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Oxidative Stress in Women Treated with Atosiban for Impending Preterm Birth.

ABSTRACT: Preterm birth is defined as delivery before 37 completed weeks of pregnancy, and it is the leading cause of neonatal morbidity and mortality. Oxidative stress is recognized as an important factor in the pathogenesis of premature labor. We conducted this analysis to investigate the safety of administration of the tocolytic drug Atosiban-a reversible, competitive antagonist of the oxytocin receptor in the treatment of preterm birth and its impact on the level of oxidative stress in pregnant women after 48 hours of tocolytic treatment. This prospective study was conducted between March 2016 and August 2017 at the Obstetric Clinic of the Polish Mother's Memorial Hospital Research Institute. Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) values as well as 3-nitrotyrosine, carbonyl, and thiol group levels were measured using an ELISA test in serum and plasma of 56 pregnant women before and after 48 hours of continuous administration of Atosiban. We found that TAS levels decreased almost twice after the 48-hour drug administration (0.936?±?0.360?mmol/L vs. 0.582?±?0.305?mmol/L, P < 0.001) while TOS increased from 18.217?±?16.093??mol/L to 30.442?±?30.578??mol/L (P < 0.001). We also found a significant increase in OSI index-almost a threefold increase from 0.022?±?0.022 to 0.075?±?0.085, P < 0.001. In addition, statistically significant differences in the level of carbonyl groups were found. It increased from 65.358?±?31.332??mol/L to 97.982?±?38.047??mol/L (P < 0.001), which indicates increased oxidation of plasma proteins. Furthermore, patients who gave birth prematurely had higher levels of TOS after a 48-hour drug administration than the second group with labor after 37 weeks of pregnancy (42.803?±?34.683??mol/L vs. 25.792?±?27.821??mol/L, P < 0.031). The obtained results clearly indicate that pregnant women during tocolytic treatment with Atosiban are in a state of increased oxidative stress and occurrence of preterm birth can be associated with this phenomenon. This trial is registered with NCT03570294.

SUBMITTER: Grzesiak M

PROVIDER: S-EPMC6304866 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Oxidative Stress in Women Treated with Atosiban for Impending Preterm Birth.

Grzesiak Mariusz M Gaj Zuzanna Z Kocyłowski Rafał R Suliburska Joanna J Oszukowski Przemysław P Horzelski Wojciech W von Kaisenberg Constantin C Banach Maciej M

Oxidative medicine and cellular longevity 20181202

Preterm birth is defined as delivery before 37 completed weeks of pregnancy, and it is the leading cause of neonatal morbidity and mortality. Oxidative stress is recognized as an important factor in the pathogenesis of premature labor. We conducted this analysis to investigate the safety of administration of the tocolytic drug Atosiban-a reversible, competitive antagonist of the oxytocin receptor in the treatment of preterm birth and its impact on the level of oxidative stress in pregnant women ...[more]

PMID: 30622667

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Project description:ImportancePosttraumatic stress disorder (PTSD) occurs in about 8% of pregnant women. Stressful conditions, including PTSD, are inconsistently linked to preterm birth. Psychotropic treatment has been frequently associated with preterm birth. Identifying whether the psychiatric illness or its treatment is independently associated with preterm birth may help clinicians and patients when making management decisions.ObjectiveTo determine whether a likely diagnosis of PTSD or antidepressant and benzodiazepine treatment during pregnancy is associated with risk of preterm birth. We hypothesized that pregnant women who likely had PTSD and women receiving antidepressant or anxiolytic treatment would be more likely to experience preterm birth.Design, setting, and participantsLongitudinal, prospective cohort study of 2654 women who were recruited before 17 completed weeks of pregnancy from 137 obstetrical practices in Connecticut and Western Massachusetts.ExposuresPosttraumatic stress disorder, major depressive episode, and use of antidepressant and benzodiazepine medications.Main outcomes and measuresPreterm birth, operationalized as delivery prior to 37 completed weeks of pregnancy. Likely psychiatric diagnoses were generated through administration of the Composite International Diagnostic Interview and the Modified PTSD Symptom Scale. Data on medication use were gathered at each participant interview.ResultsRecursive partitioning analysis showed elevated rates of preterm birth among women with PTSD. A further split of the PTSD node showed high rates for women who met criteria for a major depressive episode, which suggests an interaction between these 2 exposures. Logistic regression analysis confirmed risk for women who likely had both conditions (odds ratio [OR], 4.08 [95% CI, 1.27-13.15]). For each point increase on the Modified PTSD Symptom Scale (range, 0-110), the risk of preterm birth increased by 1% to 2%. The odds of preterm birth are high for women who used a serotonin reuptake inhibitor (OR, 1.55 [95% CI, 1.02-2.36]) and women who used a benzodiazepine medication (OR, 1.99 [95% CI, 0.98-4.03]).Conclusions and relevanceWomen with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms.

Project description:BACKGROUND:Specialised preterm birth clinics care for women at high risk of spontaneous preterm birth. This systematic review assesses current practice within preterm birth clinics globally. METHODS:A comprehensive search strategy was used to identify all studies on preterm birth clinics on the MEDLINE, Embase, PsycINFO, CENTRAL and CINAHL databases. There were no restrictions to study design. Studies were limited to the English language and publications from 1998 onwards. Two reviewers assessed studies for inclusion, performed data extraction and reviewed methodological quality. Primary outcomes were referral criteria, investigations and interventions offered in preterm birth clinics. Secondary outcomes were the timing of planned first and last appointments and frequency of review. RESULTS:Thirty-two records fulfilled eligibility criteria and 20 studies were included in the main analysis following grouping of records describing the same study or clinic. Studies were of mixed study design and methodological quality. A total of 39 clinics were described; outcome data was not available for all clinics. Referral criteria included previous spontaneous preterm birth (38/38, 100%), previous mid-trimester loss (34/38, 89%) and previous cervical surgery (33/38, 87%). All clinics offered transvaginal cervical length scans. Additional investigations varied, including urogenital swabs (16/28, 57%) and fetal fibronectin (8/28, 29%). The primary treatment of choice for a sonographic short cervix was cervical cerclage in 10/33 (30%) clinics and vaginal progesterone in 6/33 (18%), with 10/33 (30%) using multiple first-line options and 6/33 (18%) using a combination of treatments. The majority of clinics planned timing of first review for 12-16?weeks (30/35, 86%) and the frequency of review was usually determined by clinical findings (18/24, 75%). There was a wide variation in gestational age at clinic discharge between 24 and 37?weeks. CONCLUSIONS:There is variation in the referral criteria, investigations and interventions offered in preterm birth clinics and in the timing and frequency of review. Consistency in practice may improve with the introduction of consensus guidelines and national preterm birth prevention programmes. TRIAL REGISTRATION:Systematic review registration number: CRD42019131470.

Project description:BackgroundMediation analysis is useful for understanding mechanisms and has been used minimally in the study of the environment and disease.ObjectiveWe examined mediation of the association between phthalate exposure during pregnancy and preterm birth by oxidative stress.MethodsThis nested case-control study of preterm birth (n = 130 cases, 352 controls) included women who delivered in Boston, Massachusestts, from 2006 through 2008. Phthalate metabolites and 8-isoprostane, an oxidative stress biomarker, were measured in urine from three visits in pregnancy. We applied four counterfactual mediation methods: method 1, utilizing exposure and mediator averages; method 2, using averages but allowing for an exposure-mediator interaction; method 3, incorporating longitudinal measurements of the exposure and mediator; and method 4, using longitudinal measurements and allowing for an exposure-mediator interaction.ResultsWe observed mediation of the associations between phthalate metabolites and all preterm birth by 8-isoprostane, with the greatest estimated proportion mediated observed for spontaneous preterm births specifically. Fully utilizing repeated measures of the exposure and mediator improved precision of indirect (i.e., mediated) effect estimates, and including an exposure-mediator interaction increased the estimated proportion mediated. For example, for mono(2-ethyl-carboxy-propyl) phthalate (MECPP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), the percent of the total effect mediated by 8-isoprostane increased from 47% to 60% with inclusion of an exposure-mediator interaction term, in reference to a total adjusted odds ratio of 1.67 or 1.48, respectively.ConclusionsThis demonstrates mediation of the phthalate-preterm birth relationship by oxidative stress, and the utility of complex regression models in capturing mediated associations when repeated measures of exposure and mediator are available and an exposure-mediator interaction may exist. Citation: Ferguson KK, Chen YH, VanderWeele TJ, McElrath TF, Meeker JD, Mukherjee B. 2017. Mediation of the relationship between maternal phthalate exposure and preterm birth by oxidative stress with repeated measurements across pregnancy. Environ Health Perspect 125:488-494; http://dx.doi.org/10.1289/EHP282.

Project description:BackgroundPreterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery.ObjectiveThe objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women.Study designThis is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term.ResultsOf the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term.ConclusionWe identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.

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Oxidative Stress in Women Treated with Atosiban for Impending Preterm Birth.

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Oxidative Stress in Women Treated with Atosiban for Impending Preterm Birth.

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