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.

Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

Relevancia de los enterovirus en la meningitis neonatal / Relevance of enteroviruses in neonatal meningitis

Introducción: Las infecciones por enterovirus (EV) constituyen las infecciones más frecuentes en el periodo neonatal y provocan en muchos casos el ingreso hospitalario del recién nacido (RN). El objetivo del estudio es conocer la incidencia de los EV en la etiología de las meningitis neonatales y definir qué características clínicas presentan los RN con meningitis por EV. Material y método: Estudio observacional retrospectivo de cohortes. Incluye 91 RN con meningitis y edad gestacional mayor de 34 semanas (SG) atendidos en nuestro centro durante un periodo de 16 años. Resultados: El porcentaje de RN con meningitis por EV fue superior al de RN con meningitis bacteriana y representó el 78% (n=71). La mitad de los RN con infección por EV presentó antecedentes de ambiente epidémico entre sus cuidadores. La fiebre apareció en el 96% de los casos como signo clínico y, en general, las alteraciones del sensorio representaron las principales alteraciones neurológicas. Un 71,4% de los pacientes con infección por EV recibió antibióticos. La detección de EV en muestras de LCR mostró una elevada sensibilidad para el diagnóstico de meningitis por EV. Los tipos de EV más frecuentemente implicados fueron echovirus 11, coxsackievirus B5, echovirus 18, 25 y 7. Conclusiones: Los resultados de esta serie muestran que la infección por enterovirus es una causa común de meningitis neonatal. Estos datos subrayan la importancia de realizar pruebas de detección rápida de EV en lactantes con sospecha de meningitis. Ello permite obtener un diagnóstico precoz y reducir el tratamiento antibiótico, el tiempo de hospitalización y los costes relacionados.(AU)

Introduction: Enterovirus (EV) infections are the most frequent infections in the neonatal period and in many cases lead to hospital admission of the newborn (NB). The aim of this study was to determine the incidence of EV in the etiology of neonatal meningitis and to define the clinical characteristics of newborns with EV meningitis. Material and method: Retrospective observational cohort study. Including 91 NBs with meningitis and gestational age greater than 34 weeks gestational age (GA) attended in our center over a period of 16 years. Results: The percentage of NBs with EV meningitis was higher than that of NBs with bacterial meningitis (BM) and accounted for 78% (n=71). Half of the NBs with EV infection had a history of epidemic environment among their caregivers. Fever was present in 96% of cases as a clinical sign and, in general, sensory disturbances represented the main neurological alterations. Antibiotics (ATB) were given to 71.4% of patients with EV infection. Detection of EV in CSF samples showed a high sensitivity for the diagnosis of EV meningitis. The most frequently implicated EV types were echovirus 11, coxsackievirus B5, echovirus 18, 25 and 7. Conclusions: The results of this series show that enterovirus infection is a common cause of neonatal meningitis. These data underline the importance of rapid EV testing of infants with suspected meningitis. This allows early diagnosis and reduces antibiotic treatment, hospitalization time and related costs.(AU)

Relevance of enteroviruses in neonatal meningitis.

INTRODUCTION: Enterovirus (EV) infections are the most frequent infections in the neonatal period and in many cases lead to hospital admission of the newborn (NB). The aim of this study was to determine the incidence of EV in the etiology of neonatal meningitis and to define the clinical characteristics of newborns with EV meningitis. MATERIAL AND METHOD: Retrospective observational cohort study. Including 91 NBs with meningitis and gestational age greater than 34 weeks gestational age (GA) attended in our center over a period of 16 years. RESULTS: The percentage of NBs with EV meningitis was higher than that of NBs with bacterial meningitis (BM) and accounted for 78% (n=71). Half of the NBs with EV infection had a history of epidemic environment among their caregivers. Fever was present in 96% of cases as a clinical sign and, in general, sensory disturbances represented the main neurological alterations. Antibiotics (ATB) were given to 71.4% of patients with EV infection. Detection of EV in CSF samples showed a high sensitivity for the diagnosis of EV meningitis. The most frequently implicated EV types were echovirus 11, coxsackievirus B5, echovirus 18, 25 and 7. CONCLUSIONS: The results of this series show that enterovirus infection is a common cause of neonatal meningitis. These data underline the importance of rapid EV testing of infants with suspected meningitis. This allows early diagnosis and reduces antibiotic treatment, hospitalization time and related costs.

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.

Effectiveness of a probiotic combination on the neurodevelopment of the very premature infant.

Probiotics have shown a benefit in reducing necrotising enterocolitis in the premature infant, however the study of their effect on premature neonates' neurodevelopment is limited. The aim of our study was to elucidate whether the effect of Bifidobacterium bifidum NCDO 2203 combined with Lactobacillus acidophilus NCDO 1748 could positively impact the neurodevelopment of the preterm neonates. Quasi-experimental comparative study with a combined treatment of probiotics in premature infants < 32 weeks and < 1500 g birth weight, cared for at a level III neonatal unit. The probiotic combination was administered orally to neonates surviving beyond 7 days of life, until 34 weeks postmenstrual age or discharge. Globally, neurodevelopment was evaluated at 24 months corrected age. A total of 233 neonates were recruited, 109 in the probiotic group and 124 in the non-probiotic group. In those neonates receiving probiotics, there was a significant reduction in neurodevelopment impairment at 2 years of age RR 0.30 [0.16-0.58], and a reduction in the degree of impairment (normal-mild vs moderate-severe, RR 0.22 [0.07-0.73]). Additionally, there was a significant reduction in late-onset sepsis (RR 0.45 [0.21-0.99]). The prophylactic use of this probiotic combination contributed to improving neurodevelopmental outcome and reduced sepsis in neonates born at < 32 weeks and < 1500 g.Per style, a structured abstract is not allowed so we have changed the structured abstract to an unstructured abstract. Please check and confirm.Accepted.

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.

Correction: Prediction of mortality in very low birth weight neonates in Spain.

[This corrects the article DOI: 10.1371/journal.pone.0235794.].

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

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.

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.

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.

Feasibility of umbilical cord blood as a source of red blood cell transfusion in preterm infants.

BACKGROUND: Preterm infants born earlier than 32 weeks of gestational age (GA) often need red blood cell (RBC) transfusions, which have been associated with an increased incidence of complications of prematurity, due to changes in tissue oxygenation. Transfusion of umbilical cord blood (UCB) could be beneficial for this group. The aims of this study were: (i) to determine the RBC transfusion needs in infants <32 weeks in Hospital Clinic of Barcelona; (ii) to identify the target GA group that would benefit most from UCB transfusion; and (iii) to assess the current availability of UCB as a potential source of RBC transfusion for these premature infants in our tertiary referral blood bank. MATERIAL AND METHODS: A retrospective observational study was performed on infants born at <32 weeks GA, divided into two groups: (i) extremely low gestational age neonates (ELGAN) (from 230 to 276 weeks) and (ii) very preterm neonates (VPN) (from 280 to 316 weeks). Their complications and transfusion rates were compared. Processing and availability of UCB samples in the reference blood bank were assessed. RESULTS: Overall, 1,651 infants <32 weeks GA were admitted in the study period. While 12.5% of VPN received at least one RBC transfusion, the percentage increased to 60% among the ELGAN. Retinopathy of prematurity and bronchopulmonary dysplasia were diagnosed more frequently in the ELGAN group (p<0.001) than in the VPN group. The annual average volume of RBC transfusion in our study group was 1.35 L (95% CI: 1.07-1.64). The reference blood bank was able to produce 16 L (95% CI: 14-18) of UCB-RBC per year. CONCLUSION: Considering the data obtained about RBC transfusion needs and morbidities, the ELGAN group has been identified as the target group that would benefit most from UCB-RBC transfusions. We have demonstrated that our blood bank is able to produce enough RBC from UCB. Randomised control trials are warranted to study the potential benefits of UCB compared to adult blood for RBC transfusions.

Prediction of mortality in very low birth weight neonates in Spain.

OBJECTIVE: Predictive models for preterm infant mortality have been developed internationally, albeit not valid for all populations. This study aimed to develop and validate different mortality predictive models, using Spanish data, to be applicable to centers with similar morbidity and mortality. METHODS: Infants born alive, admitted to NICU (BW<1500 g or GA<30 w), and registered in the SEN1500 database, were included. There were two time periods; development of the predictive models (2009-2012) and validation (2013-2015). Three models were produced; prenatal (1), first 24 hours of life (2), and whilst admitted (3). For the statistical analysis, hospital mortality was the dependent variable. Significant variables were used in multivariable regression models. Specificity, sensitivity, accuracy, and area under the curve (AUC), for all models, were calculated. RESULTS: Out of 14953 included newborns, 2015 died; 373 (18.5%) in their first 24 hours, 1315 (65.3%) during the first month, and 327 (16.2%) thereafter, before discharge. In the development stage, mortality prediction AUC was 0.834 (95% CI: 0.822-0.846) (p<0.001) in model 1 and 0.872 (95% CI: 0.860-0.884) (p<0.001) in model 2. Model 3's AUC was 0.989 (95% CI: 0.983-0.996) (p<0.001) and 0.942 (95% CI: 0.929-0.956) (p<0.001) during the 0-30 and >30 days of life, respectively. During validation, models 1 and 2 showed moderate concordance, whilst that of model 3 was good. CONCLUSION: Using dynamic models to predict individual mortality can improve outcome estimations. Development of models in the prenatal period, first 24 hours, and during hospital admission, cover key stages of mortality prediction in preterm infants.

Fortifier selection and dosage enables control of breast milk osmolarity.

BACKGROUND: Human breast milk (BM) fortification is required to feed preterm newborns with less than 32 weeks of gestation. However, addition of fortifiers increases osmolarity and osmolarity values higher than 450 mOsm/kg may be related to gastrointestinal pathology. Hence, fortifier selection and dosage are key to achieve optimal feeding. OBJECTIVES: To compare the effect on osmolality of adding different fortifications, including recently developed formulations, to BM and to study evolution of osmolarity over time in supplemented BM. METHODS: Frozen mature BM from 10 healthy mothers of premature newborns was fortified with each of the following human milk fortifiers (HMF): AlmirónFortifier®, NANFM85®, or PreNANFM85®. In addition, fortified BMs were modified with one of the following nutritional supplements (NS): Duocal MCT®, Nutricia® AminoAcids Mix, or Maxijul®. Osmolality of BM alone, fortified and/or supplemented was measured at 1 and 22 hours after their preparation. All samples were kept at 4°C throughout the study. RESULTS: Osmolality of BM alone was close to 300 mOsm/kg and did not change over 22 hours. When equicaloric amounts of HMF AlmirónFortifier®, NANFM85®, and PreNANFM85® were added to BM, osmolality increased roughly to 480 mOsm/kg with the first two fortifiers and only to 433±6 mOsm/kg with the third one. Upon addition of any of four different NSs to BM modified with AlmirónFortifier® and NANFM85®, osmolality reached values greater than 520 mOsm/kg, while osmolality of PreNANFM85® with two out of the four NSs remained below 490 mOsm/kg. NSs supplementing carbohydrates and hydrolysed proteins resulted into a higher increase of BM osmolarity. Osmolality increased significantly with time and, after 22h, only BM modified with PreNANFM85® remained below 450 mOsm/kg. CONCLUSIONS: Upon addition of the HMFs tested, BM osmolality increases significantly and keeps raising over time. All HMFs but the recently developed PreNAN FM85® at 4% exceed the AAP recommended threshold for osmolarity of 450 mOsm/kg. Addition of NSs to PreNAN FM85® at 4% significantly increases osmolality above 450 mOsm/Kg. Thus, using PreNAN FM85® at 5% may be preferable to adding nutritional supplements since nutritional recommendations by the ESPGHAN are reached with a lower increase in osmolality.

Extrauterine growth restriction in very preterm infant: etiology, diagnosis, and 2-year follow-up.

In very-preterm small-for-gestational-age (SGA) infants, long-term postnatal growth is confused with extrauterine growth restriction (EUGR). We aimed to document EUGR in SGA infants and in non-SGA infants ("true-EUGR") and its relationship with fetal, maternal, and neonatal etiological factors. Four hundred seventy-nine very-preterm infants (< 32 weeks) born between 2003 and 2014 and attending the follow-up clinic were included. INTERGROWTH-21st preterm postnatal growth standards in conjunction with WHO Child Growth Standards were used to judge the postnatal growth patterns. EUGR was defined as weight < 10th percentile according to the sex at 36-34 weeks postmenstrual age, usually at discharge. Catch-up was evaluated at 2-2.5 years. Low-weight-for-age (wasting), low-length-for-age (stunting), and low-head-circumference-for-age were diagnosed if the z-scores were below - 2 SD. Logistic regression analysis estimated the association between the risk factors and EUGR, according to the SGA status at birth. Overall, EUGR occurred in 51% at 36-34 postmenstrual weeks and 21% at 2-2.5 years. However, among 411 non-SGA infants, "true-EUGR" rates were 43% and 15%, respectively.Conclusion: By 2-2.5 years of age, a "true-EUGR" of 15% can be expected and only the head circumference normalizes in SGA infants. Low birth weight, hyaline membrane disease, bronchopulmonary dysplasia, and male sex were associated with "true-EUGR." What is Known: • Fetal, neonatal, or postnatal charts have been considered to monitor the postnatal growth of preterm infants. • This selection influences the diagnosis of "extrauterine growth restriction" (EUGR) and the clinical strategies used. What is New: • Extrauterine growth restriction (EUGR) in small-for-gestational-age (SGA) infants can not be considered a true EUGR but a postnatal evolution of fetal growth restriction. • Preeclampsia, low gestational age, severe neonatal morbidity and male sex are independently associated with EUGR in non-SGA infants (named "true-EUGR"), which can be expected in 15% of very preterm infants by 2-2.5 years of age.

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.

Variations in the number of births by day of the week, and morbidity and mortality in very-low-birth-weight infants / Variações no número de partos por dia da semana e morbidez e mortalidade em neonatos com muito baixo peso ao nascer

Abstract Objective: To know the distribution of births of very low birth weight infants by day of the week, and whether this distribution affects the morbidity and mortality in this group of patients. Methods: This was a retrospective analysis of data collected prospectively in the Spanish SEN1500 network (2002-2011). Outborn infants, patients with major congenital anomalies, and those who died in the delivery room were excluded. Births were grouped into "weekdays" and "weekends." A multivariate logistic regression analysis was conducted to evaluate the independent effect of the birth moment on outcomes, and Cox regression for survival. Results: Out of a total of 27,205 very low birth weight infants born at and/or admitted to the participating centers, 22,961 (84.4%) met inclusion criteria. A reduction of 24% in the number of births was observed during the "weekends" compared with "weekdays". In the raw analysis, patients born on weekends exhibited higher morbidity and mortality (mortality rate: 14.2% vs. 16.5%, p < 0.001), but differences were no longer significant after adjusting for confounding factors. Conclusions: The present results suggest that current care practices reduce the proportion of births during the weekends and tend to cluster some high-risk births during this period, increasing crude morbidity and mortality. However, after adjusting for confounding factors, the differences disappear, suggesting that overall care coverage in these centers is appropriate.

Resumo Objetivo: Conhecer a distribuição dos partos de neonatos com muito baixo peso ao nascer durante a semana e se essa distribuição afeta a morbidez e a mortalidade nesse grupo de pacientes. Método: Esta é uma análise retrospectiva de dados coletados prospectivamente na rede espanhola SEN1500 (2002-2011). Foram excluídos neonatos nascidos em outro local, pacientes com grandes anomalias congênitas e pacientes falecidos na sala de parto. Os partos foram agrupados em "Dias úteis" e "Final de semana". Foi realizada uma análise de regressão logística multivariada para avaliar o efeito independente do parto sobre os resultados e uma regressão de Cox para avaliar a sobrevida. Resultados: Do total de 27.205 neonatos com muito baixo peso ao nascer nascidos e/ou internados nos centros participantes, 22.961 (84,4%) atenderam aos critérios de inclusão. Houve uma redução de 24% no número de partos no "Final de semana" em comparação com os "Dias úteis". Na análise bruta, os pacientes nascidos em finais de semana apresentaram maior morbidez e mortalidade (Taxa de mortalidade: 14,2% em comparação a 16,5%, p < 0,001), porém as diferenças não eram mais significativas após o ajuste aos fatores de confusão. Conclusões: Nossos resultados sugerem que as práticas atuais de atendimento reduzem a proporção de partos em finais de semana e tendem a agrupar alguns partos de alto risco nesse período, aumentando a morbidez e mortalidade brutas. Contudo, após o ajuste aos fatores de risco, as diferenças desaparecem, sugerindo que a cobertura de atendimento geral em nossos centros é adequada.

Variations in the number of births by day of the week, and morbidity and mortality in very-low-birth-weight infants.

OBJECTIVE: To know the distribution of births of very low birth weight infants by day of the week, and whether this distribution affects the morbidity and mortality in this group of patients. METHODS: This was a retrospective analysis of data collected prospectively in the Spanish SEN1500 network (2002-2011). Outborn infants, patients with major congenital anomalies, and those who died in the delivery room were excluded. Births were grouped into "weekdays" and "weekends." A multivariate logistic regression analysis was conducted to evaluate the independent effect of the birth moment on outcomes, and Cox regression for survival. RESULTS: Out of a total of 27,205 very low birth weight infants born at and/or admitted to the participating centers, 22,961 (84.4%) met inclusion criteria. A reduction of 24% in the number of births was observed during the "weekends" compared with "weekdays". In the raw analysis, patients born on weekends exhibited higher morbidity and mortality (mortality rate: 14.2% vs. 16.5%, p<0.001), but differences were no longer significant after adjusting for confounding factors. CONCLUSIONS: The present results suggest that current care practices reduce the proportion of births during the weekends and tend to cluster some high-risk births during this period, increasing crude morbidity and mortality. However, after adjusting for confounding factors, the differences disappear, suggesting that overall care coverage in these centers is appropriate.