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Cureus Dec 2023Preterm birth causes constant challenges, with bronchopulmonary dysplasia (BPD) being a major concern. Immediately after birth, it takes time to establish feeding... (Review)
Review
Preterm birth causes constant challenges, with bronchopulmonary dysplasia (BPD) being a major concern. Immediately after birth, it takes time to establish feeding between the mother and the premature baby. During this time, the telological shifting of fluid from extracellular space to intracellular space will help the baby; this transition should be smooth. Both normal physiologic changes and pathophysiologic events are capable of disrupting this delicate fluid shifting that occurs in very low-birth-weight infants during the first week of life. The immaturity of the renal system and evaporative losses complicate this process. This lack of fluid displacement can be associated with an increased amount of water in the lungs and reduced lung compliance. This can lead to the need for more ventilatory support and a higher oxygen requirement, which, in turn, leads to lung damage. The fluid restriction is also associated with complications such as severe dehydration, intracranial hemorrhage, and bilirubin toxicity. However, the administration of large amounts of fluid and salt is associated with an increased incidence of patent ductus arteriosus, BPD, necrotizing enterocolitis, and intraventricular hemorrhage. There were studies conducted in both the pre-surfactant and surfactant eras that were inconclusive regarding fluid restriction in BPD. We only included very recent studies. This systematic review attempts to summarize the current evidence, focusing on the efficacy and safety of early fluid management in preterm infants. This reduces the risk of BPD and improves outcomes for premature infants. As we know, intact survival is very important. Our review supported the early fluid restriction.
PubMed: 38249238
DOI: 10.7759/cureus.50805 -
Neonatology 2024Caffeine is commonly used as therapy for apnea of prematurity and has shown potential in preventing other conditions in preterm neonates. However, the optimal timing for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Caffeine is commonly used as therapy for apnea of prematurity and has shown potential in preventing other conditions in preterm neonates. However, the optimal timing for caffeine therapy remains uncertain.
OBJECTIVE
This study aimed to compare the outcomes of early versus late administration of caffeine in preterm neonates.
METHODS
PubMed, Embase, and Cochrane Library were searched for studies comparing 0-2 days to ≥3 days caffeine introduction in preterm neonates. Outcomes included were mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), late-onset sepsis, length of hospital stay, and the composite of BPD or death. RevMan 5.4.1 was used for statistical analysis.
RESULTS
A total of 122,579 patients from 11 studies were included, 2 were randomized controlled trials (RCTs), and 63.9% of the neonates received early caffeine administration. The rates of BPD (OR: 0.70; 95% CI: [0.60-0.81]; p < 0.0001), IVH (OR: 0.86; 95% CI: [0.82-0.90]; p < 0.0001), ROP (OR: 0.80; 95% CI: [0.74-0.86]; p < 0.0001), late-onset sepsis (OR: 0.84; 95% CI: [0.79-0.89]; p < 0.00001), and PDA (OR: 0.60; 95% CI: [0.47-0.78]; p < 0.0001) were significantly reduced in the early caffeine group. The composite outcome of BPD or death was also lower in the early caffeine group (OR: 0.76; 95% CI: [0.66-0.88]; p < 0.0003). Mortality rate was higher in the early caffeine group (OR: 1.20; 95% CI: 1.12-1.29; p < 0.001).
CONCLUSION
As compared with late caffeine administration, early caffeine is associated with a reduction in BPD, IVH, ROP, late-onset sepsis, and PDA in preterm neonates, albeit increased mortality. Additional RCTs are warranted to confirm these findings and evaluate whether the effect on mortality may be related to survival bias in observational studies favoring the late treatment group.
Topics: Humans; Infant, Newborn; Bronchopulmonary Dysplasia; Caffeine; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Infant, Premature; Randomized Controlled Trials as Topic; Sepsis
PubMed: 37989113
DOI: 10.1159/000534497 -
Neonatology 2024Echocardiography is the gold standard for the diagnosis hemodynamically significant-patent ductus arteriosus (hs-PDA). It requires trained personnel and is not readily...
BACKGROUND
Echocardiography is the gold standard for the diagnosis hemodynamically significant-patent ductus arteriosus (hs-PDA). It requires trained personnel and is not readily available. Urinary biomarkers can be used as an adjunct.
OBJECTIVE
The objective of this study was to systematically review the diagnostic accuracy of urinary N terminal pro-B type natriuretic peptides (NT-proBNP) for hs-PDA in preterm neonates.
METHODS
We included studies that evaluated urinary NT-proBNP and urinary NT-proBNP/creatinine ratio (index tests) in preterm neonates with hs-PDA (participants) in comparison with echocardiogram (reference standard). Methodological quality and certainty of evidence were assessed using Quality Assessment of Diagnostic-Accuracy Studies (QUADAS-2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively.
RESULTS
Low quality of evidence suggests that urinary NT-proBNP has modest sensitivity and specificity for the diagnosis of a hs-PDA, with variation in accuracy based on assay and patient characteristics.
CONCLUSION
Urinary NT-proBNP assays must be locally validated for specific patient populations and further studies to support its use must be performed.
Topics: Humans; Infant; Infant, Newborn; Biomarkers; Ductus Arteriosus, Patent; Infant, Premature; Natriuretic Peptide, Brain; Peptide Fragments
PubMed: 37899032
DOI: 10.1159/000533824 -
The Cochrane Database of Systematic... Aug 2023Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) may contribute to neonatal morbidity and mortality and result in long-term neurodevelopmental... (Review)
Review
Pharmacological pain and sedation interventions for the prevention of intraventricular hemorrhage in preterm infants on assisted ventilation - an overview of systematic reviews.
BACKGROUND
Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) may contribute to neonatal morbidity and mortality and result in long-term neurodevelopmental sequelae. Appropriate pain and sedation management in ventilated preterm infants may decrease the risk of GMH-IVH; however, it might be associated with harms.
OBJECTIVES
To summarize the evidence from systematic reviews regarding the effects and safety of pharmacological interventions related to pain and sedation management in order to prevent GMH-IVH in ventilated preterm infants.
METHODS
We searched the Cochrane Library August 2022 for reviews on pharmacological interventions for pain and sedation management to prevent GMH-IVH in ventilated preterm infants (< 37 weeks' gestation). We included Cochrane Reviews assessing the following interventions administered within the first week of life: benzodiazepines, paracetamol, opioids, ibuprofen, anesthetics, barbiturates, and antiadrenergics. Primary outcomes were any GMH-IVH (aGMH-IVH), severe IVH (sIVH), all-cause neonatal death (ACND), and major neurodevelopmental disability (MND). We assessed the methodological quality of included reviews using the AMSTAR-2 tool. We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included seven Cochrane Reviews and one Cochrane Review protocol. The reviews on clonidine and paracetamol did not include randomized controlled trials (RCTs) matching our inclusion criteria. We included 40 RCTs (3791 infants) from reviews on paracetamol for patent ductus arteriosus (3), midazolam (3), phenobarbital (9), opioids (20), and ibuprofen (5). The quality of the included reviews was high. The certainty of the evidence was moderate to very low, because of serious imprecision and study limitations. Germinal matrix hemorrhage-intraventricular hemorrhage (any grade) Compared to placebo or no intervention, the evidence is very uncertain about the effects of paracetamol on aGMH-IVH (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.38 to 2.07; 2 RCTs, 82 infants; very low-certainty evidence); midazolam may result in little to no difference in the incidence of aGMH-IVH (RR 1.68, 95% CI 0.87 to 3.24; 3 RCTs, 122 infants; low-certainty evidence); the evidence is very uncertain about the effect of phenobarbital on aGMH-IVH (RR 0.99, 95% CI 0.83 to 1.19; 9 RCTs, 732 infants; very low-certainty evidence); opioids may result in little to no difference in aGMH-IVH (RR 0.85, 95% CI 0.65 to 1.12; 7 RCTs, 469 infants; low-certainty evidence); ibuprofen likely results in little to no difference in aGMH-IVH (RR 0.99, 95% CI 0.81 to 1.21; 4 RCTs, 759 infants; moderate-certainty evidence). Compared to ibuprofen, the evidence is very uncertain about the effects of paracetamol on aGMH-IVH (RR 1.17, 95% CI 0.31 to 4.34; 1 RCT, 30 infants; very low-certainty evidence). Compared to midazolam, morphine may result in a reduction in aGMH-IVH (RR 0.28, 95% CI 0.09 to 0.87; 1 RCT, 46 infants; low-certainty evidence). Compared to diamorphine, the evidence is very uncertain about the effect of morphine on aGMH-IVH (RR 0.65, 95% CI 0.40 to 1.07; 1 RCT, 88 infants; very low-certainty evidence). Severe intraventricular hemorrhage (grade 3 to 4) Compared to placebo or no intervention, the evidence is very uncertain about the effect of paracetamol on sIVH (RR 1.80, 95% CI 0.43 to 7.49; 2 RCTs, 82 infants; very low-certainty evidence) and of phenobarbital (grade 3 to 4) (RR 0.91, 95% CI 0.66 to 1.25; 9 RCTs, 732 infants; very low-certainty evidence); opioids may result in little to no difference in sIVH (grade 3 to 4) (RR 0.98, 95% CI 0.71 to 1.34; 6 RCTs, 1299 infants; low-certainty evidence); ibuprofen may result in little to no difference in sIVH (grade 3 to 4) (RR 0.82, 95% CI 0.54 to 1.26; 4 RCTs, 747 infants; low-certainty evidence). No studies on midazolam reported this outcome. Compared to ibuprofen, the evidence is very uncertain about the effects of paracetamol on sIVH (RR 2.65, 95% CI 0.12 to 60.21; 1 RCT, 30 infants; very low-certainty evidence). Compared to midazolam, the evidence is very uncertain about the effect of morphine on sIVH (grade 3 to 4) (RR 0.08, 95% CI 0.00 to 1.43; 1 RCT, 46 infants; very low-certainty evidence). Compared to fentanyl, the evidence is very uncertain about the effect of morphine on sIVH (grade 3 to 4) (RR 0.59, 95% CI 0.18 to 1.95; 1 RCT, 163 infants; very low-certainty evidence). All-cause neonatal death Compared to placebo or no intervention, the evidence is very uncertain about the effect of phenobarbital on ACND (RR 0.94, 95% CI 0.51 to 1.72; 3 RCTs, 203 infants; very low-certainty evidence); opioids likely result in little to no difference in ACND (RR 1.12, 95% CI 0.80 to 1.55; 5 RCTs, 1189 infants; moderate-certainty evidence); the evidence is very uncertain about the effect of ibuprofen on ACND (RR 1.00, 95% CI 0.38 to 2.64; 2 RCTs, 112 infants; very low-certainty evidence). Compared to midazolam, the evidence is very uncertain about the effect of morphine on ACND (RR 0.31, 95% CI 0.01 to 7.16; 1 RCT, 46 infants; very low-certainty evidence). Compared to diamorphine, the evidence is very uncertain about the effect of morphine on ACND (RR 1.17, 95% CI 0.43 to 3.19; 1 RCT, 88 infants; very low-certainty evidence). Major neurodevelopmental disability Compared to placebo, the evidence is very uncertain about the effect of opioids on MND at 18 to 24 months (RR 2.00, 95% CI 0.39 to 10.29; 1 RCT, 78 infants; very low-certainty evidence) and at five to six years (RR 1.6, 95% CI 0.56 to 4.56; 1 RCT, 95 infants; very low-certainty evidence). No studies on other drugs reported this outcome.
AUTHORS' CONCLUSIONS
None of the reported studies had an impact on aGMH-IVH, sIVH, ACND, or MND. The certainty of the evidence ranged from moderate to very low. Large RCTs of rigorous methodology are needed to achieve an optimal information size to assess the effects of pharmacological interventions for pain and sedation management for the prevention of GMH-IVH and mortality in preterm infants. Studies might compare interventions against either placebo or other drugs. Reporting of the outcome data should include the assessment of GMH-IVH and long-term neurodevelopment.
Topics: Infant, Newborn; Female; Humans; Ibuprofen; Acetaminophen; Midazolam; Analgesics, Opioid; Respiration, Artificial; Heroin; Perinatal Death; Systematic Reviews as Topic; Infant, Premature; Pain; Cerebral Hemorrhage; Phenobarbital
PubMed: 37565681
DOI: 10.1002/14651858.CD012706.pub2 -
Respiratory Medicine and Research Jun 2024This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in preventing bronchopulmonary dysplasia (BPD) for premature infants.
METHOD
Electronic databases, including PubMed, EMBASE, Web of science, Scopus, and Cochrane library, were searched from databases inception to January 2022 for eligible randomized controlled trials. Clinical outcomes such as BPD, mortality, BPD or death, adverse events, and neurodevelopmental outcomes were assessed.
RESULTS
Overall, budesonide was significantly associated with a reduction in BPD at 36 weeks' postmenstrual age (RR 0.48; 95 % CI [0.38, 0.62]) and patent ductus arteriosus (PDA) (RR 0.75; 95 % CI [0.63, 0.89]) compared with control treatments. Early longer duration inhalation of budesonide alone was associated with a lower risk of BPD at 36 weeks' postmenstrual age and PDA compared with controls. Early shorter duration intratracheal instillation of budesonide with surfactant as vehicle was associated with a lower risk of BPD at 36 weeks' postmenstrual age and all-cause mortality compared with surfactant. There was no statistically significant difference between budesonide and control groups regarding neurodevelopmental impairment. Beclomethasone and fluticasone propionate did not show any superior or inferior effect on clinical outcomes compared to control treatments.
CONCLUSION
These findings suggest that budesonide, especially intratracheal instillation of budesonide using surfactant as a vehicle, is a safe and effective option in preventing BPD for preterm infants. More well-design large-scale trials with long-term follow-ups are necessary to verify the present findings.
Topics: Humans; Bronchopulmonary Dysplasia; Administration, Inhalation; Infant, Newborn; Infant, Premature; Budesonide; Beclomethasone; Fluticasone; Treatment Outcome; Adrenal Cortex Hormones; Randomized Controlled Trials as Topic; Ductus Arteriosus, Patent; Female; Male; Pulmonary Surfactants
PubMed: 38744231
DOI: 10.1016/j.resmer.2024.101096 -
Frontiers in Pharmacology 2023The effect of inhaled nitric oxide (iNO) in neonates >34 weeks on improving respiration is well documented. However, the efficacy of iNO in preterm infants ≤34 weeks... (Review)
Review
The effect of inhaled nitric oxide (iNO) in neonates >34 weeks on improving respiration is well documented. However, the efficacy of iNO in preterm infants ≤34 weeks remains controversial. The main purpose of this review is to assess the effectiveness and safety of iNO treatment in preterm infants ≤34 weeks. We systematically searched PubMed, Embase and Cochrane Libraries from their inception to 1 June 2023. We also reviewed the reference lists of retrieved studies. Our study involved randomized controlled trials on preterm infants ≤34 weeks, especially those receiving iNO treatment, and mainly assessed outcomes such as bronchopulmonary dysplasia (BPD) and mortality. Two authors independently reviewed these trials, extracted data, and evaluated study biases. Disagreements were resolved by consensus. We used the GRADE method to assess evidence quality. Our research included a total of 17 studies involving 4,080 neonates and 7 follow-up studies. The synthesis of results showed that in neonates, iNO treatment reduced the incidence of BPD (RR: 0.92; 95% CI: 0.86-0.98). It also decreased the composite outcome of death or BPD (RR: 0.94; 95% CI: 0.90-0.98), without increasing the risk of short-term (such as intraventricular hemorrhage, periventricular leukomalacia) and long-term neurological outcomes (including Bayley mental developmental index <70, cerebral palsy and neurodevelopmental impairment). Furthermore, iNO did not significantly affect other neonatal complications like sepsis, pulmonary hemorrhage, necrotizing enterocolitis, and symptomatic patent ductus arteriosus. Subgroup analysis revealed that iNO significantly reduced BPD incidence in neonates at 36 weeks under specific intervention conditions, including age less than 3 days, birth weight over 1,000 g, iNO dose of 10 ppm or higher, or treatment duration exceeding 7 days ( < 0.05). Inhaled NO reduced the incidence of BPD in neonates at 36 weeks of gestation, and the effect of the treatment depended on neonatal age, birth weight, duration and dose of iNO. Therefore, iNO can be considered a promising treatment for the potential prevention of BPD in premature infants. More data, however, would be needed to support nitric oxide registration in this specific patient population, to minimize its off-label use.
PubMed: 38273818
DOI: 10.3389/fphar.2023.1268795