Reviewing a review..

Infections may account for up to 15% of early miscarriages and up to 66% of late miscarriages

*Gasps of terror*

According to the latest Giakoumelou review, the role of infection in miscarriage, a whopping 78% of 101 tissue samples from miscarriages were found to be infected with bacteria. I doubt I’m alone in the fact, when I initially read these numbers I thought wow, that’s a huge problem. Why has this remained unnoticed and how can this be prevented?

Blood vessel picture

First and foremost, I’ll introduce the theory around this subject. It is often overlooked that pregnancy is an abnormal situation for woman. Immune systems are honed throughout our lives to attack anything that contains different genetic coding. So when an embryo, which also contains paternal DNA, takes up residence in the womb, factors must be in place to prevent the immune system seeing this as a threat. This is particularly important when you remember that the placenta is the site of gas, nutrient and waste material exchange; therefore blood vessels must exist in close proximity, to permit diffusion into the mother’s bloodstream.

So what prevents rejection of the foetus? Immunity is regulated by a group of proteins known as cytokines. Some cytokines are inflammatory and activate the immune system; triggering defences against pathogens, injuries and potential allergens. On the other hand, regulatory cytokines inhibit the immune system; preventing hypersensitivity and reactions to basically everything (including developing pregnancies and food). Current opinion is that when pregnancy begins, regulatory cytokines are up-regulated; preventing an immune attack and allowing the pregnancy to continue. If inflammatory cytokines are activated, there is an increased likelihood of the immune system attacking the embryo.

Seesaw

The Delicate Pregnancy Cytokine See-Saw

Where do infections come into this? Miscarriage sadly is not uncommon; occurring in around 1 in 5 pregnancies. Experts currently believe, the inflammatory cytokines activated upon infection are enough to harm and potentially abort a foetus; disrupting the normal tolerance-rejection harmony of pregnancy. This is fairly logical in my opinion.

The review however, made some pretty bold claims and upon further inspection, some claims weren’t entirely supported by the data presented.

Review pros:

  • Evidence from multiple sources showed pathogens such as malaria, HIV, influenza and bacterial vaginosis are associated with an increased risk of miscarriage. Evidence supported that the studied infections were detrimental to pregnancy outcome.
  • Review highlighted a crucial area for future research; finding how infections actually result in miscarriage. Such research has the potential to uncover fertility issues and enhance the chances of successful conception or IVF attempts.
  • Proposed a viable screening programme, implemented could protect women hoping to fall pregnant.

The cons:

  • The data acquired for this review was predominantly from less developed countries, with a higher prevalence of stated diseases. Countries with a higher prevalence, will automatically have an increased incidence of infected mothers.
  • A study based on high-prevalence groups will not accurately reflect the worldwide population.
  • Each given study only tested for a single disease; many infections are associated with other infections. This combination may influence miscarriages and therefore data lacks comprehensiveness.
  • A causal relationship between infections and miscarriage was described but not supported. Researchers continue to investigate the exact mechanisms that may terminate pregnancies. This relationship therefore, needs solid supporting evidence.
  • Although study states that further education is needed regarding the risks of infections in pregnancy, this seems premature.

Under the current UK NHS regime, infection testing for pregnant women is only offered on an optional basis. This suggests the trends described in the paper may not be consisted within the population of the UK.

The study argues further education is needed regarding the risk of infections in pregnancy. How could you educate the population when experts themselves do not clearly understand the exact mechanisms? With the UK’s drug-me-up mentality, it is likely that an education campaign will cause a stampede of women demanding tests and treatments; even though the incidence of many infections in the UK is relatively low. Aside from the previously discussed problems (see antibiotic post), some infection therapies are also associated with birth defects, among other foetal problems; therefore an education campaign should not be pursued unnecessarily.

The review certainly raises some concerning figures as previously highlighted. Although there is a clear link between infections and miscarriage, the conclusions drawn from this review would have been more convincing with mechanistic evidence. This would improve the scope of securing government funding for a compulsory screening programme. Whilst I agree these preventative measures should take place worldwide, the screening programmes should be tailored to developing countries who are exposed to higher risks of infections. Relative to the UK, a revised trial may be effective for understanding miscarriages; this would help determine the current position of miscarriages in the UK and potentially save government funding for worthwhile causes.

Although the paper raises many questions, this is what scientists live for right? The authors are perhaps causing premature alarm by publishing the article, without supportive evidence. Further research is certainly needed to uncover the full picture. In the meantime, always question what you read folks!

 

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