Serial Diurnal Salivary Cortisol Profiles in 667 pregnant women - Association with Cardiometabolic Complications.

CONTEXT:Maternal obesity, hypertensive pregnancy disorders and gestational diabetes (GDM) are linked to an increased risk of negative offspring health outcomes. This association may be mediated by maternal hypothalamic-pituitary-adrenal axis (HPA axis) activity, resulting in elevated maternal cortisol levels and fetal exposure, but evidence remains scarce. OBJECTIVE:We examined (1) maternal diurnal cortisol profiles longitudinally across gestation, and (2) explored associations with maternal cardiometabolic complications. DESIGN:Women in the InTraUterine sampling in early pregnancy (ITU) study (n=667) provided seven salivary cortisol samples from awakening to bedtime up to three times during pregnancy (median gestational week 19.3, 25.7, and 38.1, n=9,356 samples). Changes in cortisol awakening response and diurnal slope (indicative of HPA-axis activity) and their associations with maternal body mass index (BMI), hypertensive pregnancy disorders and GDM were examined using linear mixed models. RESULTS:The cortisol awakening response declined in in 60%-67% of women, and the diurnal slope attenuated from early to late pregnancy (b = 0.006, p = .001). Higher BMI was associated with less decline in cortisol awakening response (b= 0.031, p = .0004), and less attenuation in diurnal slope from early to late pregnancy (b = -0.001, p = .006). Hypertensive pregnancy disorders and GDM were not significantly associated with diurnal cortisol profiles. CONCLUSIONS:The attenuation in cortisol awakening response and diurnal slope support HPA-axis hypo-responsivity during pregnancy. Less attenuation of both markers in women with a higher BMI may indicate reduced adaption of the HPA-axis to pregnancy, presenting a mechanistic link to offspring health outcomes.