Development of the circadian system in early life: maternal and environmental factors

Abstract

In humans, an adaptable internal biological system generates circadian rhythms that maintain synchronicity of behavior and physiology with the changing demands of the 24-h environment. Development of the circadian system begins in utero and continues throughout the first few years of life. Maturation of the clock can be measured through sleep/wake patterns and hormone secretion. Circadian rhythms, by definition, can persist in the absence of environmental input; however, their ability to adjust to external time cues is vital for adaptation and entrainment to the environment. The significance of these external factors that influence the emergence of a stable circadian clock in the first years of life remain poorly understood. Infants raised in our post-modern world face adverse external circadian signals, such as artificial light and mistimed hormonal cues via breast milk, which may increase interference with the physiological mechanisms that promote circadian synchronization. This review describes the very early developmental stages of the clock and common circadian misalignment scenarios that make the developing circadian system more susceptible to conflicting time cues and temporal disorder between the maternal, fetal, infant, and peripheral clocks.

Precision caffeine therapy for apnea of prematurity and circadian rhythms: New possibilities open up

“…It is well understood that the sleep homeostasis in humans are regulated by two independent but synergistic processes (Borbély, 1982;Deboer, 2018): a Clock-dependent circadian process (Process C), controlled by the SCN circadian oscillator, determines the alternation of different sleep propensity (Cremer et al, 2016); and a Sleep-dependent homeostatic process (Process S) that is determined by the prior sleep pressure, which comes from the adenosine buildup in the basal forebrain during wakefulness (Deboer, 2018;Wong et al, 2022). However, due to the immature development of the central nervous system, especially the SCN, Process C and Process S are not stably present in preterm infants or even in term ones (Salzarulo and Fagioli, 1992;Schwichtenberg et al, 2016).…”

“…In human fetus, circadian rhythms in several physiological and endocrine functions, including heart rate ( Lunshof et al, 1998 ), breathing patterns ( Patrick and Challis, 1980 ), limb movements ( Einspieler et al, 2021 ), sleep-wake states ( Peirano et al, 2003 ; Bennet et al, 2018 ), and hormone levels ( Serón-Ferré et al, 2001a ) have been detected at different stages of pregnancy ( Seron-Ferre et al, 2007 ; Du Pre et al, 2014 ; Wong et al, 2022 ). Impressively, Frigato et al (2009) , first observed the rhythmic expression of clock genes such as Per2 in the HTR-8/SVneo cells derived from human extravillous trophoblast.…”

“…After birth, neonates immediately begin to establish their own physical and physiological independence while losing the protect of the maternal-placental barrier ( Joseph et al, 2015 ; Wong et al, 2022 ). From now on, the ontogenesis of the newborn begins to be greatly affected by the external environment ( Brooks and Canal, 2013 ; Hazelhoff et al, 2021 ).…”

“…The second thing to be discussed is the maternal care, primarily maternal feeding, but it is still the roles of hormones in nature ( Löhr and Siegmund, 1999 ; Nishihara et al, 2002 ; Park et al, 2020 ). Various hormones in breast milk, such as glucocorticoids and melatonin, can be absorbed and transferred into the neonatal circulation through the gastrointestinal tract ( Arslanoglu et al, 2012 ; Wong et al, 2022 ). Interestingly, the cortisol and cortisone concentrations in breast milk follow the circadian of maternal HPA axis activity ( van der Voorn et al, 2016 ; Italianer et al, 2020 ).…”

Effect of a standardized maternal meal on fetal middle cerebral artery Doppler indices: A single-blinded crossover study

“…In utero, maternal circadian signals (e.g., melatonin, cortisol, temperature) seem to be an important factor for fetal circadian systems and peripheral clocks [10]. The fetal-uteroplacental circulation represents a complex system with maternal, fetal and placental physiological features that can affect fetal Doppler blood flow velocity indices [11][12][13][14][15].…”