TABLE 5

Adjusted Effect Estimates of Early Childhood Health Outcomes Associated With In Utero Exposure to Influenza Vaccine, by Pandemic and Seasonal Influenza Vaccines

Author(s) (y)Outcome AssessedEffect Estimate for Vaccination at Any Time During PregnancyEffect Estimate by Trimester
First TrimesterSecond TrimesterThird Trimester
Pandemic influenza vaccine
 Bischoff et al41 (2015)All infections (common cold, pharyngitis, otitis, pneumonia, fever, gastrointestinal infection)aIRR: 0.99 (0.84–1.18)
 Ludvigsson et al34 (2015)MortalityaHR: 0.97 (0.69–1.36) vs sibling control: aHR: 0.78 (0.52–1.19)aaHR: 0.86 (0.51–1.47) versus sibling control: aHR: 0.47 (0.22–1.01)aaHR: 1.10 (0.69–1.76) versus sibling control: aHR: 1.44 (0.74–2.78)aaHR: 0.93 (0.54–1.60) versus sibling control: aHR: 0.65 (0.30–1.39)a
 van der Maas et al35 (2016)Infection-related primary care contactaIRR: 1.07 (0.91–1.28)
 Fell et al36 (2016)Influenza, by season
 2009 A/H1N1 pandemic seasonIRR: 0.61 (0.32–1.17)
 Post 2009 A/H1N1 pandemic periodaIRR: 1.05 (0.81–1.37)
 Pre-2010–2011 periodaIRR: 1.08 (0.80–1.44)
 2010–2011 periodaIRR: 0.88 (0.76–1.02)
 Post-2010–2011 periodaIRR: 0.72 (0.50–1.04)
 Pre-2011–2012 period
Influenza and pneumonia, by season
 2009 A/H1N1 pandemic seasonaIRR: 1.04 (0.84–1.29)
 Post 2009 A/H1N1 pandemic periodaIRR: 1.17 (1.05–1.31)
 Pre-2010–2011 periodaIRR: 1.07 (0.93–1.25)
 2010–2011 periodaIRR: 0.99 (0.92–1.07)
 Post-2010–2011 periodaIRR: 1.00 (0.85–1.17)
 Pre-2011–2012 periodaIRR: 0.81 (0.38–1.70)
 Hviid et al38 (2017)1-y hospitalizationaHR: 1.10 (0.89–1.37); aRR: 1.15 (0.90–1.48)aHR: 0.94 (0.89–0.99); aRR: 0.93 (0.87–0.99)
3-y hospitalizationaHR: 1.15 (0.97–1.37); aRR: 1.21 (0.98–1.50)aHR: 0.95 (0.90–0.99); aRR: 0.96 (0.90–1.01)
5-y hospitalizationaHR: 1.13 (0.96–1.32); aRR: 1.17 (0.94–1.45)aHR: 0.95 (0.91–0.99); aRR: 0.93 (0.87–0.99)
Upper respiratory tract infectionsaRR: 1.08 (0.80–1.46)aRR: 0.92 (0.85–0.99); aRR: 0.92 (0.81–1.03)b
Lower respiratory tract infectionsaRR: 0.90 (0.63–1.28)aRR: 0.92 (0.84–1.00)
Gastrointestinal infectionsaRR:1.03 (0.68–1.55)aRR: 0.84 (0.74–0.94); aRR: 0.84 (0.70–1.00)b
MeningitisaRR: 1.17 (0.61–2.24)
SepsisaRR: 1.96 (1.26–3.05); aRR: 1.96 (0.98–3.91)b
Viral infectionsaRR: 1.20 (0.82–1.73)aRR: 0.91 (0.82–1.00)
Other infectionsaRR: 1.71 (1.08–2.73); aRR: 1.71 (0.83–3.56)baRR: 0.92 (0.81–1.05)
AsthmaaRR: 1.50 (0.99–2.29)aRR: 1.02 (0.89–1.16)
Celiac diseaseaRR: 0.81 (0.31–2.12)
Crohn diseaseaRR: 1.24 (0.31–11.90)
Ulcerative colitisaRR: 2.48 (0.41–14.82)
Juvenile arthritisaRR: 0.60 (0.23–1.54)
Sjögren syndromeaRR: 1.15 (0.24–5.53)aRR: 1.59 (1.04–2.44); aRR: 1.59 (0.82–3.11)b
Vasculitis
Reactive arthropathyaRR: 0.80 (0.09–6.88)aRR: 1.40 (0.96–2.05)
Idiopathic thrombocytopenic purpuraaRR: 0.68 (0.15–3.05)
Idiopathic urticariaaRR: 1.03 (0.38–2.78)
Type-1 diabetesaRR: 0.80 (0.23–2.77)
Bell palsyaRR: 1.24 (0.34–4.57)
EpilepsyaRR: 1.01 (0.21–4.74)aRR: 0.86 (0.58–1.27)
Guillain-Barré syndrome
Autism spectrum disorderaRR: 1.22 (0.79–1.86)
Intellectual disabilityaRR: 0.66 (0.28–1.56)
 Walsh et al39 (2019)Upper respiratory tract infectionsaIRR: 1.01 (0.98–1.03)
Lower respiratory tract infectionsaIRR: 0.99 (0.95–1.03)
Gastrointestinal infectionsaIRR: 0.94 (0.91–0.98); aIRR: 0.94 (0.88–1.00)b
Otitis mediaaIRR: 1.03 (1.00–1.06)
All infectionsaIRR: 1.01 (0.98–1.03)
AsthmaaHR: 1.05 (1.02–1.09); aHR: 1.05 (1.00–1.11)b
NeoplasmsaHR: 1.12 (0.79–1.59)
Sensory disordersaHR: 0.94 (0.67–1.33)
Urgent and inpatient health services usedaIRR: 0.99 (0.98–1.01)
Pediatric complex chronic conditionsaRR: 0.98 (0.80–1.20)
5-y mortalityaHR: 0.83 (0.64–1.08)
Seasonal influenza vaccine
 Benowitz et al40 (2010)Laboratory-confirmed influenzaVE: −41.4% (−2257.4% to 91.5%)
 van Santen et al33 (2013)Acute otitis mediaaVE: 47.9% (42.0% to 53.3%)
Medically attended acute respiratory infectionsaVE: 39.6% (31.6% to 46.7%)
 Zerbo et al37 (2017)Autism spectrum disorderaHR: 1.10 (1.00–1.21)aHR: 1.20 (1.04–1.39)aHR: 1.03 (0.90–1.19)aHR: 1.03 (0.90–1.20)
  • aIRR, adjusted incidence rate ratio; aHR, adjusted hazard ratio; aRR, adjusted rate ratio; aVE, adjusted vaccine effectiveness; VE, unadjusted vaccine effectiveness; —, not applicable.

  • a Overall estimates are compared with unexposed children; an additional comparison with unexposed siblings also provided.

  • b Adjusted for multiplicity using Bonferroni correction.