Hyperemesis gravidarum and the risk of emotional distress during and after pregnancy

Nausea and vomiting in pregnancy (NVP) is common and affects up to 80% of all pregnancies, predominantly during the first trimester (Gadsby et al. 1993). Hyperemesis gravidarum (HG) is characterised by severe NVP starting before the 22nd week of gestation and can occur with or without metabolic disturbances (World Health Organization 2004). Due to the severity of NVP, HG is a main cause for sick leave (Dorheim et al. 2013) and hospitalisation during early pregnancy (Gazmararian et al. 2002), affecting between 0.3 and 2% of all pregnancies (Eliakim et al. 2000).

The aetiology of HG is unknown but has historically been explained by a variety of psychological disturbances or psychiatric diseases (Fairweather 1968). Today, HG is generally regarded as a disease of unknown pathophysiological origin (Grooten et al. 2015), although the opinion that HG is of psychological origin persists. Women with HG today report lack of support from their health care providers (Heitmann et al. 2016; Poursharif et al. 2008; Power et al. 2010), and those suffering from unremitting symptoms are still being evaluated for psychiatric conditions (Kim et al. 2009).

A recent meta-analysis showed an association between HG and depression and anxiety in pregnancy (Mitchell-Jones et al. 2016), but the direction of this association was not clarified. Some studies have found increased risk of HG in women with a history of depression (Fell et al. 2006; Kjeldgaard et al. 2017; Seng et al. 2007), whereas others found an increased risk of depression in HG women with no history of psychiatric disease (Aksoy et al. 2015; Pirimoglu et al. 2010). A relationship between the degree of nausea and vomiting and the risk of developing psychological distress including depression and anxiety has also been suggested (Koken et al. 2008; Kramer et al. 2013), but research shows conflicting results (Swallow et al. 2004; Tan et al. 2010). In addition, symptoms of anxiety and depression have been shown to decrease over time as symptoms of nausea and vomiting wear off (Annagur et al. 2013; McCarthy et al. 2011; Tan et al. 2014).

A number of studies have addressed psychological distress in the HG pregnancy (Mitchell-Jones et al. 2016), but little is known about the risk of maternal psychological distress following an HG pregnancy. Previous studies have in general been small or included limited information on possible confounders.

The aim of the present study was to assess whether HG was associated with emotional distress during pregnancy and up to 18 months after birth. The Norwegian Mother and Child Cohort Study (MoBa), comprising more than 100,000 pregnancies, provided a unique opportunity to explore this association.

Among the 92,947 women included in this study, the mean age was 30.2 years (14–47 years; SD 4.5 years) and 45.5% were primiparous. A total of 851 (0.9%) women reported hospitalisation due to nausea and vomiting during the index pregnancy. Frequencies of emotional distress at the four time points are shown in Table 1.

Covariates included in the regression model are presented in Table 2. Previous HG, history of depression, shorter education, smoking, pelvic girdle pain, low pre-pregnancy physical activity, and high pre-pregnancy BMI were positively associated with symptoms of emotional distress. Maternal age was negatively associated with symptoms of emotional distress.

Time trend analyses (Table 3) revealed a non-linear relationship between HG and emotional distress. The time profiles in adjusted odds for emotional distress were significantly different between HG and no HG groups (p = 0.035). The odds for emotional distress (Fig. 1) were statistically significant between HG and no HG groups at the 17th (p < 0.001) and 32nd gestational week (p = 0.001) in addition to 6 months postpartum (p = 0.005) but not 18 months postpartum (p = 0.430).

In subanalyses, we assessed whether having been hospitalised for HG in the first trimester only, the second trimester only, or in both trimesters had different risk profiles for developing emotional distress. The analyses were adjusted for the same covariates as the main analyses. The results showed no difference in odds for emotional distress between women who had been hospitalised in the first trimester and women who had been hospitalised in the second trimester. There was also no difference between women who had been hospitalised in one trimester only compared to those without HG. However, women who had been hospitalised in both trimesters had significantly higher odds for symptoms of emotional distress compared to women hospitalised in the first or second trimester only (data not shown).

In the present study, including 92,947 women, we assessed the development of emotional distress over time from the 17th gestational week up to 18 months after birth, depending on whether the women suffered from hyperemesis or not. At the 17th and 32nd gestational weeks and at 6 months postpartum, women with HG had higher odds for emotional distress compared to women without HG. In contrast, at 18 months postpartum, there was no difference in odds for emotional distress between the two groups.

Several previous studies have reported decreasing psychological distress over the course of pregnancy in women with HG. Annagur et al. (2013) evaluated 47 women with HG for psychiatric disease in all three trimesters. They found that the number of women with anxiety and depression was reduced as the nausea and vomiting resolved and the pregnancy progressed. Unfortunately, a comparison group was not included, which explains why it is not possible to claim that women with HG were more likely to develop anxiety and depression than women without. Tan et al. (2014) found that the psychological distress in 121 women with HG decreased from the first to the third trimester along with declining symptoms of nausea and vomiting. In the third trimester, the degree of psychological distress was even lower in the HG group than that in the comparison group. The authors therefore argued that the psychological distress observed in women with HG is self-limiting and a probable result of HG. There was, however, no data available on the psychological distress in the comparison group during the first trimester. In a study on 164 hyperemetic women, McCarthy et al. (2011) also reported decreasing psychological distress during pregnancy in women with HG. Although the psychological distress normalised when symptoms of HG improved, the psychological burden was reported to be increased for weeks after cessation of HG. Additionally, they found that women with HG had higher odds of depression at gestational weeks 15 and 20 compared to women without HG.

Senturk et al. (2017) reported that among the 207 HG women studied, there was an increased risk of depression during not only the first trimester but also postpartum (unadjusted OR 6.52 (95% CI 3.77–11.30)). The time point for assessing postpartum depression was, however, not specified. Additionally, the women were not evaluated during the second or third trimester.

Previous research has shown contradictory results regarding whether the timing and duration of HG may affect the risk of psychological distress. McCarthy et al. (2011) revealed that women with ongoing vomiting after the 15th gestational week were more likely to have depression at 20 weeks compared to HG women whose vomiting had ceased before the 15th week. On the other hand, Tan et al. (2010) found no association between psychological distress and duration of vomiting prior to hospitalisation. In the present study, we therefore assessed whether having been hospitalised for HG in the first trimester only, the second trimester only, or in both trimesters had different risk profiles for emotional distress. Results showed that women who had been hospitalised due to HG in both trimesters had significantly higher odds for subsequent emotional distress compared to women who had been hospitalised in one trimester only. The results suggest that prolonged duration of HG symptoms increases the risk of emotional distress.

To our knowledge, no previous study has estimated the associations between HG and emotional distress at several time points during pregnancy and up to 18 months after delivery. Our results suggest that psychological symptoms during the HG pregnancy and postpartum period may reflect the severity as well as the duration of HG symptoms and therefore might resolve gradually following the cessation of HG. In a previous study (Kjeldgaard et al. 2017), we found that a life-time history of depression was associated with a 50% increase in risk of HG, but that most women with HG did not have a history of depression. Hence, we did not consider a history of depression to be a main driver in the pathogenesis of HG. In the present study, we hypothesised that if women with HG are more likely to be distressed about their lives in general, we would expect a higher risk of emotional distress at all four time points. Although the current study cannot be used to determine causation, the fact that the difference in emotional distress between women with HG and women without HG decreased over time suggests that the greater risk of emotional distress seen in women with HG may be due to the severity as well as duration of their symptoms. This suggestion is further supported by our finding that it was the women who were hospitalised in both trimesters, in particular, who had a significantly greater risk of emotional distress. Our results advocate that health care providers focus first and foremost on treating dehydration and nutritional deficiencies before possible emotional distress in order to ensure the health of the mother and foetus, as inadequate care may have severe consequences including therapeutic abortions, Wernicke’s encephalopathy, and even death (Eliakim et al. 2000; Poursharif et al. 2007).

An advantage of the MoBa study is the availability of information on a history of depression. Several previous studies did not have such information and could therefore not address this question (McCarthy et al. 2011) or did not include women with previous depression (Mitchell-Jones et al. 2016). In the current study, a history of depression was the strongest risk factor (OR 3.42, 95% CI (3.29; 3.56)) for developing emotional distress during and after pregnancy. This was not surprising as a large body of research has shown that a history of depression is a main risk factor for prenatal and postpartum depressive symptoms (Biaggi et al. 2016, Norhayati et al. 2015). Having had a previous HG pregnancy is known to increase the risk of developing HG in a following pregnancy (Trogstad et al. 2005). We therefore adjusted for previous HG in the time trend analyses as women who had HG previously may be more susceptible to develop emotional distress in a current HG pregnancy. We found an adjusted OR of 1.18, 95% CI (1.12; 1.24). In agreement with previous studies, we found a positive association between emotional distress and younger age of the mother, higher pre-pregnancy BMI, shorter education, low physical activity, and pelvic girdle pain, whereas parity had a protective effect on the risk of developing emotional distress.

In the present study, we used an instrument (SCL-5) designed to measure psychological distress in population-based studies (Strand et al. 2003). It has been validated in several populations and is documented as an acceptable screening instrument for depression as defined by ICD-10 (Sandanger et al. 1998). In the MoBa study, the women’s answers to SCL-5 were the only available measures of mental health status. Generally, questionnaire studies enable larger study populations than studies utilising clinical interviews for data collection. A clinical interview, however, remains the gold standard for assessing depression and anxiety. Furthermore, it is important to note that SCL-5 is a screening tool for depressive and anxious symptoms and cannot be used for diagnosing depression or anxiety. Extensive questionnaire studies with a broad scope such as the MoBa study often have space limitations for the original lengthy psychometric instruments, and short versions may be useful to improve response rates. While the short versions affect measurement precision, the level of precision remains sufficient for epidemiological purposes (Strand et al. 2003; Tambs and Moum 1993; Tambs and Røysamb 2014).

The large number of HG pregnancies (n = 851) was a major strength of the current study. In addition, the study covered all regions of Norway, and the risk of recall bias was reduced by the prospective nature of data collection. To date, more than 400 articles have been published based on MoBa data (Magnus et al. 2016). However, some limitations may be considered. Self-selection bias might be present as only about 40% of the invited women participated in the study. However, the potential bias by skewed selection of participants in MoBa may influence the prevalence estimates rather than the exposure-outcome associations (Nilsen et al. 2009). Women known to be underrepresented in MoBa included immigrants, smokers, single women, those with shorter education, and those less than 25 years of age (Nilsen et al. 2009; Vikanes et al. 2010).

Another limitation concerns the definition of HG. Unfortunately, the MoBa does not include a validated score such as the Pregnancy Unique Quantification of Emesis (PUQE) (Birkeland et al. 2015; Koren et al. 2005) to assess the symptoms of nausea and vomiting. The data provide information about the weeks of pregnancy in which women suffered from nausea and vomiting and whether or not these women were hospitalised due to NVP. In Norway, only women with severe metabolic disturbances are admitted to the hospital for HG, and no outpatient treatment is available. Health care is free of charge in Norway, and all women in need of inpatient treatment are admitted regardless of socioeconomic status. Therefore, in order to restrict our HG group to those with the most severe symptoms, we defined HG as hospitalisation due to nausea and vomiting. As such, our conclusions can be applied only to women with severe symptoms of HG. Although hospitalisation for HG was assessed retrospectively, recall bias was highly unlikely due to the relatively short interval between hospitalisation and reporting of HG in week 32 of pregnancy (Vikanes et al. 2010).

Unfortunately, we did not have data on emotional distress during the first trimester, which is a limitation of our study. To our knowledge, no previous population-based study has succeeded in studying mental distress when HG patients are at the peak of their symptoms. The reason for this may be that the most severely affected women at that point in time are in critical condition clinically, as characterised by exhaustion due to dehydration and nutritional deficiencies.

Furthermore, regarding concurrent diseases or conditions, the comparison group comprised all other pregnant women in the study, including those with complications other than HG, thus reducing the risk of overestimating the association between HG and depression. Thyroid diseases are associated with HG as well as a variety of emotional disturbances and may hence be an important confounder to adjust for. Unfortunately, the data did not distinguish between hyperthyroid and hypothyroid diseases, and therefore we did not adjust for these conditions. This may have affected our results.

Our results should be interpreted with these limitations in mind.

Women with an HG pregnancy were more likely to report emotional distress than women without HG, but the differences between these groups disappeared 18 months after birth. Subanalyses showed that women with prolonged HG were more likely to develop symptoms of emotional distress. The findings suggest that higher risks of developing emotional distress may primarily be a consequence of HG.