Evidence map›Paper›PMID 39151420›Full record

SynthesisMed (New York, N.Y.)2024

Bilirubin metabolism in early life and respiratory health during preschool age: A combined analysis of two independent birth cohorts.

Min Kim, Nicklas Brustad, Anders U Eliasen, Mina Ali, Tingting Wang, Morten A Rasmussen, Madeleine Ernst, David Hougaard, Augusto A Litonjua, Craig E Wheelock and 9 more

Registry-linked trialAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Med (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00920621 (Randomized Trial), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00920621 phase3completednot on this map

Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART)

TypeinterventionalSponsorBrigham and Women's HospitalRan2009 to 2023Enrolled876ConditionsAsthmaArmsVitamin D 3 cholecalciferol, Vitamin D3
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Min KimCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Nicklas BrustadCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Anders U EliasenCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Mina AliCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Tingting WangCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Morten A RasmussenCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Food Science, University of Copenhagen, Copenhagen, Denmark.
Madeleine ErnstSection for Clinical Mass Spectrometry, Department of Congenital Disorders, Danish Center for Neonatal Screening, Statens Serum Institut, 2300 Copenhagen, Denmark.
David HougaardSection for Clinical Mass Spectrometry, Department of Congenital Disorders, Danish Center for Neonatal Screening, Statens Serum Institut, 2300 Copenhagen, Denmark.
Augusto A LitonjuaDivision of Pediatric Pulmonary Medicine, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY, USA.
Craig E WheelockUnit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
Rachel S KellyChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Yulu ChenChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nicole PrinceChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Paul A TownsendFaculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Jakob StokholmCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Scott T WeissChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Klaus BønnelykkeCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Jessica Lasky-SuChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Bo ChawesCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: chawes@copsac.com.

Funding

Systems Biology of Airway DiseaseP01HL132825 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WEISS, SCOTT T · 2016 to 2020
$12.6M
Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood AsthmaU01HL091528 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LITONJUA, AUGUSTO A, WEISS, SCOTT T · 2009 to 2013
$10.0M
RANDOMIZED CONTROLLED TRIAL: VDAART CONTINUATION STUDY - DCC - LEADR01HL091528 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LITONJUA, AUGUSTO A, WEISS, SCOTT T · 2014 to 2018
$9.1M
Integrative Metabolomics of Asthma SeverityR01HL123915 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LASKY-SU, JESSICA A · 2014 to 2023
$7.0M
Boston University Clinical and Translational Science Institute - U ProgramU54TR001012 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CENTER, DAVID M. · 2014 to 2014
$3.9M
Mechanistic insights into asthma pathogenesis through the integration of asthma genes, risk exposures, and metabolomicsR01HL141826 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LASKY-SU, JESSICA A · 2018 to 2021
$3.4M
Multi-omic approaches to mechanisms of vitamin D, environmental influences, and the microbiome on asthmaUG3OD023268 · OD · BRIGHAM AND WOMEN'S HOSPITAL · PI LITONJUA, AUGUSTO A, WEISS, SCOTT T · 2016 to 2017
$2.8M
Better utilization of omics data to inform precision medicine for asthma throughout the life courseR01HL169300 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI JESSICA A LASKY-SU · 2024 to 2026
$2.3M
Multi-Omic Endotyping of AsthmaK01HL146980 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KELLY, RACHEL SABINE · 2019 to 2023
$891k
NCATS NIH HHS U54 TR001012NHLBI NIH HHS K01 HL146980NHLBI NIH HHS P01 HL132825NHLBI NIH HHS R01 HL091528NHLBI NIH HHS R01 HL123915NHLBI NIH HHS R01 HL141826NHLBI NIH HHS R01 HL169300NHLBI NIH HHS U01 HL091528NIH HHS UG3 OD023268
6 · The paper itself

Abstract

backgroundBilirubin has antioxidant properties, and elevated levels within the normal range have been associated with improved lung function and decreased risk of asthma in adults, but studies of young children are scarce. Here, we investigate associations between bilirubin in early life and respiratory health endpoints during preschool age in two independent birth cohorts.

methodsBilirubin metabolites were assessed at ages 0.5, 1.5, and 6 years in COPSAC

findingsIncreasing bilirubin (Z,Z) at ages 1.5-3 years was associated with an increased risk of allergic sensitization (adjusted relative risk [aRR] = 1.85 [1.20-2.85], p = 0.005), and age 6 bilirubin (Z,Z) also showed a trend of association with allergic sensitization at age 6 (aRR = 1.31 [0.97-1.77], p = 0.08), which showed significant interaction for the age 6 bilirubin (Z,Z)xUGT1A genotype. Further, increasing bilirubin (E,E), bilirubin (Z,Z), and biliverdin at ages 1.5-3 years was associated with a lower forced expiratory volume at age 6 (aRR range = 0.81-0.91, p < 0.049) but without a significant interaction with the UGT1A genotype (p interactions > 0.05). Network analysis showed a significant correlation between bilirubin metabolism and acyl carnitines. There were no associations between bilirubin metabolites and the risk of asthma and infections.

conclusionsBilirubin metabolism in early life may play a role in childhood respiratory health, particularly in children with specific UGT1A genotypes.

fundingThe Lundbeck Foundation (Grant no R16-A1694), The Ministry of Health (Grant no 903516), Danish Council for Strategic Research (Grant no 0603-00280B), and The Capital Region Research Foundation have provided core support to the COPSAC research center. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 946228). The Vitamin D Antenatal Asthma Reduction Trial (VDDART, ClinicalTrials.gov identifier: NCT00920621) was supported by grant U01HL091528 from NHLBI, U54TR001012 from the National Centers for Advancing Translational Sciences (NCATS). Metabolomics work by VDAART was supported by the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL123915 and R01HL141826. S.T.W. was supported by R01HL091528 from the NHLBI, UG3OD023268 from Office of The Director, National Institute of Health, and P01HL132825 from the NHLBI.

Indexed as

AsthmaBilirubinGlucuronosyltransferaseBirth CohortChildChild, PreschoolFemaleGenotypeHumansHypersensitivityInfantMaleProspective StudiesUGT1A1 EnzymeBilirubinGlucuronosyltransferaseUGT1A1 Enzymeasthmabilirubinchildhoodearly lifelung functionTranslation to population health

Identifiers

PMID39151420
PMCPMC12127853

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.