Variation in delivery room management of preterm infants across Europe: a survey of the Union of European Neonatal and Perinatal Societies.

The aim of the present study, endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Italian Society of Neonatology (SIN), was to analyze the current delivery room (DR) stabilization practices in a large sample of European birth centers that care for preterm infants with gestational age (GA) < 33 weeks. Cross-sectional electronic survey was used in this study. A questionnaire focusing on the current DR practices for infants < 33 weeks' GA, divided in 6 neonatal resuscitation domains, was individually sent to the directors of European neonatal facilities, made available as a web-based link. A comparison was made between hospitals grouped into 5 geographical areas (Eastern Europe (EE), Italy (ITA), Mediterranean countries (MC), Turkey (TUR), and Western Europe (WE)) and between high- and low-volume units across Europe. Two hundred and sixty-two centers from 33 European countries responded to the survey. At the time of the survey, approximately 20,000 very low birth weight (VLBW, < 1500 g) infants were admitted to the participating hospitals, with a median (IQR) of 48 (27-89) infants per center per year. Significant differences between the 5 geographical areas concerned: the volume of neonatal care, ranging from 86 (53-206) admitted VLBW infants per center per year in TUR to 35 (IQR 25-53) in MC; the umbilical cord (UC) management, being the delayed cord clamping performed in < 50% of centers in EE, ITA, and MC, and the cord milking the preferred strategy in TUR; the spotty use of some body temperature control strategies, including thermal mattress mainly employed in WE, and heated humidified gases for ventilation seldom available in MC; and some of the ventilation practices, mainly in regard to the initial FiO2 for < 28 weeks' GA infants, pressures selected for ventilation, and the preferred interface to start ventilation. Specifically, 62.5% of TUR centers indicated the short binasal prongs as the preferred interface, as opposed to the face mask which is widely adopted as first choice in > 80% of the rest of the responding units; the DR surfactant administration, which ranges from 44.4% of the birth centers in MC to 87.5% in WE; and, finally, the ethical issues around the minimal GA limit to provide full resuscitation, ranging from 22 to 25 weeks across Europe. A comparison between high- and low-volume units showed significant differences in the domains of UC management and ventilation practices.    Conclusion: Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs. What is Known: • Delivery room (DR) support of preterm infants has a direct influence on both immediate survival and long-term morbidity. • Resuscitation practices for preterm infants often deviate from the internationally defined algorithms. What is New: • Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. • Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs.

Neonatal resuscitation practices in Italy: a survey of the Italian Society of Neonatology (SIN) and the Union of European Neonatal and Perinatal Societies (UENPS).

BACKGROUND: Providing appropriate care at birth remains a crucial strategy for reducing neonatal mortality and morbidity. We aimed to evaluate the consistency of practice and the adherence to the international guidelines on neonatal resuscitation in level-I and level-II Italian birth hospitals. METHODS: This was a cross-sectional electronic survey. A 91-item questionnaire focusing on current delivery room practices in neonatal resuscitation was sent to the directors of 418 Italian neonatal facilities. RESULTS: The response rate was 61.7% (258/418), comprising 95.6% (110/115) from level-II and 49.0% (148/303) from level-I centres. In 2018, approximately 300,000 births occurred at the participating hospitals, with a median of 1664 births/centre in level-II and 737 births/centre in level-I hospitals. Participating level-II hospitals provided nasal-CPAP and/or high-flow nasal cannulae (100%), mechanical ventilation (99.1%), HFOV (71.0%), inhaled nitric oxide (80.0%), therapeutic hypothermia (76.4%), and extracorporeal membrane oxygenation ECMO (8.2%). Nasal-CPAP and/or high-flow nasal cannulae and mechanical ventilation were available in 77.7 and 21.6% of the level-I centres, respectively. Multidisciplinary antenatal counselling was routinely offered to parents at 90.0% (90) of level-II hospitals, and 57.4% (85) of level-I hospitals (p < 0.001). Laryngeal masks were available in more than 90% of participating hospitals while an end-tidal CO2 detector was available in only 20%. Significant differences between level-II and level-I centres were found in the composition of resuscitation teams for high-risk deliveries, team briefings before resuscitation, providers qualified with full resuscitation skills, self-confidence, and use of sodium bicarbonate. CONCLUSIONS: This survey provides insight into neonatal resuscitation practices in a large sample of Italian hospitals. Overall, adherence to international guidelines on neonatal resuscitation was high, but differences in practice between the participating centres and the guidelines exist. Clinicians and stakeholders should consider this information when allocating resources and planning perinatal programs in Italy.

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic-ischemic encephalopathy.

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life.

Neonatal Resuscitation Practices in Europe: A Survey of the Union of European Neonatal and Perinatal Societies.

BACKGROUND: We aimed to evaluate the policies and practices about neonatal resuscitation in a large sample of European hospitals. METHODS: This was a cross-sectional electronic survey. A 91-item questionnaire focusing on the current delivery room practices in neonatal resuscitation domains was individually sent to the directors of 730 European neonatal facilities or (in 5 countries) made available as a Web-based link. A comparison was made between hospitals with ≤2,000 and those with >2,000 births/year and between hospitals in 5 European areas (Eastern Europe, Italy, Mediterranean countries, Turkey, and Western Europe). RESULTS: The response rate was 57% and included participants from 33 European countries. In 2018, approximately 1.27 million births occurred at the participating hospitals, with a median of 1,900 births/center (interquartile range: 1,400-3,000). Routine antenatal counseling (p < 0.05), the presence of a resuscitation team at all deliveries (p < 0.01), umbilical cord management (p < 0.01), practices for thermal management (p < 0.05), and heart rate monitoring (p < 0.01) were significantly different between hospitals with ≤2,000 births/year and those with >2,000 births/year. Ethical and educational aspects were similar between hospitals with low and high birth volumes. Significant variance in practice, ethical decision-making, and training programs were found between hospitals in 5 different European areas. CONCLUSIONS: Several recommendations about available equipment and clinical practices recommended by the international guidelines are already implemented by centers in Europe, but a large variance still persists. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs.

Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial.

BACKGROUND: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). METHODS: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. FINDINGS: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). INTERPRETATION: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy. FUNDING: None.

Seizure burden and neurodevelopmental outcome in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: A single center observational study.

OBJECTIVE: To examine the relationship between electrographic seizures and developmental outcome at 18 and 24 months in neonates with moderate and severe hypoxic-ischemic encephalopathy [HIE] treated with therapeutic hypothermia [TH]. STUDY DESIGN: 30 term infants with moderate-severe HIE treated with TH were enrolled prospectively from June 2012 to May 2018. All had continuous single channel amplitude integrated EEG (aEEG) monitoring for a minimum of 72 h and brain MR within 4 weeks. The aEEG was classified by severity of background and seizure burden. MR images were graded by the severity of injury. Outcome (defined abnormal in case of death, dyskinetic or spastic quadriplegic cerebral palsy, epilepsy, or Bayley III score < 85 in all three subscales or < 70 in any individual subscale) was assessed at 18 and 24 months. RESULTS: Seizures were recorded in 24 out of 30 [80 %] neonates and an abnormal outcome was observed in 7 [23 %] of infants. Patients with poor outcome had a statistically significant correlation with: high seizure burden (p = 0.0004), need for more than one antiepileptic drugs (p = 0.006), a persistent abnormal aEEG trace at 48 h (p = 0.0001) and moderate-severe brain injury at MRI (p = 0.0001). Moreover, infants with status epilepticus or frequent seizures reported a significantly association with abnormal MR imaging and poor outcome than patients with sporadic seizures (p = 0.0009). CONCLUSION: The role of seizures in the pathogenesis of brain injury remains controversial. In our cohort the presence of seizures, per se, was not associated with abnormal outcome; however a high seizure burden as well as a persistent abnormal aEEG background pattern and MR lesions resulted significantly associated with poor prognosis.

Electromagnetic fields in neonatal incubators: the reasons for an alert.

BACKGROUND: Neonatal incubators are important tools for sick newborns in the first few days of life. Nevertheless, their electric engine, often very close to the newborn's body, emits electromagnetic fields (EMF) to which newborns are exposed. Aim of this paper is to review the available literature on EMF exposure in incubators, and the effects of such exposures on newborns that have been investigated. METHODS: We carried out a systematic review of studies about EMF emissions produced by incubators, using Medline and Embase databases from 1993 to 2017. RESULTS: We retrieved 15 papers that described the EMF exposure in incubators and their biological effects on babies. EMF levels in incubators appear to be between 2 and 100 mG, depending on the distance of the mattress from the electric engine. In some cases, they exceed this range. These values interfere with melatonin production or with vagal tone. Even caregivers are exposed to high EMF, above 200 mG, when working at close contact with the incubators. CONCLUSION: EMF have been described as potentially hazardous for human health, and values reported in this review are an alert to prevent babies' and caregivers' exposure when close to the incubators. A precautionary approach should be adopted in future incubator design, to prevent high exposures of newborns in incubators and of caregivers as well.

Severe neurologic and hepatic toxicity in a newborn prenatally exposed to methamphetamine. A case report.

OBJECTIVE: In the recent years the increase of methamphetamines (MTA) abusers women has become an emerging problem. Very little data has been published regarding the effects of prenatal MTA exposure. We describe a case of MTA related toxicity in a term newborn which have early onset of neonatal encephalopathy and liver failure. CASE REPORT: A term infant born to a MTA abuser mother developed seizures and severe neurological symptoms shortly after birth. Methamphetamine was detected both in maternal and in neonatal urine. The laboratoristic tests revealed severe hepatic insufficiency, coagulopathy and thrombocytopenia. Due to neonatal encephalopathy the newborn underwent hypothermia. Phenobarbital, fresh frozen plasma, platelet transfusions and vitamin K were administered. Cranial ultrasonography and magnetic resonance imaging (MRI) showed diffuse white matter damage and two ischemic-hemorrhagic cerebral lesions. Gradually the clinical conditions improved, at 1 month MRI showed a stabilization of cerebral lesions with residual diffuse leukomalacia. Physiotherapy and neurological follow up is ongoing to evaluate the long term effects. CONCLUSIONS: although infrequent, MTA-related toxicity should be suspected in infants with neurologic and hepatic symptoms. Further studies are warranted to confirm our findings in order to identify newborns at high risk of acute MTA toxicity in time to provide them the appropriate support.

Delivery room management of extremely low birth weight infants in Italy: comparison between academic and non-academic birth centres.

OBJECTIVE: International Guidelines provide a standardised approach to newborn resuscitation in the DR and, in their most recent versions, recommendations dedicated to management of ELBWI were progressively increased. It is expected that introduction in clinical practice and dissemination of the most recent evidence should be more consistent in academic than in non-academic hospitals. The aim of the study was to compare adherence to the International Guidelines and consistency of practice in delivery room management of extremely low birth weight infants between academic and non-academic institutions. METHODS: A questionnaire was sent to the directors of all Italian level III centres between April and August 2012. RESULTS: There was a 92% (n = 98/107) response rate. Apart from polyethylene wrapping to optimise thermal control, perinatal management approach was comparable between academic and non-academic centres. CONCLUSIONS: There were minor differences in management of extremely low birth weight infants between Italian academic and non-academic institutions, apart from thermal management. Although there was a good, overall adherence to the International Guidelines for Neonatal Resuscitation, temperature management was not in accordance with official recommendations and every effort has to be done to improve this aspect.

Revised recommendations concerning palivizumab prophylaxis for respiratory syncytial virus (RSV).

Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease. Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection.

Delivery room management of ELBW infants in Italy.

In this article we evaluated the consistency of practice and the adherence to the International Guidelines in early delivery room management of ELBW infants in Italy. A polyethylene bag/wrap was used by 54 centres (55.1%). In Northern regions, one centre (2.5%) reported to use oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was widely used (77/97, 79.4%). A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy. Forty-seven out of 98 (47.9%) centres declared to administer prophylactic surfactant in delivery room. Although there were geographic differences in the country, our results showed a good general adherence to the International Guidelines for Neonatal Resuscitation.

Broad-spectrum light versus blue light for phototherapy in neonatal hyperbilirubinemia: a randomized controlled trial.

Phototherapy is standard care for treatment of neonatal hyperbilirubinemia. Our aim was to compare the effectiveness of broad-spectrum light (BSL) to that of blue light emitting diodes (LED) phototherapy for the treatment of jaundiced late preterm and term infants. Infants with gestational age from 35(+0) to 41(+6) weeks of gestation and nonhemolytic hyperbilirubinemia were randomized to treatment with BSL phototherapy or blue LED phototherapy. A total of 20 infants were included in the blue LED phototherapy group and 20 in the BSL phototherapy group. The duration of phototherapy was lower in the BSL than in the blue LED phototherapy group (15.8 ± 4.9 vs. 20.6 ± 6.0 hours; p = 0.009), and infants in the former group had a lower probability (p = 0.015) of remaining in phototherapy than infants in the latter. We concluded that BSL phototherapy is more effective than blue LED phototherapy for the treatment of hyperbilirubinemia in late preterm and term infants. Our data suggest that these results are not due to the different irradiance of the two phototherapy systems, but probably depend on their different peak light emissions.

Changes over time in delivery room management of extremely low birth weight infants in Italy.

AIM: To identify changes in practice between two historical periods (2002 vs. 2011) in early delivery room (DR) management of ELBWI in Italian tertiary centres. METHODS: A questionnaire was sent to the directors of all Italian level III centres between April and August 2012. The same questionnaire was used in a national survey conducted in 2002. Among the participating centres, those that filled the questionnaire in both study periods were selected for inclusion in this study. RESULTS: There was an 88% (n=76/86) and 92% (n=98/107) response rate in the 2 surveys, respectively. The two groups overlapped for 64 centres. During the study period, the use of polyethylene bags/wraps increased from 4.7% to 59.4% of the centres. The units using 100% oxygen concentrations to initiate resuscitation of ELBWI decreased from 56.2% to 6.2%. The approach to respiratory management was changed for the majority of the examined issues: positive pressure ventilation (PPV) administered through a T-piece resuscitator (from 14.0% to 85.9%); use of PEEP during PPV (from 35.9% to 95.3%); use of CPAP (from 43.1% to 86.2%). From 2002 to 2011, the percentages of ELBWI intubated in DR decreased in favor of those managed with N-CPAP; ELBWI receiving chest compressions and medications at birth were clinically comparable. CONCLUSIONS: During the two study periods, the approach to the ELBWI at birth significantly changed. More attention was devoted to temperature control, use of oxygen, and less-invasive respiratory support. Nevertheless, some relevant interventions were not uniformly followed by the surveyed centres.

Delivery room management of extremely low birthweight infants shows marked geographical variations in Italy.

AIM: To evaluate any geographical variations in practice and adherence to international guidelines for early delivery room management of extremely low birthweight (ELBW) infants in the North, Centre and South of Italy. METHODS: A questionnaire was sent to all 107 directors of Italian level III centres between April and August 2012. RESULTS: There was a 92% (n = 98) response rate. A polyethylene bag/wrap was used by 54 centres (55.1%), with the highest rate in Northern Italy (77.5%) and the lowest rate in Southern (37.7%) areas. In Northern regions, one centre (2.5%) said it used oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was more frequently available in the Northern (95%) units than in those in the Central (66.7%) and Southern (69.4%) regions. A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy: 5%, 18% and 22% in Northern, Central and Southern units, respectively. CONCLUSION: In Italy, delivery room management of ELBW infants showed marked geographical variations. Implementation of national training programmes could increase adherence to the guidelines and reduce such discordance.

Early lactation failure and formula adoption after elective caesarean delivery: cohort study.

OBJECTIVE: To investigate the effects of elective primary and elective repeat caesarean deliveries on lactation at hospital discharge. DESIGN: Cohort study. SETTING: Four Italian teaching hospitals - Padua, Brescia, L'Aquila and Udine. INTERVENTIONS: Deliveries were classified as vaginal, elective caesarean (primary and repeat) or emergency caesarean. A total of 2296 (24.7%) infants born by caesarean section (CS), 816 of which (35.5%) classified as primary elective CS and 796 (34.7%) as repeat elective CS, were studied. Moreover, 30.2% of the elective CS deliveries took place before 39 weeks. MAIN OUTCOME MEASURES: Feeding modalities at discharge: formula, complementary and breastfeeding. RESULTS: At discharge, 6.9% of the vaginal delivery mothers, 8.3% of the emergency CS mothers, 18.6% of the elective CS mothers, 23.3% of the primary CS mothers and 13.9% of the repeat CS mothers were using infant formula exclusively. Multivariate analysis (OR; 95% CI) identified primary elective delivery (3.74; 3.0 to 4.60), lower gestational age (1.16; 1.10 to 1.23), and place L'Aquila versus Udine (1.42; 1.01 to 2.09) and of Brescia versus Udine hospitals (6.16; 4.53 to 8.37) as independent predictors of formula feeding at discharge. CONCLUSIONS: These findings provide new information about the risks of breastfeeding failure connected to elective CS delivery, particularly if primary and scheduled before 39 weeks of gestation.

Oxygen administration for the resuscitation of term and preterm infants.

Oxygen has been widely used in neonatal resuscitation for about 300 years. In October 2010, the International Liaison Committee on Neonatal Resuscitation released new guidelines. Based on experimental studies and randomized clinical trials, the recommendations on evaluation and monitoring of oxygenation status and oxygen supplementation in the delivery room were revised in detail. They include: inaccuracy of oxygenation clinical assessment (colour), mandatory use of pulse oximeter, specific saturation targets and oxygen concentrations during positive pressure ventilation in preterm and term infants. In this review, we describe oxygen management in the delivery room in terms of clinical assessment, monitoring, treatment and the gap of knowledge.

Fortification of maternal milk for preterm infants.

During the last few decades, neonatal survival rates for preterm infants have markedly been improved. The American Academy of Pediatrics recommended that preterm neonates should receive sufficient nutrients to enable them to grow at a rate similar to that of fetuses of the same gestational age. Although human milk is the recommended nutritional source for newborn infants for at least the first six months of postnatal life, unfortified human breast milk may not meet the recommended nutritional needs of growing preterm infants. Human milk must therefore be supplemented (fortified) with the nutrients in short supply. The fortification of human milk can be implemented in two different forms: standard and individualized. The new concepts and recommendations for optimization of human milk fortification is the "individualized fortification". Actually, two methods have been proposed for individualization: the "targeted/tailored fortification" and the "adjustable fortification". In summary, the use of fortified human milk produces adequate growth in premature infants and satisfies the specific nutritional requirements of these infants. The use of individualized fortification is recommended.