Whooping Cough Vaccination for Pregnant Women: Neat Idea, Missed Opportunity

New medical advice is transmitted at such lightning speed these days that GPs and their patients often have to work their way through it in tandem. This was illustrated to me quite starkly on Friday morning with the announcement of a new, temporary vaccination programme in the UK for pregnant women to protect their children from whopping cough. The first I heard about the proposal was on the radio over breakfast, by mid-morning I learnt that all GPs had been sent an e-mail with the new instructions, and before lunch I was trying my best to advise one of my pregnant patients on the issue. Funny how you can feel reasonably up-to-date on Thursday evening, and behind the times only 12 hours later!

Having had the luxury of the weekend to actually read the information from the Department of Health I feel a little more prepared to advise women in the coming week – and this is what is required of a GP these days. It is not sufficient simply to adhere to the Government line on these matters; patients expect, and deserve, a doctor who will consider medical advice carefully and be willing to give thoughtful guidance. And my conclusions? In a nutshell, it’s a great idea, but why, oh why, oh why are the Department of Health not conducting a proper clinical trial?

The proposal is to vaccinate all pregnant women between 28 and 38 weeks gestation against Pertussis (whooping cough) as a temporary programme in response to the significant rise in infection rates in the last 2 years. And whatever else we think, it is certainly a neat idea. We do have a problem with Pertussis at the moment, both in the UK and worldwide. The number of confirmed cases so far in the UK in 2012 is nearly 5000, compared with around 1000 for the whole of 2011. There is no doubt that this is in part due to greater awareness of Pertussis at the moment on the part of doctors (myself included) and so increased diagnosis of cases in adults that would previously have been missed. However, this seems to be more than just an artefact, since there has been a sharp rise in the number of cases in infants under the age of 3 months, many of whom become very unwell and in whom diagnosis will always have been much more accurate. It is the very young who are the concern with Pertussis, since they will not yet have immunity from the vaccination programme, and their small lungs are especially vulnerable. So far in 2012 there have been 9 deaths in babies in the UK, and many more will have been seriously unwell.

How best to protect these babies? Well if everyone was immunised then there would be no-one to transmit the infection to them (the protection afforded by herd immunity), but this is extremely difficult with Pertussis since the protection afforded by vaccination wanes within a few years. Unlike the recent measles epidemics where poor uptake of MMR is clearly to blame, most cases of Pertussis in older children and adults occur in people who have been fully vaccinated. A programme where everyone was immunised every 5-10 years would work, but the cost of this would be enormous.

The beauty of vaccinating pregnant women is that we know the woman will make antibodies against the disease, and that these can cross the placenta in late pregnancy, be taken up by the baby and could afford protection in those crucial early weeks until the childhood vaccinations have kicked in. A single vaccine therefore protects exactly the at risk individual, and there is no need to depend on herd immunity. When a mother chooses to accept the vaccine she is choosing to protect her own child – the personal potential benefit is very clear.

We have good reason to think the vaccine is safe. It is a killed vaccine, which means it cannot possibly cause active infection, and these vaccines have reliably been shown to be safe in pregnancy. The vaccine also contains diphtheria, Tetanus and Polio vaccination (there is no single Pertussis vaccine so the combination has to be used) and the first two of these have often been used in pregnant women without difficulty. While there is not much data for this exact vaccine it seems extremely unlikely that there are any risks other than local reactions in the arm and very rare allergic reactions, and only vaccine conspiracy theorists are likely to argue against this.

It is also likely to work. I agree with the conclusions of the expert committee that:

…it is reasonable to assume that this approach would provide young infants with some important, although possibly not complete, protection against pertussis, and it is likely to be the most effective immunisation strategy to provide protection to young infants.

The report also state, however, that

the effectiveness of prenatal immunisation against pertussis to protect young infants is uncertain.

There are reasons to think it might not work. Will the maternal antibodies be sufficient to truly protect? Is there any risk that the antibodies might actually interfere with the response to the infant vaccination programme, and lead to reduced immunity later in childhood? So what should a scientist do when he or she has a good hypothesis which is uncertain: Test the hypothesis with a trial. There is such an opportunity here to answer this question for both the current and future generations – we need to conduct a Government funded, blinded, randomised clinical trial. Instead of rolling out this temporary programme as a knee jerk reaction, pregnant women could be offered the chance to be in the trial. They would receive either the vaccine or a placebo injection, meaning adverse reactions in the pregnancy could be compared, as could infection rates and outcomes in the babies.

Within a year we would start to get a real answer to this question. If it works then this could become a permanent and valuable addition to our fight against this serious disease. If it is shown to be ineffective then we could stop wasting time and money, go back to the drawing board and look for a better solution. What is more, the vaccine itself would be protected against unfounded claims of harm. Sadly the background rate of stillbirth is sufficiently high so that the Daily Mail headline “Whooping Cough Vaccine Killed my Baby” might as well have already been written, and without the robust clinical evidence available from a randomised trial these inevitable anecdotal stories will be much harder to evaluate. Granted, the trial would need to be large and the cost would not be insignificant, but the long-term gain of truly knowing how to protect babies from this infection must surely be worth it.

So how should I advise my patients in the lack of proper trial data – well it is a shame we shall never know for sure, but the issue is important enough to take action, and the balance of risk has to be in favour of the vaccine.