Hepatitis B vaccination of premature infants: A reassessment of current recommendations for delayed immunization

Objective. Current American Academy of Pediatrics and United States Public Health Service Immunization Practices Advisory Committee recommendations fo r hepatitis B immunization in premature infants weighing <2 kg at birth bor n to hepatitis B surface antigen (HBsAg)-negative mothers are to delay the initiation of vaccination until such infants reach 2 kg or until 2 months o f age. This proposal to delay vaccination at birth in these low-risk infant s was based on limited studies not conducted in the United States. We sough t to reassess current recommendations to delay administration of hepatitis B vaccine in low-risk premature infants by determining the immunogenicity o f early hepatitis B vaccination in a US population and identifying variable s associated with poor immunogenicity. Methods. A total of 148 infants <37 weeks' gestation born to mothers negati ve for HB,Ag were recruited at birth and stratified to three birth weight g roups: <1000 g, 1000 to 1500 g, and >1500 g. Recombinant hepatitis B vaccin e was administered within the first week of life, at 1 to 2 months of age, and at 6 to 7 months of age. Serum obtained at birth and after the second a nd third doses of vaccine was tested for antibody to HB,Ag. Variables assoc iated with poor response were sought prospectively by collecting demographi c and clinical data. Results. A total of 118 subjects (83%) completed the study. Postsecond dose sera were available for 117 infants and postthird dose sera were available for 112 infants. The seroprotection rate (attaining greater than or equal to 10 mIU/mL HE, antibody) after two doses was low (25%) regardless of birt h weight; infants weighing <1000 g at birth had the poorest response (11%). The seroprotection response rate after three doses of vaccine increased wi th birth weight; infants weighing less than or equal to 1500 g at birth (gr oups 1 and 2) had lower rates of response (52% and 68%, respectively) than did infants weighing >1500 g at birth (group 3; 84% response rate). The ser oprotection response rate of group 3 infants after three doses of vaccine, although low, could not be differentiated from the response rates reported for full-term infants using 95% confidence intervals. Of all infants who di d not achieve protective levels of antibody after three doses of vaccine, 9 6% (26/27) weighed <1700 g at birth. The geometric mean HE, antibody levels in responders were 88 and 386 mIU/mL after two and three doses, respective ly. Of 36 children with a birth weight >1500 g, 33 (91%) achieved levels of HE, antibody >100 mIU/mL after three doses of vaccine, compared with 25/35 (71%) of infants with birth weight <1500 g. Using logistic regression analysis, nonresponders were more likely than wer e responders to have been treated with steroids (26% vs 9%) and to have had a low birth weight (1037 g vs 1455 g). In addition, the seroresponse rate of black infants was more likely than that of white infants to be associate d with poor weight gain (falling off 2 percentile ranks in weight) in the f irst 6 months of life: 22% of black and 60% of white children who failed to gain weight adequately responded to vaccination, compared with 92% of blac k and 70% of white children who were growing adequately. Of interest, the o nly infant with a birth weight of >1700 g who did not make protective level s of specific antibody after three doses of vaccine was 2300 g at birth, bu t had inadequate weight gain in the first 6 months of life. Conclusions. This study supports current recommendations of the American Ac ademy of Pediatrics and the Centers for Disease Control and Prevention for delaying the initiation of hepatitis B immunization beyond the first week o f life for premature infants at low risk for hepatitis B infection, particu larly in newborns weighing <1700 g at birth. In addition, we have identifie d variables other than birth weight that were associated with an inadequate immune response to early hepatitis B vaccination in premature infants, suc h as poor weight gain in the first 6 months of life and steroid use in the first few months of life.