Mazaki-Tovi Shali, Romero Roberto, Vaisbuch Edi, Erez Offer, Mittal Pooja, Chaiworapongsa Tinnakorn, Kim Sun Kwon, Pacora Percy, Yeo Lami, Gotsch Francesca, Dong Zhong, Nhan-Chang Chia-Ling, Jodicke Cristiano, Yoon Bo Hyun, Hassan Sonia S, Kusanovic Juan Pedro
Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, HutzelWomen's Hospital, Bethesda, Maryland, USA.
J Matern Fetal Neonatal Med. 2009 Oct;22(10):887-904. doi: 10.1080/14767050902994655.
Intra-amniotic and systemic infection/inflammation have been causally linked to preterm parturition and fetal injury. An emerging theme is that adipose tissue can orchestrate a metabolic response to insults, but also an inflammatory response via the production of adipocytokines, and that these two phenomenons are interrelated. Adiponectin, an insulin-sensitising, anti-inflammatory adipocytokine, circulates in multimeric complexes including low-molecular weight (LMW) trimers, medium-molecular weight (MMW) hexamers and high-molecular weight (HMW) isoforms. Each of these complexes can exert differential biological effects. The aim of this study was to determine whether spontaneous preterm labor (PTL) with intact membranes and intra-amniotic infection/inflammation (IAI) is associated with changes in maternal serum circulating adiponectin multimers.
This cross-sectional study included patients in the following groups: (1) normal pregnant women (n=158); (2) patients with an episode of preterm labor and intact membranes without IAI who delivered at term (n=41); (3) preterm labor without IAI who delivered preterm (n=27); and (4) preterm labor with IAI who delivered preterm (n=36). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analyses.
(1) Preterm labor leading to preterm delivery or an episode of preterm labor that does not lead to preterm delivery was associated with a lower median maternal serum concentration of total and HMW adiponectin, a lower median HMW/total adiponectin ratio and a higher median LMW/total adiponectin ratio than normal pregnancy; (2) among patients with preterm labor, those with IAI had the lowest median concentration of total and HMW adiponectin, as well as the lowest median HMW/total adiponectin ratio; (3) the changes in maternal adiponectin and adiponectin multimers remained significant after adjusting for confounding factors such as maternal age, BMI, gestational age at sampling and parity.
(1) Preterm labor is characterised by a change in the profile of adiponectin multimers concentrations and their relative isoforms. These changes were observed in patients with an episode of preterm labor not leading to preterm delivery, in patients with intra-amniotic inflammation, or in those without evidence of intra-amniotic inflammation. (2) The changes in adiponectin multimer concentrations reported in preterm labor are different from those previously reported in spontaneous labor at term, suggesting that there is a fundamental difference between preterm labor and labor at term. (3) The findings reported herein provide the first evidence for the participation of adiponectin multimer in preterm parturition. We propose that adiponectins and adipokines in general provide a mechanism to organise the metabolic demands generated by the process of preterm parturition regardless of the nature of the insult (intra-amniotic inflammation or not).
羊膜腔内感染和全身感染/炎症与早产及胎儿损伤存在因果关系。一个新出现的观点是，脂肪组织不仅能对损伤产生代谢反应，还能通过分泌脂肪细胞因子引发炎症反应，且这两种现象相互关联。脂联素是一种具有胰岛素增敏和抗炎作用的脂肪细胞因子，以多种多聚体复合物形式循环，包括低分子量（LMW）三聚体、中分子量（MMW）六聚体和高分子量（HMW）异构体。这些复合物各自可发挥不同的生物学效应。本研究旨在确定胎膜完整的自发性早产（PTL）及羊膜腔内感染/炎症（IAI）是否与母体血清中循环脂联素多聚体的变化有关。
这项横断面研究纳入了以下几组患者：（1）正常孕妇（n = 158）；（2）有早产发作且胎膜完整但无IAI并足月分娩的患者（n = 41）；（3）无IAI的早产患者（n = 27）；（4）有IAI的早产患者（n = 36）。采用酶联免疫吸附测定法（ELISA）测定血清脂联素多聚体（总、HMW、MMW和LMW）浓度。采用非参数统计进行分析。
（1）导致早产的早产发作或未导致早产的早产发作与正常妊娠相比，母体血清中总脂联素和HMW脂联素的中位数浓度较低，HMW/总脂联素的中位数比值较低，LMW/总脂联素的中位数比值较高；（2）在早产患者中，有IAI的患者总脂联素和HMW脂联素的中位数浓度最低，HMW/总脂联素的中位数比值也最低；（3）在调整了母体年龄、体重指数、采样时的孕周和产次等混杂因素后，母体脂联素和脂联素多聚体的变化仍具有显著性。
（1）早产的特征是脂联素多聚体浓度及其相对异构体的分布发生变化。在未导致早产的早产发作患者、羊膜腔内有炎症的患者或无羊膜腔内炎症证据的患者中均观察到了这些变化。（2）早产中报道的脂联素多聚体浓度变化与足月自然分娩中先前报道的不同，表明早产和足月分娩之间存在根本差异。（3）本文报道的研究结果首次证明了脂联素多聚体参与早产的发生。我们认为，脂联素及一般的脂肪因子提供了一种机制，可协调早产过程中产生的代谢需求，而不论损伤的性质（是否存在羊膜腔内炎症）。
