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Apnoea following immunisation in premature infants
  1. D J STALKER, Specialist Registrar
  1. Bristol Royal Hospital for Sick Children
  2. St Michael's Hill, Bristol BS2 8BJ, UK

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Editor—Slack and Schapira1 are correct in drawing attention to a problem that is recognised and documented but not fully addressed or understood. Their suggestion that further studies are required to determine the optimum timing of immunisation for extremely preterm infants is sound (even though the adequate immunological response of these babies to vaccinations is well documented).

However they state that the presumed cause of the apnoeas is the pertussis component, with neither reference nor explanation of why they think this is the case. As the four antigens are given simultaneously it is not possible to identify the culprit. The American studies quoted2 ,3 could not identify whether one or a combination of antigens was the cause or indeed whether one of the several other substances contained within vaccines contributed to the reaction. Indeed Sanchez et al merely postulate that pertussis is the most likely reason because it has been reported in the past to provoke more local and systemic reactions, although the incidence of associated reactions in their cohort was low.2 Botham et al claim that pertussis endotoxin acting centrally may stimulate apnoeas3 although there is no evidence for this. To determine this matter a randomised controlled trial of whole cell pertussis, acellular pertussis, and placebo would be required. Plainly this is not an ethical or practical option, hence it would seem sensible to follow the suggested advice of monitoring these infants for 48 hours, especially in very low birth weight infants and those with chronic lung disease. The effects of implementing acellular pertussis vaccine will be awaited with interest.

In view of recent and not so recent media hysteria of unconfirmed (and indeed discounted4) claims of the adverse effects of vaccines, we should not be fuelling this matter by making suppositions which cannot yet be supported by the scientific evidence.


Dr Slack and Dr Schapira respond:

  We thank Dr Stalker for his comments about our report. He is quite correct that neither we nor any of those authors who have previously described these events have provided any evidence that it is either the pertussis component of the diphtheria/tetanus/whole cell pertussis vaccine or its endotoxin content that is responsible for these reactions. That is why we described it as “the presumed cause”.

It is possible that any of the vaccine components or adjuvants are responsible. It may simply be a response to pain, although this seems unlikely. However, given the evidence of reduced local and systemic reactions with acellular pertussis vaccines in term infants compared with the UK whole cell vaccine,1-1 it seems plausible that the pertussis component may be involved.

He is partially correct in stating that the way to answer this would be to conduct a three way randomised trial between placebo, acellular (DTaP), and whole cell pertussis (DTwP) vaccines. In fact, it would require multiple randomisations between Hib, DT, DTwP, one, two, three, and five component DTaP vaccines, and placebo. Even if the use of a placebo were ethically acceptable, which we agree would not be the case, the low incidence of these events would make the number of infants required for such a study impossibly large.

We are, however, conducting a multicentre study to determine the incidence of apnoeas following immunisation using a three component acellular vaccine.

Finally, we do not accept that we have joined the ranks of those who have shaken confidence in the vaccination programme. The question is not whether preterm infants should be immunised against pertussis but when and with what vaccine.


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