LISA Eligibility and LISA Success in Extremely Preterm Infants: A Single-Center Experience.

INTRODUCTION: Less invasive surfactant application (LISA) is associated with improved short-term outcomes in preterm infants. Data on LISA eligibility and success for infants <28 weeks of gestation are lacking. METHODS: Preterm infants <28 weeks of gestation who were born and actively treated in our tertiary care center in 2018 were included in the retrospective study. We assessed baseline characteristics, delivery room (DR) management, LISA success and complications, and short-term outcome. RESULTS: In total, 57 infants received LISA in the DR. LISA eligibility was 73% at 22 weeks, 88% at 23 weeks, and >90% at gestational ages >24 weeks. LISA was successful in 63% of infants. LISA failure was associated with increased risk for high-grade IVH (OR 17.88), death (OR 10.94), and a reduced chance for survival without complications (OR 8.75). CONCLUSION: Our report justifies LISA as a mode for surfactant application in preterm infants. It contributes to the call for studies to define risk factors for LISA failure.

Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae.

Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being "at risk" in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum.

Low incidence of acute kidney injury in VLBW infants with restrictive use of mechanical ventilation.

BACKGROUND: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV). METHODS: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria. RESULTS: AKI was identified in 25/128 patients (19.5%) with eight of them (6.3%) presenting with severe AKI. Low gestational age, birthweight and 10-minute Apgar score as well as high CRIB-1 score were all associated with incidence of AKI. Forty-five percent of the infants with MV developed AKI vs. 8.9% of those without MV (p < 0.001). Early onset of MV and administration of more than 3 dosages of NSAIDs for patent duct were identified as independent risk factors for AKI in a logistic regression analysis. CONCLUSIONS: We report a substantially lower frequency of AKI in VLBW infants as compared to previous studies, along with a very low rate of MV. A neonatal protocol focusing on avoidance of MV within the first days of life may be a key factor to decrease the risk of AKI in immature infants.

Alternative routes of surfactant application - An update.

Non-invasive modes of respiratory support have been shown to be the preferable way of primary respiratory support of preterm infants with respiratory distress syndrome (RDS). The avoidance of invasive mechanical ventilation can be beneficial for preterm infants in reduction of morbidity and even mortality. However, it is well-established that some infants managed with non-invasive respiratory support from the outset have symptomatic RDS to a degree that warrants surfactant administration. Infants for whom non-invasive respiratory support ultimately fails are prone to adverse outcomes, occurring at a frequency on par with the group intubated primarily. This raises the question how to combine non-invasive respiratory support with surfactant therapy. Several methods of less or minimally invasive surfactant therapy have been developed to address the dilemma between avoidance of mechanical ventilation and administration of surfactant. This paper describes the different methods of less invasive surfactant application, reports the existing evidence from clinical studies, discusses the limitations of each of the methods and the open and future research questions.

Extrauterine Placental Perfusion and Oxygenation in Infants With Very Low Birth Weight: A Randomized Clinical Trial.

Importance: An extrauterine placental perfusion (EPP) approach for physiological-based cord clamping (PBCC) may support infants with very low birth weight (VLBW) during transition without delaying measures of support. Objective: To test whether EPP in resuscitation of infants with VLBW results in higher hematocrit levels, better oxygenation, or improved infant outcomes compared with delayed cord clamping (DCC). Design, Setting, and Participants: This nonblinded, single-center randomized clinical trial was conducted at a tertiary care neonatal intensive care unit. Infants with a gestational age greater than 23 weeks and birth weight less than 1500 g born by cesarean delivery between May 2019 and June 2021 were included. Data were analyzed from October through December 2021. Intervention: Prior to cesarean delivery, participants were allocated to receive EPP or DCC. In the EPP group, infant and placenta, connected by an intact umbilical cord, were detached from the uterus and transferred to the resuscitation unit. Respiratory support was initiated while holding the placenta over the infant. The umbilical cord was clamped when infants showed regular spontaneous breathing, stable heart rates greater than 100 beats/min, and adequate oxygen saturations. In the DCC group, cords were clamped 30 to 60 seconds after birth before infants were transferred to the resuscitation unit, where respiratory support was started. Main Outcomes and Measure: The primary outcome was the mean hematocrit level in the first 24 hours after birth. Secondary prespecified outcome parameters comprised oxygenation during transition and short-term neonatal outcome. Results: Among 60 infants randomized and included, 1 infant was excluded after randomization; there were 29 infants in the EPP group (mean [SD] gestational age, 27 weeks 6 days [15.0 days]; 14 females [48.3%]) and 30 infants in the DCC group (mean [SD] gestational age, 28 weeks 1 day [17.1 days]; 17 females [56.7%]). The mean (SD) birth weight was 982.8 (276.6) g and 970.2 (323.0) g in the EPP and DCC group, respectively. Intention-to-treat analysis revealed no significant difference in mean hematocrit level (mean difference [MD], 2.1 percentage points; [95% CI, -2.2 to 6.4 percentage points]). During transition, infants in the EPP group had significantly higher peripheral oxygen saturation as measured by pulse oximetry (adjusted MD at 5 minutes, 15.3 percentage points [95% CI, 2.0 to 28.6 percentage points]) and regional cerebral oxygen saturation (adjusted MD at 5 minutes, 11.3 percentage points [95% CI, 2.0 to 20.6 percentage points]). Neonatal outcome parameters were similar in the 2 groups. Conclusions and Relevance: This study found that EPP resulted in similar hematocrit levels as DCC, with improved cerebral and peripheral oxygenation during transition. These findings suggest that EPP may be an alternative procedure for PBCC in infants with VLBW. Trial Registration: ClinicalTrials.gov Identifier: NCT03916159.

Surfactant delivery strategies to prevent bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is one of the most devastating morbidities of preterm infants. Antenatal factors like growth restriction and inflammation are risk factors for its development. Use of oxygen and positive pressure ventilation, which are often necessary to treat respiratory distress syndrome (RDS), increase the risk for development of BPD. Continuous positive airway pressure (CPAP) as primary respiratory support allows for avoidance of positive pressure ventilation in many cases but may lead to a delay of surfactant administration which is a proven therapy for RDS. Several alternative surfactant delivery strategies, including nebulization of surfactant, pharyngeal instillation of surfactant, delivery of surfactant via supraglottic airway device or surfactant delivery via a thin endotracheal catheter have been described which allow for the benefit of surfactant therapy while on CPAP. This review reports available data and discusses the existing evidence of their value in preventing BPD as well as further research directions.

Human preterm colostrum stimulates outgrowth in neurogenic tissue.

BACKGROUND: The olfactory bulb has a key role for nasal delivery of drugs to the brain by its access from the nasal mucosa and its connection to the subventricular zone. The aim of this study was to investigate the neuromodulatory capacity of human milk of premature infants on the olfactory bulb. METHODS: Olfactory bulbs from P1 mice were embedded in a collagen I gel and incubated with DMEM supplemented with the aqueous phase of human colostrum (Col) of five mothers after very preterm birth, mature milk (Mat) of the same mothers or without supplement (Ctrl). After 7 days, the neurite outgrowth was quantified. Proteome analysis of the milk samples was performed using unlabeled mass spectrometry. RESULTS: Outgrowth increased significantly in bulbs exposed to Col but not when exposed to Mat. Mass spectrometry revealed profound differences in the proteome of Col versus Mat. Among 21 upregulated proteins in Col were proteins involved in neurite outgrowth, axon guidance, neuromodulation and longevity. CONCLUSIONS: A high bioactivity of human preterm colostrum on murine neonatal neurogenic tissue is demonstrated to be associated with a proteome profoundly differing from mature milk. IMPACT: The hypothesis has been raised that neonatal brain damage in a preterm infant could potentially be ameliorated by intranasal application of maternal breast milk. In an in-vitro model using neonatal murine olfactory bulb explants a significant stimulatory effect by human preterm colostrum is observed. Proteomics reveals upregulated neuroactive proteins in human colostrum compared to mature milk. A confirmation of this exploratory study would indicate that preterm colostrum stimulates neurogenic tissue. Early intranasal colostrum application might attenuate perinatal loss of neurogenic tissue thereby contributing to reducing complications such as cerebral palsy.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study.

INTRODUCTION: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA). METHODS: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 220/7 and 316/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included. Non-pharmacological analgesia was performed in all infants during LISA. In case of failure of the first LISA attempt, additional analgosedation could be administered. COMFORTneo scores during LISA were assessed. RESULTS: 113 VPI with a mean gestational age of 27 weeks (+/- 2.3 weeks) and mean birth weight of 946 g (+/- 33 g) were included. LISA was successful at the first laryngoscopy attempt in 81%. COMFORTneo scores were highest during laryngoscopy. At this time point, non-pharmacological analgesia provided adequate comfort in 61% of the infants. 74.4% of lower gestational aged infants (i.e., 220-266 weeks) were within the comfort zone during laryngoscopy compared to 51.6% of higher gestational aged infants (i.e., 270-320 weeks) (p = 0.016). The time point of surfactant administration did not influence the COMFORTneo scores during the LISA procedure. CONCLUSION: Non-pharmacological analgesia provided comfort in as much as 61% of the included VPI during LISA. Further research is needed to both develop strategies to identify infants who, despite receiving non-pharmacological analgesia, are at high risk for experiencing discomfort during LISA and define patient-tailored dosage and choice of analgosedative drugs.

Indomethacin Prophylaxis Is Associated with Reduced Risk of Intraventricular Hemorrhage in Extremely Preterm Infants Born in the Context of Amniotic Infection Syndrome.

BACKGROUND: Amniotic infection syndrome (AIS) with perinatal inflammation may increase the susceptibility to intraventricular hemorrhage (IVH) in preterm infants. Given its anti-inflammatory and ductus arteriosus constricting capacities, we hypothesized that prophylactic administration of indomethacin reduces the incidence, severity, and consequences of IVH in the context of perinatal inflammation. METHODS: We evaluated data of infants born between 2009 and 2020 of 22 + 0-25+6 weeks of gestation from 68 German Neonatal Network centers. The effect of indomethacin prophylaxis on outcomes was analyzed in univariate analyses and multivariate regression models including a subgroup of infants with available data on 5-year follow-up. RESULTS: 4760 infants were included with a median gestational age of 24.6 SSW [interquartile range (IQR) 24.1w-25.2w] and a birth weight of 640 g [IQR 550-750 g]. 1767/4760 (37.1%) preterm infants were born in the context of AIS and 527/4760 (11.1%) received indomethacin prophylaxis. AIS infants receiving prophylactic indomethacin had lower rates of IVH (32.7% vs. 36.9%, p = 0.04), IVH III/IV (9.7% vs. 16.0%, p = 0.02) and the combined outcome of severe IVH or death (15.9% vs. 23.2%, p = 0.01) as compared to infants without prophylaxis. Multivariate logistic regression analyses confirmed our observations. In a subgroup analysis of 730 preterm infants at 5 years of age, we did not find any correlation between prophylactic indomethacin and intelligence quotient <70 or cerebral palsy. CONCLUSIONS: Our observational data demonstrate that prophylactic indomethacin is associated with a reduced risk of IVH in the highly vulnerable subgroup of preterm infants <26 weeks of gestation born from AIS.

Diseases associated with prematurity in correlation with N-terminal pro-brain natriuretic peptide levels during the early postnatal life.

The aim of this observational study was to investigate the influence of different typical preterm diseases on NT-proBNP serum levels in the early postnatal period of life of a preterm infant. NT-proBNP levels of 118 preterm infants born ≤ 31 weeks GA were determined at the first week of life, after 4 ± 1 weeks of life, and at a corrected gestational age of 36 + 2 weeks. Relevant complications with a possible influence on NT-proBNP values in the first week of life such as early neonatal infection, hemodynamically significant PDA (hsPDA), early pulmonary hypertension (early PH), and intraventricular hemorrhage (IVH) were evaluated; at 4 ± 1 weeks of life, bronchopulmonary dysplasia (BPD), BPD-related pulmonary hypertension (BPD-associated PH), late infection, IVH, and intestinal complications were evaluated. At a corrected gestational age of 36 ± 2 weeks, we examined the effect of retinopathy of prematurity (ROP), BPD, BPD-associated PH, and late infection on NT-proBNP levels. In the first days of life, only the isolated occurrence of hsPDA resulted in significantly increased NT-proBNP levels. In multiple linear regression analysis, early infection remained independently associated with NT-proBNP levels. At 4 ± 1 weeks of age, the isolated presence of BPD and BPD-related PH resulted in increased levels, and the effect remained significant in the multiple regression analysis. At a corrected gestational age of 36 ± 2 weeks, infants with relevant complications at this final evaluation time tended to have lower NT-proBNP values than our exploratory reference values.    Conlusion: NT-proBNP in the first week of life seems to be mainly influenced by an hsPDA and infection or inflammation. BPD and BPD-related PH are the most important factors influencing NT-proBNP serum levels in the first month of life. When preterm infants reach a corrected GA of 36 ± 2 weeks, chronological age rather than complications of prematurity must be considered when interpreting NT-proBNP levels. What is Known: • Several complications associated with prematurity, such as hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been shown to influence NT-proBNP levels in preterm infants in their early postnatal life. What is New: • Hemodynamically relevant PDA is a major factor in the increase of NT-proBNP levels in the first week of life. • Bronchopulmonary dysplasia and pulmonary hypertension associated with bronchopulmonary dysplasia are important factors in the increase in NT-proBNP levels in preterm infants at approximately 1 month of age.

High rate of insecure attachment patterns in preterm infants at early school age.

AIM: In preterm infants, insecure attachment is associated with behavioural and emotional problems but data on attachment beyond toddler age are scarce. This study assessed attachment security at 6-8 years in very and moderate or late preterm infants. The results were compared to a non-clinical full-term sample. METHODS: Attachment security of 38 very and 20 moderate or late preterm infants was assessed during a home visit with the German version of the Attachment Story Completion Task. Attachment patterns of 28 full-term controls were taken from a previous study. Primary outcomes were attachment security and attachment security score. Secondary outcomes for the preterm groups were infant behavioural problems, parental stress, perceived social support, maternal depressive symptoms, and infant development. RESULTS: Very preterm infants had the highest rate of insecure attachment (81%) compared to moderate or late preterm infants (60%) and full-term infants (47%); (p = 0.013). Attachment security scores differed significantly between very preterm and full-term infants (p = 0.001). Secondary outcomes were similar in very and moderate or late preterm cohorts. CONCLUSION: Prematurity was associated with an increased risk of insecure attachment at early school age. Interventions targeting attachment security are reasonable considering the high rate of behavioural problems following premature birth.

Association of Administration of Surfactant Using Less Invasive Methods With Outcomes in Extremely Preterm Infants Less Than 27 Weeks of Gestation.

Importance: The inclusion of less invasive surfactant administration (LISA) in the care of preterm infants has been found to be beneficial for respiratory outcomes. Recently, the OPTIMIST trial found higher mortality rates in the subgroup of infants born at 25 to 26 weeks' gestational age (GA) who received surfactant treatment while spontaneously breathing. Objective: To analyze outcomes among LISA-exposed, highly vulnerable babies born at less than 27 weeks' GA within the large-scale observational cohort of the German Neonatal Network. Design, Setting, and Participants: In this cohort study of data from 68 tertiary level neonatal intensive care units in Germany of infants born between 22 weeks 0 days to 26 weeks 6 days of gestation between April 1, 2009, and December 31, 2020, short-term outcomes among infants receiving LISA vs infants not receiving LISA were compared. Exposure: Use of LISA within the first 72 hours of life. Main Outcomes and Measures: The main outcomes were rates of LISA use, use of mechanical ventilation within the first 72 hours (considered failure of LISA), and association of LISA with outcomes, including death from all causes, bronchopulmonary dysplasia (BPD), death and BPD combined, pneumothorax, retinopathy of prematurity, intracerebral hemorrhage, and periventricular leukomalacia. To address potential confounding factors, multivariate logistic regression models were used. Results: A total of 6542 infants (3030 [46.3%] female and 3512 [53.7%] male; mean [SD] GA, 25.3 (1.1) weeks; mean [SD] birth weight, 715 [180] g) were analyzed; 2534 infants (38.7%) received LISA, which was most frequently given quasi-prophylactically during delivery room management. Among the infants who received LISA, 1357 (53.6%) did not require mechanical ventilation in the first 72 hours compared with 331 infants (8.3%) of 4008 who did not receive LISA. In a multivariate logistic regression model that adjusted for GA, small-for-GA status, sex, multiple birth, inborn status, antenatal steroid use, and maximum fraction of inspired oxygen in the first 12 hours of life, LISA was associated with reduced risks of all-cause death (odds ratio [OR], 0.74; 95% CI, 0.61-0.90; P = .002), BPD (OR, 0.69; 95% CI, 0.62-0.78; P < .001), and BPD or death (OR, 0.64; 95% CI, 0.57-0.72; P < .001) compared with infants without LISA exposure. Conclusions and Relevance: The results of this long-term multicenter cohort study suggest that LISA may be associated with reduced risks of adverse outcomes in extremely preterm infants.

Resuscitation of Term Compromised and Asphyctic Newborns: Better with Intact Umbilical Cord?

The authors hypothesize that particularly severely compromised and asphyctic term infants in need of resuscitation may benefit from delayed umbilical cord clamping (after several minutes). Although evidence is sparse, the underlying pathophysiological mechanisms support this assumption. For this review the authors have analyzed the available research. Based on these data they conclude that it may be unfavorable to immediately clamp the cord of asphyctic newborns (e.g., after shoulder dystocia) although recommended in current guidelines to provide quick neonatological support. Compression of the umbilical cord or thorax obstructs venous flow to the fetus more than arterial flow to the placenta. The fetus is consequently cut off from a supply of oxygenated, venous blood. This may cause not only hypoxemia and consecutive hypoxia during delivery but possibly also hypovolemia. Immediate cord clamping may aggravate the situation of the already compromised newborn, particularly if the cord is cut before the lungs are ventilated. By contrast, delayed cord clamping leads to fetoplacental transfusion of oxygenated venous blood, which may buffer an existing acidosis. Furthermore, it may enhance blood volume by up to 20%, leading to higher levels of various blood components, such as red and white blood cells, thrombocytes, mesenchymal stem cells, immunoglobulins, and iron. In addition, the resulting increase in pulmonary perfusion may compensate for an existing hypoxemia or hypoxia. Early cord clamping before lung perfusion reduces the preload of the left ventricle and hinders the establishment of sufficient circulation. Animal models and clinical trials support this opinion. The authors raise the question whether it would be better to resuscitate compromised newborns with intact umbilical cords. Obstetric and neonatal teams need to work even closer together to improve neonatal outcomes.

Multi-centre randomised trial of invasive and less invasive surfactant delivery methods showed similar spirometry results at 5-9 years of age.

AIM: We explored whether subnormal forced expiratory volume within 1 s (FEV1 ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube. METHODS: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values. RESULTS: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV1 was 93% (interquartile range 80%-113%) of predicted values in the LISA group and 86% (interquartile range 77-102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval -3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures. CONCLUSION: The proportion of children aged 5-9 years with subnormal FEV1 was not significantly different between the groups.

Thin-catheter Surfactant Application for Respiratory Distress Syndrome in Spontaneously Breathing Preterm Infants: A Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Surfactant application by a thin catheter represented by the term less invasive surfactant administration (LISA) for respiratory distress syndrome in spontaneously breathing preterm infants was developed as an alternative to endotracheal intubation. METHODS: We conducted a meta-analysis to assess the effects of LISA when compared to the socalled intubation-surfactant-extubation (INSURE) and the standard endotracheal intubation and mechanical ventilation (MV). The primary outcome was the composite incidence of death or bronchopulmonary dysplasia at a postmenstrual age of 36 weeks. The secondary outcome was the composite incidence of seven other severe adverse events. On 06 October 2021, we searched randomized clinical trials (RCTs) in PubMed, the Cochrane Library, ClinicalTrials.gov, and the ICTRP Registry. RESULTS: We included 18 RCTs. The pooled data on the primary outcome favored LISA when compared to either INSURE (risk ratio 0.67; 95% CI, 0.51 to 0.88) or MV (risk ratio 0.78; 95% CI, 0.61 to 0.99). The pooled data on the second outcome also favored LISA when compared to INSURE (risk ratio 0.75; 95% CI, 0.60 to 0.94) and MV (risk ratio 0.73; 95% CI, 0.55 to 0.96). CONCLUSION: The findings showed that surfactant application by non-intubation respiratory support and the use of a thin catheter may decrease the composite risk of death or bronchopulmonary dysplasia. The included data support the view that LISA should be considered the preferred treatment option in eligible infants.

Privacy, Early Colostrum, and Gestational Age are Associated with Exclusive Breastfeeding in Preterm and Sick Term Infants.

Our study was designed to assess the rates of exclusive breastfeeding (defined as direct breastfeeding) and the use of mother's own milk (MOM) in preterm infants and sick term infants at discharge and to identify potential influencing factors such as gestational age, early colostrum, and privacy. The study was conducted at a German level III neonatal department. All preterm and sick term infants admitted to the neonatal intensive care unit, the pediatric intensive care unit, the intermediate care unit, and the low care ward were included in the study. Infants were recruited between March and October 2015 (phase 1) and April to July 2016 (phase 2). Due to an emergency evacuation, privacy was limited during the first phase. Breastfeeding and the use of MOM were assessed daily using a self-designed score. In total, 482 infants of 452 mothers were included. More than 90% initiated breastfeeding and one-third were exclusively breastfed at discharge. Extremely immature infants and late preterm infants were less likely to be exclusively breastfed at discharge. Privacy (p<0.001) and early colostrum (p=0.002) significantly increased exclusive breastfeeding. Conclusion Extremely immature and late preterm infants were least likely to be exclusively breastfed at discharge and need special support. Interventions such as privacy and early colostrum should be promoted to increase breastfeeding.

A multi-centre randomised controlled trial of respiratory function monitoring during stabilisation of very preterm infants at birth.

AIM: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range. METHODS: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes. RESULTS: Among 288 infants randomised (median (IQR) gestational age 26+2 (25+3-27+1) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO2. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028). CONCLUSION: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. TRIAL REGISTRATION: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.