First-trimester increase in oxidative stress and risk of small-for-gestational-age fetus N Potdar, a R Singh, b V Mistry, c MD Evans, c PB Farmer, b JC Konje, a MS Cooke c a Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine b Cancer Biomarkers and Prevention Group, Biocentre and c Radiation and Oxidative Stress Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK Correspondence: Dr N Potdar, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, UK. Email saphaire_neelam@yahoo.com Accepted 1 December 2008. Objective Investigation of increased oxidative stress in early pregnancy and association with an increased risk of small-for- gestational-age (SGA) fetus. Design Longitudinal case–control study. Setting University Hospitals of Leicester NHS Trust, Leicester, UK. Population Low-risk pregnant women with no current or pre- existing medical illness were recruited at a large teaching hospital from 2004 to 2006. Methods Recruitment performed at the time of the dating ultrasound scan (12 ± 2 weeks of gestation). Spot urine samples collected at 12 ± 2 and 28 ± 2 weeks of gestation were analysed for 8-oxo-7,8-dihydro-2#-deoxyguanosine (8-oxodG) by liquid chromatography with tandem mass spectrometry). SGA was defined as birthweight <10th centile based on customised centile calculator (www.gestation.net). This identified the cases (n = 55), whereas controls (n = 55) were mothers whose babies were appropriate for gestational age (AGA, birthweight 10th–90th centile). Statistical analysis was performed using GraphPad Prism v.5. The relationship between maternal urinary 8-oxodG at different gestations and customised SGA was investigated by nonparametric tests. Main outcome measures Customised SGA and AGA pregnancies. Results Urinary 8-oxodG concentrations were significantly increased in pregnancies with subsequent SGA compared with concentrations in normal pregnancies; 12 weeks: 2.8 (interquartile range [IQR] 1.96–3.67) versus 2.2 (IQR 1.26–3.28) pmol 8-oxodG/ mmol creatinine (P = 0.0007); 28 weeks: 2.21 (IQR 1.67–3.14) versus 1.68 (IQR 1.16–2.82) pmol 8-oxodG/mmol creatinine (P < 0.0002). Concentrations decreased significantly between week 12 and 28 (P = 0.04 and P = 0.02 for controls and cases). Conclusions In this study, urinary 8-oxodG at 12 and 28 weeks were elevated in SGA compared with AGA pregnancies. This may reflect early placental changes predating clinical features of SGA. Keywords 8-oxo-7, 8-dihydro-2#-deoxyguanosine, DNA damage, fetal growth restriction, oxidative stress, placenta, pregnancy. Please cite this paper as: Potdar N, Singh R, Mistry V, Evans M, Farmer P, Konje J, Cooke M. First-trimester increase in oxidative stress and risk of small-for- gestational-age fetus. BJOG 2009;116:637–642. Introduction Small-for-gestational-age (SGA) babies, who are not diag- nosed before birth, have a significantly increased risk of peri- natal mortality. Specifically, it has been shown that up to 50% of unexplained stillbirths are growth restricted. 1–3 However, SGA is a heterogeneous population, which includes not only fetal growth restricted (FGR) babies but also small healthy babies. The use of customised centile calculator is a means by which the SGA group may be refined to minimise the inclusion of false positives (small healthy babies) and to max- imise the identification of FGR. 4 Therefore, while not synon- ymous with FGR, SGA, as defined by the customised centile calculator (customised SGA), represents a group with a high proportion of FGR. In the general population, FGR compli- cates ;10% of pregnancies and, in addition to increased peri- natal morbidity/mortality, is associated with an increased risk of developing the metabolic syndrome (dyslipidemia, insulin resistance and hypertension), type II diabetes and cardiovas- cular diseases in adulthood. 5–7 However, despite the severe consequences of FGR, predictive tests are lacking. The aetiopathogenesis of FGR is poorly understood, although various factors such as maternal systemic disease, smoking and recreational drugs have been implicated. 8 Various markers of oxidative stress have been studied in FGR and other pregnancy complications such as diabetes and pre-eclampsia, suggesting a role of reactive oxygen spe- cies (ROS) in their aetiopathogenesis. Oxidative stress is defined as an imbalance between prooxidant–antioxidant sys- tem, in favour of the former. 9 This imbalance can be the result ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 637 DOI: 10.1111/j.1471-0528.2008.02096.x www.blackwellpublishing.com/bjog Maternal medicine