Occult HBV Infection in Immunized Neonates Born to HBsAg-Positive Mothers: A Prospective and Follow-Up Study.
OBJECTIVE
Occult HBV infection (OBI) has been reported in infants born to HBsAg-positive mothers despite immunization. This study aims to determine the maintenance of this status in a prospective birth cohort.


METHODS
A total of 158 neonates born to HBsAg-positive mothers were enrolled. All received passive-active immunization against HBV according to a 0-1-6 schedule. Sera were collected at 7 months of age. Those diagnosed with OBI were serially followed up at 12, 24 and 36 months of age. HBV serological markers were determined by Abbott i2000 system. HBV DNA was quantitated by Abbott m2000 system. Standard PCR followed by direct sequencing were applied for mother-child HBV pairs. Homology and phylogenetic comparisons were done by BLAST and Mega 5.


RESULTS
All the 158 neonates were HBsAg-negative and anti-HBs-positive at 7 months of age, and 32 (20.3%) of them were diagnosed with OBI, with a median HBV DNA level of 1.97 (1.20-3.71) log IU/mL. Of them, HBV DNA was positive in 25.0%, 21.9% and 7.7% at 12, 24 and 36 months of age, respectively. HBV DNA disappeared at one of the follow-up points in 31 neonates, however, rebounded to low levels in 6 of them thereafter. HBV DNA persisted at low levels during follow-ups in the other one neonate apart from the above 31. All remained negative for HBsAg. Only two (6.3%) neonates were positive for anti-HBc after 24 months of age. HBV showed close homology and phylogenetic relationships for mother-child pairs. S-escape mutant, G145R, was not discovered. The first vaccine dose within 6 hours of birth significantly reduced the occurrence of OBI (59.4% vs. 83.3%, p = 0.003).


CONCLUSIONS
HBV may be controlled in immunized neonates of HBsAg-positive mothers, after being diagnosed with OBI. Timely vaccination against HBV may provide the utmost protection. Long-term and close monitorings are needed.
Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Ying
Y
Lu
Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Ya-Lin
YL
Liu
Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Jing-Jing
JJ
Nie
Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
Xiao-Feng
XF
Liang
Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Ling
L
Yan
Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
Fu-Zhen
FZ
Wang
Department of Infectious Disease, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China.
Xiang-Jun
XJ
Zhai
Department of Major Projects, Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou, 450053, China.
Jian-Xun
JX
Liu
Department of Infectious Disease, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China.
Feng-Cai
FC
Zhu
Department of Major Projects, Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou, 450053, China.
Zhan-Jun
ZJ
Chang
Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Jie
J
Li
D000328:Adult; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000276:immunology* / Q000821:virology; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control / Q000706:statistics & numerical data; D008297:Male; D009035:Mothers; D009154:Mutation; D010802:Phylogeny; D011446:Prospective Studies; D014611:Vaccination / Q000379:methods; D055815:Young Adult
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines