During the last two decades there has been an enormous development in treatment possibilities for the extremely premature infants and the Neonatologists have to face in their daily practice many ...decisional problems and ethical, moral and legal dilemmas. These concern decisions to initiate or withhold treatment directly at birth, decision to withdrawn treatment with the possible consequence that the child will die. The debate between "sanctity" and "quality" of life, aggressive treatment in relation to discrimination toward the disabled, the principle of "beneficence" and the question of "proportionality" of treatment, the concept of the newborn's "best interest" are the ethical issues discussed. According to our opinion, ethical questions should not be regulated by law and the legal system should not interfere in the relationship patient - physician. Today more than ever, every neonatologist needs to become familiar with basic ethical concepts and the legal aspects in neonatal intensive care.
The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application ...of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate IN-REC-SUR-E), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate IN-SUR-E).
We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766.
Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 40% of 107) compared with the IN-SUR-E group (60 54% of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 19% of 101 in the IN-REC-SUR-E group vs 37 33% of 111 in the IN-SUR-E group), pneumothorax (four 4% of 101 vs seven 6% of 111), or grade 3 or worse intraventricular haemorrhage (12 12% of 101 vs 17 15% of 111).
A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy.
None.
Summary Background Retinopathy of prematurity (ROP) is a multifactorial disease, but little is known about its relationships with neonatal nutritional policies. Human, maternal milk is the best ...possible nutritional option for all premature infants, including those at high risk for severe complications of prematurity, such as ROP. Objective This is a secondary analysis of data collected during two multicenter RCTs performed consecutively (years 2004 through 2008) by a network of eleven tertiary NICUs in Italy. The two trials aimed at assessing effectiveness of fluconazole prophylaxis (Manzoni et al., N Engl J Med 2007 Jun 14;356(24):2483–95), and of bovine lactoferrin supplementation (Manzoni et al., JAMA 2009 Oct 7;302(13):1421–8), in prevention of invasive fungal infection, and of late-onset sepsis in VLBW infants, respectively. We tested the hypothesis that exclusive feeding with fresh maternal milk may prevent ROP of any stage – as defined by the ETROP study – in VLBW neonates, compared to formula feeding. Methods We analyzed the database from both trials. Systematic screening for detection of ROP was part of the protocol of both studies. The definition of threshold ROP was as defined by the ETROP study. Univariate analysis was performed to look for significant associations between ROP and several possible associated factors, and among them, the type of milk feeding (maternal milk or formula for preterms). When an association was indicated by p < 0.05, multiple logistic regression was used to determine the factors significantly associated with ROP. Results In both trials combined, 314 infants received exclusively human maternal milk (group A), and 184 a preterm formula because their mothers were not expected to breastfeed. The clinical, demographical and management characteristics of the neonates did not differ between the two groups, particularly related to the presence of the known risk factors for ROP. Overall, ROP incidence (any stage) was significantly lower in infants fed maternal milk (11 of 314; 3.5%) as compared to formula-fed neonates (29 of 184; 15.8%) (RR 0.14; 95% CI 0.12–0.62; p = 0.004). The same occurred for threshold ROP (1.3% vs. 12.3%, respectively; RR 0.19; 95% CI 0.05–0.69; p = 0.009). At multivariate logistic regression controlling for potentially confounding factors that were significantly associated to ROP (any stage) at univariate analysis (birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, outborn, hyperglycaemia), type of milk feeding retained significance, human maternal milk being protective with p = 0.01. Conclusions Exclusive human, maternal milk feeding since birth may prevent ROP of any stage in VLBW infants in the NICU.
To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) ...preterm infants in the neonatal intensive care unit.
This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants.
Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants.
Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage.
isrctn.org: ISRCTN53107700.
Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis ...(LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain.
To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk.
This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM.
(A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64;
< 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96;
= 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (
= 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96;
= 0.01).
Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS.
Objectives: Lutein and its isomer zeaxanthin (L/Z) function in the eye as antioxidant agents and blue-light filters. Our aim was to evaluate whether their administration could help decrease the ...occurrence of retinopathy of prematurity (ROP) in preterm infants. Methods: Infants with gestational age ≤32 weeks were randomly assigned to receive a daily dose of L/Z (0.14 + 0.006 mg) or placebo until discharge. Results: ROP occurrence was similar in the L/Z (11/58; 19%) and placebo (15/56; 27%) groups, as the occurrence of ROP at each stage and the need of eye surgery. Conclusion: L/Z supplementation was ineffective in preventing ROP in preterm infants and did not affect the outcome at discharge of our patients.
Spinal cord injury of the newborn is a rare and critical condition which is typically reported after difficult deliveries. The few cases of spinal cord injury after caesarean section reported in ...literature are usually associated with intrauterine hyperextension of the head. However, in exceptional cases the authors described intrauterine vascular insults as a possible cause for spinal cord lesions during pregnancy.
A term infant was born after an uncomplicated caesarean section following cephalic presentation. Pregnancy was reported as uneventful. Foetal ultrasounds were normal and showed no evidence of hyperextension of the head. Although the boy was in good general conditions after birth, he showed a flaccid paralysis of both upper extremities with absent deep tendon reflexes and missing pain response. Other neurologic findings like general tonus and reactivity as well as spontaneous movements of both lower extremities were adequate. A spinal MRI performed at 48 h of life showed intact brachial plexuses with evidence of spinal cord lesion compatible with an ischemic injury. Accurate anamnesis revealed that the mother had perceived reduced foetal movements in the last 2 days before birth, suggesting a possible intrauterine origin of the ischaemic event.
Our case reinforces the hypothesis that small ischaemic spinal cord lesions may occur during uncomplicated pregnancy. Therefore, such lesions may not always be related to a difficult delivery. Irrespective of the cause, treatment and parental counselling remain challenging due to the rarity of reported cases.
Neonatal neuroimaging: Going beyond the pictures Ramenghi, Luca A; Rutherford, Mary; Fumagalli, Monica ...
Early human development,
10/2009, Letnik:
85, Številka:
10
Journal Article, Conference Proceeding
Recenzirano
Abstract The cerebral ultrasound has been used many years for the diagnosis of brain lesions in term and preterm newborns. Major improvements were obtained by the combination of different imaging ...modalities such as Magnetic Resonance Imaging with the Diffusion Weighted Imaging (DWI) and the new quantitative Diffusion Tensor Imaging (DTI). The clinical use of MRI has been validated over some years especially to depict the perinatal asphyxia lesions in term newborns, but its use in order to diagnose the typical diseases of preterm babies is very recent and useful in identifying a marker able to predict neurological outcome. The imaging correlates for motor impairment are well recognized (periventricular white matter cavitations), but no any imaging correlate for cognitive impairment and neurobehavioral disorders. While DWI has been used in term newborns to identify the ischemic areas with restricted diffusion, it may be also used to characterize brain development in preterm infants with the Apparent Diffusion Coefficient (ADC) and may allow us to detect abnormalities responsible for the non-motor impairments. Recent datas showed that in infants without focal lesions higher ADC values in WM were associated with poorer neurodevelopmental assessment at 2 years. The DTI also allows to detect the Fractional Anisotropy (FA) that measures the microstructure. DTI can also be used to map the WM tracts in the immature brain and may be applied to understand the normal development or the response of the brain to injury. Some WM regions in the preterm brain have a lower FA suggesting that widespread WM abnormalities are present in preterms even in the absence of focal lesions. The complexity of the developing brain can be explained by the new tractography that can assess the connectivity of different WM regions and the association between structure and function, such as optic radiations microstructure and visual assessment score. Technological advances in neonatal brain imaging have made a major contribution to understand the neurobehavioral disorders of the developing brain that have the origin in the early structural cerebral organization and maturation.
Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ...ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria.
In this study, 206 spontaneously breathing infants born at 24(+0)-27(+6) weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation.
From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge.
ClinicalTrials.gov identifier: NCT02482766 . Registered on 1 June 2015.
The treadmill exercise test is the most important examination of the functional ability of patients with intermittent claudication or leg pain during exercise, but it does not provide any metabolic ...information in the calf muscle. The purpose of this study was to investigate the high-energy metabolism in the calf muscle during incremental progressive plantar flexion exercise of a selected peripheral arterial disease (PAD) patient group.
Using a 1.5-T whole-body magnetic resonance scanner, 17 male patients with PAD who had 1 symptomatic and 1 asymptomatic leg and 9 healthy male controls underwent serial phosphor 31 (
31P) magnetic resonance spectroscopy during incremental exercise at 2, 3, 4, and 5 W. Furthermore, magnetic resonance angiography was performed, and the ankle-brachial pressure index was determined in the patient group. The runoff resistance (ROR) was separately assessed in each patient’s leg.
The symptomatic legs exhibited significantly increased phosphocreatine (PCr) time constants during the first three workload increments (2-4 W) and the recovery phase compared with the asymptomatic legs and the normal controls. Only two symptomatic legs reached the last increment at 5 W. Compared with the normal controls, the asymptomatic legs showed significantly increased PCr time constants only at 5 W. In the patient group, we detected significant correlations between the PCr time constants and the ROR, as well as the ankle-brachial pressure index. Moreover, the symptomatic legs presented significantly lower PCr levels and pH values at the end of exercise compared with the asymptomatic and control legs.
Our study shows that muscle function in PAD patients can be objectively quantified with the help of
31P magnetic resonance spectroscopy and correlates significantly with hemodynamic parameters such as ROR and ankle-brachial pressure index. Consequently,
31P magnetic resonance spectroscopy seems to be a useful method to monitor the muscle function of PAD patients for evaluation of established therapies or new therapeutic strategies during research trials.
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