Sanz-Cortés Magdalena, Carbajo Rodrigo J, Crispi Fatima, Figueras Francesc, Pineda-Lucena Antonio, Gratacós Eduard
Department of Maternal-Fetal Medicine, Institute Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clinic, Institut de Investigacions Biomèques August Pi-Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
PLoS One. 2013 Dec 2;8(12):e80121. doi: 10.1371/journal.pone.0080121. eCollection 2013.
To characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR).
23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA) controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight <10(th) centile, abnormal umbilical artery (UA) Doppler and delivery <35 weeks. Late IUGR was defined as a birth weight <10(th) centile with normal UA Doppler and delivery >35 weeks. This group was subdivided in 18 vasodilated (VD) and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10(th) centile. (1)H nuclear magnetic resonance (NMR) metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data.
The NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR.
IUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.
通过核磁共振波谱法对诊断为不同临床类型的宫内生长受限（IUGR）的新生儿脐静脉血浆中的代谢变化全貌进行表征。
本研究纳入了23例早期IUGR病例及与之匹配的23例适于胎龄（AGA）对照，以及56例晚期IUGR病例及与之匹配的56例AGA对照。早期IUGR定义为出生体重低于第10百分位数、脐动脉（UA）多普勒异常且分娩孕周<35周。晚期IUGR定义为出生体重低于第10百分位数、UA多普勒正常且分娩孕周>35周。该组又分为18例血管扩张型（VD）和38例非VD型晚期IUGR胎儿。所有AGA患者出生体重均高于第10百分位数。对分娩时从脐静脉采集的血样进行了氢核磁共振（NMR）代谢组学分析。多变量统计分析确定了几种可区分不同IUGR亚组的代谢物，并根据NMR数据对其相对水平进行了定量。
基于NMR的分析显示，早期和晚期IUGR样本中不饱和脂质和极低密度脂蛋白（VLDL）水平升高，早期IUGR中葡萄糖水平降低而丙酮水平升高。晚期IUGR中葡萄糖水平降低和丙酮水平升高呈非显著趋势，在考虑VD和非VD亚组时呈现严重程度梯度。关于氨基酸及其衍生物，早期IUGR中谷氨酰胺和肌酸水平显著升高，而早期和晚期VD型IUGR样本中苯丙氨酸和酪氨酸含量降低。晚期IUGR样本中缬氨酸和亮氨酸含量降低。IUGR的所有临床亚组中胆碱水平均降低。
IUGR并非与单一的代谢谱相关，但在研究和临床实践中所使用的不同临床亚组中存在重要变化。这些结果可能有助于全面表征不同IUGR亚组背后的特定改变。
