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Letters to the Editor

Indian Pediatrics 2000;37: 687-689

BCG Vaccination: Practical Dilemmas


The review on practical dilemmas on BCG vaccination by Kaur
et al. was interesting(1). The authors seek the evidenced-based answers for the following questions.

1. What is the minimum gestational age and birth weight at which BCG can be given within 2 weeks of birth?

2. At what chronlogical age a 26-32 weeks (<1.2 Kg) baby can be given BCG vaccination?

Surprisingly, Dr. Jacob John has suggested delaying BCG vaccination without carefully analyzing the currently available evidence. We had done a randomized control trial on BCG vaccination in preterm babies to address these issues(2). Sixty two consecutive preterm appropriate for date (AFD) babies born at < 35 weeks of gestation were randomly allocated into two groups. Babies in group A were vaccinated early at 34-35 weeks and group B were vaccinated late at 38-40 weeks of post-conceptional age. The cell-mediated immune response to BCG was assessed using the Mantoux test and the lymphocyte migration inhibition test (LMIT) 6-8 weeks after BCG vaccination. There was no significant difference in the tuberculin conversion rates (80% and 80.7%, respectively), positive LMIT (86.6% and 90.3%, respectively), or BCG scar (90.0% and 87.1%, respectively) among the two groups. We therefore concluded that prematurity per se is unlikely cause for poor vaccine uptake and cell mediated immune response or humoral response. Babies born at ³ 34 weeks (1.8 Kg) can be safely vaccinated with BCG and OPV within days after birth. Babies born at < 34 weeks can be vaccinated when they reach 34-35 weeks of post conceptional age, which is the time when they are usually discharged from hospital in developing countries.

Similar conclusions were reached by Dawadu et al. in a study comparing tuberculin conversion rates in preterm babies vaccinated at birth with preterm babies vaccinated at 38-40 weeks of post-conceptional age(3). Delaying vaccination till term gestation was reached did not seem to improve the conversion rates to BCG vaccination.

In a recent study Sedaghatian et al.(4) compared the tuberculin skin tests and scars following BCG vaccination in 36 preterm babies vaccinated at birth with 16 preterm babies vaccinated when they reached 40 weeks of post conceptional age. The differences in the Mantoux conversion rates and BCG scar between the two groups were not statistically significant. The authors subsequently did a multivariate analysis and found that birth-weight was significantly associated with tuberculin skin test reaction. The study however included small for date (SFD) babies.

There are several studies including our previous study to show that small for date babies indeed do have poor vaccine uptake(5,6) and delaying the vaccination as suggested by Dr. Jacob John may be considered. Sero-conversion to oral polio vaccine is reported to be similar in term and preterm babies(7). Therefore, both these vaccines can be conveniently given to a pre-term baby at 34-35 weeks of post conceptional age. Delaying vaccination beyond this is not justified(2).

Sudhin Thayyil Sudhan,
Neonatal Unit,
Leicester Royal Infirmary, UK
E-mail: [email protected]

Vinod K. Paul,
Neonatal Division,
All India Institute of Medical Sciences, 
New Delhi 110 029, India.

 References
  1. Kaur S, Faridi MMA, Ramachandran VG. BCG vaccination: Some practical dilemmas. Indian Pediatr 1999; 36: 941-944.

  2. Thayyil Sudhan S, Kumar A, Singh M, Paul VK, Deorari AK. Safety and efficacy of BCG vaccination in preterm babies. Arch Dis Child 1999; 81: F64-F66.

  3. Dawadu AH. Tuberculin conversion following BCG vaccination in preterm infants. Acta Pediatr Scand 1985; 74: 564-568.

  4. Sedaghatian MR, Hashem F, Hossain MM. Bacille Calmette Guerin vaccination in pre- term infants. Int J Tuberc Lung Dis 1998; 2: 679-682.

  5. Sedaghatian MR, Kardouni K. Tuberculin response in preterm infants after BCG vaccination at birth. Arch Dis Child 1993; 69: 309-311.

  6. Manerikar SS, Malaviya AN, Singh M, Rajagopalan P, Kumar R. Immune status and BCG vaccination in newborn infants with IUGR. Clin Exp Immunol 1976; 26: 173-175.

  7. Thayyil-Sudhan S, Singh M, Broor S, Xess I, Paul VK, Deorari AK. Is zero dose oral polio vaccine effective in preterm babies? Am Trop Pediatr 1998; 18: 321-324.

 Reply

The major issue highlighted by Drs. Thayyil Sudhan and Paul is that their paper on BCG in preterm babies had been missed out in my response to the dialogue initiated by Drs. Kaur, Faridi and Ramachandran. Indeed it was missed out both by myself and by Dr. Kaur and colleagues, simply because of the fact that the dialogue was submitted prior to its availability on literature search.

It is well known that cell mediated immune response is more primitive than antibody response and this phylogenic sequence is reflected in the ontogenic development of the fetus. The capacity to respond with CMI is present in any viable infant born even prematurely. Therefore it is quite likely that the immunogenic response to BCG should be present in the neonate even if prematurely born. But the problem is that the study by Sedaghatian and colleagues quoted both by Kaur and colleagues, and Thayyil Sudhan and Paul, showed slightly lower response (Mantoux and lymphocyte migration inhition) in small-for-date preterm babies. Thayyil Sudhan and Paul have shown that in preterm babies without intrauterine growth retardation, the response to BCG by way of Mantoux conversion or LMI were similar whether BCG was given at 34-35 weeks or at 38-40 weeks of post conception age.

My approach was from a different and a more practical angle. If a baby is born to a hepatitis B virus carrier mother, there is urgency in immunizing that infant as soon as possible in order to prevent infection even inspite of perinatal exposure to the virus. In the early days of BCG, babies born of mothers with open pulmonary tuberculosis had better survival if vaccinated soon after birth. Today, no such urgency of early immunization exists for BCG, in premature/low birth weight babies who are going to remain in the hospital for a period of time. So, I recommended that: "in general, any low birth weight baby may be given BCG as the baby is ready to be sent home". Usually the weight at discharge would be 1800 grams. Drs. Thayyil Sudhan and Paul also do not differ from this general principle, and they state that: "Babies born at <34 weeks can be vaccinated when they reach 34-35 weeks of post conceptional age, which is the time when they are usually discharged from hospital in developing countries". I was under the impression that such weight gain upto 1800 grams) would be achieved at about 38 weeks of post conceptional age, but I stand corrected that it would occur at about 36 weeks (or even 35) rather than 38 weeks.

The safety of BCG or OPV given at birth, even in low birth weight babies, has not been a question of worry for any one. Indeed, vaccine associated poliomyelitis would not occur if OPV is given when the infant has maternal antibody protection. On the other hand, to declare that "delaying vaccination (with both vaccines) beyond this (34-35 weeks) is not justified" is too strong a statement to be taken literally, from the point of view of the epidemiological need for these vaccines at that age. At-birth vaccination with these vaccines is for convenience and high compliance, whereas, for Hepatitis B vaccine for infants born of carrier mothers, it is for epidemiological necessity. Immunological response would occur in neonates to these vaccines, but not to several other antigens. That was, and is, my main message.

T. Jacob John,
Emeritus Medical Scientist (ICMR),
439, Civil Supplies Godown Lane,
Kamalakshipuram,
Vellore 632 002, India.
E-mail: tjjohn@ md4.vsnl.net.in

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