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Association of newborn screening metabolites with risk of wheezing in childhood.

ABSTRACT: BACKGROUND:There are critical gaps in our understanding of the temporal relationships between metabolites and subsequent asthma development. This is the first study to examine metabolites from newborn screening in the etiology of early childhood wheezing. METHODS:One thousand nine hundred and fifty one infants enrolled between 2012 and 2014 from pediatric practices located in Middle Tennessee in the population-based birth cohort study, the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE), were linked with metabolite data from the Tennessee Newborn Screening Program. The association between the levels of 37 metabolites and the number of wheezing episodes in the past 12 months was assessed at 1, 2, and 3 years of life. RESULTS:Several metabolites were significantly associated with the number of wheezing episodes. Two acylcarnitines, C10:1 and C18:2, showed robust associations. Increasing levels of C10:1 were associated with increasing number of wheezing episodes at 2 years (OR 2.11, 95% CI 1.41-3.17) and 3 years (OR 2.56, 95% CI 1.59-4.11), while increasing levels of C18:2 were associated with increasing number of wheezing episodes at 1 year (OR 1.38, 95% CI 1.12-1.71) and 2 years (OR 1.47, 95% CI 1.17-1.84). CONCLUSIONS:Identification of specific metabolites and associated pathways involved in wheezing pathogenesis offer insights into potential targets to prevent childhood asthma morbidity.

SUBMITTER: Donovan BM

PROVIDER: S-EPMC6274622 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Association of newborn screening metabolites with risk of wheezing in childhood.

Donovan Brittney M BM Ryckman Kelli K KK Breheny Patrick J PJ Gebretsadik Tebeb T Turi Kedir N KN Larkin Emma K EK Li Yinmei Y Dorley Mary C MC Hartert Tina V TV

Pediatric research 20180601 5

<h4>Background</h4>There are critical gaps in our understanding of the temporal relationships between metabolites and subsequent asthma development. This is the first study to examine metabolites from newborn screening in the etiology of early childhood wheezing.<h4>Methods</h4>One thousand nine hundred and fifty one infants enrolled between 2012 and 2014 from pediatric practices located in Middle Tennessee in the population-based birth cohort study, the Infant Susceptibility to Pulmonary Infect ...[more]

PMID: 29892036

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Project description:ImportanceAdult telomere length (TL) is a biological marker of aging associated with vascular health. TL at birth is associated with later life TL and may contain early biological information of later life cardiovascular health and disease.ObjectiveTo evaluate whether newborn TL is associated with early life blood pressure differences in childhood.Design, setting, and participantsThis cohort study was part of the ENVIRONAGE (Environmental Influence on Aging in Early Life) study, a birth cohort of Belgian mother-child pairs with recruitment at birth and a median follow-up of 4.5 years conducted between October 2014 and July 2021. Participants included for analysis provided full data for evaluation at follow-up visit. Data analysis was conducted between August and September 2021.Main outcomes and measuresCord blood and placental average relative TL were measured at birth using quantitative polymerase chain reaction (qPCR). Systolic, diastolic, and mean arterial pressure (MAP) were evaluated at follow-up. High childhood blood pressure (standardized for child age, sex, and height) was defined following the 2017 American Academy of Pediatrics guidelines. Multivariable adjusted linear and logistic regression models were used to associate newborn TL and blood pressure indicators in childhood.ResultsThis study included 485 newborn children (52.8% girls) with a mean (SD) age of 4.6 (0.4) years at the follow-up visit. Newborn TL was associated with lower blood pressure in childhood. A 1-IQR increase in cord blood TL was associated with a -1.54 mm Hg (95% CI, -2.36 to -0.72 mm Hg) lower diastolic blood pressure and -1.18 mm Hg (95% CI, -1.89 to -0.46 mm Hg) lower MAP. No association was observed with systolic blood pressure. Furthermore, a 1-IQR increase in cord blood TL was associated with lower odds of having high blood pressure at the age of 4 to 6 years (adjusted OR, 0.72; 95% CI, 0.53 to 0.98). In placenta, a 1-IQR increase in TL was associated with a -0.96 mm Hg (95% CI, -1.72 to -0.21 mm Hg) lower diastolic, -0.88 mm Hg (95% CI, -1.54 to -0.22 mm Hg) lower MAP, and a lower adjusted OR of 0.69 (95% CI, 0.52 to 0.92) for having a high blood pressure in childhood.Conclusions and relevanceIn this prospective birth cohort study, variation in early life blood pressure at school-age was associated with TL at birth. Cardiovascular health may to some extent be programmed at birth, and these results suggest that TL entails a biological mechanism in this programming.

Project description:Rapid postnatal weight gain is a potentially modifiable risk factor for obesity and metabolic syndrome. To identify markers of rapid infancy weight gain and childhood obesity, we analyzed the metabolome in cord blood from infants differing in their postnatal weight trajectories.We performed a nested case-control study within Project Viva, a longitudinal cohort of mothers and children. We selected cases (n=26) based on top quartile of change in weight-for-age 0-6 months and body mass index (BMI) >85th percentile in mid-childhood (median 7.7 years). Controls (n=26) were age and sex matched, had normal postnatal weight gain (2nd or 3rd quartile of change in weight-for-age 0-6 months) and normal mid-childhood weight (BMI 25th-75th percentile). Cord blood metabolites were measured using untargeted liquid chromatography-mass spectrometry; individual metabolites and pathways differing between cases and controls were compared in categorical analyses. We adjusted metabolites for maternal age, maternal BMI and breastfeeding duration (linear regression), and assessed whether metabolites improved the ability to predict case-control status (logistic regression).Of 415 detected metabolites, 16 were altered in cases versus controls (t-test, nominal P<0.05). Three metabolites were related to tryptophan: serotonin, tryptophan betaine and tryptophyl leucine (46%, 48% and 26% lower in cases, respectively, P<0.05). Mean levels of two methyl donors, dimethylglycine and N-acetylmethionine, were also lower in cases (18% and 16%, respectively, P=0.01). Moreover, the glutamine:glutamate ratio was reduced by 33% (P<0.05) in cases. Levels of serotonin, tryptophyl leucine and N-acetylmethionine remained significantly different after adjustment for maternal BMI, age and breastfeeding. Adding metabolite levels to logistic regression models including only clinical covariates improved the ability to predict case versus control status.Several cord blood metabolites are associated with rapid postnatal weight gain. Whether these patterns are causally linked to childhood obesity is not clear from this cross-sectional analysis, but will require further study.

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Association of newborn screening metabolites with risk of wheezing in childhood.

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Association of newborn screening metabolites with risk of wheezing in childhood.

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