Abstract：
BACKGROUND: Twin pregnancies are associated with complications and adverse outcomes. The number of twin pregnancies has increased in the last decades, due to the use of assisted reproductive techniques and delayed childbearing. Analysis of changes that occur during twin pregnancy progression and their association with outcome will lead to improved clinical interventions.
OBJECTIVE: We evaluated if the plasma concentration of select cytokines and the level of sequestosome-1 (p62) in peripheral blood mononuclear cells (PBMCs) during each trimester of twin gestations was predictive of pregnancy outcome.
METHODS: This prospective, observational study was conducted at Careggi University Hospital, Florence, Italy. Plasma from 82 women with twin pregnancies was collected in each trimester for measurement of interleukin (IL)-1β, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α. The intracellular PBMC concentration of p62, a protein involved in autophagy, kinase activity and cell differentiation, was also determined.
RESULTS: IL-1β (p < 0.001), IL-6 (p < 0.001), TNF-α (p < 0.001) and p62 (p < 0.05) increased from the 1st to the 2nd to the 3rd trimester. The TNF-α level was correlated with the IL-1β concentration in the 1st and 3rd trimesters p < 0.01) and with the IL-6 concentration in each of the three trimesters (p < 0.01). The intracellular p62 level in PBMCs was negatively correlated with the concentration of IL-1β in the 2nd trimester (p < 0.05) and negatively correlated with the IL-6 level in the 3rd trimester (p < 0.05). The TNF-α level was significantly higher in the 2nd (p < 0.05) and 3rd (p < 0.001) trimester in women with a spontaneous preterm delivery. The TNF-α concentrations in the 2nd (p < 0.05) and 3rd (p < 0.01) trimester, respectively, and 3rd trimester IL-6 (p < 0.01), were negatively associated with gestational age at delivery. The concentration of IL-6 was highest in the 2nd (p < 0.05) and 3rd (p < 0.05) trimesters in women who utilized assisted reproductive technologies. An elevated IL-1β level in the 3rd trimester was associated with gestational diabetes mellitus (p < 0.05).
CONCLUSIONS: Variations in cytokine levels between individual women during the three trimesters of twin gestations are predictive of spontaneous preterm delivery and the onset of gestational diabetes.
OBJECTIVE: We evaluated if the plasma concentration of select cytokines and the level of sequestosome-1 (p62) in peripheral blood mononuclear cells (PBMCs) during each trimester of twin gestations was predictive of pregnancy outcome.
METHODS: This prospective, observational study was conducted at Careggi University Hospital, Florence, Italy. Plasma from 82 women with twin pregnancies was collected in each trimester for measurement of interleukin (IL)-1β, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α. The intracellular PBMC concentration of p62, a protein involved in autophagy, kinase activity and cell differentiation, was also determined.
RESULTS: IL-1β (p < 0.001), IL-6 (p < 0.001), TNF-α (p < 0.001) and p62 (p < 0.05) increased from the 1st to the 2nd to the 3rd trimester. The TNF-α level was correlated with the IL-1β concentration in the 1st and 3rd trimesters p < 0.01) and with the IL-6 concentration in each of the three trimesters (p < 0.01). The intracellular p62 level in PBMCs was negatively correlated with the concentration of IL-1β in the 2nd trimester (p < 0.05) and negatively correlated with the IL-6 level in the 3rd trimester (p < 0.05). The TNF-α level was significantly higher in the 2nd (p < 0.05) and 3rd (p < 0.001) trimester in women with a spontaneous preterm delivery. The TNF-α concentrations in the 2nd (p < 0.05) and 3rd (p < 0.01) trimester, respectively, and 3rd trimester IL-6 (p < 0.01), were negatively associated with gestational age at delivery. The concentration of IL-6 was highest in the 2nd (p < 0.05) and 3rd (p < 0.05) trimesters in women who utilized assisted reproductive technologies. An elevated IL-1β level in the 3rd trimester was associated with gestational diabetes mellitus (p < 0.05).
CONCLUSIONS: Variations in cytokine levels between individual women during the three trimesters of twin gestations are predictive of spontaneous preterm delivery and the onset of gestational diabetes.
摘要：
背景：双胎妊娠与并发症和不良结局相关。在过去的几十年中，双胞胎怀孕的数量有所增加，由于使用辅助生殖技术和延迟生育。分析双胎妊娠进展过程中发生的变化及其与结局的关系将改善临床干预措施。
目的：我们评估了双胎妊娠每三个月血浆中某些细胞因子的浓度和外周血单个核细胞（PBMC）中隔离体-1（p62）的水平是否可以预测妊娠结局。
方法：这种前瞻性，观察性研究在Careggi大学医院进行，佛罗伦萨意大利。在每三个月收集82例双胎妊娠妇女的血浆，用于测量白细胞介素（IL）-1β，IL-6、IL-10、IL-12和肿瘤坏死因子(TNF)-α。细胞内PBMC浓度p62，参与自噬的蛋白，激酶活性和细胞分化，也决心。
结果：IL-1β（p<0.001），IL-6（p<0.001），TNF-α（p<0.001）和p62（p<0.05）从第1个月到第2个月到第3个月增加。TNF-α水平与第1和第3个月的IL-1β浓度p<0.01）和三个月的IL-6浓度相关（p<0.01）。PBMC细胞内p62水平与妊娠中期IL-1β浓度呈负相关（p<0.05），与妊娠中期IL-6水平呈负相关（p<0.05）。自发性早产妇女的第2个月（p<0.05）和第3个月（p<0.001）的TNF-α水平显着升高。TNF-α浓度在第2（p<0.05）和第3（p<0.01）三个月，分别,和妊娠晚期IL-6（p<0.01），与分娩时的胎龄呈负相关。在使用辅助生殖技术的妇女中，第2个月（p<0.05）和第3个月（p<0.05）的IL-6浓度最高。妊娠晚期IL-1β水平升高与妊娠期糖尿病相关(p<0.05)。
结论：在双胎妊娠三个月期间，个体妇女之间细胞因子水平的变化是自发性早产和妊娠期糖尿病发病的预测因素。
目的：我们评估了双胎妊娠每三个月血浆中某些细胞因子的浓度和外周血单个核细胞（PBMC）中隔离体-1（p62）的水平是否可以预测妊娠结局。
方法：这种前瞻性，观察性研究在Careggi大学医院进行，佛罗伦萨意大利。在每三个月收集82例双胎妊娠妇女的血浆，用于测量白细胞介素（IL）-1β，IL-6、IL-10、IL-12和肿瘤坏死因子(TNF)-α。细胞内PBMC浓度p62，参与自噬的蛋白，激酶活性和细胞分化，也决心。
结果：IL-1β（p<0.001），IL-6（p<0.001），TNF-α（p<0.001）和p62（p<0.05）从第1个月到第2个月到第3个月增加。TNF-α水平与第1和第3个月的IL-1β浓度p<0.01）和三个月的IL-6浓度相关（p<0.01）。PBMC细胞内p62水平与妊娠中期IL-1β浓度呈负相关（p<0.05），与妊娠中期IL-6水平呈负相关（p<0.05）。自发性早产妇女的第2个月（p<0.05）和第3个月（p<0.001）的TNF-α水平显着升高。TNF-α浓度在第2（p<0.05）和第3（p<0.01）三个月，分别,和妊娠晚期IL-6（p<0.01），与分娩时的胎龄呈负相关。在使用辅助生殖技术的妇女中，第2个月（p<0.05）和第3个月（p<0.05）的IL-6浓度最高。妊娠晚期IL-1β水平升高与妊娠期糖尿病相关(p<0.05)。
结论：在双胎妊娠三个月期间，个体妇女之间细胞因子水平的变化是自发性早产和妊娠期糖尿病发病的预测因素。
