Cyclooxygenase inhibitors for treating preterm labour: What is the molecular evidence?

2019 ◽  
Vol 97 (3) ◽  
pp. 222-231 ◽  
Author(s):  
Daniela Urrego ◽  
Anthony C. Liwa ◽  
William C. Cole ◽  
Stephen L. Wood ◽  
Donna M. Slater
Keyword(s):  
Preterm Birth ◽  
Preterm Labour ◽  
Scientific Evidence ◽  
Preterm Births ◽  
Cyclooxygenase Inhibitors ◽  
Molecular Evidence ◽  
Mortality And Morbidity ◽  
Cox Inhibitors ◽  
Increased Risk

Preterm birth (<37 weeks of gestation) significantly increases the risk of neonatal mortality and morbidity. As many as half of all preterm births occur following spontaneous preterm labour. Since in such cases there are no known reasons for the initiation of labour, treatment of preterm labour (tocolysis) has sought to stop labour contractions and delay delivery. Despite some success, the use of cyclooxygenase (COX) inhibitors is associated with maternal/fetal side effects, and possibly increased risk of preterm birth. Clinical use of these drugs predates the collection of molecular and biochemical evidence in vitro, examining the expression and activity of COX enzymes in pregnant uterine tissues with and without labour. Such evidence is important to the rationale that COX enzymes are, or are not, appropriate targets for the tocolysis. The current study systematically searched existing scientific evidence to address the hypothesis that COX expression/activity is increased with the onset of human labour, in an effort to determine whether there is a rationale for the use of COX inhibitors as tocolytics. Our review identified 44 studies, but determined that there is insufficient evidence to support or refute a role of COX-1/-2 in the onset of preterm labour that supports COX-targeted tocolysis.

scholarly journals Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 554 ◽  
Author(s):  
Harshal Nemade ◽  
Aviseka Acharya ◽  
Umesh Chaudhari ◽  
Erastus Nembo ◽  
Filomain Nguemo ◽  
...  
Keyword(s):  
Wnt Signaling Pathway ◽  
Calcium Transient ◽  
Cardiac Differentiation ◽  
Cyclooxygenase Inhibitors ◽  
Cox Inhibitors ◽  
Screening Model ◽  
Cox 2 ◽  
Transient Measurements ◽  
Cox 1

Application of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited by the challenges in their efficient differentiation. Recently, the Wingless (Wnt) signaling pathway has emerged as the key regulator of cardiomyogenesis. In this study, we evaluated the effects of cyclooxygenase inhibitors on cardiac differentiation of hPSCs. Cardiac differentiation was performed by adherent monolayer based method using 4 hPSC lines (HES3, H9, IMR90, and ES4SKIN). The efficiency of cardiac differentiation was evaluated by flow cytometry and RT-qPCR. Generated hPSC-CMs were characterised using immunocytochemistry, electrophysiology, electron microscopy, and calcium transient measurements. Our data show that the COX inhibitors Sulindac and Diclofenac in combination with CHIR99021 (GSK-3 inhibitor) efficiently induce cardiac differentiation of hPSCs. In addition, inhibition of COX using siRNAs targeted towards COX-1 and/or COX-2 showed that inhibition of COX-2 alone or COX-1 and COX-2 in combination induce cardiomyogenesis in hPSCs within 12 days. Using IMR90-Wnt reporter line, we showed that inhibition of COX-2 led to downregulation of Wnt signalling activity in hPSCs. In conclusion, this study demonstrates that COX inhibition efficiently induced cardiogenesis via modulation of COX and Wnt pathway and the generated cardiomyocytes express cardiac-specific structural markers as well as exhibit typical calcium transients and action potentials. These cardiomyocytes also responded to cardiotoxicants and can be relevant as an in vitro cardiotoxicity screening model.

Placental malperfusion as a possible mechanism of preterm birth in patients with Müllerian anomalies

2017 ◽  
Vol 45 (1) ◽  
Author(s):  
Jovana Lekovich ◽  
Joshua Stewart ◽  
Sarah Anderson ◽  
Erin Niemasik ◽  
Nigel Pereira ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Gestational Age ◽  
Placenta Previa ◽  
Preterm Births ◽  
Mullerian Anomalies ◽  
Müllerian Anomalies ◽  
Increased Risk ◽  
Uterine Anomalies ◽  
Gestational Age At Delivery ◽  
Term Births

AbstractObjective:Müllerian anomalies are associated with increased risk of miscarriage, intrauterine growth restriction (IUGR) and preterm birth. While a commonly implicated cause is restricted expansion of endometrial cavity, alternatively it could be due to abnormal placentation. We sought to examine clinical and histopathologic factors associated with preterm delivery in women with Müllerian anomalies.Study design:One hundred and eleven singleton pregnancies in 85 women were analyzed retrospectively. There were 42 pregnancies with bicornaute, 24 with unicornuate, 24 with septate, 19 with didelphys and one each with arcuate and T-shaped uterus. Primary outcomes included gestational age at delivery, placental histopathology, placenta previa and accreta.Results:Twenty-eight (25.2%) of pregnancies were delivered prior to term. Of those, only 14 (50%) were due to preterm labor or preterm premature rupture of membranes (PPROM). Histological evidence of placental malperfusion was present in 22% of all pregnancies and those delivered at an earlier median gestational age [34 (IQR 31–37) vs. 37 weeks (IQR 34–39); P=0.001]. Malperfusion was more common in preterm than in full term births (46% vs. 14%; P=0.04). Conversely, inflammation was not more common in preterm compared to term deliveries (17.9% vs. 16.9%; P=0.89). Five pregnancies had placenta previa, three of which were complicated by accreta.Conclusion:Placental malperfusion, rather than inflammation, was more commonly associated with preterm births in women with uterine anomalies.

scholarly journals Do Successive Preterm Births Increase the Risk of Postpartum Depressive Symptoms?

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Timothy O. Ihongbe ◽  
Saba W. Masho
Keyword(s):  
Depressive Symptoms ◽  
Preterm Birth ◽  
Preterm Births ◽  
Prior History ◽  
Pregnancy Risk ◽  
High Risk Women ◽  
Postpartum Depressive Symptoms ◽  
Increased Risk ◽  
Multiparous Women ◽  
History Of

Background. Postpartum depression and preterm birth (PTB) are major problems affecting women’s health. PTB has been associated with increased risk of postpartum depressive symptoms (PDS). However, it is unclear if PTB in women with a prior history of PTB is associated with an incremental risk of PDS. This study aims to determine if PTB in women with a prior history of PTB is associated with an incremental risk of PDS. Methods. Data come from the 2009–2011 national Pregnancy Risk Assessment Monitoring System. Study sample included 55,681 multiparous women with singleton live births in the index delivery. Multiple logistic regression was used to examine the association between PTB and PDS. Results. The risk of PDS was 55% higher in women with PTB in both deliveries (aRR = 1.55; 95% CI = 1.28–1.88) and 74% higher in women with PTB in the index delivery only (aRR = 1.74; 95% CI = 1.49–2.05), compared to women with term deliveries. Conclusions. Preterm birth is a risk factor for PDS. PTB in women with a prior history of PTB is not associated with an incremental risk of PDS. Routine screening for PDS should be conducted for all women and closer monitoring should be done for high risk women with PTB.

scholarly journals Clinical Pharmacology Aspects of Some Tocolytic Drugs Used in Pregnant Women at Risk of Preterm Birth

2019 ◽  
Vol 9 (3) ◽  
pp. 162-166
Author(s):  
E. A. Sоkоvа ◽  
R. A. Chilova ◽  
O. A. Demidova ◽  
K. O. Akopov
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Preterm Labour ◽  
Plasma Concentrations ◽  
Cyclooxygenase Inhibitors ◽  
Pharmacokinetic Parameters ◽  
Clinical Effects ◽  
Spontaneous Preterm Birth ◽  
Rational Pharmacotherapy ◽  
The Impact

Spontaneous preterm birth is one of the most pressing issues in obstetrics, as it remains one of the leading causes of newborn morbidity and mortality. Pending issues of aetiology, pathogenesis, and absence of medicinal products indicated for the treatment of spontaneous preterm labour pose a challenge for rational pharmacotherapy. The paper presents the results of a scientific literature review on the problem of rational pharmacotherapy of spontaneous preterm labour using tocolytic drugs — calcium channel blockers, cyclooxygenase inhibitors. The paper summarises specific pharmacokinetic parameters of these drugs during pregnancy. It discusses pharmacogenetic aspects of using tocolytic drugs in pregnant women and their potential clinical effects. It was demonstrated that women with threatened miscarriage had high interindividual variability in nifedipine plasma concentrations depending on CYP3A5 genotype. It was shown that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic rate and an increase in indomethacin clearance resulting in the reduction of its efficacy. Yet, there is minimal research regarding this issue. Therefore, further research is needed to assess the impact of CYP3A5 and CYP2C9 genotypes on the efficacy and safety of nifedipine and indomethacin used as tocolytic drugs in obstetrics.

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 The impact of interpregnancy interval on occurance of preterm births in the present pregnancy

2021 ◽  
Vol 10 (5) ◽  
pp. 2020
Author(s):  
Balaji Thanjavur Elumalai ◽  
Vaishnavi Govindarajan
Keyword(s):  
Preterm Birth ◽  
Preterm Births ◽  
Neonatal Morbidity ◽  
P Value ◽  
Interpregnancy Interval ◽  
Maternal Characteristics ◽  
Increased Risk ◽  
Pregnancy Intervals ◽  
The Impact ◽  
Present Pregnancy

Background: The pregnancy outcomes are influenced by the inter pregnancy intervals. Both short and long inter pregnancy intervals are known to adversely affect the mother and the baby. The main aim of birth spacing was to achieve ideal inter pregnancy intervals and thus to decrease maternal, neonatal morbidity and mortality.Methods: It is a prospective observational study. In this study, about 500 gravida 2 women who has delivered vaginally in the index pregnancy, with gestational age more than 28 weeks of gestation and with known interpregnancy interval were included in the study. They followed up to to delivery and occurance of preterm births in relation to maternal characteristics and interpregnancy interval were analysed.Results: Our study showed that Inter pregnancy intervals of 18-24 months were found to have the least number of preterm births when compared to intervals <18 months and >24 months. This association was found to be statistically significant (p value, Pearson chi square 0.0008). This relationship between inter pregnancy intervals and preterm births persisted when stratified according to maternal age, education, residence and BMI.A previous preterm birth was associated with increased risk of recurrent preterm birth (p value -0.034) and was statistically significant. The history of PROM in present pregnancy associated with preterm birth (p value -0.001) and association was statistically significant.Conclusions: From this study it was found that the 18-24 months birth to pregnancy interval is associated with the least incidence of preterm births. 

scholarly journals PREGNANCY RELATED PLASMA PROTEIN–A AND PREMATURE BIRTH

2021 ◽  
Vol 19 (2) ◽  
pp. 172-177
Author(s):  
Iv. Todorov ◽  
N. Tododrov ◽  
M. Angelova ◽  
K. Peeva
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Plasma Protein ◽  
Premature Birth ◽  
Chromosomal Abnormalities ◽  
Placenta Previa ◽  
Protein A ◽  
Preterm Births ◽  
Sonographic Examination ◽  
Increased Risk

Introduction: Children born prematurely are at higher risk of mortality, morbidity, and impaired motor and cognitive development in childhood than prematurely born babies. Aim: To establish the relationship between the corresponding levels of pregnancy-related plasma protein-A (PAPP-A) and the frequency of premature birth. Materials and methods: The study is prospective. The data was collected through monitoring patients through a questionnaire and sonographic examination at 11-13 gestational weeks. The study excluded all known risk factors for preterm birth, such as previous preterm births, pregnant women with gestational diabetes, preeclampsia, hypertension, placenta previa, hydramnion, multiple pregnancies, smoking, structural and chromosomal abnormalities of the fetus and planned preterm birth. The data from the measured values of PAPP-A and the frequency of premature birth in 636 pregnant women were analyzed. Conclusions: PAPP-A levels are a statistically significant factor for preterm birth. It is expected with a 95% probability in the population with PAPP-A values below 0,515 that the cases with premature birth will be from 7 to 14 times more. Pregnant women with PAPP-A level less than 10th per cent are significantly associated with an increased risk of preterm birth.

scholarly journals Use of the Pessary in the Prevention of Preterm Delivery

2019 ◽  
Vol 41 (01) ◽  
pp. 053-058
Author(s):  
Thayane Corrêa ◽  
Ester Amorim ◽  
Jade Tomazelli ◽  
Mário Corrêa
Keyword(s):  
Preterm Birth ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Preterm Births ◽  
Spontaneous Preterm Birth ◽  
Mortality And Morbidity ◽  
Pooled Data ◽  
Cervical Pessary ◽  
Significant Difference ◽  
Preventive Method

Objective The gestational complication most associated with perinatal mortality and morbidity is spontaneous preterm birth with gestational age < 37 weeks. Therefore, it is necessary to identify its risk factors and attempt its prevention. The benefits of the pessary in prematurity are under investigation. Our objective was to analyze the use of the pessary in the prevention of preterm births in published studies, and to compare its efficacy with other methods. Methods Randomized clinical trials published between 2010 and 2018 were selected from electronic databases. Studies on multiple gestations were excluded. Results Two studies were in favor of the pessary as a preventive method, one study was contrary to the method and another two showed no statistically significant difference. The meta-analysis showed no statistical difference with the use of a cervical pessary in the reduction of births < 37 (odds ratio [OR]: 0.63; confidence interval [95% CI]: 0.38–1.06) and < 34 weeks (OR: 0.74; 95% CI: 0.35–1.57) Conclusion The pooled data available to date seems to show a lack of efficacy of the cervical pessary in the prevention of preterm birth, although the heterogeneity of the studies made comparisons more difficult.

scholarly journals Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e034595
Author(s):  
Anna Lene Seidler ◽  
Lelia Duley ◽  
Anup C Katheria ◽  
Catalina De Paco Matallana ◽  
Eugene Dempsey ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Management Strategies ◽  
Preterm Births ◽  
Individual Participant Data ◽  
Mortality And Morbidity ◽  
Cord Clamping ◽  
Individual Participant ◽  
Participant Characteristics

IntroductionTiming of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons.Objectives(1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA.Methods and analysisSystematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks’ gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored.Ethics and disseminationEthics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases.Registration numberAustralian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12619001305112) and International Prospective Register of Systematic Reviews (PROSPERO, CRD42019136640).

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