Long term hepatitis B vaccine in infants born to hepatitis B e antigen positive mothers

Neonates of hepatitis B surface antigen (HBsAg) positive and hepatitis B encoded antigen (HBeAg) positive mothers received 10 µg of recombinant hepatitis B vaccine at months 0, 1, 6, or 0, 1, 2, 12, with or without immunoglobulin at birth, and were followed up to the age of 8 years for HBsAg, anti-HBc, and anti-HBs. Some were boosted at month 60. The overall vaccine protection at month 12 was 96.2%. No child became a chronic carrier beyond the age of 3 years, showing that this vaccine provides immediate protection against HBsAg carriage, and long term protection against fetally acquired HBsAg. After month 60 hepatitis B serological markers without disease, indicating re-exposure to HBV, reappeared in comparable numbers among boosted and non-boosted children (5 for a total of 167 children).  This vaccine provides long term protection against hepatitis B chronic carriage and infection in high risk neonates with or without a month 60 booster. A booster at the age of 5-6 years or 11-12 years would reduce HBV infection, viral circulation and transmission, while ensuring long term antibody persistence.     

Long term efficacy of hepatitis B vaccine in infants born to hepatitis B e antigen-positive mothers.

The long term protective efficacy of recombinant hepatitis B vaccine, administered alone or concomitantly with hepatitis B immunoglobulin, was assessed in 263 healthy neonates of hepatitis B e antigen-positive mothers. Infants received the first dose of vaccine at birth; additional doses were given at either Months 1, 2 and 12 or Months 1 and 6. During the follow-up period, which ranged from 2 to 4 years, protective titers (> or = 10 mIU/ml) of anti-hepatitis B surface antibodies were found in virtually all infants who had responded to the primary course of vaccination. "Natural boosts," without persistent infection, were observed in only a small number of children. All children who were shown to have become chronic carriers were infected within the first year of life. No statistical difference in long term protective efficacy could be shown between the two vaccination schedules used or between the use of vaccine alone or vaccine plus hepatitis B immunoglobulin for either schedule.     

Hepatitis B antigen in infants born to mothers with chronic hepatitis B antigenemia in Taiwan.

Hepatitis B antigen (HB Ag) was detected by complement fixation (CF) in serum samples of 7.5% of 1,106 pregnant Chinese women tested in Taipei, Taiwan. HG Ag persisted in all but one of 42 women followed for 1 to 18 months (average, nine months) after delivery, and 27 of the 43 infants (63%) born to those women became antigen-positive. Persistance of the antigen was more common than transient or intermittent antigenemia. Twelve had antigenemia when first tested, while 15 later developed antigenemia, usually during the first six months of life. Only one infant developed antibody to HG Ag (anti-HB Ag), and this occurred after transient antigenemia. The HB Ag was found in two of 32 (6%) fathers, and in 18 of 27 (67%) older siblings. The antigen was more common among siblings of antigen-positive than among those of antigen-negative infants. These findings demonstrate that in Taiwan, infants born to mothers who are asymptomatic carriers of HB Ag commonly become infected by heaptitis B (HB) virus. Exposure of infants near the time of birth may be important maintaining the high, chronic HB Ag carrier rate in Taiwan.     

The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers

Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasma-derived vaccines. However, its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemic area. We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen (HBsAg) carrier mothers in a study of recombinant vaccine efficacy. They were randomized into 2 groups, A (54 infants) and B (56 infants), to receive 4 doses of vaccine, containing 20 or 10 micrograms of surface antigen, respectively, at 0, 1, 2 and 12 months of age. An additional 60 high risk infants were recruited later (Group C) and received three 20-micrograms doses of vaccine at 0, 1 and 6 months of age. All infants also received a dose (145 IU) of hepatitis B immunoglobulin soon after birth. Sera were collected at 0, 1, 2, 3, 6, 12 and 14 months of age to assay HBsAg and anti-HBs. At 12 months of age the HBsAg carrier rates were 7.4 and 1.8%, in Groups A and B, respectively. In Group C the HBsAg-positive rate was 3.3%. HBsAg was invariably first observed between 0 and 2 months of age. Virtually all noncarrier infants developed substantial titers of anti-HBs at 12 months of age. No serious adverse effect was observed after vaccination.     

Significance of measurement of pre-S2 antigen for the prevention of vertical transmission of hepatitis B virus in infants born to HBsAg carrier mothers

Terazawa S, Kondo N, Orii T. Significance of measurement of pre-S2 antigen for the prevention of vertical transmission of hepatitis B virus in infants born to HBsAg carrier mothers. Acta Pædiatr 1994;83:30–4. Stockholm. ISSN 0803–5253
The significance of pre-S2 antigen (pre-S2 Ag) as a marker of hepatitis B virus (HBV) infection, especially in infants born to HBsAg carrier mothers who are HBeAg-negative or HBeAg-positive, was evaluated. Pre-S2 Ag was measured by enzyme immunoassay. HBsAg carrier mothers who were HBeAg-negative and HBeAb-positive were divided into two groups: group A, mothers whose infants were not infected with HBV ( n = 10) and group B, mothers whose infants were infected with HBV ( n = 13). Absorption rates of pre-S2 Ag in group A and B were 0.09 k 0.04 and 1.36 ± 0.95, respectively. The values for pre-S2 Ag in group B were significantly higher than those in group A. Values for pre-S2 Ag among HBsAg carrier mothers who were HBeAg-positive and HBeAb-negative were also measured by reversc passive hemagglutination. In the same way, HBsAg carrier mothers who were HBeAg-positive and HBeAb-negativc were divided into two groups: group C, mothers whose infants did not become HBsAg carriers ( n = 15) and group D, mothers whose infants became HBsAg carriers (n = 11). The titers of pre-S2 Ag (reverse passive hemagglutination) in group C and D were 2^{5.75 ± 1.68} and 2^10.45±^1.69, respectively. The values for pre-S2 Ag in group D were significantly higher than those in group C. The values for pre-S2 Ag as markers of infectivity became higher with increasing amounts of HBV-DNA. Therefore, our results show that measurement of pre-S2 Ag in HBsAg carrier mothers who are HBeAg or HBeAb-positive is useful in the detection of high-risk groups of vertical transmission of HBV.     

Different degree of antibody response to hepatitis B virus vaccine in breast- and formula-fed infants born to HBsAg-positive mothers

Antibody response to hepatitis B virus vaccine was compared in 47 breast- and 112 formula-fed infants born to hepatitis B surface antigen-(HBsAg-) positive mothers. No difference was observed as to the percentage of infants who seroconverted. However, formula-fed infants developed transient but significantly higher anti-HBs antibody levels as compared to breast-fed infants. Suppressive factors in human milk or orally induced tolerance may explain this finding. The latter hypothesis may be supported by the presence of HBsAg in more than half of the milk samples we studied.     

Vertical hepatitis B transmission by anti-HBe positive hepatitis B carrier mothers

5 infants (3 boys and 2 girls) were infected vertically with hepatitis B virus by their healthy anti-HBe positive HBsAg carrier mothers. First sign of infection in the infants occurred 1 to 6 months after birth. The course of the disease was as follows: subclinical hepatitis B (1 case), acute hepatitis B with complete resolution (1 case), fatal fulminant hepatitis B (1 case), chronic persistent hepatitis B (1 case), and chronic active hepatitis with rapid progression to cirrhosis. We conclude that anti-HBe positive hepatitis B carrier mothers may be infective and thus may cause serious, eventually fatal disease in their infants. Passive-active immunization must be given to infants of all hepatitis B carrier mothers irrespective if they are anti-HBe positive or not.     

Lymphocyte abnormalities in infants born to drug-abusing mothers

To evaluate the possible effects of maternal intravenous drug use on infant immunity, we measured the in vitro peripheral blood mononuclear cell proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen, T cell subset numbers, immunoglobulin levels, and titers of antibodies to cytomegalovirus (CMV) and human immunodeficiency virus (HIV) in a group of drug-abusing mothers and their infants. Infants of drug abusers had a lower proliferative response to mitogen, associated with altered kinetics of the maximum response to PHA. The OKT4/OKT8 ratio decreased with age in the drug-exposed infants compared with control infants (P less than 0.005). There was no evidence of CMV infection in either group. One mother and her infant had antibody to HIV. Our data demonstrate that infants of intravenous drug-using mothers have distinct immunologic differences at birth compared with non-drug-exposed infants and that these persist throughout the first year of life. The cause appears unrelated to intrauterine viral infection, suggesting a direct toxic effect of the drugs on fetal immunologic development.     

Oxidative stress in infants born to preeclamptic mothers

BACKGROUND: Oxidative stress may play an important role in the pathophysiology of preeclampsia. An increase in lipid peroxidation products and a decrease in antioxidant activity in preeclamptic women have been reported in many papers. The objective of this study was to evaluate oxidative stress in infants born to preeclamptic mothers. METHODS: Malondialdehyde (MDA) and glutathione (GSH) levels and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured in cord plasma of infants born to preeclamptic (n = 18) or normotensive (n = 9) mothers. RESULTS: Gestational age was similar in both groups. The mean birth weight was significantly lower in the preeclamptic group (P = 0.007). Maternal age, primigravidity, antenatal steroid use, premature rupture of the membranes, clinical chorioamnionitis and adverse neonatal outcomes including sepsis, respiratory distress syndrome and neonatal mortality did not differ between groups. Cesarean delivery was significantly higher in the preeclamptic group. There was no significant difference in cord plasma levels of MDA and GSH, and activity of GPx between the preeclamptic and control groups. SOD was found to be increased in preeclamptic group (P = 0.03). CONCLUSIONS: We concluded that although cord plasma MDA levels were similar in both the preeclamptic and control groups, increased SOD activity might be an indicator of increased oxidative stress in infants born to preeclamptic mothers.     

Fatal hepatitis B in infant born to a HBsAg carrier with HBeAb.

Fulminant hepatic failure occurred in an 11 week old baby of a Caucasian mother who was hepatitis B surface antigen positive, B e antigen negative, and B e antibody positive. Infants of hepatitis B e antigen positive mothers receive immunoprophylaxis against hepatitis, unlike those born to mothers who are B e antibody positive.