https://orcid.org/0000-0002-4007-1562
Abstract
This study was conducted between March 2020 and February 2021 to analyze anxiety and depression symptoms in 64 women with gestational trophoblastic disease (GTD) and 99 women who had miscarried. The Hospital Anxiety and Depression Scale (HADS) was applied by telephone three months after pregnancy loss. Multivariate analysis was performed using hierarchical logistic regression to evaluate associations between variables. Probable anxiety (HADS-A ≥ 8) and depression (HADS-D ≥ 8) were found in 53.1% and 43.8% of the GTD group and 49.5% and 39.4% of the miscarriage group, with no difference between the groups. Severe symptoms of anxiety (HADS-A 15-21) and depression (HADS-D 15-21) were found, respectively, in 12.5% and 4.7% of the GTD group and in 9.1% and 4.0% of the miscarriage group, also with no difference between the groups. Lack of partner support proved a risk factor for anxiety and depression, while poor education increased the risk of depression symptoms 3.43-fold following pregnancy loss. In conclusion, three months after pregnancy loss the frequency of anxiety and depression symptoms was similarly high in both groups, with poor education and lack of partner support being significant risk factors for the subsequent development of psychiatric morbidity.
Introduction
Pregnancy loss is a general term applied to the death of the conceptus or fetus at any moment between conception and delivery [Citation1]. Miscarriage is the most common obstetric complication and the most frequent type of pregnancy loss [Citation2] and refers to the loss, before viability, of an intrauterine pregnancy occurring up to 20 or 22 weeks of pregnancy, with the weight of the conceptus being ≤500 grams [Citation3]. Around 15% of all recognized pregnancies result in miscarriage [Citation3]. On the other hand, gestational trophoblastic disease (GTD) is an umbrella term for a set of diseases resulting from the placental trophoblast that develops in the uterus following abnormal gametogenesis and fertilization. This is an obstetric complication that results in early pregnancy loss [Citation4], with the GTD spectrum ranging from premalignant to malignant manifestations [Citation5]. In Brazil, data on the prevalence and incidence of GTD have yet to be confirmed; however, estimations suggest around 1 case for every 200-400 pregnancies [Citation6]. Treatment initially consists of manual vacuum aspiration (MVA) or curettage [Citation7] and specialized follow-up to monitor serum beta-hCG levels for at least six months [Citation8], or twelve months in cases of gestational trophoblastic neoplasia (GTN) [Citation9].
The morphological and clinical aspects of pregnancy loss have been well documented in the literature. The emotional aspects, however, only began to be described more substantially in the eighties and nineties, with studies on bereavement [Citation10,Citation11]. For centuries and in various cultures, the possibility of procreating and conceiving children was considered one of the most important tasks in a woman’s life. The female identity and the woman’s social role were historically linked to her reproductive capacity [Citation12]. Being a complete woman has been associated with the function of being a mother and, when this function is not fulfilled, feelings of failure, guilt and shame may ensue [Citation13].
The emotional impact of fertility loss has been described as a devastating, at times traumatic, experience [Citation14]. In such cases, early pregnancy loss leads to a feeling of helplessness at the death of a dream, a situation encircled by profound silence and often experienced alone [Citation15]. In the case of GTD, in addition to that loss, in a short space of time, the woman goes from being pregnant to being ill with a disease that is potentially a threat to her life and to her reproductive future. In this case, a double bereavement is experienced with the loss of a pregnancy and loss of the woman’s previous good health [Citation12,Citation16], requiring adaptation to a new reality that includes not only pregnancy loss, but also the need to undergo surgery, the possibility of requiring chemotherapy and of having to postpone a future pregnancy until the disease goes into complete remission. In this context of immediate and long-term events, the woman and her partner may experience psychic distress, social changes and, in some cases, sexual changes [Citation17]. With the aim of contributing to studies on the mental health of patients who have undergone pregnancy loss, the objective of the present study was to determine the frequency of symptoms of depression and anxiety in outpatients with GTD compared to women who had a miscarriage at an equivalent time.
Materials and methods
The sample was captured using a non-probabilistic method and convenience criteria. The sample size was calculated using the OpenEpi, version 3.01, public domain program (Atlanta, GA), considering the difference between the two proportions (). Using the continuity corrected formula of Fleiss (95% significance level and 80% power) and an expected frequency of anxiety in patients with GTD of 47% [Citation18] and 22% [Citation19] in patients with spontaneous abortion the study required at least 128 participants, 64 in each group.
Table 1. Sample size for cross-sectional, cohort and randomized clinical trial studies.
In this cross-sectional study, data were collected on 64 patients diagnosed with GTD at a referral centre for the disease in Recife, Brazil. A control group consisted of 99 women who had had a miscarriage (including spontaneous abortions only) and were admitted to maternity hospitals in the same city during the data collection period from August 2020 to February 2021.
Regarding the inclusion and exclusion criteria, patients with clinical-laboratory or histopathological diagnoses of GTD in the third month of active follow-up at the reference center for GTD were included. Patients with 3 months post-diagnosed spontaneous abortion (complete and incomplete miscarriage) were also included. The exclusion criteria for both groups consisted of the following situations: cognitive inability to understand and answer the form questions and the scale to evaluate anxiety and depression, women diagnosed with a psychiatric illness and using psychiatric medication in the last six months and also discovering the pregnancy at the time of data collection. In the case of GTD, patients diagnosed with confirmed Gestational Trophoblastic Neoplasia were excluded.
The research was conducted by telephone three months after pregnancy loss, a moment selected because it is considered the halfway point in treatment for GTD. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate symptoms of anxiety and depression in these two populations. This instrument has been validated and is frequently used in outpatient populations following pregnancy loss [Citation11]. This self-report scale consists of fourteen items divided into two subscales: the anxiety subscale (HADS-A) and the depression subscale (HADS-D), both with seven interspersed items. The total score for each scale ranges from 0 to 21 points, with higher scores being indicative of a greater level of anxiety or depression [Citation20]. On this scale, the levels of symptomatology can also be identified with the following scores: 0–7 normal or absent, 8–10 mild, 11–14 moderate and 15–21 severe. A cutoff score ≥8 points adopted as being indicative of probable cases of anxiety and depression. The cases identified with a high score of probable anxiety and depression (score greater than or equal to 15) were identified and then these people received, through a message sent by cell phone, guidance on the importance of mental health care and a list of available services of free or low-cost psychological/psychiatric care. Data on sociodemographic, obstetric, reproductive and clinical variables, as well as those related to health care, were collected on a form specifically developed for this study. The patient filled up the HADS and the form via telephone interview, under the guidance of the researcher.
Statistical analysis
The statistical analysis was conducted using Epi Info, version 7.2.5. For the descriptive analysis, frequency distribution tables were constructed, and measures of central tendency and dispersion were calculated. Contingency tables were used to compare the categorical variables, with Pearson’s chi-square test of association and Fisher’s exact test being used whenever pertinent. Student’s t-test was used to compare numerical variables, with the Mann-Whitney test being applied when more appropriate. To determine the association between the dependent and independent variables, prevalence ratios (PR) together with their 95% confidence intervals (95%CI) were calculated as a measure of relative risk. All p-values were two-tailed, and the significance level adopted was 5%. A multivariate analysis was conducted using the hierarchical logistic regression model to evaluate the association between the dependent and independent variables, with non-significant confounding variables being excluded.
Ethical aspects
The institute’s internal review board approved the study protocol under reference number 27357819.0000.5201. Thus, the board concluded that there was no need to submit the investigation to the external ethics board. All the participants freely agreed to participate in the study and signed a free and informed consent form.
Results
Overall, 119 patients who had had a miscarriage were invited to participate in the study. Of these, 14 refused, 5 could not be contacted by telephone three months later, and one patient was excluded due to a previously diagnosed psychiatric disorder. Therefore, 99 patients who had had a miscarriage were considered eligible and participated in the study as a control group.
For the GTD group, 77 patients were initially selected. Two refused to participate, ten could not be followed up by telephone, and one was excluded due to a hearing disorder, leaving a total of 64 patients with GTD in the study. Of these, the hydatidiform molar pregnancy was complete in 27 patients and partial in 20. In the remaining 17 cases, the women were either waiting for histopathology results or no data were available on the clinical form of the molar pregnancy. Patients diagnosed with GTN were excluded from the study.
Over half the patients with GTD were not from the state capital city compared to 19.2% of those in the control group (p < 0.05). Of those who were in a stable relationship, 24.5% of women in the control group and 12.3% of those with GTD reported a lack of partner support following pregnancy loss (p = 0.0688). Overall, 18.2% of women in the control group and 20.3% of those in the GTD group had a history of mental disorders (p = 0.7349). The patients in the GTD group were more likely to have been hospitalized due to complications such as a need to perform more than one curettage and blood transfusion (26.6%% vs. 8,1% in the control group; p < 0.05). Patients in the miscarriage group had had a greater number of previous pregnancies and deliveries, with medians of 2 (IQR 1-3) and 1 (IQR 0-1), respectively, compared to those in the GTD group, with medians of 1 (IQR 1-2) and 0 (IQR 0-1) (p < 0.05) (). In the current study, all cases of miscarriage and GTD were spontaneous conceptions. There was no case of Assisted Reproductive Technology (ART).
Table 2. Biological, sociodemographic, obstetric, reproductive and clinical characteristics of the women who had had a miscarriage and those who had gestational trophoblastic disease.
Frequency of anxiety and depression
The patients in the GTD group had a median HADS-A score of 8 (IQR 5–12.5) and a median HADS-D score of 6 (IQR 4-10). The women in the miscarriage group had medians of 7 (IQR 5–11) and 6 (IQR 3–10), respectively. There was no difference between the two groups ().
Table 3. Comparison of the scores for depression and anxiety in women following miscarriage compared to women with gestational trophoblastic disease (GTD).
Probable cases of anxiety (HADS-A ≥ 8; 95%CI: 0.74–1.21) and depression (HADS-D ≥ 8; 95%CI: 0.72–1.20) were identified, respectively, in 53.1% (n = 34) and 43.8% (n = 28) of the patients in the GTD group and in 49.5% (n = 49) and 39.4% (n = 39) of the women in the control group. When the degree of symptomatology was evaluated based on the scores obtained, scores suggestive of severe anxiety (HADS-A 15–21; 95%CI: 0.54–1.37) and severe depression (HADS-D 15-21; 95%CI: 0.49-1.80) were found, respectively, in 12.5% (n = 8) and 4.7% (n = 3) of women in the GTD group and 9.1% (n = 9) and 4.0% (n = 4) of those in the miscarriage group. No statistically significant difference was found between the groups ().
Table 4. Distribution of the frequency of symptoms of depression and anxiety in women who had had a miscarriage compared to those with gestational trophoblastic disease (GTD).
After controlling for confounders, multiple logistic regression showed that the type of pregnancy loss (miscarriage or GTD) did not affect the risk of developing anxiety or depression. However, lack of partner support represented a risk factor for the development of anxiety (OR 4.0; 95%CI: 1.61–9.96; p = 0.0029) () and depression (OR 4.4; 95%CI: 1.83–10.66; p = 0.0010) (). Depression was also associated with poor education (i.e. limited to elementary school) (OR 3.4; 95%CI: 1.51–7.77; p = 0.0032) ().
Table 5. Logistic regression: hospital anxiety and depression scale – anxiety subscale.
Table 6. Logistic regression: hospital anxiety and depression scale – depression subscale.
Discussion
Anxiety and depression were common in the women in both groups evaluated here and the rate of moderate to severe symptoms was high. Probable cases of anxiety were identified in half the patients in each group and probable cases of depression were found in approximately 44% of the women in the GTD and 39% in the control group. Poor education and lack of partner support were significantly associated with the development of psychiatric morbidities following miscarriage or GTD. Although there were no significant differences in the rates of anxiety and depression between the two groups, the high frequency found here suggests a strong emotional impact, even three months after pregnancy loss.
Most women experiencing pregnancy loss undergo a period of mourning equivalent to the loss of a loved one [Citation21]. This process can last for months or years, progressing in some cases to a state of depression [Citation22]. GTD involves more than pregnancy loss, as there are also issues linked to fertility, health, and a potential risk to life if untreated, which altogether generates significant stress [Citation23]. Studies aimed at evaluating the quality of life, emotional impact and fertility in patients with GTD emphasize feelings of insecurity and anxiety at the need for systematic outpatient monitoring [Citation24], apprehension with regard to chemotherapy, fear of death [Citation17] and worry of disease recurrence. The frequency of probable anxiety and depression identified in the patients three months after a diagnosis of GTD corroborates a recent systematic review that found that over half the women diagnosed with GTD had a potential risk of developing psychiatric disorders [Citation25]. The frequency of anxiety was similar to that found in a study conducted in Australia (HADS-A ≥ 8: 55.4%), which evaluated patients undergoing treatment for GTD and a random sample of patients who had received treatment in the preceding 30 years [Citation26].
Lower frequencies of psychiatric morbidities were found in a recent prospective cohort study that used the HADS to evaluate women at a median time of 39 days (IQR 25–50) following diagnosis of GTD [Citation18]. Frequencies of probable anxiety and depression were 47% and 27%, respectively; however, 88% of the patients were found to have moderate to severe adaptive problems, with the presence of intrusive thoughts and avoidant thinking following diagnosis [Citation18]. Conversely, some studies that applied the Beck Depression Inventory (BDI) at greater intervals following diagnosis reported higher frequencies of depression, particularly in patients with GTN [Citation27,Citation28]. An Italian study evaluating patients with GTD 2.3 months following diagnosis reported that 28.9% had severe symptoms of depression (BDI score ≥9) and moderate symptoms of anxiety that were linked to a constant state of alertness during disease remission [Citation23].
The rates of moderate to severe anxiety (27.3%) and depression (16.2%) found in the miscarriage group are comparable to values reported in a 2018 systematic review [Citation11], in which 8-20% of women scored above the threshold for moderate depression at 4–6 weeks following pregnancy loss, with a prevalence of symptoms of anxiety of around 18–32%. That review also found that lack of partner support and low marital satisfaction were factors consistently associated with the development of psychiatric morbidities following a miscarriage. Other factors identified included a previous history of mental illness, being single, not having children and a previous history of pregnancy loss [Citation11]. Compared to other reports, the frequency of psychiatric morbidity found in the present study was higher, closer to the frequencies found within a month of pregnancy loss [Citation19,Citation29].
The high frequency of anxiety identified in both groups may be due to the evaluation having been performed in the third month when the first menstruation following pregnancy loss often occurs. This episode is potentially mobilizing since it confirms the lost pregnancy and, for the patients who had a miscarriage, consists of a period in which the couple would normally be preparing for a new pregnancy [Citation30]. The lack of a significant difference between the groups may be due to the fact that pregnancy loss itself, the common denominator in the two groups, probably exerted greater emotional repercussions in the patients in the third month, surpassing the other issues resulting from a diagnosis of GTD.
The high frequency of psychiatric morbidity in patients with GTD could also be explained by the state of constant tension experienced by the patients over the weeks of beta-hCG measurement [Citation31]. In addition, the third month is generally a halfway point in the treatment of the disease, a period during which the emotional load experienced can be high. Miscarriage or GTD were not found to be independent risk factors for the development of psychiatric disorders in the present study; however, the multivariate analysis showed that poor education significantly increased the risk of a woman developing symptoms of probable depression following pregnancy loss by a factor of 3.4. Lack of partner support was also found to be significantly associated, with a 4.4-fold increased likelihood of developing probable depression and a 4.0-fold likelihood of developing anxiety.
The association between poor education and depression following pregnancy loss has been previously reported. In Iran, a study evaluating 185 women who had had a miscarriage found that the likelihood of a woman with a university education developing depression after pregnancy loss was 0.4 points lower compared to that of women with poor schooling [Citation32]. The higher levels of depression following pregnancy loss in women with poor education may be associated with difficulty in adopting coping strategies and resources when faced with a crisis situation such as bereavement [Citation32]. Among patients with GTD, a lack of knowledge with respect to the disease is significant [Citation33]. Poor education can hamper understanding of the diagnosis and affect compliance with treatment, representing a mobilizing factor for these women.
It is known that partner support acts as a protective factor for mental health during pregnancy and the transition to motherhood. Conversely, lack of support is a powerful risk factor for the development of anxiety and depression [Citation34]. Pregnancy loss can trigger tension in the relationship, leading to divorce, sexual problems, and the development of psychiatric morbidities [Citation35]. In patients with GTD, lack of partner and social support is perceived as an obstacle to quality of life and in the fight against the disease [Citation25].
One of the limitations of this study refers to the relatively small sample of participants compared to other studies, affecting the statistical strength of the study and the generalization of the findings. In addition, a few days after the beginning of data collection, the World Health Organization elevated the degree of contamination caused by the coronavirus to pandemic status. Therefore, the present study was conducted in a health crisis setting that has been considered a potentially traumatic moment [Citation36]. The psychological repercussions resulting from the atmosphere of fear of contamination and death, in addition to the restrictive measures of self-isolation, could have influenced the findings. Nonetheless, the pandemic affected all the participants in a similar manner and could not constitute a study bias.
In conclusion, the current study did not find GTD as an independent risk factor for anxiety and depression after pregnancy loss in its results, however, the study observed that three months after pregnancy loss, women continue to have high rates of psychiatric morbidities. Although these are two different clinical situations, risk factors were shared as lack of partner support during and following the diagnosis of miscarriage and GTD and poor education. Both variables were factors significantly associated with the risk of developing anxiety and depression symptoms following pregnancy loss. It is worth noting that anxiety and depression will tend to become chronic if health care is not provided. The psychosocial aspects involved demand greater attention and the implementation of measures of prevention and intervention in view of the mental disorders that are so persistent during this bereavement period, thereby avoiding emotional sequelae, future reproductive problems and additional health care costs. Further studies aimed at comparing the frequencies of psychiatric morbidities at different moments following pregnancy loss will facilitate the evaluation of states of remission or progression of symptoms. The inclusion of patients with GTN in future studies will also contribute toward gaining a further understanding of the effects on the mental health of these patients and the associated risk factors.
Disclosure statement
The authors report no conflicts of interest.
Data availability statement
The authors confirm that the data supporting the findings of this study are available within the article.
Additional information
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References
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