Our study demonstrated the relationship between HBV replication during pregnancy and maternal and fetal adverse outcomes. One of the main findings was that HBV replication during pregnancy had a statistically significant effect on the rate of CS, including after propensity score matching. Several well-established risk factors for CS have been reported including fetal factors, uterine scarring, abnormal fetal position, and pregnancy complications [8, 9]. However, in our analysis, there were no statistically significant differences observed between the two groups in the aforementioned factors. Therefore, other factors may affect the mode of delivery, such as family education and economic status . Another study reported that nearly 30% of women believe that a CS is the safest option for the fetus . We previously reported that most mothers believe that CS is safer than natural delivery, shortens the time of delivery, and reduces the risk of neonatal HBV infection during vaginal birth . These beliefs and opinions are considered to directly influence the mode of delivery. In addition, we believe that the CS rate of the HBV replication group was also affected by their willingness and compliance with the HBV treatment during pregnancy. Therefore, our results do not rule out that the increased CS rate may be a result of an overlap between poor willingness and compliance with antiviral therapy during pregnancy and also may be due to pregnant women choosing CS. Alternatively, an increasing number of pregnant women choose to be admitted to the hospital before their due date, which, to a certain extent, increases the psychological pressure and results in an increase in the rate of dystocia and CS . In addition, the development of aseptic surgery and the decline of CS complications have also changed patients’ attitudes toward CS . Furthermore, our study compared the CS rate between the high and low HBV replication subgroups, and found no statistically significant difference between groups (P>0.05; Table 7). In other words, the increase in the rate of CS did not seem to be influenced by HBV DNA viral load. In addition, some scholars believe that the likelihood of newborn exposure to maternal blood comparable during CS and natural delivery . Therefore, improving patient education and guidance on the mode of delivery is important and may potentially reduce the rate of selective CS.
Neonatal jaundice is divided into physiological and pathological jaundice . Severe pathological jaundice can progress to bilirubin encephalopathy and neurological damage. Our study found that the incidence of neonatal jaundice in infants born to mothers in the low HBV replication subgroup was significantly higher than that in the non-HBV replication group (P<0.05); however, the comparison between the low and high HBV replication subgroups showed no statistically significant difference (Table 7). The mechanism underlying the relationship between HBV replication and neonatal jaundice has not been clearly elucidated. A possible mechanism involves the destruction of a large number of red blood cells in newborns that leads to hemolysis and neonatal bilirubin excretion [14–16]. Other studies have revealed that maternal HBV carrier status is not an independent risk factor for neonatal jaundice, although other factors can be aggravated in carriers, such as pathological jaundice caused by breast milk . Another possible mechanism of jaundice in infants born to HBV carriers is disturbed fat metabolism in HBV patients which significantly increases maternal blood cholesterol levels and subsequently increases the neonatal blood cholesterol level through umbilical cord circulation. Thus, jaundice develops secondary to the significant increase in the erythrocyte membrane triglyceride content that changes the shape of the erythrocytes and leads to their destruction in the spleen . Other studies have suggested that CS increases the risk of neonatal jaundice , which may be related to the delayed feeding associated with CS that may cause neonatal dehydration and jaundice. By contrast, CS has also been reported as a protective factor against the development of neonatal jaundice [7, 18, 19]. Most newborns born by CS are not breastfed in time and do not pass through the birth canal, and as a result, the risk of delivery trauma or bruising is minimal . However, in our study, the incidence of CS and neonatal jaundice in the HBV replication group was high. Since CS is considered by some scholars to be protective against the development of neonatal jaundice, it suggests a clear correlation and clinical significance between the HBV replication and neonatal jaundice. Taken together, these results highlight the importance of increased awareness of the onset of neonatal jaundice in newborns born to mothers with HBV replication.
In our study, the incidence of vaginal infection in the HBV replication group was higher than that in the non-HBV replication group (P<0.05) after matching confounding factors, with no significant difference observed between the high and low HBV replication subgroups (P>0.05; Table 7); this has not been reported in any previous studies. A vaginal infection refers to a series of diseases that are caused by an imbalance in the normal vaginal microbiome. The reproductive tract microbiome has its own characteristics that vary at different ages, and its structural composition is closely related to the levels of estrogen and progesterone in the body ; the peak level of estrogen is 1000 times higher in pregnancy than in non-pregnancy. This microbiome is also affected by other interfering factors, such as the changes in maternal immune status, adaptability of major systems, and drug use . Previous studies suggested that the numbers of Lactobacillus in the vagina of pregnant women was negatively correlated with the concentration of pro-inflammatory factors interleukin (IL)-6 and IL-8 . Concurrently, some studies have shown a higher detection rate of HBV DNA in the vagina of patients with active HBV replication than that of the general population , and the concentration of IL-6 and IL-8 was also found to be higher than that of the non-HBV infected population [22, 23]. Therefore, we hypothesize that active HBV replication may interfere with the normal vaginal environment of pregnant women through pro-inflammatory factors. Furthermore, it could reduce the numbers of Lactobacillus and promote the development of a vaginal infection. Moreover, previous studies have shown that hyperglycemia is a risk factor for vaginal infections. Our analysis showed that, although there was no significant difference in the prevalence of GDM between the two groups, the difference in fasting blood glucose level was significant (P<0.05). Therefore, we speculate that hyperglycemia is another possible reason for the higher vaginal infection rate. Although HBV replication during pregnancy is linked to an increase in the vaginal infection rate, it does not increase the probability of other adverse outcomes, such as premature rupture of membranes and premature birth.
This study has some limitations worth noting. First, HBV DNA levels were not monitored dynamically, hindering a detailed comparison of our data. In addition, due to the retrospective study design, it was not possible to evaluate differences in bacterial communities before and during pregnancy between the two groups; thus, in our follow-up prospective study, we will obtain additional data to more accurately evaluate the vaginal flora of pregnant women.