RESUMEN
BACKGROUND: Neonatal Escherichia coli (E coli) meningitis results in significant morbidity and mortality. We present a case of a premature infant with extensive central nervous system (CNS) injury from recurrent E coli infection and the non-traditional methods necessary to identify and clear the infection. CASE PRESENTATION: The infant was transferred to our institution's pediatric intensive care unit (PICU) after recurrence of E coli CNS infection requiring neurosurgical intervention. He had been treated for early onset sepsis (EOS) with ampicillin and gentamicin for 10 days followed by rapid development of ampicillin-resistant E coli septic shock and meningitis after discontinuation of antibiotics. Sterility of the CNS was not confirmed at the end of 21 days of cefepime therapy and was subsequently followed by recurrent ampicillin-resistant E coli septic shock and CNS infection. Despite 6 weeks of appropriate therapy with sterility of CSF by traditional methods, he suffered from intractable seizures with worsening hydrocephalus. Transferred to our institution, he underwent endoscopic 3rd ventriculostomy with cyst fenestration revealing purulent fluid and significant pleocytosis. An additional 3 weeks of systemic and intraventricular antibiotics with cefepime and tobramycin were given but a significant CNS neutrophil-predominant pleocytosis persisted (average of â¼ 21,000 cells/mm3). Repeated gram stains, cultures, polymerase chain reaction (PCR) testing, and metagenomic next generation sequencing (NGS) testing of CSF were negative for pathogens but acridine orange stain (AO) revealed numerous intact rod-shaped bacteria. After the addition of ciprofloxacin, sterility and resolution of CSF pleocytosis was finally achieved. CONCLUSION: Neonatal E coli meningitis is a well-known entity but unlike other bacterial infections, it has not proven amenable to shorter, more narrow-spectrum antibiotic courses or limiting invasive procedures such as lumbar punctures. Further, microbiologic techniques to determine CSF sterility suffer from poorly understood limitations leading to premature discontinuation of antibiotics risking further neurologic damage in vulnerable hosts.
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Antibacterianos , Meningitis por Escherichia coli , Humanos , Recién Nacido , Antibacterianos/uso terapéutico , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/diagnóstico , Enfermedades del Prematuro/microbiología , Meningitis por Escherichia coli/tratamiento farmacológicoRESUMEN
BACKGROUND: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. INTERVENTIONS: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo. MAIN OUTCOME MEASURES: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author). RESULTS: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment. CONCLUSIONS: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.
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Cardiotónicos , Recien Nacido Prematuro , Metaanálisis en Red , Vasoconstrictores , Humanos , Recién Nacido , Cardiotónicos/uso terapéutico , Vasoconstrictores/uso terapéutico , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Dobutamina/uso terapéutico , Dobutamina/administración & dosificaciónRESUMEN
BACKGROUND: Chronic lung disease (CLD) occurs frequently in preterm infants and is associated with respiratory morbidity. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume, and decreased airway resistance, have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators are widely considered to have a role in the prevention and treatment of CLD, but there remains uncertainty as to whether they improve clinical outcomes. This is an update of the 2016 Cochrane review. OBJECTIVES: To determine the effect of inhaled bronchodilators given as prophylaxis or as treatment for chronic lung disease (CLD) on mortality and other complications of preterm birth in infants at risk for or identified as having CLD. SEARCH METHODS: An Information Specialist searched CENTRAL, MEDLINE, Embase, CINAHL and three trials registers from 2016 to May 2023. In addition, the review authors undertook reference checking, citation searching and contact with trial authors to identify additional studies. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials involving preterm infants less than 32 weeks old that compared bronchodilators to no intervention or placebo. CLD was defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age. Initiation of bronchodilator therapy for the prevention of CLD had to occur within two weeks of birth. Treatment of infants with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation or metered dose inhaler. The comparator was no intervention or placebo. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Critical outcomes included: mortality within the trial period; CLD (defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age); adverse effects of bronchodilators, including hypokalaemia (low potassium levels in the blood), tachycardia, cardiac arrhythmia, tremor, hypertension and hyperglycaemia (high blood sugar); and pneumothorax. We used the GRADE approach to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included two randomised controlled trials in this review update. Only one trial provided useable outcome data. This trial was conducted in six neonatal intensive care units in France and Portugal, and involved 173 participants with a gestational age of less than 31 weeks. The infants in the intervention group received salbutamol for the prevention of CLD. The evidence suggests that salbutamol may result in little to no difference in mortality (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.50 to 2.31; risk difference (RD) 0.01, 95% CI -0.09 to 0.11; low-certainty evidence) or CLD at 28 days (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17; low-certainty evidence), when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax. The one trial with usable data reported that there were no relevant differences between groups, without providing the number of events (very low-certainty evidence). Investigators in this study did not report if side effects occurred. We found no eligible trials that evaluated the use of bronchodilator therapy for the treatment of infants with CLD. We identified no ongoing studies. AUTHORS' CONCLUSIONS: Low-certainty evidence from one trial showed that inhaled bronchodilator prophylaxis may result in little or no difference in the incidence of mortality or CLD in preterm infants, when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax, and neither included study reported on the incidence of serious adverse effects. We identified no trials that studied the use of bronchodilator therapy for the treatment of CLD. Additional clinical trials are necessary to assess the role of bronchodilator agents in the prophylaxis or treatment of CLD. Researchers studying the effects of inhaled bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes.
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Enfermedades del Prematuro , Enfermedades Pulmonares , Neumotórax , Nacimiento Prematuro , Lactante , Femenino , Recién Nacido , Humanos , Recien Nacido Prematuro , Broncodilatadores/uso terapéutico , Enfermedad Crónica , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/prevención & control , Albuterol/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/prevención & control , OxígenoRESUMEN
OBJECTIVE: To assess the long-term neurodevelopmental impact of doxapram for treating apnoea of prematurity. DESIGN: Secondary analysis of the French national cohort study EPIPAGE-2. Recruitment took place in 2011. A standardised neurodevelopmental assessment was performed at age 5-6 years. A 2:1 propensity score matching was used to control for the non-randomised assignment of doxapram treatment. SETTING: Population-based cohort study. PATIENTS: All children born before 32 weeks' gestation alive at age 5-6 years. INTERVENTIONS: Blind and standardised assessment by trained neuropsychologists and paediatricians at age 5-6 years. MAIN OUTCOME MEASURES: Neurodevelopmental outcomes at age 5-6 years assessed by trained paediatricians and neuropsychologists: cerebral palsy, developmental coordination disorders, IQ and behavioural difficulties. A composite criterion for overall neurodevelopmental disabilities was built. RESULTS: The population consisted of 2950 children; 275 (8.6%) received doxapram. Median (IQR) gestational age was 29.4 (27.6-30.9) weeks. At age 5-6 years, complete neurodevelopmental assessment was available for 60.3% (1780 of 2950) of children and partial assessment for 10.6% (314 of 2950). In the initial sample, children receiving doxapram had evidence of greater clinical severity than those not treated. Doxapram treatment was associated with overall neurodevelopmental disabilities of any severity (OR 1.43, 95% CI 1.07 to 1.92, p=0.02). Eight hundred and twenty-one children were included in the 2:1 matched sample. In this sample, perinatal characteristics of both groups were similar and doxapram treatment was not associated with overall neurodevelopmental disabilities (OR 1.09, 95% CI 0.76 to 1.57, p=0.63). CONCLUSIONS: In children born before 32 weeks' gestation, doxapram treatment for apnoea of prematurity was not associated with neurodevelopmental disabilities.
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Apnea , Doxapram , Enfermedades del Prematuro , Recien Nacido Prematuro , Trastornos del Neurodesarrollo , Humanos , Preescolar , Femenino , Masculino , Recién Nacido , Enfermedades del Prematuro/tratamiento farmacológico , Doxapram/uso terapéutico , Niño , Apnea/tratamiento farmacológico , Trastornos del Neurodesarrollo/epidemiología , Edad Gestacional , Parálisis Cerebral/tratamiento farmacológico , Discapacidades del Desarrollo , Francia , Estudios de CohortesRESUMEN
OBJECTIVES: To assess the presence and timing of furosemide diuretic tolerance in infants with bronchopulmonary dysplasia (BPD), and to determine if tolerance is modified by thiazide co-administration. STUDY DESIGN: We performed a retrospective cohort study among infants born very preterm with BPD exposed to repeated-dose furosemide for 72 hours, measuring net fluid balance (total intake minus total output) as a surrogate of diuresis in the 3 days before and after exposure. The primary comparison was the difference in fluid balance between the first and third 24 hours of furosemide exposure. We fit a general linear model for within-subject repeated measures of fluid balance over time, with thiazide co-administration as an interaction variable. Secondary analyses included an evaluation of weight trajectories over time. RESULTS: In 83 infants, median fluid balance ranged between + 43.6 and + 52.7 ml/kg/d in the 3 days prior to furosemide exposure. Fluid balance decreased to a median of + 29.1 ml/kg/d in the first 24 hours after furosemide, but then increased to +47.5 ml/kg/d by the third 24-hour interval, consistent with tolerance (P < .001). Thiazides did not modify the change in fluid balance during furosemide exposure for any time-period. Weight decreased significantly in the first 24 hours after furosemide and increased thereafter (P < .001). CONCLUSIONS: The net fluid balance response to furosemide decreases rapidly during repeated-dose exposures in infants with BPD, consistent with diuretic tolerance. Clinicians should consider this finding in the context of an infant's therapeutic goals. Further research efforts to identify safe and effective furosemide dosage strategies are needed.
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Displasia Broncopulmonar , Enfermedades del Prematuro , Recién Nacido , Humanos , Diuréticos/uso terapéutico , Furosemida , Displasia Broncopulmonar/tratamiento farmacológico , Recien Nacido Extremadamente Prematuro , Estudios Retrospectivos , Enfermedades del Prematuro/tratamiento farmacológico , Tiazidas/uso terapéuticoRESUMEN
OBJECTIVE: To assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF). METHODS: In this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18-24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO. RESULTS: Of the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18-24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12). CONCLUSIONS: In preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18-24 months CA.
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Enfermedades del Prematuro , Trastornos del Neurodesarrollo , Óxido Nítrico , Insuficiencia Respiratoria , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Administración por Inhalación , Canadá/epidemiología , Estudios de Cohortes , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Óxido Nítrico/administración & dosificación , Estudios Retrospectivos , Resultado del Tratamiento , Trastornos del Neurodesarrollo/epidemiologíaRESUMEN
OBJECTIVE: To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA). DESIGN: Secondary analysis of a randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestational age (GA), ventilator-dependent in the second week of postnatal life. INTERVENTION: Infants were randomly assigned to systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: The composite of death or neurodevelopmental impairment (NDI) at 2 years' CA and its components. Candidate effect modifiers (GA, small for GA, respiratory index, sex, multiple births, risk of moderate/severe bronchopulmonary dysplasia or death) were analysed using regression models with interaction terms and subpopulation treatment effect pattern plots. RESULTS: The composite outcome was available in 356 (96.0%) of 371 patients (one consent withdrawn). For this outcome, treatment effect heterogeneity was seen across GA subgroups (<27 weeks: hydrocortisone (n=141) vs placebo (n=156), 54.6% vs 66.2%; OR 0.61 (95% CI 0.38 to 0.98); ≥27 weeks: hydrocortisone (n=30) vs placebo (n=31), 66.7% vs 45.2%; OR 2.43 (95% CI 0.86 to 6.85); p=0.02 for interaction). This effect was also found for the component death (<27 weeks: 20.1% vs 32.1%; OR 0.53 (95% CI 0.32 to 0.90); ≥27 weeks: 28.1% vs 16.1%; OR 2.04 (95% CI 0.60 to 6.95); p=0.049 for interaction) but not for the component NDI. No differential treatment effects were observed across other subgroups. CONCLUSION: This secondary analysis suggests that in infants <27 weeks' GA, systemic hydrocortisone may improve the outcome death or NDI, mainly driven by its component death. There was insufficient evidence for other selected candidate effect modifiers.
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Displasia Broncopulmonar , Enfermedades del Prematuro , Lactante , Recién Nacido , Humanos , Hidrocortisona , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Glucocorticoides/uso terapéutico , Enfermedades del Prematuro/tratamiento farmacológicoRESUMEN
Bronchopulmonary dysplasia (BPD) is a common, severe chronic respiratory disease that affects very preterm infants. In utero and postnatal exposure to proinflammatory stimuli contribute to the pathophysiology of BPD. Corticosteroids, because of their potent anti-inflammatory properties, may decrease respiratory morbidity and reduce the risk of BPD in very preterm infants. However, these medications can have adverse effects on the developing brain and other organ systems. This review examines current evidence on the risks and benefits of postnatal corticosteroids used to prevent BPD in preterm infants.
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Displasia Broncopulmonar , Enfermedades del Prematuro , Humanos , Lactante , Recién Nacido , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Displasia Broncopulmonar/prevención & control , Displasia Broncopulmonar/tratamiento farmacológico , Dexametasona , Glucocorticoides , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/prevención & controlRESUMEN
INTRODUCTION/OBJECTIVE: Magnesium sulfate (MgSO 4 ) treatment is widely used for fetal neuroprotection despite the controversy concerning the side effects. There is limited data regarding the impact of various cumulative maternal doses and neonatal serum magnesium (Mg) levels on short-term neonatal morbidity and mortality. We opted to carry out a study to determine the impact of neonatal serum Mg levels on neonatal outcomes. METHOD: We conducted this prospective observational study between 2017 and 2021. Antenatal MgSO 4 was used for neuroprotective purpose only during the study period. Inborn preterm infants delivered between 23 and 31 6/7 weeks of gestation were enrolled consecutively. Babies who underwent advanced resuscitation in the delivery room, inotropic treatment due to hemodynamic instability in the first 7 days of life, >12 hours since the discontinuation of maternal MgSO 4 treatment, severe anemia, and major congenital/chromosomal anomalies were excluded from the study. The subgroup of babies with serum Mg level at the 6th hour of life underwent an analysis. A neonatal Mg concentration of 2.5 mg/dL was used to classify MgSO 4 -exposed patients into 2 groups (<2.5 mg/dL and ≥2.5 mg/dL). Another analysis was performed between babies whose mothers were exposed to MgSO 4 and those not exposed. Finally, the groups' neonatal outcomes were compared. RESULTS: Of the 584 babies, 310 received antenatal MgSO 4 . The birth weights were significantly lower in the MgSO 4 exposed group (1113 ± 361 g vs 1202 ± 388 g, P = 0.005). Antenatal corticosteroid usage and intrauterine growth restriction were also noted to be higher. The MgSO 4 group was more likely to have bronchopulmonary dysplasia, prolonged invasive ventilation, necrotizing enterocolitis, delayed enteral nutrition, and feeding intolerance ( P < 0.05). MgSO 4 treatment was shown as an independent risk factor for feeding intolerance when corrected for confounders (odds ratio 2.13, 95% confidence interval: 1.4-3.1, P = 0.001). Furthermore, serum Mg level significantly correlated with feeding intolerance ( r = 0.21, P = 0.002). CONCLUSION: This study highlighted the effect of MgSO 4 treatment and the potential superiority of serum Mg level as a predictor of immediate neonatal outcomes, particularly delayed enteral nutrition and feeding intolerance. Further studies are warranted to ascertain the optimal serum Mg concentration of preterm infants in early life to provide maximum benefit with minimal side effects.
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Enfermedades del Recién Nacido , Enfermedades del Prematuro , Femenino , Humanos , Recién Nacido , Embarazo , Retardo del Crecimiento Fetal/tratamiento farmacológico , Enfermedades del Recién Nacido/tratamiento farmacológico , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/prevención & control , Enfermedades del Prematuro/inducido químicamente , Sulfato de Magnesio/uso terapéutico , NeuroprotecciónRESUMEN
INTRODUCTION: Reports on the influence of postnatal cytomegalovirus (pCMV) infection in neonatal outcomes of preterm babies vary while guidance on management including screening is lacking. We aim to determine the association between symptomatic pCMV infection and chronic lung disease (CLD) and mortality in preterm infants born less than 32 weeks gestation. METHODS: We used data from the Neonatal Intensive Care Units' (NICUS) population-based prospective data registry of infants in 10 neonatal units in New South Wales and the Australian Capital Territory, Australia. De-identified perinatal and neonatal outcome data for 40,933 infants were examined. We identified 172 infants <32 weeks gestation with symptomatic pCMV infection. Each was matched with one control infant. RESULTS: Infants with symptomatic pCMV infection were 2.7 times more likely to develop CLD (OR 2.7, 95% CI: 1.7-4.5) and spend 25.2 days more in hospital (95% CI: 15.2-35.2). Seventy-five percent (129/172) of infants with symptomatic pCMV were extremely preterm (<28 weeks). The mean age of symptomatic pCMV diagnosis was 62.5 ± 20.5 days or 34.7 ± 3.6 weeks-corrected gestational age. Ganciclovir treatment did not decrease CLD and death. CLD was 5.5 times predictive of death in patients with symptomatic pCMV infection. Symptomatic pCMV infection did not influence mortality nor increase neurologic impairment. CONCLUSION: Symptomatic pCMV is a modifiable factor affecting extreme preterm infants with significant impact on CLD. Prospective study on screening and treatment will help unveil potential benefits in our already at-risk preterm infants.
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Infecciones por Citomegalovirus , Enfermedades del Prematuro , Enfermedades Pulmonares , Femenino , Embarazo , Humanos , Recién Nacido , Recien Nacido Prematuro , Glucocorticoides , Dexametasona/uso terapéutico , Antiinflamatorios/uso terapéutico , Citomegalovirus , Estudios Prospectivos , Estudios de Casos y Controles , Enfermedades del Prematuro/diagnóstico , Enfermedades del Prematuro/epidemiología , Enfermedades del Prematuro/tratamiento farmacológico , Australia/epidemiología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/epidemiologíaAsunto(s)
Estimulantes del Sistema Nervioso Central , Enfermedades del Recién Nacido , Enfermedades del Prematuro , Recién Nacido , Humanos , Cafeína/uso terapéutico , Apnea/tratamiento farmacológico , Recien Nacido Prematuro , Estimulantes del Sistema Nervioso Central/efectos adversos , Enfermedades del Prematuro/tratamiento farmacológicoRESUMEN
Patent ductus arteriosus (PDA) is associated with neonatal morbidities in high-risk preterm infants. Early neonatal treatment by ibuprofen induces the ductus arteriosus (DA) closure in approximatively 60% of infants. Dose escalation of ibuprofen according to postnatal age has been suggested for improving the DA closure rate. The aim of this study was to assess the efficacy and tolerance of an increasing dose regimen of ibuprofen. This single-center retrospective cohort study involved infants hospitalized from 2014 to 2019 in our neonatal unit. Selection criteria were gestational age < 30 weeks, birth weight < 1000 g, and treatment by ibuprofen. Three dose levels were used and consisted of a daily intravenous injection of ibuprofen-tris-hydroxymethyl-aminomethane (ibuprofen-THAM) for three consecutive days: (i) 10 -5 -5 mg/kg before the 70th h of life (H70) (dose level 1), (ii) 14 -7 -7 mg/kg between H70 and H108 (dose level 2), (iii) 18 -9 -9 mg/kg after H108 (dose level 3). The ibuprofen-induced DA closure was compared between ibuprofen schedules, and the Cox proportional-hazard regression was performed to identify factors associated with the ibuprofen efficacy. Tolerance was assessed through renal function, acidosis, and platelet count. One hundred forty-three infants met the inclusion criteria. The ibuprofen-induced DA closure was observed in 67 infants (46.8%). One course of ibuprofen at dose level 1 was more efficient in closing the DA than other schedules (dose level 1, one course (n = 70): 71%, dose level 2 or 3, one course (n = 20): 45%, two-course schedules (n = 53): 15%, p < 0.0001). Independent factors associated with ibuprofen-induced DA closure were a complete antenatal schedule of steroids (p = 0.001), a lower CRIB II score (p = 0.009), and a lower and earlier exposure to ibuprofen (p < 0.0001 and p = 0.002). No severe side effects were observed. Neonatal mortality and morbidities were similar regardless of the infant's response to ibuprofen. Conclusion: Increasing ibuprofen doses with postnatal age failed to reach an efficacy similar to earlier treatment. Although the infant response to ibuprofen was likely to depend on multiple factors, the optimal use of ibuprofen included its early initiation. What is Known: ⢠Ibuprofen is the current first-line treatment for patent ductus arteriosus during the early neonatal period in very preterm infants. ⢠However, the ibuprofen efficacy rapidly declined with postnatal age during the first week of life. A dose escalation of ibuprofen according to postnatal age has been suggested to improve the ibuprofen-induced ductus arteriosus closure. What is New: ⢠The rapid drop of ibuprofen's ability to close hemodynamically significant patent ductus arteriosus persisted beyond the postnatal day 2 despite the dose adjustment arguing for an early initiation to optimize its efficacy. ⢠The early selection of patients who will suffer from patent ductus arteriosus-related morbidities and who will positively respond to ibuprofen is an issue that could determine the future place of ibuprofen in the patent ductus arteriosus management.
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Conducto Arterioso Permeable , Ibuprofeno , Enfermedades del Prematuro , Femenino , Humanos , Recién Nacido , Embarazo , Conducto Arterioso Permeable/tratamiento farmacológico , Ibuprofeno/administración & dosificación , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/inducido químicamente , Recién Nacido de muy Bajo Peso , Estudios RetrospectivosRESUMEN
Importance: High-dose docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, may affect the risk of bronchopulmonary dysplasia (BPD). However, high-level summative evidence supporting such clinical association in very preterm infants is lacking. Objective: To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks' gestation. Data Sources: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions. Study Selection: Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death. Data Extraction and Synthesis: Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses. Main Outcomes and Measures: Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks' postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death. Results: Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I2 = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I2 = 0%). Conclusions and Relevance: Results of this study showed that enteral supplementation with high-dose DHA in the neonatal period was not associated overall with BPD, but an inverse association was found in the included RCTs that used a more stringent BPD definition. These findings suggest that high-dose DHA supplementation should not be recommended to prevent BPD in very preterm infants.
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Displasia Broncopulmonar , Enfermedades del Prematuro , Recién Nacido , Lactante , Masculino , Femenino , Humanos , Adulto , Ácidos Docosahexaenoicos/uso terapéutico , Displasia Broncopulmonar/epidemiología , Displasia Broncopulmonar/prevención & control , Recien Nacido Prematuro , Edad Gestacional , Enfermedades del Prematuro/tratamiento farmacológico , Retardo del Crecimiento Fetal/tratamiento farmacológico , Suplementos DietéticosRESUMEN
BACKGROUND: The patent ductus arteriosus (PDA) treatment in very preterm infants is controversial. This study focused on preterm infants born at 28-32 weeks of gestation and analyzed the association between various PDA treatments and clinical outcomes. METHODS: We conducted a retrospective cohort study of infants born at 28-32 weeks of gestation between 2016 and 2019 at 22 hospitals in the Taiwan Premature Infant Follow-up Network. We categorized the infants into four groups according to treatment strategies: medication, primary surgery, medication plus surgery, or conservative treatment. RESULTS: A total of 1244 infants presented with PDA, and 761 (61.1%) were treated. Medication was the predominant treatment (50.0%), followed by conservative treatment (38.9%), medication plus surgery (7.6%), and primary surgery (3.5%). The risk of mortality was not reduced in the active treatment group compared to the conservative treatment group. There was a higher prevalence of severe intraventricular hemorrhage, necrotizing enterocolitis (NEC), and any degree of bronchopulmonary dysplasia (BPD) in both the primary surgery and medication plus surgery groups than in the conservative treatment group. After adjustment, both the primary surgery and medication plus surgery groups still had higher odds ratios for the occurrence of NEC and any degree of BPD. CONCLUSIONS: Compared with active PDA treatment, conservative treatment for PDA did not increase the risk of mortality and morbidity in very preterm infants born at 28-32 weeks of gestation. The risks and benefits of surgery (PDA ligation) in these infants must be considered cautiously.
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Displasia Broncopulmonar , Conducto Arterioso Permeable , Enterocolitis Necrotizante , Enfermedades del Prematuro , Lactante , Recién Nacido , Humanos , Recien Nacido Prematuro , Conducto Arterioso Permeable/terapia , Estudios Retrospectivos , Taiwán/epidemiología , Enfermedades del Prematuro/terapia , Enfermedades del Prematuro/tratamiento farmacológico , Displasia Broncopulmonar/epidemiología , Displasia Broncopulmonar/terapiaAsunto(s)
Estimulantes del Sistema Nervioso Central , Enfermedades del Recién Nacido , Enfermedades del Prematuro , Recién Nacido , Humanos , Cafeína/uso terapéutico , Apnea/tratamiento farmacológico , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéuticoRESUMEN
BACKGROUND: Inhaled nitric oxide (iNO) has been used as a rescue treatment for preterm infants with hypoxemic respiratory failure (HRF). However, its effectiveness remains debatable. Thus, in this study, we aimed to examine the impact of iNO therapy on HRF in extremely preterm infants. METHODS: A retrospective observational study was performed. Extremely preterm infants admitted to our neonatal intensive care unit who received iNO therapy later in their postnatal life were included. The oxygen saturation index (OSI) was used as an index of the severity of respiratory failure. RESULTS: In total, 30 extremely preterm infants were included in this study. Oxygenation was enhanced after the administration of iNO in infants with HRF. The OSI decreased by more than 20% in 12 patients (40%, positive responder) and did not decrease in 17 patients (57%, negative responder) within the first 6 h of treatment. The iNO initiation day was the significant independent factor associated with a positive response to iNO therapy in extremely preterm infants with HRF. CONCLUSIONS: iNO therapy was effective in enhancing oxygenation in extremely preterm infants with HRF. Earlier use of iNO was the significant factor associated with a positive therapeutic response to iNO, implying that iNO may be more effective in pulmonary vessels which are less damaged by shorter-term mechanical ventilation.
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Enfermedades del Prematuro , Insuficiencia Respiratoria , Recién Nacido , Humanos , Óxido Nítrico/uso terapéutico , Recien Nacido Extremadamente Prematuro , Insuficiencia Respiratoria/tratamiento farmacológico , Enfermedades del Prematuro/tratamiento farmacológico , Respiración Artificial , Administración por InhalaciónRESUMEN
OBJECTIVE: Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week. DESIGN: Randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. INTERVENTION: Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: Data on extubation, ventilator settings, glucose levels, and blood pressure were recorded daily and analysed during the first 7 days of treatment using linear mixed-effects models. RESULTS: Infants in the hydrocortisone group (24.3%) failed extubation less often compared with placebo (38.6%, crude risk difference: -14.3% (95% CI: -23.4% to -4.8%)). The estimated difference in daily rate of change between hydrocortisone and placebo was -0.42 cmH2O (95% CI: -0.48 to -0.36) for mean airway pressure, -0.02 (95% CI: -0.02 to -0.01) for fraction of inspired oxygen, -0.37 (95% CI: -0.44 to -0.30) for respiratory index, 0.14 mmol/L (95% CI: 0.08 to 0.21) for blood glucose levels and 0.83 mm Hg (95% CI: 0.58 to 1.09) for mean blood pressure. CONCLUSIONS: Systemic hydrocortisone initiated between 7 and 14 days after birth in ventilated preterm infants improves pulmonary condition, thereby facilitating weaning and extubation from invasive ventilation. The effects of hydrocortisone on blood glucose levels and blood pressure were mild and of limited clinical relevance. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR2768; https://www.trialregister.nl/trial/2640) and European Union Clinical Trials Register (EudraCT, 2010-023777-19).
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Enfermedades del Prematuro , Enfermedades Pulmonares , Lactante , Recién Nacido , Humanos , Hidrocortisona/efectos adversos , Recien Nacido Prematuro , Glucemia , Recién Nacido de muy Bajo Peso , Enfermedades del Prematuro/tratamiento farmacológicoRESUMEN
Introduction: Recent reports have described the increasing predominance of Gram-negative organisms among invasive bacterial infections affecting preterm infants. This changing pattern of infections is concerning due to the spread of antibiotic resistance among Gram-negatives. Method: We conducted a single-centre, retrospective cohort study involving very-low-birthweight (VLBW) (<1500 grams) infants born <32 weeks gestation, with culture-proven infections (blood, urine, cerebrospinal fluid [CSF]) in the neonatal intensive care unit from 1 January 2005 to 31 October 2017. Results: A total of 278 out of 2431 (11.4%) VLBW infants born <32 weeks gestation developed 334 infections, i.e. 52 (15.6%) early-onset infections (EOIs) and 282 (84.4%) late-onset infections (LOIs). The overall incidence decreased from 247 to 68 infections per 1000 infants over the study period, corresponding to reductions in LOI (211 to 62 infections per 1000 infants). A total of 378 bacteria were isolated, i.e. Gram-negatives accounted for 70.9% (45 of 59 [76.3%] EOI; 223 of 319 [69.9%] LOI). Specific resistant organisms were noted, i.e. Methicillin-resistant Staphylococcus aureus (8 of 21 S. aureus infections [38.1%]); Cephalosporin-resistant Klebsiella (18 of 62 isolates [29.0%]) and multidrug-resistant [MDR] Acinetobacter (10 of 27 isolates [37.0%]). MDR organisms accounted for 85 of 195 (43.6%) Gram-negative infections from the bloodstream and CSF. Based on laboratory susceptibility testing, only 63.5% and 49.3% of infecting bacteria isolated in blood were susceptible to empiric antibiotic regimens used for suspected EOI and LOI, respectively. Conclusion: Gram-negative bacteria are the predominant causative organisms for EOI and LOI and are frequently MDR. Understanding the pattern of antimicrobial resistance is important in providing appropriate empiric coverage for neonatal infections.
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Antibacterianos , Infecciones por Bacterias Gramnegativas , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Humanos , Singapur/epidemiología , Recién Nacido , Estudios Retrospectivos , Femenino , Masculino , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Incidencia , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Recien Nacido Prematuro , Farmacorresistencia Bacteriana , Enfermedades del Prematuro/epidemiología , Enfermedades del Prematuro/microbiología , Enfermedades del Prematuro/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Methylxanthine, including caffeine citrate and aminophylline, is the most common pharmacologic treatment for apnea of prematurity. However, due to the lack of high-quality evidence, there are no clear recommendations or guidelines on how to choose between caffeine and aminophylline. OBJECTIVE: This meta-analysis aimed to assess the comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity, and provide reliable evidence for clinical medication in the treatment for apnea of prematurity. METHODS: PubMed, Scopus, Embase, EBSCO, Web of Science, and Cochrane databases were systematically searched from May 1975 to June 2022. RESULTS: Ten studies including a total of 923 preterm infants were evaluated. Our results showed that there was no significant difference in the effective rate of 1-3days between caffeine and aminophylline (OR 1.05, 95%CI: 0.40-2.74, P = 0.914). However, for side effects such as tachycardia (OR 0.22, 95%CI: 0.13-0.37, P<0.001) and feeding intolerance (OR 0.40, 95%CI: 0.23-0.70, P = 0.001), the incidence rate was lower in the caffeine group compared with the aminophylline group. No significant difference was found in hyperglycemia (OR 0.45, 95%CI: 0.19-1.05, P = 0.064). CONCLUSION: This meta-analysis reveals that caffeine citrate and aminophylline have similar therapeutic effectiveness on respiratory function, but caffeine has fewer side effects and should be considered first for treatment.