The issue of breastfeeding by HBV-positive mothers has attracted more and more attention. Previous studies demonstrate that breastfeeding by HBV-infected mothers is safe and does not increase the risk of MTCT if the newborns have received active-passive immunoprophylaxis [23, 24], including HBeAg+ CHB mothers . Although a previous study has shown that HBsAg, HBeAg, and HBV DNA may be presented in breastmilk  but generally cannot enter the infant blood through the internal barrier of the intestinal mucosa. Only when mucosal permeability is increased due to complications or injuries, the virus has the opportunity to synthesize and enters the infant blood . Therefore, guidelines have suggested that breastfeeding should be encouraged for infants undergoing the standard passive-active immunoprophylaxis [6, 28, 29]. However, there is no consensus on whether HBV-infected mothers receiving pregnancy category B NAs treatment should breastfeed. The 2015 Chinese guideline  did not recommend breastfeeding for mothers who need to continue pregnancy category B drugs postpartum.
Based on the notions that TDF and LDT belong to pregnancy Category B medications, and TDF has low potential toxicity in breastmilk [20–22], we encourage HBV-infected mothers to breastfeed postpartum, even when continuing pregnancy category B NAs treatment. However, a large proportion of the HBV-infected mothers were not compliance to the breastfeeding recommendation. In the current study, of the 155 pregnant CHB women receiving NAs treatment during the gestational period, only 40.65% of cases underwent exclusive breastfeeding. In this study, we investigated the causes of incompliance to breastfeeding in HBV-infected mothers receiving NAs treatment during pregnancy for preventing MTCT. Our results showed that the artificial feeding group had significantly higher parity than the breastfeeding and mixed feeding groups and multivariate logistic regression analysis showed that higher parity was the independent factor associated with artificial feeding. This observation is inconsistent with previous reports that higher parity children are more likely to be breastfed . However, we did not survey the feeding habits of prior parity in those with multiple parities. Therefore, the clinical meaning of this phenomenon is limited.
Among the 110 cases of stopping NAs treatment at the delivery day in this study, 45.45% and 25.45% of cases adopted exclusive breastfeeding and mixed feeding, respectively; only 29.02% used artificial feeding. However, of the 20 continuing NAs treatment after delivery, 70.00% of the cases used artificial feeding. On the other hand, among the 120 cases with the knowledge of medication (LDT/TDF), 71.67% of cases adopted breastfeeding or mixed feeding, while 28.33% of cases used artificial feeding. By contrast, in 32 cases without the knowledge of medication, 68.75% of the cases used artificial feeding. In addition, multivariate logistic regression analysis confirmed that both postpartum timing of stopping NAs treatment and knowledge of medication were independent factors associated with incompliance to breastfeeding. The association between later postpartum timing of stopping NAs treatment and artificial feeding should be attributed to concerning the drugs remaining in breastmilk may have an adverse effect on breastfed infants. However, the previous study shows that breastfed infants have a blood TDF concentration of only 2% -4% of maternal blood , so breastfed infants have lower TDF exposure than those in exposed the fetuses [20, 21]. Recently, Hu et al. have compared the dosage levels of TDF exposure in fetuses, breastfed infants, and children receiving tenofovir treatment. Their results reveal that the daily TDF dose ingested from breastmilk represented only 0.01–0.04% of the proposed pediatric therapeutic daily dose for children receiving TDF treatment and 0.5%–16% of those in exposed the fetuses . These findings suggested that TDF has low potential toxicity in breastmilk. In fact, concerning later postpartum timing of stopping NAs treatment may harm infants is the same as a lack of knowledge of these NAs. It is worth to mentioned that even the healthcare workers may not have systematic and comprehensive knowledge about HBV MTCT . Therefore, making a health education leaflet to explain the low concentration of category B pregnancy drugs LDT / TDF in breastmilk may be an important method to improve compliance to breastfeeding in HBV-infected mothers receiving NAs treatment during pregnancy.
Our findings could provide a reference for revising the guidelines to recommend breastfeeding for HBV-infected mothers receiving pregnancy category B NAs treatment. In the least Chinese guidelines for the prevention and control of mother-to-child transmission of hepatitis B virus (2019 edition) , breastfeeding is no longer opposed for HBV-infected mothers receiving NAs treatment during pregnancy, but breastfeeding is still not explicitly recommended.
There are still some limitations to this study. First, this is a retrospective study with a relatively small sample size. In addition, we did not survey the feeding habits of prior parity in those with multiple parities. In the future, a prospective large trial should be conducted to validate the findings of this study.