Immunogenicity and safety of early vs delayed BCG vaccination in moderately preterm (31–33 weeks) infants

Abstract

Minimum gestation at which infant can be given BCG (Bacillus Calmette-Guerin) vaccine safely at birth is not clearly defined. Our objectives were the following: to compare Mantoux test after 6 months of BCG immunization in moderately preterm babies (31-33 weeks) vaccinated at birth and 34 weeks post conception age and to compare in above groups:(a) Interferon -gamma (IFN-g) levels in BCG vaccinated infants who did not react to Mantoux test (b) Local BCG reaction at 6, 10, 14 weeks and 6 months (c) Complications of BCG vaccination. Interventional, randomized comparative trial. Moderately preterm infants (31-33 weeks), 90 in each group. At birth, 180 moderately preterm infants were recruited and randomly allocated into 2 groups. Two ml venous blood was drawn for estimation of IFN-g levels. Infants were given BCG vaccine within 72 hours of birth and followed up after 2, 4, 6, 10, 14 weeks and 6 months (group 1). Infants were recruited at birth and held up till 34 weeks post conception age (group 2) and then given BCG vaccine and followed up similarly as group 1. At each visit, local BCG reaction, any local or unusual complication and anthropometric measurements were noted. At six months, Mantoux test was done and 2 ml venous blood sample was collected for IFN-g levels post vaccination. Presence or absence of BCG local reaction, PPD conversion rates and complications were analyzed using Chi square or Fisher's exact test. IFN-g levels were analyzed by ANOVA. In all 117 infants could be followed till 6 months after BCG immunization in 2 groups, and Mantoux test was positive in 38.4% of them. The rate of Mantoux test positivity was similar irrespective of the age of giving BCG immunization (group 1-39.1% vs group 2-37.5%; p > 0.05). IFN-g levels were significantly raised at 6 months in 60% (n D 21/41) and 65% (n D 15/27) Mantoux negative infants in group 1 and group 2 respectively. The sequence and order of local BCG reaction at 2, 4, 6, 10, 14 weeks and 6 months was in the form of papule, pustule, ulcer, scab and scar. Scar was formed in 94.2% and 89.5% infants in group 1 and group 2 respectively. One infant in group 1 showed abortive reaction (0.85%). Only 3.4% of infants developed lymphadenopathy and was similar in both the groups. Moderately preterm infants (31-33 weeks) exhibited 98.3% immunogenicity after BCG immunization at birth and can be safely vaccinated without any risk of severe complications.

Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn

“…Furthermore, of importance to global health, these findings support the hypothesis, that in the appropriate context in countries in which neonatal immunization with BCG is recommended, concurrent administration of (BCG + HBV) at birth to the moderate to late preterm and term newborn may enhance the protective response to HBV immunization. Of note, in relatively small preterm studies thus far, BCG has been immunogenic and safe when administered to the moderately to late preterm infant [31–33 weeks GA] ( 80 ). Further studies of the safety, efficacy and mechanism of action of the combination of (BCG + HBV) compared to each alone in newborn animals, including humans, will shed further light into this important area crucial to the protection of the most vulnerable among us.…”

Safety and Immunogenicity of Early Bacillus Calmette-Guérin Vaccination in Infants Who Are Preterm and/or Have Low Birth Weights

“…Seven studies 14 , 20 , 21 , 22 , 23 , 31 , 32 reported scar formation and TST conversion and were therefore included in a meta-analysis. Only data on infants who were preterm and/or LBW and had follow-up adequate to record scar formation (n = 515) or TST conversion (n = 397) were included.…”

“… 62 A trial in India on 180 neonates born between 31 to 33 weeks’ gestational age reported 2 infants in each of the early and late vaccination groups with nonsuppurative lymphadenopathy (a total of 4 individuals). 21 There were no other adverse reactions, and meta-analysis was not possible.…”

“…One study comparing infants who were moderately preterm and vaccinated within 7 days of birth or at 34 weeks’ postconception age reported no difference at age 6 months in interferon-γ levels in the unstimulated serum of infants who had not responded to the TST. 21 …”

Two Randomized Trials of the Effect of the Russian Strain of Bacillus Calmette-Guérin Alone or With Oral Polio Vaccine on Neonatal Mortality in Infants Weighing <2000 g in India

“…Results from other studies suggest also that the preterm infants born at 32-36 weeks of gestation can be effectively immunized with BCG at birth. 199,200,201,202 In a Brazilian study a typical BCG scar was verified in 96.9% of the control group and in 90.0% of the preterm infants. 203 In contrast a study which evaluated the efficacy of BCG vaccine in pre-term infants in UAE concluded that male pre-term infants of lower gestational ages (<33 weeks) are less likely to develop BCG scar and a reactive PPD tuberculin test after BCG vaccination.…”