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Abstract：
BACKGROUND: Spontaneous preterm delivery (<37 gestational weeks) has a multifactorial etiology with still incompletely identified pathways. Amniotic fluid is a biofluid with great potential for insights into the feto-maternal milieu. It is rich in metabolites, and metabolic consequences of inflammation is yet researched only to a limited extent. Metabolomic profiling provides opportunities to identify potential biomarkers of inflammatory conditioned pregnancy complications such as spontaneous preterm delivery.
OBJECTIVE: The aim of this study was to perform metabolomic profiling of amniotic fluid from uncomplicated singleton pregnancies in the mid-trimester to identify potential biomarkers associated with spontaneous preterm delivery and gestational duration at delivery. A secondary aim was to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers of spontaneous preterm delivery in asymptomatic women.
METHODS: A nested case-control study was performed within a larger cohort study of asymptomatic pregnant women undergoing mid-trimester genetic amniocentesis at 14-19 gestational weeks in Gothenburg, Sweden. Medical records were used to obtain clinical data and delivery outcome variables. Amniotic fluid samples from women with a subsequent spontaneous preterm delivery (n = 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n = 37). Amniotic fluid samples underwent untargeted metabolomic analyses using liquid chromatography-mass spectrometry. Multivariate random forest analyses were used for data processing. A secondary targeted analysis was performed, aiming to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers in women with a subsequent spontaneous preterm delivery.
RESULTS: Multivariate analysis did not distinguish the samples from women with a subsequent spontaneous preterm delivery from those with a subsequent term delivery. Neither was the metabolic profile associated with gestational duration at delivery. Potential metabolic biomarker candidates were identified from four publications by two different research groups relating mid-trimester amniotic fluid metabolomes to spontaneous PTD, of which fifteen markers were included in the secondary analysis. None of these were replicated.
CONCLUSIONS: Metabolomic profiles of early mid-trimester amniotic fluid were not associated with spontaneous preterm delivery or gestational duration at delivery in this cohort.
OBJECTIVE: The aim of this study was to perform metabolomic profiling of amniotic fluid from uncomplicated singleton pregnancies in the mid-trimester to identify potential biomarkers associated with spontaneous preterm delivery and gestational duration at delivery. A secondary aim was to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers of spontaneous preterm delivery in asymptomatic women.
METHODS: A nested case-control study was performed within a larger cohort study of asymptomatic pregnant women undergoing mid-trimester genetic amniocentesis at 14-19 gestational weeks in Gothenburg, Sweden. Medical records were used to obtain clinical data and delivery outcome variables. Amniotic fluid samples from women with a subsequent spontaneous preterm delivery (n = 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n = 37). Amniotic fluid samples underwent untargeted metabolomic analyses using liquid chromatography-mass spectrometry. Multivariate random forest analyses were used for data processing. A secondary targeted analysis was performed, aiming to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers in women with a subsequent spontaneous preterm delivery.
RESULTS: Multivariate analysis did not distinguish the samples from women with a subsequent spontaneous preterm delivery from those with a subsequent term delivery. Neither was the metabolic profile associated with gestational duration at delivery. Potential metabolic biomarker candidates were identified from four publications by two different research groups relating mid-trimester amniotic fluid metabolomes to spontaneous PTD, of which fifteen markers were included in the secondary analysis. None of these were replicated.
CONCLUSIONS: Metabolomic profiles of early mid-trimester amniotic fluid were not associated with spontaneous preterm delivery or gestational duration at delivery in this cohort.
摘要：
背景：自发性早产（<37孕周）具有多因素病因，仍未完全确定途径。羊水是一种生物流体，具有很大的潜力，可以深入了解胎儿-母体环境。它富含代谢物，和炎症的代谢后果还只是在有限的程度上研究。代谢组学分析提供了鉴定炎性条件妊娠并发症如自发性早产的潜在生物标志物的机会。
目的：本研究的目的是对妊娠中期无并发症单胎妊娠羊水进行代谢组学分析，以确定与自发性早产和分娩时妊娠持续时间相关的潜在生物标志物。次要目的是在无症状妇女中复制先前报道的妊娠中期羊水代谢生物标志物。
方法：在一项更大的队列研究中，在哥德堡14-19孕周进行无症状妊娠中期遗传性羊膜穿刺术的孕妇中进行了一项巢式病例对照研究，瑞典。使用医疗记录来获得临床数据和递送结果变量。随后自发早产的妇女的羊水样本（n=37）与足月随后自发分娩的妇女的羊水样本（n=37）相匹配。使用液相色谱-质谱法对羊水样品进行非靶向代谢组学分析。多变量随机森林分析用于数据处理。进行了二次靶向分析，旨在在随后有自发性早产的女性中复制先前报道的中期羊水代谢生物标志物。
结果：多变量分析没有将随后自发早产的女性样本与随后足月分娩的女性样本区分开来。代谢谱与分娩时的妊娠持续时间也不相关。两个不同的研究小组从四个出版物中确定了潜在的代谢生物标志物候选物，它们将中期羊水代谢组和自发性PTD联系起来。其中15个标记包括在二次分析中。这些都没有被复制。
结论：在该队列中，早中期羊水的代谢组学谱与自发性早产或分娩时的妊娠持续时间无关。
目的：本研究的目的是对妊娠中期无并发症单胎妊娠羊水进行代谢组学分析，以确定与自发性早产和分娩时妊娠持续时间相关的潜在生物标志物。次要目的是在无症状妇女中复制先前报道的妊娠中期羊水代谢生物标志物。
方法：在一项更大的队列研究中，在哥德堡14-19孕周进行无症状妊娠中期遗传性羊膜穿刺术的孕妇中进行了一项巢式病例对照研究，瑞典。使用医疗记录来获得临床数据和递送结果变量。随后自发早产的妇女的羊水样本（n=37）与足月随后自发分娩的妇女的羊水样本（n=37）相匹配。使用液相色谱-质谱法对羊水样品进行非靶向代谢组学分析。多变量随机森林分析用于数据处理。进行了二次靶向分析，旨在在随后有自发性早产的女性中复制先前报道的中期羊水代谢生物标志物。
结果：多变量分析没有将随后自发早产的女性样本与随后足月分娩的女性样本区分开来。代谢谱与分娩时的妊娠持续时间也不相关。两个不同的研究小组从四个出版物中确定了潜在的代谢生物标志物候选物，它们将中期羊水代谢组和自发性PTD联系起来。其中15个标记包括在二次分析中。这些都没有被复制。
结论：在该队列中，早中期羊水的代谢组学谱与自发性早产或分娩时的妊娠持续时间无关。
