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Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence-the loss of cell division potential as a consequence of stress-is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-β-galactosidase , and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor [TL]) compared to membranes prior to labor at term (term, not-in-labor [TNIL]). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition.

Background: Poor maternal vitamin D status and elevated circulating corticotropin-releasing hormone (CRH) are associated with preterm birth. It is not known if these risk factors are independent or interrelated. Both are associated with inflammation.Methods: We measured maternal circulating 25-hydroxyvitamin D (25-OH-D) and CRH from 97 samples collected from 15 early-preterm, 31 late-preterm, 21 early-term, and 30 term births. The potential involvement of vitamin D in the regulation of inflammation was evaluated by Q-PCR in human uterine smooth muscle (UTSM) cell line.Results: Maternal 25-OH-D was lowest in early-preterm births (22.9 ± 4.2 ng/ml versus 34.4 ± 1.4 ng/ml; p = .029). Circulating CRH was high in early-preterm births (397 ± 30 pg/ml). Late-preterm (304 ± 13 pg/ml) and early-term births (347 ± 17 pg/ml) were not different from term births (367 ± 19 pg/ml), after accounting for gestational age. Maternal circulating 25-OH-D and CRH were not associated in term births. In preterm births, 25-OH-D below 30 ng/ml was associated with higher CRH. Vitamin D treatment of UTSM significantly reduced mRNA for leptin and IL-6 receptors. Deletion of vitamin D receptor from UTSM promoted the expression of the cox2 inflammatory marker.Conclusion: Early-preterm birth showed a syndrome of high maternal CRH and low vitamin D status. [ABSTRACT FROM AUTHOR]

Background Massive transfusion protocols (MTPs) have been examined in trauma. The exact ratio of packed red blood cells (PRBC) to other blood replacement components in hemostatic resuscitation in obstetrics has not been well defined. Objective The objective of this study was to evaluate hemostatic resuscitation in peripartum hysterectomy comparing pre- and postinstitution of a MTP. Study Design We conducted a retrospective, descriptive study of women undergoing peripartumhysterectomies from January 2002 to January 2015 who received 4 units of PRBC. Individuals were grouped into either a pre-MTP institution group or a post-MTP institution group. The post-MTP group was subdivided into those who had the protocol activated (MTP) versus not activated (no MTP). Primary outcomes were estimated blood loss (EBL) and need for blood product replacement. The secondary outcome was a composite of maternal morbidity, including need for mechanical ventilation, venous thromboembolism, pulmonary edema, acute kidney injury, and postpartum infection. A Mann-Whitney U test was used to compare continuous variables, and a chi-squared test was used for categorical variables with significance of p < 0.05. Results Of the 165 women who had a peripartum hysterectomy during the study period, 62 received four units or more of PRBC. No significant differences were noted in EBL or blood product replacement between the pre-MTP (n = 39) and post-MTP (n = 23) groups. Similarly, the MTP (n = 6) and no MTP (n = 17) subgroups showed no significant difference between EBL and overall blood product replacement. Significant differences were seen in transfusion of individual blood products, such as fresh frozen plasma (FFP) (MTP = 4, no MTP = 2; p = 0.02) and platelets (plts) (MTP = 6, no MTP = 0; p = 0.03). The use of high ratio replacement therapy for both plasma and plts was more common in the MTP group (FFP/PRBC ratio [MTP = 0.5, no MTP = 0.3; p = 0.02]; plts/PRBC ratio [MTP = 0.7, no MTP = 0; p = 0.03]).There were no differences in the secondary outcome between pre- and post-MTP or MTP and no MTP. Conclusion Initiation of theMTP did result in an increase in transfusion of FFP and plts intraoperatively. At our institution, the MTP is underutilized, but it appears that providers are more cognizant of the use of high transfusion ratios. [ABSTRACT FROM AUTHOR]

Objective Indomethacin tocolysis is generally limited to 48 hours. Indomethacin has been administered for longer durations to prolong gestation in extreme prematurity. Our aim is to compare perinatal outcomes after a prolonged course, > 48 hours versus ≤ 48 hours in preterm labor. Methods A retrospective chart review of women admitted with preterm labor < 32 weeks gestation who received indomethacin for tocolysis. The primary maternal outcome was latency from admission until delivery. The primary neonatal outcome was a composite of severe neonatal morbidities. Results A total of 73 women were included: 32 (43.8%) received indomethacin for > 48 hours (prolonged) and 41 (56.2%) for ≤ 48 hours (standard). Prolonged group started on indomethacin at an earlier gestational age compared with standard group (23.9 [23.1-27.3] vs. 25.7 [23.8-28.5] weeks, p = 0.03). Latency from admission until delivery was longer in the prolonged group versus the standard group (1.8 [1.1-3] vs. 0.4 [0.1-0.8] weeks, p < 0.001). Prolonged use was not associated with increased risk of the composite neonatal outcome; however, there was a trend for more necrotizing enterocolitis. Conclusion A prolonged course of indomethacin may be an option for women with preterm labor at risk of extreme prematurity; it may also be associated with higher risks of some adverse neonatal outcomes. [ABSTRACT FROM AUTHOR]

Objective:  This study aimed to evaluate the safety of peripheral administration of vasopressor agents among patients with circulatory shock., Study Design:  We reviewed the published literature evaluating the use of peripheral norepinephrine in patients with shock and proposed a protocol for use in labor and delivery units., Results:  Peripheral administration of norepinephrine is a safe and potentially lifesaving intervention for patients in labor and delivery with extremely low complication rates., Conclusion:  Adoption of a protocol for peripheral administration of vasopressors in labor and delivery is safe and may prevent life threatening delays in hemodynamic resuscitation., Key Points: · Administering vasopressors through a peripheral line is safe and helps avoid delays in care.. · An established protocol is essential for the safe peripheral administration of vasopressors.. · Understanding continuous blood pressure monitoring is crucial for managing critically ill patients.., Competing Interests: None declared., (Thieme. All rights reserved.)

Study Hypothesis: In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture., Study Finding: We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation., What Is Known Already: Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM., Study Design, Samples/materials, Methods: Fetal membranes and amniotic fluid samples were collected from women with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status, DNA damage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups., Main Results and the Role of Chance: Oxidative stress was higher and antioxidant enzymes were lower in PPROM compared with PTB. PTB membranes had minimal DNA damage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence. PPROM had higher numbers of cells with DNA damage, prosenescence stress kinase (p38 MAPK) activation and signs of senescence., Limitations, Reasons for Caution: Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM., Wider Implications of the Findings: Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome., Study Funding and Competing Interests: This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of Texas Medical Branch at Galveston and funds to Dr M. Kacerovský from the Ministry of Health Czech Republic (UHHK, 001799906). The authors report no conflict of interest., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)