Tuesday, December 20, 2016

Maternal influenza vaccination and autism (surprise)

One reason why some people refuse the influenza vaccine is because they believe that it increases the risk of autism spectrum disorders (ASDs). No scientific study has ever supported this belief, however, and the Centers for Disease Control and Prevention (CDC) strongly urges that everyone who meets the criteria gets vaccinated—including pregnant women. Recent studies have found that maternal infection increases the risk of autism in offspring, but more data was needed on whether the flu is one of those infections. That’s where researchers from Kaiser Permanente Northern California come in. The team collected data from 196,929 mother-baby pairs. All of the infants had a gestational age of at least 24 weeks and were born from 2000 to 2010 at the institution. The average woman’s age was around 31.

During pregnancy, 24,231 mothers (23%) received the influenza A (H1N1) vaccine—a subtype of the influenza A virus and the most common strain of flu in 2009. Out of the entire cohort, 1,400 mothers (0.7%) were diagnosed with the flu. A total of 3,101 babies (1.6%) were diagnosed with ASD. Neither maternal flu infection or influenza vaccination were linked to an increased risk of ASD (hazard ratios: 1.04 and 1.10, respectively). This data includes getting vaccinated at any point during pregnancy and after adjusting for covariates.

“In trimester-specific analyses, first-trimester influenza vaccination was the only period associated with increased ASD risk (adjusted hazard ratio: 1.20),” the authors explained. “However, this association could be due to chance (P = 0.1) if Bonferroni corrected for multiplicity of hypotheses tested (n = 8).” In other words, these results were not statistically significant after adjusting for multiple comparisons. An increased risk was not observed in women who received the vaccine in their second or third trimester.

The researchers concluded that the results do not indicate a need to change vaccine practices in pregnant women. However, they do believe that more data is needed to better understand the relationship between maternal flu vaccination and autism.

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Ousseny Zerbo,  Yinge Qian, Cathleen Yoshida, et al.  Association Between Influenza Infection and Vaccination During Pregnancy and Risk of Autism Spectrum Disorder.  JAMA Pediatr. Published online November 28, 2016. doi:10.1001/jamapediatrics.2016.3609

Key Points
Question  Is there an association between maternal influenza infection and vaccination and autism risk?

Findings  In a cohort study of 196 929 children, of whom 3103 had austism spectrum disorder, maternal influenza infection during pregnancy was not associated with increased autism risk. There was a suggestion of increased risk of autism spectrum disorders among children whose mothers received an influenza vaccination during their first trimester, but the association was statistically insignificant after adjusting for multiple comparisons, indicating that the finding could be due to chance.

Meaning  Our findings do not call for vaccine policy or practice changes but do suggest the need for additional studies.

Abstract
Importance  Maternal infections and fever during pregnancy are associated with increased risk for autism spectrum disorders (ASDs). To our knowledge, no study has investigated the association between influenza vaccination during pregnancy and ASD.

Objective  To investigate the association between influenza infection and vaccination during pregnancy and ASD risk.

Design, Setting, and Participants  This cohort study included 196 929 children born at Kaiser Permanente Northern California from January 1, 2000 to December 31, 2010, at a gestational age of at least 24 weeks.

Exposures  Data on maternal influenza infection and vaccination from conception date to delivery date, obtained from Kaiser Permanente Northern California inpatient and outpatient databases. Influenza infection was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification codes or positive influenza laboratory test results.

Main Outcomes and Measures  Clinical diagnoses of ASDs identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes 299.0, 299.8, or 299.9 recorded in Kaiser Permanente Northern California electronic medical records on at least 2 occasions any time from birth through June 2015.

Results  Within this cohort of 196 929 children, influenza was diagnosed in 1400 (0.7%) mothers and 45 231 (23%) received an influenza vaccination during pregnancy. The mean (SD) ages of vaccinated and unvaccinated women were 31.6 (5.2) and 30.4 (5.6) years, respectively. A total number of 3101 (1.6%) children were diagnosed with ASD. After adjusting for covariates, we found that maternal influenza infection (adjusted hazard ratio, 1.04; 95% CI, 0.68-1.58) or influenza vaccination (adjusted hazard ratio, 1.10; 95% CI, 1.00-1.21) anytime during pregnancy was not associated with increased ASD risk. In trimester-specific analyses, first-trimester influenza vaccination was the only period associated with increased ASD risk (adjusted hazard ratio, 1.20; 95% CI, 1.04-1.39). However, this association could be due to chance (P = 0.1) if Bonferroni corrected for the multiplicity of hypotheses tested (n = 8). Maternal influenza vaccination in the second or third trimester was not associated with increased ASD risk.

Conclusions and Relevance  There was no association between maternal influenza infection anytime during pregnancy and increased ASD risk. There was a suggestion of increased ASD risk among children whose mothers received an influenza vaccination in their first trimester, but the association was not statistically significant after adjusting for multiple comparisons, indicating that the finding could be due to chance. These findings do not call for changes in vaccine policy or practice, but do suggest the need for additional studies on maternal influenza vaccination and autism.

1 comment:

  1. Jiang HY, Xu LL, Shao L, Xia RM, Yu ZH, Ling ZX, Yang F, Deng M, Ruan B. Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis. Brain Behav Immun. 2016 Nov;58:165-172.

    Abstract
    Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR=1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR=1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.

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