Urinary 8-hydroxy-2′-deoxyguanosine levels and small-for-gestational age infants: a prospective cohort study from the Japan Environment and Children’s Study

Abstract

ObjectivesTo evaluate the association between the urinary 8-hydroxy-2′-deoxyguanosine (U8-OHdG) levels and the incidence of small-for-gestational age (SGA) infants and to assess the utility of U8-OHdG as a biomarker to predict the incidence of SGA infants.DesignProspective cohort study.SettingThe Japan Environment and Children’s Study.ParticipantsData of participants enrolled in the Japan Environment and Children’s Study, a nationwide birth cohort study, between 2011 and 2014 were analysed; 104 062 fetal records were analysed. Data of women with singleton pregnancies ≥22 weeks of gestation were analysed.Primary and secondary outcome measuresU8-OHdG levels were assessed using liquid chromatography-tandem mass spectrometry. Participants were categorised into the following three groups according to the quartile of the distribution of U8-OHdG: low U8-OHdG (<1.95 ng/mgCre), moderate U8-OHdG (the combined second and third quartiles; 1.95–2.95 ng/mgCre) and high U8-OHdG (>2.95 ng/mgCre) groups. Additionally, participants in the 90th percentile for U8-OHdG levels were analysed. Odds ratios (ORs) for SGA infants (<−1.5 and <−2.0 SD) were calculated using a logistic regression model while adjusting for confounding factors; the moderate U8-OHdG group was used as a reference. The cut-off value of U8-OHdG to predict the incidence of SGA infants was calculated using a receiver operating characteristic (ROC) curve analysis.ResultsData of 80 212 participants were analysed. The adjusted ORs for SGA infants (<−1.5 and<−2.0 SD) in the high U8-OHdG group were 1.16 (95% CI 1.07 to 1.25) and 1.22 (95% CI 1.07 to 1.38). The cut-off value of U8-OHdG (3.26 ng/mgCre) showed a poor ability to predict SGA infants (sensitivity, 21.9%; specificity, 83.6%; area under the ROC curve, 0.530).ConclusionsElevated U8-OHdG levels were associated with an increased incidence of SGA infants. However, this parameter would not be a useful screening tool for predicting SGA infants owing to its low sensitivity and specificity.

Urinary 8-hydroxy-2′-deoxyguanosine levels and preterm births: a prospective cohort study from the Japan Environment and Children’s Study

“…We contacted pregnant women through cooperating healthcare providers and/or local government offices issuing the Maternal and Child Health Handbooks and registered those willing to participate. Self-administered questionnaires, which were completed by the women during the first trimester and second/third trimester, were used to collect information on demographic factors, medical and obstetric history, physical and mental health, lifestyle, occupation, environmental exposure at home and in the workplace, housing conditions and socioeconomic status 22 27 28…”

“…Specifically, we used three types of data: (1) M-T1, obtained from a self-reported questionnaire that was collected during the first trimester (the first questionnaire) and that included questions regarding maternal medical background; (2) M-T2, obtained from a self-reported questionnaire that was collected during the second or third trimester (the second questionnaire) and that included questions regarding partner lifestyle and socioeconomic status and (3) Dr-T1 and Dr-0m that were collected from the medical record transcripts provided by each participant’s cooperating healthcare providers, which included data on obstetric outcomes during the first, second and third trimesters, such as gestational age and birth weight. Medical record transcriptions were performed by physicians, midwives/nurses and/or research coordinators 22. This study shares common methodologies with our previous work 22…”

“…Oxidative stress (OS), as defined as an imbalance between pro-oxidants such as reactive oxygen species (ROS) and antioxidants,12 is a concomitant factor with chronic inflammation as an underlying mechanism and a potentiation factor for producing inflammatory cytokines, which causes several obstetric complications 13 14. The relationship between OS and the development of pathological processes leading to female reproductive disorders, such as recurrent pregnancy loss, PTB, chorioamnionitis, pre-eclampsia, gestational diabetes mellitus, fetal growth restriction (FGR), small-for-gestational-age (SGA) infants and fetal death, has been reported previously 15–22. However, in previous studies, the methods of evaluating OS were not unified in terms of the type of biomarkers and recommended time points for measurements.…”

“…However, in previous studies, the methods of evaluating OS were not unified in terms of the type of biomarkers and recommended time points for measurements. Moreover, there is no standardised protocol for measuring these biomarkers to estimate OS in pregnant women 22…”

Dietary and Antioxidant Vitamins Limit the DNA Damage Mediated by Oxidative Stress in the Mother–Newborn Binomial

“…Increased 8-OHdG is associated with the progression or prognosis of cardiovascular diseases, T2D [ 20 , 21 ], cancer [ 22 , 23 ], and other diseases in adults [ 24 , 25 , 26 , 27 , 28 , 29 ]. In pregnant women, high levels of 8-OHdG have been associated with restriction of foetal growth [ 30 , 31 ], neural tube defects [ 32 ], and orofacial clefts [ 33 ] in the progeny. On the other hand, in mothers, high 8-OHdG levels were associated with gestational diabetes mellitus (GDM) [ 34 , 35 ], and more recently, it was observed in pregnant women infected by severe acute respiratory syndrome coronavirus 2 [ 36 ].…”