Changes in Patent Ductus Arteriosus Treatment Strategy and Respiratory Outcomes in Premature Infants.

OBJECTIVE: To evaluate whether change in patent ductus arteriosus (PDA) management strategies over time had an impact on respiratory outcomes in premature infants. STUDY DESIGN: Prospectively collected data were included from all preterm infants born at 23-30 weeks gestational age with PDA admitted to the Children's Hospital of the University of Miami/Jackson Memorial Medical Center from January 1, 2005 to December 31, 2007 (epoch 1) and January 1, 2011 to December 31, 2015 (epoch 2). The 2 epochs were compared for approach with PDA diagnosis and subsequent management strategies and respiratory outcomes. RESULTS: Significantly fewer infants were treated for PDA in epoch 2 (54%) compared with epoch 1 (90%). Multivariable logistic regression analysis demonstrated that infants in epoch 2, with later PDA diagnosis and less frequent PDA treatment, had greater odds of bronchopulmonary dysplasia (BPD), composite of BPD or death, and more treatment with postnatal steroids than in epoch 1. CONCLUSIONS: The change in approach to diagnosis and management of PDA, from a more proactive and aggressive approach during the earlier epoch 1 to a more expectant approach during the subsequent epoch 2, was associated with worse respiratory outcomes, including increase in BPD and in BPD or death.

Maternal preeclampsia and respiratory outcomes in extremely premature infants.

BACKGROUND: Preeclampsia (PE) is a pregnancy complication characterized by an anti-angiogenic environment. This can affect fetal pulmonary vascular and alveolar development but data of the impact of PE on respiratory outcome in extremely premature infants are inconclusive. The objective of this study was to determine if PE is associated with an increased risk for severe respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in extremely premature infants. METHODS: Prospectively collected single center data from a cohort of infants born at 23-28 w gestational age between January 2005 and December 2015 were analyzed. Logistic regression analysis and generalized estimating equations were used to model the association between PE and severe RDS (≥30% supplemental oxygen on d1), BPD and severe BPD [supplemental oxygen and ≥30% oxygen at 36 w postmenstrual age (PMA), respectively]. RESULTS: The cohort included 1218 infants of whom 23% were exposed to PE. PE was associated with increased risk for severe RDS as well as severe BPD among infants alive at 36w PMA. CONCLUSION: Exposure to preeclampsia is independently associated with an increased risk for severe RDS and adverse respiratory outcome in extreme premature infants. The mechanisms behind these associations need to be investigated.

Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial.

OBJECTIVE: To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. STUDY DESIGN: Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. RESULTS: Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). CONCLUSIONS: Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01751724.

Efficacy of late postnatal dexamethasone on weaning from invasive mechanical ventilation in extreme premature infants.

OBJECTIVE: To evaluate the short-term respiratory effects of PND in a cohort of ventilator-dependent premature infants. STUDY DESIGN: Clinical data from 106 infants 23-28 weeks gestation who received PND for weaning from MV during 2011-2017 were evaluated. PND was started at a dose of 0.1 mg/kg/d tapered over 5-7 d. Treatment success was defined as extubated and free from MV on d14 after start of treatment. RESULT: Treatment was successful in 83 (78%) infants. Demographics and age of treatment did not differ between groups. In the failure group, a higher proportion were on HFOV and FiO2 ≥ 0.50 before treatment, compared to the successful group. CONCLUSION: In most infants, PND resulted in successful weaning from MV. Reduced need for oxygen in infants not extubated may be beneficial, but it is unknown if this offsets the risks. The long-term effects PND in ventilator dependent infants need to be evaluated.

The Impact of Late Onset Arterial Hypotension on Respiratory Outcome in Extremely Premature Infants.

BACKGROUND: In extremely premature infants, arterial hypotension in the first days after birth has been associated with an increased risk for bronchopulmonary dysplasia (BPD). Some infants present with hypotension at a later postnatal age, but the relationship between late onset hypotension (LOH) and BPD has not been evaluated. OBJECTIVE: To evaluate the association between LOH and BPD and to identify pre- and postnatal factors associated with LOH. METHODS: Prospectively collected data from a cohort of 23-28 weeks gestational age (GA) infants born during years 2005-2015 and alive at day 28 were analyzed. LOH was defined as the receipt of vasopressor treatment during days 8-28. BPD was defined as need for oxygen at 36 weeks postmenstrual age. Late mortality was defined as death after day 28. RESULTS: Of 1,058 infants in the cohort, 90 (9%) had LOH during days 8-28. Infants with LOH had a higher incidence of BPD than normotensive infants (55 vs. 21%, p < 0.001). Multivariate logistic regression analysis (LRA) showed that LOH was associated with an increased risk for BPD (OR 1.87, 95% CI 1.10-3.17). LOH was also associated with an increased risk for late mortality. LRA showed the risk for LOH increased with lower GA, sepsis and patent ductus arteriosus during days 8-28. CONCLUSIONS: In this cohort of extremely premature infants, LOH was associated with an increased the risk for BPD. This association could be secondary to underlying factors that predispose to LOH and BPD or to the deleterious effects of LOH or its treatments on the lung. Further investigation is needed to assess causality.

The association between early tracheal colonization and bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the relationship between early tracheal colonization and bronchopulmonary dysplasia (BPD). STUDY DESIGN: This is a retrospective cohort study which included 308 inborn neonates admitted to the newborn intensive care unit at the University of Miami Jackson Memorial Medical Center between January 1997 and December 2000 with birthweight 500 to 1000 g, who required mechanical ventilation on the first day of life. Chorioamnionitis was diagnosed by maternal symptoms and histopathopathology. Tracheal cultures were obtained immediately after tracheal intubation. BPD was diagnosed in neonates who had supplemental oxygen requirement for more than 28 days. Pearson's chi(2) and Logistic Regression Analysis were used to evaluate the relationship between chorioamnionitis, positive initial tracheal cultures and BPD, after adjusting for confounding variables. RESULTS: In patients with chorioamnionitis, the incidence of early positive tracheal cultures was 41% compared to 16% in those without chorioamnionitis, (p < 0.00001). In patients with birthweight 700 to 1000 g, a positive early tracheal culture increased the risk of BPD (OR = 2.42, CI 1.05 to 5.62, p < 0.05). CONCLUSION: Preterm infants exposed to chorioamnionitis have an increased incidence of early tracheal colonization. This early tracheal colonization may predispose them to develop BPD.

Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants.

BACKGROUND: Prolonged mechanical ventilation is associated with lung injury in preterm infants. In these infants, weaning from synchronized intermittent mandatory ventilation may be delayed by their inability to cope with increased respiratory loads. The addition of pressure support to synchronized intermittent mandatory ventilation can offset these loads and may facilitate weaning. OBJECTIVE: The purpose of this work was to compare synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in weaning from mechanical ventilation and the duration of supplemental oxygen dependency in preterm infants with respiratory failure. METHODS: Preterm infants weighing 500 to 1000 g at birth who required mechanical ventilation during the first postnatal week were randomly assigned to synchronized intermittent mandatory ventilation or synchronized intermittent mandatory ventilation plus pressure support. In both groups, weaning followed a set protocol during the first 28 days. Outcomes were assessed during the first 28 days and until discharge or death. RESULTS: There were 107 infants enrolled (53 synchronized intermittent mandatory ventilation plus pressure support and 54 synchronized intermittent mandatory ventilation). Demographic and perinatal data, mortality, and morbidity did not differ between groups. During the first 28 days, infants in the synchronized intermittent mandatory ventilation plus pressure support group reached minimal ventilator settings and were extubated earlier than infants in the synchronized intermittent mandatory ventilation group. Total duration of mechanical ventilation, duration of oxygen dependency, and oxygen need at 36 weeks' postmenstrual age alone or combined with death did not differ between groups. However, infants in synchronized intermittent mandatory ventilation plus pressure support within the 700- to 1000-g birth weight strata had a shorter oxygen dependency. CONCLUSIONS: The results of this study suggest that the addition of pressure support as a supplement to synchronized intermittent mandatory ventilation during the first 28 days may play a role in reducing the duration of mechanical ventilation in extremely low birth-weight infants, and it may lead to a reduced oxygen dependency in the 700- to 1000-g birth weight strata.