*4.2.2 Pathophysiological mechanisms of circadian sleep–wake rhythm disorders in pregnancy.*

Circadian rhythms that may be altered as consequence of sleep–wake disorders are: body temperature, physical activities, eating patterns, melatonin and glucocorticoids secretion [14]. The activation of this system occurs through the action of light, which activates photoreceptive cells in the retina that produce melanopsin and through the retino-hypothalamic tract projected to the suprachiasmatic nucleus of the hypothalamus, regulating various pathways. Alterations in circadian rhythms are known to occur in depressed patients. Indeed, this population of subjects can present abnormalities in the secretion of cortisol, TSH and melatonin, as well as increased internal body temperature at night. Furthermore, there is a clear worsening of depressive symptoms with darkness, which may be clearly evident in seasonal affective disorder, as light therapy is effective in circadian rhythms disorder and SAD [14, 69, 70]. Of particular importance is the interaction between maternal melatonin and glucocorticoid secretion and effects in the foetus [71], as melatonin has a pleiotropic biological action with consequent antioxidant, antidepressant, antihypertensive, epigenetic, and trophic effects on the foetus [72, 73]. At the same time, increased cortisol leads to elevated levels of glucocorticoids and if these are excessive could interfere with foetal tissue [74].

#### *4.2.3 Main clinical manifestations in pregnancy.*

Pregnant women may also be affected by circadian rhythms disorders and in this case, in addition to the mood disorders mentioned above, they may present with other pathological conditions and the effects of these alterations are clearly evident in shift workers, who have a higher risk of low birth weight, spontaneous abortion and premature birth, but also a higher risk of infertility, miscarriage, pre-eclampsia [7, 14, 15]. In pregnant rats subjected to altered sleep–wake rhythms an increase of adiposity may occur, together with impaired glucose tolerance, and insulin resistance manifesting in offspring 12 months later [75].
