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Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries less than 28 weeks of gestation.

ABSTRACT: PROBLEM:Inflammation within the preterm placenta is common and leads to adverse outcomes for premature infants. The risks of complications are different between iatrogenic (e.g. PE) and spontaneous (e.g. PL and membrane rupture) causes of preterm delivery, suggesting different underlying biology contributes to these placental conditions. METHOD OF STUDY:Thirty preterm singleton placentas from the following groups were analyzed: (i) severe PE, (ii) preterm premature membrane rupture (pPROM), and (iii) PL. Proinflammatory and anti-inflammatory cytokines, adhesion and angiogenic molecules were measured in placental lysates using a multiplex assay. K-means cluster analysis was used to generate patterns of protein level intensity. RESULTS:Three cluster patterns were apparent. Placentas from PE had high levels of vascular endothelial growth factor (VEGF) combined with low levels of acute inflammatory proteins (IL-1?, IL-18, IL-6, TNF-?), low IL-1 RA, and high transforming growth factor ? (TGF-?). PL and pPROM had higher anti-inflammatory IL-1 RA and thrombomodulin combined with lower VEGF, regardless of proinflammatory cytokines and adhesion molecules. Half of the PL and pPROM cases had clusters of heightened inflammatory responses (lower TGF-? clustered with higher intensity of inflammatory mediators). CONCLUSION:Discriminating protein patterns were elucidated and may serve as a foundation from which to understand the biologic mechanisms underlying these pregnancy complications.

SUBMITTER: Faupel-Badger JM

PROVIDER: S-EPMC3165070 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries less than 28 weeks of gestation.

Faupel-Badger Jessica M JM Fichorova Raina N RN Allred Elizabeth N EN Hecht Jonathan L JL Dammann Olaf O Leviton Alan A McElrath Thomas F TF

American journal of reproductive immunology (New York, N.Y. : 1989) 20110530 6

<h4>Problem</h4>Inflammation within the preterm placenta is common and leads to adverse outcomes for premature infants. The risks of complications are different between iatrogenic (e.g. PE) and spontaneous (e.g. PL and membrane rupture) causes of preterm delivery, suggesting different underlying biology contributes to these placental conditions.<h4>Method of study</h4>Thirty preterm singleton placentas from the following groups were analyzed: (i) severe PE, (ii) preterm premature membrane ruptur ...[more]

PMID: 21623999

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Project description:ImportanceAspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy.ObjectiveTo determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia.Design, setting, and participantsMulticenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants.InterventionsEnrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group).Main outcomes and measuresNoninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%.ResultsAmong the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48% (7/473) in the intervention group and 1.73% (8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority.Conclusions and relevanceAspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio.Trial registrationClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.

Project description:OBJECTIVE:To evaluate whether labor is associated with lower odds of respiratory morbidity among neonates born from 36 to 40 weeks of gestation and to assess whether this association varies by gestational age and maternal diabetic status. METHODS:We conducted a secondary analysis of women in the Assessment of Perinatal Excellence obstetric cohort who delivered across 25 U.S. hospitals over a 3-year period. Women with a singleton liveborn nonanomalous neonate who delivered from 36 to 40 weeks of gestation were included in our analysis. Those who received antenatal corticosteroids, underwent amniocentesis for fetal lung maturity, or did not meet dating criteria were excluded. Our primary outcome was composite neonatal respiratory morbidity, which included respiratory distress syndrome, ventilator support, continuous positive airway pressure, or neonatal death. Maternal characteristics and neonatal outcomes between women who labored and those who did not were compared. Multivariable logistic regression models were used to evaluate the association between labor and the primary outcome. Interactions between labor and diabetes mellitus and labor and gestational age were tested. RESULTS:Our analysis included 63,187 women who underwent labor and 10,629 who did not. There was no interaction between labor and diabetes mellitus (P=.90). However, there was a significant interaction between labor and gestational age (P=.01). In the adjusted model, labor was associated with lower odds of neonatal respiratory morbidity compared with no labor for neonates delivered from 36-39 weeks of gestation. A 1-week increase in gestational age was associated with a 1.2 times increase in the adjusted odds ratio for the neonatal outcome comparing labor and no labor. CONCLUSION:Labor was associated with lower odds of the composite outcome among neonates delivered from 36-39 weeks of gestation. The magnitude of this association varied by gestational age. The association was similar for women with or without diabetes mellitus.

Project description:IntroductionThere is little evidence to guide the timing of delivery of women with early-onset severe preeclampsia. We hypothesize that immediate delivery is not inferior for neonatal outcome but reduces maternal complications compared with temporizing management.Material and methodsThis Dutch multicenter open-label randomized clinical trial investigated non-inferiority for neonatal outcome of temporizing management as compared with immediate delivery (TOTEM NTR 2986) in women between 27+5 and 33+5 weeks of gestation admitted for early-onset severe preeclampsia with or without HELLP syndrome. In participants allocated to receive immediate delivery, either induction of labor or cesarean section was initiated at least 48 hours after admission. Primary outcomes were adverse perinatal outcome, defined as a composite of severe respiratory distress syndrome, bronchopulmonary dysplasia, culture proven sepsis, intraventricular hemorrhage grade 3 or worse, periventricular leukomalacia grade 2 or worse, necrotizing enterocolitis stage 2 or worse, and perinatal death. Major maternal complications were secondary outcomes. It was estimated 1130 women needed to be enrolled. Analysis was by intention-to-treat.ResultsThe trial was halted after 35 months because of slow recruitment. Between February 2011 and December 2013, a total of 56 women were randomized to immediate delivery (n = 26) or temporizing management (n = 30). Median gestational age at randomization was 30 weeks. Median prolongation of pregnancy was 2 days (interquartile range 1-3 days) in the temporizing management group. Mean birthweight was 1435 g after immediate delivery vs 1294 g after temporizing management (P = .14). The adverse perinatal outcome rate was 55% in the immediate delivery group vs 52% in the temporizing management group (relative risk 1.06; 95% confidence interval 0.67-1.70). In both groups there was one neonatal death and no maternal deaths. In the temporizing treatment group, one woman experienced pulmonary edema and one placental abruption. Analyses of only the singleton pregnancies did not result in other outcomes.ConclusionsEarly termination of the trial precluded any conclusions for the main outcomes. We observed that temporizing management resulted in a modest prolongation of pregnancy without changes in perinatal and maternal outcome. Conducting a randomized study for this important research question did not prove feasible.

Project description:It is now recognized that preterm infants ?28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the "Hobart method") has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial.This is a multicentre, randomised, masked, controlled trial in preterm infants 25-28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2???0.30 at an age ?6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2???0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017.Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25-28 weeks gestation.Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.

Project description:BackgroundAccurate prediction of infection, including maternal chorioamnionitis and early-onset neonatal infection, remains a critical challenge in cases of preterm rupture of membranes and may influence obstetrical management. The aim of our study was to investigate the predictive value for early-onset neonatal infection and maternal histological and clinical chorioamnionitis of maternal biological markers in routine use at or after 34 weeks of gestation in women with premature rupture of membranes.MethodsWe conducted a two-center prospective study of all women admitted for premature rupture of membranes at or after 34 weeks of gestation. The association of C-reactive protein, white blood cell count, vaginal sample bacteriological results, and a prediction model at admission, for early-onset neonatal infection and maternal chorioamnionitis were analyzed by comparing areas under the receiver operating characteristic curves and specificity.ResultsThe study included 399 women. In all, 4.3% of the newborns had an early-onset neonatal infection and 5.3% of the women had clinical chorioamnionitis. Histological chorioamnionitis was detected on 10.8% of 297 placentas tested. White blood cell counts and C-reactive protein concentrations were significantly associated with early-onset neonatal infection and included in a prediction model. The area under the receiver operating characteristic curve of this model was 0.82 (95% CI [0.72, 0.92]) and of C-reactive protein, 0.80 (95% CI [0.68, 0.92]) (p = 1.0). Specificity was significantly higher for C-reactive protein than for the prediction model (48% and 43% respectively, p < 0.05). C-reactive protein was associated with clinical and histological chorioamnionitis, with areas under the receiver operating characteristic curve of 0.61 (95% CI [0.48, 0.74]) and 0.62 (95% CI [0.47, 0.74]), respectively.ConclusionsThe concentration of C-reactive protein at admission for premature rupture of membranes is the most accurate infectious marker for prediction of early-onset neonatal infection in routine use with a sensitivity > 90%. A useful next step would be a randomized prospective study of management strategy comparing CRP at admission with active management to assess whether this more individualized care is a safe alternative strategy in women with premature rupture of membranes at or after 34 weeks.

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Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries less than 28 weeks of gestation.

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Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries less than 28 weeks of gestation.

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