Immunization Responses in Preterm Infants Who Receive Postnatal Steroid Treatment: In Reply

This is the authors' abstract. We don't add key points for this paper.

In Reply.—The points raised by Drs Berrington and Fenton illustrate difficulties inherent in comparing outputs of necessarily small studies by using different antigens and combinations over different epochs.We studied diphtheria, tetanus, and whole-cell pertussis vaccine (DTwP) and separately administered Haemophilus influenzae type b (Hib).1 It is not true that Hib geometric mean titers (GMTs) reported for our non–steroid-treated subgroup were unusually higher than in any other United Kingdom preterm cohort, because GMTs obtained in the study by Heath et al,2 for which identical antigens were used, were not significantly different (GMT [95% confidence interval] 2.73 μg/ml [1.63–4.58]).Slack et al3 used diphtheria-tetanus-acellular pertussis (DTaP) with combined Hib and serogroup C meningococcal conjugate vaccine C (Meningitec) in a temporally later study and observed substantially lower Hib geometric mean concentration titers. This reduced immunogenicity in infants given an acellular pertussis-Hib combination mirrors that observed in term infants.4 It is interesting that when a fourth Hib as DTwP-Hib was given at a mean of 7.8 months to this group, Hib titers rose to 4.68 μg/ml, which correlates closely with our own observed titers after 3 doses of DTwP and separate Hib.5We presented data for diphtheria, tetanus, and 4 pertussis antibodies.6 Postimmunization diphtheria antibodies in non–steroid-treated infants are comparable with those of Ramsay et al,7 who did not give Hib, and with Slack et al,3 who used combined DTaP-Hib. Postimmunization tetanus antibody titers were substantially higher than those observed by Ramsay et al and less so than those of Slack et al. The titers of the unpublished work by Berrington and Fenton are less easy to interpret because 2 different diphtheria and tetanus toxoids and pertussis-Hib combinations were pragmatically used. Without more detailed information including population characteristics, vaccine schedule, immunoglobulin data, and numbers receiving postnatal steroids, meaningful comparisons are not possible.Group contamination by inclusion of steroid-treated infants in comparator studies may have accounted for some observed differences in titers. The marginal delay in completion of the vaccination schedule in our study6 could have increased the antibody response; the more-substantial delay in drawing blood for antibody levels may have reduced titers. There may have been a “dose effect” caused by giving a standard antigenic vaccine load to infants of different weights, but this issue cannot be addressed further, because weights at immunization have generally not been presented in published work and were not offered by Berrington and Fenton. It is difficult to explain why tetanus antibody levels are relatively elevated while diphtheria levels are in keeping with those of other investigators, and this indeed may reflect selective vaccine-antigen interactions.