Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn.

OBJECTIVE: Prolonged neonatal jaundice, beyond day 14 of life, is very common and of concern to the clinician. The aim of this study was to investigate whether a genetic mutation in the bilirubin UGT1A1 gene, which has been associated with Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal jaundice. STUDY DESIGN: Blood was collected from 85 term newborns with unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided into 6 groups depending on whether they were breast-fed or bottle-fed and whether they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and analysis of the entire UGT1A1 coding sequence was performed in a representative sample (11 of 26) of very prolonged cases. RESULTS: In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified. Statistical analysis of the TATA genotype distributions within the group of breast-fed neonates revealed significant differences among the acute, prolonged, and very prolonged subgroups (.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the Gilbert's phenotype as children or young adults. CONCLUSIONS: A genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood.

Immune response to simultaneous administration of a combined measles, mumps and rubella vaccine with booster doses of diphtheria-tetanus and poliovirus vaccine.

A combined vaccine against measles (Edmonston-Zagreb 19 strain), mumps (Rubini strain) and rubella (Wistar RA 27/3 strain) was administered to a group of 46 children aged 10-12 months simultaneously with booster doses of compulsory diphtheria-tetanus toxoid and oral poliovirus vaccine. A second group of 53 children aged 15-24 months who had received booster doses of the compulsory vaccines 5 to 12 months before was also vaccinated. The same seroconversion rates (100%) and similar antibody titers for rubella were observed in both groups. The same seroconversion rates for mumps (93%) and similar rates for measles (98 and 94%) were observed in the two groups. Significantly lower antibody titers for measles and mumps were found in the first group, but they were compensated by an earlier protection, a reduction of number of visits for immunization, costs for the community, and improvement in parental compliance. These results confirm that Edmonston-Zagreb 19 and Rubini strains are still immunogenic even when they are combined with Wistar RA 27/3 strain. Moreover, a long term follow-up in order to verify the persistence of protective antibody levels in both groups of children, could suggest that combined measles, mumps and rubella vaccine could be given earlier (at 10-12 months of age), simultaneously with booster doses of diphtheria and tetanus toxoid and of trivalent oral poliovirus vaccine.

Immune response to simultaneous administration of a recombinant DNA hepatitis B vaccine and multiple compulsory vaccines in infancy.

The reactogenicity and immunogenicity of simultaneous administration of recombinant DNA hepatitis B vaccine with diphtheria and tetanus toxoids (DT) and oral poliovirus vaccine (OPV) in 111 infants were compared with those of DT and OPV alone in a control group of 21 infants. All subjects received three doses of the vaccine according to one of three different schedules of vaccination. Reactions following simultaneous administration of vaccines were all but absent, with mild pain reported for four out of 111 subjects, compared with one of 21 in the control group. Seroconversion rates of 98-100% and high anti-HBs geometric mean titres (GMTs) were observed in all study groups after three doses of hepatitis B vaccine. Significantly higher anti-HBs were seen in Group III, where six months is allowed between the second and the third hepatitis B vaccine doses, compared with Group I and II, where only 1-2 months separate the second and third doses. A fourth dose of vaccine was needed in both these groups to obtain anti-HBs levels as high as seen in Group III after three vaccine doses at 3, 4 and 10 months of age. The immune response to DT and OPV was similar in the study groups and the control group. It is concluded that a course of 10 micrograms doses of recombinant hepatitis B vaccine given simultaneously with DT and OPV elicits a strong anti-HBs response and does not interfere with the immune response to the other antigens.