Cord blood metabolites and rapid postnatal growth as multiple mediators in the prenatal propensity to childhood overweight.
Cord blood metabolites and rapid postnatal growth as multiple mediators in the prenatal propensity to childhood overweight.
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脐带血代谢物和出生后快速生长作为儿童期超重的产前倾向的多种介导因素
DOI：
10.1038/s41366-022-01108-0
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发表时间：
2022-07
影响因子：
4.9
通讯作者：
Zugna, Daniela
中科院分区：
文献类型：
--
作者：
Alfano, Rossella;Plusquin, Michelle;Robinson, Oliver;Brescianini, Sonia;Chatzi, Lida;Keski-Rahkonen, Pekka;Handakas, Evangelos;Maitre, Lea;Nawrot, Tim;Robinot, Nivonirina;Roumeliotaki, Theano;Sassi, Franco;Scalbert, Augustin;Vrijheid, Martine;Vineis, Paolo;Richiardi, Lorenzo;Zugna, Daniela
儿童超重和肥胖的潜在机制鲜为人知。在此，我们研究了不同的产前暴露通过脐带血代谢物对后代出生后快速生长和儿童期超重的直接和间接影响。此外，出生后快速生长被视为儿童超重的一个潜在中介因素，无论是单独作用还是在每种代谢物之后依次发挥作用。
在四个欧洲出生队列（N = 375对母婴）中，收集了七种产前暴露的信息（母亲教育程度、孕前体重指数、孕期体重增加和吸烟情况、分娩年龄、产次以及胎儿胎龄），这些信息是根据先验知识被选作致肥胖因素的。通过液相色谱 - 四极杆 - 飞行时间质谱法测量了31种代谢物的脐带血水平，这些代谢物在先前的研究中与出生后快速生长和/或儿童期超重有关。参照世界卫生组织生长图表确定了12个月时的快速生长以及4至8岁之间的儿童超重（包括肥胖）情况。使用插补法进行了单一中介分析，使用扩展插补法进行了多重中介分析。
单一中介分析表明，母亲教育程度、孕期体重增加、产次和胎龄对出生后快速生长（而非对儿童期超重）的影响部分是由七种代谢物介导的，这些代谢物包括胆甾烯酮、癸烯酰肉碱（C10:1）、磷脂酰胆碱（C34:3）、孕酮以及三种未确定的代谢物；胎龄对儿童期超重的影响主要是由出生后快速生长介导的。多重中介分析表明，胎龄对儿童期超重的影响主要是由出生后快速生长介导的，代谢物的中介作用很小。
我们的研究结果提供了证据，证明子宫内代谢与出生后快速生长倾向有关，出生后快速生长与儿童期超重倾向有关。我们没有发现证据支持所研究的代谢物在产前暴露与儿童期超重倾向之间单独起中介作用。
The mechanisms underlying childhood overweight and obesity are poorly known. Here, we investigated the direct and indirect effects of different prenatal exposures on offspring rapid postnatal growth and overweight in childhood, mediated through cord blood metabolites. Additionally, rapid postnatal growth was considered a potential mediator on childhood overweight, alone and sequentially to each metabolite. Within four European birth-cohorts (N = 375 mother-child dyads), information on seven prenatal exposures (maternal education, pre-pregnancy BMI, weight gain and tobacco smoke during pregnancy, age at delivery, parity, and child gestational age), selected as obesogenic according to a-priori knowledge, was collected. Cord blood levels of 31 metabolites, associated with rapid postnatal growth and/or childhood overweight in a previous study, were measured via liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry. Rapid growth at 12 months and childhood overweight (including obesity) between four and eight years were defined with reference to WHO growth charts. Single mediation analysis was performed using the imputation approach and multiple mediation analysis using the extended-imputation approach. Single mediation suggested that the effect of maternal education, pregnancy weight gain, parity, and gestational age on rapid postnatal growth but not on childhood overweight was partly mediated by seven metabolites, including cholestenone, decenoylcarnitine(C10:1), phosphatidylcholine(C34:3), progesterone and three unidentified metabolites; and the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth. Multiple mediation suggested that the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth and that the mediating role of the metabolites was marginal. Our findings provide evidence of the involvement of in utero metabolism in the propensity to rapid postnatal growth and of rapid postnatal growth in the propensity to childhood overweight. We did not find evidence supporting a mediating role of the studied metabolites alone between the studied prenatal exposures and the propensity to childhood overweight.
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影响因子：
16.2
作者：
Lowe WL Jr;Bain JR;Nodzenski M;Reisetter AC;Muehlbauer MJ;Stevens RD;Ilkayeva OR;Lowe LP;Metzger BE;Newgard CB;Scholtens DM;HAPO Study Cooperative Research Group
通讯作者：
HAPO Study Cooperative Research Group
影响因子：
4.9
作者：
Dulloo, A. G.;Jacquet, J.;Montani, J-P
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Montani, J-P
影响因子：
3.6
作者：
Ernst, Madeleine;Rogers, Simon;Cohen, Arieh S.
通讯作者：
Cohen, Arieh S.
影响因子：
4.9
作者：
Freedman, DS;Wang, J;Horlick, M
通讯作者：
Horlick, M
影响因子：
8.3
作者：
Gaillard, Romy;Rurangirwa, Akashi A.;Jaddoe, Vincent W. V.
通讯作者：
Jaddoe, Vincent W. V.