Armstrong-Wells Jennifer, Donnelly Meghan, Post Miriam D, Manco-Johnson Marilyn J, Winn Virginia D, Sébire Guillaume
Department of Pediatrics (Neurology), University of Colorado School of Medicine/Children's Hospital Colorado, Aurora, CO; Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO.
Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO.
Am J Obstet Gynecol. 2015 Feb;212(2):212.e1-9. doi: 10.1016/j.ajog.2014.09.016. Epub 2014 Sep 16.
The maternal-fetal inflammatory response contributes to both preterm premature rupture of membranes (PPROM) and adverse neurological outcomes. Additionally, cytokines associated with fetal placental inflammation can be detrimental to brain development regardless of inciting infection. We investigated whether differential patterns of cytokine markers in maternal and fetal plasma samples reflect subtypes of placental inflammation and neurological outcomes at 6 months in infants born to mothers with PPROM.
Within a prospective cohort study of 25 women with PPROM, plasma cytokines (interleukin [IL]-1β, IL-6, IL-8, and tumor necrosis factor-α) were measured by enzyme-linked immunosorbent assay from maternal blood samples at rupture and delivery, and from fetal umbilical cord blood samples. Patterns of cytokine expression were correlated with specific placenta pathologies. Infants underwent cranial ultrasound after birth and standardized neurological examinations at 6 months' corrected gestational age. Predictors of inflammation and adverse neurological outcome were assessed by logistic regression, adjusting for gestational age at birth.
Inflammation of the fetal side of the placenta was associated with elevated maternal IL-6 and IL-8 at delivery and fetal IL-1β, IL-6, IL-8, and tumor necrosis factor-α. Worse neurological outcome at 6 months was associated with inflammation of the fetal side of the placenta and shorter duration from rupture of membrane to delivery, independent of gestational age at birth or cranial ultrasound results.
Our findings support the connection between fetal inflammation with adverse neurological outcome with PPROM, regardless of cranial ultrasound results. Further longitudinal studies are needed to adequately examine these patterns, and will aid in risk assessment and intervention strategies.
母胎炎症反应与胎膜早破(PPROM)及不良神经结局均有关联。此外,无论是否有感染诱因,与胎儿胎盘炎症相关的细胞因子都可能对脑发育有害。我们调查了PPROM母亲所生婴儿出生6个月时,母胎血浆样本中细胞因子标志物的差异模式是否反映胎盘炎症亚型及神经结局。
在一项对25例PPROM女性的前瞻性队列研究中,通过酶联免疫吸附测定法测量了破裂时和分娩时母亲血样以及胎儿脐带血样中的血浆细胞因子(白细胞介素[IL]-1β、IL-6、IL-8和肿瘤坏死因子-α)。细胞因子表达模式与特定的胎盘病理相关。婴儿出生后接受头颅超声检查,并在矫正胎龄6个月时进行标准化神经检查。通过逻辑回归评估炎症和不良神经结局的预测因素,并对出生时的胎龄进行校正。
胎盘胎儿侧的炎症与分娩时母亲IL-6和IL-8升高以及胎儿IL-1β、IL-6、IL-8和肿瘤坏死因子-α升高有关。6个月时较差的神经结局与胎盘胎儿侧的炎症以及从胎膜破裂到分娩的持续时间较短有关,与出生时的胎龄或头颅超声结果无关。
我们的研究结果支持了PPROM时胎儿炎症与不良神经结局之间的联系,无论头颅超声结果如何。需要进一步的纵向研究来充分研究这些模式,并将有助于风险评估和干预策略。