Abstract Background and aims Melatonin (MT) is rapidly transferred from the maternal to fetal circulation in humans. There is little knowledge about factors which influence the MT concentration (MTc) ...in the umbilical cord (UC) blood during delivery. The aim of our study was to evaluate the MT status in the UC blood according to the time and mode of delivery. Subjects and methods Blood samples from umbilical artery (UA) and vein (UV) were collected from spontaneous vaginal deliveries (SVD, n = 122) and cesarean section deliveries (CSD, n = 188). MTc was measured using a commercially available radioimmunoassay. Results The MTc was not significantly different between UA and UV blood both at daytime and at nighttime (p = 0.216 and p = 0.440, respectively). Both in UA and in UV, the MTc was significantly higher at nighttime than at daytime (p < 0.0001). Compared with the CSD group, MTc in the SVD group was significantly higher both at night- and daytime (p < 0.05). MTc both in UA and in UV was found to be not significantly different between patients with and without risk factors for stress including pregnancy complications (e.g., preeclampsia) and intrapartum complications (e.g., emergency section, pathological doppler, and pathological cardiotocography) (p > 0.05). Conclusion Our study revealed for the first time that MTc both in UA and in UV depends on modus of labor. In agreement with other studies, we found a clear circadian MT rhythm in the UC blood of neonates. The results of our study may suggest to a physiological role of MT at the onset of labor.
IMPORTANCE: Treatment of respiratory distress syndrome in premature infants with continuous positive airway pressure (CPAP) preserves surfactant and keeps the lung open but is insufficient in severe ...surfactant deficiency. Traditional surfactant administration is related to short periods of positive pressure ventilation and implies the risk of lung injury. CPAP with surfactant but without any positive pressure ventilation may work synergistically. This randomized trial investigated a less invasive surfactant application protocol (LISA). OBJECTIVE: To test the hypothesis that LISA increases survival without bronchopulmonary dysplasia (BPD) at 36 weeks’ gestational age in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS: The Nonintubated Surfactant Application trial was a multicenter, randomized, clinical, parallel-group study conducted between April 15, 2009, and March 25, 2012, in 13 level III neonatal intensive care units in Germany. The final follow-up date was June 21, 2012. Participants included 211 of 558 eligible (37.8%) spontaneously breathing preterm infants born between 23.0 and 26.8 weeks’ gestational age with signs of respiratory distress syndrome. In an intention-to-treat design, infants were randomly assigned to receive surfactant either via a thin endotracheal catheter during CPAP-assisted spontaneous breathing (intervention group) or after conventional endotracheal intubation during mechanical ventilation (control group). Analysis was conducted from September 6, 2012, to June 20, 2013. INTERVENTION: LISA via a thin catheter. MAIN OUTCOMES AND MEASURES: Survival without BPD at 36 weeks’ gestational age. RESULTS: Of 211 infants who were randomized, 104 were randomized to the control group and 107 to the LISA group. Of the infants who received LISA, 72 (67.3%) survived without BPD compared with 61 (58.7%) of those in the control group. The reduction in absolute risk was 8.6% (95% CI, −5.0% to 21.9%; P = .20). Intervention group infants were less frequently intubated (80 infants 74.8% vs 103 99.0%; P < .001) and required fewer days of mechanical ventilation. Significant reductions were seen in pneumothorax (5 of 105 intervention group infants 4.8% vs 13 of 103 12.6%; P = .04) and severe intraventricular hemorrhage (11 infants 10.3% vs 23 22.1%; P = .02), and the combined survival without severe adverse events was increased in the intervention group (54 infants 50.5% vs 37 35.6%; P = .02; absolute risk reduction, 14.9; 95% CI, 1.4 to 28.2). CONCLUSIONS AND RELEVANCE: LISA did not increase survival without BPD but was associated with increased survival without major complications. Because major complications are related to lifelong disabilities, LISA may be a promising therapy for extremely preterm infants. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN64011614
Aim
The aim of this study was to evaluate neurocognitive outcome at 24 months of corrected age after less invasive surfactant application (LISA) in preterm infants born at 23‐26 weeks of gestational ...age.
Methods
Surviving participants of a LISA trial conducted in 13 German level III neonatal intensive care units were reviewed for assessment of developmental outcome, hearing and vision problems, growth and rehospitalisation days. Maternal depression, breastfeeding rates and socio‐economic factors were evaluated as potentially confounding factors.
Results
In total, 156/182 infants took part in the study, 78 had received surfactant via LISA and 78 via endotracheal intubation. 22% of LISA infants compared to 42% of intubated infants had a psychomotor development index (PDI) <70 (0.012). A significant difference in mental development index (MDI) was observed in the stratum of more mature infants (25 and 26 weeks of GA). For this group, MDI < 70 was observed in 4% of LISA infants vs 21% of intubated infants (P = 0.008).
Conclusion
At 24 months of age, the LISA‐treated infants scored less often PDI < 70 and had similar results in MDI. Infants born at 25 and 26 weeks treated with LISA had lower rates of severe disability. LISA is safe and may be superior.
Remifentanil is a relatively new synthetic opioid, which is not licensed worldwide for neonates and infants. Because of its unique pharmacokinetic properties with a short recovery profile, it could ...be the ideal opioid for neonates and infants, who are especially sensitive to respiratory depression by opioids. Therefore, we conducted a MEDLINE search on all articles dealing with the use of remifentanil in this important subgroup of patients. Most experience with remifentanil in neonates and infants is as maintenance anaesthesia during surgery. In approximately 300 neonates and infants, remifentanil proved to be an effective and safely used opioid for this indication. However, very limited data exist on remifentanil for analgesia and sedation of mechanically ventilated paediatric intensive care patients. Further research with remifentanil in neonates and infants should focus on this group of patients because remifentanil, with its very short context-sensitive half-life, could result in shorter extubation times compared with commonly used opioids such as morphine or fentanyl.
Summary
Background: Propofol is gaining increasing popularity as induction agent for pediatric endotracheal intubation. Recently, propofol has been described for the first time as induction agent ...for endotracheal intubation in preterm neonates. Propofol seemed to be efficient, safe and ideally suited for the INSURE (Intubation SURfactant Extubation) procedure in preterm neonates. The purpose of this study was to document intubating conditions, vital signs, extubation times and outcome in preterm neonates receiving propofol as induction agent for the INSURE procedure.
Patients and Methods: Preterm neonates with a gestational age of 29–32 weeks and respiratory distress were eligible for INSURE with propofol if their postnatal age was <8 h. Exclusion criteria were any kind of disease not allowing early extubation.
Results: There were 13 inborn neonates enrolled for INSURE, mean gestational age was 30 weeks + 3 days, and mean birth weight was 1428 g (range 1170–1780 g). We stopped our observational study ahead of time as a result of significant cardiovascular side effects. Propofol generally offered good intubating conditions, but we encountered severe problems with arterial hypotension. A low propofol bolus of 1 mg·kg−1 caused a distinctive decline in mean arterial blood pressure from 38 mmHg (range 29–42 mmHg) prior premedication to 24 mmHg (22–40 mmHg) 10 min after propofol application.
Conclusions: Our experience with propofol as induction agent for endotracheal intubation in preterm neonates reveals distinctive cardiovascular effects, which represent an important risk factor for serious complications of prematurity like intraventricular hemorrhage or periventricular leucomalacia. Propofol should be used with caution in very preterm neonates with respiratory distress during the first hours of life.
AimWe explored whether subnormal forced expiratory volume within 1 s (FEV1) at 5–9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather ...than surfactant via an endotracheal tube.MethodsThe multi‐centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23–26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow‐up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values.ResultsSpirometry was successful in 102/121 children. The other children died or were lost to follow‐up. Median FEV1 was 93% (interquartile range 80%–113%) of predicted values in the LISA group and 86% (interquartile range 77–102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval −3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures.ConclusionThe proportion of children aged 5–9 years with subnormal FEV1 was not significantly different between the groups.
Aim
We explored whether subnormal forced expiratory volume within 1 s (FEV1) at 5–9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather ...than surfactant via an endotracheal tube.
Methods
The multi‐centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23–26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow‐up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values.
Results
Spirometry was successful in 102/121 children. The other children died or were lost to follow‐up. Median FEV1 was 93% (interquartile range 80%–113%) of predicted values in the LISA group and 86% (interquartile range 77–102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval −3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures.
Conclusion
The proportion of children aged 5–9 years with subnormal FEV1 was not significantly different between the groups.
Purpose
Common opioids for analgesia and sedation of mechanically ventilated infants may tend to accumulate and cause prolonged sedation with an unpredictable extubation time. Remifentanil is a ...promising option due to its unique pharmacokinetic properties, which seem to be valid in adults as well as in infants.
Methods
In this double-blind, randomized, controlled trial mechanically ventilated neonates and young infants (<60 days) received either a remifentanil or fentanyl-based analgesia and sedation regimen with low dose midazolam. The primary endpoint of the trial was the extubation time following discontinuation of the opioid infusion. Secondary endpoints included efficacy and safety aspects.
Results
Between November 2006 and March 2010, we screened 431 mechanically ventilated infants for eligibility. The intention to treat group included 23 infants who were assigned to receive either remifentanil (
n
= 11) or fentanyl (
n
= 12). Although this was designed as a pilot study, median extubation time was significantly shorter in the remifentanil group (80.0 min, IQR = 15.0–165.0) compared to the fentanyl group (782.5 min, IQR = 250.8–1,875.0) (
p
= 0.005). Remifentanil and fentanyl provided comparable efficacy with more than two-thirds of the measurements indicating optimal analgesia and sedation (66.4 and 70.2 %, respectively;
p
= 0.743). Overall, both groups had good hemodynamic stability and a comparably low incidence of adverse events.
Conclusions
As neonates and young infants have a decreased metabolism of common opioids like fentanyl and are more prone to respiratory depression, remifentanil could be the ideal opioid for analgesia and sedation of mechanically ventilated infants.
No pharmacokinetic data about remifentanil in preterm infants exist, although remifentanil is increasingly used in this especially vulnerable subgroup of pediatric patients. Unfortunately, ethical ...restrictions in the volume of blood that can be withdrawn for kinetic sampling nearly prohibit pharmacokinetic studies in preterm infants.
Because remifentanil is rapidly metabolized by nonspecific blood esterases, we collected umbilical cord serum of preterm and term infants to investigate whether the activity of nonspecific blood esterases depends on gestational age. Umbilical cord serum, buffer solution, ascorbic acid, and remifentanil were mixed in a glass vial placed in a shaking water bath at 37°C. Subsequently, serum samples were subjected to liquid chromatography-mass spectrometry-based analysis of remifentanil and its metabolite GR90291 after 0, 30, 60, 100, and 150 min.
We analyzed umbilical cord serum samples of 34 preterm infants (24-36 gestational weeks) and six term infants. The degradation rates of remifentanil to its major metabolite GR90291 were comparable in preterm and term infants. The overall median degradation half-life of remifentanil was 143 ± (interquartile range) 47 min (minimum, 76 min; maximum, 221 min) without significant differences between very preterm infants (less than 28 gestational weeks) and term infants. The remifentanil concentration remained stable in control runs without serum.
Our study demonstrates that very preterm infants exhibit a high nonspecific esterase activity in umbilical cord blood that is comparable with that of term infants. These results support clinical experiences that remifentanil is rapidly metabolized by preterm infants without prolonged side effects.
Abstract Background : There are important physiological changes in the maternal, placental, and fetal compartments during pregnancy and labor. Increased oxidative stress has been demonstrated during ...labor. Melatonin has been reported to serve as an indirect antioxidant via the stimulation and induction of antioxidant enzymes as superoxide dismutase (SOD) and glutathione peroxidase (Gpx) in several tissues. Aim : To assess whether the melatonin status, presence of labor at the time of birth and the time of delivery influence the extracellular antioxidative enzymes and DNA oxidative stress in newborns. Methods : The extracellular antioxidative status and oxidative stress were analyzed by measuring the concentrations of the SOD3, Gpx3 and 8-hydroxydeoxyguanosine (8-OHdG) in the cord blood of 135 newborns. Newborns delivered during the day and at night and newborns delivered by spontaneous vaginal delivery (labor group) or elective caesarean section delivery (no labor group) were studied. Outcome measures : The concentration of melatonin, SOD3, Gpx3 and 8-OHdG. Results : Independent of the time of delivery, we found significantly higher melatonin, SOD3 and Gpx3 but lower 8-OHdG concentrations in the labor group than in the no labor group. We did not observe a correlation between the concentration of melatonin and SOD3, Gpx3 or 8-OHdG, or a day–night difference in SOD3, Gpx3 or 8-OHdG. Conclusion : Our findings suggest that oxidative stress during labor leads to an elevation of melatonin, SOD3 and Gpx3 in the fetal circulation, protecting the newborn from serious impairment, which is reflected by lower 8-OHdG levels. The melatonin status at the time of birth does not influence the extracellular SOD3 or Gpx3 concentrations.
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