**4. Insights into the most common sleep disorders during pregnancy**

The following is a description of the most common psychiatric disorders that can be found in pregnant women. Undoubtedly, the most common disorder is insomnia [42], but other disorders such as restless legs syndrome and narcolepsy are should also be considered in order to preserve the health of both mothers and children. Respiratory disorders, such as sleep apnoea syndrome and snoring, may also be encountered during pregnancy [9]; these disorders are not of direct psychiatric interest, but can be differentially diagnosed from other sleep disorders and can sometimes be the cause for these (as in the case of insomnia) and therefore require specialist monitoring [10].

### **4.1 Insomnia**

#### *4.1.1 Definition, predisposing factors and epidemiology*

Recent classifications listed in the Diagnostic and Statistical Manual-5th Edition (DSM-5) [43] and in the International Classification of Sleep Disorder- Third Edition (ICSD-3) [44] deleted the distinction between primary and secondary insomnia (that is, dependent on other medical and mental disorders) in favour of a single diagnostic category. Insomnia is defined whether as an independent diagnostic entity or as a comorbidity of other mental, medical, and sleep disorders without the need to establish causal relationships. Spielmann et al. in 1987 proposed the diathesis-stress model of insomnia, which relies on the conceptualisation of the 3P model: predisposing, precipitating and perpetuating factors contribute to the development and maintenance of insomnia [27, 45]. Predisposing factors are already present before the onset of insomnia. Female sex, pre-menstrual syndrome, pregnancy,

#### *Sleep Disorders in Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.100300*

post-partum, and menopause may influence the risk of developing insomnia. Moreover, reduced melatonin levels, which may be inversely related to gonadotropin secretion, play a relevant role. Anyway, the main of these is represented by sleep vulnerability in response to stress, namely sleeping difficulty due to stressful precipitating stimuli [46]. Furthermore, internalisation, perfectionism, obsessive, neurotic, and dependent personality traits are other factors that may contribute to these effects [47–49]. All this explains particular sleep vulnerability in pregnancy, both because pregnancy itself is a predisposing factor, but also since stress and sex hormones interfere with sleep [16, 17, 50]*.* Among precipitating factors, there are mechanisms that promote higher likelihood of developing sleep disorders, thus determining the transition from pre-morbid insomnia to acute insomnia. If these disturbing factors are not eliminated, early insomnia may evolve into a chronic form*.* The main among these precipitating factors are: stress, health problems, pain, anxiety, mood lowering [45].

Insomnia in pregnancy has a prevalence from 5–38% of women in early pregnancy, and it is reported as high as 60% in the eight weeks before the childbirth [7, 9]. Pregnancy is a period characterised by worries, fears and doubts about the health of the baby and this can be a precipitating factor of insomnia as well. As for perpetuating factors, these are mainly represented by behavioural, cognitive and physiological factors that persist in subjects already presenting with insomnia and may lead to chronic insomnia in 80% cases, such as drinking caffeinated beverages in the evening or engaging in stressful activities while lying in bed [45, 51]. Pregnant women with predisposing factors for insomnia and some neuroendocrine alterations can develop precipitating factors, increasing both inflammation modulating factors and amplifying hypothalamic–pituitary–adrenal axis with activation of allostatic load that can cause adverse pregnancy outcomes [16, 17]. Sleep also plays a fundamental role in learning through new neuronal circuits development, and sleep restriction can thus lead to a disruption of neuroplasticity and to the development of the pathological mechanism of depression, given the correlation between the two systems. Therefore, insomnia may compromise adequate emotional processing and may predispose to greater susceptibility to the development of psychiatric symptoms, such as anxiety, depression and, to a lesser extent, psychosis and substance or alcohol abuse [26].

Insomnia in pregnancy can be differentially diagnosed with various disorders that may in turn be comorbidities, causes or consequences of insomnia. The adequate identification of insomnia, as well as other comorbidities, is crucial in order to. The conditions that may underpin differential diagnosis issues with insomnia are the following: Major Depressive Disorder (MDD); Bipolar Disorder (BD); Generalised Anxiety Disorder (GAD); Post-Traumatic Stress Disorder (PTSD); Panic Disorder (PD); Obsessive Compulsive Disorder (OCD); Obstructive Sleep Apnea-Hypopnea (OSAH*)*; Restless Leg Syndrome (RLS) [42].

#### *4.1.2 Pathophysiological mechanisms underlying the development of insomnia during pregnancy*

Hormonal changes are the most important factors influencing duration, quality, and physiology of sleep. The action of sex hormones in sleep could be observed in preclinical studies conducted on ovariectomised rats [52]. Steroid hormones, namely oestrogen and progesterone, increase during pregnancy with different and often complementary effects on sleep and respiratory physiology. The early increase in progesterone during the first trimester improves slow-wave sleep and activity through induction of GABA receptors. Indeed, allopregnanolone, a metabolite of progesterone, is a strong modulator of the GABA-A receptor and produces sedative

and anxiolytic effects. Progesterone acts as a stimulant of the respiratory drive, as in obese women, increasing the activity of the genioglossus muscle, thereby dilating the diameter of the upper airways. Counterpart to this protective effect against obstructive sleep apnoea (OSA) may be an increased risk of central apnoea, due to hormone-induced re-setting of chemoreceptors that favours hyperventilation/ hypocapnia coupling, as well as an increased pressor response to hypercapnia and apnoea [10, 23, 53, 54]. Literature shows that high levels of oestrogens promote sleep [55]. At the same time, some studies report that during the luteal phase of the menstrual cycle (the phase where progesterone levels evidently increase) some women may experience worse sleep [56, 57]. Low levels of oestradiol (E2) due, for example, to lower ovarian production, are associated with worst sleep quality and higher prevalence of insomnia [58]. Studies in rats that were administered oestradiol after sleep deprivation have shown variable results, as sleep worsened according to some authors, while according to others sleep recovery could be facilitated [59]. In postmenopausal women that were given hormone replacement therapy with oestrogen, a subjective improvement in sleep was detected, whether oestrogen was administered orally or transdermal, or when combined with progestin [60, 61]. Different results from several reports may be consequence of a different individual sleep responses to sex hormones activities [55].

#### *4.1.3 Treatment for insomnia*

For ethical reasons, investigational drugs are never tested on pregnant women and literature focused on treatments for this population is scant. However, some reports seem to provide preliminary answers. Approximately 1% of women use melatonin during pregnancy. Melatonin is not monitored by the Food and Drug Administration and therefore doses and timing of administration are not wellknown or regulated yet [62, 63]. Maternal melatonin is required to synchronise foetal circadian rhythms, but an alteration in endogenous production, including external administration, could alter the amount of melatonin receptors in the foetus. In fact, clinical studies on its use during pregnancy are inconclusive and conflicting [64] Some studies show that melatonin does not cause adverse effects in the offspring and it and may have a protective activity due to its antioxidant properties. Particularly, a study conducted in 2016 showed that prenatal treatment with melatonin significantly reduced neonatal biometry and birth weight [65]. In addition, melatonin treatment increased the duration of gestation by 7.5% and shifted childbirth time, also reducing glucose tolerance and altering hormone levels [19]. Subsequently, the use of melatonin in pregnancy is currently discouraged until more reliable data are available [63]. Although there are concerns about the administration of exogenous melatonin in pregnancy and its impact on the development of circadian rhythms and reproductive function in offspring, exogenous melatonin may also have some potential protective effects on the foetus [9].

Among the drugs most safely used in pregnancy antihistamines are listed, which are used by 10-15% of pregnant women for nausea and vomiting, and which also present sedative effects, so these properties seem to be useful for insomnia treatment [10, 63]. Trazodone can also be proposed as a sedative drug during pregnancy [10, 30] since some studies exclude an association with congenital malformations, although literature is limited [42]. Sedative-hypnotics such as zolpidem have limited data on reproductive safety and therefore their use in pregnancy is limited [33]. However, benzodiazepines can be considered for treatment during pregnancy, taking into account the risk/benefit ratio [9, 42].

Insomnia can be treated both with medication and non-pharmacological treatments. Short-duration and self-limited conditions may not need to be treated,

#### *Sleep Disorders in Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.100300*

whilst if the disorders are debilitating, it is necessary to assess maternal or foetal adverse effects and impact on quality of life [9].

Pregnant women are reluctant to the assumption of drugs, due to the fear of adverse events on the foetus. For these reasons, women are willing to accept nonpharmacological treatments such as cognitive behavioural therapy (CBT), for which promising results are demonstrated [66, 67]. Further non-pharmacological interventions, such as sleep restriction, stimulus control, relaxation techniques, sleep hygiene and sleep education led to a subjective improvement in sleep quality as well as subclinical anxiety and depressive symptoms [9].

## **4.2 Disorders of circadian sleep–wake rhythms in pregnancy**

#### *4.2.1 Definition and prevalence*

According to DSM-5, the diagnostic criteria for circadian sleep–wake rhythm disorders are: persistent or recurrent pattern of sleep disruption due mainly to an alteration of the circadian system or a mismatch between endogenous circadian rhythm and the sleep–wake rhythm required by an individual's physical condition or imposed by social or work commitments; sleep disruption leads to excessive sleepiness, insomnia or both and sleep disruption causes clinically significant distress or impaired functioning in cognitive, social, occupational or other important areas. The prevalence of circadian rhythms disorders is about 3-10% [68].
