Project description:BACKGROUND:Many premature infants with respiratory failure are deficient in surfactant, but the relationship to occurrence of bronchopulmonary dysplasia (BPD) is uncertain. METHODS:Tracheal aspirates were collected from 209 treated and control infants enrolled at 7-14 days in the Trial of Late Surfactant. The content of phospholipid, surfactant protein B, and total protein were determined in large aggregate (active) surfactant. RESULTS:At 24?h, surfactant treatment transiently increased surfactant protein B content (70%, p?<?0.01), but did not affect recovered airway surfactant or total protein/phospholipid. The level of recovered surfactant during dosing was directly associated with content of surfactant protein B (r?=?0.50, p?<?0.00001) and inversely related to total protein (r?=?0.39, p?<?0.0001). For all infants, occurrence of BPD was associated with lower levels of recovered large aggregate surfactant, higher protein content, and lower SP-B levels. Tracheal aspirates with lower amounts of recovered surfactant had an increased proportion of small vesicle (inactive) surfactant. CONCLUSIONS:We conclude that many intubated premature infants are deficient in active surfactant, in part due to increased intra-alveolar metabolism, low SP-B content, and protein inhibition, and that the severity of this deficit is predictive of BPD. Late surfactant treatment at the frequency used did not provide a sustained increase in airway surfactant.
Project description:The inverse relationship between gestational age at birth and postviral respiratory morbidity suggests that infants born preterm (PT) may miss a critical developmental window of T cell maturation. Despite a continued increase in younger PT survivors with respiratory complications, we have limited understanding of normal human fetal T cell maturation, how ex utero development in premature infants may interrupt normal T cell development, and whether T cell development has an effect on infant outcomes. In our longitudinal cohort of 157 infants born between 23 and 42 weeks of gestation, we identified differences in T cells present at birth that were dependent on gestational age and differences in postnatal T cell development that predicted respiratory outcome at 1 year of age. We show that naive CD4+ T cells shift from a CD31-TNF-α+ bias in mid gestation to a CD31+IL-8+ predominance by term gestation. Former PT infants discharged with CD31+IL8+CD4+ T cells below a range similar to that of full-term born infants were at an over 3.5-fold higher risk for respiratory complications after NICU discharge. This study is the first to our knowledge to identify a pattern of normal functional T cell development in later gestation and to associate abnormal T cell development with health outcomes in infants.
Project description:Although the risk of neonatal mortality is generally low for late preterm and early term infants, they are still significantly predisposed to severe neonatal morbidity (SNM) despite being born at relatively advanced gestations. In this study, we investigated maternal and intrapartum risk factors for early SNM in late preterm and early term infants. This was a retrospective cohort study of non-anomalous, singleton infants (34+0-38+6 gestational weeks) born at the Mater Mother's Hospital in Brisbane, Australia from January 2015 to May 2020. Early SNM was defined as a composite of any of the following severe neonatal outcome indicators: admission to neonatal intensive care unit (NICU) in conjunction with an Apgar score <4 at 5 min, severe respiratory distress, severe neonatal acidosis (cord pH < 7.0 or base excess <-12 mmol/L). Multivariable binomial logistic regression analyses using generalized estimating equations (GEE) were used to identify risk factors. Of the total infants born at 34+0-38+6 gestational weeks, 5.7% had at least one component of the composite outcome. For late preterm infants, pre-existing diabetes mellitus, instrumental birth and emergency caesarean birth for non-reassuring fetal status were associated with increased odds for early SNM, whilst for early term infants, pre-existing and gestational diabetes mellitus, antepartum hemorrhage, instrumental, emergency caesarean and elective caesarean birth were significant risk factors. In conclusion, we identified several risk factors contributing to early SNM in late preterm and early term cohort. Our results suggest that predicted probability of early SNM decreased as gestation increased.
Project description:In this study, we sought to ascertain a relationship between gestational age at birth and infectious morbidity of the offspring via population-based cohort analysis comparing the long-term incidence of infectious morbidity in infants born preterm and stratified by extremity of prematurity (extreme preterm birth: 24 + 0-27 + 6, very preterm birth: 28 + 0-31 + 6, moderate to late preterm birth: 32 + 0-36 + 6 weeks of gestation, and term deliveries). Infectious morbidity included hospitalizations involving a predefined set of International Classification of Diseases 9 (ICD9) codes, as recorded in hospital records. A Kaplan-Meier survival curve compared cumulative incidence of infectious-related morbidity. A Cox proportional hazards model controlled for confounders and time to event. The study included 220,594 patients: 125 (0.1%) extreme preterm births, 784 (0.4%) very preterm births, 13,323 (6.0%) moderate to late preterm births, and 206,362 term deliveries. Offspring born preterm had significantly more infection-related hospitalizations (18.4%, 19.8%, 14.9%, and 11.0% for the aforementioned stratification, respectively, p < 0.001). Multivariate analysis found being born very or late to moderate preterm was independently associated with long-term infectious morbidity (adjusted hazard ratio (aHR) 1.5, 95% confidence interval (CI) 1.27-1.77 and aHR 1.23, 95% CI 1.17-1.3, respectively, p < 0.001). A comparable risk of long-term infectious morbidity was found in the two groups of premature births prior to 32 weeks gestation. In our population, a cutoff from 32 weeks and below demarks a significant increase in the risk of long-term infectious morbidity of the offspring.
Project description:This study evaluated whether early pulmonary hypertension (PH) in extremely preterm infants (EPIs) at 22-27 weeks of gestation detected clinically with echocardiography at 4-7 postnatal days (PND) is a risk factor for death before 36 weeks post-menstrual age (PMA) or late PH in moderate or severe (m/s) bronchopulmonary dysplasia (BPD) (BPD-PH). We analyzed risk factors for death before 36 weeks PMA or BPD-PH. Among 247 EPIs enrolled, 74 (30.0%) had early PH. Twenty-one (28.4%) infants with early PH and 18 (10.4%) without early PH died before 36 weeks PMA; 14 (18.9%) infants with early PH and 9 (5.2%) without early PH had BPD-PH at 36-38 weeks PMA. Multivariate analysis revealed that early PH (adjusted odds ratio, 6.55; 95% confidence interval, 3.10-13.82, P < 0.05), clinical chorioamnionitis (2.50; 1.18-5.31), intraventricular hemorrhage (grade 3-4) (3.43; 1.26-9.37), and late sepsis (6.76; 3.20-14.28) independently increased the risk of development of death before 36 weeks PMA or BPD-PH. Subgroup analysis among m/s BPD patients revealed that early PH (4.50; 1.61-12.58) and prolonged invasive ventilator care (> 28 days) (4.91; 1.02-23.68) increased the risk for late PH independently. In conclusion, EPIs with early PH at 4-7 PND should be monitored for BPD-associated late PH development.
Project description:BACKGROUND:Inappropriate nutritional intake in premature infants may be responsible for postnatal growth restriction (PGR) and adverse long-term outcomes. OBJECTIVE:We evaluated the impact of an updated nutrition protocol on very premature infants' longitudinal growth and morbidity, and secondly the compliance to this new protocol. DESIGN:All infants born between 26-32 weeks gestation (GA) were studied retrospectively during two 6-month periods before (group 1) and after (group 2) the introduction of an optimized nutrition protocol, in a longitudinal comparative analysis. RESULTS:158 infants were included; 72 before and 86 after the introduction of the protocol (Group 1: (mean±SD) birthweight (BW) 1154±276 g, GA 29.0±1.4 weeks; Group 2: BW 1215±332 g, GA 28.9±1.7 weeks). We observed growth improvement in Group 2 more pronounced in males (weight z-score) at D42 (-1.688±0.758 vs. -1.370±0.762, p = 0.045), D49 (-1.696±0.776 vs. -1.370±0.718, p = 0.051), D56 (-1.748±0.855 vs. -1.392±0.737, p = 0.072), D63 (-1.885±0.832 vs. -1.336±0.779 p = 0.016), and D70 (-2.001±0.747 vs. -1.228±0.765 p = 0.004). There was no difference in females or in morbidities between the groups. We observed low compliance to the protocol in both groups: similar energy intake but higher lipid intake in Group 1 and higher protein intake in Group 2. CONCLUSION:The quality of nutritional care with a strictly-defined protocol may significantly improve weight gain for very preterm infants. As compliance remained low, an educational reinforcement is needed to prevent PGR. CLINICAL TRIAL REGISTRATION:This retrospective study was registered by ClinicalTrials.gov under number NCT03217045, and by the CNIL (Commission Nationale de l'Informatique et des Libertés) under study number R2015-1 for the Maternity of the CHRU of Nancy.
Project description:ObjectiveTo investigate factors associated with development of early and late pulmonary hypertension (E/LPH) in preterm infants with bronchopulmonary dysplasia (BPD).Study designA retrospective case-control observational study of preterm infants with BPD admitted to a level IV referral neonatal intensive care unit over 5 years. We compared pre- and postnatal characteristics between infants with or without BPD-associated EPH and LPH.ResultsFifty-nine out of 220 infants (26.8%) had LPH, while 85 out of 193 neonates (44%) had EPH. On multiple logistic regression, novel factors associated with development of BPD-LPH included presence of maternal diabetes, EPH, tracheostomy, tracheitis, intraventricular hemorrhage (IVH, grade ?3) and systemic steroid use. For EPH, these were maternal diabetes, IVH grade ?3, high frequency ventilator use, and absence of maternal antibiotics use.ConclusionWe identified novel factors and confirmed previously established factors with development of LPH and EPH, which can help develop a screening strategy in BPD patients.
Project description:BackgroundProlonged early antibiotics in extremely premature infants may have negative effects. We aimed to assess prevalence and outcomes of provision of prolonged early antibiotics to extremely premature infants in the absence of culture-confirmed infection or NEC.MethodsCohort study of infants from 13 centers born without a major birth defect from 2008-2014 who were 401-1000 grams birth weight, 22-28 weeks gestation, and survived ≥5 days without culture-confirmed infection, NEC, or spontaneous intestinal perforation. We determined the proportion of infants who received prolonged early antibiotics, defined as ≥5 days of antibiotic therapy started at ≤72 h of age, by center and over time. Associations between prolonged early antibiotics and adverse outcomes were assessed using multivariable logistic regression.ResultsA total of 5730 infants were included. The proportion of infants receiving prolonged early antibiotics varied from 30-69% among centers and declined from 49% in 2008 to 35% in 2014. Prolonged early antibiotics was not significantly associated with death (adjusted odds ratio 1.17 [95% CI: 0.99-1.40], p = 0.07) and was not associated with NEC.ConclusionsThe proportion of extremely premature infants receiving prolonged early antibiotics decreased, but significant center variation persists. Prolonged early antibiotics were not significantly associated with increased odds of death or NEC.
Project description:BackgroundThe objective was to develop a risk scoring tool which predicts respiratory syncytial virus hospitalisation (RSVH) in moderate-late preterm infants (32-35 weeks' gestational age) in the Northern Hemisphere.MethodsRisk factors for RSVH were pooled from six observational studies of infants born 32 weeks and 0 days to 35 weeks and 6 days without comorbidity from 2000 to 2014. Of 13?475 infants, 484 had RSVH in the first year of life. Logistic regression was used to identify the most predictive risk factors, based on area under the receiver operating characteristic curve (AUROC). The model was validated internally by 100-fold bootstrapping and externally with data from a seventh observational study. The model coefficients were converted into rounded multipliers, stratified into risk groups, and number needed to treat (NNT) calculated.ResultsThe risk factors identified in the model included (i) proximity of birth to the RSV season; (ii) second-hand smoke exposure; and (iii) siblings and/or daycare. The AUROC was 0.773 (sensitivity: 68.9%; specificity: 73.0%). The mean AUROC from internal bootstrapping was 0.773. For external validation with data from Ireland, the AUROC was 0.707 using Irish coefficients and 0.681 using source model coefficients. Cut-off scores for RSVH were ?19 for low- (1.0%), 20-45 for moderate- (3.3%), and 50-56 (9.5%) for high-risk infants. The high-risk group captured 62.0% of RSVHs within 23.6% of the total population (NNT 15.3).ConclusionsThis risk scoring tool has good predictive accuracy and can improve targeting for RSVH prevention in moderate-late preterm infants.