Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.
Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts.
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怀孕前体重指数与后代代谢概况的关联：3个欧洲前瞻性出生队列的分析。
DOI：
10.1371/journal.pmed.1002376
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发表时间：
2017-08
期刊：
影响因子：
15.8
通讯作者：
Lawlor DA
中科院分区：
文献类型：
--
作者：
Santos Ferreira DL;Williams DM;Kangas AJ;Soininen P;Ala-Korpela M;Smith GD;Jarvelin MR;Lawlor DA
很大比例的妇女在怀孕时超重或肥胖。根据发育性营养过剩假说，这可能导致后代一生中代谢紊乱，从而使肥胖症在几代人中持续流行。对这一假设的关切正在影响产前保健。然而，目前尚不清楚母亲妊娠肥胖是否与后代不良代谢特征的长期风险相关，如果是这样，这种关联是否是因果关系，通过宫内机制，或由共同的家族（遗传，生活方式，社会经济）特征解释。我们的目的是确定母亲的体重指数（BMI）和后代的全身心脏代谢谱之间的关联是因果关系，通过宫内机制，或由于共享的家族因素。我们使用1-和2-阶段个体参与者数据（IPD）荟萃分析，以及阴性对照（父亲BMI）来检查3个欧洲出生队列（采血时的后代年龄：16岁，17岁和31岁）的母体孕前BMI与后代血清代谢组之间的关联。循环代谢特征通过高通量核磁共振代谢组学进行定量。一阶段IPD荟萃分析（N = 5327至5377名母亲-父亲-后代三人组）的结果显示，母亲和父亲BMI的增加与后代的不良心脏代谢特征相关。我们观察到极低密度脂蛋白（VLDL）-脂蛋白、VLDL-胆固醇（C）、VLDL-甘油三酯、VLDL-直径、支链/芳香族氨基酸、糖蛋白乙酰基和甘油三酯与高密度脂蛋白（HDL）、HDL-直径、HDL-C、HDL 2-C和HDL 3-C之间存在强正相关性，与高密度脂蛋白（HDL）、HDL-C、HDL 2-C和HDL 3-C之间存在强负相关性（均P < 0.003）。在这些关联中，与父亲BMI相比，母亲BMI的关联程度略强;然而，它们之间的异质性没有强有力的统计学证据（所有自举P > 0.003，相当于多重检验后的P > 0.05）。每个单独队列和2阶段分析的结果相似。后代BMI与代谢谱的横截面关联模式与父母孕前BMI关联相似，但幅度更大。将父母BMI-后代代谢性状关联调整为后代BMI，表明父母BMI与后代BMI的关联在很大程度上是由于父母BMI与后代BMI的关联。这项研究的局限性是不能推断循环母体胎儿燃料的作用（即，葡萄糖、脂质、脂肪酸和氨基酸）对后代代谢谱的影响。此外，BMI可能无法反映母体妊娠脂肪分布的潜在影响。我们的研究结果表明，母亲的BMI-后代代谢组协会可能主要是由于共同的遗传或家庭生活方式的混淆，而不是子宫内的机制。Debbie Lawlor及其同事评估了母亲妊娠肥胖与儿童心脏代谢紊乱之间的联系，并表明共同的家族因素而不是子宫内因素是负责任的。目前尚不清楚母亲妊娠肥胖是否与后代不良代谢特征的长期风险相关，如果是，这种关联是否是通过宫内机制的因果关系或由共同的家族（遗传，生活方式，社会经济）特征解释。我们的研究旨在通过使用父亲的BMI-后代代谢性状关联作为阴性对照，来分析母亲妊娠BMI-后代代谢性状关联是由于宫内机制（涉及发育中胎儿的过度喂养）还是共同的家族特征（或两者兼而有之）。如果母亲的关联代表因果宫内效应，而不是由于共同的家族因素，他们应该比父亲的关联具有相同的代谢特征。我们在3个独立的欧洲出生队列（> 10，000）中研究了母亲怀孕前BMI与153个后代青春期和成年期血清代谢特征之间的关联，并将这些与父亲BMI后代代谢特征进行了比较作为阴性对照。父亲的BMI被用作阴性对照，因为它与主要暴露（母亲BMI）的大多数混杂因素相同，但不能通过宫内效应直接影响后代的代谢特征。我们发现很少有证据表明母亲BMI与后代结局有明显更强的关联。我们的研究结果更支持共同的家庭因素比宫内发育营养过剩机制的母亲体重指数与后代代谢特征的关联。降低所有家庭成员的BMI的干预措施可能比专注于降低孕产妇孕前或妊娠BMI更有益于心脏代谢健康。
A high proportion of women start pregnancy overweight or obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives and thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) and offspring systemic cardio-metabolic profile are causal, via intrauterine mechanisms, or due to shared familial factors. We used 1- and 2-stage individual participant data (IPD) meta-analysis, and a negative-control (paternal BMI) to examine the association between maternal pre-pregnancy BMI and offspring serum metabolome from 3 European birth cohorts (offspring age at blood collection: 16, 17, and 31 years). Circulating metabolic traits were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from 1-stage IPD meta-analysis (N = 5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with very-low-density lipoprotein (VLDL)-lipoproteins, VLDL-cholesterol (C), VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with high-density lipoprotein (HDL), HDL-diameter, HDL-C, HDL2-C, and HDL3-C (all P < 0.003). Slightly stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations; however, there was no strong statistical evidence for heterogeneity between them (all bootstrap P > 0.003, equivalent to P > 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the 2-stage analysis. Offspring BMI showed similar patterns of cross-sectional association with metabolic profile as for parental pre-pregnancy BMI associations but with greater magnitudes. Adjustment of parental BMI–offspring metabolic traits associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI with offspring BMI. Limitations of this study are that inferences cannot be drawn about the role of circulating maternal fetal fuels (i.e., glucose, lipids, fatty acids, and amino acids) on later offspring metabolic profile. In addition, BMI may not reflect potential effects of maternal pregnancy fat distribution. Our findings suggest that maternal BMI–offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding rather than to intrauterine mechanisms. Debbie Lawlor and colleagues assess the link between maternal pregnancy adiposity and disrupted childhood cardio-metabolic profiles and show that shared familial factors are responsible rather than intrauterine ones. It is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal via intrauterine mechanisms or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. Our study was designed to unpick whether maternal pregnancy BMI–offspring metabolic traits associations were due to intrauterine mechanisms (involving overfeeding of the developing fetus) or shared familial characteristics (or both of these) by using paternal BMI–offspring metabolic traits associations as a negative control. If maternal associations represent causal intrauterine effects, as opposed to being due to shared familial factors, they should be stronger than paternal associations with the same metabolic traits. We looked at associations between maternal pre-pregnancy BMI and 153 offspring serum metabolic traits, in adolescence and adulthood, in 3 independent European birth cohorts (>10,000) and compared these to paternal BMI–offspring metabolic traits as a negative control. Paternal BMI was used as a negative control as it will share most of the confounders of the main exposure (maternal BMI) but could not directly influence offspring’s metabolic traits via an intrauterine effect. We found very little evidence of a markedly stronger association of maternal BMI with offspring outcomes. Our findings are more supportive of shared familial factors than intrauterine developmental overnutrition mechanisms for associations of maternal BMI with offspring metabolic traits. Interventions to reduce BMI in all family members may be more beneficial for cardio-metabolic health than focusing on reducing maternal pre-conception or pregnancy BMI.
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影响因子：
30.8
作者：
Kettunen, Johannes;Tukiainen, Taru;Sarin, Antti-Pekka;Ortega-Alonso, Alfredo;Tikkanen, Emmi;Lyytikainen, Leo-Pekka;Kangas, Antti J.;Soininen, Pasi;Wuertz, Peter;Silander, Kaisa;Dick, Danielle M.;Rose, Richard J.;Savolainen, Markku J.;Viikari, Jorma;Kahonen, Mika;Lehtimaki, Terho;Pietilainen, Kirsi H.;Inouye, Michael;McCarthy, Mark I.;Jula, Antti;Eriksson, Johan;Raitakari, Olli T.;Salomaa, Veikko;Kaprio, Jaakko;Jarvelin, Marjo-Riitta;Peltonen, Leena;Perola, Markus;Freimer, Nelson B.;Ala-Korpela, Mika;Palotie, Aarno;Ripatti, Samuli
通讯作者：
Ripatti, Samuli
影响因子：
8.3
作者：
Gaillard, Romy;Steegers, Eric A. P.;Jaddoe, Vincent W. V.
通讯作者：
Jaddoe, Vincent W. V.
影响因子：
2.1
作者：
Gao, Xiaoyi;Stamier, Joshua;Martin, Eden R.
通讯作者：
Martin, Eden R.
DOI：
10.1002/j.1550-8528.1999.tb00712.x
发表时间：
1999-11-01
期刊：
OBESITY RESEARCH
影响因子：
--
作者：
Katzmarzyk, PT;Pérusse, L;Bouchard, C
通讯作者：
Bouchard, C
影响因子：
5
作者：
Lawlor, Debbie A.;Smith, George Davey;Najman, Jake M.
通讯作者：
Najman, Jake M.