scholarly journals Sphingosine Kinase: A Novel Putative Target for the Prevention of Infection-Triggered Preterm Birth

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Vibhuti Vyas ◽  
Charles R. Ashby ◽  
Sandra E. Reznik
Keyword(s):  
Preterm Birth ◽  
Preterm Births ◽  
Sphingosine Kinase ◽  
The United States ◽  
High Rate ◽  
Survival Pathways ◽  
Extremely Preterm ◽  
Sphingosine 1 Phosphate ◽  
Potent Vasoconstrictor

Preterm birth is defined as any delivery before 37 complete weeks of gestation. It is a universal challenge in the field of obstetrics owing to its high rate of mortality, long-term morbidity, associated human suffering and economic burden. In the United States, about 12.18% deliveries in 2009 were preterm, producing an exorbitant cost of $5.8 billion. Infection-associated premature rupture of membranes (PROM) accounts for 40% of extremely preterm births (<28 weeks of gestation). Major research efforts are directed towards improving the understanding of the pathophysiology of preterm birth and ways to prevent or at least postpone delivery. Endothelin-1 (ET-1) is a potent vasoconstrictor that plays a significant role in infection-triggered preterm birth. Its involvement in a number of pathological mechanisms and its elevation in preterm delivered amniotic fluid samples implicate it in preterm birth. Sphingosine kinase (SphK) is a ubiquitous enzyme responsible for the production of sphingosine-1-phosphate (S1P). S1P acts as second messenger in a number of cell proliferation and survival pathways. SphK is found to play a key role in ET-1 mediated myometrial contraction. This review highlights SphK as a prospective target with great potential to prevent preterm birth.

Impact of smoking and fetal gender on preterm delivery

2020 ◽  
pp. 1-6
Author(s):  
Veronika Günther ◽  
Ibrahim Alkatout ◽  
Alexandra Stein ◽  
Nicolai Maass ◽  
Alexander Strauss ◽  
...  
Keyword(s):  
Risk Factors ◽  
Preterm Birth ◽  
Preterm Delivery ◽  
Preterm Infants ◽  
Preterm Births ◽  
World Health ◽  
Smoking During Pregnancy ◽  
Fetal Gender ◽  
Extremely Preterm ◽  
Heavy Smokers

Abstract According to the World Health Organization, smoking is the most important risk factor for adverse pregnancy outcomes in industrialized nations. We aimed to establish how fetal gender and smoking interact with regard to perinatal outcomes, especially preterm delivery. Data from 220,339 singleton pregnancies, obtained from the German Perinatal Survey in Schleswig-Holstein and registered between 2004 and 2017 were analyzed in regard to smoking behavior, fetal gender, and preterm delivery. The rate of preterm births was directly proportional to the women’s consumption of nicotine. The rate of preterm deliveries was 6.8% among nonsmokers, and 13.2% in women who were very heavy smokers (≥22 cigarettes/day). Very heavy smoking (≥22 cigarettes/day) had a marked impact on extremely preterm births (<28 weeks of gestation) and very preterm births (28–31 weeks of gestation). Preterm births increased by 1.2% from heavy smokers to very heavy smokers; the differences between the other groups ranged between 0.1% and 0.4%. Fetal gender also had an impact on preterm birth: male infants were predominant in nearly all groups of women who delivered preterm infants. Smoking during pregnancy and male gender are both risk factors for preterm delivery. Fetal gender should be given greater attention as one of the several risk factors of preterm birth. Due to the high rate of morbidity among preterm infants and enormous costs for the healthcare system, women should be encouraged to cease or at least reduce smoking during pregnancy.

scholarly journals Gestation-Based Viability–Difficult Decisions with Far-Reaching Consequences

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 593
Author(s):  
Sumesh Thomas ◽  
Elizabeth Asztalos
Keyword(s):  
Decision Making ◽  
Preterm Birth ◽  
Current Knowledge ◽  
First Trimester ◽  
Perinatal Period ◽  
Outcome Data ◽  
Future Research ◽  
Extremely Preterm ◽  
Fetal Maturity

Most clinicians rely on outcome data based on completed weeks of gestational of fetal maturity for antenatal and postnatal counseling, especially for preterm infants born at the margins of viability. Contemporary estimation of gestational maturity, based on ultrasounds, relies on the use of first-trimester scans, which offer an accuracy of ±3–7 days, and depend on the timing of the scans and the measurements used in the calculations. Most published literature on the outcomes of babies born prematurely have reported on short- and long-term outcomes based on completed gestational weeks of fetal maturity at birth. These outcome data change significantly from one week to the next, especially around the margin of gestational viability. With a change in approach solely from decisions based on survival, to disability-free survival and long-term functional outcomes, the complexity of the parental and care provider’s decision-making in the perinatal and postnatal period for babies born at less than 25 weeks gestation remains challenging. While sustaining life following birth at the margins of viability remains our priority—identifying and mitigating risks associated with extremely preterm birth begins in the perinatal period. The challenge of supporting the normal maturation of these babies postnatally has far-reaching consequences and depends on our ability to sustain life while optimizing growth, nutrition, and the repair of organs compromised by the consequences of preterm birth. This article aims to explore the ethical and medical complexities of contemporary decision-making in the perinatal and postnatal periods. We identify gaps in our current knowledge of this topic and suggest areas for future research, while offering a perspective for future collaborative decision-making and care for babies born at the margins of viability.

scholarly journals Preterm birth and sustained inflammation: consequences for the neonate

2020 ◽  
Vol 42 (4) ◽  
pp. 451-468 ◽  
Author(s):  
Alexander Humberg ◽  
◽  
Ingmar Fortmann ◽  
Bastian Siller ◽  
Matthias Volkmar Kopp ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Infants ◽  
Defense Mechanisms ◽  
Preterm Births ◽  
Immune Defense ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Organ Systems ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Abstract Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome.

Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1

2012 ◽  
Vol 444 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Mark E. Schnute ◽  
Matthew D. McReynolds ◽  
Tom Kasten ◽  
Matthew Yates ◽  
Gina Jerome ◽  
...  
Keyword(s):  
Potent Inhibitor ◽  
Inflammatory Diseases ◽  
Specific Inhibitor ◽  
Sphingosine Kinase ◽  
Head And Neck Carcinoma ◽  
High Rate ◽  
Neck Carcinoma ◽  
Sphingosine 1 Phosphate ◽  
Proportional Increase ◽  
And Migration

SphK (sphingosine kinase) is the major source of the bioactive lipid and GPCR (G-protein-coupled receptor) agonist S1P (sphingosine 1-phosphate). S1P promotes cell growth, survival and migration, and is a key regulator of lymphocyte trafficking. Inhibition of S1P signalling has been proposed as a strategy for treatment of inflammatory diseases and cancer. In the present paper we describe the discovery and characterization of PF-543, a novel cell-permeant inhibitor of SphK1. PF-543 inhibits SphK1 with a Ki of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform. In 1483 head and neck carcinoma cells, which are characterized by high levels of SphK1 expression and an unusually high rate of S1P production, PF-543 decreased the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine. In contrast with past reports that show that the growth of many cancer cell lines is SphK1-dependent, specific inhibition of SphK1 had no effect on the proliferation and survival of 1483 cells, despite a dramatic change in the cellular S1P/sphingosine ratio. PF-543 was effective as a potent inhibitor of S1P formation in whole blood, indicating that the SphK1 isoform of sphingosine kinase is the major source of S1P in human blood. PF-543 is the most potent inhibitor of SphK1 described to date and it will be useful for dissecting specific roles of SphK1-driven S1P signalling.

scholarly journals Optimal well-being in the aftermath of anxiety disorders: A 10-year longitudinal investigation

2021 ◽  
Author(s):  
David Disabato ◽  
Todd Barrett Kashdan ◽  
James Doorley ◽  
Kerry Kelso ◽  
Kristina Volgenau ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Well Being ◽  
The United States ◽  
High Rate ◽  
Major Depressive ◽  
Longitudinal Investigation ◽  
Nationally Representative ◽  
Primary Hypothesis

Background: Although preliminary research has explored the possibility of optimal well-being after depression, it is unclear how rates compare to anxiety. Using Generalized Anxiety Disorder (GAD) and Panic Disorder (PD) as exemplars of anxiety, we tested the rates of optimal well-being one decade after being diagnosed with an anxiety disorder. Based on reward deficits in depression, we pre-registered our primary hypothesis that optimal well-being would be more prevalent after anxiety than depression as well as tested two exploratory hypotheses.Method: We used data from the Midlife in the United States (MIDUS) study, which contains a nationally representative sample across two waves, 10 years apart. To reach optimal well-being, participants needed to have no symptoms of GAD, PD, or major depressive disorder (MDD) at the 10 year follow-up and exceed cut-offs across nine dimensions of well-being.Results: The results failed to support our primary hypothesis. Follow-up optimal well-being rates were highest for adults previously diagnosed with MDD (8.7%), then PD (6.1%), and finally GAD (0%). Exploratory analyses revealed optimal well-being was approximately twice as prevalent in people without anxiety or depression at baseline and provided partial support for baseline well-being predicting optimal well-being after anxiety. Results were largely replicated across different classifications of optimal well-being.Limitations: Findings are limited by the somewhat unique measurement of anxiety in the MIDUS sample as well as the relatively high rate of missing data.Conclusions: We discuss possible explanations for less prevalent optimal well-being after anxiety vs. depression and the long-term positivity deficits from GAD.

scholarly journals Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth

2021 ◽  
Author(s):  
Julja Burchard ◽  
Ashoka D. Polpitiya ◽  
Angela C. Fox ◽  
Todd Randolph ◽  
Tracey C. Fleischer ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Observational Study ◽  
Preterm Births ◽  
The United States ◽  
Elevated Risk ◽  
Clinical Validation ◽  
Spontaneous Preterm Birth ◽  
Effective Interventions ◽  
Increased Risk ◽  
Risk Predictor

AbstractPreterm births are prevalent and a leading cause of neonatal death in the United States. Despite the availability of effective interventions, to date there is not a robust and widely applicable test to identify pregnancies at high risk for spontaneous preterm birth (sPTB). Previously, a sPTB predictor based on the ratio of two proteins, IBP4/SHBG, was validated as an accurate predictor of sPTB in the observational study Proteomic Assessment of Preterm Risk (PAPR). Here it is demonstrated that the same predictor threshold associated with 2-fold increased risk of sPTB, namely −1.4, is also statistically significant for predicting elevated risk of sPTB in the observational study Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TreeToP).

scholarly journals Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
J. Klumper ◽  
B. M. Kazemier ◽  
J. V. Been ◽  
K. W. M. Bloemenkamp ◽  
M. A. de Boer ◽  
...  
Keyword(s):  
Preterm Birth ◽  
The Netherlands ◽  
Risk Mitigation ◽  
Preterm Births ◽  
Multiple Pregnancies ◽  
Very Preterm ◽  
Extremely Preterm ◽  
Using Data ◽  
Extremely Preterm Birth ◽  
Singleton Pregnancies

Abstract Background The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. Methods Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015–2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. Results The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015–2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). Conclusion This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

Abstract P138: Alterations in Cardiac Structure and Function in Young Adults Born Extremely Preterm: Impact of Neonatal Bronchopulmonary Dysplasia

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Muhammad Oneeb Rehman Mian ◽  
Jean-Luc Bigras ◽  
Rafael Fernandes ◽  
Mariane Bertagnolli ◽  
Li Feng Xie ◽  
...  
Keyword(s):  
Young Adults ◽  
Preterm Birth ◽  
Cardiac Remodeling ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Lv Mass ◽  
Extremely Preterm ◽  
Cardiac Structure And Function ◽  
And Function

Objective: Studies support a causal association between preterm birth and increased risk of cardiovascular diseases. Increased left and right ventricular mass and impaired systolic and diastolic function has been reported in young adults born preterm. However, the impact of extreme preterm birth and prematurity-specific complications on adult cardiac structure and function has not been evaluated. We assessed cardiac structure and function in young adults born extremely preterm (EPT) versus term, and correlated long term cardiac remodeling with neonatal bronchopulmonary dysplasia (BPD). Methods: Eighty five EPT (gest. age = 27.1±1.4 weeks) were recruited along with term-born controls matched for age, sex and socioeconomic status. Birth and neonatal data (gestational age, birth weight, BPD indicated by O 2 requirements at 36 weeks postmenstrual age) was collected. Ambulatory blood pressure (Spacelabs) and echocardiographic measurements (Phillips) were taken. Comparisons were performed using ANOVA or T-test. Results: EPT presented with increased systolic (119±9 vs 116±8 mmHg, P<0.05) and diastolic (68±5 vs 66±6 mmHg, P<0.05) blood pressures. EPT exhibited reduced septal thickness (IVS, 6.8±0.8 vs 7.1±1.1 mm, P<0.05), left ventricular internal dimension (LVID, 46±4 vs 48±5 mm, P<0.05), LV end-diastolic (98±20 vs 106±24 ml, P<0.05) and end-systolic (36±9 vs 40±11 ml, P<0.01) volumes, right ventricular internal dimension (RVID, 22±3 vs 24±4 mm, P<0.05), and LV mass (104±27 vs 115±30 g, P<0.05), but similar LV mass and volume indexes. EPT exhibited increased LV myocardial performance index (0.41±0.04 vs 0.39±0.04, P<0.01), reduced mitral lateral e’ (17.6±2.8 vs 19.1±2.6 cm/s, P<0.01), mitral s’ (10.7±2.3 vs 11.6±2.3 cm/s, P<0.01), tricuspid E’ (15.8±2.7 vs 16.8±2.1 cm/s, P<0.05), and tricuspid S’ (13.1±2.0 vs 14.0±2.0 cm/s, P<0.01) waves, and a trend in reduced mitral E wave (81±14 vs 85±15 cm/s, P=0.09). EPT with neonatal BPD exhibited greater reduction in IVS (6.5±0.8 mm, P<0.05 vs terms), LVID (45±4 mm, P<0.05), LV Mass (98±22 g, P<0.05), and RVID (20±3 mm, P<0.01). Conclusions: EPT exhibit cardiac structural and functional alterations compared to term-born individuals. Neonatal BPD in EPT is a key contributor to long term cardiac remodeling.

scholarly journals Preterm birth, stillbirth and early neonatal mortality during the Danish COVID-19 lockdown

2021 ◽  
Author(s):  
Paula L. Hedley ◽  
Gitte Hedermann ◽  
Christian M. Hagen ◽  
Marie Bækvad-Hansen ◽  
Henrik Hjalgrim ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Perinatal Mortality ◽  
Birth Rate ◽  
Preterm Births ◽  
Extended Period ◽  
Stillbirth Rate ◽  
Early Neonatal Mortality ◽  
Extremely Preterm ◽  
Preterm Birth Rate ◽  
Extremely Preterm Birth

AbstractUsing provisional or opportunistic data, three nationwide studies (The Netherlands, the USA and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, none of the studies accounted for perinatal deaths. To determine whether the reduction in extremely preterm births, observed in Denmark during the COVID-19 lockdown, could be the result of an increase in perinatal deaths and to assess the impact of extended COVID-19 restrictions, we performed a nationwide Danish register-based prevalence proportion study. We examined all singleton pregnancies delivered in Denmark during the COVID-19 strict lockdown calendar periods (March 12–April 14, 2015-2020, N = 31,164 births) and the extended calendar periods of COVID-19 restrictions (February 27–September 30, 2015-2020, N = 214,862 births). The extremely preterm birth rate was reduced (OR 0.27, 95% CI 0.07 to 0.86) during the strict lockdown period in 2020, while perinatal mortality was not significantly different. During the extended period of restrictions in 2020, the extremely preterm birth rate was marginally reduced, and a significant reduction in the stillbirth rate (OR 0.69, 0.50 to 0.95) was observed. No changes in early neonatal mortality rates were found.Conclusion: Stillbirth and extremely preterm birth rates were reduced in Denmark during the period of COVID-19 restrictions and lockdown, respectively, suggesting that aspects of these containment and control measures confer an element of protection. The present observational study does not allow for causal inference; however, the results support the design of studies to ascertain whether behavioural or social changes for pregnant women may improve pregnancy outcomes. What is Known:• The aetiologies of preterm birth and stillbirth are multifaceted and linked to a wide range of socio-demographic, medical, obstetric, foetal, psychosocial and environmental factors.• The COVID-19 lockdown saw a reduction in extremely preterm births in Denmark and other high-income countries. An urgent question is whether this reduction can be explained by increased perinatal mortality. What is New:• The reduction in extremely preterm births during the Danish COVID-19 lockdown was not a consequence of increased perinatal mortality, which remained unchanged during this period.• The stillbirth rate was reduced throughout the extended period of COVID-19 restrictions.

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