Effect of maternal antibody on immunogenicity of hepatitis A vaccine in infants

OBJECTIVE: To determine the effect of maternal antibody on hepatitis A vaccine immunogenicity in infants.Study design Infants of mothers negative for antibody to hepatitis A virus (anti-HAV; group 1) were administered hepatitis A vaccine at 2, 4, and 6 months of age, and infants of anti-HAV-positive mothers were randomized to receive either hepatitis A vaccine (group 2) or hepatitis B vaccine (group 3) on the same schedule. Group 3 infants subsequently received hepatitis A vaccine at 8 and 10 months of age. RESULTS: At 15 months of age, 100% of infants in group 1, 93% in group 2, and 92% in group 3 had protective levels of antibody. However, there were significant differences in the geometric mean concentration (GMC) of anti-HAV between groups. Group 1 GMC was 231 mIU/mL, compared with 85 mIU/mL for group 2 and 84 mIU/mL for group 3 (P<.001, group 1 vs group 3). CONCLUSIONS: Passively acquired maternal anti-HAV resulted in a significantly lower final antibody response when infants were administered hepatitis A vaccine at 2, 4, and 6 months of age or at 8 and 10 months of age.     

Decline of maternal hepatitis A virus antibody levels in infants

Hepatitis A is a common viral infection causing substantial morbidity and mortality. The anti-hepatitis A virus (HAV) vaccination in infants would guarantee control of the infection. However, the immunogenicity of the HAV vaccine in infants could be impaired by the presence of passively acquired maternal HAV antibodies. This study evaluated the prevalence of HAV antibodies in 103 women at delivery and in their babies in the first year of life. Eighteen mothers (17.5%) had anti-HAV serum level >10 mIU ml(-1). In their infants the anti-HAV level was still positive in 11 out of 18 (61.1%) at 12 mo. Two out of 85 infants born to anti-HAV-negative mothers and anti-HAV negative at birth were found to be positive at 5 mo of age. Conclusion: It is proposed that all women be screened at delivery for anti-HAV antibodies. Children born to anti-HAV-negative mothers could be vaccinated early during the first year of life, whereas vaccination could be postponed in children born to anti-HAV-positive mothers, if necessary.     

Immunogenicity of hepatitis B vaccine in preterm infants

AIM: To assess the immunogenicity of hepatitis B vaccine in preterm and term infants, given in a sequence of three doses beginning soon after birth. METHOD: The immunogenicity of hepatitis B vaccine was assessed in 176 preterm infants (< 35 weeks of gestation), immunised soon after birth, and compared with that in 46 term infants. Titres of hepatitis B antibodies were determined one to two months after the third vaccine. The significance of the differences between the term and preterm groups was determined using Student's t test. RESULTS: A similar proportion of infants in both preterm and term groups attained protective titres of hepatitis B antibodies (88.7% vs 93.4%, respectively; p = NS). However, the term infants had a higher geometric mean titre of antibodies after the third vaccine than did the preterm infants (701.2 (745.0) vs 469.1 (486.2) mU/ml, respectively; p < 0.03). CONCLUSION: Hepatitis B vaccine is effective in most preterm infants when given soon after birth. It may be advisable to determine the immune response at 12-24 months of age to booster the non-responders.     

不同孕周早产儿接种乙肝疫苗后的免疫反应性

目的 探讨不同孕周早产儿生后短时间内接种乙肝疫苗的免疫反应性.方法 将孕周为30～36周的早产儿分为两组:组Ⅰ 30～33周,组Ⅱ34～36周;组Ⅲ为≥38周的健康足月儿.组Ⅰ、组Ⅱ于生后1周内接种基因乙肝疫苗5 μg(0.5 ml),第2、第3次于生后1、6月龄时接种;组Ⅲ按(0、1、6月,5 μg)方案常规接种,三组均于第3次乙肝疫苗接种后4个月左右查抗-HBs滴度.若母亲是乙肝病毒携带者,出生12 h内注射抗乙肝免疫球蛋白(HBIg)0.5 ml.结果 完成随访者组Ⅰ 28例,组Ⅱ32例,组Ⅲ39例.抗-HBs滴度:组Ⅰ为(570±388)mIU/ml,组Ⅱ(669±401)mIU/ml,组Ⅲ(693±286)mIU/ml,三组比较,差异无统计学意义(H=1.20,P＞0.05);抗HBs强应答所占百分比:组Ⅰ 22/28例(78.6%),组Ⅱ28/32例(87.5%),组Ⅲ37/39例(94.9%),三组比较差异有统计学意(x2=198,P＜0.01).结论 早产儿出生不久即接种乙肝疫苗,其抗体水平产生较好,早产儿强应答百分比低于足月儿,以30～33周早产儿更为明显.     

Immunogenicity of hepatitis B vaccine in term and preterm infants

Some studies have suggested that decreased seroconversion rates might be found in premature infants with low birthweight (< 2000 g) following administration of hepatitis B vaccine at birth. The aim of the present investigation was to evaluate possible differences in seropositive rates between full-term and preterm infants after primary vaccination, in particular when gestational age or birthweight is very low. Two-thousand and nine neonates born to HBs Ag-negative mothers were vaccinated with 10 μg of recombinant hepatitis B virus (HBV) vaccine, from May 1991 to October 1994. Children with infections, congenital malformations or serious illnesses were excluded. HBV vaccine was administered intramuscularly, on the fourth day of life and again at 1 and 6 months of age. A 1-ml blood sample was drawn from each infant 1 month after the third vaccine dose for determination of the level of anti-HBs antibody. The response to HBV vaccination was evaluated in 241 preterm (gestational age < 38 weeks) infants and 1727 term neonates. No statistical difference was observed in the distribution of anti-HBs antibody level, either between preterm infants (< 38 weeks) and newborns of normal gestational age, or between low birthweight (< 2500 g) and normal weight infants. The results suggest that preterm and low birthweight infants (< 2500 g) respond to HBV vaccine in the same measure as normal-term infants.     

Effect of a prepregnancy pertussis booster dose on maternal antibody titers in young infants

To examine the influence of a pertussis booster vaccination on the transfer of maternal antibodies, 24 nonpregnant women received a tetanus, diphtheria, acellular pertussis booster vaccine between 2 consecutive pregnancies. Blood was drawn from mothers and off-spring. Efficient transplacental antibody transfer and significantly higher antibody titers against 3 pertussis antigens were observed in cord blood and in blood of 1-month-old infants born after a maternal booster vaccination compared with results in their siblings born before the booster administration.     

Hepatitis A vaccination of infants: effect of maternal antibody status on antibody persistence and response to a booster dose

BACKGROUND: Infants with passively transferred maternal antibody (PMA) to hepatitis A virus (HAV) have lower concentrations of antibody to HAV (anti-HAV) after vaccination. We examined the effect of PMA on persistence of anti-HAV and on immune memory. METHODS: We measured anti-HAV concentrations of 6-year-old children who had responded to a three dose hepatitis A vaccine series at ages 2, 4 and 6 months. Group 1 children were born to anti-HAV-negative women; Group 2 children had anti-HAV-positive mothers and PMA at 2 months of age. Children without detectable antibody at 6-year follow-up were offered a booster dose [360 enzyme-linked immunosorbent units (ELU)]. An anamnestic response was defined as a postbooster anti-HAV concentration of > or =400 mIU/ml. RESULTS: At follow-up, before the booster dose, Group 1 subjects had a higher geometric mean concentration (50 mIU/ml vs.18 mIU/ml, P = 0.007), and a larger proportion retained seroprotective concentrations of anti-HAV [21 of 31 (68%) vs.4 of 17 (24%)] compared with Group 2 subjects. The two stage antibody decline curves for the two groups from 8 months old to follow-up testing were parallel. An anamnestic response occurred in all (5 of 5) Group 1 and 67% (4 of 6) of Group 2 children. The geometric mean antibody concentrations after the booster were 1102 and 406 mIU/ml for Groups 1 and 2, respectively (P = 0.10). CONCLUSIONS: Infants with PMA who receive hepatitis A vaccine have significantly lower concentrations of anti-HAV 6 years later than infants with no PMA who receive hepatitis A vaccine. Immune memory may remain functional despite these lower anti-HAV concentrations.     

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.     

Current update of pediatric hepatitis vaccine use

Vaccines are now available for the prevention of hepatitis A and hepatitis B. In this article, biologics are reviewed with special attention to their use in the pediatric patient. Special attention is paid to issues that developed in 1999. For hepatitis A vaccine, it is the change in US recommendations regarding increased use in higher-risk US locations. For hepatitis B vaccine, it is the concern about toxicity, real or imagined.     

Response of preterm infants to hepatitis B vaccine.

Ninety-nine preterm infants with birth weights < 1750 gm had three doses of hepatitis B vaccine. Fifty-seven received the first dose when they weighed > or = 1000 gm (group 1) and 42 when they weighed > or = 2000 gm (group 2). The final seropositive rates and geometric mean titers of group 1 infants (79%, 61 mIU/ml) and group 2 infants (91%, 262 mIU/ml) were less than that of 43 normal term infants (100%, 679 mIU/ml).     

Inflammatory responses to hepatitis B virus vaccine in healthy term infants

Hepatitis B virus (HBV) infection continues to be a serious global health problem. During the course of HBV vaccination, we observed C-reactive protein (CRP) elevation in term infants without sepsis. Therefore, we prospectively studied interleukin-6 (IL-6) and CRP responses to HBV immunization. In 70 healthy term infants without signs and symptoms of sepsis and sepsis risk factors, IL-6, CRP, and white blood cell count levels were determined before and 24 h after immunization. Significant increases in CRP levels were seen 24 h after vaccination (p?<?0.001). Although CRP levels of 22 infants at second evaluation were above the cutoff level for sepsis (4.82 mg/L), they had no clinical signs and symptoms of sepsis. After 48–72 h, CRP levels of these infants returned to normal levels with no blood culture positivity. Conclusion: our study showed that HBV vaccine is responsible for CRP elevation in term infants after vaccination at birth. To the best of our knowledge, this is the first study evaluating CRP response to HBV vaccine at birth in term infants. We suggest that this response should be considered in differentiation of early neonatal sepsis to avoid unnecessary antibiotic use.     

Drug-exposed infants and developmental outcome: effects of a home intervention and ongoing maternal drug use

OBJECTIVE: To evaluate the effects of a home intervention and ongoing maternal drug use on the developmental outcome of drug-exposed infants. DESIGN: Longitudinal randomized cohort study of a home intervention with substance-abusing mothers and their infants. Mother-infant dyads were randomly assigned to a control or intervention group at 2 weeks' post partum. Control families received brief monthly tracking visits. Intervention families received weekly home visits from 0 to 6 months and biweekly visits from 6 to 18 months by trained lay visitors. PARTICIPANTS: One hundred eight low-income, inner-city, drug-exposed children (control, 54; intervention, 54) who underwent developmental testing at 6, 12, and 18 months post partum and who remained with their biological mothers through 18 months. MAIN OUTCOME MEASURES: Infant scores from the Bayley Scales of Infant Development (BSID) at 6, 12, and 18 months post partum. Maternal report of drug use during the pregnancy and ongoing drug use through 18 months post partum was assessed. RESULTS: In the repeated-measures analyses, intervention infants had significantly higher BSID Mental Developmental Index (MDI) and Psychomotor Developmental Index scores than control infants. Ongoing maternal cocaine and/or heroin use was associated with lower MDI scores. Finally, MDI scores decreased significantly in both groups. CONCLUSIONS: Ongoing maternal drug use is associated with worse developmental outcomes among a group of drug-exposed infants. A home intervention led to higher BSID scores among drug-exposed infants. However, BSID MDI scores decreased during the first 18 months post partum among inner-city, low-socioeconomic-status infants in the present study.     

Immunogenicity of an inactivated hepatitis A vaccine in infants and young children

BACKGROUND: Infants with passively transferred maternal antibody, born to mothers immune to hepatitis A virus (HAV), have a blunted response to hepatitis A (HA) vaccine. We compared HA vaccine immunogenicity among infants born to immune and susceptible mothers, vaccinated on different schedules. METHODS: Infants were randomized into 3 groups, each receiving 2 doses of 720 EL.U. of HA vaccine (HAVRIX; Glaxo SmithKline): group 1 at ages 6 and 12 months, group 2 at ages 12 and 18 months and group 3 at ages 15 and 21 months. We determined mothers' antibody to HAV (anti-HAV) status and infants' anti-HAV concentrations at the first vaccine dose (baseline) and at 1, 7 and 12 months thereafter. All were tested at age 13 months for responses to recommended routine vaccinations administered during infancy. RESULTS: Of 248 participants, 140 were born to HA-susceptible mothers and 108 to immune mothers. At baseline, 34 of 36 (94%) group 1, 5 of 34 (15%) group 2 and one of 38 (3%) group 3 infants born to immune mothers were seropositive. By month 7, all participants in all groups were seropositive except group 1 infants born to immune mothers (34 of 36 [94%], seropositive). In group 1, peak geometric mean concentrations between infants born to immune (794 mIU/mL) and susceptible (2083 mIU/mL) mothers were significantly different. Across groups, peak geometric mean concentrations were similar among infants born to susceptible mothers (3166 mIU/mL, group 2; 3153 mIU/mL, group 3). Among infants born to immune mothers, the difference between groups 1 and 3 (2715 mIU/mL) was significant. There were no differences in responses to routine vaccinations. CONCLUSIONS: HA vaccine is immunogenic among infants born to HA-susceptible mothers and those born to immune mothers and vaccinated beginning > or =12 months old. Passively transferred maternal antibody persists for at least 6 months and results in a blunted response to HA vaccination.     

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.