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Preterm infants respond well to the three doses of diphtheria, tetanus, and whole cell pertussis (DTP) vaccine,1 but dexamethasone treatment may impair immunogenicity.2,3 We investigated whether four, rather than three, DTP doses may be preferable for primary immunisation of steroid treated preterm infants. Twelve infants born at < 30 weeks gestation who had received dexamethasone for chronic lung disease were given doses of DTP vaccine combined with Hib (ActHIB DTP; Pasteur-Mèrieux-MSD) at 2, 3, and 4 months of age. A fourth dose was administered six weeks after the third immunisation (table 1). With the use of standardised enzyme linked immunosorbent assay (ELISA) methods, paired sera obtained before and eight weeks after the fourth DTP dose were analysed at the Health Protection Agency (Porton Down, Wilts, UK) for antibody titres against diphtheria toxoid (DT), tetanus toxoid (TT), and three pertussis antigens (fimbrial agglutinogens 2+3 (FIM), pertussis toxin (PT), filamentous haemagglutinin (FHA)). A pre-fourth DTP serum sample was available for 12 infants, and 11 infants had paired sera. Median (range) gestational age was 25 weeks (24–29) and birth weight was 830 g (550–1235). Median (range) duration of dexamethasone treatment was 15 days (3–153), and cumulative dose was 3.9 mg/kg (1.5–25.6).
Antibody titres of 0.1 IU/ml against DT and TT are considered to correlate with individual protection.4 After three doses, all infants had already achieved titres > 0.1 IU/ml against DT and TT, and titres remained above this concentration after the fourth dose. No significant increase in antibody titres against diphtheria or tetanus antitoxins resulted from the fourth DTP immunisation (table 2). Despite a trend towards higher mean pertussis antibody titres after four DTP doses compared with after three doses, the increase was not significant in any of the three pertussis antibodies. Although there are no reference protective antibody concentrations for pertussis, mean antibody titres achieved against the three pertussis antigens after three DTP doses compared favourably with those in historical cohorts of UK term1,5 and preterm1 infants who received the accelerated DTP schedule.
All infants showed excellent immunogenicity to three DTP doses; a fourth dose did not improve antibody responses further. In a recent study using diphtheria/tetanus/acellular pertussis vaccine, responses of 15 preterm infants appeared unaffected by recent steroid treatment.6 These data suggest that dexamethasone treated preterm infants are able to mount satisfactory responses to a standard three dose DTP regimen administered at the same chronological age as term infants, and that supplementary doses are unnecessary in early infancy.
We warmly thank the parents and infants for participating in this study. We thank Carol Thornton and Moya Burrage at the Health Protection Agency for respectively performing the serological testing and assisting with data retrieval, and Dr Stephen Roberts for allowing study of one of his patients.