Clinical reviewThe development of cardiovascular and cerebral vascular control in preterm infants
Introduction
Preterm birth, defined as birth prior to 37 wk of gestation, has been steadily increasing in recent years and now accounts for 9.6% of births worldwide, a total of approximately 13 million births annually [1]. The rate of preterm birth is rising due in part to advances in assisted reproduction technology leading to an increase in the number of multiple births and an increase in the number of medically indicated preterm births [2].
Increasing rates of preterm birth are being accompanied by increasing survival rates in infants born prematurely, particularly those born very prematurely. Prior to the introduction of assisted ventilation, antenatal corticosteroids and artificial surfactant, survival rates of infants born prior to 28 wk gestational age (GA) were low. Currently, survival rates for infants born at 22 wk vary from 0 to 12%, increasing to 53–88% at 26 wk GA [3].
However, despite improved survival, prematurity is associated with a range of both short and long-term poor outcomes. At the time of birth, preterm infants are more likely to be growth restricted, exposed to intrauterine inflammation in the form of chorioamnionitis or to have experienced foetal distress, as these are common reasons for preterm labour or early delivery [2]. In the immediate neonatal period, preterm infants are at an increased risk of short-term complications including respiratory distress syndrome, necrotising enterocolitis and intracranial haemorrhage. As a consequence, poor long-term outcomes including neurodevelopmental delay and chronic lung disease are also common in preterm infants [3]. The risk of major medical disability as a result of preterm birth increases significantly with decreasing GA, with one in nine infants born at 23–27 wk GA receiving a disability pension at 19–35 y compared with one in 42 for those born at 34–36 wk GA [4].
Although the major morbidities associated with preterm birth are well documented, the more subtle effects of premature birth on development are largely unexplored. It has been suggested that cardiovascular and central nervous system (CNS) disease may develop later in life as a result of disrupted development following preterm birth [5]. The exact mechanisms resulting in disrupted development remain unclear but are likely to be complex and multifactorial; we suggest impaired vascular control may play a role. As such, this review aims to investigate the influence of premature birth on the development of cardiovascular and cerebral vascular control early in infancy.
Section snippets
Development and control of the cardiovascular system
At term the cardiovascular system is not yet fully mature and maturation continues for several weeks after birth. Mitotic divisions of the myocardium have been found to continue for several weeks after birth and the mechanical performance of the myocardium shows improvement with increasing postnatal age [6]. An additional challenge during this period of rapid cardiovascular development is the transition from intrauterine to extrauterine life which occurs at birth and requires significant
Heart rate
Preterm birth has a considerable effect on cardiovascular parameters including HR and BP. Preterm infants at term-equivalent age have higher resting HRs than infants born at term and this persists up until seven months of age [18], [19]. It has been suggested that while HR is primarily dependent on post-conceptional age, fluctuations in HR are also influenced by postnatal age, with HR in both preterm and term infants peaking between 4 and 10 wk postnatal age [18]. Similar studies have also
Cerebrovascular control
The brain is a highly metabolically active organ, requiring 3.5 ml of oxygen per 100 g of brain tissue per minute which accounts for approximately 15% of the total resting cardiac output. Approximately 60% of the total energy usage of the brain is for generation of continuous electrical activity by neurons. The remaining 40% of energy usage is responsible for homeostatic cellular functions undertaken largely by the supporting cells within the brain. The neuronal component of cerebral energy
Cerebral autoregulation in preterm infants
With the preterm brain being particularly susceptible to haemorrhage and ischaemia, which may be due to fluctuations in CBF, there has been much interest in the ability of preterm infants to regulate their cerebral haemodynamics (Table 1). A number of studies have found that cerebral autoregulation is impaired in preterm infants *[76], [77], [78]. Tsuji et al., found that in 32 infants with gestational ages ranging from 23 to 31 wk, 17 exhibited a high correlation between MAP and HbD, a measure
Long-term cardiovascular outcomes
It is becoming increasingly apparent that infants born preterm are at increased risk of developing cardiovascular disease in adulthood. The theory “foetal origins of adult disease” was first described more the 20 years ago by Barker et al., who found an increased risk of death from ischaemic heart disease amongst adult men who had been born with a low birth weight [108]. They suggested that an adverse intrauterine environment results in increased cardiovascular risk in adulthood due to the
Conclusions
The rate of preterm birth across the world is increasing and due to significant improvements in neonatal intensive care, the survival rates for infants born preterm have increased dramatically. However, despite improved mortality, preterm infants still experience considerable morbidity and are at increased risk for a range of adverse outcomes later in life. Preterm birth is associated with impaired cardiovascular control largely due to immaturity of the ANS which manifests as higher HRs,
Acknowledgements
The authors have no conflicts of interest to declare. Karinna Fyfe is supported by an Australian Postgraduate Award. Stephanie Yiallourou is supported by a project grant from the National Health and Medical Research Council of Australia. Flora Wong is a National Health and Medical Research Council of Australia Health Professional Research Fellow. Rosemary Horne is a National Health and Medical Research Council of Australia Senior Research Fellow. All of the research was supported by the
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Variable Association of Physiologic Changes With Electrographic Seizure-Like Events in Infants Born Preterm
2023, Journal of PediatricsHeart rate surge at respiratory event termination in preterm and term born children with sleep disordered breathing
2023, Sleep MedicineCitation Excerpt :A study of preterm and term born infants reported impaired autonomic control of HR and BP in preterm born infants up to 5–6 months of age, exhibiting reduced parasympathetic modulation of the HR concomitant with greater respiratory-mediated changes and lower sympathetic modulation of blood pressure [42] Very preterm infants (<32 weeks GA) have altered maturation of their baroreflex sensitivity during the first 6 months post-term, resulting in reduced baroreflex sensitivity at 5–6 months (corrected age), which was purported to be driven by reduced parasympathetic activity and may predispose very pre-term infants to cardiovascular disease in adolescence and adulthood [43]. Other studies have also suggested that deficiencies in cardiovascular control seen early in infancy following preterm birth may be early manifestation of long-term impairment (for review see Ref. [44]). Not all respiratory events are associated with an arousal; indeed, in the present study 32% of events in the preterm born children and 16% in the term born children were not associated with arousal during NREM, and 44% (preterm) and 49% (term) during REM.
Gentle as a mother's touch: C-tactile touch promotes autonomic regulation in preterm infants
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