Mother-to-child transmission of hepatitis B virus (HBV) is among the most important causes of chronic HBV infection and is the commonest mode of transmission worldwide. Currently, the presence of HBsAg, HBeAg and HBV DNA in breast milk is confirmed. Several studies have reported that breastfeeding carries no additional risk that might lead to vertical transmission. Beyond some limitations, the surveys have not demonstrated any differences in HBV transmission rate regarding feeding practices in early childhood. Promotion of breastfeeding is substantial, especially for low-income individuals and regions with uncertain, unfeasible, and unsafe water supplies. Lactoferrin, minimal inflammation or activation within the infant gut during exclusive breastfeeding, and nonspecific biological molecules in the milk are identified as major factors of breast-milk defense. This review discusses preemptive antiviral therapy during pregnancy and lactation. Long-term follow up of breast-milk HBV concentrations and correlation with serum viral load; nucleos(t)ide analogue concentrations in breast milk in HBV-positive mothers in the setting of chronic HBV infection; safety of antiviral therapy during pregnancy and lactation; and the difference in viral load in the milk in exclusive or non-exclusive breastfeeding are still open questions. The paper reviews the current data and outlines the course of further investigation into this often underestimated issue.
VERTICAL TRANSMISSION OF HEPATITIS B VIRUS
It is estimated that almost 50% of the cases of chronic hepatitis B virus (HBV) infection result from vertical transmission or are acquired in early childhood, especially in endemic areas. The prevalence of chronic HBV infection in pregnant women reflects that in the general population. About 5% of mothers worldwide are chronic HBV carriers; ranging from 0.6% in low-endemic regions to > 20% in high-endemic areas in the Far East and Africa[4,5]. The prevalence of HBeAg in pregnant HBV-positive women exceeds 50% in some high-endemic regions.
Mother-to-child transmission (MTCT, or vertical transmission) of HBV is one of the most important causes of chronic HBV infection and is the most common mode of transmission worldwide. Maternal screening programs and universal active and passive immunoprophylaxis of newborn have reduced dramatically the HBV transmission rates by 95%. However, vertical transmission is still responsible for a significant number of cases of chronic infection and remains a serious problem. MTCT can occur prenatally, during delivery, or postpartum. HBV is found in amniotic fluid, breast milk, vaginal fluids, cord blood and infant gastric content[9,10].
A large number of vertically transmitted cases occur intrapartum due to possible transfusion of the mother’s blood to the fetus during contractions, as a consequence of membrane rupture, and via direct contact of the fetus with infected secretions, blood or other fluids from the maternal genital tract. The risk of intrauterine infection is relatively low because the fetus is protected from HBV by the placenta. However, reported vaccination failures imply in utero transmission especially in high-risk groups (highly viremic and/or HBeAg-positive mothers)[12,13]. Furthermore, the risk is related to the presence of HBV DNA in the placenta and to maternal viremia, which supports an association between maternal HBV load during pregnancy and the risk of transmission to the baby.
Despite successful screening and vaccination programs, high maternal HBV DNA is correlated with perinatal transmission. Wiseman et al have shown a transmission rate of 8.5% for infants born to mothers with virus levels > 8 log10 copies/mL and no transmission below this cut-off. We need additional studies to assess the potential risk reduction associated with treatment of high maternal viremia during pregnancy. A study from India has found that maternal viral load > 1.5 × 105 copies/mL is associated with intrauterine transmission. This presumes that nucleos(t)ide therapy during the third trimester with lamivudine (greater experience; FDA Category C) or tenofovir and telbivudine (Category B) might be beneficial. All these data concern prevention of intrauterine and perinatal transmission in mothers with HBeAg-positive chronic hepatitis and/or high titers of HBV DNA.
Some questions arise regarding breastfeeding in cases of chronic hepatitis B. Firstly, most studies that have been concerned with vertical or early childhood transmission have not reported breastfeeding rates, or if they have, the data are still the subject of debate. Secondly, the nucleoside analogues are likely to pass into breast milk to some degree. We have not established a policy for what to do in the case of nucleos(t)ide prevention in mothers who chose to breast feed. Thirdly, we have to measure the risk of breast-milk transmission in low-income individuals and regions with uncertain, unacceptable, unfeasible, and unsafe water supplies, or replacement feeding.
Recent studies have demonstrated the short- and long-term benefits of breastfeeding both for mothers and children. Breastfeeding, especially if exclusive and prolonged, leads to significant reduction in hospitalization rates for gastroenteritis, respiratory infections, and sepsis in the early months of life. The benefits for low-resource countries are even greater because breastfeeding is related to better infant and childhood survival. Exclusive breastfeeding for 6 mo, followed by continued breastfeeding at least to 12 mo, could prevent 1 301 000 deaths or 13% of all child deaths under 5 years of age in a hypothetical year. New findings have emerged for older children, which support the role of prolonged breastfeeding in their cognitive functions. A gene related to neuronal growth that depends for its effects on breastfeeding has been found recently. Individuals who carry at least one copy of this gene have higher IQ scores, but only if they have been breast-fed.
For older children and adults, long-term effects most probably include a possible impact of breastfeeding on cholesterol levels, body mass index, obesity and type 2 diabetes[23-25].
The benefits for breastfeeding mothers have been well described. Shorter recovery and oxytocin-stimulated uterus contraction prevents anemia. Lactation-induced suppression of ovulation has contraceptive effect during the period of exclusive breastfeeding. Lactating women seem to regain their pre-pregnant weight sooner, and in the long-term have reduced obesity risk. The risks of breast and ovarian cancer and osteoporosis are also decreased[27-29]. When considering breastfeeding, we cannot omit the positive emotions and close mother-to-infant contact.
Despite consistent global policies in support of breastfeeding for the general population and World Health Organization (WHO) recommendations, the debate regarding HBV-infected women is still open in some countries. Guo et al recently have reported an embarrassing number of HBV-positive women who opted for bottle feeding because of concern about the risk of transmission of HBV via breast milk.