Use Of Postnatal Corticosteroids Research Articles

End-organ damage from neonatal invasive fungal infection: a 14-year retrospective study from a tertiary center in China

BackgroundInvasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future.MethodsThe clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared.ResultsIncluded in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28, <32 weeks, and 37.7% with BW of 1000–1499 g. Candida albicans (C. albicans) was the most common Candida spp. in these neonates, accounting for 41.3% of all cases, followed by C. parapsilosis (30.5%) and C. glabrata (7.2%). EOD occurred in 40 (17.9%) of the 223 cases. Fungal meningitis was the most common EOD, accounting for 13.5% of the 40 EOD cases. There was no significant difference in the premature birth rate, delivery mode, GA and BW between EOD and NEOD groups, but the proportion of male infants with EOD was higher than that without. There was no significant difference in antenatal corticosteroid use, endotracheal intubation, invasive procedures, use of antibiotics, total parenteral nutrition, blood transfusion, postnatal corticosteroid use, fungal prophylaxis and the incidence of necrotizing enterocolitis between the two groups, but the proportion of C. albicans infection cases in EOD group was higher than that in NEOD group (57.5% vs. 37.7%). Compared with NEOD group, the proportion of cured or improved infants in EOD group was significantly lower (P < 0.05), and the number of infants who died or withdrew from treatment was larger (P < 0.05).ConclusionsOur retrospective study showed that preterm infants were prone to fungal infection, especially very preterm infants. C. albicans was the most common Candida spp. for IFI, and was a high-risk factor for EOD. EOD can occur in both full-term and premature infants, so the possibility of EOD should be considered in all infants with IFI.

Prevalence of osteopenia of prematurity before and after implementing an early strategy with the use of calcium and phosphate.

Introduction. With the use of aggressive parenteral nutrition in very low birth weight infants, alterations in calcium and phosphate metabolism were detected. In 2016, a prevention strategy was implemented through calcium phosphate monitoring and early supplementation. Our objective was to study whether this strategy reduces the prevalence of osteopenia and to identify associated risk factors. Population and methods. Quasi-experiment comparing the prevalence of osteopenia between two groups: one after implementing the calcium phosphate monitoring and supplementation strategy (01/01/2017-12/31/2019) and another prior to such intervention (01/01/2013-12/31/2015). Results. A total of 226 patients were included: 133 in the pre-intervention period and 93 in the post-intervention period. The overall prevalence of osteopenia was 26.1% (95% CI: 20.5-32.3) and it was reduced from 29.3% (95% CI: 21.7-37.8) in the pre-intervention period to 21.5% (95% CI: 13.6-31.2) in the post-intervention period, with no statistical significance (p = 0.19). In the multivariate analysis, the NEOCOSUR score for risk of death at birth, use of postnatal corticosteroids, and the intervention period were independently associated with osteopenia. Being born after the intervention reduced the probability of alkaline phosphatase > 500 IU/L by 71%, regardless of the other variables included in the model. Conclusion. Calcium phosphate monitoring and early supplementation is a protective factor against the development of osteopenia in very low birth weight infants.

Postnatal corticosteroid usage in United Kingdom and Ireland neonatal units.

To perform a survey on postnatal corticosteroids usage in neonatal units in the United Kingdom and Ireland. An 18-item structured questionnaire was created asking for the level of neonatal care and corticosteroid prescribing practices. A consultant neonatologist or senor specialty training registrar/advanced neonatal nurse practitioner was contacted in every neonatal unit in the UK and Ireland between September and December 2022. The response rate to the survey was 96% (203 of 211 units). Postnatal corticosteroids were prescribed in 48% of units: 5% of special care units, 43% of local neonatal units and 100% of neonatal intensive care units. Most units (90%) prescribed dexamethasone, which was prescribed to infants born at gestational ages less than 30 weeks in all those units prescribing postnatal corticosteroids, however, eight units also reported use in infants greater than 30 weeks of gestation. Dexamethasone regimens varied with starting doses from 50 to 500 μg/kg/day. Most tertiary units (97%) prescribed repeated courses of dexamethasone. In all levels of neonatal care, postnatal corticosteroids were prescribed to ventilated infants as well as those receiving non-invasive respiratory support. There is use of postnatal corticosteroids in all levels of neonatal care and much of the practice is not evidence based.

Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard

IntroductionBronchopulmonary dysplasia (BPD) is associated with adverse long-term respiratory and neurodevelopmental outcomes. No recent studies examined the changing respiratory management and outcomes, particularly severe BPD, across a whole population.PurposeEvaluate the...

Pre-Flight Hypoxemia Challenge Testing in Bronchopulmonary Dysplasia.

Former premature infants with bronchopulmonary dysplasia (BPD) are at risk for hypoxemia during air travel, but it is unclear until what age. We aimed to determine pass rates for high altitude simulation testing (HAST) by age in children with BPD and identify risks for failure. Retrospective, observational analysis of HAST in children with BPD at Boston Children's Hospital, using interval censoring to estimate the time-to-event curve of first pass. Curves were stratified by neonatal risk factors. Pass was considered lowest Spo2 ≥ 90%, or ≥94% for subjects with ongoing pulmonary hypertension (PH). Ninety four HAST studies were analyzed from 63 BPD subjects; 59 studies (63%) were passed. At 3 months corrected gestational age (CGA), 50% of subjects had passed; at 6 months CGA, 67% has passed; at 12 and 18 months CGA, 72% had passed; and at 24 months CGA, 85% had passed. Neonatal factors associated with delayed time-to-pass included postnatal corticosteroid use, respiratory support at NICU discharge, and tracheostomy. BPD infants who did not require respiratory support at 36 weeks were likely to pass (91%) at 6 months CGA. At 24 months, children least likely to pass included those with a history of PH (63%) and those discharged from the NICU with oxygen or respiratory support (71%). Children with BPD on respiratory support at 36 weeks should be considered for preflight hypoxemia challenges through at least 24 months CGA, and longer if they had PH or went home from NICU on respiratory support.

Preterm lung and brain responses to mechanical ventilation and corticosteroids.

Mechanical ventilation is necessary to maintain oxygenation and ventilation in many preterm infants. Unfortunately, even short periods of mechanical ventilation can cause lung and airway injury, and initiate the lung inflammation that contributes to the development of bronchopulmonary dysplasia (BPD). The mechanical stretch leads to airway cell differentiation and simplification of the alveoli, and releases cytokines that cause systemic response in other organs. Mechanical ventilation also leads to brain injury (IVH, white and gray matter) and neuronal inflammation that can affect the neurodevelopment of preterm infants. In efforts to decrease BPD, corticosteroids have been used for both prevention and treatment of lung inflammation. Corticosteroids have also been demonstrated to cause neuronal injury, so the clinician must balance the negative effects of both mechanical ventilation and steroids on the brain and lungs. Predictive models for BPD can help assess the infants who will benefit most from corticosteroid exposure. This review describes the lung and brain injury from mechanical ventilation in the delivery room and chronic mechanical ventilation in animal models. It provides updates on the current guidelines for use of postnatal corticosteroids (dexamethasone, hydrocortisone, budesonide, budesonide with surfactant) for the prevention and treatment of BPD, and the effects the timing of each steroid regimen has on neurodevelopment.

Systemic postnatal corticosteroid use for the prevention of bronchopulmonary dysplasia and its relationship to early neurodevelopment in extremely preterm infants

BackgroundSystemic postnatal corticosteroid use in extremely preterm infants poses a risk of adverse neurodevelopmental outcomes. This study explores their use beyond seven days of age with early neurodevelopmental assessments during the fidgety period (9–20 weeks postterm age).MethodsThis retrospective single-center cohort study included inborn extremely preterm infants from 1 January 2014 to 31 December 2018. Outborn infants, those with congenital or genetic abnormalities, and those who received postnatal corticosteroids for nonrespiratory reasons were excluded. The cohort was dichotomized based on the status of corticosteroid receipt. Early neurodevelopmental outcomes were reported using Prechtl’s General Movements Assessment.ResultsOf the 282 infants, 67 (23.75%) received corticosteroids. Of these, 34 (50.75%) received them for dependency on invasive ventilation (intermittent positive-pressure ventilation), and the remainder received them for dependency on non-invasive ventilation continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP). Abnormal or absent fidgety movements were observed in 13% of infants (7/54) who received corticosteroids compared to 2% of infants (3/146) who did not. An increased odds for an abnormal general movements assessment from corticosteroid use after adjusting for gestational age [adjusted odds ratio (aOR) = 5.5, 95% confidence interval (CI) = 1.14–26.56] was observed. The motor optimality scores differed between the two groups [corticosteroid group: 25.5 (23–26) versus no-corticosteroid group: 26 (24–28); z = − 2.02]. A motor optimality score < 20 was observed in 14.8% of infants (8/54) in the corticosteroid group compared to 2% of infants (3/146) in the noncorticosteroid group. This difference was significant after adjustment for gestational age (aOR 5.96, 95% CI 1.28–27.74).ConclusionsAbnormal early neurodevelopment was observed in infants who received systemic postnatal corticosteroids. The relationship between these findings and other factors influencing early neurodevelopment needs further exploration.

Postnatal corticosteroid use for prevention or treatment of bronchopulmonary dysplasia in England and Wales 2012–2019: a retrospective population cohort study

ObjectiveDescribe the population of babies who do and do not receive postnatal corticosteroids for prevention or treatment of bronchopulmonary dysplasia (BPD).DesignRetrospective cohort study using data held in the National Neonatal...

Postnatal Corticosteroids to Prevent or Treat Chronic Lung Disease Following Preterm Birth.

The American Academy of Pediatrics continues to provide guidance on the use of postnatal corticosteroids to manage or prevent chronic lung disease following preterm birth (formerly referred to as bronchopulmonary dysplasia). Since the last revision of such guidance in 2010, several prospective randomized trials have been published. This revision provides a review of those studies as well as updated recommendations, which include the use of systemic low-dose corticosteroid in preterm neonates with or at high risk for chronic lung disease. High-dose dexamethasone (≥0.5 mg/kg per day) is not recommended. New evidence suggests that inhaled corticosteroids may confer benefit if provided with surfactant as a vehicle, but safety data are lacking. Evidence remains insufficient to make any recommendations regarding routine use of postnatal corticosteroids in preterm infants. Neonatologists and other hospital care providers must continue to use their clinical judgment in individual patients, balancing the potential adverse effects of corticosteroid treatment with those of chronic lung disease. The decision to use postnatal corticosteroids for this purpose should be made together with the infant's parents, and the care providers should document their discussions with parents in the patient's medical record.

Respiratory distress syndrome in preterm infants of less than 32 weeks: What difference does giving 100 or 200 mg/kg of exogenous surfactant make?

BackgroundSurfactant dosing and effective delivery could affect continuous positive airways pressure (CPAP)‐failure. Nevertheless, information on exogenous surfactant dosing with current administration methods is limited.ObjectiveTo describe the effect of 100 or 200 mg/kg of surfactant as first‐line treatment of respiratory distress syndrome in preterm infants of less than 32 weeks gestation.Study DesignA retrospective single‐center cohort study comparing two epochs, before and after switching from 100 to 200 mg/kg surfactant therapy.ResultsSix hundred and fifty‐eight of the 1615 infants of less than 32 weeks were treated with surfactant: 282 received 100 mg/kg (S‐100) and 376 received 200 mg/kg (S‐200). There were no differences between S‐100 and S‐200 in perinatal data including prenatal corticosteroids, medication use, age at first surfactant administration and respiratory severity before surfactant.The S‐200 vs. S‐100 had fewer retreatments (17.0% vs. 47.2%, p < 0.001) and a shorter duration of oxygen therapy and mechanical ventilation (315 vs. 339 h, p = 0.018; 37 vs. 118 h, p = 0.000, respectively). There was no difference in postnatal corticosteroid use (S‐200 10.0% vs. S‐100 11.0%, p = 0.361). Bronchopulmonary dysplasia (BPD) was significantly lower in S‐200 vs. S‐100 when comparing either the 4 and 6‐year periods before and after the dose switch (29.4% vs. 15.7%, p = 0.003, and 18.7% vs. 27.3%, p = 0.024, respectively)ConclusionsThe switch from 100 to 200 mg/kg was associated with a marked reduction in the need for surfactant redosing, respiratory support, and BPD. This information could be important when designing a study in the modern era of less invasive administration as surfactant dosing and its effective delivery may affect the outcome.

Noninvasive High-Frequency Oscillatory Ventilation vs Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation as Postextubation Support for Preterm Neonates in China

Several respiratory support techniques are available to minimize the use of invasive mechanical ventilation (IMV) in preterm neonates. It is unknown whether noninvasive high-frequency oscillatory ventilation (NHFOV) is more efficacious than nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV) in preterm neonates after their first extubation. To test the hypothesis that NHFOV is more efficacious than NCPAP or NIPPV in reducing IMV after extubation and until neonatal intensive care unit discharge among preterm neonates. This multicenter, pathophysiology-based, assessor-blinded, 3-group, randomized clinical trial was conducted in 69 tertiary referral neonatal intensive care units in China, recruiting participants from December 1, 2017, to May 31, 2021. Preterm neonates who were between the gestational age of 25 weeks plus 0 days and 32 weeks plus 6 days and were ready to be extubated were randomized to receive NCPAP, NIPPV or NHFOV. Data were analyzed on an intention-to-treat basis. The NCPAP, NIPPV, or NHFOV treatment was initiated after the first extubation and lasted until discharge. Primary outcomes were total duration of IMV, need for reintubation, and ventilator-free days. These outcomes were chosen to describe the effect of noninvasive ventilation strategy on the general need for IMV. A total of 1440 neonates (mean [SD] age at birth, 29.4 [1.8] weeks; 860 boys [59.7%]) were included in the trial. Duration of IMV was longer in NIPPV (mean difference, 1.2; 95% CI, 0.01-2.3 days; P = .04) and NCPAP (mean difference, 1.5 days; 95% CI, 0.3-2.7 days; P = .01) compared with NHFOV. Neonates who were treated with NCPAP needed reintubations more often than those who were treated with NIPPV (risk difference: 8.1%; 95% CI, 2.9%-13.3%; P = .003) and NHFOV (risk difference, 12.5%; 95% CI, 7.5%-17.4%; P < .001). There were fewer ventilator-free days in neonates treated with NCPAP than in those treated with NIPPV (median [25th-75th percentile] difference, -3 [-6 to -1] days; P = .01). There were no differences between secondary efficacy or safety outcomes, except for the use of postnatal corticosteroids (lower in NHFOV than in NCPAP group; risk difference, 7.3%; 95% CI, 2.6%-12%; P = .002), weekly weight gain (higher in NHFOV than in NCPAP group; mean difference, -0.9 g/d; 95% CI, -1.8 to 0 g/d; P = .04), and duration of study intervention (shorter in NHFOV than in NIPPV group; median [25th-75th percentile] difference, -1 [-3 to 0] days; P = .01). Results of this trial indicated that NHFOV, if used after extubation and until discharge, slightly reduced the duration of IMV in preterm neonates, and both NHFOV and NIPPV resulted in a lower risk of reintubation than NCPAP. All 3 respiratory support techniques were equally safe for this patient population. ClinicalTrials.gov Identifier: NCT03181958.

Implementation of Bubble Continuous Positive Airway Pressure in the Delivery Room and NICU.

Implementation of Bubble Continuous Positive Airway Pressure in the Delivery Room and NICU.

EBNEO Commentary: A network meta-analysis of postnatal corticosteroids for bronchopulmonary dysplasia: Has the most appropriate treatment been revealed?

Ramaswamy VV, Bandyopadhyay T, Nanda D, Bandiya P, Ahmed J, Garg A, Roehr CC, Nangia S. Assessment of Postnatal Corticosteroids for the Prevention of Bronchopulmonary Dysplasia in Preterm Neonates: A Systematic Review and Network Meta-analysis. JAMA Pediatr 2021; 175(6): e206826. PMID 33720274. Systemic postnatal corticosteroids (PNCs) reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants but may contribute to long-term neurodevelopmental harm. The need to identify a treatment regimen with a reassuring risk-benefit balance remains.1 In an extraordinary feat of data aggregation, Ramaswamy and colleagues include 62 randomised clinical trials (RCTs) enrolling 5559 neonates in a systematic review and network meta-analysis (NMA) to determine which of 14 distinct PNC exposures (Table) may be most appropriate.2 The authors suggest moderately early-initiated medium cumulative dose systemic dexamethasone is the best regimen. Unlike traditional pairwise meta-analyses, NMAs compare multiple interventions, adding relevance to clinical scenarios with various alternative treatment options. NMAs also allow indirect comparisons between interventions, linking them through a common comparator.3 For example, no RCTs have compared early systemic hydrocortisone (EHC) to late-initiated low-cumulative dose systemic dexamethasone (LaLdDx), but a shared comparison to placebo in separate RCTs allows a relative risk estimation. The validity of NMA results relies on specific assumptions. A critical one is that the data linked to produce indirect evidence display ‘transitivity’.3 In essence, that aggregation may be justified by similarities in key population characteristics. Tools that guide this subjective judgement include assessment of whether the populations are similar on important effect modifiers and whether the indirect comparisons could be assessed in head-to-head trials. Extending the example above, we consider the tools against the PREMILOC (EHC) and DART (LaLdDx) trials.4, 5 A meta-regression identified the baseline risk of developing BPD as an important effect modifier for the effect of PNCs on death or cerebral palsy.6 The rates of death or BPD in the control groups of PREMILOC and DART were 49% and 91%, respectively, questioning their similarity.4, 5 In turn, a hypothetical trial of EHC versus LaLdDx would presumably compare prophylactic EHC to LaLdDx only amongst infants remaining on mechanical ventilation at 14 days. Exposing subjects to LaLdDx irrespective of respiratory status would raise ethical concerns. However, the indirect comparison generated by the NMA is not of prophylactic EHC versus expectant management with rescue LaLdDx. Though we focus on EHC versus LaLdDx as an example, these concerns extend to various comparisons. One could argue that transitivity is generally violated when comparing interventions applied in distinct stages of disease progression, and that use of PNCs as prophylaxis versus treatment of evolving severe BPD are distinct indications best suited to distinct comparisons.3 Lastly, we should avoid labelling the PNC regimen most effective against BPD as ‘most appropriate’. Although a reduction in BPD with various PNC regimens is probable, the avoidance of risk for adverse long-term neurodevelopmental outcomes is uncertain, and the latter will guide appropriateness. Further, as the authors acknowledge, the quality of evidence supporting the conclusion is low. Despite these points of caution, Ramaswamy and colleagues add a rich contribution to the literature, shining a helpful light on the path forward. Conclusively arriving at best practice will require additional high-quality research, followed by cautious data synthesis that prioritises long-term outcomes of importance to patients and their families. URL: https://ebneo.org/postnatal-corticosteroids-meta-analysis. None.

Postnatal steroid management in preterm infants with evolving bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting extremely preterm infants. Although mechanical ventilation and oxygen requirements in premature infants are identified as inciting mechanisms for inflammation and the development of BPD over time, data now support an array of perinatal events that may stimulate the inflammatory cascade prior to delivery. Corticosteroids, such as dexamethasone and hydrocortisone, have proven beneficial for the prevention and management of BPD postnatally due to their anti-inflammatory characteristics. This review aims to examine the pharmacologic properties of several corticosteroids, appraise the existing evidence for postnatal corticosteroid use in preterm infants, and assess steroid management strategies to ameliorate BPD. Finally, we aim to provide guidance based on clinical experience for managing adrenal suppression resulting from prolonged steroid exposure since this is an area less well-studied.

Intrauterine growth retardation and lung function of very prematurely born young people.

To assess if intrauterine growth retardation (IUGR) was associated with reduced lung function at 16-19 years. Very prematurely born young people who had IUGR would have reduced lung function postpuberty. Prospective follow-up study. One hundred and fifty-nine 16-19 year olds born before 29 weeks of gestation; 37 had IUGR. Lung function tests were performed: spirometry was used to assess forced expiratory volume in one second (FEV1), forced expiratory flow at 75%, 50% and 25% of expired vital capacity (FEF75, FEF50 and FEF25), peak expiratory flow (PEF) and forced vital capacity (FVC). Functional residual capacity (FRCpleth) total lung capacity (TLCpleth) and residual volume (RVpleth) were measured. Alveolar function was assessed by diffusion capacity within the lungs of carbon monoxide (DLCO). Impulse oscillometry was used to assess respiratory resistance and lung clearance index to assess ventilation homogeneity. Exercise capacity was assessed using a shuttle sprint test. After adjustment for BMI, the mean FEV-1/FVC, FEF75, FEF25-75, FRCpleth and RVpleth were poorer in those who had had IUGR, with differences between 0.56 and 0.75 z-scores. After further adjustment for BPD and postnatal corticosteroid use, only the difference in RVpleth z-scores remained statistically significant, adjusted difference (95% CI): 0.66 (0.18,1.13). Exercise capacity was lower in those with IUGR and this was more pronounced in males (p=0.04). At 16-19 years of age, those who had IUGR had poorer lung function and exercise capacity compared with those with adequate intrauterine growth.

Postnatal Corticosteroids Policy for Very Preterm Infants and Bronchopulmonary Dysplasia

Introduction: Postnatal corticosteroids (PNC) are effective for reducing bronchopulmonary dysplasia (BPD) in very preterm neonates but are associated with adverse effects including an increased risk of cerebral palsy. PNC use in Europe is heterogeneous across regions. This study aimed to assess whether European neonatal intensive care units (NICUs) with a low use of PNC or an explicit policy to reduce PNC use had higher risks of mortality or BPD. Methods: We included 3,126 infants in 105 NICUs born between 24 + 0 and 29 + 6 weeks’ gestational age in 19 regions in 11 countries in the EPICE cohort. First, we identified clusters of NICUs using hierarchical clustering based on PNC use and BPD prevalence and compared case mix and mortality between the clusters. Second, a multilevel analysis was performed to evaluate the association between a restrictive PNC policy and BPD occurrence. Results: There were 3 clusters of NICUs: 52 with low PNC use and a low BPD rate, 37 with low PNC use and a high BPD rate, and 16 with high PNC use and a medium BPD rate. Neonatal mortality did not differ between clusters (p = 0.88). A unit policy of restricted PNC use was not associated with a higher risk of BPD (odds ratio 0.68; 95% confidence interval: 0.45–1.03) after adjustment. Conclusion: Up to 49% of NICUs had low PNC use and low BPD rates, without a difference in mortality. Infants hospitalized in NICUs with a stated policy of low PNC use did not have an increased risk of BPD.

Review of use of postnatal corticosteroids in evolving or established bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a condition that affects a significant proportion of infants born prematurely. Whilst there have been advances in many aspects of neonatal respiratory care the rates of BPD remain relatively static. Much effort has been put into exploring the role of corticosteroids in potentially reducing inflammation in the developing lung; however, research has been hindered by concerns regarding adverse side–effect profiles and difficulties recruiting adequate numbers to power the results. Currently, two strategies are gaining popularity: low-dose dexamethasone after 7 days of age to facilitate ventilator weaning and prophylactic physiological hydrocortisone use from the first day of life. However, use in practice is limited whilst awaiting full-powered randomised trials. This article briefly discusses the evidence for each approach.

Prolonged ventilation and postnatal growth of preterm infants.

Background Extremely premature infants often need invasive respiratory support from birth, but have low nutritional reserves and high metabolic demands. Our aim was to determine if there was a relationship between prolonged ventilation and reduced postnatal growth in such infants. Methods A retrospective, observational study was undertaken. Data from infants born at less than 28 weeks of gestational age and ventilated for 7 days or more were collected and analysed including gestational age, gender, birth and discharge weight, birth and discharge head circumference, days of invasive mechanical ventilation and use of postnatal corticosteroids. The duration of invasive mechanical ventilation and the differences in weight (ΔWz) and head circumference (ΔHz) z-score from birth to discharge were calculated. Results Fifty-five infants were studied with a median [interquartile range (IQR)] gestational age at birth of 25.3 (24.3-26.7) weeks and birth weight of 0.73 (0.65-0.87) kg. The median duration of mechanical ventilation was 45 (33-68) days. Both ΔWz and ΔHz were significantly negatively correlated to the number of invasive mechanical ventilation days (P = 0.01 and P = 0.03, respectively), but not to the use of postnatal corticosteroids. Conclusion Poor postnatal growth is significantly negatively associated with a longer duration of mechanical ventilation in extremely prematurely born infants.

Adding to the controversy of postnatal steroids for preterm infants

The use of postnatal corticosteroids for extremely preterm infants continues to be one of the most controversial therapies in neonatology. The risk of off-target effects on neurodevelopment have led to the creation of lower dosage regimens used for shorter periods of time. As reported in this volume of The Journal, Marr et al randomized 59 extremely preterm infants with significant evolving chronic lung disease between 10 and 21 days of life to 1 of 2 regimens of dexamethasone. Both groups began at 0.5 mg/kg/day for 3 days; 1 group was then tapered over 42 days (total dose of ∼8 mg/kg) and the second group was tapered over 9 days (∼2.6 mg/kg for each course, with the possibility of up to 2 more 9-day courses if clinical deterioration occurred). The study was masked and did not allow for any open label use of inhaled or intravenous steroids during the study period. Infants who received the 42-day course were extubated almost 2 weeks earlier, although rates of bronchopulmonary dysplasia (BPD) and use of discharge on home oxygen therapy were similar between the groups. The most remarkable feature of this study was that 96% of the infants were evaluated with cognitive testing at age 7. Children in the 42-day group were more likely to be without neurodevelopmental impairment, have an IQ >70, and be in regular school without an individualized educational plan (75% vs 38% for the 9-day taper). There continues to be uncertainty about which infants with BPD benefit from corticosteroids and about which infants might be harmed without benefit. The study by Marr et al cannot fully answer these questions as it was conducted in a single center with a high survival rate and did not have an untreated control group. However, few studies include the all-important school age outcomes, which pediatricians and parents will certainly view as more meaningful than interim outcomes such as BPD. These findings suggest that if a high-risk, ventilator dependent infant is committed to a course of dexamethasone, there may be an important long-term advantage to continuing treatment through and beyond the time of extubation. Article page 20▸ Randomized Trial of 42-Day Compared with 9-Day Courses of Dexamethasone for the Treatment of Evolving Bronchopulmonary Dysplasia in Extremely Preterm InfantsThe Journal of PediatricsVol. 211PreviewTo compare pulmonary and neurodevelopmental outcomes in extremely preterm infants with evolving bronchopulmonary dysplasia treated with either a 42-day course of dexamethasone or 9-day course(s) of dexamethasone. Full-Text PDF

Changes in long-term prognosis with increasing postnatal survival and the occurrence of postnatal morbidities in extremely preterm infants offered intensive care: a prospective observational study

Decisions regarding provision of intensive care and post-discharge follow-up for infants born extremely preterm (<28 weeks' gestation) are based on the risks of mortality and neurodevelopmental disability. We aimed to elucidate the changes in probability of three outcomes (death, survival with major disability, and survival without major disability) with postnatal age in extremely preterm infants offered intensive care, and the effect of postnatal events on the probability of survival without major disability. In this prospective observational study, we used data from three geographical cohorts composed of all extremely preterm livebirths offered intensive care at birth during three distinct periods (1991-92, 1997, and 2005) in Victoria, Australia. Participants were assessed at 8 years' corrected age for major neurodevelopmental disability, defined as moderate or severe cerebral palsy, general intelligence more than 2 SDs below term-born control means, blindness, or deafness. Probabilities of outcomes conditional on survival to different postnatal ages were calculated by logistic regression. Multivariable logistic regression was used to assess factors predictive of survival with major disability. 751 (82%) of 915 extremely preterm livebirths free of lethal anomalies were offered intensive care, of whom 546 (73%) survived to age 8 years. Of the 499 survivors assessed, 86 (17%) had a major disability. With increasing gestational age at birth or days of postnatal survival, the probability of death decreased and of survival without major disability increased. By contrast, the probability of survival with major disability varied little with gestational age or postnatal survival. In survivors, major disability was associated with the occurrence of four important postnatal events: grade 3 or 4 intraventricular haemorrhage (odds ratio 2·61 [95% CI 1·11-6·15]), cystic periventricular leukomalacia (9·17 [3·57-23·53]), postnatal corticosteroid use (1·99 [1·03-3·85]), and surgery (2·78 [1·51-5·13]). 241 survivors (48%) had no major postnatal events during the newborn period, and had the lowest prevalence of major disability (17 participants [7%]). The probability of survival without major disability decreased with increasing number of major events (0·93 [0·89-0·96] for no events vs 0·31 [0·11-0·59] for three or more events). Long-term prognosis in terms of death and major neurodevelopmental disability changes rapidly after birth for extremely preterm infants. Counselling of families and post-discharge planning should be individualised to changing circumstances following birth. National Health and Medical Research Council of Australia.