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Keywords:

  • 8-oxo-7;
  • 8-dihydro-2′-deoxyguanosine;
  • DNA damage;
  • fetal growth restriction;
  • oxidative stress;
  • placenta;
  • pregnancy

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.