Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Human Milk Feeding Is Associated with Decreased Incidence of Moderate-Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants.

BACKGROUND: An increased rate of bronchopulmonary dysplasia (BPD) is reported in extremely preterm infants. A potential role of human milk feeding in protecting against this condition has been suggested. METHODS: A retrospective descriptive study was conducted based on data about morbidity in the population of infants born between 22+0 and 26+6 weeks of gestation, included in the Spanish network SEN1500 during the period 2004-2019 and discharged alive. The primary outcome was moderate-severe BPD. Associated conditions were studied, including human milk feeding at discharge. The temporal trends of BPD and human milk feeding rates at discharge were also studied. RESULTS: In the study population of 4341 infants, the rate of moderate-severe BPD was 43.7% and it increased to >50% in the last three years. The factors significantly associated with a higher risk of moderate-severe BPD were birth weight, male sex, high-frequency oscillatory ventilation, duration of invasive mechanical ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis. Exclusive human milk feeding and any amount of human milk at discharge were associated with a lower incidence of moderate-severe BPD (OR 0.752, 95% CI 0.629-0.901 and OR 0.714, 95% CI 0.602-0.847, respectively). During the study period, the proportion of infants with moderate-severe BPD fed any amount of human milk at discharge increased more than twofold. And the proportion of infants with moderate-severe BPD who were exclusively fed human milk at discharge increased at the same rate. CONCLUSIONS: Our work shows an inverse relationship between human milk feeding at discharge from the neonatal unit and the occurrence of BPD.

Physiological responses and behavioural organization of very low birth weight infants during swaddled versus traditional weighing.

AIM: Despite the consequences of neonatal distress and agitation, preterm infants undergo stress owing to weighing procedures. The objective of this study was to enable very low birth weight infants to maintain adequate self-regulation during weighing. DESIGN: This prospective crossover study utilizes a within-subjects design, where intervention days were compared to control days. METHOD: Infants were exposed to both swaddled and unswaddled weighing in an intensive care nursery setting. Nineteen very low birth weight infants were weighed on two consecutive days. Variables of heart rate, respiratory rate and ALPS-Neo score were recorded. RESULTS: Stress score decreased significantly from 1.65 (pre-weight) to 0.23 (weight measurement) in swaddled-intervention periods; conversely, it increased significantly from 1.26 (pre-weight) to 4.97 (weight measurement) in control periods. During weight measurement, heart and respiratory rate were significantly lower for swaddled-intervention days when compared to control days. Given the significant impact of swaddled weighing in reducing stress, this method can be used as an appropriate weighing procedure in intensive care. This research has no patient or public contribution.

The role of human milk feeds on inotrope use in newborn infants with sepsis.

Background: Regarding neonatal hypotension, there is no certainty as to whether inotrope properties are beneficial or whether they may be harmful. However, given that the antioxidant content of human milk plays a compensatory role in neonatal sepsis and that human milk feeding has direct effects in modulating the cardiovascular function of sick neonates, this research hypothesized that human milk feeds might predict lower requirements of vasopressors in the management of neonatal septic shock. Method: Between January 2002 and December 2017, all late preterm and full-term infants attending a neonatal intensive care unit, with clinical and laboratory findings of bacterial or viral sepsis, were identified in a retrospective study. During their first month of life, data on feeding type and early clinical characteristics were collected. A multivariable logistic regression model was constructed to determine the impact of human milk on the use of vasoactive drugs in septic newborns. Results: 322 newborn infants were eligible to participate in this analysis. Exclusively formula-fed infants were more likely to be delivered via C-section, to have a lower birth weight and a lower 1-minute Apgar score than their counterparts. Human milk-fed newborns had 77% (adjusted OR = 0.231; 95% CI: 0.07-0.75) lower odds of receiving vasopressors than exclusively formula-fed newborns. Conclusion: We report that any human milk feeding is associated with a decrease in the need for vasoactive medications in sepsis-affected newborns. This observation encourages us to undertake further research to determine whether human milk feeds mitigate the use of vasopressors in neonates with sepsis.

Active approach in delivery room and survival of infants born between 22 and 26 gestational weeks are increasing in Spain.

AIM: To describe the trends in the delivery room approach and survival of extremely premature infants over the past two decades. METHODS: Time-series analysis of infants included in the Spanish SEN1500 network from 2004 to 2019. Patients born from 22 + 0 to 26 + 6 weeks were included. The primary outcome was an active approach in the delivery room. Survival and temporal trends were also studied. RESULTS: The study population included 8284 patients. At 22 and 23 weeks, an active approach was followed in 41.4% and 80.8%. A temporal trend toward a more active approach was observed at 23 weeks. Antenatal steroids were administered in 19.6% and 58.1% at 22 and 23 weeks. From 24 weeks, an active approach was applied in nearly all cases throughout the period, and more than 80% of patients received antenatal steroids. The rates of survival after an active approach were 8.7%, 21.6%, 40.6%, 59.9%, and 74.7% at 22, 23, 24, 25, and 26 weeks and significantly increased over the period, except for infants born at 22 weeks. CONCLUSION: Active management and survival of infants born from 23 weeks increased over the period, but the frequency of antenatal steroid administration was lower than the intention to resuscitate.

Human Milk Feeding for Septic Newborn Infants Might Minimize Their Exposure to Ventilation Therapy.

Background. It has been well established that human milk feeding contributes to limiting lung diseases in vulnerable neonates. The primary aim of this study was to compare the need for mechanical ventilation between human milk-fed neonates with sepsis and formula-fed neonates with sepsis. Methods. All late preterm and full-term infants from a single center with sepsis findings from 2002 to 2017 were identified. Data on infant feeding during hospital admission were also recorded. Multivariate logistic regression analyses were performed to assess the impact of feeding type on ventilation support and main neonatal morbidities. Results. The total number of participants was 322 (human milk group = 260; exclusive formula group = 62). In the bivariate analysis, 72% of human milk-fed neonates did not require oxygen therapy or respiratory support versus 55% of their formula-fed counterparts (p < 0.0001). Accordingly, invasive mechanical ventilation was required in 9.2% of any human milk-fed infants versus 32% of their exclusively formula-fed counterparts (p = 0.0085). These results held true in multivariate analysis; indeed, any human milk-fed neonates were more likely to require less respiratory support (OR = 0.44; 95% CI:0.22, 0.89) than those who were exclusively formula-fed. Conclusion. Human milk feeding may minimize exposure to mechanical ventilation.

Maternal mental health and breastfeeding amidst the Covid-19 pandemic: cross-sectional study in Catalonia (Spain).

BACKGROUND: Covid-19 pandemic became an unexpected stressor for the entire population and, particularly, for pregnant women and lactating mothers. The alarming infectious risk together with the lockdown period could affect the emotional state of mothers-to-be, as well as breastfeeding rates, mother-baby bonding, or neonatal weight gain. The aim of this study is to describe the impact of this world health emergency in mother-baby pairs right after the first wave of Sars-Cov-2 pandemic (from March to May 2020). STUDY DESIGN: A prospective observational study was carried out in mother-child dyads from those women who gave birth between June and August 2020 in a tertiary hospital. 91 mother-baby pairs were initially enrolled and 56 of them completed the follow-up. The study design had two separate steps: i) Step one: A clinical interview plus three psychometric tests (EPDS: Edinburgh Postnatal Depression Scale, PBQ: Postpartum Bonding Questionnaire and STAI-S: State-Trait Anxiety Inventory); ii) Step two: mother-child dyads were followed using a round of three brief telephone interviews (conducted at the newborn's 7, 14 and 28 days of age) to accurately depict the newborn's outcome in the neonatal period. RESULTS: In terms of maternal mental health, 25% of the sample screens positively in the EPDS, requiring further evaluation to rule out depressive symptoms. STAI-state and PBQ detect no abnormalities in either anxiety levels or mother-child bonding in our sample, as 100% of the mothers score below the cut-off points in each test (34 and 26 respectively). When comparing feeding practices (breast/bottle feeding) in 2020 to those practices during pre-pandemic years (2017-2019), a significant increase in breastfeeding was found in pandemic times. All newborns in the sample showed an adequate weight gain during their first month of life. CONCLUSION: Women and newborns in our sample did not experience an increase in adverse outcomes in the neonatal period in terms of maternal mental health, breastfeeding rates, bonding and further neonatal development.

Changes in perinatal management and outcomes in infants born at 23 weeks of gestational age during the last decade in Spain.

INTRODUCTION: The 2021-updated guidelines of the Spanish Society of Neonatology Guidelines have moved the zone of parental discretion to 23 + 0-23 + 6 weeks. The objective of this study was to describe the changes in perinatal management at this gestational age along the last decade and to determine if a more active perinatal management has contributed to improved outcomes. METHODS: Retrospective analysis of prospectively collected data from the 23-week infants included in the Spanish SEN 1500 neonatal network during the period 2010-2019. The main study outcomes were survival at discharge and survival without major morbidity of actively managed infants. Two periods were compared: 2010-2014 (Period 1) and 2015-2019 (Period 2). NICUs were classified into low activity NICUs (less than 50 admissions of very low birth weight infants per year) and high activity NICUs (50 or more admissions). RESULTS: A total of 381 infants were included, 182 in Period 1 and 199 in Period 2. In Period 2 an increase in the use of intrapartum magnesium sulfate (21.5% vs 39.9%, p .002), antenatal steroids (56.6% vs 69.3%, p .011) and active neonatal approach in delivery room (76.9% vs 86.9%, p .011) were observed.The clinical outcomes of the actively managed 313 infants were similar in both periods, except for less arterial hypotension in Period 2. Survival was 27.1% in Period 1 and 25% in Period 2 (p .068) and survival without major morbidity was 2.1% and 2.3% respectively (p .914). No difference was found between low and high activity NICUs. CONCLUSION: A change to a more active intention to treat infants born at 23 weeks is taking place in Spain. But the survival rate of the actively-managed infants has remained stable around 25-30% during the study period. A multidisciplinary effort is needed to improve outcomes in this population.

Inadequate Weight Gain According to the Institute of Medicine 2009 Guidelines in Women with Gestational Diabetes: Frequency, Clinical Predictors, and the Association with Pregnancy Outcomes.

BACKGROUND: In the care of women with gestational diabetes mellitus (GDM), more attention is put on glycemic control than in factors such as gestational weight gain (GWG). We aimed to evaluate the rate of inadequate GWG in women with GDM, its clinical predictors and the association with pregnancy outcomes. METHODS: Cohort retrospective analysis. OUTCOME VARIABLES: GWG according to Institute of Medicine 2009 and 18 pregnancy outcomes. Clinical characteristics were considered both as GWG predictors and as covariates in outcome prediction. STATISTICS: descriptive, multinomial and logistic regression. RESULTS: We assessed 2842 women diagnosed with GDM in the 1985-2011 period. GWG was insufficient (iGWG) in 50.3%, adequate in 31.6% and excessive (eGWG) in 18.1%; length of follow-up for GDM was positively associated with iGWG. Overall pregnancy outcomes were satisfactory. GWG was associated with pregnancy-induced hypertension, preeclampsia, cesarean delivery and birthweight-related outcomes. Essentially, the direction of the association was towards a higher risk with eGWG and lower risk with iGWG (i.e., with Cesarean delivery and excessive growth). CONCLUSIONS: In this cohort of women with GDM, inadequate GWG was very common at the expense of iGWG. The associations with pregnancy outcomes were mainly towards a higher risk with eGWG and lower risk with iGWG.

Breastfeeding Disparities between Multiples and Singletons by NICU Discharge.

Multiple pregnancy increases the risk of a range of adverse perinatal outcomes, including breastfeeding failure. However, studies on predictive factors of breastfeeding duration in preterm twin infants have a conflicting result. The purpose of this observational study was to compare feeding practices, at hospital discharge, of twin and singleton very low birth weight infants. The study is part of a prospective survey of a national Spanish cohort of very low birth weight infants (SEN1500) that includes 62 neonatal units. The study population comprised all infants registered in the network from 2002 to 2013. They were grouped into singletons and multiples. The explanatory variables were first analyzed using univariate models; subsequently, significant variables were analyzed simultaneously in a multiple stepwise backward model. During the twelve-year period, 32,770 very low birth weight infants were included in the database, of which 26.957 were discharged alive and included in this analysis. Nine thousand seven hundred and fifty-eight neonates were multiples, and 17,199 were singletons. At discharge, 31% of singleton infants were being exclusively breastfed, 43% were bottle-fed, and 26% were fed a combination of both. In comparison, at discharge, only 24% of multiple infants were exclusively breastfed, 43% were bottle-fed, and 33% were fed a combination of both (p < 0.001). On multivariable analysis, twin pregnancy had a statistically significant, but small effect, on cessation of breastfeeding before discharge (OR 1.10; 95% CI: 1.02, 1.19). Risks of early in-hospital breastfeeding cessation were also independently associated with multiple mother-infant stress factors, such as sepsis, intraventricular hemorrhage, retinopathy, necrotizing enterocolitis, intubation, and use of inotropes. Instead, antibiotic treatment at delivery, In vitro fertilization and prenatal steroids were associated with a decreased risk for shorter in-hospital breastfeeding duration. Multiple pregnancy, even in the absence of pathological conditions associated to very low birth weight twin infants, may be an impeding factor for in-hospital breastfeeding.