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EURO-6842; No of Pages 6 European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2010) xxx–xxx

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European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb

Anxiety and depression in hyperemesis gravidarum: prevalence, risk factors and correlation with clinical severity Peng Chiong Tan *, Subramaniam Vani, Boon Kiong Lim, Siti Zawiah Omar Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Wilayah Persekutuan, Malaysia

A R T I C L E I N F O

A B S T R A C T

Article history: Received 14 April 2009 Received in revised form 20 October 2009 Accepted 22 December 2009

Objective: To evaluate prevalence, risk factors and clinical severity correlates of anxiety and depression caseness in hyperemesis gravidarum (HG). Study design: A prospective study of self-assessment using the Hospital Anxiety and Depression Scale (HADS) was performed. Women at their first hospitalization for HG were recruited as soon as possible after hospital admission. Cut-off at the score of 7/8 was used for both the anxiety and depression subscales of HADS to denote anxiety and depression caseness respectively. Risk factors for anxiety and depression caseness were identified using Chi-square test, Fisher’s exact test, Mann–Whitney’s U-test or the Student’s t-test. Multivariable logistic regression analysis incorporating all co-variables with crude P < 0.1 was performed to identify independent risk factors. Bivariate analyses were performed to identify associations between clinical markers of severity and anxiety and depression caseness. Prolonged hospitalization and a number of biochemical and hematological abnormalities were used as clinical markers of HG severity. Results: Criteria for anxiety and depression caseness were fulfilled in 98/209 (46.9%) and 100/209 (47.8%) women respectively. 78 (37.3%) participants fulfilled the criteria for both anxiety and depression caseness, 89 (42.6%) neither, 20 (9.6%) anxiety caseness only and 22 (10.5%) depression caseness only. Gestational age at commencement of vomiting, duration of vomiting leading up to hospitalization and paid employment status had crude P < 0.1 in association with anxiety caseness. After adjustment, only paid employment was independently associated with anxiety caseness (AOR 2.9 95% CI 1.3–6.5; P = 0.009). Previous miscarriage, gestational age at commencement of vomiting and duration of vomiting leading up to hospitalization all had P < 0.1 in association with depression caseness. After adjustment, only previous miscarriage was negatively associated with depression caseness (AOR 0.4 95% CI 0.2–0.9; P = 0.022). There was no marker of HG severity associated with anxiety caseness on bivariate analysis. High hematocrit was associated with depression caseness (OR 2.1 95% CI 1.1–3.9; P = 0.027). Conclusion: Anxiety and depression caseness is common in HG and risk factors can be identified. There is no convincing association between anxiety and depression and more severe illness. Psychological symptoms may be a response to physical illness but further studies are needed. ß 2009 Elsevier Ireland Ltd. All rights reserved.

Keywords: Hyperemesis gravidarum Hospital Anxiety and Depression Scale Employment Miscarriage

1. Introduction Hyperemesis gravidarum (HG) occurs in 0.3–2% of pregnancies [1]. HG is characterised by intractable nausea and vomiting due to pregnancy, resulting in dehydration and metabolic and biochemical disturbances [2]. HG is empirically differentiated from the commoner nausea and vomiting of pregnancy (NVP) which affects up to 80% of pregnancies [3] by the need for hospitalization [2,4].

* Corresponding author. Tel.: +60 3 79492059; fax: +60 3 79551471. E-mail addresses: pctan@um.edu.my, tanpengchiong@yahoo.com, tanpengchiong@gmail.com (P.C. Tan).

HG is the second ranked indication for hospitalization during pregnancy in women with live births [5]. Poor maternal weight gain is associated with low birth weight and being small for gestational age [6]. Endocrine associations with HG are often reported, most consistently with high levels of human chorionic gonadotropin, but the etiology and pathogenesis of HG remain uncertain and can be multi-factorial with biologic, psychological and socio-economic antecedents [2]. Historically, nausea and vomiting in pregnancy were thought to have a psychological basis with various rationales propounded, e.g. arising from resentment or ambivalence towards pregnancy due to immaturity of personality, strong mother dependence, anxiety and tension related to pregnancy, a sexual disorder resulting from

0301-2115/$ – see front matter ß 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2009.12.031

Please cite this article in press as: Tan PC, et al. Anxiety and depression in hyperemesis gravidarum: prevalence, risk factors and correlation with clinical severity. Eur J Obstet Gynecol (2010), doi:10.1016/j.ejogrb.2009.12.031


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sexuality aversion, a conversion symptom and a symptom of hysteria, neurosis or depression, but it is also plausible that psychological symptoms are a result of the stress and the physical burden of HG rather than a cause [2]. HG could also be the result of psycho-social stresses, poverty and marital conflicts [2]. Women who terminate their pregnancies secondary to HG often reported perceived inability to care for the family and self, fear that themselves or their baby could die or that the baby would be abnormal as reasons for their decision, signifying the tremendous physical and psychological burden of the disease to them [7]. Women with prior psychiatric or medical conditions are more likely to develop HG when pregnant [8]. In contrast, women with HG were no more likely than controls to have psychological morbidity after birth [9]. Data on the prevalence of risk factors of anxiety and depression states in clearly defined HG cases are not available. It is also not known whether psychological distress adversely impact on the clinical severity of HG. We hypothesise that HG will exacerbate the psychological stress of pregnancy. This may result in anxiety and depression which in turn can have an adverse impact on the severity of HG. We sought to estimate the prevalence and identify of the risk factors of anxiety and depression caseness in women at first hospitalization for HG. We also sought to evaluate the relationship of anxiety and depression caseness with severity of HG as denoted by laboratory and clinical markers. 2. Materials and methods Women diagnosed with hyperemesis gravidarum and hospitalized in the University of Malaya Medical Center from 11 March to 11 November 2008 were identified and approached on hospital admission to enter the study. The patient information sheet was given and queries were answered by the recruiting provider. Patients who agreed to participate gave their written consent. The study was carried out in compliance with the Code of Ethics of the Declaration of Helsinki. Ethical approval and oversight were provided by our institutional review board. The Hospital Anxiety and Depression Scale (HADS) questionnaire comprises 14 stems with four possible answer choices to each stem. Each answer is scored 0–3. It comprises two subscales for anxiety and depression caseness. The HADS has been validated as a useful tool to identify anxiety and depression cases in antenatal patients and gynecology clinic patients (10). The subscale score was summated and cut-off of 7/8 was used for the summated anxiety and depression scores to differentiate between caseness and non-cases [11]. HADS is particularly suited to investigate psychological distress in pregnancy as it does not have questions on somatic symptoms [12] – normal pregnancyrelated physical symptoms might have inflated the score of other scales that incorporated somatic symptoms. The HADS questionnaire and data sheet of personal and socioeconomic characteristics were given to participants for selfcompletion. Oral and written instructions for form filling were provided. The forms were collected within 6 h of admission and checked for completeness. If the questionnaire or data sheet were incomplete, a further request was made for the forms to be completed but it was reiterated that a deliberate choice not to provide specific information would be fully respected. The HADS questionnaire was reviewed and scored. Any clinical concern arising from participants’ responses was followed by a discussion to ascertain appropriateness for formal psychiatric evaluation. Study data were not routinely made available to providers. Inclusion criteria for participation were hospitalization for presumed HG, a positive urine pregnancy test if a very early

pregnancy was not visible on ultrasound or a viable singleton fetus on ultrasound with gestational age < 14 weeks. Women with recurrent admissions for HG to our center were only recruited during their first hospitalization. Women were excluded if they had thyroid disease, gestational trophoblastic disease, psychiatric illness or any other acute confounding illness that could cause nausea or vomiting. Laboratory results and clinical data were abstracted onto the case report form from case notes and computerized laboratory records. Ketonuria [13], renal function and serum electrolytes [14] and full blood count [15] results were used as measures of severity of HG on hospitalization. These investigations were performed before substantive treatment had started. Ketonuria of 3+ to 4+ on urine dipstick was classified as severe. Cut-offs for high urea, creatinine and hematocrit were set to demarcate the upper quartile in our study population for these parameters as pregnancy significantly lowered their range. The laboratory-supplied normal range was used to demarcate low serum sodium, low serum potassium, anemia and leucocytosis. The length of hospital stay was also used as a measure of disease severity: 4 days’ stay was categorised as prolonged as this cut-off demarcated the upper quartile. Standard inpatient management of HG was given to participants. All were initially rehydrated with intravenous fluids, and given intravenous anti-emetics and oral thiamine. Oral intake was resumed based on clinical judgment. Patients were discharged once they were rehydrated and capable of maintaining adequate oral intake. About 50% of women with nausea and vomiting in pregnancy have been reported to have potential psychiatric problems [16]. In a recent report from our center, about 25% required prolonged (4 days) hospitalization at their first admission for HG [15]. Sample size calculation using prolonged hospitalization as the prime marker for clinical severity, a 0.05, power 0.8, 1 to 1 ratio of psychological caseness to non-caseness, applying Fisher’s exact test and factoring in an absolute 20% increase from 25% to 45% for prolonged hospitalization, indicated that 196 women in total were required for a powered study. Statistical analysis was performed using the SPSS 15 (SPSS Inc., Chicago, IL, USA). The one sample Kolmogorov–Smirnoff test was used to assess normality of data distribution. Fisher’s exact test was used for 2  2 categorical data, Chi-square test for larger than 2  2 categorical data sets. The means of normally distributed continuous data were assessed by Student’s t-test. The Mann– Whitney’s U-test was used for non-normally distributed data and ordinal data. Multivariable logistic regression analysis was used to control for co-variables with P  0.1 on bivariate analysis. P < 0.05 on two-sided tests was taken as a level of significance. 3. Results There were a total of 284 admissions to our center for HG over the study period of March–November 2008. The recruitment flow chart (Fig. 1) depicted the movement of all potential participants and their removal from study participation due to criteria exclusions, failure to recruit and refusal to participate. 209/215 (97%) of eligible patients were recruited and analysed. No woman was excluded because of a previous psychiatric history. 98/209 (46.9%) of participants scored 8 on the anxiety component of the HADS and fulfilled the criterion for anxiety caseness. 100/209 (47.8%) similarly fulfilled criterion for depression caseness. There was a strong association and overlap between caseness for anxiety and depression caseness (OR 15.8 95% CI 8.0–31.1; P < 0.001). 78 (37.3%) participants fulfilled the criteria for both anxiety and depression caseness, 89 (42.6%) neither, 20 (9.6%) anxiety caseness only and 22 (10.5%) depression caseness only.

Please cite this article in press as: Tan PC, et al. Anxiety and depression in hyperemesis gravidarum: prevalence, risk factors and correlation with clinical severity. Eur J Obstet Gynecol (2010), doi:10.1016/j.ejogrb.2009.12.031


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Fig. 1. Recruitment flow chart of hyperemesis gravidarum patients into study.

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Results of bivariate analyses performed for the recorded characteristics stratified according to anxiety caseness or depression caseness followed by multivariable logistic regression analyses incorporating and controlling for all co-variables with crude P < 0.1 were shown in Tables 1 and 2 respectively. On bivariate analyses for anxiety caseness, gestational age at commencement of vomiting, duration of vomiting leading up to hospitalization and paid employment status of the participants all had P < 0.1. After adjustment, only paid employment was identified as an independent risk factor for anxiety caseness (AOR 2.9 95% CI 1.3–6.5; P = 0.009). For depression caseness, previous miscarriage, gestational age at commencement of vomiting and duration of vomiting leading up to hospitalization all had P < 0.1 on bivariate analyses. Following adjustment, only previous miscarriage had an independent negative association with depression caseness (AOR 0.4 95% CI 0.2–0.9; P = 0.022). Table 3 shows the results of the bivariate analyses performed separately for anxiety and depression caseness against a number of clinical, metabolic and laboratory markers of severity of HG. There was no marker of HG severity against anxiety caseness on bivariate analysis with a P < 0.05; only hyponatremia (OR 0.6 95% CI 0.3– 1.0; P < 0.073) was borderline for a negative association with

Table 1 Risk factors for high anxiety score (8) using the Hospital Anxiety and Depression Scale in hyperemesis gravidarum. High anxiety score (8) n = 98

Normal anxiety score (7) n = 111

P value

Age

28.2  4.3

28.0  4.7

0.86

Ethnicity Malay Chinese Indian Others Gravidity Parity Nulliparous Previous miscarriage Gestational age at admission (weeks) Gestational age at start of vomiting (weeks) Duration of vomiting at admission (days) Frequency of vomiting (per day) Hyperemesis in a previous pregnancy Medical illnessb Planned pregnancy Previous use of combined contraceptive pill Married Local family support

74 (75.5) 7 (7.1) 15 (15.3) 2 (2.0) 2 [1] 0 [1] 55 (56.1) 15 (15.3) 9.0  2.3 6.4  2.5 14 [21] 7 [5] 34 (34.7) 13 (13.3) 45 (45.9) 16 (16.3) 95 (96.9) 64 (65.3)

78 (70.3) 6 (5.4) 19 (17.1) 8 (7.2) 2 [2] 1 [2] 54 (48.6) 24 (21.6) 9.1  2.3 6.9  2.3 14 [14] 8 [5] 48 (43.2) 15 (13.5) 45 (40.5) 21 (18.9) 109 (98.2) 67 (60.4)

0.33

Incomec Higher income (>RM3000 per month) Low income (RM 3000 per month)

49 (50.5) 48 (49.5)

55 (49.5) 56 (50.5)

1.0

Housing Owned Rented Living in extended family

37 (37.8) 52 (53.1) 9 (9.2)

40 (36.0) 60 (54.1) 11 (9.9)

0.96

Educational attainment Tertiary Up to secondary

59 (60.2) 39 (39.8)

57 (51.4) 54 (48.6)

0.21

Employment Paid Otherd Regular exercise before pregnancy

88 (89.8) 10 (10.2) 34 (34.7)

85 (76.6) 26 (23.4) 41 (36.9)

0.016

AOR (95% CI)a

0.13 0.19 0.28 0.29 0.67 0.08 0.06 0.24 0.26 1.0 0.49 0.72 0.67 0.48

Adjusted P value

0.27 0.31

AOR 2.9 (95% CI 1.3–6.5)

0.009

0.78

Values expressed as mean  standard deviation, number (%) or median [interquartile range]. Student’s t-test was used to analyse continuous data that is normally distributed, Mann–Whitney’s U-test for ordinal data and non-normally distributed continuous data and Fisher’s exact test (2  2 datasets) or Chi-square test (larger than 2  2 datasets) for categorical data. Multivariable logistic regression analysis model incorporated all variables with crude P  0.1 on bivariate analysis. a Adjusted odds ratio AOR (95% Confidence Interval) shown where adjusted P < 0.05. b Medical illness included cases with mainly asthma (15 women), chronic hypertension (4), diabetes (3), combined hypertension diabetes (1) and others (5). c Family income: US $1 = RM3.5. d Included housewives (32 women) and students (4).

Please cite this article in press as: Tan PC, et al. Anxiety and depression in hyperemesis gravidarum: prevalence, risk factors and correlation with clinical severity. Eur J Obstet Gynecol (2010), doi:10.1016/j.ejogrb.2009.12.031


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Table 2 Risk factors for high depression score (8) using the Hospital Anxiety and Depression Scale in hyperemesis gravidarum. High depression score (8) n = 100

Normal depression score (7) n = 109

P value

Age

27.9  4.3

28.2  4.7

0.66

Ethnicity Malay Chinese Indian Others Gravidity Parity Nulliparous Previous miscarriage Gestational age at admission (weeks) Gestational age at start of vomiting (weeks) Duration of vomiting at admission (days) Frequency of vomiting (per day) Hyperemesis in a previous pregnancy Medical illnessb Planned pregnancy Previous use of combined contraceptive pill Married Local family support

78 (78) 5 (5.0) 14 (14.0) 3 (3.0) 1.5 [1] 0 [1] 53 (53.0) 12 (12.0) 9.0  2.3 6.3  2.6 14 [21] 7 [5] 35 (35.0) 12 (12.0) 45 (45.0) 14 (14.0) 97 (97.0) 65 (65.0)

74 (67.9) 8 (7.3) 20 (18.3) 7 (6.4) 2 [2] 0 [2] 56 (51.4) 27 (24.8) 9.1  2.3 7.0  2.2 14 [10.5] 8 [5] 47 (43.1) 16 (14.7) 45 (41.3) 23 (21.1) 107 (98.2) 66 (60.6)

0.38

Incomec Higher income (>RM3000 per month) Low income (RM3000 per month)

52 (52.5) 47 (47.5)

52 (47.5) 57 (52.3)

0.58

Housing Owned Rented Living in extended family

35 (35.0) 55 (55.0) 10 (10)

42 (38.5) 57 (52.3) 10 (9.2)

0.87

Educational attainment Tertiary Up to secondary

60 (60.0) 40 (40.0)

56 (51.4) 53 (48.6)

0.27

Employment Paid Otherd Regular exercise before pregnancy

87 (87.0) 13 (13.0) 38 (38.0)

86 (78.9) 23 (21.1) 37 (33.9)

0.144

0.12 0.51 0.89 0.021 0.78 0.043 0.011 0.63 0.26 0.69 0.68 0.21 0.67 0.57

AOR (95% CI)a

Adjusted P value

AOR 0.4 (95% CI 0.2–0.9)

0.022 0.19 0.32

0.57

Values expressed as mean  standard deviation, number (%) or median [interquartile range]. Student’s t-test was used to analyse continuous data that is normally distributed, Mann–Whitney’s U-test for ordinal data and non-normally distributed continuous data and Fisher’s exact test (2  2 datasets) or Chi-square test (larger than 2  2 datasets) for categorical data. Multivariable logistic regression analysis model incorporated all variables with crude P  0.1 on bivariate analysis. a Adjusted odds ratio AOR (95% Confidence Interval) shown where adjusted P < 0.05. b Medical illness included cases with mainly asthma (15 women), chronic hypertension (4), diabetes (3), combined hypertension diabetes (1) and others (5). c Family income: US $1 = RM3.5. d Housewives (32 women) and students (4).

anxiety caseness. High hematocrit was associated with depression caseness (OR 2.1 95% CI 1.1–3.9; P = 0.027). We approached participants who fulfilled caseness criteria for anxiety or depression with an offer for a formal psychiatric appointment. The offer was not taken up by any woman.

4. Comments Anxiety and depression caseness were common in women affected by HG – more than a third of our participants fulfilled criteria for both anxiety and depression caseness. Almost half the

Table 3 Laboratory and clinical markers of the severity of hyperemesis gravidarum and high anxiety or depression score (8) using the Hospital Anxiety and Depression Scale. High anxiety score (8) n = 98

Normal anxiety score (7) n = 111

P value

High depression score (8) n = 100

Normal depression score (7) n = 109

P value

Prolonged hospitalization (4 days)a

40 (40.8)

35 (31.5)

0.19

40 (40.0)

35 (32.1)

0.25

Ketonuria 3+ to 4+ 1+ to 2+ Hyponatremia (135 mmol/l)b Hypokalemia (3.5 mmol/l)b High urea (3.3 mmol/l)a High creatinine (55 mmol/l)a Anemia (hemoglobin <11.5 g/dL)b High hematocrit (0.41)a Leucocytosis (>11  109/l)b

66 32 46 20 21 31 11 30 35

80 31 66 22 30 24 14 24 35

0.55

68 32 51 23 23 31 8 33 38

78 31 61 19 28 24 17 21 32

0.65

(67.3) (32.7) (46.9) (20.4) (21.4) (31.6) (11.2) (30.6) (35.7)

(72.1) (27.9) (59.5) (19.8) (27.0) (21.6) (12.6) (21.6) (31.5)

0.073 1.0 0.42 0.12 0.83 0.16 0.56

(68.0) (32.0) (51.0) (23.0) (23.0) (31.0) (8.0) (33.0) (38.0)

(71.6) (28.4) (56.0) (17.4) (25.7) (22.0) (15.6) (19.3) (29.4)

0.49 0.39 0.75 0.16 0.13 0.027 0.19

Values expressed as number (%). Fisher’s exact test (2  2 datasets) used for analysis. Multivariable logistic regression analysis was planned incorporating co-variables with crude P < 0.1 on bivariate analyses. a Cut-offs demarcating the upper quartile of values in our study population. b Cut-off values supplied by our hospital laboratory.

Please cite this article in press as: Tan PC, et al. Anxiety and depression in hyperemesis gravidarum: prevalence, risk factors and correlation with clinical severity. Eur J Obstet Gynecol (2010), doi:10.1016/j.ejogrb.2009.12.031


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participants were potential cases for anxiety and a similar proportion for depression caseness. These prevalence rates were higher than that found in unselected antenatal population from Hong Kong who were also assessed with HADS in the first trimester of pregnancy. Their anxiety caseness prevalence rate was 36.3%, depression caseness rate 22.1% and 14.2% had both anxiety and depression caseness [12]. A recent Scottish study on anxiety and depression after miscarriage using HADS but with cut-off set at 10/ 11 shows prevalence rates for anxiety caseness of 28.3% and for depression caseness of 10% 1 month after miscarriage [17]. Reconfiguring our data to reflect HADS subscale cut-off at 10/11, prevalence rates for our HG women were 20.6% and 29.2% respectively for anxiety and depression caseness. This suggests that women hospitalized for HG experienced psychological distress of a similar magnitude to women with a recent miscarriage. We were unable to identify other studies of anxiety and depression in clearly defined HG cases to compare our findings. Paid employment was found to be an independent risk factor for anxiety in our participants. The anxiety felt by women in paid employment seemed to be well placed and perceptive. A recent survey has indicated that 82.8% of women with HG reported negative psycho-social changes: socio-economic consequences involving job loss being an important burden [18]. The median duration of symptoms in our study population was 14 days [interquartile range 14.5] and mean gestational age at hospitalization was 9 weeks. Employees in our country are typically allowed 14 days ‘‘sick leave’’ per year before potentially facing pay reductions. It is well known that vomiting is an early pregnancy problem that resolves in 90% of cases by the 16th week of gestation [3]. It is conceivable that even a relatively short period of illness of about 2 weeks coupled with the perception that they might not completely recover for another few weeks could have raised the anxiety level of women who were in paid employment. We did not pose questions about how much time the women had already taken off work by the time of hospitalization or employment concerns in our study design. No woman in our study population was ‘‘unemployed’’. Those classified as not in paid employment were housewives or students. Hence our finding should be appropriately interpreted. Previous miscarriage was the only independent ‘‘protective’’ factor against depression caseness. Nausea and vomiting in pregnancy have long been known to be strongly associated with reduced risk of miscarriage in early pregnancy as reported by a meta-analysis from 1989 [19]. Vomiting in pregnancy may even be associated with reduced miscarriage risk in threatened miscarriage [20]. However, we did not ascertain whether knowledge about this protective association was widespread in our study population. Awareness that vomiting in pregnancy is associated with reduced risk of miscarriage could account for our finding of previous miscarriage being a protective factor against depression caseness. Of the many markers of laboratory and clinical severity of HG analysed against anxiety and depression caseness, only a high hematocrit on hospitalization was positively associated with depression caseness. No other co-variables reached P < 0.1 against depression caseness. High hematocrit in HG could be secondary to severe dehydration and it has been independently associated with prolonged hospitalization [15]. However, depression caseness was not significantly associated with prolonged hospitalization in our analysis. There was no significant association of any of the severity markers considered with anxiety caseness. There was a borderline negative association between hyponatremia and anxiety caseness (P = 0.07). Given the multiple analyses performed, the isolated association with high hematocrit should be interpreted with caution. Overall there is no convincing pattern of anxiety and

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depression caseness being more associated with more severe HG since many other markers were tested besides hematocrit. A recent report on NVP has concluded that there is an association between anxiety and depression early in pregnancy and severity of nausea and vomiting [21]. Taken in their entirety, our data did not support an association between psychological caseness in HG and a more severe physical illness as characterised by metabolic and biochemical disturbances at presentation or by prolonged hospitalization. Duration of vomiting prior to hospitalization and frequency of vomiting were also not independently associated with psychological caseness. Our findings in women with HG seemed to be different from the aforementioned study on women with NVP. Previous reports evaluating psychology in the etiology and pathogenesis of HG have been conflicting. While a psychiatric history prior to HG is reportedly uncommon, a psychiatric history may increase the risk of HG [8], but psychological disorder commonly resolves simultaneously with physical symptoms [9]. We did not have to exclude any HG cases from the study based on pre-established criteria of prior psychiatric illness, implying that women admitted to our institution generally did not have prior major psychological issues. Also when women were identified as fulfilling anxiety or depression caseness, none took up the offer of formal psychological assessment. None of these women merited compulsory psychological assessment based on normal clinical practice. We do not think these women lacked insight – we believe they declined the offer of formal assessment because they thought that any psychological disturbance they experienced was due to the physical illness of HG and should resolve once the nausea and vomiting remitted. Women with HG viewed HG as biologically determined [22]. Our finding that psychological caseness was not associated with more severe HG, and the independent risk factors identified, would be more consistent with psychological distress being a response to the physical illness rather than the driver in the pathogenesis of HG. There were other limitations to our study. HADS has not been validated in HG though it is validated for the pregnant population [10]. Longitudinal as well as control data on psychological distress prior to pregnancy and after recovery from HG were not available so the mechanism whereby psychological distress led to HG or HG contributed to subsequent psychological consequences cannot be conclusively evaluated with our data. 40.8% of women with anxiety caseness required prolonged hospitalization compared to 31.5% of non-anxious controls. Post hoc analysis indicated that our study had 24% power only to detect the above stated difference in the rate of prolonged hospitalization, which would suggest that the assumption made in our sample size calculation was optimistic. There is a heavy burden of psychological distress in women with HG. It is unclear how these stresses evolve over the course of the illness and pregnancy. A powered prospective longitudinal study starting from before pregnancy and followed into the postnatal period in women at high risk of HG will help provide quality data on the cause and effect between HG and psychological states. It is not established whether support and therapy aimed at anxiety and depression would be useful avenues to better outcome. However, a lack of health care provider support and appreciation of disease severity was more often reported by women with HG who underwent termination of pregnancy [7]. Also patients’ perceptions about physician humanism and perceived agreement about the cause and impact of HG can help patient satisfaction [23]. Further research in this direction is warranted. 5. Conclusion Anxiety and depression caseness is common in hyperemesis gravidarum. Independent risk factors for psychological distress can be identified. There is no convincing association between anxiety

Please cite this article in press as: Tan PC, et al. Anxiety and depression in hyperemesis gravidarum: prevalence, risk factors and correlation with clinical severity. Eur J Obstet Gynecol (2010), doi:10.1016/j.ejogrb.2009.12.031


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and depression and more severe illness. Psychological symptoms may be a response to physical illness but further studies are needed. References [1] Ismail SK, Kenny L. Review on hyperemesis gravidarum. Best Pract Res Clin Gastroenterol 2007;21(5):755–69. [2] Verberg MF, Gillott DJ, Al-Fardan N, Grudzinskas JG. Hyperemesis gravidarum, a literature review. Hum Reprod Update 2005;11(September–October (5)):527– 39. [3] Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy. Br J Gen Pract 1993;43(June (371)):245–8. [4] Bailit JL. Hyperemesis gravidarium: epidemiologic findings from a large cohort. Am J Obstet Gynecol 2005;193(September (3 Pt 1)):811–4. [5] Gazmararian JA, Petersen R, Jamieson DJ, et al. Hospitalizations during pregnancy among managed care enrollees. Obstet Gynecol 2002;100(July (1)):94–100. [6] Dodds L, Fell DB, Joseph KS, Allen VM, Butler B. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol 2006;107(February (2 Pt 1)):285–92. [7] Poursharif B, Korst LM, Macgibbon KW, Fejzo MS, Romero R, Goodwin TM. Elective pregnancy termination in a large cohort of women with hyperemesis gravidarum. Contraception 2007;76(February (6)):451–5. [8] Seng JS, Schrot JA, van De Ven C, Liberzon I. Service use data analysis of prepregnancy psychiatric and somatic diagnoses in women with hyperemesis gravidarum. J Psychosom Obstet Gynaecol 2007;28(December (4)):209–17. [9] Simpson SW, Goodwin TM, Robins SB, et al. Psychological factors and hyperemesis gravidarum. J Womens Health Gend Based Med 2001;10(June (5)):471–7. [10] Abiodun OA. A validity study of the Hospital Anxiety and Depression Scale in general hospital units and a community sample in Nigeria. Br J Psychiatry 1994;165(November (5)):669–72. [11] Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67(June (6)):361–70.

[12] Lee AM, Lam SK, Sze Mun Lau SM, Chong CS, Chui HW, Fong DY. Prevalence, course, and risk factors for antenatal anxiety and depression. Obstet Gynecol 2007;110(November (5)):1102–12. [13] Tan PC, Jacob R, Quek KF, Omar SZ. The fetal sex ratio and metabolic, biochemical, haematological and clinical indicators of severity of hyperemesis gravidarum. BJOG 2006;113(June (6)):733–7. [14] Tan PC, Jacob R, Quek KF, Omar SZ. Pregnancy outcome in hyperemesis gravidarum and the effect of laboratory clinical indicators of hyperemesis severity. J Obstet Gynaecol Res 2007;33(August (4)):457–64. [15] Tan PC, Jacob R, Quek KF, Omar SZ. Indicators of prolonged hospital stay in hyperemesis gravidarum. Int J Gynaecol Obstet 2006;93(June (3)):246–7. [16] Swallow BL, Lindow SW, Masson EA, Hay DM. Psychological health in early pregnancy: relationship with nausea and vomiting. J Obstet Gynaecol 2004; 24(January (1)):28–32. [17] Cumming GP, Klein S, Bolsover D, et al. The emotional burden of miscarriage for women and their partners: trajectories of anxiety and depression over 13 months. BJOG 2007;114(January (9)):1138–45. [18] Poursharif B, Korst LM, Fejzo MS, MacGibbon KW, Romero R, Goodwin TM. The psychosocial burden of hyperemesis gravidarum. J Perinatol 2008;March (28):176–81. [19] Weigel RM, Weigel MM. Nausea and vomiting of early pregnancy and pregnancy outcome. A meta-analytical review. Br J Obstet Gynaecol 1989; 96(March (11)):1312–8. [20] Weigel MM, Weigel RM. Nausea and vomiting of early pregnancy and pregnancy outcome. An epidemiological study. Br J Obstet Gynaecol 1989;96(November (11)):1304–11. [21] Koken G, Yilmazer M, Cosar E, Sahin FK, Cevrioglu S, Gecici O. Nausea and vomiting in early pregnancy: relationship with anxiety and depression. J Psychosom Obstet Gynaecol 2008;29(June (2)):91–5. [22] Munch S. Women’s experiences with a pregnancy complication: causal explanations of hyperemesis gravidarum. Soc Work Health Care 2002;36(1):59–76. [23] Munch S, Schmitz MF. Hyperemesis gravidarum and patient satisfaction: a path model of patients’ perceptions of the patient–physician relationship. J Psychosom Obstet Gynaecol 2006;27(March (1)):49–57.

Please cite this article in press as: Tan PC, et al. Anxiety and depression in hyperemesis gravidarum: prevalence, risk factors and correlation with clinical severity. Eur J Obstet Gynecol (2010), doi:10.1016/j.ejogrb.2009.12.031


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