Risk factors and mechanism of transplacental transmission of hepatitis B virus: A case‐control study

Abstract

Intrauterine hepatitis B virus (HBV) infection has been suggested to be caused by transplacental transmission that cannot be blocked by hepatitis B vaccine. This would decrease the effectiveness of hepatitis B vaccine. This study examined the risk factors and mechanism of transplacental HBV transmission. A case-control study included 402 newborn infants from 402 HBsAg-positive pregnant women. Among these, 15 newborn infants infected with HBV by intrauterine transmission were selected as cases, and the rest as controls. A pathology study included 101 full-term placentas from the HBsAg-positive pregnant women above and 14 from HBsAg-negative pregnant women. Immunohistochemistry staining and HBV DNA in situ hybridization were used to estimate the association of intrauterine HBV infection and HBV infection in the placentas. HBeAg positivity in mothers' sera (OR = 17.07, 95%CI 3.39-86.01) and threatened preterm labor (OR = 5.44, 95%CI 1.15-25.67) were found to be associated with transplacental HBV transmission. The intrauterine infection rate increased linearly and significantly with maternal serum HBsAg titers (trend test P = 0.0117) and HBV DNA concentration (trend test P < 0.01). Results of the pathology study showed that HBV infection rates decreased gradually from the maternal side to the fetal side (trend test P = 0.0009) in the placental cell layers. There was a significant association between intrauterine HBV transmission and HBV infection in villous capillary endothelial cells (VCEC) in the placenta (OR = 18.46, P = 0.0002). The main risk factors for intrauterine HBV infection are maternal serum HBeAg positivity, history of threatened preterm labor, and HBV in the placenta especially the villous capillary endothelial cells. Previous reports of transplacental leakage of maternal blood causing intrauterine infection are confirmed. In addition, there appears to be a "cellular transfer" of HBV from cell to cell in the placenta causing intrauterine infection. This latter hypothesis needs to be confirmed.

Chronic Hepatitis B Virus Infection and Pregnancy

“…31 Although, maternal HBeAg positivity has been suggested as an independent risk factor for mother to infant transmission, 32 this finding has not been confirmed by other studies. 33,34 In a study from China, in 54 mother-infant pairs (33 mothers were HBeAg positive, and 21 HBeAg negative; all babies received passive-active immunoprophylaxis with hepatitis B immune globulin and hepatitis B vaccine), 70% (23/33) of neonates from HBeAg-positive mothers were HBeAg positive at birth compared with 0% (0/21) of neonates from HBeAg-negative mothers.…”

Tenofovir in the Management of Chronic Hepatitis B Infection During Pregnancy

“…Since maternal HBeAg positivity, HBsAg titer and HBV DNA level are considered among the risk factors for transplacental transmission of HBV (14), our administration of HBIG and HBV vaccine which is a regimen considered to be effective in preventing transmission of hepatitis B in more than 95% of children, seems to be in line with current recommendations for prevention of maternal-infant transmission of hepatitis B (6,15).…”

HBV Infection in Pregnancy-Management and Definition of Risk Factors for Vertical Transmission

“…Doğumda, maternal HBV DNA düzeyinin >10⁶ kopya/ml olması abg için en önemli prediktördür. [18][19][20][21][22][23][24] …”

“…Öne sü-rülen IUT mekanizmaları: a)İnfekte sperm veya oosit yoluyla, erken embriyolojik dönem-de [28] b)Maternal periferal mononükleer hücreler yoluyla [29] c)Hücresel transfer yoluyla: HBV, plasentanın villöz kapiller endotel hücreleri ve trofoblastlarında saptanmıştır [30]. d)Erken doğum tehdidinde, plasental kaçış ile [19] e)Amniosentez ile: Amniosentez teorik olarak, olarak plasental bariyerin(özellikle anterior yerleşimliyse) bozulmasıyla anneden bebeğe geçiş riskini artırır. Ancak yapılan çalışmalarda amniosentezin abg riskini anlamlı olarak artırmadığı ortaya konmuş-tur.…”

“…Ayrıca erken doğum eylemi ve doğum sıra-sında instrumasyona bağlı travma da maternofetal mikrotransfüzyona ve HBV transmisyon riskinin artmasına neden olmaktadır. [19] İnfektif sıvılarla kaplı, maternal genital trakt ile direkt temas HBV transmiyonundan sorumludur. [47].…”