Rescue Paracetamol in Postoperative Pain Management in Extremely Low Birth Weight Neonates Following Abdominal Surgery: A Single Unit Retrospective Study.

Background: Intravenous paracetamol added to morphine reduces postoperative morphine consumption in (near)term neonates. However, there are only sparse data on intravenous paracetamol as multimodal strategy in extremely low birth weight (ELBW) neonates. Objectives: This study aims to assess the effects of rescue intravenous paracetamol on postoperative pain management (≤48 h postoperatively) in relation to both analgesic efficacy (validated pain assessment, drug consumption, adequate rescue medication) and safety (hypotension and bradycardia). This rescue practice was part of a standardized pain management approach in a single neonatal intensive care unit (NICU). Methods: A single-center retrospective observational study included 20 ELBW neonates, who underwent major abdominal surgery. The primary endpoints of the postoperative study period were pain intensity, over-sedation, time to first rescue analgesic dose, and the effect of paracetamol on opiate consumption. Secondary endpoints were safety parameters (hypotension, bradycardia). And as tertiary endpoints, the determinants of long-term outcome were evaluated (i.e., duration of mechanical ventilation, intraventricular hemorrhage - IVH, periventricular leukomalacia - PVL, postnatal growth restriction, stage of chronic lung disease - CLD or neurodevelopmental outcome according to Bayley-II Scales of Infant Development at 18-24 months). Results: All neonates received continuous opioids (sufentanil or morphine) and 13/20 also intravenous paracetamol as rescue pain medication during a 48-h postoperative period. Although opioid consumption was equal in the non-paracetamol and the paracetamol group over 48 h, the non-paracetamol group was characterized by oversedation (COMFORTneo < 9), a higher incidence of severe hypotension, and younger postnatal age (p < 0.05). All long-term outcome findings were similar between both groups. Conclusions: Our study focused on postoperative pain management in ELBW neonates, and showed that intravenous paracetamol seems to be safe. Prospective validation of dosage regimens of analgesic drugs is needed to achieve efficacy goals.

Early inhaled budesonide in extremely preterm infants decreases long-term respiratory morbidity.

BACKGROUND: There is no strict correlation between early bronchopulmonary dysplasia and long-term respiratory disease. Early inhaled corticosteroids seem to reduce the incidence of bronchopulmonary dysplasia, but the long-term outcome remains unknown. RESEARCH QUESTION: The aim of this study was to evaluate the effect of early inhaled corticosteroids on chronic respiratory morbidity. METHODS: Fifty-nine survivors from the Prague cohort included in Neonatal European Study of Inhaled Steroids underwent further follow-up comprising of respiratory morbidity monitoring during the first 2 years of life followed by objective lung function testing performed at the age of 5.9 years (range 5-7 years). Both outcomes were pursued and finalized before the unblinding of budesonide subgroups. RESULTS: Fifty randomized (budesonide vs placebo group, 56% vs 44%) survivors were included in the study. Spirometry was successfully performed in 48 children. No statistically significant differences were found in the lung function test (forced expiratory flow [FEF] - FEF75 , FEF50, FEF25 , and FEF25-75; FEV1 , forced vital capacity [FVC], FEV1 /FVC) although mild trend to the improvement of expiratory flow pattern was observed in the budesonide group (median z-score of FEV1 /FVC -0.376 vs -0.983, P = .13; median z-score of FEF25-75 -1.004 vs -1.458, P = .13; median z-score of FEF75 -0.527 vs -0.996, P = .17). Children assigned to budesonide had a significantly lower rate of symptoms of chronic lung disease (34.6% vs 68.2%; P = .04) than children assigned to placebo. INTERPRETATION: Our study suggests that early inhaled budesonide was associated with the trend to the improvement of functional lung parameters and with a lower rate of symptoms of chronic lung disease within the first 2 years of life.

Post-natal growth of 157 children born as extremely premature neonates.

AIM: With increasing survival rate of extremely premature neonates, their long-term outcomes including growth and risk factors for later disorders need to be considered. We prospectively evaluated anthropometric parameters in children born as extremely premature neonates. METHODS: Anthropometric parameters were measured at the ages of 2 and 5 years in 72 extremely premature children born between the 22nd and 25 + 6th weeks of gestation (group I) and 85 children born between the 26th and 27 + 6th weeks of gestation (group II). RESULTS: Although catch-up in the postnatal growth was observed in both groups of children, resulting in growth improvement, the height of the extremely premature children at the ages of 2 and 5 years remains lower (P < 0.01) compared with the control population. A decline in head growth was observed in both groups between the ages of 2 and 5 years, resulting in decrease of standard deviation score (SDS) for head circumference (HC) in comparison with that of the control population, accompanied by an increased number of children with microcephaly, defined as HC < -2 SD. At the age of five, microcephaly was found in 18% of children from group I and 11.7% of children from group II. At the age of 5 years, the waist and hip circumferences and ten skinfolds were not different between both groups of children. CONCLUSION: Long-term follow-up of extremely premature neonates is important not only to establish their growth patterns but also for risk factors assessment including adiposity for later development of adult-onset diseases.

Cytosine-Adenosine (CA)n repeats polymorphism in IGF-I gene and early growth in infants born appropriate and small for gestational age.

BACKGROUND: IGF-I gene polymorphisms might alter IGF-I level resulting in decreased foetal and postnatal growth and increased risk for diabetes mellitus type 2 and cardiovascular diseases in adulthood. OBJECTIVES: We analyzed the association between Cytosine-Adenosine (CA)10-24 repeats polymorphism in promoter region of the IGF-I gene and early growth in infants with birth weight appropriate for gestational age (AGA) and small for gestational age (SGA). DESIGN AND METHODS: All neonates were born at term, 196 of them were AGA and 26 SGA. Blood for DNA analyses was obtained from placental part of umbilical vein. Genotyping was performed using fragment analyses of IGF-I gene promoter region. The data about postnatal growth in the group of AGA children were obtained at the age of 18 months, in SGA children at 12 months. RESULTS: No differences in the frequency of wild type allele with (CA)19 repeats and polymorphisms with (CA)<19 or (CA)>19 repeats were observed between AGA and SGA children. The average birth weight and length in AGA wild type (CA)19 homozygotes were lower in comparison with AGA carriers of various (CA)n polymorphisms but all observed anthropometric differences disappeared at the age of 18 months. In SGA children, no differences were found between number of (CA)n repeats and anthropometric parameters both at birth and at the age of 12 months. CONCLUSIONS: Although (CA)n repeats polymorphism in IGF-I gene might affect prenatal growth in AGA children, our results have not shown any impact of variable number of (CA) n repeats in IGF-I gene on postnatal growth.

Early versus delayed surfactant administration in extremely premature neonates with respiratory distress syndrome ventilated by high-frequency oscillatory ventilation.

OBJECTIVE: To determine whether early surfactant administration is superior to selective delayed treatment in terms of improving survival and/or reducing chronic lung disease in extremely premature neonates with respiratory distress syndrome (RDS) treated by high-frequency oscillatory ventilation (HFOV). DESIGN: Prospective randomized clinical trial. SETTING: Tertiary neonatal intensive care unit (NICU) in the Perinatology Center of Prague. PATIENTS: Forty-three extremely premature infants who needed artificial ventilation within 3 h after delivery. INTERVENTIONS: Patients were randomly assigned to either early ( n=21) or delayed (n=22) administration of surfactant. All were ventilated by HFOV as the primary mode of ventilation using the high volume strategy aimed at optimizing lung volume. Curosurf at a dose of 100 mg/kg was given as a single bolus via the endotracheal tube within 1 min immediately after intubation in the early group (EARL), or during HFOV only when defined criteria were reached in the delayed (DEL) group. MEASUREMENTS AND RESULTS: No differences were noted in demographic data between the two groups. Fewer infants randomized to the EARL group required oxygen use or died at 36 weeks (combined outcome 29% vs 64%, p=0.021), and there was a lower incidence of any intraventricular hemorrhage in this group (43 vs 82%, p=0.008). CONCLUSIONS: When compared to delayed dosing, early administration of surfactant followed by HFOV facilitates and accelerates respiratory stabilization during the acute phase of severe RDS, may reduce the incidence of chronic lung disease or death and may positively influence the incidence of severe intracranial pathology in extremely premature infants with primary surfactant insufficiency.