Hepatitis B virus (HBV) infection is a global public health issue (1–3). More than 240 million people have chronic HBV infection, which may develop into hepatitis, cirrhosis, and hepatocellular carcinoma without timely treatment (4). HBV prevalence was 7.18% in China, with approximately 93 million individuals infected with chronic HBV (5). A recent national study showed that the chronic HBV infection prevalence in Chinese pregnant women was 6.17% (6). Chronic hepatitis B is a contagious disease that transmits through blood, sexual activities, and mother-to-child transmission (MTCT). Therefore, patients with HBV infection often experience stigma and discrimination (7). People with chronic hepatitis B infection of any severity were associated with worse mental and physical health than healthy controls (8).

Postpartum depression (PPD), a common perinatal complication, affects 6.9–20% of puerperal women (9, 10), which significantly increases the morbidity and mortality of both mothers and children (11–15). Several studies have found that women who were diagnosed with PPD had an increased risk of future depression, suicide, or increased infant mortality (16–18). In addition, accumulated evidence showed that maternal PPD has deleterious effects on children's physical growth and mental development (19). Therefore, understanding the determinants of PPD and preventing its occurrence is vital.

Previous studies have demonstrated an association between other antenatal diagnoses and birth outcomes with PPD, including gestational diabetes (20), gestational hypertension (21), and preterm birth (22). The impact of maternal HBV infection on PPD is unknown. Previous study has examined the psychiatric effects of HBV infection outside of pregnancy and the puerperium (23). Researchers have suggested that comorbid depression is common in patients with HBV infection. For instance, a Vietnamese study showed that the prevalence of depressive symptoms in patients with chronic hepatitis B was 37.5% (24). Another study by Qureshi et al. reported that 58.6% patients with chronic hepatitis B had depression (25). In 2005, Atesci et al. assessed the incidence of mental disorders in 43 patients with HBV infection and 43 healthy controls, and reported that HBV-infected patients had significantly higher depression and anxiety scores than healthy controls (26). Similar result was found in the study conducted by Yilmaz et al. (27). The impact of maternal HBV infection on PPD, however, is still unknown. Hepatitis B e antigen (HBeAg) positivity has been frequently reported to be associated with MTCT of HBV (28). Therefore, we speculated that HBeAg positivity may increase the psychological burden on these mothers, resulting in a higher PPD risk.

Therefore, there is a need to evaluate the relationship between maternal HBV infection and PPD, and determine whether HBeAg positivity increases the risk of PPD among HBsAg-positive carriers. We conducted a large-scale retrospective cohort study to identify the potential association between HBV infection and PPD.

To the best of our knowledge, this is the first study to assess the relationship between maternal HBV infection and PPD in a large Chinese population. Our study showed that 11.9% of the mothers were considered as PPD at 6 weeks postpartum. We did not observe a greater risk of PPD in mothers with HBV infection. In addition, HBeAg positivity did not increase PPD risk among mothers living with HBV. Remarkably, our study suggested that parity and postpartum hemorrhage were associated with the risk of PPD.

This study found that 11.9% of Chinese postpartum women had PPD, slightly lower than the results of a meta-analysis conducted by Nisar et al., which reported a PPD prevalence of 14.8% in women from mainland China (33). The possible reason is that the latter analysis included studies where participants had a past history of mental illness. In addition, Liu et al. conducted a cross-sectional study in Shanghai, China, and found that 23.2% of women had depressive symptoms at 6 weeks postpartum (34), which is approximately twice the proportion in our study. Possible explanations for the difference in the results includes the study design and sampling method. Their study was a cross-sectional study based on convenience sampling, higher participation rate of women with high-risk pregnancies or complications may contribute to a higher prevalence. Our study was a hospital-based cohort study, and excluded those mothers with stillbirth, birth defect, past psychiatric diseases, or family history of mental illness that may increase the risk of PPD, leading to a lower prevalence of PPD.

A cross-sectional study conducted by Liu et al. suggested that hepatitis B self-awareness was significantly associated with depression in a Chinese study of 500,000 adults (35). Additionally, several studies found that people with chronic hepatitis B had higher depressive scores (26, 27). However, a case-control study conducted by Arslan et al. showed no difference in depression and anxiety between HBV-infected children and healthy control children (36). Similarly, Gale's study did not find a significant association of hepatitis B and depression in adult population (37). Our study showed that maternal HBV infection did not increase the risk of PPD. Therefore, the association between HBV infection and depression differs greatly across studies. It is known that specific populations have higher rates of mental health disorders with internalized stigma contributing to this, such as those with HIV/AIDS (38). It is possible that internalized stigma, common in patients with HBV may also contribute to increased risk of depression (39). Several reasons may contribute to explain the result difference between our study and Liu' study. First, participants with higher education in our study accounted for 66.9%, which is much higher than the 5.9% reported by Liu et al. (35). The HBV infection rate of 7.3% in our study is also 2.3 times that of their study (3.2%). A recent review reported that a higher education level, having a family member with HBV infection, and knowing someone with HBV infection are associated with the reduced stigma (40). Second, Interferon, the common drug for the treatment of hepatitis B, has a side effect of depression (41). But it is a contraindication for pregnancy women to receive Interferon therapy. Third, free antenatal education was offered to expectant mothers in China, which protects the attenders from adverse mental health outcomes (42).

The positive status of HBeAg in the serum is considered a credible marker of viral replication, which is associated with a higher risk of HBV MTCT. Our study indicated that HBeAg positivity was not associated with PPD risk. Viral load and antiviral use during pregnancy were identified as strong predictors of HBV MTCT (43). However, our study lacks data on viral load and antiviral use, which prevents us assessing the association between HBV MTCT and PPD directly. Therefore, this may be an important area for future studies to evaluate.

Consistent with our study, previous study indicated that primiparity was a risk factor for PPD during the first month postpartum (44). The main reason is that primipara may have many concerns, such as baby care, crying, and feeding, which are strongly associated with depressive symptoms in the early postpartum period (45, 46). In addition, our study suggested that women with postpartum hemorrhage still had higher risk of PPD. Similar results could be found in the study by Parry-Smith et al. (47) and our previous research (48). Postpartum hemorrhage usually leads to an increase in hospital stay and comorbidities, which may exacerbate the psychological burden of women who have suffered from postpartum hemorrhage.

Our study has several strengths. First, the cohort study design that enabled us to assess HBV infection status before PPD screening, which contributed to understanding the association between HBV infection and PPD. Second, data from a large sample cohort were used, which yielded more convincing results. However, the following limitations should be considered. First, the assessment of PPD was based on a self-reported scale instead of a psychiatric examination, although the EPDS is a validated tool for screening PPD with high sensitivity and specificity. Second, some confounding variables that may contribute to the risk of PPD were not considered, such as social support (from a husband, parents, or friends). Third, our study excluded patients with past history of mental illness, family history, or infants with birth defects, which may underestimate the impacts of HBV infection on PPD. Fourth, one-fifth participants was excluded because some women receiving PPD screening did not have a prenatal examination in this hospital during pregnancy, resulting in missing data on HBsAg and HBeAg.

In summary, this study is the first to explore the relationship between maternal HBV infection and PPD, although HBV infection did not increase the risk of PPD in puerperium women with no psychiatric or family history. The absence of an association may be explained by the diversity of sociological, behavioral, and psychological factors that affect the mental health of puerperal women. However, there were a number of issues that would be worth addressing in future research, e.g., HBeAg positivity, prior history of mental health.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by Institutional Review Board of the Baoan Maternal and Child Health Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

WH and XW did the statistical analysis and drafted the initial manuscript. ZY, YG, and XL contributed to assist with data collection and revised the manuscript. LM took part in the sample collection. SP contributed to the critical revision of the article. All authors contributed significantly to this work. All authors have contributed to and have approved the final manuscript.