[Prenatal rescue dose of betamethasone in the preterm infant with intrauterine growth restriction]. / Dosis prenatal de rescate de betametasona en el prematuro con restricción del crecimiento intrauterino.

Antenatal corticosteroids reduce mortality and respiratory distress syndrome (RDS) in preterm newborns. These benefits decrease after a week of administration, recommending a rescue therapy if there is a new threat of premature delivery. Repeated administration of antenatal corticosteroids may have deleterious effects and their benefits are controversial in intrauterine growth restriction (IUGR). OBJECTIVE: to verify the effects in the IUGR population of antenatal betamethasone rescue therapy on neonatal morbidity and mortality, RDS, and neurodevelopment at 2 years. PATIENTS AND METHOD: Retrospective study including ≤ 34 weeks and ≤ 1,500g preterm newborns divided according to antenatal betamethasone exposure: Single-cycle (2 doses) vs Rescue therapy (3 doses). Subgroups were created for those ≥ 30 weeks. Both cohorts were followed up to 24 months of corrected age. The Ages & Stages Questionnaires (ASQ)® was administered to assess neurodevelopment. RESULTS: 62 preterm infants with a diagnosis of IUGR were included. The rescue therapy group compared with the single-dose group showed no differences in morbidity and mortality and less intubation rate at birth (p = 0.02), with no differences in respiratory support at 7 days of life. Preterm newborns ≥ 30 weeks exposed to rescue therapy showed higher morbidity and mortality (p = 0.03) and bronchopulmonary dysplasia (BPD) (p = 0.02), showing no differences in RDS. The rescue therapy group showed worse mean scores on the ASQ-3 scale, with no significant differences in cerebral palsy or sensory deficits. CONCLUSIONS: Rescue therapy reduces intubation at birth but does not reduce morbidity and mortality. However, at > 30 weeks, this benefit is not observed and the IUGR population exposed to rescue therapy presented more BPD and lower scores on the ASQ-3 scale at 2 years. Future studies should be aimed at the individualization of antenatal corticosteroid therapy.

Risk factors associated with Retinopathy of Prematurity development and progression.

Several studies propose that Retinopathy of Prematurity (ROP) is a multifactorial disorder implicating many prenatal and postnatal factors. The objective of our study was to determine the incidence and the risk factors that influenced ROP development and progression. We retrospectively compiled data of preterms with birth weight (BW) ≤ 1.500 g and/or gestational age (GA) < 32 weeks, or BW between 1.501 and 2.000 g and/or GA ≥ 32 weeks with oxygen supply > 72 h or unstable clinical course screened for ROP in Regional University Hospital of Málaga from 2015 to 2018. 202 infants (44.7%) developed ROP and 66 exhibited progression (32.7% of ROP infants). In the univariate analysis, many risk factors were associated with ROP. In the subsequent multivariate analysis, GA, oxygen therapy and weight at 28 days of life, mechanical ventilation duration, non-invasive ventilation, surfactant administration and late-onset sepsis were independently associated with the development. However, oxygen therapy duration, late-onset sepsis and weight at 28 days were associated with the progression. The ROP development and progression risk factors were different. Our results are important to facilitate screening, early diagnosis and ROP treatment while reducing unneeded examinations.

Antenatal Betamethasone Every 12 Hours in Imminent Preterm Labour.

BACKGROUND: Benefits of antenatal corticosteroids have been established for preterm infants who have received the full course. In imminent preterm labours there is no time to administer the second dose 24 h later. OBJECTIVE: To determine whether the administration of two doses of betamethasone in a 12 h interval is equivalent to the effects of a full maturation. METHODS: We performed a retrospective cohort study including preterm infants ≤34 weeks gestational age at birth and ≤1500 g, admitted to an NICU IIIC level in a tertiary hospital from 2015 to 2020. The population was divided into two cohorts: complete maturation (CM) (two doses of betamethasone 24 h apart), or advanced maturation (AM) (two doses of betamethasone 12 h apart). The primary outcomes were mortality or survival with severe morbidities. The presence of respiratory distress syndrome and other morbidities of prematurity were determined. These variables were analysed in the neonates under 28 weeks gestational age cohort. Neurodevelopment at 2 years was evaluated with the validated Ages and Stages Questionnaires®, Third Edition (ASQ®-3). Multiple regression analyses were performed and adjusted for confounding factors. RESULTS: A total of 275 preterm neonates were included. Serious outcomes did not show differences between cohorts, no increased incidence of morbidity was found in AM. A lower percentage of hypotension during the first week (p = 0.04), a tendency towards lower maximum FiO2 (p = 0.14) and to a shorter mechanical ventilation time (p = 0.14) were observed for the AM cohort. Similar results were found in the subgroup of neonates under 28 weeks gestational age. There were no differences in cerebral palsy or sensory deficits at 24 months of corrected age, although the AM cohort showed a trend towards better scores on the ASQ3 scale. CONCLUSIONS: Administration of betamethasone every 12 h showed similar results to the traditional pattern with respect to mortality and severe morbidities. No deleterious neurodevelopmental effects were found at 24 months of corrected age. Earlier administration of betamethasone at 12 h after the first dose would be an alternative in imminent preterm delivery. Further studies are needed to confirm these results.

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.

Benefits of a Single Dose of Betamethasone in Imminent Preterm Labour.

BACKGROUND: A complete course of prenatal corticosteroids reduces the possibility of morbimortality and neonatal respiratory distress syndrome (RDS). Occasionally, it is not possible to initiate or complete the maturation regimen, and the preterm neonate is born in a non-tertiary hospital. This study aimed to assess the effects of a single dose of betamethasone within 3 h before delivery on serious outcomes (mortality and serious sequelae) and RDS in preterm neonates born in tertiary vs. non-tertiary hospitals. MATERIALS AND METHODS: Preterm neonates who were <35 weeks and ≤1500 g, treated during a period of five years in a level IIIC NICU, were included in this retrospective cohort study. Participants were divided into groups as follows: NM, non-matured; PM, partial maturation (one dose of betamethasone up to 3 h antepartum). They were further divided based on their place of birth (NICU-IIIC vs. non-tertiary hospitals). The morbimortality rates and the severity of neonatal RDS were evaluated. RESULTS: A total of 76 preterm neonates were included. A decrease in serious outcomes was found in the PM group in comparison to the NM group (OR = 0.2; 95%CI (0.07-0.9)), as well as reduced need for mechanical ventilation (54% vs. 68%). The mean time between maternal admission and birth was similar in both cohorts. The mean time from the administration of betamethasone to delivery was 1 h in the PM cohort. With regard to births in NICU-IIIC, the PM group performed better in terms of serious outcomes (32% vs. 45%) and the duration of mechanical ventilation (117.75 vs. 132.18 h) compared to the NM group. In neonates born in non-tertiary hospitals with PM in comparison to the NM group, a trend towards a reduced serious outcome (28.5% vs. 62.2%) and a decreased need for mechanical ventilation (OR = 0.09; 95%CI (0.01-0.8)) and maximum FiO2 (p = 0.01) was observed. CONCLUSIONS: A single dose of betamethasone up to 3 h antepartum may reduce the rate of serious outcomes and the severity of neonatal RDS, especially in non-tertiary hospitals.

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.

[Variability in enteral feeding practices of preterm infants among hospitals in the SEN1500 Spanish neonatal network]. / Variabilidad en las prácticas sobre alimentación enteral del prematuro entre hospitales españoles de la red SEN-1500.

INTRODUCTION: Proper nutrition is one of the primary objectives in the management of preterm infants. However, lack of evidence on the best strategy to achieve this objective has led to a great variability in feeding practices. This variability may be related to the differences in the incidence of complications, such as necrotising enterocolitis (NEC). OBJECTIVE: The aim of this study is to assess the variability in clinical practice regarding enteral feeding in SEN-1500 Spanish network. METHOD: An observational study was conducted using a questionnaire sent out in 2013 requesting information about feeding very low birth weight (VLBW) neonates (bank milk, start time, trophic feeding, increases, fortifiers and probiotics). RESULTS: Responses were received from 60 of the 98 hospitals. The response rate was higher in centres with more than 50VLBW/year (30/31). Just over two-thirds (67%) have feeding protocols, and 52% refer to variability within their unit. A milk bank is available in 25% of the units. First feeding occurs fairly evenly throughout first 48hours, although it is delayed in lower gestational ages, even when there is no haemodynamic failure. In addition to hemodynamic instability there are other situations when the start is delayed (absence of breast milk, CIR, altered umbilical flow, asphyxia), while it is rarely delayed by absence of meconium or maintain an umbilical catheter.Half of those under 25 weeks begin directly with progressive increases instead of trophic feeding. Increases rarely reach 30ml/kg/day. Almost all use fortification and vitamins. There was a significant use of probiotics at the time of the survey. CONCLUSIONS: There is great variability in enteral nutrition policies in VLBW in Spain. Although some differences are justified by the lack of evidence, there are other interventions that have proven to be effective, such as evidence-based protocols or access to donor milk. Implementation in all the units could reduce the incidence of NEC and improve the nutritional status.

[Reduction in necrotising enterocolitis after implementing an evidence-based enteral nutrition protocol in very low birth weight newborns]. / Reducción de la enterocolitis necrosante tras la introducción de un protocolo de alimentación enteral basado en la evidencia en recién nacidos de muy bajo peso.

INTRODUCTION: An unexpected increase in the incidence of necrotising enterocolitis (NEC) cases was observed in our hospital. Just in case, our feeding policy could be responsible, it was decided to conduct a systematic review and develop a clinical guideline regarding enteral nutrition of very low birth weight infants (VLBW). OBJECTIVE: To assess the impact of the new feeding protocol in the incidence of NEC. METHOD: A "before" (2011) and "after" (May 2012 - April 2013) study was performed on the new feeding protocol. This included initiation of enteral feeding in the absence of haemodynamic problems, a trophic feeding period of 5-7 days, and subsequent increments of 20-30ml/kg/day, of breast milk/donor human milk from the beginning. Probiotics were not administered. PRIMARY OUTCOME: incidence of NEC II 2 Bell's stage. SECONDARY OUTCOMES: focal intestinal perforation, overall mortality and mortality due to NEC, nosocomial sepsis; weight at 28 days and 36 weeks; % of infants with weight

New clinical practice guideline on enteral feeding in very low birth weight infants; first part.

INTRODUCTION: The nutrition of very low birth weight (VLBW) infants is aimed at promoting a similar growth to that occurring in the uterus. However, in practice this is difficult to achieve and extrauterine growth restriction is frequent. The current tendency is to avoid this restriction by means of early parenteral and enteral nutrition. Nonetheless, uncertainty about many of the practices related with nutrition has resulted in a great variation in the way it is undertaken. In 2009 and 2011 in our hospital there was an unexpected increase in necrotizing enterocolitis. To check to see whether our nutrition policy was involved, we undertook a systematic review and drew up clinical practice guidelines (CPG) about enteral feeding in VLBW infants. New considerations about the duration of the fortification and the use of probiotics have led to an update of these CPG. METHODS: A total of 21 clinical questions were designed dealing with the type of milk, starting age, mode of administration, rate and volume of the increments, fortification, use of probiotics and protocol. After conducting a systematic search of the available evidence, the information was contrasted and summarized in order to draw up the recommendations. The quality of the evidence and the strength of the recommendations were determined from the SIGN scale. COMMENT: These CPG aim to help physicians in their decision making. The protocolized application of well-proven measurements reduces the variation in clinical practice and improves results.

Introducción: La nutrición de recién nacidos con peso muy bajo peso al nacer (MBPN) busca fomentar un crecimiento similar al que tiene lugar en el útero. Sin embargo, en la práctica, esto resulta difícil de conseguir y es frecuente encontrar una restricción del crecimiento extrauterino. La tendencia actual es evitar esta restricción por medio de una nutrición temprana parenteral y enteral. No obstante, la falta de certeza sobre muchas de las prácticas relacionadas con la nutrición ha dado lugar a una gran variación en los métodos. En 2009 y 2011 en nuestro hospital se dio un aumento inesperado de enterocolitis necrosante. Para comprobar la posible implicación de nuestra política de nutrición, pusimos en marcha una revisión sistemática y redactamos unas directrices para la práctica clínica (DPC) sobre la alimentación enteral en recién nacidos con MBPN. Las nuevas consideraciones sobre la duración de la fortificación y el uso de probióticos han dado lugar a una actualización de estas DPC. Métodos: Se definió un total de 21 preguntas clínicas sobre el tipo de leche, edad de inicio, modo de administración, porcentaje y volumen de los incrementos, fortificación, uso de probióticos y protocolo. Tras realizar una investigación sistemática de la evidencia disponible, la información fue contrastada y resumida para redactar las recomendaciones. La calidad de la evidencia disponible y la fuerza de las recomendaciones quedaron determinadas conforme a la escala SIGN. Comentario: Estas DPC pretenden ayudar a los médicos en su toma de decisiones. La aplicación protocolizada de mediciones bien probadas reduce la variación en la práctica clínica y mejora los resultados.

New clinical practice guideline on enteral feeding in very low birth weight infants; second part.

INTRODUCTION: The nutrition of very low birth weight (VLBW) infants is aimed at promoting a similar growth to that occurring in the uterus. However, in practice this is difficult to achieve and extrauterine growth restriction is frequent. The current tendency is to avoid this restriction by means of early parenteral and enteral nutrition. Nonetheless, uncertainty about many of the practices related with nutrition has resulted in a great variation in the way it is undertaken. In 2009 and 2011 in our hospital there was an unexpected increase in necrotizing enterocolitis. To check to see wether our nutrition policy was involved, we underlook a systematic review and drewup clinical practice guidelines (CPG) about enteral feeding in VLBW infants. New considerations about the duration of the fortification and the use of probiotics have led to an update of these CPG. METHODS: A total of 21 clinical questions were designed dealing with the type of milk, starting age, mode of administration, rate and volume of the increments, fortification, use of probiotics and protocol. Afete conducting a systematic search of the available evidence, the information was contrasted and summarized in order to draw up the recommendations. The quality of the evidence and the strength of the recommendations were determined from the SIGN scale. COMMENT: These CPG aim to help physicians in their decision making. The protocolized application of well-proven measurements reduces the variation in clinical practice and improves results.

Introducción: La nutrición de recién nacidos con peso muy bajo peso al nacer (MBPN) busca fomentar un crecimiento similar al que tiene lugar en el útero. Sin embargo, en la práctica, esto resulta difícil de conseguir y es frecuente encontrar una restricción del crecimiento extrauterino. La tendencia actual es evitar esta restricción por medio de una nutrición temprana parenteral y enteral. No obstante, la falta de certeza sobre muchas de las prácticas relacionadas con la nutrición ha dado lugar a una gran variación en los métodos. En 2009 y 2011 en nuestro hospital se dio un aumento inesperado de enterocolitis necrosante. Para comprobar la posible implicación de nuestra política de nutrición, pusimos en marcha una revisión sistemática y redactamos unas directrices para la práctica clínica (DPC) sobre la alimentación enteral en recién nacidos con MBPN. Las nuevas consideraciones sobre la duración de la fortificación y el uso de probióticos han dado lugar a una actualización de estas DPC. Métodos: Se definió un total de 21 preguntas clínicas sobre el tipo de leche, edad de inicio, modo de administración, porcentaje y volumen de los incrementos, fortificación, uso de probióticos y protocolo. Tras realizar una investigación sistemática de la evidencia disponible, la información fue contrastada y resumida para redactar las recomendaciones. La calidad de la evidencia disponible y la fuerza de las recomendaciones quedaron determinadas conforme a la escala SIGN. Comentario: Estas DPC pretenden ayudar a los médicos en su toma de decisiones. La aplicación protocolizada de mediciones bien probadas reduce la variación en la práctica clínica y mejora los resultados.

Combined Haemophilus Influenzae type B-Neisseria meningitidis serogroup C vaccine is immunogenic and well tolerated in preterm infants when coadministered with other routinely recommended vaccines.

BACKGROUND: Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. METHODS: In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks' gestation; n = 107, 31-36 weeks' gestation) and 150 full-term infants (>36 weeks' gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4-6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. RESULTS: There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. CONCLUSIONS: Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.