Flu vaccination in pregnancy
BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4454 (Published 10 July 2019) Cite this as: BMJ 2019;366:l4454Linked research
Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy
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Cunningham writes, referring to a study by Zerbo (2017) that the BMJ article & RR: “do not mention the 20% increase in the subsequent risk of autism spectrum disorder/ASD among the offspring of women in a large cohort study who got flu shots during the first trimester. The adjusted hazard ratio was 1.20 [CI 1.04-1.39], P=0.01. This amounts to 4 additional ASD cases for every 1000 women vaccinated . . The authors concluded, however, that the association was insignificant (P=0.1) after statistical correction for multiple comparisons. However, subsequent letters to the journal asserted that such statistical corrections were unwarranted.”
So what adjustments were made? These included variables where the mothers of children with ASD vs Without ASD differed significantly: Gestational age (< 37 wks vs 37 or more wks); Gestational diabetes; maternal history of Asthma and Hypertension. Medical research shows each one of the aforementioned can affect the fetus.
The authors also write: “Although the study had a large sample size, the number of exposed ASD cases was not large enough to provide a stable statistical estimate of the trimester-specific HR associated with influenza infection. Finally, our findings may be due to chance because the results were statistically insignificant after correcting for multiple comparisons.” But the adjusted ratio confidence interval means, if a one-sided analysis, that 5% of the time the results could be less than 1.04, even less than 1.00. Given that the sample size was too small, a valid risk.
Statistical significance doesn’t mean importance, it means that despite the best efforts to equalize groups on all variables except the one of interest, random chance means that the results of a study could be the result of some unmeasured variable(s), not the variable being studied. So, a p = 0.01 means that one would expect the result to occur 1% of the time from uncontrolled variables, which is why various replications are the sine qua non of science, not cherry-picking the studies that confirm one's bias ! ! !
There have been numerous studies on influenza vaccinations, pregnant women, and offspring. The vast majority have found NO serious associations (e.g., Chambers, 2016; Giles, 2019; McMillan, 2015; Moro, 2017; Nordin, 2014; Numes, 2016). While none of these studies looked at ASD, they do discuss risks for pregnant women, for instance, dying from influenza during pregnancy, and birth outcomes, e.g. malformations, low birthweight, etc.
Cunningham doesn’t seem to understand statistics, including adjusting for multiple comparisons or problems with “exposed ASD cases was not large enough to provide a stable statistical estimate of the trimester-specific HR associated with influenza infection.” However, this isn’t the first time Cunningham has posted on Rapid Responses and I have clearly refuted a number of other claims made by him, including limitations of VAERS (Harrison, 2019a), relationship between vaccinations and SIDs or Kawaski Disease (Harrison, 2019b), flu shots and miscarriage risk (Harrison, 2019c).
Despite protestations that he is not anti vaccine, Cunningham finds one study and interprets it based on his bias. He ignores the risks of death to pregnant women from the flu, up to five times higher, and the risks to the fetus from the flu; yet, jumps at the chance to exaggerate and misinterpret the findings of one study!
REFERENCES:
[Note that where I give link to an ABSTRACT, that I have the complete papers]
Chambers CD, Johnson DL, Xu R et al. (2016). Safety of the 2010–11, 2011–12, 2012–13, and 2013–14 seasonal influenza vaccines in pregnancy: Birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants, a study from the
cohort arm of VAMPSS; 34: 4443-4449.
Cunningham AS (2019 Jul 17). FIRST TRIMESTER FLU SHOTS: NOT A GOOD IDEA. BMJ Rapid Responses. Available at: https://www.bmj.com/content/366/bmj.l4454/rr-0
Giles ML, Krishnaswamy S, Macartney K, Cheng A (2019). The safety of inactivated influenza vaccines in pregnancy for birth outcomes: a systematic review. Human Vaccines & Immunotherapeutics; 15(3): 687-699. Available at: https://www.tandfonline.com/doi/pdf/10.1080/21645515.2018.1540807?needAc...
Harrison JA (2019a Jul 1). Wrong About Post-Marketing Surveillance of Vaccine Adverse Events. Response to Jacob Puliyel, John Stone, Allan Cunningham, etc. BMJ Rapid Responses. Available at: https://www.bmj.com/content/365/bmj.l2268/rr-7
Harrison JA (2019b May 20). Response 4 to Allan S. Cunningham. Unlimited tolerance of vaccines? BMJ Rapid Responses. Available at: https://www.bmj.com/content/364/bmj.l1481/rr-33
Harrison JA (2019c May 15). Response 3 to Allan S. Cunningham. BMJ Rapid Responses. Available at: https://www.bmj.com/content/364/bmj.l1481/rr-26
McMillan M, Porritt K, Kralik D et al. (2015 Apr). Influenza vaccination during pregnancy: A systematic review of fetal death, spontaneous abortion, and congenital malformation safety outcomes. Vaccine; 33: 2109-2117. ABSTRACT Available at: https://www.ncbi.nlm.nih.gov/pubmed/25758932
Moro P, Baumblatt j, Lewis P et al. (2017 Feb). Surveillance of Adverse Events After Seasonal Influenza Vaccination in Pregnant Women and Their Infants in the Vaccine Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602065/pdf/nihms-1025222.pdf
Nordin JD, Kharbanda EO, Benitez GV (2014 May). Maternal Influenza Vaccine and Risks for Preterm or Small for Gestational Age Birth. The Journal of Pediatrics; 164(5): 1051-1057. ABSTRACT Available at: https://www.ncbi.nlm.nih.gov/pubmed/24582484
Numes MC, Aqil AR, Omer SB, Madhi SA (2016). The Effects of Influenza Vaccination during Pregnancy on Birth Outcomes: A Systematic Review and Meta-Analysis. American Journal of Perinatology; 33: 1104-1114. Available at: https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0036-158...)
Competing interests: No competing interests
FIRST TRIMESTER FLU SHOTS: NOT A GOOD IDEA
The Haberg/Wilcox editorial about flu vaccination in pregnancy (BMJ 10 July 2019) and the linked article by Walsh, et al (BMJ 10 July 2019) both do not mention the 20% increase in the subsequent risk of autism spectrum disorder/ASD among the offspring of women in a large cohort study who got flu shots during the first trimester. (Zerbo, et al. JAMA Pediatr 2017;171e163602) The adjusted hazard ratio was 1.20 [CI 1.04-1.39], P=0.01. This amounts to 4 additional ASD cases for every 1000 women vaccinated.
The authors concluded, however, that the association was insignificant (P=0.1) after statistical correction for multiple comparisons. However, subsequent letters to the journal asserted that such statistical corrections were unwarranted. They presented data showing that a vaccine/autism link was biologically plausible and asserted that we should refrain from flu shots, at least in the first trimester of pregnancy. (Hooker, Dozelli, et al. JAMA Pediatr 2017;171:600)
ALLAN S. CUNNINGHAM 17 July 2019
Competing interests: No competing interests
It is troubling that Siri Håberg and Allen Wilcox [1] extrapolate from the Walsh paper [2] about the safety of vaccinating pregnant women, and by implication about the programme in general. In this regard it should not be forgotten that the Arepanrix vaccine studied by Walsh, which was made available to public in Canada in 2009, had a superior safety profile to the Pandemrix product offered to the public in the United Kingdom [3,4].
Furthermore, the circumstances of the swine flu episode remain controversial [5-9].
Even on the basis of articles published in the BMJ the British public may have been right to be more wary of the vaccine than the disease (only about 6 million rounds of Pandemrix had been used by June the following year) [10] .
I agree with Håberg and Wilcox that no one should spread false information but truth is complex.
[1] Håberg and Wilcox, 'Flu vaccination in pregnancy', BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4454 (Published 10 July 2019)
[2] Walsh et al, 'Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study', BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4151 (Published 10 July 2019)
[3] Peter Doshi, 'Pandemrix vaccine: why was the public not told of early warning signs?', BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3948 (Published 20 September 2018)
[4] Fiona Godlee, 'Pandemrix vaccine: why was the public not told of early warning signs?', BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3948 (Published 20 September 2018)
[5] Deborah Cohen & Philip Carter, 'WHO and the pandemic flu “conspiracies”' BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c2912 (Published 04 June 2010)
[6] 'Interview with Epidemiologist Tom Jefferson 'A Whole Industry Is Waiting For A Pandemic'', Der Spiegel, 21 July 2009, http://www.spiegel.de/international/world/interview-with-epidemiologist-...
[7] Peter Doshi, 'Calibrated response to emerging infections', BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b3471 (Published 03 September 2009)
[8] Tom Jefferson, The UK turns to Witty, Vallance, and Van Tam for leadership: revolving doors?, 6 December 2017, http://blogs.bmj.com/bmj/2017/12/06/tom-jefferson-the-uk-turns-to-witty-...
[9] 'Trust WHO: The Business of Global Health 'Investigating the hidden motives behind actions of the World Health Organisation and the real powers that control it', Al Jazeera 15 Dec 2018, https://www.aljazeera.com/programmes/specialseries/2018/12/trustwho-busi...
[10] John Stone, 'Re: A tale of two vaccines - how the British people averted disaster?', 13 October 2018, https://www.bmj.com/content/363/bmj.k4152/rr-17
Competing interests: No competing interests
Benefits of vaccination against influenza in pregnant women
Influenza is more likely to cause serious illness in pregnant women than in women of reproductive age who are not pregnant. Changes in the immune system, heart and lungs during pregnancy (and up to two weeks after delivery) make pregnant women more likely to develop a serious illness from influenza that may require hospitalization. Influenza can also be harmful to the fetus. A symptom of common influenza is fever that may be associated with neural tube defects and other adverse outcomes for the fetus. In addition, the influenza vaccine helps protect the newborn. The mother transmits antibodies to the fetus.
Influenza vaccines that are administered during pregnancy help protect both the mother and future newborn against influenza. It is shown that vaccination reduces the risk of an acute respiratory infection associated with influenza in pregnant women.
The CDC continues to recommend that pregnant women be vaccinated against influenza during any trimester of pregnancy since influenza poses a risk to pregnant women and this vaccine can prevent serious illness and even pregnant women are hospitalized.
Women who are breast-feeding should be given the influenza vaccine to protect themselves from the disease. Vaccination decreases the mother's risk of becoming ill and transmitting the influenza to her infant and protecting them from the disease. This is especially important for children younger than 6 months, who are too young to receive the influenza vaccine.
References
1. Jamieson DJ, Kissin DM, Bridges CB, Rasmussen SA. Benefits of influenza vaccination during pregnancy for pregnant women. Am J Obstet Gynecol 2012; 207: S17–20.
2. Thompson MG, Li DK, Shifflett P , et al. Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010–2011 and 2011–2012 influenza seasons. Clin Infect Dis 2014; 58: 449–57.
3. Fell DB, Azziz-Baumgartner E, Baker MG, et al. WHO taskforce to evaluate influenza data to inform vaccine impact and economic modelling. Influenza epidemiology and immunization during pregnancy: final report of a World Health Organization working group. Vaccine 2017; 35:5738–50.
4. Wong VW, Lok KY, Tarrant M. Interventions to increase the uptake of seasonal influenza vaccination among pregnant women: a systematic review. Vaccine 2016; 34: 20–32.
5. Durand LO, Cheng PY, Palekar R, et al. Timing of influenza epidemics and vaccines in the American tropics, 2002–2008, 2011–2014. Influenza Other Respir Viruses 2016; 10:170.
6. Hirve S, Newman LP, Paget J, et al. Influenza seasonality in the tropics and subtropics: when to vaccinate? PLoS One 2016; 11:e0153003.
7. Sokolow LZ, Naleway AL, Li DK, et al. Severity of influenza and noninfluenza acute respiratory illness among pregnant women, 2010–2012. Am J Obstet Gynecol 2015; 212: 202 e1–e11.
Competing interests: No competing interests