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EDUCATIONAL AIMS
Preterm infants postnatal adaptation is a complex process that often requires the intervention of especially trained caregivers.
The cornerstone of a successful switch from a fetal to an adult type of cardiorespiratory circulation is to provide adequate lung
ventilation. Both alveolar recruitment and achievement of a functional residual capacity are essential for establishing an adequate
gas exchange.
The use of non invasive ventilation and individual oxygen titration according to oxygen saturation provide the best and less
aggressive means for achieving a successful postnatal adaptation of the preterm infant.
A R T I C L E I N F O S U M M A R Y
Keywords: Premature infants often experience difculties adapting to postnatal life. The most relevant ones are
Prematurity
related to establishing an adult type cardiorespiratory circulation and acquiring hemodynamic stability,
Resuscitation
aerating the lung and attaining a functional residual capacity, performing an adequate gas exchange and
Oxygen
Cord clamping switching to an oxygen enriched metabolism, and keeping an adequate body temperature. In recent
Ventilation years a body of evidence supports a trend towards gentle management in the delivery room aiming to
Delivery room reduce damage especially to the lungs in the so-called rst golden minutes. Herewith, we describe and
Temperature update four of the most relevant interventions performed in the delivery room: delayed cord clamping,
non-invasive ventilation, individualized oxygen supplementation, and maintaining an adequate body
temperature so as to avoid hyperthermia and/or hypothermia.
2015 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.prrv.2015.02.004
1526-0542/ 2015 Elsevier Ltd. All rights reserved.
152 M. Vento, G. Lista / Paediatric Respiratory Reviews 16 (2015) 151156
Allowing placental transfusion immediately after birth no clear differences were found in the primary outcome of death,
severe IVH or periventricular leukomalacia.
In general there is agreement that delaying clamping of the cord The optimal time to clamp the umbilical cord after delivery is
is of benet to the term and preterm infant. Maintaining blood still controversial. There are several small-randomized controlled
supply to the heart (pre-load) while the lung vascular system gets trials (RCTs) that have compared early (20 s) to late (430 s) cord
replenished contributes to keeping an adequate left ventricular clamping following preterm birth as well as several prospective
output, thus avoiding reduced blood ow to the CNS, coronary observational studies [7]. Of note, no conclusive data regarding the
arteries, kidneys and the rest of the body [5]. Recent experimental benets of DCC in depressed infants and especially in very preterm
studies in a sheep model of fetal to neonatal transition have clearly infants are yet available. Although experimental studies support a
shown that delaying cord clamping after the initiation of positive positive effect on cardiorespiratory circulation, brain perfusion,
pressure ventilation and establishment of a functional residual and hemodynamic stability with delayed cord clamping, the setup
capacity favours myocardial stability, carotid ow, and brain needed to physically perform resuscitation maneuvers with an
oxygenation, thus prompting a smoother foetal to neonatal intact cord still constitutes an important impediment in most
transition [6]. In 2010 ILCOR guidelines stated that for the term delivery rooms. In addition, in asphyxiated newborn infants there
infant after a normal delivery there is evidence of the benecial is a vasoconstriction of the placental vessels accompanied by
effects of delaying the clamping of the cord for at least one minute vasodilatation of the umbilical vessels, thus increasing the
but it might be delayed until cessation of cord pulsation. In preterm circulating blood volume in the foetus. However, pulmonary
infants, for uncomplicated deliveries, cord clamping should be vasoconstriction and reduced myocardial contractility occur,
delayed for a minimum of 30 seconds to 3 minutes after delivery. which may prompt cardiac insufciency and compromise recovery
However, in extremely preterm infants or preterm infants who are of the spontaneous circulation [8]. Under these circumstances cord
born moderately to severely depressed there is no evidence as to milking has been suggested as a valid alternative. This manoeuver
whether delaying cord clamping would be of benet instead of consists of clamping the cord near the placenta and stripping
initiating the resuscitation manoeuvers immediately [2]. A recent (milking) approximately 20 cm several times (2 to 4) from the
systematic review comprising the available information since the distal (placental) to the proximal (foetal) site of the cord. It can be
publication of the 2010 ILCOR guidelines indicates that delaying performed in few seconds and provides the newly born with a
cord clamping (DCC) up to 3 min in vigorous preterm babies substantial amount of blood that at least theoretically may
signicantly reduces hemodynamic instability, improves cerebral contribute to hemodynamic stabilization. To date only three
circulation, reduces intraventricular hemorrhage (IVH) all grades, clinical trials have been performed in preterm infants, including a
necrotizing enterocolitis and the need for transfusions, although total of 100 babies. Cord milking resulted in increased placental
peak serum bilirubin was higher in the transfused group. However, transfusion and apparently appeared to be as effective as DCC.
M. Vento, G. Lista / Paediatric Respiratory Reviews 16 (2015) 151156 153
Authors of these small trials concluded that cord milking may be an of time signicantly more prolonged that the normal inspiratory
option when DCC is not an option because the newly born baby time (e.g.: 15-25 s), is considered an alternative to clear uid-lled
requires immediate resuscitation measures. However, there are lung and achieve an early FRC [20]. Immediately after birth, when
still some questions that need to be answered. Hence, how rapid the initial inations are to be provided, it should be remembered
should the cord be stripped, or how often, or whats the minimum that the uid lled lung has a prolonged time constant. The rst
or maximum length of the cord that should be stripped? In breaths of life in healthy term infants are characterized by a
addition, there is some concern about the rapid perfusion of a prolonged inspiratory time (4-5 s per breath, according to the
signicant blood volume into the infants circulation that does not long time constant of the uid-lled lung), prolonged expiratory
resemble the physiologic ow of DCC [9]. phase and high ination pressure (30-35 cmH2O) along the major
airways [21]. During these rst prolonged inations, the delta
Ventilatory support pressure moves the air/liquid interface distally towards the
alveoli, thus facilitating direct lung aeration and clearance of
Very preterm babies frequently experience difculties initiat- lung liquid from the major airways within seconds after birth, that
ing spontaneous effective respiration because of poor respiratory will be completed by the interstitial lymphatic and venous
drive, poor muscle strength, surfactant deciency, and high chest reabsorption (in the hours following the birth). In several minutes,
wall compliance. As a consequence, they need respiratory by the achievement of an early FRC, the healthy term infant is able
assistance to clear lung uid, aerate the lungs, and establish a to maintain normal values of SpO2 while breathing in room-air
consistent functional residual capacity (FRC) to ensure gas [22].
exchange [10]. Failure to perform a uniform and functionally Therefore to mimic the delta pressure generated by the high
adequate lung expansion causes the coexistence of areas of and prolonged ination pressure of the newly born infant, a SI has
atelectasis and over-distension which characterize respiratory been suggested for infants at high risk of respiratory failure. The
distress syndrome (RDS) [3]. Preterm babies with RDS often need application of a SI maneuver (prolonged ination for 5 s) during
intubation and mechanical ventilation in the delivery room. These resuscitation procedures was demonstrated to be efcacious in a
aggressive interventions although life-saving may cause trauma to population of asphyxiated term infants in relation to lung volume
the lung structure and lead to chronic lung disease [11] changes [23]. A rapid increase in heart rate and oxygen saturation
Therefore, there is a search for ventilatory strategies in the reected the efcacy of the resuscitation maneuvers. [24,25]
delivery room (DR) capable of helping spontaneously breathing Clinical observations of the rst breath during neonatal
infants to adequately perform postnatal transition whilst reducing resuscitation of preterm infants show that an initial inating
the risk of lung damage. pressure around 20-25 cmH2O is generally effective in improving
heart rate and chest expansion [2]. Nevertheless, the premature
Ventilatory strategies that promote airway liquid clearance and infant is often unable to generate such high inating pressures
alveolar recruitment within the rst inspiratory excursions and is, therefore, incapable
of achieving a homogeneous and generalized alveolar recruitment.
At birth a pressure gradient is required to overcome airow As a consequence, many preterm infants need respiratory support
resistance and move lung uid distally through the airways; then and/or oxygen supplementation [26,27]. Intriguingly, SI manoeu-
to advance air to the terminal airspaces where the opening vers have not to markedly improved all the respiratory outcomes
pressure is necessary to overcome the surface tension and open in clinical practice. Hence, the application after birth of SI
the alveoli [12]. This rst lung recruitment manoeuver (LRM) may manoeuvers consisting of a peak pressure of 20-25 cmH2O for
be considered the pre-requisite to enable surfactant to reach a 10-20 seconds using a nasopharyngeal tube or an adequately sized
large proportion of alveoli, to begin its action, and to promote mask and a Neo-puff (Fisher & Paykel Healthcare Ltd, Auckland,
a more uniform lung volume [13]. This LRM is the rst step of a New Zealand) device, followed by the application of an adequate
high lung volume (open lung) strategy that is the key to protect PEEP (e.g.: 5 cmH2O) were shown to be effective in the
the neonatal lung during mechanical ventilation [14]. Interestingly, achievement of FRC and in improving short-term respiratory
the optimal technique of lung recruitment immediately after birth outcomes [reduction of tracheal intubation in DR and the need of
still remains unknown. To prompt lung expansion and establish an mechanical ventilation (MV)] in preterm infants < 29 weeks
early functional residual capacity [FRC] the use of positive end- gestation at risk for respiratory distress syndrome [28]. Recently, a
expiratory pressure (PEEP) or continuous positive airway pressure study was launched which focused on the effect upon heart rate,
(CPAP) of at least 4-6 cm H2O has been advocated [1518]. Thus, SpO2 and cerebral tissue oxygenation of applying SI to a small
resuscitation guidelines underscore the efcacy of PEEP during group of preterm infants of 28 weeks gestation immediately
resuscitation of preterm infants for the establishment and after birth to enhance lung recruitment and consisted of three
maintenance of an early FRC. FRC was achieved both by airway sustained inations of 20, 25 and 30 cm H2O each of 15 sec
stabilization and prevention of alveoli collapse during expiration duration followed by nasal CPAP. The majority of these infants
[2]. However, the use of xed PEEP/CPAP in very preterm infants needed more than one SI (with the application of growing
in the delivery room has not always been successful in establishing pressures) because of persistent hypoxia or bradycardia. Sustained
an adequate FRC. In a recent study, it was shown that a stepwise ination did not negatively affect heart rate, arterial saturation
PEEP strategy after birth improved gas exchange, lung mechanics, or cerebral tissue oxygen saturation and a rapid increase in the
and end expiratory volume without increasing lung injury in infants heart rate and an increase in cerebral tissue oxygen
preterm lambs [19]. Delivery room management with stepwise saturation were observed [29]. The results of these small clinical
increments of PEEP before giving surfactant has been satisfactorily trials seem to indicate that, under certain clinical conditions, SI
applied via face mask in non-spontaneously breathing very could contribute to enhance alveolar recruitment and help to
preterm infants in order to reach a heart rate >100 beats per stabilize preterm infants in the DR without intubation. However,
minute [bpm] and an SpO2 >85% within the rst 10 minutes after there are still many unanswered questions that need to be
birth, increasing the rates of survival and reducing morbidity evaluated including appropriate setting of SI (duration and peak
[20]. In the study protocol sustained ination (SI) maneuvers were pressure), selection of patients (rescue or prophylactic proce-
employed before intubating the babies. In fact SI, dened as the dure?), individually tailored setting of respiratory parameters used
application of an ination pressure (e.g.: 25 cm H2O) for a period to manage the preterm infants, effects upon cerebral circulation,
154 M. Vento, G. Lista / Paediatric Respiratory Reviews 16 (2015) 151156
management of a brisk increase in SpO2, and short and long-term has to be removed. The rst inspiratory efforts cause an elevation
outcomes of respiratory conditions. of the negative intra-thoracic pressure that highly contributes to
the passage of lung uid to the interstitium. In addition, blockage
Oxygen supplementation of the active chloride mediated secretion and efcient Na+/K+
ATPase dependent pumps in type II alveolar cells both contribute
Oxygen in foetal life to virtually clearing the uid from the airways. Components of the
Foetal life elapses in an environment, which is relatively lung uid are cleared directly into the vasculature or via lymphatic
hypoxic compared to the extra uterine world. The arterial partial from the lung interstitium over many hours. Processes that
pressure of oxygen (paO2) in utero is 25-30 mmHg (3.0-3.5 kPa) interfere with this mechanism such as prematurity, operative
while in the rst minutes after birth it will increase to 80- delivery and/or excessive sedation will delay airway uid
90 mmHg (10.5-12.0 kPa) [30]. Of note, oxygen delivery to tissue clearance and the establishment of effective gas exchange.
does not substantially differ in the foetus from the newborn. The Simultaneously, with the onset of labour, surfactant is secreted
reasons are: (i) the presence of foetal hemoglobin with a greater into the foetal lung uid in large quantities. Surfactant deposition
afnity for oxygen facilitates foetal oxygen uptake from the favouring alveolar distension upon expiration is essential for the
intervillous spaces from the placenta and increases oxygen establishment of a functional residual capacity (FRC) [10]. Preterm
saturation for a given paO2; (ii) extremely high foetal cardiac infants have delayed maturation of both, the Na+/K+ ATPase
output as compared with adults (250-300 mL/kg/min); (iii) dependent pumps and surfactant metabolism, have a compliant
shunting from venous return coming from the placenta to organs chest wall and muscular weakness, or do not spontaneously
with high oxygen needs ex-utero [31]. The intervillous partial initiate respiratory efforts [poor respiratory drive]. Altogether
pressure of oxygen is of 60 mmHg at 24-30 weeks gestation and these factors will predispose preterm infants to respiratory
of 45-48 mmHg at term. These values correspond to an SpO2 of insufciency and the need for positive pressure ventilation and
50%-60% in the foetus [32]. Interestingly, oxygen supplementation oxygen supplementation. In this scenario, the achievement of a
to the mother will cause a signicant increase of foetal paO2 and stable pre-ductal SpO2 is substantially delayed even in healthy
oxidative stress. In addition, conditions of the mother causing well-adapted preterm infants [10,37]. Recently, a group of
foetal hypoxaemia, such as preeclampsia or insulin dependent researchers developed a SpO2 reference range for the rst ten
diabetes, also cause oxidative stress to the foetus, and provoke minutes after birth for term and preterm infants who did not
postnatal maladaptation [32]. receive any medical intervention in the delivery room. Three
databases were merged, two from the Royal Womens Hospital
Use of the pulse oximeter in the delivery room (Melbourne; Australia) and another from the University &
Pulse oximetry is now widely employed in the DR to objectively Polytechnic Hospital La Fe (Valencia; Spain). Caregivers put a
evaluate newborn postnatal arterial oxygen saturation instead pre-ductal pulse oximeter (right hand or wrist) immediately after
of color, which has been traditionally employed but is subject to birth on all recruited babies and stored the data during the rst ten
great individual variability [33]. Oxygen saturation (SpO2) reects minutes of postnatal adaptation. Pulse oximeters were adjusted to
the percentage of oxy-hemoglobin present in the arterial blood. measure SpO2 every 2 seconds with maximum sensitivity. A total
The pulse oximeter transforms, by means of specic algorithms, of 468 infants and 61650 data points were studied. Centile charts
the degree of light absorption of oxygenated and deoxygenated were elaborated for term, late preterm and very preterm infants.
haemoglobin at different infrared light spectra, compared to These charts can be used to monitor SpO2 after birth and intervene
reference values of adult volunteers, and displays it as a when titrating FiO2 individually according to the infants response
percentage. This is the reason why no saturation values below [4]. Interestingly, term infants needed a mean of approximately
60%-70% are reliable. Pulse oximetry in the delivery room should 4-5 minutes to reach SpO2 of 90%; however, preterm infants
be put at maximum sensitivity with averaging measurements needed 6-7 minutes to reach the same SpO2. Moreover, very
every 2 seconds in order to detect minimal changes in a rapidly preterm infants of <32 weeks needed almost 9-10 minutes to
evolving clinical situation. The sensor is preferably put on the right reach a similar SpO2 [4]. In addition, heart rate was simultaneously
hand or wrist to evaluate oxygenation of pre-ductal blood recorded and independently of the time needed to achieve SpO2
perfusing the central nervous system. Importantly, the sensor heart rate was above 100 beats per min indicating that cardiac
should be protected from intense light to avoid false readings. To oxygenation was adequate [39]. At present, Dawsons nomogram
achieve a rapid and reliable reading the oximeter should be turned is the best available reference for titrating FiO2 in newly born
on, then the sensor should be applied rst to the baby and preterm infants in the delivery room. It is important to note that
thereafter to the oximeter cable. In this way reliable readings can Dawsons nomogram was made retrieving SpO2 in preterm babies
be mostly achieved with 60-90 seconds after birth. The presence of spontaneously breathing air. However, a substantial number of
foetal hemoglobin, which represents almost 100% of the hemoglo- preterm infants and especially those who are below 28 weeks
bin present in very preterm infants, may slightly alter the reading gestation receive continuous positive pressure (CPAP) ventilation
but lacks clinical relevance [3436]. Pulse oximeters also display for stabilization in the rst minutes after birth. In a recent study,
heart rate with great accuracy. This is extremely useful when it was shown that preterm babies breathing air, but supported
evaluating the response to resuscitation since heart rate is with CPAP, achieve higher SpO2 signicantly earlier than reected
probably the most practical clinical parameter reecting a good in Dawsons nomogram, and therefore caregivers in the DR
or bad response [37]. For all the above-mentioned reasons, pulse should be aware of a rapid increase of SpO2 and avoid
oximetry together with an air/oxygen blender and a well-trained hyperoxaemia [40].
and sufcient human team round the clock altogether have
optimised the resuscitation of term but especially very preterm Titrating oxygen in preterm infants in the rst minutes after birth
infants [38]. The initial steps once the baby is born are to achieve
stabilization from a cardio-respiratory and thermal perspective
Postnatal oxygen saturation following the ILCOR 2010 guidelines. This includes delayed cord
Immediately after birth the newly born infant has to aerate the clamping, keeping a neutral temperature, applying pulse oximetry
lungs and establish a functional residual capacity to initiate an on the right hand or wrist and non-invasive ventilation if the baby
effective gas exchange. In order to do so liquid lling the airspaces needs it [2]. Independently of the respiratory support needed, the
M. Vento, G. Lista / Paediatric Respiratory Reviews 16 (2015) 151156 155
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