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Fetal Hypothalamic-Pituitary-Adrenal Stress Responses to Invasive Procedures Are Independent of Maternal Responses¹

Fetal and Neonatal Stress Research Centre (R.G., N.M.F., J.M.A.T., V.G.), Department of Maternal and Fetal Medicine, Division of Paediatrics, Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Hammersmith Campus, London W12 0NN, United Kingdom; and The Queen Mother’s Hospital (A.C.), Yorkhill, Glasgow G3 8SJ, United Kingdom

Address all correspondence and requests for reprints to: Rachel Gitau, Fetal and Neonatal Stress Research Centre, Department of Maternal and Fetal Medicine, Division of Paediatrics, Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Hammersmith Campus, London W12 0NN, United Kingdom.

Paired fetal and maternal samples were obtained, at fetal blood sampling and intrauterine transfusion, to study hypothalamic-pituitary-adrenal stress responses. This confirmed that the fetus mounts an hypothalamic-pituitary-adrenal stress response to transfusion via the intrahepatic vein, which involves piercing the fetal trunk, but not to transfusion via the placental cord insertion [mean cortisol response via intrahepatic vein = 52.6 nmol/L, 95% CI (25.3–79.9), P = 0.001; mean ß-endorphin response =106 pg/mL, 95% CI (45.3–167), P = 0.002]. Baseline maternal fetal ratios were 13 [95% CI (10.7–15.2)] for cortisol and 0.8 [95% CI (0.5–1.0)] for ß-endorphin. The novel findings were: 1) that the fetal responses were independent of those of the mother, which did not change during transfusion at either site; 2) that there was a correlation between baseline fetal and maternal cortisol levels (r = 0.58, n = 51, P < 0.0001) but not between baseline fetal and maternal ß-endorphin levels, suggesting cortisol transfer across the placenta, rather than joint control by placental CRH; and 3) that fetal ß-endorphin responses were apparent from 18 weeks gestation and independent of gestational age, whereas fetal cortisol responses were apparent from 20 weeks gestation and were dependent on gestational age (y = -91.4 + 5.08x, r = 0.51; n = 16; P = 0.04; CI for slope, 0.16–10.0), consistent with the maturation of the fetal pituitary before the fetal adrenal.

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