Hellmuth C, Lindsay K L, Uhl O, Buss C, Wadhwa P D, Koletzko B, Entringer S
Ludwig-Maximilian-University Munich, Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, University of Munich Medical Center, Muenchen, Germany.
UC Irvine Development, Health and Disease Research Program, Department of Pediatrics, University of California, Irvine, Irvine, CA, USA.
Int J Obes (Lond). 2017 Jan;41(1):159-169. doi: 10.1038/ijo.2016.153. Epub 2016 Aug 29.
BACKGROUND/OBJECTIVES: Elevated prepregnancy body mass index (pBMI) and excess gestational weight gain (GWG) constitute important prenatal exposures that may program adiposity and disease risk in offspring. The objective of this study is to investigate the influence of pBMI and GWG on the maternal metabolomic profile across pregnancy, and to identify associations with birth weight.
SUBJECTS/METHODS: This is a longitudinal prospective study of 167 nondiabetic women carrying a singleton pregnancy. Women were recruited between March 2011 and December 2013 from antenatal clinics affiliated to the University of California, Irvine, Medical Center. Seven women were excluded from analyses because of a diagnosis of diabetes during pregnancy. A total of 254 plasma metabolites known to be related to obesity in nonpregnant populations were analyzed in each trimester using targeted metabolomics. The effects of pBMI and GWG on metabolites were tested through linear regression and principle component analysis, adjusting for maternal sociodemographic factors, diet, and insulin resistance. A Bonferroni correction was applied for multiple comparison testing.
pBMI was significantly associated with 40 metabolites. Nonesterified fatty acids (NEFA) showed a strong positive association with pBMI, with specificity for mono-unsaturated and omega-6 NEFA. Among phospholipids, sphingomyelins with two double bonds and phosphatidylcholines containing 20:3 fatty acid chain, indicative of omega-6 NEFA, were positively associated with pBMI. Few associations between GWG, quality and quantity of the diet, insulin resistance and the maternal metabolome throughout gestation were detected. NEFA levels in the first and, to a lesser degree, in the second trimester were positively associated with birth weight percentiles.
Preconception obesity appears to have a stronger influence on the maternal metabolic milieu than gestational factors such as weight gain, dietary intake and insulin resistance, highlighting the critical importance of preconception health. NEFA in general, as well as monounsaturated and omega-6 fatty acid species in particular, represent key metabolites for a potential mechanism of intergenerational transfer of obesity risk.
背景/目的：孕前体重指数（pBMI）升高和孕期体重增加过多（GWG）是重要的产前暴露因素，可能会影响子代的肥胖及疾病风险。本研究旨在探讨pBMI和GWG对孕期母体代谢组学特征的影响，并确定其与出生体重的关联。
对象/方法：这是一项对167名单胎妊娠非糖尿病女性的纵向前瞻性研究。研究对象于2011年3月至2013年12月间从加利福尼亚大学欧文分校医学中心附属的产前诊所招募。7名女性因孕期诊断为糖尿病而被排除在分析之外。在每个孕期使用靶向代谢组学分析了总共254种已知与非孕期人群肥胖相关的血浆代谢物。通过线性回归和主成分分析测试pBMI和GWG对代谢物的影响，并对母体社会人口统计学因素、饮食和胰岛素抵抗进行校正。采用Bonferroni校正进行多重比较检验。
pBMI与40种代谢物显著相关。非酯化脂肪酸（NEFA）与pBMI呈强正相关，对单不饱和脂肪酸和ω-6 NEFA具有特异性。在磷脂中，具有两个双键的鞘磷脂和含有20:3脂肪酸链的磷脂酰胆碱（指示ω-6 NEFA）与pBMI呈正相关。在整个孕期，未检测到GWG、饮食质量和数量、胰岛素抵抗与母体代谢组之间的关联。孕早期和孕中期程度较轻时的NEFA水平与出生体重百分位数呈正相关。
孕前肥胖似乎比孕期因素如体重增加、饮食摄入和胰岛素抵抗对母体代谢环境的影响更大，这突出了孕前健康的关键重要性。一般而言，NEFA，尤其是单不饱和脂肪酸和ω-6脂肪酸种类，代表了肥胖风险代际传递潜在机制的关键代谢物。
