**3.2 Gestational diabetes**

Sleep disruptions can exacerbate glucose intolerance. This mechanism can explain why mothers with gestational sleep deprivation during early pregnancy may be up to 4.5 times more likely to develop gestational diabetes than other mothers [32]. Furthermore, mothers with sleep deprivation during pregnancy more frequently give birth to children with a 40% increased risk of overweight and obesity [21].

#### **3.3 Hypertension, pre-eclampsia and eclampsia**

Hypertension and pre-eclampsia present an incidence of 5–10% during pregnancy and they can be identified as the main causes of maternal and perinatal morbidity and mortality [33, 34]. Sleep disturbances during pregnancy have been associated with increased gestational weight gain, which can lead to hypertension, pre-eclampsia, and eclampsia [9, 6, 17, 32]. This risk can be even higher during the last trimester, when the increase in oestrogen levels leads to an increase the development of these complications [7].

#### **3.4 Low birth weight and preterm birth**

The World Health Organisation (WHO) defines low birth weight (LBW) as a birth weight under 2,500 g, very low birth weight (VLBW) as less than 1,500 g and extremely low birth weight (ELBW) as <1,000. Pre-term delivery is the main cause of perinatal morbidity and mortality. It is also the cause of 75% deaths during childbirth and represents half of long-term neonatal morbidity causes [35]. Reduced maternal sleep duration tends to be associated with lower birth weight [36]. Indeed, LBW incidence appears to be lower among sons/daughters born from women who sleep 9-9.9 hours every night, than among those women sleeping 6-7.9 hours [37]. Sleep deprivation during pregnancy is associated with longer labour during childbirth, lower pain threshold and discomfort, higher caesarean section rates, and preterm delivery [36]. These factors can result from the increase of proinflammatory cytokines, such as interleukin-6, promoting the release of prostaglandins that trigger the onset of labour, thus leading to an increased risk of preterm delivery [36]. This is particularly evident among specific populations, i.e., Afro-American women, that show a risk of pre-term birth increased by 10 times in the presence of sleep disorders when compared to those who have good sleep quality [38]. At the same time, babies who were born prematurely cause concern in new mothers,

who will sleep worse and will be more susceptible to postpartum depression [38, 39]. However, further studies on the relationship between sleep and inflammatory markers are needed to better understand their actual correlations [18].

#### **3.5 Morphological alterations and foetal disorders**

An association among maternal breathing disorders during sleep and foetal pathologies is already known, but during recent years specific foetal problems also appeared to be associated with other sleep disorders. Indeed. sleep disorders can lead to altered hormone levels, which can activate pathophysiological mechanisms that cause dysfunctions in offspring [40]. Short sleep duration is associated with an exaggerated inflammatory response, i.e., increased circulating and stimulated levels of inflammatory cytokines and sleep disturbances, particularly during the first 20 weeks of pregnancy, may contribute to the activation of inflammatory processes, also by causing stress, which represents a well-known activator of inflammation [16–18]. This hypothesis is based on *in vitro* data, suggesting that an increase in cytokine levels inhibits trophoblast invasion, that would result in subsequent disruption of maternal vascular bed and placental remodelling, an abnormality present in pre-eclampsia, premature birth, and pregnancies with intrauterine growth retardation [18]. Sleep deprivation during the last week of pregnancy caused reductions in the number of nephrons and increased blood pressure in the offspring [41]. Furthermore, gestational sleep deprivation may be associated with an increased risk of overweight and higher blood pressure in offspring up to the age of 11 years, with more pronounced effects in girls than boys [32].
