Hepatitis B Vaccination in Premature Babies

 1 Published: 17.11.04 Updated: 17.11.2004 11:53:16
E. Yu. Kozubova and I. I. Mebelova
State Children`s Hospital, Department of Health Care and Social Defence, Petrozavodsk, Republic of Karelia
152 premature infants, vaccinated against virushepatitis B, were studied for hyperbilirubinemia and liver enzyme activity. Grade 1 and 2 hyperbilirubinemia had 67% study-group infants compared to 93% of the control group nonvaccinated premature infants. Of 151 immunized infants eleven had elevated levels of ALAT and ASAT


Premature and small for gestation age babies undergo numerous invasive diagnostic procedures and treatment such as transfusion therapy and surgical interventions. For this reason they are at high risk for hepatitis B virus infection. Hepatitis B vaccination is vital for this group of patients.
Since the beginning of 2000, all newborns in Petrozavodsk are subjects of specific prevention of hepatitis B according to the Russian Immunization Calendar (the order of the Ministry of Health Care of the Russian Federation no 375 from 18. 12. 1997).

The objective of this study was to follow up premature infants immunized against hepatitis B on the first day of life.


The main group of the study included 152 premature babies with a birth weight between 1500 and 3050 grams and gestation age from 31 to 37 weeks. They were immunized on the first day of life in Maternity Homes with  “Engerix B” vaccine. Subsequently, the premature neonates were transferred to the Premature Babies Department of the State Children’s Hospital.
For comparison, we performed a retrospective survey of 231 medical histories of premature babies (gestation age 30-37 weeks and birth weight 1300-3000 grams) treated in the same department in 1999 prior to implementation of the hepatitis B immunization.

We compared the diagnoses and the bilirubin levels in the two groups of babies.

Results and discussion

The total number of infants with grade 1 and 2 hyperbilirubinemia in the vaccinated group was 67% compared to 93% in the control group (table 1).

Table 1. Bilirubin levels in newborn infants hepatitis B vaccination


Immunized infants

Control group

Number of infants



Range of birth weights

1500 – 3050 g

1300 – 3000 g

Range of gestational age

31 – 37 weeks

30 – 37 weeks

Normal bilirubin levels

52 (33%)

18 (8%)

Grade 1 hyperbilirubinemia


38 (25%)


124 (54%)

Grade 2 hyperbilirubinemia


25 (16%)


67 (29%

Grade 3 hyperbilirubinemia


36 (14%) [14 and 9%]*


22 (9%) [11 and 5%]*

* Bilirubin levels above 320 micromol/l

The number of infants with grade 3 hyperbilirubinemia was 14% higher in the vaccinated group than in the control group (36 versus 22 infants). 14 (9%) of the vaccinated infants and 11 (5%) infants in the control group had bilirubin levels of more than 320 micromol/l.

The vaccinated infants were tested for enzyme liver activity (transferase levels). Of 151 of immunized babies 11 had elevated levels of ALAT and ASAT. ALAT was above the normal level in nine infants (0.9 – 1.0 micromol/l  in six; 1.0 – 1.2 in two and above 1.6 in one). ASAT was above the normal level in 11 (0.7 – 1.1 micromol/l in 6, 1.1 – 1.2 in 3 and 1.2 – 1.34 in two). Among the eleven infants with elevated transferase levels, one had persistent elevation (ALAT 1.6 and ASAT 1.34). Eventually, this child was found to be HbsAg-positive. We are currently investigating whether this infection represents a vertical infection or an infection after vaccination. In the other cases the elevated level of enzymes was temporary, and soon returned to normal.

There were no differences in the diagnoses in the vaccinated and in the control group (intrauterine infections of different etiologies, intracranial hemorrhages, respiratory distress syndrome, hypoxia and ischemia of the brain, and congenital malformations) infants.
Children were discharged from the hospital. Follow–up activities included weight control, dietary prescriptions and immunization according to the schedule.
The incidence of vertically transmitted hepatitis B cases per 1000 live births has decreased in Petrozavodsk following the implementation of the Neonates Vaccination Programme: in 1998 – 5,2, 1999 – 5,1 and 2000 – 2,9.

Further studies are necessary to analyze the possible effects of hepatitis B vaccine on liver function in premature babies, including detailed tests of liver enzymes activity as well as their immunological status.