Is neurodevelopment influenced by atopy in the mother or infant? Exploring the role of infant and maternal atopic status, infant gut microbiome, and metabolites in early child neurodevelopment

• Author / Creator

  Rodriguez, Nicole Anne Marie

• Background: Allergic diseases affect about 30% to 35% of all children, and the frequency of
  these diseases has been increasing in recent years. Growing epidemiological data suggests
  interactions exist between infant neurodevelopment and inflammatory immune diseases,
  including food sensitization and allergies. In this study, we aim to characterize and determine how atopic disease in both the infant and the mother shape infant neurodevelopment, as well as explore factors that play a role in this relationship.

  Research Aims:
  Research Aim I - I will investigate the association of allergic sensitization in 1-year old infants, especially food sensitization, in relation to the Bayley's scale of neurodevelopment.

  Research Aim II - I will test the association between maternal prenatal atopy status and infant
  neurodevelopment.

  Research Aim III - I will determine the mediating role of the gut microbiome and metabolome
  (short-chain fatty acids and amino acids metabolites) in the pathway between maternal atopic
  disease and infant neurodevelopmental scores.

  Methods:
  As assessed by the Bayley’s neurodevelopmental scale at 1 year
  and 2 years of age, statistical analysis will be performed to determine the association between infant and maternal allergic sensitization and infant neurodevelopment. Using 16S rDNA sequencing and NMR methods to profile gut microbe and metabolite abundance at 1 year, mediating tests on infant gut microbial and metabolite abundance will be conducted to determine whether certain metabolites or infant gut microbiome is in the pathway between prenatal maternal atopic status and infant neurodevelopment.

  Results:
  Result for Research Aim I - In the current study, AS was present among 16.4% of infants, while 13.4% had FS. Both atopic and food sensitization at 1 year of age were associated with statistically significantly lower social-emotional scores at that age, independent of the infant’s ethnicity. These findings were sex-specific and only observed among boys, among whom social- emotional scores were lowered by 5 points if AS was present (-5.22 [95%CI: -9.96, -0.47] p = 0.03) or if FS was present (-4.85 [95%CI: -9.82, 0.11], p=0.06).

  Result for Research Aim II & III – Combined atopic conditions is present among 66.57% of mothers and 22.39% live with maternal asthma. Combined maternal atopy is associated with decrease in cognitive and motor scores at 2 years of age among male infants; and with increased cognitive scores at 2 years of age among female infants. In particular, cognitive scores are lowered by 3.87 points (-3.87 [95%CI: -8.28, 0.54], p = 0.09) and motor scores are lowered by 3 points (-3.00 [95%CI: -6.28,0.27], p = 0.072). Female infants whose mothers have combined maternal atopy experience an increase of 4.12 points in cognitive scores (4.12 [95%CI: -0.85, 9.08), p = 0.10). Infants born from Moms of Asian ethnicity experience the greatest decrease in infant neurodevelopmental scores (Table 3.5). On the other hand, maternal asthma decreases socio-emotional scores at 2 years among all infants (-3.70 [95%CI: -8.05, 0.64], p = 0.094). Sex-stratification demonstrate an increase in male infant language scores at 1 year (6.56, [95%CI: 1.76, 11.37], p = 0.008) and a decrease in male socio-emotional scores at 2 years (-6.60 [95%CI: -14.07, 0.88], p = 0.08). In the mediation analysis, creatinine mediates the association between maternal asthma and infant cognitive scores at 2 years, specifically of female infants with White Caucasian mothers. Furthermore, when sequential mediation was performed with prenatal depression as mediator 1 and infant gut microbiome as mediator 2 in the pathway between maternal atopic status and child neurodevelopment, this resulted in no statistically significant mediating effect.

  Conclusion:
  Allergic symptomatology may adversely affect neurodevelopment because of the related clinical manifestations and necessary treatments. Creating a pathway from food sensitization to infant neurodevelopment through the gut microbiome will fill the existing knowledge gap in understanding the interaction between neurological and immunological development. Interventions in preventing atopic disease associated with impaired neurodevelopment are valuable to clinicians, mothers, and their families, as they help increase positive maternal and neonatal health outcomes and overall quality of life.

• Subjects / Keywords

  • infant gut microbiome
  • atopic sensitization
  • food sensitization
  • maternal asthma
  • infant neurodevelopment

• Graduation date

  Fall 2022

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-zdzd-ay23

• License

  This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.