Abstract for presentation at 11th International Congress of Human Genetics

First trimester serum markers of adverse pregnancy outcome.

  • Dr Jennifer Crossley, Institute of Medical Genetics, United Kingdom
  • Nicola Jenkins, Institute of Medical Genetics, Yorkhill, United Kingdom
  • Prof Gordon Smith, Department of Obstetrics and Gynaecology, Cambridge University, United Kingdom
  • David Aitken, Institute of Medical Genetics, United Kingdom
  • Prof Fiona Lyall, Institute of Medical Genetics, United Kingdom
  • Prof Michael Connor, Institute of Medical Genetics, United Kingdom

    • Purpose: Screening markers for Down's syndrome may identify pregnancies with other abnormalities. For example, lower levels of maternal serum pregnancy associated plasma protein A at 9-14 weeks are associated with low birth weight, extremely and moderately pre-term delivery, stillbirth and pre-eclampsia.
    Methods: In a series of first trimester pregnancies with various adverse outcomes and 936 control samples form unaffected pregnancies at 9-14 weeks we measured a range of factors in maternal serum: Insulin-like growth factors 1 and 2 (IGF-1, IGF-2), Insulin-like growth factor binding proteins 1 and 3 (IGFBP-1, IGFBP-3), placental growth factor (PlGF), vascular endothelial growth factor receptor 1 (VEGFR-1), matrix metalloproteinase 9 (MMP-9) and leptin. All results were converted to multiples of the appropriate gestational median (MoM).
    Results: In the low birth weight group (n=325), significant reductions in median were found for VEGFR-1 (0.94 MoM, p<0.0001) and PlGF (0.94 MoM, p = 0.018) and significant elevation for leptin (1.08 MoM, p=0.003). Extremely preterm delivery (n=118) was associated with significant reductions in VEGFR-1 (0.95 MoM, p=0.011) and PlGF (0.93 MoM, p=0.029) and significant elevations in IGF-1 (1.24 MoM, p=0.029), IGF-2 (1.05 MoM, p=0.009) and leptin (1.19 MoM, p=0.001). The moderately preterm delivery group (n=225) showed a reduction in median MoM in VEGFR-1 (0.89 MoM, p=0.003) and elevations in IGF-1 (1.25 MoM, p=0.001) and leptin (1.05 MoM, p=0.025). Samples from pregnancies which subsequently developed pre-eclampsia (n=305) showed elevations in IGF-1 (1.18 MoM, p=0.001), IGF-2 (1.09 MoM, p<0.0001), IGFBP-3 (1.11 MoM, p<0.0001), leptin (1.08 MoM, p=0.003) and MMP-9 (1.13 MoM, p=0.004). No significant changes were found for any marker in pregnancies which resulted in stillbirth (n=24),
    Conclusions: Combinations of these markers in the first trimester may form the basis of a predictive test for subsequent poor pregnancy outcome.

    Conference Organiser - ICMS Pty Ltd