Use of neonatal lung ultrasound in European neonatal units: a survey by the European Society of Paediatric Research.

OBJECTIVE: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved. DESIGN AND INTERVENTION: International online survey. RESULTS: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique. CONCLUSIONS: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline.

Future of clinical trials in the delivery room: time for pragmatism.

Despite increased amounts of research, most of the evidence that supports treatment of newborns in the delivery room is rated 'low' rather than 'high' quality. This assessment stems largely from a lack of evidence from clinical trials. When trials have been performed, the evidence has often been downgraded due to enrolment of small or poorly representative samples, and for lack of blinding of caregivers and outcome assessors. Delivery room trials present particular challenges when obtaining consent, enrolling participants, taking measures to limit bias and identifying appropriate outcome measures. We hope our suggestions as to how future delivery room trials could be more pragmatic will inform the design of large studies that are necessary to allow clinical practice to evolve.

Prospective comparison of thermometers used in very preterm infants.

We measured temperature on admission to the neonatal unit in a cohort of 54 very preterm infants. We measured rectal temperature with a digital thermometer (Microlife MT-1931) as the gold standard (MT-R). We also measured axillary temperature with the MT (MT-A), with the Welch Allyn SureTemp Plus 692 in 'continuous' (WAC) mode and in the default 'predictive' (WAP) mode. While MT-A and WAC frequently differed from MT-R by ≥0.3°C, they were both reasonably sensitive and specific for hypothermia (MT-R <36.5°C). WAP overestimated MT-R by ≥0.5°C on 37/53 (70%) occasions and had poor sensitivity for hypothermia, identifying only 2 of 29 infants with MT-R <36.5°C as hypothermic.

Hypotension in Preterm Infants (HIP) randomised trial.

OBJECTIVE: To determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation. DESIGN: Double-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment. SETTING: 10 sites across Europe and Canada. PARTICIPANTS: Infants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage. INTERVENTION: Participants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management). PRIMARY OUTCOME: Survival to 36 weeks of PMA without severe brain injury. RESULTS: The trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038). CONCLUSION: Though this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area. TRIAL REGISTRATION NUMBER: NCT01482559, EudraCT 2010-023988-17.

Comparison of rectal and axillary temperature measurements in preterm newborns.

OBJECTIVE: To compare rectal and axillary temperatures in preterm newborns on admission to the neonatal intensive care unit (NICU). DESIGN: Secondary analysis of data collected in a randomised controlled trial (RCT). SETTING: Maternity hospital, level 3 NICU. PATIENTS: Seventy-two newborns <31 weeks who were enrolled in the BAMBINO RCT (A randomised trial of exothermic mattresses to prevent heat loss in preterm infants at birth, ISRCTN31707342). INTERVENTIONS: Newborns were placed in polyethylene bags and were randomised to placement on exothermic mattresses, or not in the delivery room. All infants had rectal and axillary temperatures measured in immediate succession using a digital thermometer on NICU admission. OUTCOME MEASURES: Admission rectal and axillary temperatures. RESULTS: Mean (SD) gestational age was 28 (2) weeks and birth weight was 1138 (374) g. Mean rectal-axillary temperature difference was 0.1 (0.5°C) (range -1.4°C to +1.5°C). Rectal and axillary temperatures differed by ≥0.5°C in 18/72 (25%) infants; axillary temperature was higher than rectal in 6 (8%) and lower in 12 (17%). There was a positive linear relationship between rectal and axillary measurements (Pearson's correlation R=0.84). Applying the Bland-Altman technique, the width of 95% prediction interval was 1.8°C (-0.8°C to 1.0°C) implying that rectal and axillary measurements may vary by up to 1.0°C. Axillary temperature had a sensitivity of 65% when used to detect rectal hyperthermia and 100% sensitivity for hypothermia. CONCLUSION: Paired rectal and axillary temperature measurements in preterm newborns on NICU admission vary significantly. Axillary temperature was sensitive at detecting rectal hypothermia but not hyperthermia. Axillary temperature may not be an accurate proxy for rectal temperature measurement in all preterm newborns on NICU admission.

Randomised study of heart rate measurement in preterm newborns with ECG plus pulse oximetry versus oximetry alone.

AIM: To determine whether the IntelliVue monitor (ECG plus Masimo pulse oximeter (PO)) displays heart rate (HR) at birth more quickly than Nellcor PO (PO alone) among infants of 29-35 weeks' gestational age. METHODS: Unmasked parallel group randomised (1:1) study. RESULTS: We planned to enrol 100 infants; however, the study was terminated due to the COVID-19 pandemic when 39 infants had been enrolled (17 randomised to IntelliVue, 22 to Nellcor). We found no differences between the groups in the time to first HR display (median (IQR) IntelliVue ECG 49 (33, 71) vs Nellcor 47 (37, 86) s, p>0.999), in the proportion who had a face mask applied for breathing support, or in the time at which it was applied. Infants monitored with IntelliVue were handled more frequently and for longer. CONCLUSION: IntelliVue ECG did not display HR more quickly than Nellcor PO in preterm infants. We found no differences in the rate of or time to intervention between groups. Our study was terminated early so these findings should be interpreted with caution. TRIAL REGISTRATION NUMBER: ISRCTN16473881.

Bench-top comparison of thermometers used in newborn infants.

We wished to determine the accuracy of thermometers used to measure temperature in newborn infants. We measured the temperature of a water bath with three types of thermometer set at 0.5°C increments between 32.5°C and 38.5°C and compared the values to a control. We recorded the time to display steady-state temperature. The Microlife thermometer most closely approximated control temperature (mean difference <0.1°C (SD<0.1°C)) and displayed a reading in a mean time of 29 s (SD 2 s). Used in 'predictive' (default) mode, the Welch Allyn SureTemp Plus 692 thermometer differed from the control by a mean of 0.6°C (SD 0.3°C), displaying a temperature at 15 s (SD 3 s). This device consistently overestimated temperature. In 'continuous' mode, the mean difference was <0.1°C (SD<0.1°C) at 5 min. The Phillips probe differed from the control by a mean of 0.4°C (SD 0.2°C). Thermometers used to measure temperature in newborn infants may underestimate hypothermia. A prospective study in newborn infants is needed.

Randomised trial of estimating oral endotracheal tube insertion depth in newborns using suprasternal palpation of the tip or weight.

BACKGROUND: Endotracheal tube (ETT) tip position is determined on chest X-ray (CXR) and should lie between the upper border of the first thoracic vertebra (T1) and the lower border of second thoracic vertebra (T2). Infant weight is commonly used to estimate how far the ETT should be inserted but frequently results in malpositioned ETT tips. Palpation of the ETT tip at the suprasternal notch has been recommended as an alternative. OBJECTIVE: To determine whether estimating ETT insertion depth using suprasternal palpation of the ETT tip rather than weight results in more correctly positioned ETT tips. DESIGN: Single-centre randomised controlled trial. SETTING: Level III neonatal intensive care unit (NICU) at a university maternity hospital. PATIENTS: Newborn infants without congenital anomalies intubated in the NICU. INTERVENTIONS: Participants were randomised to have ETT insertion depth estimated using palpation of the ETT tip at the suprasternal notch or weight [insertion depth (cm)=6 + wt (kg)]. MAIN OUTCOME MEASURE: Correct ETT position, that is, between the upper border of T1 and lower border of T2 on CXR, determined by one consultant paediatric radiologist masked to group assignment. RESULTS: There was no difference in the proportion of correctly placed ETT tips between the groups (suprasternal palpation 27/58 (47%) vs weight 23/60 (38%), p=0.456). Most incorrectly positioned ETTs were too low (56/68 (82%)). CONCLUSION: Estimating ETT insertion depth using suprasternal palpation did not result in more correctly positioned ETTs. TRIAL REGISTRATION NUMBER: ISRCTN13570106.

Crying and breathing by new-born preterm infants after early or delayed cord clamping.

Guidelines recommend delayed cord clamping (DCC) of at least 30 s for vigorous preterm infants who do not require resuscitation. It is not known whether DCC affects the rate of crying and breathing after birth. We reviewed videos of 80 preterm infants in the delivery room. Most infants cried and breathed after both immediate and delayed cord clamping before respiratory support was given. Infants arrived at the resuscitaire in similar physiological condition, regardless of the time after birth at which they arrived.

Randomised study comparing heart rate measurement in newly born infants using a monitor incorporating electrocardiogram and pulse oximeter versus pulse oximeter alone.

AIM: To determine whether IntelliVue (ECG plus Masimo pulse oximeter (PO)) measures heart rate (HR) in low-risk newborns more quickly than Nellcor PO (PO alone). METHODS: Unmasked parallel group randomised (1:1) study. RESULTS: We studied 100 infants, 47 randomised to IntelliVue, 53 to Nellcor. Time to first HR was shorter with IntelliVue ECG than Nellcor (median (IQR) 24 (19, 39) vs 48 (36, 69) s, p<0.001). There was no difference in time to display both HR and SpO2 (52 (47, 76) vs 48 (36, 69) s, p=0.507). IntelliVue PO displayed initial bradycardia more often than the Nellcor (55% vs 6%). Infants monitored with IntelliVue were handled more frequently and for longer. CONCLUSIONS: IntelliVue ECG displayed HR more quickly than Nellcor PO. IntelliVue PO often displayed initial bradycardia. Infants monitored with IntelliVue were handled more often. Study of ECG in high-risk infants is warranted.

Comparison of infant heart rate assessment by auscultation, ECG and oximetry in the delivery room.

Clinical assessment of an infant's heart rate (HR) in the delivery room (DR) has been reported to be inaccurate. We compared auscultation of the HR using a stethoscope with electrocardiography (ECG) and pulse oximetry (PO) for determining the HR in 92 low-risk newborn infants in the DR. Caregivers auscultated the HR while masked to the HR on the monitor. Auscultation underestimated ECG HR (mean difference (95% CI) by -9 (-15 to -2) beats per minute (bpm)) and PO HR (mean difference (95% CI) by -5 (-12 to 2) bpm). The median (IQR) time to HR by auscultation was 14 (10-18) s. As HR was determined quickly and with reasonable accuracy by auscultation in low-risk newborns, study in high-risk infants is warranted.

2% chlorhexidine-70% isopropyl alcohol versus 10% povidone-iodine for insertion site cleaning before central line insertion in preterm infants: a randomised trial.

OBJECTIVE: To determine whether 2% chlorhexidine gluconate-70% isopropyl alcohol (CHX-IA) is superior to 10% aqueous povidone-iodine (PI) in preventing catheter-related blood stream infection (CR-BSI) when used to clean insertion sites before placing central venous catheters (CVCs) in preterm infants. DESIGN: Randomised controlled trial. SETTING: Two neonatal intensive care units (NICUs). PATIENTS: Infants <31 weeks' gestation who had a CVC inserted. INTERVENTIONS: Insertion site was cleaned with CHX-IA or PI. Caregivers were not masked to group assignment. MAIN OUTCOME MEASURES: Primary outcome was CR-BSI determined by one microbiologist who was masked to group assignment. Secondary outcomes included skin reactions to study solution and thyroid dysfunction. RESULTS: We enrolled 304 infants (CHX-IA 148 vs PI 156) in whom 815 CVCs (CHX-IA 384 vs PI 431) were inserted and remained in situ for 3078 (CHX-IA 1465 vs PI 1613) days. We found no differences between the groups in the proportion of infants with CR-BSI (CHX-IA 7% vs PI 5%, p=0.631), the proportion of CVCs complicated by CR-BSI or the rate of CR-BSI per 1000 catheter days. Skin reaction rates were low (<1% CVC insertion episodes) and not different between the groups. More infants in the PI group had raised thyroid-stimulating hormone levels and were treated with thyroxine (CHX-IA 0% vs PI 5%, p=0.003). CONCLUSIONS: We did not find a difference in the rate of CR-BSI between preterm infants treated with CHX-IA and PI, and more infants treated with PI had thyroid dysfunction. However, our study was not adequately powered to detect a difference in our primary outcome and a larger trial is required to confirm our findings. TRIAL REGISTRATION: This study was registered with the EU clinical trials register before the first patient was enrolled (Eudract 2011-002962-19). (https://www.clinicaltrialsregister.eu).

Randomised trial of estimating oral endotracheal tube insertion depth in newborns using weight or vocal cord guide.

BACKGROUND: When intubating newborns, clinicians aim to position the endotracheal tube (ETT) tip in the midtrachea. The depth to which ETTs should be inserted is often estimated using the infant's weight. ETTs are frequently incorrectly positioned in newborns, most often inserted too far. Using the vocal cord guide (a mark at the distal end of the ETT) to guide insertion depth has been recommended. OBJECTIVE: To determine whether estimating ETT insertion depth using the vocal cord guide rather than weight results in more correctly positioned ETT tips. DESIGN: Single-centre randomised controlled trial. SETTING: Level III neonatal intensive care unit (NICU) at a university maternity hospital (National Maternity Hospital, Dublin, Ireland). PATIENTS: Newborn infants without congenital anomalies intubated in the NICU. INTERVENTIONS: Participants were randomised to have ETT insertion depth estimated using weight [insertion depth (cm) = weight (kg) +6] or vocal cord guide. MAIN OUTCOME MEASURE: Correct ETT position, that is, tip between the upper border of the first thoracic vertebra (T1) and the lower border of the second thoracic vertebra (T2) on a chest X-ray as determined by one paediatric radiologist masked to group assignment. RESULTS: 136 participants were randomised. The proportion of correctly positioned ETTs was similar in both groups (weight 30/69 (44%) vs vocal cord guide 27/67 (40%), p=0.731). Most incorrectly positioned ETT (69/79, 87%) were too low. CONCLUSION: Estimating ETT insertion depth using the vocal cord guide did not result in more correctly positioned ETT tips. TRIAL REGISTRATION NUMBER: ISRCTN39654846.

A randomised crossover study of low-flow air or oxygen via nasal cannulae to prevent desaturation in preterm infants.

OBJECTIVE: To compare the efficacy of low-flow oxygen, low-flow air and sham treatment given via nasal cannulae in preventing desaturation (falls in oxygen saturation (SpO2)) in preterm infants. STUDY DESIGN: Infants born at <33 weeks gestation receiving gas at flow rates <1 l/min via nasal cannulae were eligible for inclusion. Enrolled infants received three treatments-0.1 l/min 100% oxygen, 0.1 l/min air, (21% oxygen) and sham (tubing disconnected from flow-meter)-via nasal cannulae, each for 3 h. Treatments were given in a randomly assigned order and caregivers were masked to treatment. Infants were monitored with a pulse oximeter that recorded SpO2 and heart rate every 2 s. Treatment was stopped before 3 h if infants reached prespecified failure criteria. We compared the rates of failure and the frequency and duration of desaturation episodes that occurred during each treatment. RESULTS: Of 14 infants enrolled, 2 (14%) reached failure criteria during treatment with oxygen compared with 7 (50%) during treatment with air and sham. Among infants who completed the 3-h study periods, there were fewer episodes and shorter duration of desaturation with oxygen compared with air and sham. CONCLUSIONS: At a flow rate of 0.1 l/min via nasal cannulae, air is no better than sham treatment in preventing desaturation in preterm infants, while 100% oxygen is superior to both.