TY - JOUR

T1 - Maternal metabolome in pregnancy and childhood asthma or recurrent wheeze in the vitamin d antenatal asthma reduction trial

AU - Huang, Mengna

AU - Kelly, Rachel S.

AU - Chu, Su H.

AU - Kachroo, Priyadarshini

AU - Gürdeniz, Gözde

AU - Chawes, Bo L.

AU - Bisgaard, Hans

AU - Weiss, Scott T.

AU - Lasky-Su, Jessica

N1 - Funding Information: Metabolomics work was supported by the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL123915 and R01HL141826. Efforts of M.H. and J.L.-S. were supported by R01HL141826 from the NHLBI. Effort of R.S.K. was additionally supported by K01HL146980-01 from NHLBI. Efforts of J.L.-S. and R.S.K. were also supported by W81XWH-17-1-0533 from the Department of Defense. Effort of S.H.C. was supported by R01AR049880 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and U01HG008685 from the National Human Genome Research Institute. Effort of P.K. was supported by P01HL132825 from the NHLBI. Efforts of G.G., B.L.C., and H.B. were supported by private and public research funds all listed on www.copsac.com; The Lundbeck Foundation; Danish State Budget; Danish Council for Strategic Research; Danish Council for Independent Research and The Capital Region Research Foundation have provided core support for the Copenhagen Prospective Studies on Asthma in Childhood. For this project B.L.C also received funding from the European Research Council (ERC) under the European Union?s Horizon 2020 research and innovation programme (grant agreement No. 946228). Effort of 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. The Vitamin D Antenatal Asthma Reduction Trial (ClinicalTrials.gov identifier: NCT00920621) was supported by grant U01HL091528 from NHLBI. Additional support was provided by grant U54TR001012 from the National Centers for Advancing Translational Sciences (NCATS) for participant visits at the Boston Medical Center. The funders had no role in study design, data collection, data analysis and interpretation, decision to publish, or preparation of the manuscript. Funding Information: Author Contributions: Conceptualization, J.L.-S. and R.S.K.; methodology, M.H., R.S.K., S.H.C., P.K., G.G., B.L.C., H.B., S.T.W., J.L.-S.; validation, R.S.K.; formal analysis, M.H.; data curation, J.LA.-Su.t,hSo.Tr.WCo.;nwtrriibtiuntgio—nos:rigCionnacl edprtaufta plirzeaptiaorna,tiJo.nL,.-MS..Han.,d RR.S..SK.K.; .w; rmiteinthgo—droelvoigeyw, Man.Hd .e,dRit.iSn.Kg,.,MS..HH..,C ., R.SP..KK..,, SG.H.G.C.,.B, P.L.K.C..,, GH.G.B..,, BS..LT..CW..,, HJ.L.B.-.,S S.;.Tv.aWlid.,a Jt.iLo-nS,.;R s.uSp.Ke.r;vfiosrimona,lJa.Ln-aSl.y; sfuisn, dMin.Hg.a; cdqautaiscituiorant,ioSn.T,.JW.L..,- S., J.LS-S.T. .AWl.l; awurtihtionrgs —haovreig rienaadl darnadft apgrreepeadr atotiothne, Mpu.Hbl.i,sRh.eSd.Kv.e; rwsiroitnin ogf— threevmieawnuasncdripedt.iting, M.H., R.S.K., S.H.C., P.K., G.G., B.L.C., H.B., S.T.W., J.L-S.; supervision, J.L-S.; funding acquisition, S.T.W., J.L-S. Funding: Metabolomics work was supported by the National Heart, Lung, and Blood Institute All authors have read and agreed to the published version of the manuscript. (NHLBI) grant R01HL123915 and R01HL141826. Efforts of M.H. and J.L.-S. were supported by R0F1HunLd1i4n1g8:26M fertoambo tlhoem NicHs wLBoIr.k Ewffoarst soufpRp.oSr.tKe.dwbays tahdedNitiaotnioanllayl sHuepaprot,rtLeudn bgy, aKn0d1HBlLo1o4d69In80st-i0t1u te fro(mN HNLHBLIB) Ig. rEafnfot rRts0 1oHf JL.L1.2-S3.9 a1n5da nRd.S.RK0. 1wHeLre14a1ls8o2 6s.upEpffoorrttesd obfyM W.H81.XaWndHJ-.1L7.--S1-.0w53e3r efrsoumppthoer tDede-by parRt0m1eHnLt 1o4f1 D82e6fefnrosme. tEhfefoNrtH oLfBSI..HE.fCfo. rwt oafs Rsu.Sp.Kp.owrtaesd abdyd iRti0o1nAaRlly04s9u8p8p0o frrtoedmb tyheK 0N1aHtiLo1n4a6l9 I8n0s-t0i1tuftreom of NAHrthLrBitIi.sE affnodrt sMoufsJ.cLu.-loS.skaneldetRa.lSa.Kn.dw Sekriena Dlsoisesuaspepsoartnedd Uby01WH8G1X00W86H8-51 7fr-1o-m05 t3h3ef rNomatitohneaDl eHpuamrtmane nt GeonfoDmeef eRnessee.aErcffho rItnostfitSu.Hte..C E.fwfoarst osuf pPp.Ko.r wtedasb syuRpp01oArtRed0 4b9y8 8P001frHomL1t3h2e82N5a ftrioomna tlhIne sNtiHtuLteBoI.f EAffrothrtrsi tis of aGn.dG.M, Bu.sLc.uCl.o,skanelde taHl.Ban. dwSekrein sDupispeoarsteesdabnyd pUr0iv1HatGe 0a0n8d6 8p5ufbrolimc rtehseeaNrcaht iofunnaldHs ualml alinstGedenoonm e www.copsac.com; The Lundbeck Foundation; Danish State Budget; Danish Council for Strategic Research; Danish Council for Independent Research and The Capital Region Research Foundation have provided core support for the Copenhagen Prospective Studies on Asthma in Childhood. For this project B.L.C also received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 946228). Effort of 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. The Vitamin D Antenatal Asthma Reduction Trial (ClinicalTrials.gov identifier: NCT00920621) was supported by grant U01HL091528 from NHLBI. Additional support was provided by grant U54TR001012 from the National Centers for Advancing Translational Sciences (NCATS) for participant visits at the Boston Medical Center. The funders had no role in study design, data collection, data analysis and Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/2

Y1 - 2021/2

N2 - The in utero environment during pregnancy has important implications for the developing health of the child. We aim to examine the potential impact of maternal metabolome at two different timepoints in pregnancy on offspring respiratory health in early life. In 685 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial, we assessed the prospective associations between maternal metabolites at both baseline (10–18 weeks gestation) and third trimester (32–38 weeks gestation) and the risk of child asthma or recurrent wheeze by age three using logistic regression models accounting for confounding factors. Subgroup analyses were performed by child sex. Among 632 metabolites, 19 (3.0%) and 62 (9.8%) from baseline and third trimester, respec-tively, were associated with the outcome (p-value < 0.05). Coffee-related metabolites in the maternal metabolome appeared to be of particular importance. Caffeine, theophylline, trigonelline, quinate, and 3-hydroxypyridine sulfate were inversely associated with asthma risk at a minimum of one timepoint. Additional observations also highlight the roles of steroid and sphingolipid metabolites. Overall, there was a stronger relationship between the metabolome in later pregnancy and offspring asthma risk. Our results suggest that alterations in prenatal metabolites may act as drivers of the development of offspring asthma.

AB - The in utero environment during pregnancy has important implications for the developing health of the child. We aim to examine the potential impact of maternal metabolome at two different timepoints in pregnancy on offspring respiratory health in early life. In 685 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial, we assessed the prospective associations between maternal metabolites at both baseline (10–18 weeks gestation) and third trimester (32–38 weeks gestation) and the risk of child asthma or recurrent wheeze by age three using logistic regression models accounting for confounding factors. Subgroup analyses were performed by child sex. Among 632 metabolites, 19 (3.0%) and 62 (9.8%) from baseline and third trimester, respec-tively, were associated with the outcome (p-value < 0.05). Coffee-related metabolites in the maternal metabolome appeared to be of particular importance. Caffeine, theophylline, trigonelline, quinate, and 3-hydroxypyridine sulfate were inversely associated with asthma risk at a minimum of one timepoint. Additional observations also highlight the roles of steroid and sphingolipid metabolites. Overall, there was a stronger relationship between the metabolome in later pregnancy and offspring asthma risk. Our results suggest that alterations in prenatal metabolites may act as drivers of the development of offspring asthma.

KW - Childhood asthma

KW - Maternal child health

KW - Metabolomic epidemiology

KW - Pregnancy metabolome

KW - Vitamin D Antenatal Asthma Reduction Trial (VDAART)

U2 - 10.3390/metabo11020065

DO - 10.3390/metabo11020065

M3 - Journal article

C2 - 33498644

AN - SCOPUS:85099981373

VL - 11

SP - 1

EP - 12

JO - Metabolites

JF - Metabolites

SN - 2218-1989

IS - 2

M1 - 65

ER -