Miscarriage occurs in 10% to 15% of pregnancies, mainly in the first trimester.1 Spontaneous miscarriage is associated with psychological problems such as anxiety and depression.2 3 4 Post-traumatic stress disorder may also occur after a miscarriage.3 Threatened miscarriage affects 15% to 20% of pregnant women.5 Management of threatened miscarriage involves reassurance and counselling. Women with threatened miscarriage and/or pregnancy-related uncertainty may experience frustration and anxiety. Although there are extensive data regarding the association between miscarriage and psychological morbidity, higher incidences of anxiety and depression among women with threatened miscarriage have only been detected in small studies.6 7

Antenatal depression and anxiety disorders are associated with increased fetal risks, such as low birth weight; antenatal symptoms of depression have been positively associated with postnatal depression.8 9 Furthermore, antenatal maternal stress and anxiety appear to predict long-term behavioural and emotional problems in children.10 11 Therefore, early detection and intervention are needed in women with antenatal psychological symptoms to minimise the impacts of those symptoms.

This study assessed psychological morbidity in women with threatened miscarriage, with the goal of identifying early interventions for women at risk of anxiety or depression.

This cross-sectional study, conducted at a university hospital in Hong Kong between July 2013 and June 2015, was part of a study that examined the ability of an early pregnancy viability scoring system to support counselling for women.12 In this hospital, an outpatient Early Pregnancy Assessment Clinic (EPAC) provides medical care for women experiencing abdominal pain, vaginal bleeding, or other problems in early pregnancy (gestational age ≤12 weeks). Referrals are usually made by medical officers from the Accident and Emergency Departments across Hong Kong, as well as general practitioners. All gynaecologists at the EPAC have ≥3 years of experience performing ultrasound scans. All Chinese women attending the EPAC were invited to participate; written informed consent was obtained from women who agreed to take part in the study.

Exclusion criteria were age <18 years, ectopic pregnancy, multiple pregnancies, gestational age >84 days (>12 weeks), requested termination of pregnancy, and loss to follow-up. Demographic data, obstetric history, smoking status, alcohol consumption, and body mass index were recorded. Details of early pregnancy complaints were assessed, including abdominal pain (graded by a pain score of 0 to 3, where a higher score represents greater pain) and vaginal bleeding (determined by a pictorial blood loss chart according to the number of pads used, where 0 corresponds to no bleeding and 4 corresponds to clots or flooding).

Chinese validated versions of five questionnaires were used to assess psychological well-being among the participants: the 12-item General Health Questionnaire (GHQ-12), the Beck Depression Inventory (BDI), Spielberger’s State Anxiety Inventory State form (STAI-S), the Fatigue Scale–14 (FS-14), and the Profile of Mood States (POMS). All questionnaires have demonstrated reliability and validity in previous studies.13 14 15 The GHQ-12 and BDI scores were reported as both continuous and categorical variables, while the scores of other questionnaires were reported as continuous variables.

The GHQ-12 is a self-reporting rating scale intended to identify individuals with reduced psychological well-being or diminished quality of life. It is sensitive to short-term psychiatric disorders. A total score of ≥4 using the bi-modal scoring method (0-0-1-1) is considered ‘high distress’. When using the Likert scoring method (0-1-2-3), scores ≤12 are considered normal, while scores >12 are considered evidence of psychological distress.16 17 The questionnaire has been used as a tool to evaluate women with miscarriage.18 19 20

The BDI is a 21-item self-reporting rating scale intended to measure symptoms of depression in both general and psychiatric populations.21 It is used to measure depression severity, and psychological morbidity is defined as a score of >12, indicating probable depressive disorder. The STAI-S is a 20-item self-reporting inventory that measures state anxiety, including transitory and situational feelings of worry.22 Its use has been validated in pregnant women.23 A higher score indicates a higher level of anxiety. The FS-14 is a 14-item self-rating questionnaire that measures fatigue severity. A lower score indicates a higher level of fatigue.

The POMS is a self-reporting tool for the assessment of mood alterations in clinical and psychiatric populations.24 This 65-item questionnaire contains seven components: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, confusion-bewilderment, vigour-activity, and total mood disturbance. Scores range from 0 (not at all) to 4 (extremely). Higher positive mood scores indicate an ideal mood, whereas higher negative mood scores indicate severe mood disturbance.

In addition to the above questionnaires, each woman’s level of anxiety and worry before consultation was assessed using a 0 to 10 cm visual analogue scale (VAS). A higher value represents a higher level of anxiety and worry about their pregnancies. The VAS has previously been validated with respect to its correlations with other measures of anxiety.25 26

During the consultation, women were counselled based on their ultrasound findings and clinical diagnosis. These women used the VAS to indicate their level of pregnancy-related anxiety after consultation. Follow-up scans (1-2 weeks later) were offered for women with a pregnancy of uncertain viability. Actual pregnancy outcomes were reassessed at 13 to 16 weeks, either by phone or by retrieval of information from the hospital’s centralised computer antenatal records system.

The sample size was calculated based on the number of participants required for the primary study to validate the scoring system.12 SPSS software (Windows version 26.0; IBM Corp, Armonk [NY], United States) was used for data entry and analysis. A 95% confidence interval (95% CI) was calculated to determine the estimated errors and prevalence. Descriptive analyses were used for demographic data. The Chi squared test was used to explore associations between categorical variables. The Mann-Whitney U test was used to compare median values when data were not normally distributed, while the t test was used to compare means when data were normally distributed. Univariate analyses were performed to identify factors associated with psychological distress or morbidity. Factors with P values <0.1 in univariate analysis were entered into multivariate analysis, which was conducted via binary logistic regression. P values <0.05 were considered statistically significant.

Among the 1508 women who attended the EPAC during the study period, 64 were excluded and 54 declined to participate; thus, 1390 women completed the study (Fig). The demographic data are shown in Table 1. At the first clinic visit, most women (n=1048, 75.4%) had a viable pregnancy, 223 women (16.0%) had a pregnancy of uncertain viability, and 119 (8.6%) women had a miscarriage. At 13 to 16 weeks of gestation, 1111 women (79.9%) had a viable pregnancy, and an additional 160 (11.5%) women had a miscarriage.

The GHQ-12 (both bi-modal and Likert), BDI, STAI-S, FS-14, POMS, and VAS results are presented in Table 2. Overall, 48.4% and 76.7% of women had a GHQ-12 (bi-modal) score ≥4 and a GHQ-12 (Likert) score >12, respectively, indicating distress. Among the viable pregnancy, uncertain viability, and miscarriage groups, the percentages of women with a GHQ-12 (bi-modal) score ≥4 (43-52%) and a GHQ-12 (Likert) score >12 (73-83%) were similar. Women with miscarriage had the highest GHQ-12 score and the highest percentages of a GHQ-12 (bi-modal) score ≥4 and a GHQ-12 (Likert) score >12. The miscarriage group also had relatively higher POMS subscale scores for tension-anxiety, depression-dejection, anger-hostility, confusion-bewilderment, and total mood disturbance compared with women who had other diagnoses.

The VAS scores for anxiety are also presented in Table 2. The score before consultation was the highest among women with a miscarriage (mean ± standard deviation=7.02 ± 2.50). Although the scores for the viable pregnancy and uncertain viability groups were significantly lower after consultation, the score was substantially higher in the uncertain viability group than in the viable pregnancy group.

Subgroup analysis showed that GHQ-12, BDI, and POMS (except fatigue-inertia and vigour-activity subscales) scores were significantly higher among women with previous miscarriage than among those without (Table 3). The bleeding score was strongly positively correlated with the GHQ-12 (Likert) score (correlation coefficient=0.56; P=0.032). Univariate analysis revealed that compared with women who had a lower bleeding score (<2), women with a higher bleeding score (≥2) had a significantly higher risk of having a GHQ-12 (bi-modal) score ≥4 (P=0.041), a GHQ-12 (Likert) score >12 (P=0.025), and a BDI score >12 (P=0.022) [Table 4]. There were statistically significant but weak positive correlations between the pain score and a GHQ-12 (bi-modal) score ≥4 (P=0.001), a BDI score >12 (P<0.001), and a POMS total mood disturbance score (P<0.001), as well as various subscales. Notably, the POMS confusion-bewilderment subscale (correlation coefficient=0.93; P<0.001) demonstrated a strong positive correlation with the pain score.

Statistically significant factors associated with the various psychometric instrument scores were subjected to multivariate analysis (Table 4). Previous miscarriage was an independent risk factor for a GHQ-12 (bi-modal) score ≥4 (odds ratio [OR]=1.570, 95% CI=1.19-2.07) and a GHQ-12 (Likert) score >12 (OR=1.459, 95% CI=1.04-2.06), indicating distress; it was also a risk factor for a BDI score >12 (OR=1.717, 95% CI=1.28-2.30), suggesting probable depression. A bleeding score ≥2 was an independent risk factor for a GHQ-12 (Likert) score >12 (OR=1.506, 95% CI=1.05-2.17) and a BDI score >12 (OR=1.423, 95% CI=1.04-1.95).

In this cohort study, nearly 50% and approximately 77% of women had a GHQ-12 (bi-modal) score ≥4 and a GHQ-12 (Likert) score >12, indicating distress. Around one-fourth (24.5%) of women had a BDI score >12, suggesting probable depression.

Regardless of diagnosis, the VAS score decreased after consultation. However, the decrease in VAS score was smaller for the uncertain viability group, which may be attributed to the enhanced anxiety resulting from uncertainty among these women. This anxiety would be alleviated after an ultrasound examination and consultation with an accurate diagnosis. These findings emphasise the need to implement an early pregnancy assessment service that provides both clinical and psychological guidance to alleviate anxiety among women with problems in early pregnancy.

Emotional disturbances can have long-term effects on women with a previous miscarriage. Lok et al19 reported consistently higher scores on the GHQ-12 and BDI among women with a previous miscarriage, although these scores could decrease over time. In the present study, we observed a higher level of distress among women with a previous miscarriage, as demonstrated by the significantly greater proportion of women with GHQ-12 (bi-modal) score ≥4, GHQ-12 (Likert) score >12, and BDI score >12. Profile of Mood States scores were also significantly higher on all subscales, except for the fatigue-inertia and vigour-activity subscales. Similarly, the baseline VAS score before consultation was significantly higher among women with a previous miscarriage than among those without. In multivariate analysis, previous miscarriage was an independent risk factor for GHQ-12 (bi-modal) score >4, GHQ-12 (Likert) score >12, and BDI score >12. Baseline psychological morbidity may be greater among women with a previous miscarriage than among those without, consistent with findings in other studies.3 27 Therefore, additional attention and psychological support would be beneficial for women with greater distress and worse mood status.

A higher pain score was positively correlated with higher levels of distress and anxiety, as indicated by the positive relationships with various scales used in the present study. Pain is associated with anxiety and depression in pregnant women.28 Nevertheless, we observed weak relationships between pain and anxiety or distress, which might be related to the subjective nature of pain assessment.

Women with moderate to heavy bleeding (bleeding score ≥2) had significantly higher GHQ-12 (bi-modal), GHQ-12 (Likert), and BDI scores. Additionally, multivariate analysis showed that moderate to heavy bleeding (bleeding score ≥2) was an independent risk factor for a GHQ-12 (bi-modal) score ≥4, a GHQ-12 (Likert) score >12, and a BDI score >12. Heavy bleeding is often regarded as a common sign of threatened miscarriage. These findings highlight the importance of addressing pain and bleeding symptoms among women who attend early pregnancy services. The underlying complications of pregnancy, as well as anxiety and low mood in affected women, should be promptly managed.

Pregnancy loss is associated with negative mood status, including depression and anxiety.3 18 19 27 29 Whereas many studies have investigated the effects of miscarriage or pregnancy loss on depression, the effects of threatened miscarriage or early pregnancy-related complaints on women have not been extensively explored, despite the burdensome experience of a threatened miscarriage that appropriately causing anxiety in affected women. Our results are consistent with findings by Zhu et al,6 who reported that a substantial proportion of women with threatened miscarriage had symptoms of depression or anxiety.

The present study had a large sample size and a high rate of participation. Additionally, multiple psychometric instruments were used to assess the participants. The findings emphasise the importance of assessing and managing depression and anxiety symptoms in women with threatened miscarriage. Mental health assessments should be performed when women with threatened miscarriage attend clinics and hospitals. Early recognition of relevant mood problems will facilitate timely management. Non-pharmacological interventions, such as antenatal group therapy, constitute effective treatment for pregnant women with anxiety and depression.6 Pharmacological therapies (eg, most selective serotonin reuptake inhibitors and benzodiazepines) can be administered after considering the side-effects of medications relative to the risk of untreated antenatal depression and anxiety.30

Nevertheless, this study had some limitations. First, it used a cross-sectional design without longitudinal follow-up, and the subgroup analysis might have been underpowered. Second, information was unavailable regarding social factors (eg, education level or marital status) and the presence of an underlying psychiatric disorder, which might contribute to differences in baseline mood status. Third, the study did not include a comparison group of women without symptoms of threatened miscarriage.

There is a considerable psychological burden among women with early pregnancy problems and concerns about future pregnancy viability. These women experience emotional disturbances, as indicated by a significant proportion of women in this study who had high scores on psychometric tests. A gynaecologist consultation, in combination with an ultrasound assessment, is reassuring and can alleviate anxiety among women with early pregnancy problems. This study on maternal psychological outcomes provides insights concerning psychological morbidity among women with threatened miscarriage in the first trimester, while also demonstrating the usefulness and feasibility of various psychometric instruments in identifying women who require additional psychological support. Further studies exploring maternal psychological well-being later in pregnancy, as well as fetal outcomes, are needed to determine the long-term effects of anxiety and depression among women with threatened miscarriage in the first trimester.

Concept or design: OYK Wan, SSC Chan.
Acquisition of data: OYK Wan, JWK Kwok.
Analysis or interpretation of data: PNP Ip, K Ng.
Drafting of the manuscript: PNP Ip, K Ng.
Critical revision of the manuscript for important intellectual content: PNP Ip, K Ng, OYK Wan, JPW Chung, SSC Chan.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

As an editor of the journal, JPW Chung was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

This research was supported by a grant from the Health and Medical Research Fund of the former Food and Health Bureau, Hong Kong SAR Government (Ref No.: 12131091). The study sponsor was not involved in the collection, analysis, or interpretation of data, or in the writing of the manuscript.

This research was approved by the Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committee (Ref No.: CRE.2013.348). Written informed consent was obtained from all participants.

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