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Technology in the delivery room supporting the neonatal healthcare provider's task

Open AccessPublished:March 31, 2022DOI:https://doi.org/10.1016/j.siny.2022.101333

      Abstract

      Very preterm infants are a unique and highly vulnerable group of patients that have a narrow physiological margin within which interventions are safe and effective. The increased understanding of the foetal to neonatal transition marks the intricacy of the rapid and major physiological changes that take place, making delivery room stabilisation and resuscitation an increasingly complex and sophisticated activity for caregivers to perform. While modern, automated technologies are progressively implemented in the neonatal intensive care unit (NICU) to enhance the caregivers in providing the right care for these patients, the technology in the delivery room still lags far behind. Diligent translation of well-known and promising technological solutions from the NICU to the delivery room will allow for better support of the caregivers in performing their tasks. In this review we will discuss the current technology used for stabilisation of preterm infants in the delivery room and how this could be optimised in order to further improve care and outcomes of preterm infants in the near future.

      1. Introduction

      Because of their immaturity, very preterm infants are a unique and highly vulnerable group of patients that have a narrow physiological margin within which interventions are safe and effective. A large amount of scientific research along with technological innovations have improved care for preterm infants in the neonatal intensive care unit (NICU). In the NICU, infants are monitored meticulously and devices are used to provide treatment in a safe and sophisticated manner. The arrival of automated technologies, whether or not in combination with artificial intelligence (servo-controlled incubator, algorithm driven ventilators, automated oxygen titration, predictive monitoring) has decreased the manual work in the NICU and improved care and outcome in the last twenty years.
      While these automated technologies are increasingly being used in the NICU, technology in the delivery room still lags far behind. Preterm infants can be difficult to manage in the intensive care unit, but this task is considerably more complex at birth due to the infant's rapidly changing physiology. Particularly at birth, automated technologies and/or artificial intelligence could be highly relevant, since the infant's physiology is undergoing large and rapid changes. We now start to understand that the transition to life after birth is an extremely critical phase of life which greatly impacts an individual's risk of death, injury [
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      Circulatory responses to asphyxia differ if the asphyxia occurs in utero or ex utero in near-term lambs.
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      ] or life-long disability [
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      ,
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      ], particularly infants born very preterm.
      Stabilisation of preterm infants in the delivery room is usually brief, but many interventions need to be performed in order to stabilise the infant's temperature, (spontaneous) ventilation and oxygenation in a time sensitive manner. It has been shown that some interventions are not as effective as caregivers assumed and that the provision of an optimal and safe treatment during this stressful moment is a major challenge for caregivers [
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      ]. It also has been demonstrated that caregivers have difficulty in assimilating the complex and rapidly changing physiological information that is required to make accurate strategic decisions with regard to assisting preterm infants as they transition to newborn life [
      • Huberts T.J.P.
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      ,
      • Schilleman K.
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      • Walther F.J.
      • te Pas A.B.
      Evaluating manual inflations and breathing during mask ventilation in preterm infants at birth.
      ,
      • Schilleman K.
      • Siew M.L.
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      • Morley C.J.
      • Walther F.J.
      • Te Pas A.B.
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      ,
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      Cardiorespiratory monitoring during neonatal resuscitation for direct feedback and audit.
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      ].
      In this review we will discuss the current technology used for stabilisation of preterm infants in the delivery room and how this could be optimised by the provision of purpose-built devices and technology that assimilates all of the physiology data and supports decision making processes.

      2. Temperature management

      The first step of neonatal stabilisation is the prevention of heat loss, which easily occurs in the exposed and wet infants through convection, conduction, radiation and evaporation, resulting in a decreased body temperature. Hypothermia after birth has been recognised as a significant contributor to neonatal morbidity and mortality [
      • Chitty H.
      • Wyllie J.
      Importance of maintaining the newly born temperature in the normal range from delivery to admission.
      ,
      • Laptook A.R.
      • Salhab W.
      • Bhaskar B.
      • Neonatal Research N.
      Admission temperature of low birth weight infants: predictors and associated morbidities.
      ]. Although less is known about the acute and long-term impact of hyperthermia after birth, the potential risks for both hypothermia and hyperthermia are currently recognised in the international resuscitation guidelines with the advice to keep the body temperature of the infant between 36.5 and 37.5 °C [
      • Wyllie J.
      • Bruinenberg J.
      • Roehr C.C.
      • Rudiger M.
      • Trevisanuto D.
      • Urlesberger B.
      European resuscitation council guidelines for resuscitation 2015: section 7. Resuscitation and support of transition of babies at birth.
      ,
      • Madar J.
      • Roehr C.C.
      • Ainsworth S.
      • et al.
      European Resuscitation Council Guidelines 2021: newborn resuscitation and support of transition of infants at birth.
      ]. While measures to prevent hypothermia – such as increased room temperature and the use of a head cap, a wrap, a radiant heater, a thermal mattress and heated and humidified gases - are commonly performed, keeping the body temperature within the normal range during stabilisation at birth proves to be challenging [
      • Wilson E.
      • Maier R.F.
      • Norman M.
      • et al.
      Admission hypothermia in very preterm infants and neonatal mortality and morbidity.
      ,
      • Mank A.
      • van Zanten H.A.
      • Meyer M.P.
      • Pauws S.
      • Lopriore E.
      • Te Pas A.B.
      Hypothermia in preterm infants in the first hours after birth: occurrence, course and risk factors.
      ,
      • Lyu Y.
      • Shah P.S.
      • Ye X.Y.
      • et al.
      Association between admission temperature and mortality and major morbidity in preterm infants born at fewer than 33 weeks' gestation.
      ,
      • de Almeida M.F.
      • Guinsburg R.
      • Sancho G.A.
      • et al.
      Hypothermia and early neonatal mortality in preterm infants.
      ].
      Currently, the temperature is often only measured at NICU admission, which does not allow us to take correcting measures until that moment. Although standardised thermoregulation protocols, training, and audits have shown to improve our temperature management [
      • Choi H.S.
      • Lee S.M.
      • Eun H.
      • Park M.
      • Park K.I.
      • Namgung R.
      The impact of a quality improvement effort in reducing admission hypothermia in preterm infants following delivery.
      ,
      • Yip W.Y.
      • Quek B.H.
      • Fong M.C.W.
      • et al.
      A quality improvement project to reduce hypothermia in preterm infants on admission to the neonatal intensive care unit.
      ,
      • Billimoria Z.
      • Chawla S.
      • Bajaj M.
      • Natarajan G.
      Improving admission temperature in extremely low birth weight infants: a hospital-based multi-intervention quality improvement project.
      ], frequent or continuous measurement of temperature, in combination with a temperature dependent protocol, can further improve this [
      • Russo A.
      • McCready M.
      • Torres L.
      • et al.
      Reducing hypothermia in preterm infants following delivery.
      ,
      • Harer M.W.
      • Vergales B.
      • Cady T.
      • Early A.
      • Chisholm C.
      • Swanson J.R.
      Implementation of a multidisciplinary guideline improves preterm infant admission temperatures.
      ]. However, temperature management based on continuous measurements requires constant attention and is more labour intensive. Technology could assist in this process by providing visual or audible cues when the recommended ranges are exceeded in order to capture the attention of the caregiver or by providing decision support on the timing and type of heat loss measures to take. Technology could even further assist caregivers by enabling automated regulation via servo-controlled mattresses and radiant warmers, which are commonly used in the NICU.
      Although a recent multi-centre study reported that the use of servo-controlled radiant warmers on the delivery room showed no benefits over the use of radiant warmers on maximal output [
      • Cavallin F.
      • Doglioni N.
      • Allodi A.
      • et al.
      Thermal management with and without servo-controlled system in preterm infants immediately after birth: a multicentre, randomised controlled study.
      ], studies implementing servo-controlled radiant warmers combined with a temperature dependent protocol for additional measures show the highest overall scores of normothermia at NICU admission, ranging from 74% to 100% [
      • Young A.
      • Azeez F.
      • Godad S.P.
      • Shetty P.
      • Sharma A.
      A multimodal quality improvement approach to promote normothermia in very preterm infants.
      ,
      • Pinheiro J.M.
      • Furdon S.A.
      • Boynton S.
      • Dugan R.
      • Reu-Donlon C.
      • Jensen S.
      Decreasing hypothermia during delivery room stabilization of preterm neonates.
      ,
      • Manani M.
      • Jegatheesan P.
      • DeSandre G.
      • Song D.
      • Showalter L.
      • Govindaswami B.
      Elimination of admission hypothermia in preterm very low-birth-weight infants by standardization of delivery room management.
      ,
      • DeMauro S.B.
      • Douglas E.
      • Karp K.
      • et al.
      Improving delivery room management for very preterm infants.
      ]. As infants are much more exposed in the delivery room as compared to the NICU, full automation of thermoregulation in the delivery room probably asks for completely different closed-loop solutions minimising the effects of the environment on their temperature.

      3. Tactile stimulation

      As of 2005, local and international resuscitation guidelines recommend tactile stimulation in the form of warming, drying and rubbing the back or soles of the feet to evoke spontaneous breathing in newborn infants [
      • Wyllie J.
      • Bruinenberg J.
      • Roehr C.C.
      • Rudiger M.
      • Trevisanuto D.
      • Urlesberger B.
      European resuscitation council guidelines for resuscitation 2015: section 7. Resuscitation and support of transition of babies at birth.
      ,
      • Madar J.
      • Roehr C.C.
      • Ainsworth S.
      • et al.
      European Resuscitation Council Guidelines 2021: newborn resuscitation and support of transition of infants at birth.
      ,
      • Wyckoff M.H.
      • Aziz K.
      • Escobedo M.B.
      • et al.
      Part 13: neonatal resuscitation: 2015 American heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care.
      ]. While experimental studies demonstrated tactile stimulation to increase respiratory effort [
      • Scarpelli E.
      • Condorelli S.
      • Cosmi E.
      Cutaneous stimulation and generation of breathing in the fetus.
      ,
      • Ronca A.E.
      • Alberts J.R.
      Cutaneous induction of breathing in perinatal rats.
      ], the clinical guidelines are still largely based on many years of experience and expert opinion as there is lack of data on this topic in human infants.
      Several retrospective studies recently evaluated current practice, showing a wide variation between caregivers and between centres concerning timing, duration and method of stimulation [
      • Dekker J.
      • Martherus T.
      • Cramer S.J.E.
      • van Zanten H.A.
      • Hooper S.B.
      • Te Pas A.B.
      Tactile stimulation to stimulate spontaneous breathing during stabilization of preterm infants at birth: a retrospective analysis.
      ,
      • Pietravalle A.
      • Cavallin F.
      • Opocher A.
      • et al.
      Neonatal tactile stimulation at birth in a low-resource setting.
      ,
      • van Henten T.M.A.
      • Dekker J.
      • Te Pas A.B.
      • Zivanovic S.
      • Hooper S.B.
      • Roehr C.C.
      Tactile stimulation in the delivery room: do we practice what we preach?.
      ,
      • Gaertner V.D.
      • Flemmer S.A.
      • Lorenz L.
      • Davis P.G.
      • Kamlin C.O.F.
      Physical stimulation of newborn infants in the delivery room.
      ,
      • Baik-Schneditz N.
      • Urlesberger B.
      • Schwaberger B.
      • et al.
      Tactile stimulation during neonatal transition and its effect on vital parameters in neonates during neonatal transition.
      ]. In addition, stimulation turned out to be often omitted, in particular in preterm infants placed in a polyethylene bag [
      • van Henten T.M.A.
      • Dekker J.
      • Te Pas A.B.
      • Zivanovic S.
      • Hooper S.B.
      • Roehr C.C.
      Tactile stimulation in the delivery room: do we practice what we preach?.
      ,
      • Gaertner V.D.
      • Flemmer S.A.
      • Lorenz L.
      • Davis P.G.
      • Kamlin C.O.F.
      Physical stimulation of newborn infants in the delivery room.
      ,
      • Baik-Schneditz N.
      • Urlesberger B.
      • Schwaberger B.
      • et al.
      Tactile stimulation during neonatal transition and its effect on vital parameters in neonates during neonatal transition.
      ]. A recent randomised trial showed that repetitive tactile stimulation in preterm infants increased oxygenation, while less oxygen was needed, and improved respiratory effort [
      • Dekker J.
      • Hooper S.B.
      • Martherus T.
      • Cramer S.J.E.
      • van Geloven N.
      • Te Pas A.B.
      Repetitive versus standard tactile stimulation of preterm infants at birth - a randomized controlled trial.
      ]. However, the trial also led to a high incidence of stimulation in the standard group. This effect could be attributed to the Hawthorne effect and/or the increased focus on tactile stimulation during the study, which in turn implies that omission of stimulation happens because it is simply forgotten.
      Albeit the most optimal way of stimulation remains unclear, automated mechanical stimulation could ensure tactile stimulation to be provided, in a more consistent way [
      • Cramer S.J.E.
      • Dekker J.
      • Dankelman J.
      • Pauws S.C.
      • Hooper S.B.
      • Te Pas A.B.
      Effect of tactile stimulation on termination and prevention of apnea of prematurity: a systematic review.
      ]. Several closed-loop vibratory stimulation devices to treat apnoea's of preterm infants admitted to the NICU have been described in literature, but currently none of these are commercially available [
      • Marcotte A.L.
      • Rosow E.
      • Eisenfeld L.
      • Bronzino J.D.
      Development of apnea interruption system by vibratory stimulus.
      ,
      • Faille E.O.
      • Setya A.
      • Eisenfeld L.
      A computerized system to diagnose and treat neonatal apnea using vibrotactile stimulation.
      ,
      • Marayong P.
      • Mostoufi M.S.
      Foot vibrotactile device for central apnea interruption in premature infants.
      ,
      • Pichardo R.
      • Eisenfeld L.
      • Adam J.
      • Rosow E.
      • Escabi M.
      • Enderle J.
      Validation of a vibrotactile stimulation system.
      ]. No studies have been performed in the delivery room, but mechanical vibratory stimulation in preterm infants in the NICU proved to be as effective as manual stimulation in aborting apnoeic episodes in two preliminary studies [
      • Pichardo R.
      • Eisenfeld L.
      • Adam J.
      • Rosow E.
      • Escabi M.
      • Enderle J.
      Validation of a vibrotactile stimulation system.
      ,
      • Lovell J.R.
      • Eisenfeld L.
      • Rosow E.
      • Adam J.
      • Lapin C.
      • Bronzino J.D.
      Vibrotactile stimulation for treatment of neonatal apnea: a preliminary study.
      ], and two other observational studies reported that their closed-loop pulsating and vibrating devices were able to terminate 90% of all apnoeas [
      • Frank U.A.
      • Bordiuk J.M.
      • Borromeo-McGrail V.
      • Saltzman M.B.
      • Hg K.
      Treatment of apnea in neonates with an automated monitor-actuated apnea arrestor.
      ,
      • Camargo V.C.
      • Honorato da Silva S.
      • Freitas de Amorim M.
      • Nohama P.
      Instrumentation for the detection and interruption of apnea.
      ]. Applying this technique in the delivery room has the potential to replace manual intervention, eliminating the chance that stimulation will be forgotten.

      4. Oxygenation

      Currently, oxygen administration is guided by predefined oxygen saturation (SpO2) target ranges [
      • Dawson J.A.
      • Kamlin C.O.
      • Vento M.
      • et al.
      Defining the reference range for oxygen saturation for infants after birth.
      ]. Caregivers manually titrate the fraction of inspired oxygen (FiO2) accordingly to avoid hypoxia and hyperoxia. At birth, hypoxia can lead to suppression of spontaneous breathing, and hypoxia that persists for more than 5 min after birth is associated with an increased risk of mortality and the development of intraventricular hemorrhages [
      • Dekker J.
      • van Kaam A.H.
      • Roehr C.C.
      • et al.
      Stimulating and maintaining spontaneous breathing during transition of preterm infants.
      ,
      • Davey M.G.
      • Moss T.J.
      • McCrabb G.J.
      • Harding R.
      Prematurity alters hypoxic and hypercapnic ventilatory responses in developing lambs.
      ,
      • Dekker J.
      • Hooper S.B.
      • Croughan M.K.
      • et al.
      Increasing respiratory effort with 100% oxygen during resuscitation of preterm rabbits at birth.
      ,
      • Oei J.L.
      • Finer N.N.
      • Saugstad O.D.
      • et al.
      Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants.
      ]. On the other hand, hyperoxia needs to be avoided as this increases the production of free radicals, but also can inhibit the respiratory centre [
      • Clyman R.I.
      • Saugstad O.D.
      • Mauray F.
      Reactive oxygen metabolites relax the lamb ductus arteriosus by stimulating prostaglandin production.
      ,
      • Saugstad O.D.
      Oxidative stress in the newborn--a 30-year perspective.
      ]. As such, it is critical to adequately control oxygenation during this period. However, this is an incredibly difficult and complex task given the fact that immediately after birth, the lung is constantly and rapidly changing.
      It has been shown that maintaining SpO2 values within a predefined target range with manual titration is extremely difficult in the delivery room as well as in the NICU [
      • White L.N.
      • Thio M.
      • Owen L.S.
      • et al.
      Achievement of saturation targets in preterm infants <32 weeks' gestational age in the delivery room.
      ,
      • Goos T.G.
      • Rook D.
      • van der Eijk A.C.
      • et al.
      Observing the resuscitation of very preterm infants: are we able to follow the oxygen saturation targets?.
      ,
      • Phillipos E.
      • Solevåg A.L.
      • Aziz K.
      • et al.
      Oxygen saturation and heart rate ranges in very preterm infants requiring respiratory support at birth.
      ,
      • Hagadorn J.I.
      • Furey A.M.
      • Nghiem T.H.
      • et al.
      Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks' gestation: the AVIOx study.
      ,
      • Laptook A.R.
      • Salhab W.
      • Allen J.
      • Saha S.
      • Walsh M.
      Pulse oximetry in very low birth weight infants: can oxygen saturation be maintained in the desired range?.
      ,
      • Lim K.
      • Wheeler K.I.
      • Gale T.J.
      • et al.
      Oxygen saturation targeting in preterm infants receiving continuous positive airway pressure.
      ,
      • Schmidt B.
      • Whyte R.K.
      • Asztalos E.V.
      • et al.
      Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial.
      ]. Randomised trials demonstrated the potential of closed-loop titration of FiO2 in the NICU, increasing the time spent within the SpO2 target range with a decrease in extreme deviations in oxygenation, including both the duration and the number of episodes [
      • Claure N.
      • D'Ugard C.
      • Bancalari E.
      Automated adjustment of inspired oxygen in preterm infants with frequent fluctuations in oxygenation: a pilot clinical trial.
      ,
      • Plottier G.K.
      • Wheeler K.I.
      • Ali S.K.
      • et al.
      Clinical evaluation of a novel adaptive algorithm for automated control of oxygen therapy in preterm infants on non-invasive respiratory support.
      ,
      • Lal M.
      • Tin W.
      • Sinha S.
      Automated control of inspired oxygen in ventilated preterm infants: crossover physiological study.
      ,
      • van Kaam A.H.
      • Hummler H.D.
      • Wilinska M.
      • et al.
      Automated versus manual oxygen control with different saturation targets and modes of respiratory support in preterm infants.
      ,
      • Urschitz M.S.
      • Horn W.
      • Seyfang A.
      • et al.
      Automatic control of the inspired oxygen fraction in preterm infants: a randomized crossover trial.
      ,
      • Hallenberger A.
      • Poets C.F.
      • Horn W.
      • Seyfang A.
      • Urschitz M.S.
      Closed-loop automatic oxygen control (CLAC) in preterm infants: a randomized controlled trial.
      ,
      • Waitz M.
      • Schmid M.B.
      • Fuchs H.
      • Mendler M.R.
      • Dreyhaupt J.
      • Hummler H.D.
      Effects of automated adjustment of the inspired oxygen on fluctuations of arterial and regional cerebral tissue oxygenation in preterm infants with frequent desaturations.
      ,
      • Claure N.
      • Bancalari E.
      • D'Ugard C.
      • et al.
      Multicenter crossover study of automated control of inspired oxygen in ventilated preterm infants.
      ,
      • Zapata J.
      • Gómez J.J.
      • Araque Campo R.
      • Matiz Rubio A.
      • Sola A.
      A randomised controlled trial of an automated oxygen delivery algorithm for preterm neonates receiving supplemental oxygen without mechanical ventilation.
      ,
      • Van Zanten H.A.
      • Kuypers K.
      • Stenson B.J.
      • Bachman T.E.
      • Pauws S.C.
      • Te Pas A.B.
      The effect of implementing an automated oxygen control on oxygen saturation in preterm infants.
      ]. The use of a closed-loop oxygen controller in the delivery room has so far only been studied once in a preterm lamb model [
      • Hütten M.C.
      • Goos T.G.
      • Ophelders D.
      • et al.
      Fully automated predictive intelligent control of oxygenation (PRICO) in resuscitation and ventilation of preterm lambs.
      ]. In this study, the effect of a closed-loop oxygen controller with timeout restrictions of 30s after each titration step was compared to manual titration of oxygen after evaluation of SpO2 to be performed every 30s. Results show similar time within the SpO2 target range and below the target range, while time above the target range was significantly shorter in the automatic titration group [
      • Hütten M.C.
      • Goos T.G.
      • Ophelders D.
      • et al.
      Fully automated predictive intelligent control of oxygenation (PRICO) in resuscitation and ventilation of preterm lambs.
      ].
      However, this technique cannot just simply be extrapolated to the delivery room, as there are considerable differences with regard to target ranges, physiology and devices used. In the NICU, the SpO2 target range is static, while this is dynamic in the first minutes after birth. Oxygen exchange in the lungs is largely determined by the surface area available for gas exchange and the oxygen concentration gradient between the alveoli and adjacent capillaries. At birth, when the airways are mostly liquid-filled, the surface area available for gas exchange is small and a high oxygen concentration is required for adequate exchange (Fig. 1A). As the lungs aerate, the surface area available for gas exchange increases exponentially and as such a much lower oxygen concentration is needed for adequate oxygenation (Fig. 1B). The oxygen concentration administered after birth should thus be adjusted according to the degree of lung aeration. This would require the closed-loop titration mechanism to adjust the SpO2 target range continuously based on the time after birth. In addition, the algorithm of the closed-loop oxygen controller should also be calibrated based on the factors present at birth which influence the position of the oxygen-haemoglobin dissociation curve.
      Fig. 1
      Fig. 1Overview of the alveoli, surrounded by capillaries. A: Directly at birth, lung liquid needs to be replaced with air. The movement of liquid into the interstitial tissue causes a high airway resistance and the partially liquid-filled alveoli reduces the surface area available for gas exchange. B: As the liquid moves into the interstitial tissue surrounding the alveoli, the airway resistance decrease while the interstitial pressure and lung recoil increase. This causes alveolar collapse and liquid re-entry at end-expiration. Nevertheless, the surface area available for gas exchange increases.
      Furthermore, titration of oxygen using a T-piece ventilator, which is commonly used for respiratory support at birth [
      • Madar J.
      • Roehr C.C.
      • Ainsworth S.
      • et al.
      European Resuscitation Council Guidelines 2021: newborn resuscitation and support of transition of infants at birth.
      ], can result in a delay between the moment of titration and the delivery of the corresponding FiO2 at the face mask of the infant [
      • Dekker J.
      • Stenning F.J.
      • Willms L.
      • Martherus T.
      • Hooper S.B.
      • Te Pas A.B.
      Time to achieve desired fraction of inspired oxygen using a T-piece ventilator during resuscitation of preterm infants at birth.
      ]. The algorithm used by the closed-loop oxygen controller that is used with the T-piece resuscitator should therefore reckon with this delay.

      5. Continuous positive airway pressure

      Although most preterm infants breathe at birth, the breathing effort is often insufficient to ensure the large pulmonary physiological changes that are needed to survive the foetal to neonatal transition. While continuous positive airway pressure (CPAP) is often used to support the infant's breathing, there is no data on the optimal pressure level. The CPAP level of 4–8 cmH2O that is currently used is predominantly extrapolated from data from CPAP later in the NICU, while the underlying physiology during the neonatal transition is strikingly different [
      • Wyllie J.
      • Bruinenberg J.
      • Roehr C.C.
      • Rudiger M.
      • Trevisanuto D.
      • Urlesberger B.
      European resuscitation council guidelines for resuscitation 2015: section 7. Resuscitation and support of transition of babies at birth.
      ,
      • Wyckoff M.H.
      • Wyllie J.
      • Aziz K.
      • et al.
      Neonatal life support 2020 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
      ].
      Considering the physiological changes that need to occur during transition, it would be more logical to use a dynamic CPAP strategy wherein the CPAP levels suit the different phases of the transition. In the first phase of the transition (Fig. 1A), the role of CPAP is to promote lung aeration and assist movement of lung liquid across the distal airway wall into the interstitial tissue. As a result, the resistance in the airways is high due to the high viscosity of liquid (compared with air) moving across the airway epithelium requiring higher CPAP levels to overcome this [
      • Hooper S.B.
      • Kitchen M.J.
      • Wallace M.J.
      • et al.
      Imaging lung aeration and lung liquid clearance at birth.
      ,
      • Siew M.L.
      • Wallace M.J.
      • Kitchen M.J.
      • et al.
      Inspiration regulates the rate and temporal pattern of lung liquid clearance and lung aeration at birth.
      ,
      • Siew M.L.
      • Wallace M.J.
      • Allison B.J.
      • et al.
      The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits.
      ,
      • te Pas A.B.
      • Siew M.
      • Wallace M.J.
      • et al.
      Effect of sustained inflation length on establishing functional residual capacity at birth in ventilated premature rabbits.
      ,
      • te Pas A.B.
      • Siew M.
      • Wallace M.J.
      • et al.
      Establishing functional residual capacity at birth: the effect of sustained inflation and positive end-expiratory pressure in a preterm rabbit model.
      ]. Once the lungs become more aerated and liquid is accumulated in the interstitial tissue, the lung characteristics change quickly and the role of CPAP converts to maintaining lung aeration. During this phase of the transition (Fig. 1B), airway resistance is considerably lower (∼100 fold), but lung recoil and interstitial tissue pressure increase which promote alveolar collapse and liquid re-entry at end-expiration [
      • Hooper S.B.
      • Kitchen M.J.
      • Wallace M.J.
      • et al.
      Imaging lung aeration and lung liquid clearance at birth.
      ,
      • Siew M.L.
      • Wallace M.J.
      • Kitchen M.J.
      • et al.
      Inspiration regulates the rate and temporal pattern of lung liquid clearance and lung aeration at birth.
      ,
      • Siew M.L.
      • Wallace M.J.
      • Allison B.J.
      • et al.
      The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits.
      ,
      • te Pas A.B.
      • Siew M.
      • Wallace M.J.
      • et al.
      Effect of sustained inflation length on establishing functional residual capacity at birth in ventilated premature rabbits.
      ,
      • te Pas A.B.
      • Siew M.
      • Wallace M.J.
      • et al.
      Establishing functional residual capacity at birth: the effect of sustained inflation and positive end-expiratory pressure in a preterm rabbit model.
      ,
      • Siew M.L.
      • Te Pas A.B.
      • Wallace M.J.
      • et al.
      Surfactant increases the uniformity of lung aeration at birth in ventilated preterm rabbits.
      ,
      • Miserocchi G.
      • Poskurica B.H.
      • Del Fabbro M.
      Pulmonary interstitial pressure in anesthetized paralyzed newborn rabbits.
      ,
      • Bland R.D.
      • McMillan D.D.
      • Bressack M.A.
      • Dong L.
      Clearance of liquid from lungs of newborn rabbits.
      ,
      • Hooper S.B.
      • Te Pas A.B.
      • Kitchen M.J.
      Respiratory transition in the newborn: a three-phase process.
      ]. Lower CPAP levels are likely sufficient to maintain aeration and support breathing, while decreasing the risk for lung overexpansion and/or adverse effect on pulmonary blood flow. This dynamic CPAP approach, following the pulmonary physiological changes during transition, has been called physiological based (PB)-CPAP.
      Experimental studies in spontaneously breathing preterm animal models demonstrated that PB-CPAP should ideally start with CPAP of 15 cmH2O which is stepwise decreased to 8 cmH2O. These studies also showed that PB-CPAP promotes lung aeration (functional residual capacity; FRC)), breathing effort and pulmonary blood flow, without causing bulging of the lungs or pneumothoraxes [
      • Martherus T.
      • Crossley K.J.
      • Rodgers K.A.
      • et al.
      High-CPAP does not impede cardiovascular changes at birth in preterm sheep.
      ,
      • Martherus T.
      • Croughan M.K.
      • Crossley K.J.
      • et al.
      Higher CPAP levels improve functional residual capacity at birth in preterm rabbits.
      ]. These results were translated into a small randomised controlled trial wherein PB-CPAP was compared to 5–8 cmH2O CPAP. This feasibility study demonstrated that PB-CPAP led to a quicker restoration of heart rate and shorter duration of mask ventilation, likely reflecting lung aeration. Nevertheless, post-trial evaluations indicated that caregivers found it difficult to combine standard care with a CPAP protocol that requires constant evaluations and changes in CPAP levels [
      • Martherus T.
      • Kuypers K.L.A.M.
      • Böhringer S.
      • et al.
      Feasibility and effect of physiological-based CPAP in preterm infants at birth.
      ].
      This is where technological innovation could help the caregiver in assimilating complex physiological changes and fine-tuning and optimising the respiratory support. Mathematical modelling with currently available physiological data could be used to create algorithms, which will allow us to develop a decision or even automated pressure support system in the delivery room.

      6. Positive pressure ventilation

      If preterm infants fail to clear their lung liquid, establish FRC and initiate spontaneous breathing to facilitate gas exchange [
      • Mian Q.N.
      • Pichler G.
      • Binder C.
      • et al.
      Tidal volumes in spontaneously breathing preterm infants supported with continuous positive airway pressure.
      ], manual non-invasive positive pressure ventilation (NIPPV) is provided by occluding the aperture of a T-piece resuscitator with a thumb or finger. The sufficiency of the provided tidal volumes is confirmed by adequate chest rise, auscultation or, indirectly, by an increase in heart rate [
      • Jain D.
      • D'Ugard C.
      • Aguilar A.
      • Del Moral T.
      • Bancalari E.
      • Claure N.
      Use of a mechanical ventilator with respiratory function monitoring provides more consistent ventilation during simulated neonatal resuscitation.
      ]. However, due to rapidly changing pulmonary physiology and inconsistent respiratory drive of infants at birth, variable tidal volume are administered that might be inadequate or excessive. Large tidal volumes could overstretch the delicate alveoli and airways (volutrauma), while small tidal volumes could lead to loss of lung volume or cycling between collapse and recruitment (atelectotrauma) thereby injuring the lungs [
      • Morley C.J.
      Volume-limited and volume-targeted ventilation.
      ,
      • Singh J.
      • Sinha S.K.
      • Alsop E.
      • Gupta S.
      • Mishra A.
      • Donn S.M.
      Long term follow-up of very low birthweight infants from a neonatal volume versus pressure mechanical ventilation trial.
      ]. A recent multicentre trial evaluating tidal volume monitoring during manual ventilation reported that, despite using a respiratory function monitor (RFM) (Fig. 2) , ineffective ventilation <4 mL/kg and potentially harmful ventilation >8 mL/kg was provided 40.7% and 20.0% of the time, respectively [
      • van Zanten H.A.
      • Kuypers K.
      • van Zwet E.W.
      • et al.
      A multi-centre randomised controlled trial of respiratory function monitoring during stabilisation of very preterm infants at birth.
      ].
      The high percentage of ineffective manual ventilation could be caused by pharyngeal ventilation as the glottis is predominantly closed after birth and only opens when a spontaneous breath is taken [
      • Crawshaw J.R.
      • Kitchen M.J.
      • Binder-Heschl C.
      • et al.
      Laryngeal closure impedes non-invasive ventilation at birth.
      ]. When ventilation is provided to a closed glottis, no air is able to enter into the lungs [
      • Crawshaw J.R.
      • Kitchen M.J.
      • Binder-Heschl C.
      • et al.
      Laryngeal closure impedes non-invasive ventilation at birth.
      ]. Providing inflations which coincides with spontaneous breaths would be more effective, but also increases the risks of high tidal volumes and thus the risk of lung and/or cerebral injury [
      • Morley C.J.
      Monitoring noenatal resuscitation: why is it needed?.
      ]. As it is difficult for caregivers to evaluate the presence and quality of spontaneous breathing at birth [
      • Schilleman K.
      • Siew M.L.
      • Lopriore E.
      • Morley C.J.
      • Walther F.J.
      • Te Pas A.B.
      Auditing resuscitation of preterm infants at birth by recording video and physiological parameters.
      ], especially during manual ventilation [
      • Schilleman K.
      • van der Pot C.J.
      • Hooper S.B.
      • Lopriore E.
      • Walther F.J.
      • te Pas A.B.
      Evaluating manual inflations and breathing during mask ventilation in preterm infants at birth.
      ], this hampers safe and effective ventilation at birth.
      Again, automation can offer a solution. In this case, several solutions already exist and are being applied as features of a neonatal ventilator. Replacing the T-piece resuscitator for a regular neonatal ventilator in the delivery room therefore brings several opportunities to prevent inappropriate ventilation. The first solution is automated synchronised NIPPV (sNIPPV). Caregivers can only detect breathing after a breath has been taken, while a ventilator can detect the start of a breath. This enables ventilators to synchronise their ventilation. In addition, caregivers have to keep overview of the clinical condition of the infant and are, therefore, not able to continuously focus on the infant's breathing while a ventilator can. Although there is no evidence for the effectiveness of synchronised ventilation in the delivery room, it has shortened the duration and improved the effectiveness of ventilation in the NICU [
      • Greenough A.
      • Rossor T.E.
      • Sundaresan A.
      • Murthy V.
      • Milner A.D.
      Synchronized mechanical ventilation for respiratory support in newborn infants.
      ,
      • Claure N.
      • Bancalari E.
      New modes of mechanical ventilation in the preterm newborn: evidence of benefit.
      ].
      Even with sNIPPV, it remains difficult to provide tidal volumes in a safe target range. To date, caregivers are only able to apply pressure-limited manual ventilation in the delivery room due to the lack of appropriate technology. However, a recent neonatal resuscitation simulation study showed it is feasible to use a ventilator with RFM in the delivery room as it increased the proportion of tidal volumes within the target range and reduced the number of large tidal volumes during different simulated scenarios of changing pulmonary mechanics commonly encountered at birth [
      • Jain D.
      • D'Ugard C.
      • Aguilar A.
      • Del Moral T.
      • Bancalari E.
      • Claure N.
      Use of a mechanical ventilator with respiratory function monitoring provides more consistent ventilation during simulated neonatal resuscitation.
      ]. Also, the delivery of consistent tidal volumes during changing pulmonary mechanics could be improved by implementing volume-targeted ventilation. While, this ventilation mode showed to improve outcome and is a widely accepted in the NICU, there is no data on using this mode in preterm infants at birth [
      • Morley C.J.
      Volume-limited and volume-targeted ventilation.
      ,
      • Keszler M.
      Volume-targeted ventilation: one size does not fit all. Evidence-based recommendations for successful use.
      ,
      • Klingenberg C.
      • Wheeler K.I.
      • McCallion N.
      • Morley C.J.
      • Davis P.G.
      Volume-targeted versus pressure-limited ventilation in neonates.
      ]. This effect might even be increased when using a ventilator with synchronised ventilation and/or volume-targeted ventilation.

      7. Monitoring

      Regular feedback on the patient's physiological state is a pivotal element of neonatal stabilisation after birth, guiding corrective actions and clinical decision making of the caregivers. Despite its importance, monitoring in this critical period is still relatively basic compared to the continuous and extensive monitoring techniques used in the NICU.
      The current guidelines recommend the use of pulse oximetry and/or ECG for physiological feedback instead of rudimentary methods such as auscultation, palpation of the umbilical cord and assessment of skin color, as these methods proved to be prone to subjectivity [
      • O'Donnell C.P.
      • Kamlin C.O.
      • Davis P.G.
      • Carlin J.B.
      • Morley C.J.
      Clinical assessment of infant colour at delivery.
      ,
      • Schmolzer G.M.
      • Morley C.J.
      • Wong C.
      • et al.
      Respiratory function monitor guidance of mask ventilation in the delivery room: a feasibility study.
      ]. The same applies to the assessment of administered tidal volumes by observing chest excursions [
      • Schmolzer G.M.
      • Kamlin O.C.
      • O'Donnell C.P.
      • Dawson J.A.
      • Morley C.J.
      • Davis P.G.
      Assessment of tidal volume and gas leak during mask ventilation of preterm infants in the delivery room.
      ] but the evidence for using a RFM instead remains conflicting. Although manikin studies demonstrated that providing continuous feedback on ventilation pressures, tidal volumes, mask leak, SpO 2, heart rate and FiO2 via a RFM improved the performance of the caregiver during PPV [
      • Jain D.
      • D'Ugard C.
      • Aguilar A.
      • Del Moral T.
      • Bancalari E.
      • Claure N.
      Use of a mechanical ventilator with respiratory function monitoring provides more consistent ventilation during simulated neonatal resuscitation.
      ,
      • Wood F.E.
      • Morley C.J.
      • Dawson J.A.
      • Davis P.G.
      A respiratory function monitor improves mask ventilation.
      ,
      • Binder C.
      • Schmolzer G.M.
      • O'Reilly M.
      • Schwaberger B.
      • Urlesberger B.
      • Pichler G.
      Human or monitor feedback to improve mask ventilation during simulated neonatal cardiopulmonary resuscitation.
      ,
      • Kelm M.
      • Dold S.K.
      • Hartung J.
      • Breckwoldt J.
      • Schmalisch G.
      • Roehr C.C.
      Manual neonatal ventilation training: a respiratory function monitor helps to reduce peak inspiratory pressures and tidal volumes during resuscitation.
      ], a recent multicenter randomised controlled trial showed no difference between neonatal resuscitation with or without integrated feedback by RFM [
      • van Zanten H.A.
      • Kuypers K.
      • van Zwet E.W.
      • et al.
      A multi-centre randomised controlled trial of respiratory function monitoring during stabilisation of very preterm infants at birth.
      ]. This result might be explained by previous findings that the use and interpretation of a RFM in the delivery room is experienced as challenging and therefore not helpful to all caregivers in critical decision making [
      • Schilleman K.
      • van der Pot C.J.
      • Hooper S.B.
      • Lopriore E.
      • Walther F.J.
      • te Pas A.B.
      Evaluating manual inflations and breathing during mask ventilation in preterm infants at birth.
      ,
      • Milner A.
      • Murthy V.
      • Bhat P.
      • et al.
      Evaluation of respiratory function monitoring at the resuscitation of prematurely born infants.
      ].
      Although continuous, objective and accurate data acquisition is necessary to further implement modern technological innovations such as closed-loop interventions and prediction models, the question is whether presenting all this data directly to the caregivers is always useful. Future research should also be focused on which data to present, and in particular in what manner, to facilitate quick assimilation and easy interpretation by caregivers so that they can recognize and act upon abnormalities or changes in physiology. In other words, in the design or development of monitoring methods, one should consider carefully whether the data is processed by algorithms or a human brain.

      8. Man and machines

      Our understanding of the foetal to neonatal transition and the underlying physiological changes has evidently increased in the recent decades, facilitating clear opportunities aiming to improve clinical outcome. However, these insights also underscore the eminent complexity of the transition process, especially in ill or preterm infants who cannot meet the required physiological challenges on their own.
      Whilst the expansion of monitoring solutions and intervention strategies and the finetuning of protocols and target ranges can definitely aid caregivers in providing the right support, it makes the resuscitation process increasingly sophisticated. As of today, caregivers continuously have to assimilate and interpret many physiological parameters from different devices in order to decide if, when and which intervention is required, in just a small-time window. The more difficult, dynamic and versatile the process, the more prone it becomes to human errors such as forgetfulness and lack of continued focus.
      Over the last decades the development and adoption of automated medical technology has tremendously increased and accordingly revolutionised medical practice, but not yet in the delivery room. We argue that the development and implementation of automation, closed-loop systems and artificial intelligence could serve as a next iteration in improving resuscitation management by reducing human error and unwanted variability in human behaviour. However, this can only be achieved if we critically validate the added value using a holistic approach; not only taking into account the patient but also the caregivers. This means that we should not blindly use existing solutions for new problems but find new ones fitting the entire context. We should not use or implement innovations because it is technically feasible, but because it is desirable and we should not endlessly extend and expand existing solutions but come up with solutions that replace a bundle of existing ones.
      Although some might dream, and others fear, a completely automated transition support system, it is more likely that technology will take on an integral part of resuscitation management, resulting in an increased caregiver-machine interaction. Given the growing complexity of automated systems, the poor explainability of artificial intelligence and the consequences of possible erroneous automated interventions, a paradigm shift is necessary. Caregivers should not only be clinically aware, understanding the status of the patient with regard to the interlinked physiological changes, but be situational aware, also understanding the status of all automated devices, systems and software during the transition process. Shaping this role is however not the sole responsibility of the caregivers. To make the most out of it, designers and developers should indeed focus on the explainability and interpretability of automated systems and error prone interfaces including clear user feedback. Managers and medical engineers should moreover ensure that caregivers are trained like pilots; focussing on the capabilities to identify and respond to system errors or failure. As it is utopian to think that capitalising some strength of computers will fully replace human weaknesses, caregivers have to accept that improvement of care will always remain an iterative process.

      9. Conclusion

      Although the complexity of stabilisation after birth increases by our growing understanding of the complex physiology, the development and implementation of technology to assist in this process lags behind. Implementing state-of-the-art technology during the neonatal stabilisation would enable us to i) prevent hypo- and hyperthermia through closed-loop temperature management, ii) stimulate spontaneous breathing by providing automatic repetitive tactile stimulation to all infants, iii) control oxygenation in relation to neonatal transition through closed-loop oxygenation, iv) support spontaneous breathing during neonatal transition by automated PB-CPAP algorithms and v) provide safe and effective ventilation by using synchronised volume targeted ventilation (Fig. 3). By using technology to assist caregivers to provide the optimal care, caregivers would be able to comprehend an overview of the infant's clinical condition more easily and finetune the stabilisation where appropriate.
      Fig. 3
      Fig. 3Visualisation of evolving technologies for use in the delivery room. From providing manual heat loss measures, manual tactile stimulation, manual supplemental oxygen control and manual CPAP and NIPPV with a T-piece resuscitator (A) to automated thermoregulation, automated tactile stimulation, automated oxygen control and automated ventilation using a ventilator (B).
      Although most of the technology discussed in this review is already used in the NICU, it cannot simply be extrapolated to the delivery room because of the difference in physiology, environment and situation. The adoption of automation has great potential to improve the care we provide in the delivery room, as long as we put humans, not technology, first. Above all, we must realise that technology does not make man superfluous: the clinical view remains necessary.

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