Effect of perfluoroalkyl exposure in pregnancy and infancy on intrauterine and childhood growth and anthropometry. Sub study from COPSAC2010 birth cohort.
Effect of perfluoroalkyl exposure in pregnancy and infancy on intrauterine and childhood growth and anthropometry. Sub study from COPSAC2010 birth cohort.
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DOI：
10.1016/j.ebiom.2022.104236
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发表时间：
2022-09
期刊：
影响因子：
11.1
通讯作者：
Chawes, Bo
中科院分区：
文献类型：
--
作者：
Sevelsted, Astrid;Gurdeniz, Gozde;Rago, Daniela;Pedersen, Casper-Emil Tingskov;Lasky-Su, Jessica A.;Checa, Antonio;Zhang, Pei;Wheelock, Craig E.;Normann, Stine S.;Kristensen, David M.;Rasmussen, Morten Arendt;Schullehner, Jorg;Sdougkou, Kalliroi;Martin, Jonathan W.;Stokholm, Jakob;Bonnelykke, Klaus;Bisgaard, Hans;Chawes, Bo
关键词：
全氟烷基物质全氟辛烷磺酸和全氟辛酸是人体内具有持久性和生物累积性的外源性化学品，可能对健康产生一系列不利影响。据推测，产前和产后早期的接触可能对子宫内和儿童期的生长产生特别有害的影响。在丹麦纵向母婴队列研究中，我们调查了妊娠期和婴儿期全氟辛烷磺酸和全氟辛酸对宫内和儿童期生长和人体测量的影响。COPSAC 2010是一项正在进行的基于人群的母婴队列研究，包括738名孕妇及其子女，从妊娠24周开始进行纵向深度临床表型分析，直至10岁。在这项观察性队列子研究中，通过非靶向代谢组学对产后24周和1周的母亲以及6个月和18个月的儿童的血浆全氟辛烷磺酸和全氟辛酸浓度进行了半定量，并使用靶向管道进行了校准。我们研究了子宫内和儿童期生长和人体测量的相关性，包括与儿童性别的相互作用。整合非靶向和靶向血液代谢组学谱以研究潜在机制。妊娠期血浆PFOA浓度与较低的出生尺寸-0. 19 [-0. 33;-0. 05] BMI z评分/1-ng/mL和6岁时儿童身高（z评分）增加相关：0. 18 [0. 05; 0. 31]，但查尔兹自己的婴儿期血浆PFOA浓度与身高之间没有关联。妊娠期血浆全氟辛烷磺酸浓度也与出生体重指数较低有关（− 0.04 [− 0.08; − 0.01]），但在儿童期，妊娠期血浆全氟辛烷磺酸浓度与6岁时体重指数和脂肪百分比的儿童性别相互作用，女孩与体重指数呈负相关，男孩与体重指数呈正相关。母体血浆全氟辛烷磺酸浓度对女孩体重指数较低的影响是通过增加儿童血浆乳糖神经酰胺水平介导的（p-介导值= 0.08）。同样，母亲血浆中全氟辛烷磺酸浓度对男孩脂肪百分比较高的影响也是通过增加儿童血浆中乳糖基神经酰胺水平介导的（p-介导值= 0.07）。婴儿血浆中全氟辛烷磺酸浓度与儿童身高较低相关，6岁时z值为− 0.06 [− 0.19; − 0.03]。怀孕期间全氟辛烷磺酸和全氟辛酸血浆浓度较高，对胎儿生长有不利影响。在多污染物模型中，全氟辛酸会增加儿童身高，对儿童生长的影响与全氟辛烷磺酸不同，这表明胎儿发育的影响不同。性别特异性生长效应是通过改变乳糖基神经酰胺代谢介导的，在这项观察性研究中，提出了全氟辛烷磺酸对健康产生长期影响的可能机制。COPSAC收到的所有资金都列在www.copsac.com上。伦贝克基金会（批准号R16-A1694）; Novo Nordic基金会（批准号：NNF20OC0061029、NNF170C0025014、NNF180C0031764）（批准号：903516）;丹麦战略研究理事会（批准号0603 - 00280B）和首都地区研究基金会提供了核心支持COPSAC研究中心。JALS的工作得到了NIH/NHLBI的R01HL123915、R01HL141826和R01HL155742的支持。CEW得到了瑞典心肺基金会（HLF 20180290，HLF 20200693）的支持。不列颠哥伦比亚省已收到欧洲研究理事会在欧洲联盟地平线2020研究和创新方案下为该项目提供的资金（赠款协议编号：946228）。资助机构在研究的设计和实施;数据的收集、管理和解释;或手稿的编写、审查或批准方面没有任何作用。
Perfluoroalkyl substances PFOS and PFOA are persistent and bioaccumulative exogenous chemicals in the human body with a range of suspected negative health effects. It is hypothesised that exposure during prenatal and early postnatal life might have particularly detrimental effects on intrauterine and childhood growth. In a Danish longitudinal mother-child cohort we investigate effect of PFOS and PFOA in pregnancy and infancy on intrauterine and childhood growth and anthropometry. COPSAC2010 is an ongoing population based mother-child cohort of 738 pregnant women and their children followed from 24 week gestation with longitudinal deep clinical phenotyping until age 10 years. In this observational cohort sub study plasma PFOS and PFOA concentrations were semi-quantified by untargeted metabolomics in the mothers at week 24 and 1 week postpartum and in the children at ages 6 and 18 months and calibrated using a targeted pipeline. We examined associations to intrauterine and childhood growth and anthropometry, including interactions with child sex. Untargeted and targeted blood metabolomics profiles were integrated to investigate underlying mechanisms. Pregnancy plasma PFOA concentrations were associated with lower birth size −0.19 [−0.33; −0.05] BMI z-score per 1-ng/mL and increased childhood height (z-scored) at age 6: 0.18 [0.05; 0.31], but there was no association between childs’ own infancy plasma PFOA concentration and height. Pregnancy plasma PFOS concentrations were also associated with lower birth BMI (−0.04 [−0.08; −0.01]), but in childhood pregnancy plasma PFOS concentration interacted with child sex on BMI and fat percentage at 6 years with negative associations in girls and positive in boys. The effect of maternal plasma PFOS concentration on lower girl BMI was borderline mediated through increasing child plasma lactosyl-ceramide levels (p-mediation=0.08). Similarly the effect of maternal plasma PFOS concentration on higher boy fat percentage was borderline mediated through increasing child plasma lactosyl-ceramide levels (p-mediation=0.07). Infancy concentrations of plasma PFOS associated with lower height in childhood, −0.06 z-score at age 6 [−0.19; −0.03]. Higher PFOS and PFOA plasma concentrations during pregnancy had detrimental effects on fetal growth. The effects on childhood growth were not similar as PFOA increased child height, opposite of PFOS in multipollutant models suggesting a differing fetal programming effect. Sex specific growth effects were borderline mediated through an altered lactosyl-ceramide metabolism, proposing a possible mechanism of PFOS that has long-lasting health consequences in this observational study. All funding received by COPSAC are listed on www.copsac.com. The Lundbeck Foundation (Grant no R16-A1694); The Novo Nordic Foundation (Grant nos NNF20OC0061029, NNF170C0025014, NNF180C0031764) 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. Effort from JALS is supported by R01HL123915, R01HL141826, and R01HL155742 from NIH/NHLBI. CEW was supported by the Swedish Heart Lung Foundation (HLF 20180290, HLF 20200693). BC has received funding for this project from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 946228). The funding agencies did not have any role in design and conduct of the study; collection, management, and interpretation of the data; or preparation, review, or approval of the manuscript.
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影响因子：
8.8
作者：
Geiger, Sarah Dee;Yao, Ping;Qian, Zhengmin
通讯作者：
Qian, Zhengmin
影响因子：
10.4
作者：
Jensen, Richard Christian;Andersen, Marianne S.;Jensen, Tina Kold
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产前暴露于全氟辛酸和20岁时超重的风险：一项前瞻性队列研究。
影响因子：
10.4
作者：
Halldorsson TI;Rytter D;Haug LS;Bech BH;Danielsen I;Becher G;Henriksen TB;Olsen SF
通讯作者：
Olsen SF
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
14.2
作者：
Lehtimaki, Jenni;Thorsen, Jonathan;Stokholm, Jakob
通讯作者：
Stokholm, Jakob