8-epi-prostaglandin-f2alpha and Premature-Birth

Inflammation and oxidative stress play a key role in the development of bronchopulmonary dysplasia (BPD), possibly contributing to persistent respiratory morbidity after preterm birth. We aimed to assess if inflammatory markers were elevated in exhaled breath condensate (EBC) of infants born very prematurely (< 32 weeks gestation) at 12-16 corrected months of age, and if increased levels were associated with BPD diagnosis and respiratory morbidity.. EBC samples and respiratory questionnaires were collected from 15 term-born infants and 33 preterm-born infants, 12 with a neonatal BPD diagnosis. EBC samples were analysed for leukotriene B4 (inflammation) and 8-isoprostane (oxidative stress) concentrations using enzyme-linked immune-assays. Differences between groups were analysed by Kruskal-Wallis Test with post-hoc comparisons, independent samples t-test or Mann-Whitney U test depending on normality of the data.. Leukotriene B4 and 8-isoprostane levels were elevated in exhaled breath condensate of preterm-born infants compared to those born at term (mean difference [95% CI]; 1.52 [0.45, 2.59], p = 0.02; 0.77 [0.52, 1.02], p < 0.001, respectively). Leukotriene B4 and 8-isoprostane levels were independent of BPD diagnosis and respiratory morbidity over the first year of life.. Infants born very prematurely exhibit elevated markers of airway neutrophilic inflammation and oxidative stress beyond the first year of life, regardless of a neonatal diagnosis of chronic lung disease or respiratory morbidity during infancy. These findings may have implications for future lung health.. N/A.

Topics: Breath Tests; Bronchopulmonary Dysplasia; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Inflammation; Leukotriene B4; Premature Birth

Oxidative stress has been implicated in numerous birth outcomes, including spontaneous preterm birth. However, the relationship with presentation at delivery has been less well studied. We assessed the relationship between oxidative stress biomarkers and gestational duration with a focus on spontaneous presentation for delivery.. Our sample included 740 women from a multi-center prospective cohort study, recruited from 2010 to 2012. Resultant measures of oxidative stress in pregnancy prostaglandin F. The 8-iso-PGF. Our data suggest that increased oxidative stress, as indicated by the 8-iso-PGF

Topics: Adult; Biomarkers; Dinoprost; Female; Humans; Infant, Newborn; Lipid Peroxidation; Oxidative Stress; Pregnancy; Pregnancy Trimester, Third; Premature Birth

To determine whether antenatal depression is associated with oxidative stress and inflammation, and secondarily, whether the association between antenatal depression and spontaneous preterm birth (SPTB) is mediated by these biomarkers.. The primary outcome included urine oxidative stress biomarkers 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane and plasma inflammatory biomarkers measured at 10, 18, and 26 weeks and averaged within individual. Linear and logistic regression models were used, adjusting for age, race, parity, and pre-pregnancy body mass index.. Among 462 women, 8-isoprostane was higher among depressed women (geometric mean: 299.96 pg/mL vs. 237.01 pg/mL; p = 0.001). In multivariable analyses, antenatal depression was significantly associated with an increase in average 8-isoprostane (β: 0.25; 95% CI: 0.05-0.44; p = 0.01). The association of antenatal depression with SPTB was partially mediated by 8-isoprostane. Antenatal depression was not associated with 8-OHdG or inflammatory biomarkers.. Antenatal depression was associated with higher oxidative stress across pregnancy, namely 8-isoprostane, and may impact SPTB via oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Cytokines; Depression; Dinoprost; Female; Humans; Inflammation; Oxidative Stress; Pregnancy; Pregnancy Complications; Premature Birth; Regression Analysis; Young Adult

The purpose of this study was to investigate oxidative stress as a mechanism of preterm birth in human subjects; we examined associations between urinary biomarkers of oxidative stress that were measured at multiple time points during pregnancy and preterm birth.. This nested case-control study included 130 mothers who delivered preterm and 352 mothers who delivered term who were originally recruited as part of an ongoing prospective birth cohort at Brigham and Women's Hospital. Two biomarkers that included 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine samples that were collected at up to 4 time points (median 10, 18, 26, and 35 weeks) during gestation.. Urinary concentrations of 8-isoprostane and 8-OHdG decreased and increased, respectively, as pregnancy progressed. Average levels of 8-isoprostane across pregnancy were associated with increased odds of spontaneous preterm birth (adjusted odds ratio, 6.25; 95% confidence interval, 2.86-13.7), and associations were strongest with levels measured later in pregnancy. Average levels of 8-OHdG were protective against overall preterm birth (adjusted odds ratio, 0.19; 95% confidence interval, 0.10-0.34), and there were no apparent differences in the protective effect in cases of spontaneous preterm birth compared with cases of placental origin. Odds ratios for overall preterm birth were more protective in association with urinary 8-OHdG concentrations that were measured early in pregnancy.. Maternal oxidative stress may be an important contributor to preterm birth, regardless of subtype and timing of exposure during pregnancy. The 2 biomarkers that were measured in the present study had opposite associations with preterm birth; an improved understanding of what each represents may help to identify more precisely important mechanisms in the pathway to preterm birth.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Deoxyguanosine; Dinoprost; Female; Humans; Infant, Newborn; Longitudinal Studies; Male; Odds Ratio; Oxidative Stress; Pregnancy; Premature Birth; Prospective Studies

Phthalate exposure occurs readily in the environment and has been associated with an array of health end points, including adverse birth outcomes. Some of these may be mediated by oxidative stress, a proposed mechanism for phthalate action.. In the present study, we explored the associations between phthalate metabolites and biomarkers of oxidative stress measured in urine samples from multiple time points during pregnancy.. Women were participants in a nested case-control study of preterm birth (n = 130 cases, n = 352 controls). Each was recruited early in pregnancy and followed until delivery, providing urine samples at up to four visits. Nine phthalate metabolites were measured to assess exposure, and 8-hydroxydeoxyguanosine and 8-isoprostane were also measured in urine as markers of oxidative stress. Associations were assessed using linear mixed models to account for intraindividual correlation, with inverse selection probability weightings based on case status to allow for greater generalizability.. Interquartile range increases in phthalate metabolites were associated with significantly higher concentrations of both biomarkers. Estimated differences were greater in association with monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), and monoisobutyl phthalate (MiBP), compared with di(2-ethylhexyl) phthalate (DEHP) metabolites.. Urinary phthalate metabolites were associated with increased oxidative stress biomarkers in our study population of pregnant women. These relationships may be particularly relevant to the study of birth outcomes linked to phthalate exposure. Although replication is necessary in other populations, these results may also be of great importance for a range of other health outcomes associated with phthalates.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Deoxyguanosine; Dinoprost; Environmental Pollutants; Female; Humans; Linear Models; Oxidative Stress; Phthalic Acids; Pregnancy; Premature Birth

To investigate the association between maternal oxidative stress at mid-gestation and subsequent development of pregnancy complications.. A total of 503 healthy pregnant women provided their blood and urine samples at 24 to 26 weeks of gestation and were prospectively followed through postpartum. These samples were used to assess a variety of oxidative stress markers, including plasma total antioxidant capacity, 8-isoprostane, erythrocyte glutathione peroxidase and superoxide dismutase activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG).. Compared with women with uncomplicated pregnancies, significantly higher plasma 8-isoprostane levels were noted in women who developed preeclampsia (P = .008) and small-for-gestational age infants (P = .002), while higher urinary 8-OHdG concentrations were noted in women who subsequently had low-birth-weight neonates (<2500 g, P = .043).. Increased maternal oxidative stress at mid-gestation was associated with subsequent pregnancy complications.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Deoxyguanosine; Dinoprost; Erythrocytes; Female; Gestational Age; Glutathione Peroxidase; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Premature Birth; Prospective Studies; Superoxide Dismutase

Cord blood 8-isoprostane (8-IP) is a marker of lipid peroxidation in the peripartum period. The independent association with degree of prematurity is not well-described.. To identify patterns of lipid peroxidation among early, moderate and late preterm infants, and to understand how cord blood 8-IP varies with gestational age (GA) and related covariates.. Mother-infant pairs from 237 preterm births were studied as part of a longitudinal birth cohort study. GA subgroups were defined as extremely (≤28w), moderately (29-33w), and late (34-36w) preterm. Cord blood 8-IP was measured using EIA. Elevated 8-IP (4th quartile) was the primary outcome for multivariate logistic regression models, which were adjusted for maternal age/race, multiple gestation and infant gender, as well as other relevant covariates.. Elevated 8-IP was associated with extremely preterm birth (OR=4.31; 95% CI=1.90, 9.76), and was inversely associated with increasing GA (OR=0.88; 95% CI=0.80, 0.97). Elevated 8-IP was also associated with decreasing birth weight (BW), clinical chorioamnionitis, fetal inflammatory response of the placenta (FIR), and signs of perinatal depression. The GA on 8-IP association appeared to be modified by several maternal disease and fetal-infant factors. Lastly, the indirect associations between log-transformed 8-IP, GA and BW appeared to be most prominent for GA<30w and for BW<2000g.. Lipid peroxidation in preterm birth, and the relative influence of accompanying peripartum factors, varies according to degree of prematurity. These findings have important implications for the developmental regulation of antioxidant defense and its impact on neonatal outcomes.

Topics: Adult; Birth Weight; Dinoprost; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Lipid Peroxidation; Male; Pregnancy; Premature Birth; Sex Factors

Increased oxygen tension at birth regulates physiologic events that are essential to postnatal survival, but the accompanying oxidative stress may also generate isoprostanes. We hypothesized that isoprostanes regulate ductus arteriosus (DA) function during postnatal vascular transition.. Isoprostanes were measured by gas chromatography-mass spectrometry. DA tone was assessed by pressure myography. Gene expression was measured by quantitative PCR.. Oxygen exposure was associated with increased 8-iso-prostaglandin (PG)F2α in newborn mouse lungs. Both 8-iso-PGE2 and 8-iso-PGF2α induced concentration-dependent constriction of the isolated term DA, which was reversed by the thromboxane A2 (TxA2) receptor antagonist SQ29548. SQ29548 pretreatment unmasked an isoprostane-induced DA dilation mediated by the EP4 PG receptor. Exposure of the preterm DA to 8-iso-PGE2 caused unexpected DA relaxation that was reversed by EP4 antagonism. In contrast, exposure to 8-iso-PGF2α caused preterm DA constriction via TxA2 receptor activation. Further investigation revealed the predominance of the TxA2 receptor at term, whereas the EP4 receptor was expressed and functionally active from mid-gestation onward.. This study identifies a novel physiological role for isoprostanes during postnatal vascular transition and provide evidence that oxidative stress may act on membrane lipids to produce vasoactive mediators that stimulate physiological DA closure at birth or induce pathological patency of the preterm DA.

Topics: Analysis of Variance; Animals; Animals, Newborn; Bridged Bicyclo Compounds, Heterocyclic; Dinoprost; Dinoprostone; Ductus Arteriosus; Ductus Arteriosus, Patent; Fatty Acids, Unsaturated; Female; Gas Chromatography-Mass Spectrometry; Gene Expression Profiling; Hydrazines; Isoprostanes; Mice; Myography; Oxidative Stress; Oxygen; Pregnancy; Premature Birth; Receptors, Prostaglandin E, EP4 Subtype; Receptors, Thromboxane A2, Prostaglandin H2; Vasodilation

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Birth Weight; Congenital Abnormalities; Deoxyguanosine; Dinoprost; DNA Damage; Female; Gestational Age; Humans; Infant, Newborn; Lipid Peroxidation; Male; Middle Aged; Oxidants; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prospective Studies; Young Adult

This study examined the reliability of assessing clinical periodontal measures on third molars, and the association between oral inflammation with periodontal pathology including third molars, and systemic inflammation including negative obstetric outcomes.. Reliability of third molar probing depth (PD) was assessed for 41 patients by trained examiners. The data for the association between oral inflammation with periodontal pathology and systemic outcomes were derived from an IRB-approved study, "Oral Conditions and Pregnancy." Full mouth periodontal exams including third molars were conducted at less than 24 weeks of pregnancy. Periodontal status, moderate/severe periodontal disease (15 or more sites PD > or =4 mm) was considered as a possible predictor of systemic inflammation and pre-term birth. The upper quartile of the extent of PD for third molars alone (PD > or =4 mm) also was considered as a possible exposure variable for the same outcomes. Chi-square and t tests were used to determine statistical significance (0.05). Significant predictor variables were included in multivariate models. Unconditional logistic multivariate models were used to derive odds ratios (OR) and 95% confidence intervals (CI).. Reliability of PD within 1 mm was excellent, and similar for third molars and non-third molars. Data from 1,020 obstetric patients were available for analysis. Eighteen percent of the patients delivered preterm, at less than 37 weeks. Having moderate/severe periodontal disease excluding third molars, was significantly associated with preterm birth (P = .008). Results were more significant if third molars were included (P = .0005). With multivariate models moderate/severe periodontal disease at enrollment including third molar PD, was associated with preterm birth (OR, 1.7; 95% CI, 1.1, 2.6). If only the extent of third molar PD was considered, odds also were increased for preterm birth (OR, 2.4; 95% CI, 1.1, 5.2). If only the extent of third molar PD was considered at enrollment, odds were increased for serum markers of systemic inflammation, elevated serum CRP, and oxidative stress, 8-isoPGF(2alpha).. Dental examiners could reliably assess clinical periodontal measures on third molars. Third molars should be included in studies of systemic outcomes associated with oral inflammation. Women of child-bearing age should be made aware of the systemic risks of oral inflammation with third molar periodontal pathology.

Topics: Adult; C-Reactive Protein; Dinoprost; Female; Humans; Logistic Models; Molar, Third; Odds Ratio; Periodontitis; Pregnancy; Premature Birth; Reproducibility of Results