Correlation between early postnatal body weight changes and lung ultrasound scores as predictors of bronchopulmonary dysplasia in preterm infants: A secondary analysis of a prospective study.

Recent research links early weight changes (EWC) with bronchopulmonary dysplasia (BPD) in preterm neonates, while lung ultrasound score (LUS) has shown promise in predicting BPD. We aimed to explore the correlation between LUS and EWC as markers of extravascular lung edema and to investigate the correlation between LUS and EWC in preterm infants with respiratory distress syndrome regarding future BPD development. This secondary analysis of a prospective study involved infants ≤ 28 weeks gestation. Enrolled infants underwent lung ultrasound assessment on postnatal days 3, 7 and 14, measuring LUS. EWC was computed on the same time points. Infants were classified as either having BPD or not. Descriptive statistics, correlation coefficient, and area under the receiver operating characteristic (AUROC) curve analysis were utilized. Of 132 infants, 70 (53%) had BPD. Univariate analysis revealed statistically significant differences in LUS and EWC at days 3, 7, and 14 between BPD and no-BPD groups (p < 0.001). A statistically significant but weak positive correlation existed between LUS and EWC (r0.37, r0.29, r0.24, and p < 0.01) at postnatal days 3, 7, and 14, respectively. AUROC analysis indicated LUS having superior predictive capacity for the need for invasive mechanical ventilation at day 14 as well as the later BPD development compared to EWC (p < 0.0001). CONCLUSION: In a cohort of extreme preterm infants, our study revealed a positive yet weak correlation between LUS and EWC, suggesting that EWC was not the major contributing to the evolving chronic lung disease. WHAT IS KNOWN: • Recent evidence links Early Weight-Changes with bronchopulmonary dysplasia in preterm neonates. • Lung ultrasound score has shown promise in early prediction of the subsequent development of bronchopulmonary dysplasia in preterm infants. No studies have examined the correlation between Early Weight-Changes and Lung ultrasound score in preterm infants during first 2 weeks after birth. WHAT IS NEW: • Our study demonstrated a positive and statistically significant correlation between early LUS and EWC, indicating their potential role as early predictors for the subsequent development of BPD in extreme preterm infants. • The weak correlation between the two parameters may stem from the possible restricted influence of EWC, given that it may not be the primary factor contributing to the evolving chronic lung disease.

Online pilot intervention to improve nutritional and lifestyle in Spanish breast-feeding women.

INTRODUCTION: breastfeeding women often cannot adequately follow dietary and healthy habits recommendations. In addition, after labor, their care is usually focused on the newborn and the mother´s health may be neglected. The Mediterranean Diet is the standard of healthy eating, with the Healthy Food Pyramid (HFP) being its graphical representation. OBJECTIVE: the aim of this study was to determine whether a nutritional and lifestyle online intervention may improve HFP adherence in breastfeeding women. METHODS: a total of 181 breastfeeding women in the first sixth months postpartum were enrolled in a non-randomized interventional pilot study. These women answered three questionnaires: sociodemographic and for adherence to Healthy Food Pyramid (APQ), before and after an online intervention for 13 weeks, providing information about nutrition and healthy habits. The APQ ranges from 0 to 10, with higher scores corresponding to greater adherence to HFP. The intervention consisted of lifestyle and nutritional information, which was provided through e-mail. RESULTS: a low adherence to HFP was found, which was improved after 13 weeks of intervention. The online intervention significantly increased the scores for physical activity, grain, seeds and legumes consumption, olive oil use, dairy products, and ani-mal proteins, as well as the HFP adherence global score. The adjusted models showed that the online intervention was associated with adherence to the HFP and physical activity. CONCLUSION: we conclude that an online intervention for breastfeeding women had an impact on their lifestyle, improving nutritional and healthy habits, and can be a useful tool to monitor their health status. Given the importance of this stage for women and their newborns, this is an aspect postnatal healthcare professionals should consider.

Remote ischaemic conditioning in necrotising enterocolitis: a phase I feasibility and safety study.

OBJECTIVE: Remote ischaemic conditioning (RIC) improves the outcome of experimental necrotising enterocolitis (NEC) by preserving intestinal microcirculation. The feasibility and safety of RIC in preterm infants with NEC are unknown. The study aimed to assess the feasibility and safety of RIC in preterm infants with suspected or confirmed NEC. DESIGN: Phase I non-randomised pilot study conducted in three steps: step A to determine the safe duration of limb ischaemia (up to 4 min); step B to assess the safety of 4 repeated cycles of ischaemia-reperfusion at the maximum tolerated duration of ischaemia determined in step A; step C to assess the safety of applying 4 cycles of ischaemia-reperfusion on two consecutive days. SETTING: Level III neonatal intensive care unit, The Hospital for Sick Children (Toronto, Canada). PATIENTS: Fifteen preterm infants born between 22 and 33 weeks gestational age. INTERVENTION: Four cycles of ischaemia (varying duration) applied to the limb via a manual sphygmomanometer, followed by reperfusion (4 min) and rest (5 min), repeated on two consecutive days. OUTCOMES: The primary outcomes were (1) feasibility defined as RIC being performed as planned in the protocol, and (2) safety defined as perfusion returning to baseline within 4 min after cuff deflation. RESULTS: Four cycles/day of limb ischaemia (4 min) followed by reperfusion (4 min) and a 5 min gap, repeated on two consecutive days was feasible and safe in all neonates with suspected or confirmed NEC. CONCLUSIONS: This study is pivotal for designing a future randomised controlled trial to assess the efficacy of RIC in preterm infants with NEC. TRIAL REGISTRATION NUMBER: NCT03860701.

Nasal Intermittent Positive Pressure Ventilation and Bronchopulmonary Dysplasia Among Very Preterm Infants Never Intubated During the First Neonatal Admission: A Multicenter Cohort Study.

Introduction: While non-invasive positive-pressure ventilation (NIPPV) is increasingly used as a mode of respiratory support for preterm infants, it remains unclear whether this technique translates into improved respiratory outcomes. We assessed the association between NIPPV use and bronchopulmonary dysplasia (BPD)-free survival in never intubated very preterm infants. Methods: This multicenter cohort study analyzed data from the Spanish Neonatal Network SEN1500 corresponding to preterm infants born at <32 weeks gestational age and <1,500 g and not intubated during first admission. The exposure of interest was use of NIPPV at any time and the main study outcome was survival without moderate-to-severe BPD. Analyses were performed both by patients and by units. Primary and secondary outcomes were compared using multilevel logistic-regression models. The standardized observed-to-expected (O/E) ratio was calculated to classify units by NIPPV utilization and outcome rates were compared among groups. Results: Of the 6,735 infants included, 1,776 (26.4%) received NIPPV during admission and 6,441 (95.6%) survived without moderate-to-severe BPD. After adjusting for confounding variables, NIPPV was not associated with survival without moderate-to-severe BPD (OR 0.84; 95%CI 0.62-1.14). A higher incidence of moderate-to-severe BPD-free survival was observed in high- vs. very low-utilization units, but no consistent association was observed between O/E ratio and either primary or secondary outcomes. Conclusion: NIPPV use did not appear to decisively influence the incidence of survival without moderate-to-severe BPD in patients managed exclusively with non-invasive ventilation.

Remote ischemic conditioning in necrotizing enterocolitis: study protocol of a multi-center phase II feasibility randomized controlled trial.

PURPOSE: Remote ischemic conditioning (RIC) is a maneuver involving brief cycles of ischemia reperfusion in an individual's limb. In the early stage of experimental NEC, RIC decreased intestinal injury and prolonged survival by counteracting the derangements in intestinal microcirculation. A single-center phase I study demonstrated that the performance of RIC was safe in neonates with NEC. The aim of this phase II RCT was to evaluate the safety and feasibility of RIC, to identify challenges in recruitment, retainment, and to inform a phase III RCT to evaluate efficacy. METHODS: RIC will be performed by trained research personnel and will consist of four cycles of limb ischemia (4-min via cuff inflation) followed by reperfusion (4-min via cuff deflation), repeated on two consecutive days post randomization. The primary endpoint of this RCT is feasibility and acceptability of recruiting and randomizing neonates within 24 h from NEC diagnosis as well as masking and completing the RIC intervention. RESULTS: We created a novel international consortium for this trial and created a consensus on the diagnostic criteria for NEC and protocol for the trial. The phase II multicenter-masked feasibility RCT will be conducted at 12 centers in Canada, USA, Sweden, The Netherlands, UK, and Spain. The inclusion criteria are: gestational age < 33 weeks, weight ≥ 750 g, NEC receiving medical treatment, and diagnosis established within previous 24 h. Neonates will be randomized to RIC (intervention) or no-RIC (control) and will continue to receive standard management of NEC. We expect to recruit and randomize 40% of eligible patients in the collaborating centers (78 patients; 39/arm) in 30 months. Bayesian methods will be used to combine uninformative prior distributions with the corresponding observed proportions from this trial to determine posterior distributions for parameters of feasibility. CONCLUSIONS: The newly established NEC consortium has generated novel data on NEC diagnosis and defined the feasibility parameters for the introduction of a novel treatment in NEC. This phase II RCT will inform a future phase III RCT to evaluate the efficacy and safety of RIC in early-stage NEC.

Association of Weight Changes by Three Days after Birth and Mortality and/or Severe Neurological Injury in Preterm Infants < 29 Weeks Gestational Age: A Multicenter Cohort Study.

OBJECTIVE: This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants <29 weeks gestational age (GA). STUDY DESIGN: This multicenter retrospective cohort study employed data from the Canadian Neonatal Network database. The primary outcome was a composite of mortality and/or severe neurological injury. Multivariable quadratic and linear regression models which adjusted for potential confounders were built. RESULTS: A total of 9275 preterm infants (median GA 26, IQR 25, 28 weeks) were included. The optimal weight change range at day three, after adjustment for potential confounders for the primary outcomes, was -15 to -8.9%. CONCLUSIONS: There is a 'U'-shaped relationship between weight change from birth to day three and mortality and/or severe neurological injury. Interventional studies, which target weight loss within the range found in this study and evaluate the impact on neonatal outcomes, are needed to corroborate our findings.

Time at birth and short-term outcomes among extremely preterm infants in Spain: a multicenter cohort study.

The first hours after birth entail a window of opportunity to decrease morbidity and mortality among extremely preterm infants. The availability of staff and its tiredness vary depending on the timing and day of the week. We hypothesized that these circumstances may impact neonatal outcomes. We have conducted a multicenter cohort study with data obtained from the Spanish neonatal network database SEN1500, where staff doctors are in the house 24/7. The main study exposure was the time of birth; secondary exposures were cumulative work hours from the medical and nurses' shifts and day of the week. The primary outcome was survival to hospital discharge. Secondary outcomes included common preterm infants' in-hospital complications. Univariate and multivariate analysis adjusting for potential confounders was performed. All extremely preterm infants (N = 8798) born between 2011 and 2019 were eligible; 35.7% of them were admitted during the night shift. No differences were found between day and night births regarding survival or morbidity. No differences were found between weekdays and weekends or when considering cumulative worked hours in the shifts. Infants born during the night shift were more likely to be intubated at birth (OR 1.20, CI95% 1.06-1.37), receive surfactant (OR 1.24, CI95% 1.08-1.44), and having anemia requiring transfusion (OR 1.23, CI 95% 1.08-1.42). CONCLUSION: the time of birth did not seem to affect mortality and morbidity of extremely preterm infants. WHAT IS KNOWN: • The first hours after birth in extremely preterm infants are a very valuable opportunity to decrease mortality and morbidity. • Time and day of birth have long been linked to outcomes in preterm infants, with night shifts and weekends classically having higher rates of mortality and morbidity. WHAT IS NEW: • In this study, no differences were found between day and night births regarding survival or major morbidity. • Infants born during the night shift were more likely to be intubated at birth, receive surfactant and having anemia requiring transfusion.

Temporal trends in respiratory care and bronchopulmonary dysplasia in very preterm infants over a 10-year period in Spain.

OBJECTIVE: To evaluate trends in respiratory care practices and bronchopulmonary dysplasia (BPD) among very preterm infants born in Spain between 2010 and 2019. STUDY DESIGN: This was a retrospective cohort study of data obtained from a national population-based database (SEN1500 network). Changes in respiratory care and BPD-free survival of infants with gestational age (GA) of 230-316 weeks and <1500 g were assessed over two 5-year periods. Temporal trends were examined by joinpoint and Poisson regression models and expressed as the annual per cent change and adjusted relative risk (RR) for the change per year. RESULTS: A total of 17 952 infants were included. In the second period, infants were less frequently intubated in the delivery room and during neonatal intensive care unit stay. This corresponded with an increase in use of non-invasive ventilation techniques. There were no significant differences between the periods in BPD-free survival or survival without moderate-to-severe BPD. After adjusting for covariates, the RR for the change per year was significant for the following variables: never intubated (RR 1.03, 95% CI 1.02 to 1.04); intubation in the delivery room (RR 0.98, 95% CI 0.97 to 0.99); use of nasal intermittent positive pressure ventilation (RR 1.08, 95% CI 1.05 to 1.11); and BPD-free survival (only in the group with the lowest GA; RR 0.98, 95% CI 0.97 to 0.99). CONCLUSION: Our findings reveal significant changes in respiratory care practices between 2009 and 2019. Despite an increase in use of non-invasive respiratory strategies, BPD-free survival did not improve and even worsened in the group with the lowest GA (230-256).

SARS-CoV-2 genome and antibodies in breastmilk: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyse the rate of SARS-CoV-2 genome identification and the presence of SARS-CoV-2 antibodies in breastmilk of mothers with COVID-19. DESIGN: A systematic review of studies published between January 2019 and October 2020 without study design or language restrictions. SETTING: Data sourced from Ovid Embase Classic+Embase, PubMed, Web of Science, Scopus, relevant bibliographies and the John Hopkins University COVID-19 database. PATIENTS: Mothers with confirmed COVID-19 and breastmilk tested for SARS-CoV-2 by RT-PCR or for anti-SARS-CoV-2 antibodies. MAIN OUTCOME MEASURES: Presence of SARS-CoV-2 genome and antibodies in breastmilk. RESULTS: We included 50 articles. Twelve out of 183 women from 48 studies were positive for SARS-CoV-2 genome in their breastmilk (pooled proportion 5% (95% CI 2% to 15%; I2=48%)). Six infants (50%) of these 12 mothers tested positive for SARS-CoV-2, with one requiring respiratory support. Sixty-one out of 89 women from 10 studies had anti-SARS-CoV-2 antibody in their breastmilk (pooled proportion 83% (95% CI 32% to 98%; I2=88%)). The predominant antibody detected was IgA. CONCLUSIONS: SARS-CoV-2 genome presence in breastmilk is uncommon and is associated with mild symptoms in infants. Anti-SARS-CoV-2 antibodies may be a more common finding. Considering the low proportion of SARS-CoV-2 genome detected in breastmilk and its lower virulence, mothers with COVID-19 should be supported to breastfeed.

Neurodevelopmental and growth outcomes of extremely preterm infants with necrotizing enterocolitis or spontaneous intestinal perforation.

PURPOSE: To evaluate neurodevelopment and growth in extremely preterm infants with or without necrotizing enterocolitis or spontaneous intestinal perforation. METHODS: We conducted a retrospective cohort study of infants admitted to Canadian neonatal intensive care units in 2010 to 2011. We assessed outcomes at 18 to 24 months' corrected ages for preterm infants <29 weeks of gestational age at birth with spontaneous intestinal perforation or non-perforated or perforated necrotizing enterocolitis, and for preterm infants with none of these gastrointestinal complications. The primary outcome was a composite of death or significant neurodevelopmental impairment at 18 to 24 months' corrected age. We used multivariable logistic regression models to adjust for gestational age, small for gestational age, prenatal steroids, cesarean section, multiple gestations, and SNAP-II score. RESULTS: Of 2,019 infants total, 39 (1.9%) had spontaneous intestinal perforation, 61 (3%) had perforated necrotizing enterocolitis, and 115 (5.7%) had non-perforated necrotizing enterocolitis. Infants with spontaneous intestinal perforation (aOR 2.11; 95% CI 1.01-4.42), necrotizing enterocolitis (aOR 2.58; 95% CI 1.81-3.68), or any bowel perforation (aOR 3.97; CI 2.43-6.48) had higher odds of death or significant neurodevelopmental impairment compared to infants with none of these bowel diseases. CONCLUSIONS: Spontaneous intestinal perforation, necrotizing enterocolitis, or any bowel perforation are risk factors for death or significant neurodevelopmental impairment in extremely preterm infants. LEVEL OF EVIDENCE: Study type: prognosis study (cohort study: retrospective) LEVEL OF EVIDENCE RATING: II.

Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation.

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC.

Prevención, diagnóstico y tratamiento de la enterocolitis necrosante en recién nacidos menores de 32 semanas al nacimiento en España / Prevention, diagnosis and treatment of necrotising enterocolitis in newborns less than 32 weeks at birth in Spain

OBJETIVO: Describir la prevención, diagnóstico y tratamiento de la enterocolitis necrosante en hospitales españoles e identificar puntos fuertes, áreas de mejora y líneas de investigación pendientes. MÉTODOS: Se realizaron 2 encuestas sobre manejo de pacientes en riesgo o diagnóstico de enterocolitis necrosante en recién nacidos pretérmino menores de 32 semanas, distribuidas entre representantes de los cirujanos pediátricos y neonatólogos de los centros participantes en la red española SEN 1500 con Servicio de Cirugía Pediátrica. RESULTADOS: El porcentaje de respuestas fue del 77,1% y del 88,6% entre los cirujanos y neonatólogos contactados, respectivamente. El 52% de los hospitales dispone de un protocolo de diagnóstico y manejo médico de la enterocolitis y el 33% uno sobre tratamiento quirúrgico. El acceso a leche de banco y disponer de personal dedicado a la promoción de la lactancia materna es común (87%), por el contrario, la ligadura tardía de cordón solo se realiza en el 52% de los centros y en un 23% se administran probióticos. La ecografía abdominal está cada vez más extendida. No hay grandes diferencias en cuanto a la duración de los antibióticos y del reposo intestinal, pero sí en cuanto a los antibióticos seleccionados, la indicación quirúrgica y el tipo de intervención. CONCLUSIONES: La implementación de la ligadura tardía de cordón y la extensión del acceso a leche de banco son áreas de mejora en el aspecto preventivo. En cuanto al diagnóstico y tratamiento existe una gran división que afecta precisamente a las áreas donde la evidencia en la literatura es menor

OBJECTIVES: To describe preventive, diagnostic and therapeutic strategies regarding necrotising enterocolitis in Spain and to identify the strengths, areas of further improvement, and future research lines. METHODS: Two questionnaires on the management of preterm infants less than 32 weeks, at risk of, or with diagnosed necrotising enterocolitis, were distributed among selected representatives of the surgeons and neonatologists of the Spanish Neonatal Network (SEN1500) participant hospitals with a Paediatric Surgery Department. RESULTS: Percentage of response was 77.1% of contacted surgeons and 88.6% of neonatologists. There is a written protocol on the diagnosis and medical management of necrotising enterocolitis in 52% of the hospitals, and as regards surgical treatment in 33%. There is wide access to donor bank milk and to staff dedicated to breastfeeding promotion (87%). On the contrary, only 52% of the centres perform delayed cord clamping, and probiotics are used in just 23%. The use of abdominal ultrasound is increasing. There are no large differences as regards duration of antibiotic use and bowel rest, whereas there was as regards antibiotic selection, surgical indication, and type of intervention. CONCLUSIONS: As regards prevention, delayed cord clamping and extended access to donor milk are two possible aspects of further improvement. The observed discrepancies noted in diagnostic and therapeutic aspects are common in precisely the areas where evidence in the literature is weakest

Incidence, Treatment, and Outcome Trends of Necrotizing Enterocolitis in Preterm Infants: A Multicenter Cohort Study.

Background: Data regarding the incidence and mortality of necrotizing enterocolitis trends are scarce in the literature. Recently, some preventive strategies have been confirmed (probiotics) or increased (breastfeeding rate). This study aims to describe the trends of necrotizing enterocolitis incidence, treatment, and mortality over the last decade in Spain. Methods: Multicenter cohort study with data from the Spanish Neonatal Network-SEN1500 database. The study period comprised from January 2005 to December 2017. Preterm infants <32 weeks of gestational age at birth without major congenital malformations were included for analysis. The main study outcomes were necrotizing enterocolitis incidence, co-morbidity (bronchopulmonary dysplasia, late-onset sepsis, cystic periventricular leukomalacia, retinopathy of prematurity, acute kidney injury), mortality, and surgical/non-surgical treatment. Results: Among the 25,821 included infants, NEC incidence was 8.8% during the whole study period and remained stable when comparing 4-year subperiods. However, more cases were surgically treated (from 48.8% in 2005-2008 to 70.2% in 2015-2017, p < 0.001). Mortality improved from 36.7% in the 2005-2008 to 26.6% in 2015-2017 (p < 0.001). Breastfeeding rates improved over the studied years (24.3% to 40.5%, p < 0.001), while gestational age remained invariable (28.5 weeks, p = 0.20). Prophylactic probiotics were implemented during the study period in some units, reaching 18.6% of the patients in 2015-2017. Conclusions: The incidence of necrotizing enterocolitis remained stable despite the improvement regarding protective factors frequency. Surgical treatment became more frequent over the study period, whereas mortality decreased.

[Prevention, diagnosis and treatment of necrotising enterocolitis in newborns less than 32 weeks at birth in Spain]. / Prevención, diagnóstico y tratamiento de la enterocolitis necrosante en recién nacidos menores de 32 semanas al nacimiento en España.

OBJECTIVES: To describe preventive, diagnostic and therapeutic strategies regarding necrotising enterocolitis in Spain and to identify the strengths, areas of further improvement, and future research lines. METHODS: Two questionnaires on the management of preterm infants less than 32 weeks, at risk of, or with diagnosed necrotising enterocolitis, were distributed among selected representatives of the surgeons and neonatologists of the Spanish Neonatal Network (SEN1500) participant hospitals with a Paediatric Surgery Department. RESULTS: Percentage of response was 77.1% of contacted surgeons and 88.6% of neonatologists. There is a written protocol on the diagnosis and medical management of necrotising enterocolitis in 52% of the hospitals, and as regards surgical treatment in 33%. There is wide access to donor bank milk and to staff dedicated to breastfeeding promotion (87%). On the contrary, only 52% of the centres perform delayed cord clamping, and probiotics are used in just 23%. The use of abdominal ultrasound is increasing. There are no large differences as regards duration of antibiotic use and bowel rest, whereas there was as regards antibiotic selection, surgical indication, and type of intervention. CONCLUSIONS: As regards prevention, delayed cord clamping and extended access to donor milk are two possible aspects of further improvement. The observed discrepancies noted in diagnostic and therapeutic aspects are common in precisely the areas where evidence in the literature is weakest.

The Impact of Postnatal Systemic Steroids on the Growth of Preterm Infants: A Multicenter Cohort Study.

Postnatal steroids, often used to prevent and treat bronchopulmonary dysplasia, may influence the growth of preterm infants, although data are scarce in the literature. This is a multicenter cohort study including surviving preterm infants <32 weeks at birth (n = 17,621) from the Spanish Neonatal Network SEN1500 database, without major congenital malformations. Linear regression models were adjusted for postnatal steroids, respiratory severity course (invasive mechanical ventilation at 28 days), progression to moderate-severe bronchopulmonary dysplasia (O2 at 36 weeks), length of stay, sex, gestational age and z-scores at birth. A subgroup analysis depending on the timing of administration, ventilation status at 28 days and moderate-severe BPD diagnosis was also performed. Overall, systemic postnatal steroids were not independently associated with poorer weight gain (0.1; 95% CI: -0.05 to 0.2 g/kg/day), linear growth (0; 95% CI: -0.03 to 0.01 cm/week) or head circumference growth (-0.01; 95% CI: -0.02 to 0 cm/week). Patients who received steroids after 28 days or who were not O2 dependent at 36 weeks after having received steroids gained more weight (0.22; 95% CI: 0.04 to 0.4 and 0.2; 95% CI: 0.004 to 0.5 g/kg/day, respectively). Globally, systemic postnatal steroids had no significant adjusted effect on postnatal growth.

Usefulness of transcutaneous bilirubin assessment measured in non-photo-exposed skin to guide the length of phototherapy: an observational study.

Background Transcutaneous bilirubinometers are a non-invasive tool to estimate serum bilirubin. However, once on phototherapy (PHT) and after PHT, its usefulness is precluded. The objective of this study was to prove the hypothesis that transcutaneous bilirubin (TcB) assessment in a covered skin area during PHT could be used to guide the duration of PHT in term and moderate-late preterm infants with non-isoimmune hyperbilirubinemia. Methods A small area of parasternal skin was covered before starting on PHT. Total serum and TcB (both in exposed and non-exposed areas) were determined before starting treatment, every 12 h once on PHT and 12 h after its discontinuation. Pearson's correlation coefficient and paired mean differences between TcB and total serum bilirubin (TSB) were calculated. Bland-Altman plots were obtained. The percentage of correct treatment decisions made based on non-exposed TcB values was calculated. Results During PHT, there was a relatively good correlation between TSB and non-exposed TcB (0.74) estimates, in contrast to exposed TcB estimates (0.52). However, even when comparing non-exposed TcB with TSB, there was a wide range of agreement limits (-3.8 to 4.6 mg/dL). Decisions based on non-exposed TcB values would have been incorrect in 26.6% of the cases. Conclusion Although there is a relatively strong correlation between total serum and TcB in non-PHT-exposed regions, the difference is not narrow enough to be utilized in guiding clinical decisions on the duration of PHT.

Cohort study showed that growth rate increment has not been enough to prevent growth retardation of preterm infants and raised concerns about unbalanced growth.

AIM: We describe the postnatal weight gain, linear and head growth trends of surviving preterm infants from 2005 to 2017. METHODS: Multicentre cohort study, including surviving preterm infants <32 weeks (n = 21 084), from the Spanish Neonatal Network database, without major congenital malformations who were less than 50 weeks postmenstrual age at discharge. Outcomes were weight gain (g/kg/day), linear and head growth (cm/week) and changes in weight, length and head circumference z-scores from birth to discharge. The study period was divided into 2005-8, 2009-11, 2012-14 and 2015-17. RESULTS: Weight gain, linear growth and head growth were slightly higher in 2015-2017 than in 2005-2008: 12.2 ± 2.6 to 13.1 ± 2.5 g/kg/day, 0.98 ± 0.6 to 1.03 ± 0.6 cm/week and 0.76 ± 0.2 to 0.77 ± 0.3 cm/week, respectively. It was associated with a decreased fall in weigh, length and head circumference z-scores from birth to discharge (-1.32 ± 0.9 to -1.01 ± 0.84, -1.38 ± 1.2 to -1.18 ± 1.2 and -0.41 ± 1.2 to -0.33 ± 1.3, respectively). CONCLUSION: Postnatal growth restriction remained a common complication of prematurity despite some increment over the last years. Growth disproportionality seemed to be worsening as weight gain was increased more than linear growth.

Exploring clinical, echocardiographic and molecular biomarkers to predict bronchopulmonary dysplasia.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in childhood, related to prematurity, and the most common cause of pulmonary hypertension (PH) secondary to pulmonary disease in children. Moderate and severe BPD have a worse outcome and relate more frequently with PH. The prediction of moderate or severe BPD development in extremely premature newborns is vital to implement preventive strategies. Starting with the hypothesis that molecular biomarkers were better than clinical and echocardiographic factors, this study aims to explore the ability of clinical, echocardiographic and analytical variables to predict moderate or severe BPD in a cohort of extremely preterm infants. PATIENTS AND METHODS: We designed a prospective longitudinal study, in which we followed a cohort of preterm newborns (gestational age <28 weeks and weight ≤ 1250 grams). In these newborns we recorded weekly clinical and echocardiographic variables as well as blood and tracheal aspirate samples, to analyze molecular biomarkers (IL-6, IL-1, IP10, uric acid, HGF, endothelin-1, VEGF, CCL5). Variables and samples were collected since birth up to week 36 (postmenstrual age), time-point at which the diagnosis of BPD is established. RESULTS: We included 50 patients with a median gestational age of 26 weeks (IQR 25-27) and weight of 871 g (SD 161,0) (range 590-1200g). Three patients were excluded due to an early death. Thirty-five patients (74.5%) developed BPD (mild n = 14, moderate n = 15, severe n = 6). We performed a logistic regression in order to identify risk factors for moderate or severe BPD. We compared two predictive models, one with two variables (mechanical ventilation and inter-ventricular septum flattening), and another-one with an additional molecular biomarker (ET-1). CONCLUSIONS: The combination of clinical and echocardiographic variables is a valuable tool for determining the risk of BPD. We find the two variable model (mechanical ventilation and echocardiographic signs of PH) more practical for clinical and research purposes. Future research on BPD prediction should be oriented to explore the potential role of ET-1.

The Effect of Morbidity and Sex on Postnatal Growth of Very Preterm Infants: A Multicenter Cohort Study.

BACKGROUND: Extrauterine growth restriction is common in the preterm infant, and it is associated with poor neurodevelopment. Nutrition plays an important role in postnatal growth, but growth is also influenced by other factors like co-morbidity, and, also, there might be sex differences. METHODS: This is a cohort study including preterm infants < 32 weeks at birth (n = 21,825) from the Spanish Neonatal Network database. The effect of sex and morbidity (patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing enterocolitis and late-onset sepsis) on weight gain as well as linear and head growth from birth to discharge/death was assessed with linear regression models adjusted by gestational age and Z-scores at birth. RESULTS: The 4 selected morbidities had an independent effect on all 6 growth parameters studied, which was greater in the case of necrotizing enterocolitis: changes in weight, length and head Z-scores were -0.60 (95% CI: -0.66 to -0.55), -0.62 (95% CI: -0.70 to -0.54) and -0.63 (95% CI: -0.71 to -0.56), respectively. Weight gain and linear growth were overall more affected than head growth. Girls lost slightly more weight Z-scores (-0.03; 95% CI: -0.06 to -0.002) than boys after adjustment by morbidity. There were no significant gender differences regarding linear and head growth velocity (cm/week), although girls lost more head Z-scores (-0.14; 95% CI: -0.18 to -0.10). CONCLUSIONS: Main co-morbidities associated with prematurity have an impact on postnatal growth. Head growth is less affected than length and weight. Girls are at slightly higher risk of postnatal weight and head restriction after adjustment by morbidity.