The Washington Post dropped this provocative headline on its readers yesterday, “Researchers find a hint of a link between flu vaccine and miscarriage.” And you know what will happen next –every anti-vaccine website will claim that the flu vaccine causes miscarriages.
Of course, the evidence based facts fail to support the future trope that the flu vaccine causes miscarriages. A careful reading of the Washington Post article is filled with nuance and hedging, because the underlying published article does not actually provide robust evidence that any flu vaccine increases the risk of miscarriages.
The Washington Post made several points that are important to consider, and we’ll examine the underlying research in more depth. But the most important point they made is that,
The findings suggest an association, not a causal link, and the research is too weak and preliminary, experts said, to change the advice, which is based on a multitude of previous studies, that pregnant women should get a flu vaccine to protect them from influenza, a deadly disease that may cause serious birth defects and miscarriage.
I wonder how many anti-vaccine radicals will fail to make that point, instead, screaming that “vaccines are dangerous and the worthless flu vaccine causes miscarriages.”
— Del Bigtree (@delbigtree) September 13, 2017
Well, of course. Del Bigtree isn’t known for his scientific knowledge.
Well, we don’t cherry pick our evidence here, so we’re going to look at the broad body of evidence with respect to the flu, flu vaccines and pregnancy. Because that’s how we roll here. And because we think pregnant women deserve the best information possible to protect themselves and their developing babies. Because that’s also how we roll here.
The flu vaccine causes miscarriages paper
The paper by Donahue et al., recently published in the journal Vaccine, was a case-control study utilizing data from the Vaccine Safety Datalink that suggested a link between a flu vaccine and miscarriages. And thus we start with the first concern with the study – the design.
Finding associations like this can come from these observational studies, which are relatively good at finding links between what appears to be two independent events. On the other hand, they are terrible at establishing causal links. All this study was able to uncover was that women who had miscarriages also tended to have received the flu vaccine two years in a row. Receiving the vaccine once did not show this result.
Why would I think that the research does not show a compelling link? Well, I could think of several reasons:
- Women who seek medical help after a miscarriage (many women don’t) are also more likely to have been vaccinated as part of their overall medical care.
- Women who are more at risk of miscarriage may be more likely to get vaccinated regularly.
- The apparent link may result from the fact that the study looked at 2010-2012, the years of the H1N1 pandemic, when more people got vaccinated.
These are just some of the questions that would lead to alternate hypotheses based on this observational data. Donahue et al. stated that:
This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB (spontaneous abortion), but further research is warranted.
Furthermore, I cannot stress this enough – a lot more is necessary to establish causality between flu vaccines and miscarriage. The most important of which is that plausibility be established. Can anyone pushing this narrative explain to me how it is plausible? What is the plausible mechanism between the flu vaccine and miscarriage? Inventing magical pathways with a heavy reliance on the Gish Gallop and special pleading won’t convince anyone.
So what we’re looking at is an association, nothing more. It’s an association with a lot of caveats, too. Basically, having found nothing more than one association with an aOR of 2.0 for the 1-28 day window of exposure to the influenza vaccine before miscarriage that was barely statistically significant (95% confidence interval: 1.1-3.6), the authors did a post hoc analysis looking for other associations. (Never mind that the “association” they found was eminently unimpressive given the size of the confidence intervals.) “Post hoc” means that they did additional analyses not originally specified.
Basically you don’t usually do post hoc analyses if there is a robust association in your data. You do it when you fail to find anything that interesting and want to salvage the study. Also, post hoc analyses are prone to type 1 errors, which means finding a statistically significant “association” where there is none; i.e., finding a false positive. When the numbers in the subgroup are so small and the study is observational (i.e., retrospective), that tendency is even stronger. Then there was the issue that the cases and controls were not as comparable as one would like in a case control study. For example, cases were significantly older than controls and more likely to be African-American, to have a history of 2 spontaneous abortions, and to have smoked during pregnancy. The authors did some correcting for age and history of spontaneous abortions, but it’s questionable to me whether it was adequate.
The design of the study wasn’t my only problem with the study. The study numbers were unimpressively low. The researchers stated that they found a fairly high aOR (adjusted odds ratio) of 7.7 for cases versus controls for two years of flu vaccine within 1-28 days before miscarriages. This was based on 21 miscarriages, which seems to fall within the realm of a chance result – because the numbers are so small, even a small random change in these numbers could change our overall interpretation of these results.
Just to be fair, if this were a significantly larger study, and it showed these results, it could be convincing. But as it stands, chance variation in miscarriages could greatly affect the statistical results. And that should give pause to anyone who will claim that the flu vaccine causes miscarriages.
Let’s not cherry pick
I have written numerous articles that have shown that receiving flu vaccines not only do not increase the risk of miscarriages, but actually may decrease it. There are also a lot of studies that show that the flu vaccine is safe to use with pregnant women.
- Pregnant women who received the flu vaccine had lower rates of still births, premature births or neonatal death. (My review of the study here.)
- The flu vaccine protects infants born to women who receive the flu vaccine during pregnancy. (My review here.)
- A systematic review (the top of the hierarchy of biomedical research) of seven research studies, published in Clinical Infectious Diseases, concluded that there was no relationship between vaccination during pregnancy and spontaneous abortions.
- A study that followed 1,032 pregnant Canadian women – 81% received the H1N1 flu vaccine. There were no differences in miscarriage rates or babies’ weights or lengths between the two groups.
- A study published in the New England Journal of Medicine followed over 117,000 pregnant women in Norway found that the risk of miscarriage was almost double in pregnant women who contracted the flu vs. those who didn’t. This is a point missed by Donahue et al. – maybe, just maybe, they uncovered a very small risk of the flu vaccine. But comparing that risk to the risk to the fetus in a pregnant mother who has contracted the flu puts the equation firmly on the side of the flu vaccine.
- A review of influenza vaccines delivered to pregnant women found that, “no study has demonstrated an increased risk of maternal complications or adverse fetal outcomes associated with inactivated influenza vaccine.”
- Research found that women who had the flu during pregnancy were twice as likely to have a child that will be eventually diagnosed with autism. (See my review of the article here.) It’s a little ironic that a vaccine preventable disease may increase the risk of autism, because we know that vaccines are not linked to autism.
I didn’t want to write a 5000 word article, but there are literally two dozen more studies that show that the flu vaccine is safe for pregnant mothers. Or that contracting the flu by pregnant mothers had a negative effect on maternal and/or fetal outcomes.
Flu vaccine causes miscarriages? Final answer, no
So if we avoid cherry picking the one study that is being trumpeted across the anti-vaccine world, what do we find? We find a robust number of studies that show us that vaccines during pregnancy are safe, that the flu vaccine is not linked to miscarriages, and catching the flu is linked to lower maternal outcomes. This is why we look at the whole body of evidence and come to a conclusion. Not the other way around.
Now, this does not mean this recent study from Donahue et al. should be completely dismissed out of hand. I think it’s a weak study, but it was co-authored by some of the leading researchers in vaccines (see Ironic note below). And published in a leading journal for vaccines.
But, is this study enough to overturn what we know about the flu vaccine during pregnancy? No.
Does this study say that the risk of miscarriage from vaccines is higher than the risk of miscarriage from catching the flu during pregnancy? Absolutely not.
Ignore the nonsense from the anti-vaccine front. They’ve got it all wrong.
Given that the anti-vaccine front will embrace this study as if it came down from Olympus and was delivered by Zeus himself, Orac pointed out the following:
I can’t help but note that Frank DeStefano of the CDC is a co-author. DeStefano, as you might recall, is one of those CDC investigators that antivax conspiracy theorists like those who made the propaganda film VAXXED portray as one of the main villains in the “CDC whistleblower” conspiracy theory.
Also, several of the authors receive pharma money for research support. Nicola Klein, for instance, receives research support from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Merck, MedImmune, Novartis, and Protein Science, while Allison Naleway receives funding from GlaxoSmithKline, MedImmune, and Pfizer. Others receive support from MedImmune and Novavax. So basically, this was a study funded by the CDC and carried out by CDC scientists and scientists receiving significant pharma funding.
I just couldn’t resist pointing that out. I know, I know, antivaxers will claim that the findings were so compelling that not even the CDC and pharma shills could hide them, but it would amuse me to point these things out to antivaxers.
Oh those precious anti-vaccine snowflakes might burst one of their two remaining neurons.
- Atladóttir HO, Henriksen TB, Schendel DE, and Parner ET. Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study. Pediatrics peds.2012-1107; published ahead of print November 12, 2012, doi:10.1542/peds.2012-1107.
- Bratton KN, Wardle MT, Orenstein WA, Omer SB. Maternal influenza immunization and birth outcomes of stillbirth and spontaneous abortion: a systematic review and meta-analysis. Clin Infect Dis. 2015 Mar 1;60(5):e11-9. doi: 10.1093/cid/ciu915. Epub 2014 Nov 18. Review. PubMed PMID: 25409473.
- Chambers CD, Johnson D, Xu R, Luo Y, Louik C, Mitchell AA, Schatz M, Jones KL; OTIS Collaborative Research Group.. Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants. Vaccine. 2013 Oct 17;31(44):5026-32. doi: 10.1016/j.vaccine.2013.08.097. Epub 2013 Sep 7. PubMed PMID: 24016809.
- Donahue JG, Kieke BA, King JP, DeStefano F, Mascola MA, Irving SA, Cheetham TC, Glanz JM, Jackson LA. Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010–11 and 2011–12. Vaccine 25 Sep 2017;35(40):5314-5322. doi: https://doi.org/10.1016/j.vaccine.2017.06.069
- Håberg SE, Trogstad L, Gunnes N, Wilcox AJ, Gjessing HK, Samuelsen SO, Skrondal A, Cappelen I, Engeland A, Aavitsland P, Madsen S, Buajordet I, Furu K, Nafstad P, Vollset SE, Feiring B, Nøkleby H, Magnus P, Stoltenberg C. Risk of fetal death after pandemic influenza virus infection or vaccination. N Engl J Med. 2013 Jan 24;368(4):333-40. doi: 10.1056/NEJMoa1207210. Epub 2013 Jan 16. PubMed PMID: 23323868; PubMed Central PMCID: PMC3602844.
- Naleway AL, Smith WJ, Mullooly JP. Delivering influenza vaccine to pregnant women. Epidemiol Rev. 2006;28:47-53. Epub 2006 May 26. Review. PubMed PMID: 16731574.
- Shakib JH, Korgenski K, Presson AP, Sheng X, Varner MW, Pavia AT, Byington CL. Influenza in Infants Born to Women Vaccinated During Pregnancy. Pediatrics; May 2016. doi: 10.1542/peds.2015-2360.
- Sheffield JS, Greer LG, Rogers VL, Roberts SW, Lytle H, McIntire DD, Wendel GD Jr. Effect of influenza vaccination in the first trimester of pregnancy. Obstet Gynecol. 2012 Sep;120(3):532-7. doi: 10.1097/AOG.0b013e318263a278. PubMed PMID: 22914461.