we suggest a potential connectionbetween HG and anxiety disorders and MDD. Despite the commonbelief that NV is a phenomenon of early pregnancy, NV symptoms canpersist into the third trimester. Additionally, the NV symptoms inwomen with HG and psychiatric disorder may persist duringpregnancy. Women with persistent NV during pregnancy should beevaluated in terms of psychiatric disorders as much as their medicalconditions. Psychiatric liaison is important in these women topromote optimal management, care and support for these women.Further study should focus on the effective treatment measures andthe neonatal outcomes of women with HG and psychiatric disorders.

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