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Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis

ABSTRACT

DOI: 10.1136/archdischild-2015-310299
Context In spontaneously breathing preterm infants with respiratory distress syndrome (RDS) receiving nasal continuous positive airway pressure, a method of less invasive surfactant administration (LISA) using a thin catheter has been described as an alternative to endotracheal intubation for surfactant delivery to reduce lung injury.
Objective A systematic review of randomised controlled trials (RCTs) comparing LISA with the standard method of surfactant delivery for clinical outcomes. Methods Medline, CENTRAL and Embase databases were searched (until 29 October 2015). Additional citations were identified from trial registries, conference proceedings and the bibliographies of selected articles. The included studies were RCTs enrolling preterm infants with RDS and compared LISA technique with intubation for surfactant delivery for any of the prespecified clinical outcomes.
Results Six RCTs were identified, enrolling a total of 895 infants. The use of LISA technique reduced the composite outcome of death or bronchopulmonary dysplasia (BPD) at 36 weeks (risk ratio (RR)=0.75 (95% CI 0.59 to 0.94), p=0.01), BPD36 among survivors (RR=0.72 (0.53 to 0.97), p=0.03), need for mechanical ventilation within 72 hours of birth (RR=0.71 (0.53 to 0.96), p=0.02) or need for mechanical ventilation anytime during the neonatal intensive care unit stay (RR=0.66 (0.47 to 0.93), p=0.02). There were no differences noted for the outcome of death and other neonatal morbidities. Procedure failure rate on the first attempt and the need for additional doses of surfactant were not different between the intervention groups.
Conclusions LISA technique for surfactant delivery results in a lesser need for mechanical ventilation in infants with RDS, reduction in the composite outcome of death or BPD at 36 weeks, and BPD36 among survivors.

 

Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a network meta-analysis

ABSTRACT

DOI: 10.1136/archdischild-2017-313759
Objective To determine the comparative efficacy and safety of corticosteroids in the prevention of bronchopulmonary dysplasia (BPD) in preterm infants.
Study design We systematically searched PubMed, EMBASE and the Cochrane Library. Two reviewers independently selected randomised controlled trials (RCTs) of postnatal corticosteroids in preterm infants. A Bayesian network meta-analysis and subgroup analyses were performed.
Results We included 47 RCTs with 6747 participants. The use of dexamethasone at either high dose or low dose decreased the risk of BPD (OR 0.29, 95% credible interval (CrI) 0.14 to 0.52; OR 0.58, 95% CrI 0.39 to 0.76, respectively). High-dose dexamethasone was more effective than hydrocortisone, beclomethasone and low-dose dexamethasone. Early and long-term dexamethasone at either high dose or low dose decreased the risk of BPD (OR 0.11, 95% CrI 0.02 to 0.4; OR 0.37, 95% CrI 0.16 to 0.67, respectively). There were no statistically significant differences in the risk of cerebral palsy (CP) between different corticosteroids. However, high-dose and long-term dexamethasone ranked lower than placebo and other regimens in terms of CP. Subgroup analyses indicated budesonide was associated with a decreased risk of BPD in extremely preterm and extremely low birthweight infants (OR 0.60, 95% CrI 0.36 to 0.93).
Conclusions Dexamethasone can reduce the risk of BPD in preterm infants. Of the different dexamethasone regimens, aggressive initiation seems beneficial, while a combination of high-dose and long-term use should be avoided because of the possible adverse neurodevelopmental outcome. Dexamethasone and inhaled corticosteroids need to be further evaluated in large-scale RCTs with long-term follow-ups.

Efficacy and safety of pulmonary application of corticosteroids in preterm infants with respiratory distress syndrome: a systematic review and metaanalysis

ABSTRACT

DOI: 10.1136/archdischild-2017-314046
Background Systemic corticosteroids as the frontline treatment of respiratory distress syndrome (RDS) in preterm infants are associated with adverse effects on growth and neurodevelopmental outcome, but the pulmonary administration of steroids may help prevent the development of bronchopulmonary dysplasia (BPD) without these side effects.

Objectives To evaluate the efficacy and safety of pulmonary application of corticosteroids in preterm infants with RDS.

Conclusions Pulmonary administration of corticosteroids reduces the incidence of BPD or death, pneumonia, PDA without causing any major side effects in preterm infants with RDS.

 

Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence

ABSTRACT

DOI: 10.1136/archdischild-2017-314264
Bronchopulmonary dysplasia (BPD) is one of the most frequent complications in extremely low gestational age neonates, but has remained largely unchanged in rate. We reviewed data on BPD prevention focusing on recent meta-analyses. Interventions with proven effectiveness in reducing BPD include the primary use of non-invasive respiratory support, the application of surfactant without endotracheal ventilation and the use of volume-targeted ventilation in infants requiring endotracheal intubation. Following extubation, synchronised nasal ventilation is more effective than continuous positive airway pressure in reducing BPD. Pharmacologically, commencing caffeine citrate on postnatal day 1 or 2 seems more effective than a later start. Applying intramuscular vitamin A for the first 4 weeks reduces BPD, but is expensive and painful and thus not widely used. Low-dose hydrocortisone for the first 10 days prevents BPD, but was associated with almost twice as many cases of late-onset sepsis in infants born at 24–25 weeks’ gestation. Inhaled corticosteroids, despite reducing BPD, were associated with a higher mortality rate. Administering dexamethasone to infants still requiring mechanical ventilation around postnatal weeks 2–3 may represent the best trade-off between restricting steroids to infants at risk of BPD while still affording high efficacy. Finally, identifying infants colonised with ureaplasma and treating those requiring intubation and mechanical ventilation with azithromycin is another promising approach to BPD prevention. Further interventions yet only backed by cohort studies include exclusive breastmilk feeding and a better prevention of nosocomial infections.

 

Fetal neuroprotection by Magnesium Sulfate: From Translational Research to Clinical Application

ABSTRACT

DOI: 10.3389/fneur.2018.00247
Despite improvements in perinatal care, preterm birth still occurs regularly and the associated brain injury and adverse neurological outcomes remain a persistent challenge. Antenatal magnesium sulfate administration is an intervention with demonstrated neuroprotective effects for preterm births before 32 weeks of gestation (WG). Owing to its biological properties, including its action as an N-methyl-d-aspartate receptor blocker and its anti-inflammatory effects, magnesium is a good candidate for neuroprotection. In hypoxia models, including hypoxia-ischemia, inflammation, and excitotoxicity in various species (mice, rats, pigs), magnesium sulfate preconditioning decreased the induced lesions’ sizes and inflammatory cytokine levels, prevented cell death, and improved long-term behavior. In humans, some observational studies have demonstrated reduced risks of cerebral palsy after antenatal magnesium sulfate therapy. Meta-analyses of five randomized controlled trials using magnesium sulfate as a neuroprotectant showed amelioration of cerebral palsy at 2 years. A meta-analysis of individual participant data from these trials showed an equally strong decrease in cerebral palsy and the combined risk of fetal/infant death and cerebral palsy at 2 years. The benefit remained similar regardless of gestational age, cause of prematurity, and total dose received. These data support the use of a minimal dose (e.g., 4 g loading dose ± 1 g/h maintenance dose over 12 h) to avoid potential deleterious effects. Antenatal magnesium sulfate is now recommended by the World Health Organization and many pediatric and obstetrical societies, and it is requisite to maximize its administration among women at risk of preterm delivery before 32 WG.

 

Management and investigation of neonatal encephalopathy: 2017 update

ABSTRACT

DOI: 10.1136/archdischild-2015-309639
This review discusses an approach to determining the cause of neonatal encephalopathy, as well as current evidence on resuscitation and subsequent management of hypoxic-ischaemic encephalopathy (HIE). Encephalopathy in neonates can be due to varied aetiologies in addition to hypoxic-ischaemia. A combination of careful history, examination and the judicious use of investigations can help determine the cause. Over the last 7 years, infants with moderate to severe HIE have benefited from the introduction of routine therapeutic hypothermia; the number needed to treat for an additional beneficial outcome is 7 (95% CI 5 to 10). More recent research has focused on optimal resuscitation practices for babies with cardiorespiratory depression, such as delayed cord clamping after establishment of ventilation and resuscitation in air. Around a quarter of infants with asystole at 10 min after birth who are subsequently cooled have normal outcomes, suggesting that individualised decision making on stopping resuscitation is needed, based on access to intensive treatment unit and early cooling. The full benefit of cooling appears to have been exploited in our current treatment protocols of 72 hours at 33.5°C; deeper and longer cooling showed adverse outcome. The challenge over the next 5–10 years will be to assess which adjunct therapies are safe and optimise hypothermic brain protection in phase I and phase II trials. Optimal care may require tailoring treatments according to gender, genetic risk, injury severity and inflammatory status.