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Abstract：
BACKGROUND: Women with spontaneous preterm birth have an increased risk of cardiovascular disease later in life. Studies suggest potential pathophysiological mechanisms in common, but whether these could be identified by measurement of soluble circulating protein biomarkers in women with spontaneous preterm birth is unknown. The aim of this study was to determine if protein biomarkers associated with cardiovascular disease distinguish women with spontaneous preterm birth from healthy controls, both at pregnancy and at follow up.
METHODS: Study participants were identified in the population-based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid-pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow-up visit 4-15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up.
RESULTS: gov registration NCT05693285.
RESULTS: In the screening phase, fibrinogen, cadherin-5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D-binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow-up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up.
CONCLUSIONS: Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid-pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease.
METHODS: Study participants were identified in the population-based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid-pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow-up visit 4-15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up.
RESULTS: gov registration NCT05693285.
RESULTS: In the screening phase, fibrinogen, cadherin-5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D-binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow-up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up.
CONCLUSIONS: Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid-pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease.
摘要：
背景：自发性早产妇女在以后的生活中患心血管疾病的风险增加。研究表明，共同的潜在病理生理机制，但这些是否可以通过检测自发性早产女性的可溶性循环蛋白生物标志物来确定,目前尚不清楚.这项研究的目的是确定与心血管疾病相关的蛋白质生物标志物是否将自发性早产妇女与健康对照区分开来。在怀孕和随访期间。
方法：研究参与者是在瑞典以人群为基础的Uppsala孕妇生物样本库中确定的，在妊娠中期收集血浆样本。在第一个筛选阶段，我们确定了随后在指数妊娠中经历自发性早产(<37周)的参与者(N=13)和对照组(N=6).在这些样本中,通过比较质谱检查蛋白质表达的差异。在第二个验证阶段，我们在索引妊娠中邀请了100例先前自发性早产的病例和100例对照(年龄相匹配，身体质量指数,和交付年份)来自同一来源人口，怀孕后4-15年的随访。在跟进时，我们收集了血浆样本和心血管危险因素数据.我们测量了筛选阶段确定的选定生物标志物的浓度，以及来自妊娠（生物库）和随访的样本中的脂质分布。
结果：政府注册NCT05693285。
结果：在筛查阶段，纤维蛋白原，钙黏着蛋白-5，补体C5，因子XII，血浆激肽释放酶,载脂蛋白M,维生素D结合蛋白在怀孕时差异显著。在验证阶段，65名妇女同意参加（35例和30个对照），自怀孕以来的中位随访时间为11.8年。在随访中，与匹配的对照组相比，纤维蛋白原（p=0.02）和甘油三酸酯（p=0.03）的浓度略高。
结论：与无早产妇女相比，自发性早产者的纤维蛋白原浓度略高，在怀孕中期和怀孕后十年。此外,我们发现,既往有自发性早产的女性在随访时甘油三酯浓度略高.这一发现的相关性尚不确定，但可能表明自发性早产和心血管疾病之间共同的潜在病理生理机制。
方法：研究参与者是在瑞典以人群为基础的Uppsala孕妇生物样本库中确定的，在妊娠中期收集血浆样本。在第一个筛选阶段，我们确定了随后在指数妊娠中经历自发性早产(<37周)的参与者(N=13)和对照组(N=6).在这些样本中,通过比较质谱检查蛋白质表达的差异。在第二个验证阶段，我们在索引妊娠中邀请了100例先前自发性早产的病例和100例对照(年龄相匹配，身体质量指数,和交付年份)来自同一来源人口，怀孕后4-15年的随访。在跟进时，我们收集了血浆样本和心血管危险因素数据.我们测量了筛选阶段确定的选定生物标志物的浓度，以及来自妊娠（生物库）和随访的样本中的脂质分布。
结果：政府注册NCT05693285。
结果：在筛查阶段，纤维蛋白原，钙黏着蛋白-5，补体C5，因子XII，血浆激肽释放酶,载脂蛋白M,维生素D结合蛋白在怀孕时差异显著。在验证阶段，65名妇女同意参加（35例和30个对照），自怀孕以来的中位随访时间为11.8年。在随访中，与匹配的对照组相比，纤维蛋白原（p=0.02）和甘油三酸酯（p=0.03）的浓度略高。
结论：与无早产妇女相比，自发性早产者的纤维蛋白原浓度略高，在怀孕中期和怀孕后十年。此外,我们发现,既往有自发性早产的女性在随访时甘油三酯浓度略高.这一发现的相关性尚不确定，但可能表明自发性早产和心血管疾病之间共同的潜在病理生理机制。
