Delivery Room Handling of the Newborn: Filling the Gaps

Newborn resuscitation and physiology related to the transition from intra- to extrauterine life have been studied for decades [1, 2]. Before the 1990s, few randomized controlled studies had been published in this field. Hutchinson et al. [3] published in 1964 a study testing out hyperbaric oxygen versus 100% oxygen after birth asphyxia. In 1992, the American Heart Association (AHA) published guidelines for newborn resuscitation [4]. The practices supporting the handling of the newborn in the delivery room were based on experts’ opinions since there was no support from evidence-based scientific literature.

Since then, we have learned that “expert opinion” is considered one of the lowest grades of evidence. From 1992 to 2024, the evidence behind neonatal resuscitation has evolved and so have the International Liaison Committee on Resuscitation (ILCOR) guidelines.

The indications for bag and mask ventilation in the 1992 algorithm were (1) apnea or gasping respirations, (2) heart rate less than 100 beats per minute (bpm), and (3) persistent central cyanosis despite application of 100% oxygen. Ventilation was to be initiated with a rate of 40–60/min. The response was assessed by chest wall motion, auscultation of breath sounds, and any increase in the heart rate. The inspiratory pressure was adjusted to a visible rise and fall of the chest. Chest compressions were to be performed if the heart rate was less than 60 bpm or if heart rate was between 60 and 80 bpm and not rising despite adequate ventilation with 100% oxygen for approximately 30 s. The recommended ventilation to chest compression ratio was 3:1, that is 30 ventilation and 90 compressions per minute. If the heart rate was >100 bpm, one should check for spontaneous respirations. If respiration seemed adequate, then positive pressure ventilation (PPV) could be discontinued. If the heart rate was between 60 and 100 bpm, one should continue ventilation and consider intubation [4].

The 1992 AHA guidelines recommended the use of 100% oxygen if PPV was needed. Sodium bicarbonate was freely given if a metabolic acidosis was developed or assumed to develop. Regarding the application of oxygen for newborn resuscitation, it was stated: “Therefore, if cyanosis, bradycardia, or other signs of neonatal distress are noted in a breathing newborn during stabilization, early administration of 100% oxygen is important while the neonate is being assessed for need of additional resuscitative measures. Initially, oxygen can be delivered by free flow through a face mask attached,” and further “If respiratory efforts are absent or inadequate so that assisted ventilation is required, 100% oxygen should be delivered by positive pressure ventilation using a face mask or endotracheal tube. Ideally, oxygen should be passed through a warmer and humidifier, although this is not always practical in the delivery room. The hazards of administering too much oxygen during the brief period required for resuscitation should not be a concern” [4].

The 1992 AHA guidelines recommended routine suction of the mouth, nose, and posterior pharynx if there was meconium-stained amniotic fluid even before delivery of the shoulders and thorax to decrease the risk of meconium aspiration syndrome (MAS), regardless of whether the meconium was thick or thin [4].

In 1990s, scientists started to conduct randomized controlled trials (RCTs) to generate evidence behind newborn resuscitation with a hope to change from expert-based to evidence-based newborn resuscitation guidelines. In 1993 and 1998, two quasi-randomized trials regarding newborn resuscitation were carried out. Both studies examined the effect of 100% versus 21% oxygen for newly born infants requiring PPV in the delivery room [5, 6]. The first genuine randomized and blinded study in the delivery room that compared 100% oxygen with room air was published by Vento et al. [7] in 2001. The results of these studies indicated that 100% oxygen even for a brief period of newborn resuscitation could be harmful. The 1992 AHA guidelines therefore needed to be modified.

Simultaneously routine tracheal suctioning for meconium aspiration was questioned by Wiswell et al. [8] who in a randomized controlled trial (RCT) in 2000 found that compared with expectant management, intubation and suctioning of vigorous meconium-stained infants did not result in a decreased incidence of MAS [9]. Vain et al. [10] also concluded that routine oropharyngeal suctioning of term infants born through meconium-stained amniotic fluid does not prevent MAS. These studies on room air versus 100% oxygen and suctioning or not of meconium-stained amniotic fluid were probably the first to collect evidence that systematically improved the algorithm of newborn resuscitation.

Colin Morley and his group in Melbourne, Australia, subsequently challenged several of the remaining steps of the algorithm for newborn resuscitation. Timing of interventions, face mask shapes and leakage, tidal volume, obstruction, oxygenation, pulse oximetry monitoring, testing out positive end expiratory pressure devices, and sustained inflation were systematically studied. Assessment of chest rise and heart rate detection and changes in end-tidal carbon dioxide detection, manual ventilation devices, manometers in use, and respiratory function monitoring were examined. This group also questioned the reliability of clinical observations such as infant’s color, tidal volume assessment, and Apgar score variability. They were also pioneering video recording of neonatal resuscitation [11‒24]. In the last decade, there have been numerous randomized controlled trials and observational studies that focused on the various steps of newborn resuscitation algorithm. This article aims to summarize the development of the ILCOR newborn resuscitation algorithm and to present a comprehensive review of the gaps in newborn resuscitation, thus being helpful in underscore the research priorities in this field.

From the year 2000, the ILCOR recommendations for newborn resuscitation have been more and more evidence-based. Systematic review protocols are submitted to prospective registries of systematic reviews. Data gathered are assessed for risk of bias, and analysis is conducted using GRADE methodology utilizing GRADEpro [25, 26]. Based on the summary of evidence, Neonatal Life Support (NLS) task force develops consensus of science and treatment recommendations and posts it for public comments. The process of evidence to decision on treatment recommendations is guided by and summarized in Evidence to Decision framework which is published along with each Consensus on Science with Treatment Recommendations (CoSTR) on ILCOR website [27]. This process is overseen by the ILCOR Scientific Advisory Committee.

Previously, new recommendations were published every 5th year. Since 2020, ILCOR has presented focused annual updates.

Since the adoption of these strict procedures, ILCOR guidelines have evolved significantly to incorporate emerging evidence. Between 1992 and 2010, ILCOR changed its recommendations for using oxygen in the delivery room in several steps. First, in 1992, AHA/ILCOR recommended the use of 100% oxygen for resuscitation [4]; in 2000, ILCOR opened up for using air if oxygen was not available [28]; in 2005, ILCOR suggested insufficient evidence to specify the concentration of oxygen to initiate resuscitation [29]; and in 2010, they recommended 21% oxygen for initial oxygen concentration for the term and near-term infants [30]. In 2015, ILCOR warned strongly against hyperoxia during the resuscitation process [31]. In 2015, 21–30% oxygen concentration was recommended for initiating resuscitation of preterm infants [31].

Handling of meconium aspiration has also dramatically changed from tracheal suctioning for all infants born through meconium-stained amniotic fluid including those who are vigorous at birth to not recommending tracheal suctioning except in instances where meconium is obstructing the airway and preventing adequate ventilation [29‒31].

In 2010, the strict timing of 30 s sequences was removed; instead, the first minute, the golden minute, was introduced. Drying, warming the infant, and wrapping it in plastic (<28 weeks gestational age), stimulation to breathe, airway positioned, heart rate, and breathing rate should have been assessed within 30 s. Within 60 s, respiratory support should be established if needed, and pulse oximetry, if available, should be started [30].

In 2015, the terminology was changed from “resuscitation” to “support of transition.” For uncompromised infants, a delay of cord clamping ≥1 min was recommended. It was also recommended that body temperature for non-asphyxiated infants should be kept between 36.5 and 37.5°C. Further, maintenance of temperature for newborns <32 weeks’ gestation of 36.5–37.5°C should be achieved by warmed humidified respiratory gases, increased room temperature (<28 weeks room temp >25°C), plastic wrapping, cap, and thermal mattress [31].

In 2015, continuous positive airways pressure rather than intubation for spontaneously breathing preterm infants and hypothermia therapy in low-income settings and cooling with ice packs were recommended [31]. ILCOR suggested that, where resources permit, the use of electrocardiogram for heart rate assessment of a newly born infant in the delivery room is reasonable, but pulse oximetry and auscultation may be alternatives for heart rate assessment at birth [31]. In our opinion, a combination of these methods should be used to assess the heart rate as false-positive or false-negative assessment can have adverse consequences [32]. In 2020 and 2024, ILCOR clearly mentions that newer modalities need further evaluation before they can be adopted widely [33‒35].

Twenty-two procedures were reviewed in 2020, and only 6 of these were new since 2015. The evidence for all these new procedures was, however, low or very low, or nonexistent. The strength of recommendations was weak for 5 and not-existent for one [33]. In a review, we identified some weaknesses and gaps in the 2020 ILCOR recommendations [36]. One of these was that time of birth was not clearly defined. This is critical when the so-called “golden minute” is so important. We suggested that the baby is delivered when the whole body is out [37]. The concept of the first golden minute as well as the Apgar scoring does not make meaning if the time of birth is not exactly defined.

Online supplementary Table 1 (for all online suppl. material, see https://doi.org/10.1159/000540079) summarizes the 22 topics reviewed by ILCOR, the recommendations, and their strength of evidence. Out of these 22 recommendations, there were 15 assessments of strength of recommendation and degree of evidence. Fourteen of the recommendations were based on weak evidence and 1 only on strong evidence [33]. This latter is the recommendation to avoid 100% O₂ for resuscitation of term infants [31]. Eight recommendations were based on very low, 6 on low and only 1 on moderate evidence, and 1 on no evidence [33]. This reveals that there are still large gaps in the evidence the newborn resuscitation algorithm is based upon.

ILCOR publishes summaries of gaps in knowledge with the aim to stimulate investigators to pursue more targeted studies to help close the gaps. In 2012, ILCOR identified several gaps which the following years have been explored in more detail [38]. In Table 1, we list 15 topics not reviewed by ILCOR in 2020. Several of these may not have needed an update, and several of them have already been tested. However, several of these topics indicate a lack of evidence to make strong recommendations.

Table 2 summarizes 32 knowledge gaps identified by ILCOR 2020. Eight of these are related to epinephrine (adrenaline), 11 to vascular access, and 4 to sustained inflation. Tables 1 and 2 summarize much of the knowledge gap for newborn resuscitation.

In addition to the topics listed above, we would add: how to oxygenate infants <32 weeks of gestational age who need PPV in the delivery room? This applies both to initial FiO₂ and how to titrate up or down during the first 10 min of life. There is also a need to collect information on the optimal rise in oxygen saturation targets for different gestational ages in the first minutes of life. A recent individual patient meta-analysis of 12 RCTs has provided important information regarding the optimal initial FiO₂ and saturation targets for preterm infants in the first 10 min after birth [39].

Further, Ortiz-Movilla et al. [40] recently concluded that using random audits, checklists, briefings, and debriefings in the resuscitation of newborns delivered before 32 weeks is feasible but has no impact on short-term clinical outcomes or correct performance of the procedure. Audits of neonatal resuscitation beds significantly improved their preparation.

In 2021 [41], 2022 [42], 2023 [43], and 2024 [33], updates on several topics were published by ILCOR. These are summarized in Table 3. Some of these conclusions include that regarding devices for administering PPV, a T-piece is preferable over the use of self-inflating bags (weak recommendation, very low certainty evidence). However, a self-inflating bag should be available as backup. Family presence during neonatal resuscitation is also recommended, provided the circumstances allow this (weak recommendation, very low certainty of evidence) [41]. Regarding cord clamping, deferring clamping of the umbilical cord for at least 60 s is recommended for preterm infants less than 37 weeks deemed not to require immediate resuscitation at birth (strong recommendation, moderate-certainty evidence).

In preterm infants born at 28 + 0 to 36 + 6 weeks’ gestational age who do not receive deferred cord clamping, ILCOR suggests umbilical cord milking as a reasonable alternative to immediate cord clamping to improve infant hematologic outcomes. Individual maternal and infant circumstances should be considered (conditional recommendation, low certainty evidence). ILCOR suggests against intact cord milking for infants born at less than 28 weeks of gestation (weak recommendation, low certainty evidence) [43].

Further, in newborn infants who are unintentionally hypothermic after birth, rewarming should be commenced, but there is according to ILCOR insufficient evidence to recommend either rapid (≥0.5°C/h) or slow (<0.5°C/h) rates of rewarming. Frequent or continuous monitoring of the temperature should be undertaken, particularly if using a supraphysiological set temperature point to accelerate the rewarming rate, because of the risk of causing hyperthermia. In any hypothermic infant, blood glucose should be monitored because there is a risk of hypoglycemia [41].

The neonatal resuscitation algorithm has for 30 years been developed stepwise. An important shift occurred about 25–30 years ago when it was understood that each intervention should be studied in randomized controlled blinded trials. Still, it is surprising how little evidence has been collected. Further, if evidence is available, it is mostly weak and of low or very low grade. The need for evidence to fill knowledge gaps is therefore still immense. However, collecting solid evidence is also challenging. Funding is often limited, and industry-funded studies may not be reliable. Another reason these gaps are not filled are due to challenges in getting informed consent. Deferred consent may not be accepted by the Ethical Committee [44]. Chest compressions, for instance, are rare and may require large networks and multicenter studies to test out in randomized ways different aspects of this procedure [45]. Trial insurance may also be difficult to obtain. It is therefore of utmost importance that conflicts of interest are declared when ILCOR and other international bodies are recommending new techniques and equipment [32]. It is not uncommon to find changes in study design and primary outcomes to favor one device over other in industry-sponsored studies [46, 47]. It is also important to see such findings are replicable in independent assessment by investigators without any conflict of interest [47, 48].

The research leading to a refined newborn resuscitation algorithm may have contributed to a substantial reduction in global neonatal mortality. For instance, the introduction of ventilating with air instead of pure oxygen reduced the mortality of term asphyxiated newborn infants by approximately 30% [49, 50] and paved the way for resuscitation programs such as Helping Babies Breathe [51]. These measures may have contributed substantially to the reduction of the approximately 300,000 annual newborn deaths due to birth asphyxia in the recent 20–25 years [52]. A major remaining challenge is to develop algorithms and procedures that are applicable in low- and middle-income countries (LMIC) based on studies from the relevant populations [53]. ILCOR suggests for LMIC, “the use of therapeutic hypothermia in comparison with standard care alone for term (≥37 + 0 weeks’ gestational age) newborn infants with evolving moderate-to-severe hypoxic-ischemic encephalopathy. A suitable level of supportive neonatal care should be available (weak recommendation, low certainty evidence).” Therapeutic hypothermia should only be conducted in neonatal care facilities with specific capabilities such as availability of adequate resources to offer intravenous therapy, respiratory support, pulse oximetry, antibiotics, antiseizure medication, transfusion services, radiology (including ultrasound), and pathology testing, as required [33].

The recommendations on post-asphyxic hypothermia therapy mentioned above illustrate some of the challenges in making global recommendations; one size does not fit all. The Helix trial sparked a discussion on the usefulness of post-asphyxial hypothermia therapy in LMIC finding increased mortality after hypothermia treatment [54]. The study has both its proponents and opponents [55, 56]. Contradictory results regarding this issue are according to Kumar and Kumar mainly due to differences in the populations included and possible imbalances between the groups at enrollment. More than two thirds of the neonates included were born in other facilities which may indicate less training in some of these sites [57].

Bruckner et al. [58] recently published recommendations for delivery room handling in high- and low-income countries, respectively. Regionalization of high-risk deliveries in level III institutions with experience in newborn resuscitation and the establishment of efficient transport systems that rapidly take care of complex cases, stabilize them, and transport them to the level III center are of utmost importance [53]. Lack of oxygen blenders, continuous positive airways pressure, ventilators, and other equipment contributes to maintaining a still too high neonatal mortality rate in LMIC.

Recently, Foglia et al. [59] published recommended guidelines for uniform reporting of neonatal resuscitation according to the so-called Utstein style. Seven relevant domains were identified: setting, patient, antepartum, birth, pre-resuscitation, resuscitation process, post-resuscitation process, and outcome. Guidelines with standard definitions for clinical studies of resuscitation of the newly born child were reported.

Newborn resuscitation has the last 30 years become more evidence-based. However, there are still numerous gaps to fill, and RCTs are needed. Specific studies in LMIC are urgently needed because we aim at a world where “Every Newborn Counts. Everywhere.”

O.D.S. was a member of the author group of the 2000 AHA/ILCOR recommendations. O.D.S. has received funding from Laerdal Global Health. V.K. is a member of the ILCOR group.

No funding was received.

O.D.S. wrote the first draft. V.K. and M.V. contributed with critical and constructive comments. All authors approved the final version.