The complement system plays an important role in normal human pregnancy. Uncontrolled activation of this system has been associated with many disease states. We tested the hypothesis that the C5b-9 membrane attack complex (MAC) localizes to sites of villous injury and modulates trophoblast function. Placental sections from pregnancies with no complications, intrauterine growth restriction, or preeclampsia were immunostained and the surface density for MAC and fibrin was determined by morphometric analysis. Primary cytotrophoblasts from term placentas were cultured in a FiO2 of < 1%, 8% and 20% with 10% human serum containing active MAC or heat-inactivated control serum. Immunofluorescent MAC binding to trophoblast was quantified, and the neoepitopes formed in cytokeratin 18 filaments and poly-ADP-ribose polymerase during apoptosis were used to measure cell death. Trophoblast differentiation was assessed by HCG secretion, formation of syncytia, and expression of syncytin. MAC localized to fibrin deposits in normal placentas, and especially in placentas from IUGR and preeclampsia. MAC binding to cytotrophoblasts was inversely proportional to FiO2 and enhanced apoptosis. MAC increased markers of differentiation in cultures at 72h (medium HCG, syncytia and syncytin expression). Our findings demonstrate that MAC associates with fibrin deposits at sites of villous injury in vivo. Hypoxia also enhances MAC deposition in cultured trophoblasts and MAC alters trophoblast function in a phenotype specific manner.
Background A number of evidence-based interventions have been proposed to reduce post cesarean wound complications. Examples of such interventions include appropriate timing of preoperative antibiotics, appropriate choice of skin antisepsis, closure of the subcutaneous layer if subcutaneous depth is ≥ 2 cm, and subcuticular skin closure with suture rather than staples. However, the collective impact of these measures is unclear. Objective We sought to estimate the impact of a group of evidence-based surgical measures (prophylactic antibiotics administered prior to skin incision, chlorhexidine-alcohol for skin antisepsis, closure of subcutaneous layer, and subcuticular skin closure with suture) on wound complications after cesarean, and to estimate residual risk factors for wound complications. Study Design We conducted a secondary analysis of data from a randomized controlled trial of chlorhexidine-alcohol versus iodine-alcohol for skin antisepsis at cesarean from 2011–2015. The primary outcome for this analysis was a composite of wound complications, including surgical site infection (SSI), cellulitis, seroma, hematoma, and separation within 30 days. Risk of wound complications in women who received all four evidence-based measures (prophylactic antibiotics within 60 minutes of cesarean and prior to skin incision, chlorhexidine-alcohol for skin antisepsis with three minutes of drying time prior to incision, closure of subcutaneous layer if ≥ 2 cm of depth and subcuticular skin closure with suture) were compared to those who did not. We performed logistic regression analysis limited to patients who received all the evidence-based measures to estimate residual risk factors for wound complications and SSI. Results Of 1082 patients with follow-up, 349 (32.3%) received all the evidence-based measures and 733 (67.7%) did not. The risk of wound complications was significantly lower in patients who received all the evidence-based measures compared to those who did not (20.3% vs 28.1%; aRR 0.75, 95% CI 0.58, 0.95). The impact appeared to be largely driven by a reduction in surgical site infections. Among patients who received all the evidence-based measures, unscheduled cesarean was the only significant risk factor for wound complications (27.5% vs. 16.1%, aRR 1.71, 95% CI 1.12, 2.47) and SSI (6.9% vs. 1.6%, RR 3.74, 95% CI 1.18, 11.92). Other risk factors, including obesity, smoking, diabetes, chorioamnionitis, surgical experience, and skin incision type were not significant among patients who received all of the four evidence-based measures. Conclusion Implementation of evidence-based measures significantly reduces wound complications, but the residual risk remains high. This suggests the need for additional interventions, especially in patients undergoing unscheduled cesareans, who are at risk for wound complications even after receiving current evidence-based measures.
Staple closure is faster to perform but associated with a higher risk of wound complications.
Objective To estimate the risk of adverse perinatal outcomes among women with isolated fetal growth restriction from 17 to 22 weeks of gestation. Methods This was a retrospective cohort study of all singleton, non-anomalous pregnancies undergoing ultrasound to assess fetal anatomy between 17 and 22 weeks of gestation at a single center from 2010 to 2014. After excluding patients with fetal structural malformations, chromosomal abnormalities, or identified infection etiologies, we compared perinatal outcomes between pregnancies with and without fetal growth restriction, defined as estimated fetal weight <10th percentile for gestational age. Our primary outcome was small for gestational age (SGA) at birth, defined as birthweight < 10th percentile. Secondary outcomes included preterm delivery <37 weeks and <28 weeks, preeclampsia, abruption, stillbirth, neonatal death, neonatal intensive care unit (NICU) admission, intraventricular hemorrhage, need for respiratory support, and necrotizing enterocolitis. Results Of 12,783 eligible patients, 355 (2.8%) had early second-trimester fetal growth restriction. Risk factors for growth restriction were African American race and tobacco use. Early second-trimester growth restriction was associated with over a fivefold increase in risk of SGA at birth (36.9% vs 9.1%, aOR 5.5, 95% CI 4.3, 7.0), stillbirth (2.5% vs 0.4%, OR 6.2, 95% CI 2.7, 12.8), and neonatal death (1.4% vs 0.3%, OR 5.2, 95% CI 1.6, 13.5). Rates of indicated preterm birth <37 weeks (7.3% vs 3.3%, OR 2.3, 95% CI 1.5,3.5) and <28 weeks (2.5% vs 0.2%, OR 10.8, 95% CI 4.5,23.4), neonatal need for respiratory support (16.9% vs 7.8%, aOR 1.6, 95% CI 1.1,2.2), and necrotizing enterocolitis (1.4% vs 0.2%, OR 7.7, 95% CI 2.3, 20.9) were also significantly higher for those with growth restriction. Rates of preeclampsia, abruption, and other neonatal outcomes were not significantly different. Conclusion Although fetal growth restriction in the early second trimester occurred in less than 3% of our cohort and most of those with isolated growth restriction did not have adverse outcomes, it is a strong risk factor for SGA, stillbirth, neonatal death, and indicated preterm birth.
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