Comparative analysis of foetal and neonatal growth curves.

INTRODUCTION: Our aim was to determine which foetal or neonatal growth curves discriminate the probability of dying of newborns with low birth weight for their gestational age (small for gestational age, SGA) and sex (weight < 10th percentile) and to establish the curves that are presumably most useful for monitoring growth through age 10 years. MATERIAL AND METHODS: The analysis included every neonate (15 122) managed in our hospital (2013-2022) and all neonates born preterm before 32 weeks (6913) registered in the SEN1500 database (2019-2022). We considered most useful those curves with the highest likelihood ratio (LR) for dying with or without a history of SGA in each subgroup of gestational ages. Theoretically, the optimal curves for monitoring growth would be those with a higher R2 in the quantile regression formulas for the 50th percentile. RESULTS: The growth curves exhibiting the strongest association between SGA and hospital mortality are the Intergrowth fetal curves and the Fenton neonatal curves in infants born preterm before 32 weeks. However, the optimal curves for premature babies and neonates overall were those of Olsen and Intergrowth. The most useful curves to monitor anthropometric values alone until age 10 years of age are the longitudinal Intergrowth curves followed by the WHO standards, but if a single reference is desired from birth through age 10 years, the best option is the Fenton curves followed by the WHO standards. CONCLUSIONS: The Intergrowth reference provides the most discriminating foetal growth curves. In neonatal clinical practice, the optimal references are the Fenton followed by the WHO charts.

Lung Microbiota and Ventilator-Associated Pneumonia in the Neonatal Period.

The lung microbiota is a complex community of microorganisms that colonize the respiratory tract of individuals from, or even before, birth. Although the lungs were traditionally believed to be sterile, recent research has shown that there is a diversity of bacterial species in the respiratory system. Knowledge about the lung microbiota in newborns and its relationship with bacterial infections is of vital importance to understand the pathogenesis of respiratory diseases in neonatal patients undergoing mechanical ventilation. In this article, the current evidence on the composition of the lung microbiota in newborns will be reviewed, as well as the risks that an altered microbiota can impose on premature newborns. Although advances in neonatal intensive care units have significantly improved the survival rate of preterm infants, the diagnosis and treatment of ventilator-associated pneumonia has not progressed in recent decades. Avoiding dysbiosis caused by inappropriate use of antibiotics around birth, as well as avoiding intubation of patients or promoting early removal of endotracheal tubes, are among the most important preventive measures for ventilator-associated pneumonia. The potential benefit of probiotics and prebiotics in preventing infectious, allergic or metabolic complications in the short or long term is not clearly established and constitutes a very important field of research in perinatal medicine.

Prediction of bronchopulmonary dysplasia in very preterm infants: competitive risk model nomogram.

Objective: To develop predictive clinical models of bronchopulmonary dysplasia (BPD) through competing risk analysis. Methods: Retrospective observational cohort study, including preterm newborns ≤32 weeks gestational age, conducted between January 1, 2013 and September 30, 2022 in a third-level Neonatal Intensive Care Unit in Spain. A prediction study was carried out using competing risk models, where the event of interest was BPD and the competing event was death. A multivariate competing risk model was developed separately for each postnatal day (days 1, 3, 7 and 14). Nomograms to predict BPD risk were developed from the coefficients of the final models and internally validated. Results: A total of 306 patients were included in the study, of which 73 (23.9%) developed BPD and 29 (9.5%) died. On day 1, the model with the greatest predictive capacity was that including birth weight, days since rupture of membranes, and surfactant requirement (area under the receiver operating characteristic (ROC) curve (AUC), 0.896; 95% CI, 0.792-0.999). On day 3, the final predictive model was based on the variables birth weight, surfactant requirement, and Fraction of Inspired Oxygen (FiO2) (AUC, 0.891; 95% CI, 0.792-0.989). Conclusions: Competing risk analysis allowed accurate prediction of BPD, avoiding the potential bias resulting from the exclusion of deceased newborns or the use of combined outcomes. The resulting models are based on clinical variables measured at bedside during the first 3 days of life, can be easily implemented in clinical practice, and can enable earlier identification of patients at high risk of BPD.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation.

OBJECTIVE: To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. METHOD: Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. RESULTS: A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. CONCLUSIONS: The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation

Abstract Objective To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. Method Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. Results A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. Conclusions The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Morbidity and Mortality of Very-Low-Birthweight Twin Infants according to Their Sex and the Sex of the Co-Twin: A Retrospective Cohort Study.

INTRODUCTION: The concept of male disadvantage regarding the prognosis of premature newborns was introduced more than half a century ago, and it has been corroborated over time. However, the influence of the sex of one twin on the outcomes of the other has yielded contradictory results. OBJECTIVE: The aim of the study was to determine if, in twin pregnancies of VLBW infants, the outcomes of one twin are modified by the sex of the co-twin. METHODS: A multicentre retrospective study of a cohort of infants admitted to the collaborating units of the Spanish SEN1500 neonatal network was conducted. Liveborn VLBW twin infants, from 23+0 to 31+6 weeks of gestational age (GA), admitted from 2011 to 2020 were included. Outborn patients, infants with major congenital anomalies, and cases with only one twin admitted were excluded. The main outcomes were survival until first hospital discharge, survival without moderate or severe bronchopulmonary dysplasia (BPD), survival without major brain damage (MBD), and survival without major morbidity. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated. RESULTS: 2,111 twin pairs were included. Male infants exhibited worse outcomes than females (IRR; 95% CI) regarding survival (0.96; 0.94, 0.98), survival without moderate or severe BPD (0.89; 0.86, 0.93), survival without MBD (0.94; 0.91, 0.97), and survival without major morbidity (0.87; 0.81, 0.93). Differences disappeared when the co-twin was a female infant: survival (1.00; 0.97, 1.03), survival without moderate or severe BPD (0.96; 0.91, 1.01), survival without MBD (0.99; 0.95, 1.04), and survival without major morbidity (0.94; 0.85, 1.03). Results for female infants did not change significantly with co-twin sex. CONCLUSIONS: Among VLBW twins from 23+0 to 31+6 weeks of GA, male infants have higher risk of morbidity and mortality overall. In cases of pregnancies with different-sex foetuses, males seem to improve their results, while these do not change for females. The underlying mechanism of this influence deserves further investigation.

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.

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.

Birth order and morbidity and mortality to hospital discharge among inborn very low-birthweight, very preterm twin infants admitted to neonatal intensive care: a retrospective cohort study.

OBJECTIVE: To know the association of birth order with the risk of morbidity and mortality in very low-birthweight (VLBW) twin infants less than 32 weeks' gestational age (GA). DESIGN: Retrospective cohort study. SETTING: Infants admitted to the collaborating centres of the Spanish SEN1500 neonatal network. PATIENTS: Liveborn VLBW twin infants, with GA from 23+0 weeks to 31+6 weeks, without congenital anomalies, admitted from 2011 to 2020. Outborn patients were excluded. MAIN OUTCOME MEASURES: Respiratory distress syndrome (RDS), patent ductus arteriosus, bronchopulmonary dysplasia (BPD), necrotising enterocolitis, major brain damage (MBD), late-onset neonatal sepsis, severe retinopathy of prematurity, survival and survival without morbidity. Crude and adjusted incidence rate ratios were calculated. RESULTS: Among 2111 twin pairs included, the second twin had higher risk (adjusted risk ratio (aRR) of RDS (aRR 1.08, 95% CI 1.03 to 1.12) and need for surfactant (aRR1.10, 95% CI 1.05 to 1.16). No other significant differences were found, neither in survival (aRR 1.01, 95% CI 0.99 to 1.03) nor in survival without BPD (aRR 1.02, 95% CI 0.99 to 1.05), survival without MBD (aRR 1.02, 95% CI 0.99 to 1.06) nor in survival without major morbidity (aRR 0.97, 95% CI 0.92 to 1.03). However, second twins born by caesarean section (C-section) after a vaginally delivered first twin had less overall survival and survival without MBD. CONCLUSION: In modern perinatology, second twins are still more unstable immediately after birth and require more resuscitation. After admission to the neonatal intensive care unit, they are at increased risk of RDS, but not other conditions, except for second twins delivered by C-section after a first twin delivered vaginally, who have decreased overall survival and survival without major brain injury.

Survival and Survival without Major Morbidity Seem to Be Consistently Better throughout Gestational Age in 24- to 30-Week Gestational Age Very-Low-Birth-Weight Female Infants Compared to Males.

INTRODUCTION: Several studies showed advantages in outcomes for very-low-birth-weight (VLBW) female infants. It has been suggested that recent advances in perinatal care might have benefited boys relatively more than girls, making differences disappear. OBJECTIVES: The aims of the study were (1) to determine if sex differences in survival and survival without morbidity in VLBW infants are still present in the context of more advanced perinatal care and (2) to know whether these differences are consistent throughout gestational age (GA). METHODS: Retrospective cohort study in seven countries participating in the Spanish SEN1500 and the South American NEOCOSUR neonatal networks. We included VLBW infants 24-30 weeks' GA, born alive without major congenital anomalies (2013-2016). Major morbidity, survival, and survival without morbidity were compared between male and female infants overall and stratified by GA. RESULTS: 10,565 patients were included: 5,620 (53.2%) males and 4,945 (46.8%) females. Female infants exhibited a lower incidence rate ratio (95% CI) of respiratory distress syndrome: 0.91 (0.88, 0.94), necrotizing enterocolitis: 0.83 (0.74, 0.93), major brain damage: 0.79 (0.72, 0.86), moderate-severe bronchopulmonary dysplasia (BPD): 0.77 (0.72, 0.83), higher survival: 1.03 (1.01, 1.05), survival without BPD: 1.11 (1.07, 1.16), survival without major brain damage: 1.05 (1.02, 1.08), and survival without major morbidity: 1.14 (1.07, 1.21). Survival and survival without morbidity were almost consistently favourable to females throughout GA. CONCLUSIONS: Our findings suggest that perinatal results continue to be favourable for VLBW female infants in the context of current perinatology, and that they are almost consistent throughout GA.

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.

Management of neonates with 35 weeks of gestational age or more with infectious risk factors at birth: opportunities for improvement.

OBJECTIVES: The Northern California Kaiser-Permanente Neonatal Sepsis Risk Calculator (SRC) has proved to be safe and effective in reducing laboratory tests, hospital admissions, and administration of antibiotics to patients at risk of early-onset neonatal sepsis (EONS). Many studies have focused on maternal chorioamnionitis as the principal risk factor for EONS. We wanted to know if the use of the SRC could be equally efficient in the context of several other infectious risk factors (IRF), in addition to chorioamnionitis, such as intrapartum maternal fever, GBS colonization and/or prolonged rupture of membranes (PROM). METHODS: Systematic study of neonates with ≥35 weeks gestational age (GA), born in our tertiary university hospital during a period of 18 months. Patients were retrospectively assessed with the SRC and its recommendations were compared with the actual management. A bivariate analysis of perinatal interventions, and outcomes was performed. RESULTS: A total of 5,885 newborns were born during the study period and 1783 mothers (31%) had at least one IRF. The incidence of culture-proven EONS was 0.5‰. The use of the SRC would have reduced laboratory evaluations (CBC and CRP) from 56.2 to 23.3%, and blood cultures, hospital admissions and antibiotic therapy from 22.9 to 15.5%, 17.8 and 7.6%, respectively. The management based on patients' symptoms would have shown a reduction to 7.5% in all the outcomes of interest. CONCLUSIONS: Both, the SRC and the management based on clinical findings, are safe and efficient to reduce the number of analytical studies, hospital admissions and administration of antibiotics to neonates with IRF.

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.

Effects of public health measures during the SARS-CoV-2 pandemic on the winter respiratory syncytial virus epidemic: An interrupted time series analysis.

BACKGROUND: Public health measures (PHM) designed to contain the spread of COVID-19 pandemic have influenced the epidemiological characteristics of other viral infections. Its impact on acute RSV bronchiolitis in infants of ≤24 months old has not been systematically studied in our setting. OBJECTIVES: To describe the monthly pattern of visits to the Paediatric Emergency Department (PED) of patients 0 to 14 years of age, the rate of patients diagnosed with RSV acute bronchiolitis per thousand inhabitants of 0 to 24 months, and the rate of them requiring hospital admission during the winter 2020-2021, in the context of local and national COVID-19 restrictions and compare them to the four previous seasons. METHODS: Interrupted time series analysis of patients assisted in the PED and diagnosed with or admitted for RSV acute bronchiolitis in a tertiary University Hospital from January 2016 to February 2020 (pre-intervention period) and from March 2020 to June 2021 (post-intervention period). INTERVENTION: Preventive PHM implemented by the Spanish government weighted by the Containment and Health Index of the Oxford COVID-19 Government Response Tracker. RESULTS: The intervention was followed by an immediate reduction of the rate of visits to the PED of -19.5 (95% confidence interval [CI] -24.0, -14.9) per thousand, and the rate of diagnoses and admissions for RSV acute bronchiolitis of -44.3 (95% CI -73.8, -14.8) and -1.4 (95% CI -2.7, -0.1) per thousand, respectively, with a delayed rebound. CONCLUSIONS: After the implementation of PHM to prevent the spread of SARS-CoV-2 infection, an immediate and important decline in the visits to the PED was observed, with an upward change thereafter. There was also an initial reduction in the diagnoses of and admissions by RSV acute bronchiolitis. An upward trend was observed six to nine months after the usual time of the winter RSV epidemic, coinciding with the relaxation of the preventive PHM.

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).

Factors Associated with Survival and Survival without Major Morbidity in Very Preterm Infants in Two Neonatal Networks: SEN1500 and NEOCOSUR.

INTRODUCTION: Very low-birth weight (VLBW) infants represent a high-risk population for morbidity and mortality in the neonatal period. Variability in practices and outcomes between centers has been acknowledged. Multicenter benchmarking studies are useful to detect areas of improvement and constitute an interesting research tool. OBJECTIVES: The aim of the study was to determine the perinatal variables and interventions associated with survival and survival without major morbidity in VLBW infants and compare the performance of 2 large networks. METHODS: This is a prospective study analyzing data collected in 2 databases, the Spanish SEN1500 and the South American NEOCOSUR networks, from January 2013 to December 2016. Inborn patients, from 240 to 306 weeks of gestational age (GA) were included. Hazard ratios for survival and survival without major morbidity until the first hospital discharge or transfer to another facility were studied by using Cox proportional hazards regression. RESULTS: A total of 10,565 patients, 6,120 (57.9%) from SEN1500 and 4,445 (42.1%) from NEOCOSUR, respectively, were included. In addition to GA, birth weight, small for gestational age (SGA), female sex, and multiple gestation, less invasive resuscitation, and the network of origin were significant independent factors influencing survival (aHR [SEN1500 vs. NEOCOSUR]: 1.20 [95% CI: 1.15-1.26] and survival without major morbidity: 1.34 [95% CI: 1.26-1.43]). Great variability in outcomes between centers was also found within each network. CONCLUSIONS: After adjusting for covariates, GA, birth weight, SGA, female sex, multiple gestation, less invasive resuscitation, and the network of origin showed an independent effect on outcomes. Determining the causes of these differences deserves further study.

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.

Intercenter variability and factors associated with survival without bronchopulmonary dysplasia in extremely preterm newborns.

Background: Variability in clinical practice may influence morbidity and mortality in extremely preterm infants. We aimed to know if there are differences in survival and survival without bronchopulmonary dysplasia (BPD) in extremely preterm infants in Spanish tertiary hospitals and the potential associated factors.Methods: Fifteen hospitals from the SEN1500 network were studied. The overall rate of survival without BPD was 61.4%. Hospitals with extreme results were grouped for comparison (Group 1; N = 2480 versus Group 2; N = 2367). A bivariate analysis of the characteristics of patients and perinatal interventions was carried out and the probability of survival without BPD was studied by Cox regression.Results: Survival (79.0 versus 72.9%; p < .001) and survival without BPD (72.5 versus 49.1%; p < .001) were greater in Group 1. Higher gestational age, birth weight, and female sex were associated with better outcomes. Oxygen administration (aHR: 0.868 [95%CI: 0.782, 0.964]; p=.008) and intubation (aHR: 0.767 [95%CI: 0.701, 0.839]; p < .001) in delivery room were associated with lower survival without BPD. The occurrence of patent ductus arteriosus (PDA), sepsis and/or necrotizing enterocolitis (NEC) was independently associated with worse outcomes. After adjusting for confounders, the probabilities of survival without BPD were significantly higher among patients in Group 1: aHR: 1.557 [95% CI: 1.458, 1.662]; p < .001.Conclusions: Among the studied hospitals, we found great variability in clinical practice and in the rates of survival and survival without BPD. A more conservative approach to the use of oxygen and respiratory support seems to be related to an increase in survival without BPD. Complications such as PDA, sepsis, and/or NEC decrease survival without BPD. Other variables not included in the present study could be relevant and deserve further study.