First‐trimester increase in oxidative stress and risk of small‐for‐gestational‐age fetus

• Published in: BJOG : an international journal of obstetrics and gynaecology Vol. 116; no. 5; pp. 637 - 642
• Main Authors: Potdar, N, Singh, R, Mistry, V, Evans, MD, Farmer, PB, Konje, JC, Cooke, MS
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2009; Blackwell; Wiley Subscription Services, Inc
• Subjects: 8‐dihydro‐2′‐deoxyguanosine; 8‐oxo‐7; Adolescent; Adult; Biological and medical sciences; Biomarkers - analysis; Biomarkers - urine; Birth Weight; Case-Control Studies; Cotinine - analysis; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - urine; Diseases of mother, fetus and pregnancy; DNA damage; Female; fetal growth restriction; Fetal Growth Retardation - etiology; Fetal Growth Retardation - metabolism; Follow-Up Studies; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Obstetrics; Oxidative Stress; placenta; Pregnancy; Pregnancy - urine; Pregnancy Trimester, First - urine; Pregnancy Trimester, Second - urine; Pregnancy. Fetus. Placenta; Prospective Studies; Risk Assessment - methods; Risk factors; Saliva - chemistry; Smoking - adverse effects; Statistics, Nonparametric; Oxidative stress; Intrauterine growth retardation; Pregnancy disorders; Gynecology; Low birth weight; First trimester; Obstetrics; Pregnancy; Fetal diseases; Newborn diseases; Prematurity; Risk factor; Fetus
• ISSN: 1470-0328; 1471-0528
• DOI: 10.1111/j.1471-0528.2008.02096.x

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/μmol creatinine (P= 0.0007); 28 weeks: 2.21 (IQR 1.67–3.14) versus 1.68 (IQR 1.16–2.82) pmol 8‐oxodG/μmol 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.