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.

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.

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.

Neural breathing patterns in preterm newborns supported with non-invasive neurally adjusted ventilatory assist.

OBJECTIVE: To characterize the neural breathing pattern in preterm infants supported with non-invasive neurally adjusted ventilatory assist (NIV-NAVA). STUDY DESIGN: Single-center prospective observational study. The electrical activity of the diaphragm (EAdi) was periodically recorded in 30-second series with the Edi catheter and the Servo-n software (Maquet, Solna, Sweden) in preterm infants supported with NIV-NAVA. The EAdiPeak, EAdiMin, EAdiTonic, EAdiPhasic, neural inspiratory, and expiratory times (nTi and nTe) and the neural respiratory rate (nRR) were calculated. EAdi curves were generated by Excel for visual examination and classified according to the predominant pattern. RESULTS: 291 observations were analyzed in 19 patients with a mean GA of 27.3 weeks (range 24-36 weeks), birth weight 1028 g (510-2945 g), and a median (IQR) postnatal age of 18 days (4-27 days). The distribution of respiratory patterns was phasic without tonic activity 61.9%, phasic with basal tonic activity 18.6, tonic burst 3.8%, central apnea 7.9%, and mixed pattern 7.9%. In addition, 12% of the records showed apneas of >10 seconds, and 50.2% one or more "sighs", defined as breaths with an EAdiPeak and/or nTi greater than twice the average EAdiPeak and/or nTi of the recording. Neural times were measurable in 252 observations. The nTi was, median (IQR): 279 ms (253-285 ms), the nTe 764 ms (642-925 ms), and the nRR 63 bpm (51-70), with a great intra and inter-subjects variability. CONCLUSIONS: The neural breathing patterns in preterm infants supported with NIV-NAVA are quite variable and are characterized by the presence of significant tonic activity. Central apneas and sighs are common in this group of patients. The nTi seems to be shorter than the mechanical Ti commonly used in assisted ventilation.

Perinatal risk factors for pneumothorax and morbidity and mortality in very low birth weight infants.

AIM: To determine the perinatal risk factors for pneumothorax in Very-Low-Birth-Weight (VLBW) infants and the associated morbidity and mortality in this population. METHODS: Retrospective analysis of data collected prospectively from a cohort of VLBW neonates assisted in our Unit (2006-2013). We included all consecutive in-born patients with ≤ 1500 g, without severe congenital anomalies. Perinatal history, demographics, interventions and clinical outcomes were collected. Associations were evaluated by logistic regression analysis. RESULTS: During the study period, 803 VLBW infants were assisted in our Unit, of whom 763 were inborn. Ten patients (1.2%) died in delivery room, and 18 (2.2%) with major congenital anomalies were excluded. Finally, 735 (91.5%) neonates were included in the study. Seventeen (2.3%) developed pneumothorax during the first week of life [median (IQR): 2 (1-2) days]. After correcting for GA and other confounders, prolonged rupture of membranes [aOR =1.002 (95% CI 1.000-1.003); p = 0.040] and surfactant administration [aOR = 6.281 (95% CI 1.688-23.373); p = 0.006] were the independent risk factors associated with pneumothorax. Patients with pneumothorax had lower probabilities of survival without major brain damage (MBD): aOR = 0.283 (95% CI = 0.095-0.879); p = 0.029. CONCLUSIONS: Pneumothorax in VLBW seems to be related to perinatal inflammation and surfactant administration, and it is significantly associated with a reduction in the probabilities of survival without MBD.

Outcomes of very-low-birth-weight infants exposed to maternal clinical chorioamnionitis: a multicentre study.

BACKGROUND: Chorioamnionitis is a recognized risk factor of preterm delivery; however, controversy still persists concerning the relationship between maternal inflammation and neonatal morbidity and mortality. OBJECTIVE: To determine the incidence of clinical chorioamnionitis and its relationship to morbidity and mortality among very-low-birth-weight (VLBW) infants. METHODS: This was a retrospective analysis of prospectively collected data of VLBW neonates ≤ 32 weeks' gestational age (GA) admitted to collaborating units in the Spanish SEN1500 Network between January 2008 and December 2011. Clinical chorioamnionitis was defined by obstetricians based on clinical findings, and neonatal outcomes were compared between exposed and non-exposed infants by multivariate logistic regression analysis. RESULTS: During the study period, 11,464 VLBW newborns were admitted to our units and 10,026 were ≤ 32 weeks' GA. Among them, 8,330 (83.1%) had complete data and were included. Of these, 1,480 (17.8%) were exposed to maternal clinical chorioamnionitis. The incidence was higher at lower GA and, after adjusting for confounding factors, exposed infants had higher risks of early-onset neonatal sepsis (EONS) (10.0 vs. 2.8%; aOR 3.102; 95% CI 2.306-4.173; p < 0.001) and necrotizing enterocolitis (NEC) (11.2 vs. 7.7%; aOR 1.300; 95% CI 1.021-1.655; p < 0.033), but lower risks of patent ductus arteriosus (PDA) (43.2 vs. 34.9%; aOR 0.831; 95% CI 0.711-0.971; p < 0.02) and late-onset bacterial sepsis (LONS) (36.6 vs. 32.5%; aOR 0.849; 95% CI 0.729-0.989; p < 0.035). There were no differences in mortality between the groups. CONCLUSIONS: The incidence of maternal clinical chorioamnionitis is inversely related to GA at delivery, and in VLBW infants ≤ 32 weeks' GA it is associated with higher risks of EONS and NEC, but lower risks of PDA and LONS. We did not found differences in survival.

Morbidity and mortality among very-low-birth-weight infants born to mothers with clinical chorioamnionitis.

BACKGROUND: Controversy exists about the relationship between maternal inflammation and the development of different morbidities and mortality in the newborn. We aimed to establish the incidence of clinical chorioamnionitis in our Neonatal Intensive Care Unit and its relation to morbidity and mortality among very-low-birth-weight infants. METHODS: This was an observational study of a cohort of very-low-birth-weight neonates admitted to our Neonatal Intensive Care Unit, between January 2008 and December 2012. Demographic characteristics and outcomes were analyzed and a comparison between exposed and non-exposed infants was carried out. RESULTS: During the study period, 451 very-low-birth-weight infants were admitted to our Neonatal Intensive Care Unit, and 31 (6.87%) were exposed to maternal clinical chorioamnionitis. The incidence was higher at lower gestational ages: 13.2% (23-26 weeks), 8.1% (27-30 weeks), and 2.6% (31-34 weeks) (p = 0.022). After correcting by gestational age and birth weight, early-onset neonatal sepsis (adjusted relative risk = 6.13; 95% confidence interval = 1.67-22.58; p = 0.006) and periventricular leukomalacia (adjusted relative risk = 24.62; 95% confidence interval = 1.87-324.28; p = 0.015) were significantly associated with maternal clinical chorioamnionitis. There were no differences in mortality or in survival without major morbidity. CONCLUSION: Clinical chorioamnionitis confers an increased risk of early-onset neonatal sepsis and periventricular leukomalacia to exposed very-low-birth-weight infants.