H1N1 Flu Vaccination During Pregnancy Did Not Increase Risk of Autism in Kids

-Even in first trimester, no link observed, Swedish registry study finds

by Zeena Nackerdien PhD, CME Writer, MedPage Today 2020-09-21

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Study Authors: Jonas F. Ludvigsson, Henric Winell, et al.; Anders Hviid

Target Audience and Goal Statement: Obstetrician-gynecologists, pediatricians, infectious disease specialists

The goal of this study was to examine the risk for autism spectrum disorder (ASD) in offspring of mothers who were vaccinated against H1N1 (« swine flu ») during pregnancy.

Question Addressed:

  • What was the risk for ASD in the offspring of mothers who were vaccinated against H1N1 during pregnancy?

Study Synopsis and Perspective:

Evidence from the literature has suggested that pregnancy is a risk factor for influenza severity. Moreover, pandemic influenza during pregnancy might increase risks for stillbirth and preterm birth.

Action Points

  • There was no association between maternal H1N1 (« swine flu ») vaccination during pregnancy and risk for autism spectrum disorder in offspring, according to a large Swedish-based population study.
  • Note that flu vaccination coverage among pregnant women remains moderate, according to the CDC, despite the health benefits to mothers and offspring.

Maternal and offspring health benefits resulting from influenza vaccination during pregnancy are matters of record. However, flu vaccination coverage among pregnant women remains moderate, with only a 49.1% uptake during the 2017-2018 flu season, according to the CDC.

Reasons cited for this included the perception of influenza as not serious, the vaccine’s often moderate effectiveness, and perceptions of safety issues.

Many observational studies on the safety of flu shots in pregnancy have focused on possible adverse events during pregnancy and in the period immediately after birth, such as birth defects and fetal death. However, little is known about the potential for adverse events in childhood following in utero exposure to vaccines.

While the potential for inactivated flu shots to disrupt the intrauterine environment to a harmful extent remains unlikely, there is still a need to conduct credible safety research to ensure that vaccination programs are not derailed by false accusations, such as the widely debunked vaccine-autism link first espoused in the retracted Wakefield et al. study.

In a recent Swedish-based population study published in the Annals of Internal Medicine, researchers found that children born to women receiving the 2009-2010 H1N1 influenza vaccine during pregnancy had no higher likelihood of developing autism later in life.

Babies exposed to the « swine flu » vaccine during pregnancy did not have an increased risk of developing ASD or autistic disorder (AD) compared with those born to unvaccinated women, reported Jonas F. Ludvigsson, MD, PhD, of Karolinska Institutet in Stockholm, and colleagues.

This study benefited from high-quality Nordic register data, with less concern about selection bias and very limited loss to follow-up because of free, state-funded healthcare and nationwide linkable health registers.

Ludvigsson’s group collected data on singleton live births in Sweden when much of the population was immunized in a swine flu pandemic vaccination campaign. They linked vaccination data to national patient registers, including participants from seven healthcare regions in Sweden.

The group controlled for maternal age at delivery, BMI, parity, smoking, country of birth, disposable income, healthcare region, comorbidities, infant sex, and prenatal study time.

Of the more than 69,000 included infants, 39,276 were prenatally exposed to the H1N1 vaccine (13,845 during the first trimester) and 29,293 were unexposed.

Mothers of vaccine-exposed infants were older at delivery and had a higher disposable income, and were less likely to have higher BMI, to have smoked, or to have been born outside of Sweden.

The researchers found that 1.0% (394) of children who were prenatally exposed to the H1N1 vaccine were diagnosed with ASD, compared with 1.1% (330) of children who were unexposed, during the mean follow-up period of 6.7 years.

H1N1 vaccine exposure during fetal life was not associated with a later childhood diagnosis of ASD (adjusted hazard ratio [aHR] 0.95, 95% CI 0.81-1.12). Importantly, the researchers observed similar findings for vaccinations in the first trimester. There was also no increase in the risk for the secondary outcome of AD in children prenatally exposed to the vaccine (aHR 0.96, 95% CI 0.80-1.16).

A sensitivity analysis examining maternal epilepsy, and neurologic and psychiatric diseases did not change their risk estimates.

Ludvigsson and colleagues recognized that their analysis may be limited by a lack of information on H1N1 infection in pregnant women, and may be subject to additional unmeasured confounding.

Source References: Annals of Internal Medicine 2020; DOI: 10.7326/M20-0167

Editorial: Annals of Internal Medicine 2020; DOI: 10.7326/M20-5489

Study Highlights and Explanation of Findings:

Findings from a large Swedish population-based cohort study showed no association between vaccination of mothers against H1N1 influenza and childhood ASD in offspring.

In an analysis of first trimester exposures — a period when vaccines could potentially have the most profound effect on fetal neurodevelopment — there was still no link between immunization and autism risk, said Ludvigsson and team.

« Our null findings are important since some people have suspected that vaccinations could cause autism, and the anti-vaccine movement seems to be growing in the Western world, » explained Ludvigsson in a press release. « H1N1 vaccination has previously been linked to an increased risk of narcolepsy in young people, but vaccinating pregnant women does not seem to influence the risk of autism spectrum disorder in the offspring. »

« Vaccination research has never been more important. Anticipating a vaccine against COVID-19, millions of pregnant women are likely to be offered such a vaccination. While our research group did not study COVID-19 vaccine effects, our research on H1N1 vaccination adds to the current knowledge about vaccines, pregnancy and offspring disease in general, » he added.

In an accompanying editorial, Anders Hviid, MSc, DrMedSci, of the Statens Serum Institut and University of Copenhagen in Denmark, stated that this research « is a rare and welcome contribution to a more comprehensive safety evaluation, which goes significantly beyond the perinatal period. »

In his editorial, Hviid cited another study, which evaluated the health outcomes of nearly 100,000 Canadian children born to mothers who received the 2009 H1N1 influenza vaccine during pregnancy, which also supported the safety of the vaccine. Similarly, a Danish study of an H1N1 vaccine found no elevated risk for early childhood morbidity in vaccinated offspring followed until age 5.

Hviid also underscored the need for a comprehensive and proactive approach to vaccine safety « with the hopefully imminent arrival of COVID-19 vaccines. » Due to limited information on pregnancy safety from ongoing trials, observational studies should be in place to « promptly evaluate the overall safety of vaccination in pregnancy, » he noted.

Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College

Primary Source

Annals of Internal Medicine

Source Reference: Ludvigsson JF, et al « Maternal influenza A(H1N1) immunization during pregnancy and risk for autism spectrum disorder in offspring: a cohort study » Ann Intern Med 2020; DOI: 10.7326/M20-0167.

Secondary Source

Annals of Internal Medicine

Source Reference: Hviid A « Vaccine safety in pregnancy: going beyond the perinatal period » Ann Intern Med 2020; DOI: 10.7326/M20-5489.

Additional Source

MedPage Today

Source Reference: D’Ambrosio A « No Autism Risk Connected to H1N1 Flu Vaccine » 2020.