Measurement of cardiovascular parameters in neonates – value and recent knowledge

Summary

Postnatal transition is a complex process predominantly affecting cardiovascular and respiratory system immediately after birth. This includes spontaneous and regular breathing and physiological, as well as anatomical cardiovascular changes.

Technological progress offers new possibilities for monitoring of vital signs more effectively and non-invasively. Heart rate is the most useful parameter reflecting the course of immediate postnatal adaptation and together with blood oxygen saturations belong to standard monitoring of adaptation process. New technologies, such as heart rate variability and near-infrared spectroscopy have been recently implemented into neonatal clinical research and practice.

Better understanding of physiology and pathophysiology of postnatal adaptation mechanisms can help the practitioners to adjust preventative and therapeutic interventions and minimize their adverse effects, especially in preterm babies. Recent data about cardiovascular and haemodynamic monitoring during the early postnatal and neonatal period is presented in this article.

Key words:
postnatal adaptation, heart rate, heart rate variability, blood pressure, blood oxygen saturation, tissue oxygenation

INTRODUCTION

Transition to extrauterine life after delivery is characterized by physiological changes in cardiovascular and respiratory system initiated by umbilical cord clamping, functional changes in arrangement of blood circulation and breathing. Cord clamping causes a decrease in cardiac preload and a rise in systemic vascular resistance. These events result in sudden blood flow changes through both intracardial and extracardial shunts leading to functional closure of these structures and separation of pulmonary and systemic circulation [1]. Lung aeration causes reduction of pulmonary vascular resistance and subsequently leads to increased pulmonary blood flow. Postnatal adaptation of premature infants is very often compromised and most of the difficulties start early after birth. Maladaptation in preterm babies results mainly from anatomical and functional immaturity of organs and systems but concomitant factors, such as infection, can be present.

Majority of our knowledge about neonatal transition is based on clinical studies from the 70´s and information derived from animal experiments [1]. Currently, methodological progress in medicine allows for the application of new non-invasive and more precise technologies. Modern approaches are useful in acquisition of information about physiological adaptation processes and in understanding of pathophysiological conditions, thus improving the neonatal care.

This article aims to present current knowledge on possibilities of cardiovascular and haemodynamic monitoring and their role in evaluation of the transition process in the early neonatal period.

HEART RATE

Heart rate (HR) is the most sensitive parameter reflect-ing postnatal adaptation. There are several methods for HR monitoring including auscultation, electrocardiography (ECG), pulse oximetry (PO), and Doppler ultrasound. ECG is the gold standard in HR monitoring and provides signals superior to PO [2]. However, PO is more suitable for monitoring early after birth because at the same time it also provides information about blood oxygen satura-tion (SpO₂). According to the resuscitation guidelines [3], continuous monitoring of SpO₂ as well as HR using PO in the delivery room is recommended. Doppler ultrasound for HR monitoring in newborns seems to be promising but needs further investigations [4].

Worldwide accepted HR limit 100 beats per minute has been established long time ago [5]. If HR is lower, the resuscitation guidelines suggest initiation of respiratory support [3]. Nevertheless, transient bradycardia can be also present in healthy full-term neonates shortly after birth followed by a rapid increase of HR [1]. The main cause of this bradycardia is vagal inhibition mediated by transient hypoxia. Another cause is umbilical cord clamping before the onset of breathing leading to delayed decrease of pulmonary vascular resistance and therefore slower increase in left cardiac preload [1, 6].

Several papers have been published concerning HR monitoring early after birth [7, 8]. In 2010, reference ranges for healthy term and preterm neonates without the need of any intervention within the first 10 minutes of life have been published [9] (Table 1). It has been also found that HR increase is slower in preterm when compared to term infants [9]. Similar values of HR in term babies have been presented in another study [10].

Changes in HR after birth are affected by mode of delivery and maternal anaesthesia. Several studies showed that spontaneously delivered newborns had significantly higher HR compared to neonates born by caesarean section and with maternal epidural analgesia (EDA) administration [8, 9]. Most likely the cause is the effect of medication administration [9] and lower delivery stress. In contrast, previously published work presented significantly higher initial HR in spontaneously born neonates with EDA compared to neonates without administration of maternal analgesia. However, duration of higher HR in EDA group was 10 minutes after birth only [8].

In our clinical study consisting of 46 healthy full-term newborns HR was measured between the first and third hour after birth. No significant differences in HR according to the mode of delivery (normal vaginal delivery, EDA group, caesarean section group) were observed [11].

Recently, delayed umbilical cord clamping has been implemented into neonatal care with beneficial impact, especially in preterms. This procedure affects the cardiovascular system adaptation process, which is now of high research interest. The latest study reported that delayed cord clamping results in lower HR and a slower rise of HR [12]. Similar results were published also by other authors [13].

Further changes in HR values after immediate postnatal transition are affected by many other factors. In term newborns HR declines as the postnatal age increases, whereas in preterm babies the mean HR remains higher for longer time. During the first 4 days of life a significant decrease in mean HR values, especially during the second day, has been observed in term newborns [14]. In healthy preterm neonates an increase in mean HR after the first day of life until to the end of the first week was found [15].

HEART RATE VARIABILITY

Heart rate variability (HRV) is characterized by short-lasting oscillations of HR around the baseline. HRV recording can be performed in two ways. Short-term variability is based on 5-minute beat-to-beat record and long term variability uses 24 hours Holter recording. There are several methods of the HRV analysis, the most common being the time and frequency domain processing. The data sampling and processing is non-invasive and reproducible in individual subjects [16]. Evaluation of the HR provides information about dynamic balance of autonomic nervous system (ANS) in the chronotropic cardiac regulation. HRV evaluation can also be useful for assessment of the ANS maturation, of the regulation of the cardiovascular system as well as for early detection of various disorders, cardiac dysregulation and diseases even before the onset of clinical manifestation.

The data about changes of HRV parameters shortly after birth is sparse. There is only one paper focused on HRV measuring during the first hours of postnatal life in healthy term newborns [17]. In this study, spectral analysis showed significantly higher low-frequency (LF) as well as high-frequency (HF) parameters at 30 mi-nutes after delivery followed by sudden decrease at first hour of life and subsequent progressive increase within following 4 hours. HF band values reflecting vagal activity were lower than LF band values during the entire time of measurement. HRV tends to increase rapidly after transition period; this is caused by reduction of delivery stress, accelerated maturation of heart regulation and by respiratory movements [18]. Reference HRV values obtained by time and spectral analysis for full-term healthy neonates within the first three days of life were published a long time ago [19]. In contrast to term newborns, preterm babies had significantly lower HRV resulting from immaturity of autonomic nervous system [16].

Our results showed predominance of sympathetic activity in surgically delivered mature babies with higher LF power compared to vaginally born newborns. This was most likely secondary to the effect of maternal anaesthesia. In contrast, vaginally delivered babies regardless of the analgesia use, had higher absolute and relative HF power as a sign of better parasympathetic regulation [11].

Reduction in HRV parameters is an indicator of degree of hypoxia and severity of hypoxic-ischemic encephalopathy [20] and accompanies deterioration of clinical status in conditions such as respiratory distress syndrome [21] and sepsis [22] among the others. According to these findings the HeRO (heart rate observation) monitor using scoring system based on heart rate characteristic (HRC) was developed as a suitable tool for implementation into clinical practice [23]. HRC is based on detection of decreased HRV and transient bradycardia and both are calculated into the HRC index and displayed on HeRO monitor as HeRO score. This number score represents the risk of clinical deterioration in the next 24 hours (higher number means higher risk). HeRO was originally developed as an early warning system for sepsis in preterm infants in the neonatal intensive care unit (NICU), nevertheless, this device has a potential to identify more pathologies, e.g. necrotizing enterocolitis, central nervous system impairment and others [23]. Randomized clinical trial showed a significantly lower mortality rate in preterm neonates with HRC based therapeutic interventions [24].

Similarly to HR, HRV is also affected by many other factors which can modulate HRV for a long time periods, maybe even lifetime. Recent study showed that infants born to women who participated in regular physical activity during pregnancy continued to have higher HRV during the whole infancy [25]. Other study reported lower HRV parameters in children born prematurely as well as in small for gestational age infants (SGA) when compared to term and appropriate for gestational age (AGA) controls [26]. It has been found that SGA newborns differed from AGA newborns by shorter RR intervals on ECG, resulting in higher mean HR and reduced HRV in all bands [27]. Similar results with a tendency to higher mean heart rate in SGA newborns were reported by another study [28]. Autonomic nervous system is an important regulator of metabolism and energy balance. SGA infants have higher metabolic rate per kilogram of body weight and these factors may explain the higher HR in SGA newborns. The results of time and spectral frequency analysis of the HRV on the 1st and 4th postnatal days have shown no differences between SGA and AGA newborns. However, significant differences in HRV during the first day of life were found between these two groups by sequence plot method [18]. Abovementioned and other similar studies regarding maturation of the ANS indicate a great potential of HRV evaluation.

BLOOD PRESSURE

Blood pressure (BP) is determined by cardiac output and systemic vascular resistance. It is an important haemodynamic indicator especially in critically ill newborns, despite the fact, that after birth BP does not fully correlate with perfusion of peripheral tissues [1]. Hypotension in neonates may be the first symptom of developing pathology, such as sepsis, internal bleeding and others. BP is monitored routinely in neonatal intensive care unit (NICU). In critically ill neonates, an indwelling arterial catheter is usually inserted for continuous and accurate BP monitoring. An oscillometric method is used for non-invasive BP measurement, although it is sensitive to motion artefacts. However, there is good correlation between oscillometric and invasive methods with the exception of blood pressure values at the lower limit [29]. Another possibility of non-invasive beat-to-beat BP recording is a volume-clamp method [30], which was originally developed for adult patients and later modified for use in paediatrics and neonatology. Results of several studies proved relevance and validity of this modified method in comparison to invasive monitoring [31, 32].

Several papers concerning BP changes in immediate postnatal period with establishment of reference values have been published in previous years [33, 34, 35]. Higher BP values early after birth have been observed in neonates born vaginally compared to surgical delivery [33, 34] and after vaginal delivery with EDA with exception of systolic BP [11]. Besides determining the reference ranges (Table 1) higher BP in newborns after receiving delayed umbilical cord clamping has been observed [34]. Same paper refers that preterm infants receiving continuous positive pressure ventilation (CPAP) in delivery room had significantly higher BP compared to those receiving intermittent positive pressure ventilation (IPPV) [34]. Further research focused on the impact of delayed umbilical cord clamping and different modes of ventilatory support on later BP development seems interesting. Another important and poorly understood issue is the relation between hypotension and cerebral perfusion, especially in preterm babies. It seems that mild short-term hypotensive episodes in preterm infants after birth with borderline hypotension (mean blood pressure value equal to gestational age) do not alter cerebral perfusion significantly but further research is required [36].

Results of many clinical studies showed rapid BP in-crease during the first seven postnatal days [37]. This rise reflects haemodynamic changes resulting from functional cardiovascular system remodelling, elevation of vascular resistance, changes in humoral substances level, stabilization of fluid balance, maturation of regulatory mechanisms and also environmental factors among many others [38]. Standard values of BP in the first days of life in very low birth weight neonates have been published [39] as well as standard values in preterm [40, 41] and full-term [41] babies for longer time period. BP values in healthy preterm babies tend to stabilize after 14 days of postnatal life and since that time they are similar to those of term infants [40].

In clinical practice the evaluation of haemodynamic status is based mainly on the mean blood pressure, though there are many controversies about its acceptable lower limit value and optimal therapy. There is still little knowledge about BP characteristic, its variability, baroreflex sensitivity and other regulatory mechanisms in newborns, especially in preterm ones. All this data is essential for more complete understanding of physiology and pathophysiology during the transition into extrauterine life.

BLOOD OXYGEN SATURATION

Pulse oximetry (PO) is a method of continuous and non-invasive monitoring of blood oxygen saturation (SpO₂) together with HR. It is included in the standard monitoring methods in NICUs. In the delivery room a preductal SpO₂ monitoring acquired from the right upper extremity provides information about cerebral oxygen supply. Recent resuscitation guidelines outline the use of the PO in the delivery room [3].

The level of SpO₂ during intrauterine life is approximately 60% and can be even lower immediately after delivery [42]. Every newborn experiences a time period of physiological transient cyanosis during transition [43]. SpO₂ monitoring after birth in preterm or compromised term newborns is important for appropriate preventative management and therapy. Several studies described SpO₂ values early after birth in term and preterm neonates [42, 43]. Standard values of SpO₂ within the first minutes of postnatal life according to the gestational ages have been presented and recommended for clinical practice [42] (Table 1). Higher SpO₂ immediately after delivery were observed in term versus preterm infants [42] as well as in extremely premature neonates requiring CPAP only versus those in need of IPPV who also required much higher inspiratory fraction of oxygen [44]. Blood oxygen saturation is also affected by the mode of delivery [42]. Lower SpO₂ in surgically born newborns results most likely from the absence of spontaneous delivery mechanisms and delayed pulmonary fluid elimination and reabsorption [38]. In our clinical study no significant differences in SpO₂ were observed in healthy term babies according to the mode of delivery at approximately three hours after birth [11].

Several papers reported significantly lower postductal versus preductal SpO₂ early after birth [45, 46]. It has been shown that except for some neonates with complex or duct dependent congenital heart disease and with persistent pulmonary hypertension there was no difference comparing the left vs. right hand SpO₂. Therefore left hand SpO₂ can be considered equally preductal [46]. Another interesting finding was the deterioration of acid-base parameters and oxygen saturation values after delayed umbilical cord clamping in term babies [47]. However, this effect seems to be transient.

Both preductal and postductal SpO₂ values should exceed 95% in term healthy newborns after transition period. If desaturation persists, further investigation is required to exclude pathology, especially congenital heart defects. Screening for congenital heart defects using PO shows high negative predictive value. To minimize the false positive results PO screening is recommended after the first 24 postnatal hours [48]. The nomograms of preductal and postductal SpO₂ at 24 hours of postnatal life in term asymptomatic newborns have been published recently [49]. Such nomograms are important for clinicians to optimize screening thresholds and methodology for detection of congenital heart defects.

Determination of optimal SpO₂ values in preterm neonates requiring ventilation support and oxygen therapy is still a topical issue. Several multicentre randomized studies aimed to establish SpO₂ range in this vulnerable group of newborns in order to avoid hypoxia or hyperoxia and resulting consequences. The latest meta-analysis of 5 major multicentre trials showed lower mortality in newborns with higher oxygen values (91–95%) than in infants with a lower oxygen target (85–89%), but with low quality of evidence. Necrotizing enterocolitis occurred less frequently in the higher SpO₂ group, whereas no difference in retinopathy of prematurity, bronchopulmonary dysplasia and other adverse outcome was found [50]. In conclusion, at present no optimal range of SpO₂ for extremely preterm neonates has been established. American Academy of Paediatrics recommends using oxygen therapy to keep SpO₂ in the 85% to 95% range. Further research using more precise methodology is needed to clarify this issue [51].

TISSUE OXYGEN SATURATION

Near-infrared spectroscopy (NIRS) is a technique designed for continuous non-invasive monitoring of tissue and organ oxygenation. This method provides information about selected tissue oxygenation in the arteriolar, capillary and venular compartment. Therefore, changes in tissue oxygenation can be due to changes in oxygen delivery, oxygen consumption or both [52]. In neonatal practice, it is used mainly for evaluation of regional cerebral oxygenation (rcSO₂) but it can be used for renal and splanchnic oxygenation monitoring as well. The most widely used NIRS devices in neonates are the NIRO 300 (Hamamatsu, Japan), the Invos TM (Somanetics, USA) and the FORE-SIGHT (Casmed, USA). Differences in determined rcSO₂ values after the transition period among these devices are up to 10%. This has to be taken into account when using reference ranges or limits [52]. The differences in the values measured by various devices during the first minutes after birth are smaller and they are within a range of 2–3% [53]. However, in another study [54] the difference in the low area oxygenation (rcSO₂ below 50%) was more than 20% between Invos and FORE-SIGHT devices [54]. Food and Drug Administration (FDA) approved Invos as the trend cerebral oxygenation monitor, whereas FORE-SIGHT is considered to be a cerebral oximeter with relevant absolute values [55]. Recently, new generation of FORE-SIGHT (Elite Tissue Oximeter) representing the most advanced NIRS device providing better accuracy of tissue oxygenation measurement has been introduced into clinical practice.

Interest in continuous monitoring of rcSO₂ during the early neonatal period rises. In term neonates, a rapid increase in rcSO₂ within the first minutes after delivery was reported with stabilization after 7–8 minutes, earlier than peripheral tissue oxygen saturation. The same time course was observed for cerebral fractional tissue oxygen extraction (FTOE) in comparison with peripheral FTOE [56]. These findings confirm predominant oxygen delivery to the brain due to a rise in cerebral blood flow in the first minutes after birth at the expense of organs like kidneys and splanchnic tissue [57]. Mode of delivery does not affect rcSO₂, although significantly lower values of SpO₂ and HR have been described in newborns delivered by ceasarean section [58]. The explanation for similar rcSO₂ in both groups of neonates regardless of the mode of delivery is most likely due to cerebro-vascular autoregulation. It was an interesting finding that infants with a left-to-right shunt via the ductus arteriosus had higher rcSO₂ than infants without a shunt 15 min after birth. This fact is most likely the result of transient period of reduced left ventricular output in neonates without presence of left-to-right shunt, which affects cerebral blood flow [59].

Reference values of cerebral tissue oxygenation and cerebral FTOE in term and preterm neonates requiring no medical support during transition immediately after birth were recently reported with no significant difference between term and preterm neonates [60]. There is some evidence about significantly lower values of rcSO₂ in preterm neonates requiring ventilation support versus neonates without resuscitation interventions in the delivery room. In compromised babies cerebral FTOE was significantly elevated as the compensatory mechanism for lower cerebral oxygen delivery [61].

Changes of rcSO₂ occur within several days after birth in both term and preterm newborns. These changes presumably reflect progressive maturation of regulatory mechanisms of oxygen delivery and utilization in tissues. Standard values of rcSO₂ for term infants within the first three days of life are between 64 to 89% [62]. Normal reference ranges for preterm newborns in the same time period have been established between 55–85% depending on several factors (monitoring methods, postnatal age, clinical condition) [63]. Higher rcSO₂ and simultaneously lower FTOE were observed in stable healthy preterm compared with term infants during the first day of life [64].

Recent study evaluated an impact of hypotension and rcSO₂ on neurodevelopmental outcome in preterm babies. Results showed that lower rcSO₂ (below 50%) were associated with worse outcome regardless of the presence of hypotension [65]. This suggests a great importance of complex perfusion / oxygenation variables in preterm newborns. RcSO₂ monitoring is also useful tool for identification of patients with hypoxic-ischemic brain injury with close MRI correlation [66]. Splanchnic tissue oxygenation (rsSO₂) together with splanchnic-cerebral oxygenation ratio (SCOR) is valuable parameter in identifying pathological conditions manifested with altered splanchnic perfusion in preterm infants [67].

Regional tissue oxygenation using NIRS technology is a marker of early organ dysfunction. It has the potential to predict adverse short – and long – term outcomes in critically ill neonates. Although NIRS is a promising technique for monitoring neonates in NICUs, large population-based reference data is lacking. Further studies are needed to establish absolute standard values in neonates [66].

CONCLUSIONS

Valuable data about physiological-cardiorespiratory processes during transition period have been published during the last few years. These findings could be helpful for understanding cardiovascular changes after delivery and for adjustment of therapeutic interventions. Standard values of described cardiovascular and haemo-dynamic parameters have been established for this purpose. More precise and non-invasive technologies, such as HRV and NIRS evaluation allow clinicians to detect various pathological conditions before their clinical manifestation, which is crucial for optimization of therapy and better outcome of individual newborn patients.

This article was supported by grants VEGA 1/0100/15, 1/0202/16 and APVV-0235-12.

Došlo: 12. 4. 2016

Přijato: 4. 6. 2016

Corresponding author:

Doc. MUDr. Katarína Maťašová, PhD.

Clinic of Neonatology

Jessenius Medical Faculty and University Hospital in Martin

Kollarova 2

036 01 Martin

Slovakia