Annals Int. Med: A(H1N1) Maternal Vaccination & Risk Of Autism Spectrum Disorder in Offspring

Photo Credit – CDC 

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We know that pregnant women and their offspring have fared poorly during influenza pandemics of the past (see Pandemic Influenza and Pregnant Women) - and multiple studies have shown they did so again during the 2009 novel influenza (see Study: Outcomes Of Infants Born To Women With Influenza A(H1N1)pdm09). 

• In the fall of 2009 we learned that pregnant women were six times more likely to be hospitalized than non-pregnant women (see Pregnancy & Flu: A Bad Combination).
• And in 2011, in BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection we saw a study where pregnant women who were admitted to the hospital with an H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.

At the same time we've seen numerous studies confirming the benefits of flu vaccination and the early use of antivirals in protecting the lives of pregnant women and their unborn child, including:

Pediatrics: Maternal Flu Vaccination Extends Protection To Infants

Clinical Infectious Diseases: Flu Vaccine May Reduce Incidence of Stillbirth

JID: Benefits Of Early Use of Influenza Antivirals In Pregnancy

Despite ample evidence of harm to expectant mothers and their offspring from influenza infection - and studies that show the benefits of influenza vaccination to this vulnerable cohort - many pregnant women remain reluctant to take the flu vaccine over persistent concerns - often fanned by social media - that maternal flu shots are somehow linked to autism spectrum disorder in offspring. 

While it probably won't alter the opinion of many hardcore anti-vaccine activists, we've a new comprehensive population study out of Sweden that confirms that the offspring of pregnant women who received the 2009 A(H1N1) pandemic vaccine were less likely to have developmental problems, including autism spectrum disorder. 

First, a link to the study published today in the Annals of Internal Medicine, then I'll return with a postscript.

Original Research 1 Sep 2020

Maternal Influenza A(H1N1) Immunization During Pregnancy and Risk for Autism Spectrum Disorder in Offspring

A Cohort Study

Jonas F. Ludvigsson, MD, PhD, Henric Winell, MSc, … View all authors 

 

https://doi.org/10.7326/M20-0167

 

Background:

There are concerns that influenza vaccine exposure during pregnancy may be associated with increased risk for autism spectrum disorder (ASD).

Objective:

To examine the risk for ASD in offspring of mothers who were vaccinated against influenza A(H1N1)pdm09 (“swine flu”) during pregnancy.

Design:

Population-based cohort study using nationwide registers.

Setting:

Seven health care regions in Sweden.

Participants:

Live births between October 2009 and September 2010, with follow-up through December 2016. In total, 39 726 infants were prenatally exposed to H1N1 vaccine (13 845 during the first trimester) and 29 293 infants were unexposed.

Measurements:

Cox regression was used to estimate hazard ratios (HRs) for the primary outcome, ASD, before and after adjustment for potential confounders. The secondary outcome was autistic disorder (AD).

Results:

Mean follow-up was 6.7 years in both unexposed and exposed children. During follow-up, 394 (1.0%) vaccine-exposed and 330 (1.1%) unexposed children had a diagnosis of ASD. In adjusted analyses, prenatal exposure to H1N1 vaccination was not associated with a later diagnosis of ASD (adjusted HR [aHR], 0.95 [95% CI, 0.81 to 1.12]) or AD (aHR, 0.96 [CI, 0.80 to 1.16]). The 6-year standardized cumulative incidence difference between the unexposed and exposed children was 0.04% (CI, −0.09% to 0.17%) for ASD and 0.02% (CI, −0.09% to 0.14%) for AD. Restricting the analysis to vaccination in the first trimester of pregnancy did not influence risk estimates (aHR, 0.92 [CI, 0.74 to 1.16] for ASD and 0.91 [CI, 0.70 to 1.18] for AD).

Limitation:

Data on H1N1 influenza infection are lacking.

Conclusion:

This large cohort study found no association between maternal H1N1 vaccination during pregnancy and risk for ASD in the offspring.

          (Continue . . .  ) 

While there is no evidence of autism and other developmental disorders being linked to material flu vaccination during pregnancy, there is a growing body of evidence that suggests that maternal infections - and fevers - may cause long-term harm to the developing fetus. 

In 2019's JAMA Psych: Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero we looked at an impressively large, multi-decade study published in JAMA Psychiatry on the risks of developing neuropsychiatric disease later in life that found (emphasis mine).

`. . . those people whose mothers had been hospitalized for any infection during pregnancy had a 79 percent higher risk of being diagnosed with autism and a 24 percent increased risk of being diagnosed with depression.'

Some previous studies along the same lines include:

• In 2017's Molecular Psy.: Increased Autism Risk Linked To Prenatal Fever, we saw study that found maternal fever in the 2nd trimester was linked to a 40% increased risk of autism. 

• Un May, 2013), we looked at a JAMA Psychiatry report that linked bipolar disorder (BD) to influenza exposure while still in the womb  (see Pregnancy, Influenza, & Bipolar Disorder In Offspring). 
• In November of  2012, in Of Pregnancy, Flu & Autism, we saw a study that found a twofold increase in autism among children with prenatal influenza exposure, and a threefold increase in autism among children with prolonged prenatal fever exposure 
• In 2012 research by a team at UC Davis found that fever (from any cause) during pregnancy more than doubled the odds of having a child with autism or developmental delays (see  Is Maternal Influenza or Fever During Pregnancy Associated with Autism or Developmental Delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study Zerbo et al.)  

• And finally, a study from 2008 (Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8  Ellman et al.) suggested that it was prenatal exposure to a type of protein - (proinflammatory cytokines, specifically interleukin-8) – produced by the body during viral infections, that can lead (in rare cases) to brain abnormalities.

 
While influenza vaccines provide only limited protection against the flu - and rare (and usually mild) adverse events have been reported - these studies (and others) should provide some comfort and reassurance to pregnant women who are advised by their doctors to get the flu shot.