Article Text
Abstract
Background Women of advanced maternal age (AMA; ≥35 years) have increased risk of fetal growth restriction and stillbirth. The aetiology is unknown; however both conditions are linked with placental dysfunction, including reduced nutrient transport and altered placental morphology. Ageing is associated with increased systemic inflammation; whether this contributes to poor pregnancy outcome is unknown. We hypothesise an ageing maternal environment adversely affects placental function, resulting in poor pregnancy outcome.
Methods Women (20–30, 35–39 and ≥40 years) with singleton pregnancies are being recruited to MAMAS. Maternal serum samples are collected at 28 and 36 weeks gestation for measurement of inflammatory markers by ELISA. Placental function is assessed by amino acid uptake by placental villous tissue. Placental morphology was quantified by density of Syncytial Nuclear Aggregates (SNA’s), fetal capillaries and quantification of proliferation.
Results Preliminary ELISA analysis of 40 samples revealed lower anti-inflammatory cytokine interleukin-10 (IL-10) in maternal serum of women ≥35 (p = 0.016, Kruskal-Wallis test). Other cytokines were unchanged. Preliminary data suggests higher placental uptake of taurine in women ≥35, but system A activity appears unaltered. SNA’s were increased, but vascularity and proliferation were unchanged in placentas from women ≥35 (p < 0.05 Kruskal-Wallis test).
Conclusion MAMAS is the only prospective observational study investigating AMA and placental function. Preliminary data indicate accelerated placental ageing with increased SNA and an altered maternal environment with reduced anti-inflammatory cytokines. Understanding the mechanisms underlying AMA and pregnancy complications may help improve outcome for these women. Measuring circulating biomarkers of ageing prenatally may enable detection of high risk pregnancies.