Infant inflammation predicts childhood emotional and behavioral problems and partially mediates socioeconomic disadvantage

Pham, Cindy; Bekkering, Siroon; O’Hely, Martin; Burgner, David; Thomson, Sarah; Vuillermin, Peter; Collier, Fiona; Marx, Wolfgang; Mansell, Toby; Symeonides, Christos; Sly, Peter D.; Tang, Mimi L.K.; Saffery, Richard; Ponsonby, Anne‐Louise

doi:10.1016/j.bbi.2022.05.011

Cited by 13 publications

(20 citation statements)

References 106 publications

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“…Socioeconomic status (SES) was considered as a potential confounder. It has previously been shown in this cohort that inflammation partially mediates the relationship between socioeconomic disadvantage and emotional and behavioural problems in children (25). Education is the socioeconomic indicator recommended by the Organisation for Economic Co-operation and Development for reporting and monitoring socioeconomic inequalities as it is reported with reasonable reliability, can be harmonized across cohorts and countries, generally has few missing data, is relatively stable across adulthood, and is less subject to reverse causality than measures such as income (34,35).…”

Section: Sensitivity Analysesmentioning

confidence: 65%

“…Prior to analysis, the urinary OS biomarkers measures were pre-processed to correct for i) time interval between urine collection, processing and storage by fitting a linear model and retaining the residuals (27); ii) batch effects (28); and iii) urine dilution using specific gravity (29). Given the left-skewed distribution, a base-2 log transformation was applied to all OS biomarkers for subsequent analyses (30).…”

Section: Oxidative Stress Biomarkers and Gene Pathway Function Scorementioning

confidence: 99%

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Association of maternal air pollution exposure and infant lung function is modified by genetic propensity to oxidative stress

Vilcins,

Lee,

Pham

et al. 2023

Preprint

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IntroductionThe association between air pollution and poor respiratory health outcomes is well established, however less is known about the biological mechanisms, especially in early life. Children are particularly at risk from air pollution, especially during the prenatal period as their organs and systems are still undergoing crucial development. Therefore, our study aims to investigate if maternal exposure to air pollution during pregnancy is associated with oxidative stress (OS) and inflammation in pregnancy or infant lung function at 4 weeks of age, and the extent to which the association is modified by an infant’s genetic risk of OS.MethodsThe Barwon Infant Study (BIS) is a longitudinal study of Australian children from the region of Geelong, Victoria. A total of 314 infants had available lung function and maternal OS markers. Exposure to annual air pollutants (NO2and PM2.5) were estimated using validated, satellite-based, land-use regression models. Infant lung function was measured by multiple-breath washout, and the ratio of peak tidal expiratory flow over expiratory time was calculated at 4 weeks of age. An inflammation biomarker, glycoprotein acetyls (GlycA), was measured in maternal (36 weeks) and cord blood, and oxidative stress (OS) biomarkers, 8-hydroxyguanine (8-OHGua) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) were measured in maternal urine at 28 weeks. A genetic pathway score for OS (gPFSox) was calculated for each infant participant in the BIS cohort, and high risk defined as score >8. Linear regression was used to explore the association of maternal air pollution exposure with infant lung function, and potential modification by OS genotype was tested through use of interaction terms and other methods.ResultsThere was no evidence of a relationship between maternal exposure to air pollution and infant lung function in the whole population. We did not find an association between air pollution and GlycA or OS during pregnancy. We found evidence of an association between NO2and lower in functional residual capacity (FRC) for children with a high genetic risk of OS (β=-5.3 mls, 95% CI (−9.3, -1.3), p=0.01). We also found that when NO2was considered in tertiles, the highest tertile of NO2was associated with increase in lung clearance index (LCI) (β=0.46 turnovers, (95% CI 0.10, 0.82), p=0.01) in children with a genetic propensity to OS.ConclusionOur study found that high prenatal levels of exposure to ambient NO2levels is associated with lower FRC and higher LCI in infants with a genetic propensity to oxidative stress. There was no relationship between maternal exposure to air pollution with maternal and cord blood inflammation or OS biomarkers.

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Section: Sensitivity Analysesmentioning

confidence: 65%

Section: Oxidative Stress Biomarkers and Gene Pathway Function Scorementioning

confidence: 99%

Association of maternal air pollution exposure and infant lung function is modified by genetic propensity to oxidative stress

Vilcins,

Lee,

Pham

et al. 2023

Preprint

Self Cite

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“…Cord blood samples were checked for maternal blood contamination using DNA methylation profiling as described elsewhere. 48 , 49 Contamination status (yes/no) was included as a covariate in analyses.…”

Section: Methodsmentioning

confidence: 99%

Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort study

Vacy,

Thomson,

Moore

et al. 2024

eBioMedicine

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“…Furthermore, there is a growing body of literature identifying elevated peripheral inflammatory biomarkers, such as CRP and IL6, in children and adolescents with externalizing (Mitchell and Goldstein, 2014; Pham et al., 2022; Slopen et al., 2013) and internalizing behaviors (Belem da Silva et al., 2017; Copeland et al., 2012; Mitchell and Goldstein, 2014; Pham et al., 2022; Slopen et al., 2013). A recent prospective study of 482 infants found that higher glycoprotein acetyls (GlycA, a measure of cumulative inflammation) levels at birth were associated with externalizing and internalizing problems at age two, underscoring the impact of inflammation during sensitive periods of early brain development (Pham et al., 2022). Overall, it appears that inflammation may be an important biological pathway underlying aggressive and internalizing behaviors in at least a subset of children and adolescents.…”

Section: Introductionmentioning

confidence: 99%

“…Longitudinal studies have also found that baseline blood levels of inflammatory biomarkers—including C‐reactive protein (CRP), interleukin 1 beta (IL1B), and interleukin 6 (IL6)–predict the development of both aggressive and internalizing behaviors in animal and human studies (Costello et al., 2019; Graham et al., 2006; Lamers et al., 2019; Valkanova et al., 2013). Furthermore, there is a growing body of literature identifying elevated peripheral inflammatory biomarkers, such as CRP and IL6, in children and adolescents with externalizing (Mitchell and Goldstein, 2014; Pham et al., 2022; Slopen et al., 2013) and internalizing behaviors (Belem da Silva et al., 2017; Copeland et al., 2012; Mitchell and Goldstein, 2014; Pham et al., 2022; Slopen et al., 2013). A recent prospective study of 482 infants found that higher glycoprotein acetyls (GlycA, a measure of cumulative inflammation) levels at birth were associated with externalizing and internalizing problems at age two, underscoring the impact of inflammation during sensitive periods of early brain development (Pham et al., 2022).…”

Section: Introductionmentioning

confidence: 99%

Exploring the association of interleukin polymorphisms with aggression and internalizing behaviors in children and adolescents

et al. 2022

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Background: There is growing evidence that inflammation influences mental health.Blood interleukin levels, which regulate inflammation, have been linked to aggression and internalizing behaviors. We performed a hypothesis-driven genetic study to (1) evaluate the association of IL1B, IL2, and IL6 gene variants with aggression and internalizing behaviors and (2) explore gene-environment interactions with childhood adversity in a deeply phenotyped childhood-onset aggression sample including 255 cases and 226 controls of European ancestry. Methods:We evaluated the association of putative functional and tag SNPs within IL1B, IL2, and IL6 with aggression case status, parent-reported internalizing problems, self-reported anxiety symptoms, and self-reported depressive symptoms in our sample. We also performed exploratory GxE analyses within cases, testing for statistical interaction between interleukin SNP genotype and childhood adversity for depressive symptoms.Results: No significant association was observed between any of the interleukin SNPs and childhood-onset aggression. We observed association of IL6 variant rs2069827 with depressive symptoms (p = 7.15×10 -4 ), and trends for an interaction between severe childhood adversity and SNPs in IL1B and IL2 for depressive symptoms.Conclusions: Our findings provide preliminary evidence that common variation in IL6 may be associated with depressive symptoms in children and adolescents, and that common variation in interleukin genes may sensitize individuals to the depressogenic effects of traumatic life experiences. Replication in independent samples is needed.

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Infant inflammation predicts childhood emotional and behavioral problems and partially mediates socioeconomic disadvantage

Cited by 13 publications

References 106 publications

Association of maternal air pollution exposure and infant lung function is modified by genetic propensity to oxidative stress

Association of maternal air pollution exposure and infant lung function is modified by genetic propensity to oxidative stress

Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort study

Exploring the association of interleukin polymorphisms with aggression and internalizing behaviors in children and adolescents

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