Postnatal Dexamethasone Research Articles

Incidence, Risk Factors, Short-term Outcomes, and Microbiome of Ventilator-associated Pneumonia in Very-low-birth-weight Infants: Experience at a Single Level III Neonatal Intensive Care Unit.

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection in neonates on invasive mechanical ventilation, resulting in high morbidity and mortality. The objective of this study is to determine the incidence, risk factors, short-term outcomes and microbiome associated with VAP in very-low-birth-weight (VLBW) infants born at <32 weeks of gestational age (GA). Retrospective study of intubated VLBW infants born at <32 weeks of GA admitted to the Los Angeles General Medical Center neonatal intensive care unit from July 2015 to July 2021 who had routine tracheal aspirate cultures obtained. Neonates were retrospectively classified into 3 groups, confirmed VAP, suspected VAP and no VAP, for comparison of risk factors, outcomes and airway microbial colonization. Eighty-seven infants met inclusion criteria with a mean GA of 26.1 ± 1 weeks and mean birth weight of 812 ± 281 g. The incidence of VAP was 7.8 per 1000 ventilator days, and the most common causative organisms were Gram-positive organisms (39%), predominantly coagulase-negative Staphylococcus. Duration of postnatal dexamethasone exposure predicted VAP compared to no VAP (coefficient, 0.31; 95% CI 0.03-0.59; P = 0.03) after adjusting for duration of intubation, surfactant use and antenatal steroid exposure. Infants with VAP had higher rate of grade 2/3 bronchopulmonary dysplasia (P = 0.03) and longer hospital stay (P = 0.04). VAP occurs at a high rate in VLBW infants who are exposed to prolonged dexamethasone use. It is predominantly caused by Gram-positive organisms.

Postnatal steroids as lung protective and anti-inflammatory in preterm lambs exposed to antenatal inflammation.

Lung inflammation and impaired alveolarization precede bronchopulmonary dysplasia (BPD). Glucocorticoids are anti-inflammatory and reduce ventilator requirements in preterm infants. However, high-dose glucocorticoids inhibit alveolarization. The effect of glucocorticoids on lung function and structure in preterm newborns exposed to antenatal inflammation is unknown. We hypothesise that postnatal low-dose dexamethasone reduces ventilator requirements, prevents inflammation and BPD-like lung pathology, following antenatal inflammation. Pregnant ewes received intra-amniotic LPS (E.coli, 4 mg/mL) or saline at 126 days gestation; preterm lambs were delivered 48 h later. Lambs were randomised to receive either tapered intravenous dexamethasone (LPS/Dex, n = 9) or saline (LPS/Sal, n = 10; Sal/Sal, n = 9) commencing <3 h after birth. Respiratory support was gradually de-escalated, using a standardised protocol aimed at weaning from ventilation towards unassisted respiration. Tissues were collected at day 7. Lung morphology and mRNA levels for inflammatory mediators were measured. Respiratory support requirements were not different between groups. Histological analyses revealed higher tissue content and unchanged alveolarization in LPS/Sal compared to other groups. LPS/Dex lambs exhibited decreased markers of pulmonary inflammation compared to LPS/Sal. Tapered low-dose dexamethasone reduces the impact of antenatal LPS on ventilation requirements throughout the first week of life and reduces inflammation and pathological thickening of the preterm lung IMPACT: We are the first to investigate the combination of antenatal inflammation and postnatal dexamethasone therapy in a pragmatic study design, akin to contemporary neonatal care. We show that antenatal inflammation with postnatal dexamethasone therapy does not reduce ventilator requirements, but has beneficial maturational impacts on the lungs of preterm lambs at 7 days of life. Appropriate tapered postnatal dexamethasone dosing should be explored for extuabtion of oxygen-dependant neonates.

Factors associated with the response to postnatal dexamethasone use in very low birthweight infants: a nationwide cohort study

BackgroundDexamethasone is widely used as a systemic corticosteroid to treat and prevent bronchopulmonary dysplasia (BPD) in preterm infants. We evaluated the current epidemiology of dexamethasone use to prevent BPD and...

Improved Cardiac Performance with Dexamethasone Therapy in Premature Neonates: Novel Insights Using Serial Echocardiographic Assessments

(1) Background: dexamethasone is used for the prevention and treatment of chronic lung disease (CLD) in premature neonates, and its impact on cardiac performance and pulmonary vascular resistance has not been well studied. (2) Methods: eligible neonates of &lt;30 weeks gestational age (GA) had echocardiograms performed on them at three time points—before the initiation of dexamethasone (Echo-1), 24–48 h post the completion of dexamethasone therapy (Echo-2), and 7–14 days after course completion (Echo-3). (3) Results: 28 neonates with a 25.2 week mean GA and 652.9 g birthweight were included. The mean cumulative dose of dexamethasone was 0.98 mg/kg, given over 8–10 days. Echo-1 and Echo-2 showed a significant improvement in the right ventricular fractional area change (RV FAC 44.88 vs. 49.71, p = 0.025), tricuspid annular plane systolic excursion (TAPSE 0.65 cm vs. 0.70 cm, p = 0.013), and RV S’ (7.18 vs. 8.56, p = 0.05). The left ventricular (LV) ejection fraction was similar but with a significant increase in the LV S’ (4.77 vs. 6.01, p = 0.006). A longitudinal analysis at three time points showed a significant increase in RV FAC (0.02 units 95% CI (0.00–0.04), p = 0.037), TAPSE (0.09 units 95% CI (0.06–0.13), p &lt; 0.001), RV S’ (0.97 units (95% CI = 0.11–1.84), p = 0.028), a reduction in the eccentricity index (0.07 units 95% CI (−0.14–−0.01), p = 0.030), and an increase in the LV S’ (0.56 units (95% CI = 0.18–0.94)). (4) Conclusion: The use of postnatal dexamethasone for the prevention/treatment of CLD in premature neonates resulted in an expected improvement in respiratory status along with a significant improvement in the echocardiographic measures of biventricular heart performance.

Impact of postnatal dexamethasone timing on preterm mortality and bronchopulmonary dysplasia: a propensity score analysis.

Postnatal dexamethasone (PND) is used in high-risk preterm infants after the first week of life to facilitate extubation and prevent bronchopulmonary dysplasia (BPD) but the optimal treatment timing remains unclear. Our objective was to explore the association between the timing of PND commencement and mortality and respiratory outcomes. This was a retrospective National Neonatal Research Database study of 84 440 premature infants born <32 weeks gestational age from 2010 to 2020 in England and Wales. Propensity score weighting analysis was used to explore the impact of PND commenced at three time-points (2-3 weeks (PND2/3), 4-5 weeks (PND4/5) and after 5 weeks (PND6+) chronological age) on the primary composite outcome of death before neonatal discharge and/or severe BPD (defined as respiratory pressure support at 36 weeks) alongside other secondary respiratory outcomes. 3469 infants received PND. Compared with PND2/3, infants receiving PND6+ were more likely to die and/or develop severe BPD (OR 1.68, 95% CI 1.28-2.21), extubate at later postmenstrual age (mean difference 3.1 weeks, 95% CI 2.9-3.4 weeks), potentially require respiratory support at discharge (OR 1.34, 95% CI 1.06-1.70) but had lower mortality before discharge (OR 0.38, 95% CI 0.29-0.51). PND4/5 was not associated with severe BPD or discharge respiratory support. PND treatment after 5 weeks of age was associated with worse respiratory outcomes although residual bias cannot be excluded. A definitive clinical trial to determine the optimal PND treatment window, based on early objective measures to identify high-risk infants, is needed.

Dose-related cardiac outcomes in response to postnatal dexamethasone treatment in premature lambs.

Postnatal corticosteroids are used in the critical care of preterm infants for the prevention and treatment of bronchopulmonary dysplasia. We aimed to investigate the effects of early postnatal dexamethasone therapy and dose on cardiac maturation and morphology in preterm lambs. Lambs were delivered prematurely at ~128 days of gestational age and managed postnatally according to best clinical practice. Preterm lambs were administered dexamethasone daily at either a low-dose (n=9) or a high-dose (n=7), or were naïve to steroid treatment and administered saline (n=9), over a 7-day time-course. Hearts were studied at postnatal Day 7 for gene expression and assessment of myocardial structure. High-dose dexamethasone treatment in the early postnatal period led to marked differences in cardiac gene expression, altered cardiomyocyte maturation and reduced cardiomyocyte endowment in the right ventricle, as well as increased inflammatory infiltrates into the left ventricle. Low-dose exposure had minimal effects on the preterm heart. Neonatal dexamethasone treatment led to adverse effects in the preterm heart in a dose-dependent manner within the first week of life. The observed cardiac changes associated with high-dose postnatal dexamethasone treatment may influence postnatal growth and remodeling of the preterm heart and subsequent long-term cardiac function.

Vitamin A Status in Preterm Infants Is Associated with Inflammation and Dexamethasone Exposure.

Vitamin A has a key role in lung development and its deficiency is associated with an increased risk of bronchopulmonary dysplasia. This secondary cohort analysis of the ImNuT trial (Immature, Nutrition Therapy NCT03555019) aimed to (1) explore vitamin A status in preterm infants <29 weeks gestation and (2) assess the influence of inflammation and postnatal dexamethasone exposure on vitamin A concentrations in blood. We report detailed information on vitamin A biochemistry, vitamin A intake, markers of inflammation and dexamethasone exposure. After four weeks of age, infants exposed to dexamethasone (n = 39) showed higher vitamin A concentrations compared to unexposed infants (n = 41); median (IQR) retinol was 1.0 (0.74, 1.5) vs. 0.56 (0.41, 0.74) µmol/L, p < 0.001. Pretreatment retinol concentrations were lower in the dexamethasone group compared to non-exposed infants (p < 0.001); 88% vs. 60% of the infants were considered deficient in vitamin A (retinol < 0.7 µmol/L) at one week of age. Small size for gestational age, mechanical ventilation and elevated levels of interleukin-6 were factors negatively associated with first-week retinol concentrations. In conclusion, preterm infants <29 weeks gestation are at risk of vitamin A deficiency despite intakes that accommodate current recommendations. The presence of inflammation and dexamethasone exposure should be considered when interpreting vitamin A status.

Dexamethasone may affect the occurrence of parenteral nutrition-associated cholestasis in preterm neonates.

Glucocorticoids are currently used for the co-therapeutic management of autoimmune hepatitis and some cholestatic diseases. Thus far, we do not know the efficacy of glucocorticoids in the treatment of parenteral nutrition-associated cholestasis. We aimed to analyze whether the administration of late postnatal dexamethasone for treating bronchopulmonary dysplasia influence the occurrence of parenteral nutrition-associated cholestasis in preterm neonates. A retrospective study was conducted for 78 preterm neonates without major anomalies (gestational age was <30 weeks, and birthweight was ≤1000 g) hospitalized in a neonatal unit. Total and direct serum bilirubin levels were measured about every two weeks for all neonates. Data including the administration of dexamethasone, intravenous nutrition, and enteral feeding were collected by at least three audits. A total of 15 preterm neonates were diagnosed with parenteral nutrition-associated cholestasis, and after stopping parenteral nutrition, the direct bilirubin value decreased to the normal level for no longer than 150 days. The prolonged duration of parenteral nutrition was a risk factor, and late postnatal dexamethasone treatment was a protective factor in reducing the incidence of parenteral nutrition-associated cholestasis. Dexamethasone treatment may reduce the occurrence of parenteral nutrition-associated cholestasis in preterm neonates.

Survival and care practices of periviable births of

Data from the China Neonatal Network currently shows that the survival rate of very preterm infants in China has improved in recent years. However, due to the unequal economic and medical development of each city in China, the national data do not completely represent the level of neonatal care in the metropolitan areas. Though many studies have published their short- or long-term survival, very few have described the care practices and the course of stay of these neonates in detail. Our objective was to examine the survival and clinical practices among preterm infants born at <24 weeks' gestational age (GA) in a high-income city in China, from 2015 to 2021. Retrospective study of preterm infants <24 weeks GA in a level 3 neonatal intensive care unit in China, over a period of 7 years (2015-2021). Care practices in neonatal intensive care units (NICU) and short- and long-term survival were measured. A total of 32 periviable infants were included, with a median GA of 23.0 weeks and mean (SD) birth weight of 497 (94) g; 17 infants (53.1%) were female. While none of the infants born at 21 weeks of gestation survived until discharge, the survival rates were 25.0% (3 of 12) for infants born at 22 weeks and 58.8% (10 of 17) at 23 weeks. Antenatal corticosteroids were used in 56.3%, and 100% were vaginal birth. In the delivery room, surfactant was prescribed for 46.9% of the infants, and postnatal dexamethasone (≥2 courses) was prescribed to 61.5% of the infants. Logistic regression analysis showed that Apgar score at 5 minutes (OR = 2.007, 95% CI, 1.031 to 3.906, P < 0.05) increased the risk of death, while the increase in gestational age (OR = 0.238, 95% CI, 0.060-0.936, P < 0.05), antenatal use of steroids (OR = 0.287, 95% CI, 0.106-0.778, P < 0.01), and premature rupture of membranes (OR = 0.141, 95% CI, 0.024 -0.847, P = 0.032) could decrease the risk. No or mild neurodevelopmental impairment in surviving infants was 76.9% (10 of 13). Although the survival rate of periviable infants was shown to be improved in our study, there is still much room for improvement, and active follow-up information should be conducted.

23 Assessing the effects of introducing prophylactic hydrocortisone in extremely low gestational age infants in a tertiary Canadian NICU

Abstract Background Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. A large trial and a meta-analysis support the early use of physiologic doses of hydrocortisone to reduce the incidence of death or moderate/severe BPD. In 2019, this practice was introduced for all preterm infants &amp;lt;28 weeks gestational age (GA) at our university-affiliated tertiary care NICU. Objectives To determine the effect of prophylactic hydrocortisone on the incidence of survival with mild or no BPD in neonates born &amp;lt;28 weeks GA. Secondary objectives were to compare safety outcomes related to prophylactic hydrocortisone use: late onset sepsis, gastrointestinal perforation, severe intraventricular hemorrhage (IVH) and use of postnatal dexamethasone. Design/Methods We performed a retrospective cohort study of infants born &amp;lt;28 weeks GA admitted to our NICU during 2 epochs, before and after the implementation of prophylactic hydrocortisone. The primary objective was evaluated using logistic regression adjusted for GA. Safety outcomes were compared using chi-square or Fisher’s exact test. Results Epoch 1 included 76 infants and epoch 2 included 71 infants, of whom 63 (88.7%) received prophylactic hydrocortisone. Infants in the two epochs were similar in terms of median (IQR) GA 26.5 (25.0, 27.2) vs 26.7 (25.1, 27.1) weeks GA, mean (SD) weight at admission (882g +/- 212 vs 841g +/- 176), APGAR at 5 minutes, use of antenatal steroids and/or surfactant, and need for intubation at delivery (all p&amp;gt;0.5). Three infants were transferred to another hospital and their BPD status could not be determined. Adjusting for GA, there was a statistically non-significant signal for increased survival with mild or no BPD in epoch 2 (adjusted odds ratio 1.68, 95% CI 0.80, 3.59, p= 0.17) compared to epoch 1. The two epochs had similar incidence of late onset sepsis, gastrointestinal perforation and need for postnatal dexamethasone, however, in epoch 2, fewer infants developed grade 3/4 IVH on head ultrasound within the first two weeks of life (7/71, 9.9%) compared to epoch 1 (21/76, 27.6%, p= 0.01). Conclusion Prophylactic hydrocortisone may be associated with increased survival with mild or no BPD. Safety outcomes in both epochs were similar, but with a significantly decreased incidence of grade 3/4 IVH in the prophylactic hydrocortisone group. Larger cohort studies are required before a clear recommendation for prophylactic hydrocortisone can be made.

Risk factors and prediction score model for unplanned readmission among neonates with NRDS under one year of age: A retrospective cohort study.

ObjectiveThis study aimed to analyze the risk factors and establish a prediction score model for unplanned readmission among neonates with neonatal respiratory distress syndrome (NRDS) for respiratory problems under one year of age.MethodsThis retrospective cohort study enrolled 230 neonates with NRDS who were admitted between January 2020 and December 2020. The infants were classified into two subgroups based on whether they were readmitted for respiratory problems under one year of age: readmit group and non-readmit group. Readmission risk factors for NRDS were analyzed by logistic regression and a prediction score model was generated.ResultsAmong the 230 enrolled infants, 51 (22%) were readmitted, and 179 (78%) were not readmitted. In univariate analysis, compared with non-readmit group infants, readmit group infants had a significantly younger birth gestational age (31.9 ± 2.3 vs. 32.8 ± 2.5 weeks, p = 0.012), lower birth weight (1,713.7 ± 501.3 g vs. 1,946.8 ± 634.4 g, p = 0.007), older age at discharge (41.7 vs. 31.7 days, p = 0.012), higher proportion of necrotizing enterocolitis (NEC) (31% vs. 16%, p = 0.016), higher rate of blood transfusion (39% vs. 25%, p = 0.049), higher rate of postnatal dexamethasone (DEX) administration (28% vs. 9.5%, p = 0.001), and higher rate of home oxygen therapy (HOT) (57% vs. 34%, p = 0.003). Moreover, readmit group infants had significantly longer antibiotic days usage (12.0 vs. 10.0 days, p = 0.026) and a longer duration of hospital stay (41.0 vs. 31.0 days, p = 0.012) than non-readmit group infants. The multivariate logistic regression analysis showed that taking readmission as a target variable, postnatal DEX administration (OR: 2.689, 95% CI: 1.168–6.189, p = 0.020), HOT (OR: 2.071, 95% CI: 1.060–4.046, p = 0.033), and NEC (OR: 2.088, 95% CI: 0.995–4.380, p = 0.051) could be regarded as risk factors for readmission. A scoring model predicting readmission was administered with a positive predictive value of 0.651 (95% CI: 0.557–0.745, p = 0.002), with a sensitivity of 0.412 and a specificity of 0.888 at a cut-off of 3.5 points, which were evaluated on the receiver operating characteristic curve.ConclusionsPostnatal DEX administration, HOT, and NEC were risk factors for readmission of NRDS. NRDS infants with a predictive score of 3.5 points or more were at high risk for unplanned readmission.

Dexamethasone Alters Tracheal Aspirate T-Cell Cytokine Production in Ventilated Preterm Infants.

Postnatal corticosteroids improve respiratory status and facilitate respiratory support weaning in preterm infants with bronchopulmonary dysplasia (BPD). Older literature describes characteristic cytokine profiles in tracheal aspirates (TA) of BPD patients which are altered with corticosteroids. Corticosteroids also influence peripheral blood T-cell presence. However, little is known regarding TA T-cell phenotype and cytokine production before or after exogenous corticosteroids. We hypothesized that postnatal dexamethasone alters the TA T-cell cytokine profiles of preterm infants. TA samples were collected from 14 infants born from 23 0/7 to 28 6/7 weeks who were mechanically ventilated for at least 14 days. Samples were collected up to 72 h before a ten-day dexamethasone course and again 1 to 3 calendar days after dexamethasone initiation. The primary outcome was change in T cell populations present in TA and their intracellular cytokine profile after dexamethasone treatment, ascertained via flow cytometry. Following dexamethasone treatment, there were significant decreases in respiratory severity score (RSS), percent CD4+IL-6+ cells, CD8+IL-6+ cells, CXCR3+IL-6+ cells, and CXCR3+IL-2+ cells and total intracellular IFN-γ in TA. RSS significantly correlated with TA percent CD4+IL-6+ cells. To our knowledge, this is the first study demonstrating that dexamethasone reduced T-cell IL-6 and this reduction was associated with improved RSS in pre-term infants with evolving BPD.

The contribution of postnatal steroid administration to early brain damage in preterm babies with bronchopulmonary dysplasia

Background/aimPostnatal corticosteroids are commonly used to treat bronchopulmonary dysplasia (BPD). We aimed to show whether S100 calcium-binding B (S100B), neuron-specific enolase (NSE), Tau protein or microtubule-associated protein tau (MAPT), and glial fibrillary acid protein (GFAP) levels would provide any evidence of early neurological damage in premature infants receiving postnatal low dose dexamethasone therapy for BPD treatment.Materials and methods In this cohort study, 136 preterm infants diagnosed with BPD at ≤32 weeks of gestation formed the study group, and 64 preterm infants formed the control group. NSE, S100B, GFAP, and MAPT levels were first measured before the postnatal corticosteroid treatment in both the patient and the control group on the 28th day and, for a second time, after treatment termination in the patient group.Results There were significant differences between the measured GFAP, MAPT, and NSE values of the BPD and control groups on the 28th day, whereas there was no significant difference between the measured S100B values of the two groups. There were a statistically significant difference between the NSE values measured on the 28th day and after the treatment within the BPD group, whereas no significant difference existed between the GFAP, MAPT, and S100B values.Conclusion NSE levels, which indicate brain damage in the early period, increased in preterm babies with BPD who had been administered postnatal dexamethasone.

Assessment of Neonatal Intensive Care Unit Practices, Morbidity, and Mortality Among Very Preterm Infants in China

The Chinese Neonatal Network was established in 2018 and maintains a standardized national clinical database of very preterm or very low-birth-weight infants in tertiary neonatal intensive care units (NICUs) throughout China. National-level data on outcomes and care practices of very preterm infants (VPIs) in China are lacking. To assess the care practices in NICUs and outcomes among VPIs in China. A cohort study was conducted comprising 57 tertiary hospitals from 25 provinces throughout China. All infants with gestational age (GA) less than 32 weeks who were admitted to the 57 NICUs between January 1 and December 31, 2019, were included. Care practices, morbidities, and survival were the primary outcomes of the study. Major morbidities included bronchopulmonary dysplasia, severe intraventricular hemorrhage (grade ≥3) and/or periventricular leukomalacia, necrotizing enterocolitis (stage ≥2), sepsis, and severe retinopathy of prematurity (stage ≥3). A total of 9552 VPIs were included, with mean (SD) GA of 29.5 (1.7) weeks and mean (SD) birth weight of 1321 (321) g; 5404 infants (56.6%) were male. Antenatal corticosteroids were used in 75.6% (6505 of 8601) of VPIs, and 54.8% (5211 of 9503)were born through cesarean delivery. In the delivery room, 12.1% of VPIs received continuous positive airway pressure and 26.7% (2378 or 8923) were intubated. Surfactant was prescribed for 52.7% of the infants, and postnatal dexamethasone was prescribed to 9.5% (636 of 6675) of the infants. A total of 85.5% (8171) of the infants received complete care, and 14.5% (1381) were discharged against medical advice. The incidences of the major morbidities were bronchopulmonary dysplasia, 29.2% (2379 of 8148); severe intraventricular hemorrhage and/or periventricular leukomalacia, 10.4% (745 of 7189); necrotizing enterocolitis, 4.9% (403 of 8171 ); sepsis, 9.4% (764 of 8171); and severe retinopathy of prematurity, 4.3% (296 of 6851) among infants who received complete care. Among VPIs with complete care, 95.4% (7792 of 8171) survived: 65.6% (155 of 236) at 25 weeks' or less GA, 89.0% (880 of 988) at 26 to 27 weeks' GA, 94.9% (2635 of 2755)at 28 to 29 weeks' GA, and 98.3% (4122 of 4192) at 30 to 31 weeks' GA. Only 57.2% (4677 of 8171) of infants survived without major morbidity: 10.5% (25 of 236) at 25 weeks' or less GA, 26.8% (48 of 179) at 26 to 27 weeks' GA, 51.1% (1409 of 2755) at 28 to 29 weeks' GA, and 69.3% (2904 of 4192) at 30 to 31 weeks' GA. Among all infants admitted, the survival rate was 87.6% (8370 of 9552)and survival without major morbidities was 51.8% (4947 of 9552). The findings of this study suggest that survival and survival without major morbidity of VPIs in Chinese NICUs have improved but remain lower than in high-income countries. Comprehensive and targeted quality improvement efforts are needed to provide complete care for all VPIs, optimize obstetrical and neonatal care practices, and improve outcomes.

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

ObjectiveTo evaluate the short-term respiratory effects of PND in a cohort of ventilator-dependent premature infants.Study designClinical 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.ResultTreatment 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.ConclusionIn 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.

Perinatal Risk and Protective Factors in the Development of Diffuse White Matter Abnormality on Term-Equivalent Age Magnetic Resonance Imaging in Infants Born Very Preterm

To identify perinatal clinical diseases and treatments that are associated with the development of objectively diagnosed diffuse white matter abnormality (DWMA) on structural magnetic resonance imaging (MRI) at term-equivalent age in infants born very preterm. A prospective cohort of 392 infants born very preterm (≤32weeks of gestational age) was enrolled from 5 level III/IV neonatal intensive care units between September 2016 and November 2019. MRIs of the brain were collected at 39 to 45weeks of postmenstrual age to evaluate DWMA volume. A predefined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal intensive care unit data were collected for enrolled patients to identify antecedents of objectively diagnosed DWMA. Of the 392 infants in the cohort, 377 (96%) had high-quality MRI data. Their mean (SD) gestational age was 29.3 (2.5) weeks. In multivariable linear regression analyses, pneumothorax (P=.027), severe bronchopulmonary dysplasia (BPD) (P=.009), severe retinopathy of prematurity (P<.001), and male sex (P=.041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA: postnatal dexamethasone therapy for severe BPD (P=.004), duration of caffeine therapy for severe BPD (P=.009), and exclusive maternal milk diet at neonatal intensive care unit discharge (P=.049). Severe retinopathy of prematurity and BPD exhibited the strongest adverse association with development of DWMA. We also identified treatments and nutritional factors that appear protective against the development of DWMA that also have implications for the clinical care of infants born very preterm.

Ex Vivo MRI Analytical Methods and Brain Pathology in Preterm Lambs Treated with Postnatal Dexamethasone †.

Postnatal glucocorticoids such as dexamethasone are effective in promoting lung development in preterm infants, but are prescribed cautiously due to concerns of neurological harm. We developed an analysis pipeline for post-mortem magnetic resonance imaging (MRI) to assess brain development and hence the neurological safety profile of postnatal dexamethasone in preterm lambs. Lambs were delivered via caesarean section at 129 days’ (d) gestation (full term ≈ 150 d) with saline-vehicle control (Saline, n = 9), low-dose tapered dexamethasone (cumulative dose = 0.75 mg/kg, n = 8), or high-dose tapered dexamethasone (cumulative dose = 2.67 mg/kg, n = 8), for seven days. Naïve fetal lambs (136 d gestation) were used as end-point maturation controls. The left-brain hemispheres were immersion-fixed in 10 % formalin (24 h), followed by paraformaldehyde (>6 months). Image sequences were empirically optimized for T1- and T2-weighted MRI and analysed using accessible methods. Spontaneous lesions detected in the white matter of the frontal cortex, temporo-parietal cortex, occipital lobe, and deep to the parahippocampal gyrus were confirmed with histology. Neither postnatal dexamethasone treatment nor gestation showed any associations with lesion incidence, frontal cortex (total, white, or grey matter) or hippocampal volume (all p > 0.05). Postnatal dexamethasone did not appear to adversely affect neurodevelopment. Our post-mortem MRI analysis pipeline is suitable for other animal models of brain development.

Antenatal betamethasone enhanced the detrimental effects of postnatal dexamethasone on hyperoxic lung and brain injuries in newborn rats.

PurposeTo determine the effects of antenatal betamethasone and/or postnatal dexamethasone administration on hyperoxic lung and brain injuries in newborn rats.MethodsNewborn Sprague-Dawley rats were divided into five experimental groups: normoxia-vehicle-vehicle group, hyperoxia-vehicle-vehicle group, hyperoxia-betamethasone-vehicle group, hyperoxia-vehicle-dexamethasone group, and hyperoxia-betamethasone-dexamethasone group according to (i) whether rats were exposed to normoxia or hyperoxia after birth to postnatal day (P) 14, (ii) whether antenatal betamethasone (0.2mg/kg) or vehicle was administered to pregnant rats at gestation days 19 and 20, and (iii) whether three tapering doses of dexamethasone (0.5, 0.3, 0.1mg/kg per day) or vehicle were administered on P5, 6 and 7, respectively. The lungs and brains were harvested for histological and biochemical analyses at P8 and P14.ResultsPostnatal dexamethasone but not antenatal betamethasone significantly enhanced hyperoxia-induced reduction in body weight gain and alveolarization and increased lung terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells both at P8 and P14, transiently increased hyperoxia-induced reductions in brain weight gain and angiogenesis, and increase in brain TUNEL-positive cells at P8 but not at P14. Co-administration of antenatal betamethasone significantly enhanced dexamethasone-induced impairments in alveolarization both at P8 and P14, transient increases in lung and brain oxidative stresses, and increases in brain TUNEL-positive cells at P8 but not at P14.ConclusionAlthough postnatal dexamethasone but not antenatal betamethasone alone significantly increased hyperoxic lung and brain injuries, co-administration of antenatal betamethasone significantly enhanced the detrimental effects of postnatal dexamethasone on hyperoxic lung and brain injuries in newborn rats.

Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely.

The objective of this study was to determine the impact of postnatal dexamethasone treatment on the neonatal unit on the school age lung function of very prematurely born children. Children born prior to 29 weeks of gestational age had been entered into a randomised trial of two methods of neonatal ventilation (United Kingdom Oscillation Study). They had comprehensive lung function measurements at 11 to 14 years of age. One hundred and seventy-nine children born at a mean gestational age of 26.9 (range 23–28) weeks were assessed at 11 to 14 years; 50 had received postnatal dexamethasone. Forced expiratory flow at 75% (FEF75), 50%, 25% and 25–75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes including total lung capacity and residual volume were assessed. Lung function outcomes were compared between children who had and had not been exposed to dexamethasone after adjustment for neonatal factors using linear mixed effects regression. After adjustment for confounders all the mean spirometry results were between 0.38 and 0.87 standard deviations lower in those exposed to dexamethasone compared to the unexposed. For example, the mean FEF75 z-score was 0.53 lower (95% CI 0.21 to 0.85). The mean lung function was lower as the number of courses of dexamethasone increased. In conclusion, postnatal dexamethasone exposure was associated with lower mean lung function at school age in children born extremely prematurely. Our results suggest the larger the cumulative dose the greater the adverse effect on lung function at follow-up.

Does duration of caffeine therapy in preterm infants born ≤1250 g at birth influence neurodevelopmental (ND) outcomes at 3 years of age?

To evaluate the effect of duration of caffeine use on long-term neurodevelopmental (ND) outcomes at 3 years corrected age (CA) in preterm infants with birthweights (BW) ≤ 1250 g. All surviving infants with BW ≤ 1250 g admitted to the Foothills Medical Center neonatal intensive care unit (NICU) from January 2002 to December 2009 who received the first dose of caffeine in the first week of life and were followed up at three years CA were included in the study. Demographics and follow-up outcomes were compared based on early cessation of caffeine ≤ 14 days (ECC), intermediate cessation of caffeine 15-30 days (ICC), and late cessation of caffeine >30 days (LCC). The primary outcome of ND impairment was present if a child had any one of the following: cerebral palsy, cognitive delay, visual impairment, or hearing impairment or deafness. Univariate and logistic regression analyses were performed. Of the 508 eligible infants, 448 (88%) were seen at 3 years CA at follow-up. ECC (n = 139), ICC (n = 122) and LCC (n = 187) groups had a median (range) BW of 979 (560-1250), 1010 (530-1250), and 980 (520-1250) g (p = 0.524) and median (range) gestational age (GA) of 27 (23-33), 28 (24-33), and 27 (24-32) weeks, respectively (p = 0.034). In logistic regression models adjusting for GA,maternal smoking, and each neonatal risk factorseparately (IVH, NEC, sepsis, blood transfusions, BPD, postnataldexamethasone, SNAP-II, and ventilator days), none of the models showed a statistically significant association between caffeine duration and ND impairment. The duration of caffeine use in premature infants in the NICU does not impact on long-term ND outcomes at 3 years CA.