8-hydroxy-2--deoxyguanosine and Premature-Birth

8-Hydroxy-2-deoxyguanosine (8-OH-2dG) is a measurable biomarker of oxidative DNA damage. This study was designed to determine amniotic fluid 8-OH-2dG levels in healthy full-term pregnant women and preterm pregnant women. To reveal the effect of reactive oxygen species on 8-OH-2dG levels, amniotic fluid total oxidant capacity (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI) were also measured.. A total of 60 patients, 35 patients with full-term pregnancy and 25 patients with preterm pregnancy, participated in the study. Labor occurring before 37 weeks of gestation was considered as spontaneous preterm birth. Amniotic fluid samples were collected from full-term patients during cesarean section or normal vaginal delivery. 8-OH-2dG concentrations in amniotic fluid samples were measured quantitatively by Enzyme-Linked Immunosorbent Assay (ELISA). Amniotic fluid total antioxidant capacity (TAC) and total oxidant capacity (TOC) was determined in amniotic samples.. The amniotic fluid 8-OH-2dG levels of the preterm group were significantly higher than the full-term group (60.8±7.02 ng/mL vs. 33.6±4.11 ng/mL, p<0.01). Similarly, TOC levels of the preterm group were significantly higher than the full-term group (89.7±4.80 µmol/L vs. 54.3±6.60 µmol, p<0.02). TAC was significantly higher in the full-term group compared to the preterm group (1.87±0.10 mmol/L vs. 0.97±0.44 mmol/L, p<0.01). The OSI values of the preterm group were significantly higher than the full-term group. A negative and significant correlation was found between gestational age and amniotic fluid 8-OH-2dG levels in the full-term pregnancy group (r=-0.78, p<0.01). A negative and significant correlation was observed between TAC and amniotic fluid 8-OH-2dG levels in the full-term group (r=-0.60, p<0.02). A positive and significant correlation was also detected between TOC, OSI and amniotic fluid 8-OH-2dG levels in the full-term group. There was a negative but insignificant correlation between fetal weight and amniotic fluid 8-OH-2dG levels. The correlation analysis results of the preterm pregnancy group were similar to the full-term group.. Increased reactive oxygen derivatives in preterm birth increase amniotic fluid levels of DNA degradation product 8-OH2dG and may lead to premature rupture of fetal membranes. This is the first clinical study investigating 8-OH-2dG levels in amniotic fluid of preterm birth.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Amniotic Fluid; Antioxidants; Cesarean Section; DNA; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Oxidants; Oxidative Stress; Pregnancy; Premature Birth

To explore whether salivary inflammatory mediators and periodontal indices at different gestational stages can be taken as indicators of preterm birth (PTB).. This nested case-control study enrolled systemically healthy pregnant women at 9 to 36 weeks of gestation. Periodontal indices were measured at the enrollment date, and interleukin-1. PTB occurred in 26 women. A total of 104 matched women with full-term birth (FTB) were used as controls. The PTB women enrolled at 24-28 gestational weeks displayed a significantly greater bleeding index (BI), probing pocket depth (PD), PD ≥ 4 mm sites (%), saliva-TNF-. The combination of BI and PGE2 in saliva at 24-28 gestational weeks could be a predictor of PTB in asymptomatic women. However, the results should be further explored with larger sample size.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Case-Control Studies; China; Dinoprostone; Female; Humans; Infant, Newborn; Inflammation Mediators; Pregnancy; Premature Birth; Saliva; Tumor Necrosis Factor-alpha

The profile of sirtuin 3 (SIRT3), 8-hydroxy-2'-deoxyguanosine (8-OHdG), brain-derived neurotrophic factor (BDNF) and serotonin (5-HT) in cord blood and in early breast milk was studied and it was related to perinatal factors. 5-HT and BDNF signalling systems have been claimed to play a critical role in intrauterine development, postnatal adaptation and lactation. Since prematurity and Caesarean birth are frequently associated with inflammation and related oxidative stress, an attempt was made to reveal the adaptive changes of the protective SIRT3 and the complex interplay among these bioactive components in cord blood and early breast milk.. Three groups each consisting of 30 mothers were included in the study: mothers who underwent spontaneous vaginal birth at term (group I), Caesarean section at term (group II) and preterm birth (group III). Venous cord blood and early breast milk samples were collected for measuring the biomarkers. SIRT3, 8-OHdG, BDNF and 5-HT levels were determined by using commercially available ELISA kits.. It was demonstrated that cord blood levels of SIRT3, BDNF and 5-HT were markedly reduced whereas those of 8-OHdG were significantly elevated after preterm birth when compared with birth at term. The Caesarean section was associated with a moderate decrease in BDNF and 5-HT, however, both SIRT3 and 8-OHdG remained unaffected. Breast milk levels of all biomarkers studied proved to be independent of their corresponding cord blood concentrations. In response to preterm birth breast milk SIRT3, 8-OHdG and 5-HT increased significantly, while a drastic fall occurred in BDNF. A significant positive relationship was found of 5-HT with SIRT3 and 8-OHdG irrespective of the gestational age and the mode of delivery.. It is suggested that the selected biomarkers in the breast milk mostly derive from local production by the mammary glands and 5-HT may have an essential role in the control of this process.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Brain-Derived Neurotrophic Factor; Breast Feeding; Cesarean Section; Delivery, Obstetric; Female; Fetal Blood; Humans; Hungary; Infant, Newborn; Male; Milk, Human; Parturition; Pregnancy; Premature Birth; Serotonin; Sirtuin 3

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

In an effort to mitigate the major morbidities and mortality associated with extreme prematurity, we have developed an EXTrauterine Environment for Neonatal Development (EXTEND) designed to provide physiologic support of extremely premature infants.. We have previously shown that long-term, physiologic support of premature fetal lambs is possible with EXTEND, but in this study, we sought to demonstrate bioenergetic equipoise at the tissue level.. Four premature fetal lambs were delivered by hysterotomy at gestational ages (GA) of 105-107 days (term ∼145 days), cannulated via the umbilical vessels, and transitioned to support on EXTEND for 3-4 weeks. Five control fetuses were age-matched to the GA of experimental fetuses at the time of study end (128-134 days GA) and immediately sacrificed after hysterotomy. Mitochondria were isolated from the heart, liver, kidney, and skeletal muscle of fetuses at the time of sacrifice, and oxygen consumption rates (OCRs) were measured.. There were no differences in basal mitochondrial OCR between EXTEND and control fetuses for heart, kidney, or skeletal muscle. For liver, the basal OCR was higher in EXTEND fetuses compared to controls. There were no differences in physiologic maximal OCR or reserve capacity for any tissue analyzed.. Fetal lambs supported by EXTEND demonstrate physiologic mitochondrial function as evidenced by adequate basal and physiologic maximal cellular respiration as well as preserved reserve capacity.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Animals, Newborn; Artificial Organs; Bilirubin; Biomarkers; Cell Respiration; Energy Metabolism; Extracorporeal Membrane Oxygenation; Female; Fetal Monitoring; Gestational Age; Mitochondria; Oxygen Consumption; Oxygenators, Membrane; Pregnancy; Premature Birth; Sheep, Domestic; Time Factors

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

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