End-of-life decisions and practices for very preterm infants in the Wallonia-Brussels Federation of Belgium.

BACKGROUND: Very preterm birth (24 to < 32 week's gestation) is a major public health issue due to its prevalence, the clinical and ethical questions it raises and the associated costs. It raises two major clinical and ethical dilemma: (i) during the perinatal period, whether or not to actively manage a baby born very prematurely and (ii) during the postnatal period, whether or not to continue a curative treatment plan initiated at birth. The Wallonia-Brussels Federation in Belgium counts 11 neonatal intensive care units. METHODS: An inventory of key practices was compiled on the basis of an online questionnaire that was sent to the 65 neonatologists working in these units. The questionnaire investigated care-related decisions and practices during the antenatal, perinatal and postnatal periods, as well as personal opinions on the possibility of standardising and/or legislating for end-of-life decisions and practices. The participation rate was 89% (n = 58). RESULTS: The results show a high level of homogeneity pointing to overall agreement on the main principles governing curative practice and the gestational age that can be actively managed given the current state of knowledge. There was, however, greater diversity regarding principles governing the transition to end-of-life care, as well as opinions about the need for a common protocol or law to govern such practices. CONCLUSION: Our results reflect the uncertainty inherent in the complex and diverse situations that are encountered in this extreme area of clinical practice, and call for qualitative research and expert debates to further document and make recommendations for best practices regarding several "gray zones" of end-of-life care in neonatology, so that high quality palliative care may be granted to all neonates concerned with end-of-life decisions.

Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial).

BACKGROUND: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. METHODS: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. DISCUSSION: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks. TRIAL REGISTRATION: This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28 .

Remifentanil versus morphine-midazolam premedication on the quality of endotracheal intubation in neonates: a noninferiority randomized trial.

OBJECTIVE: To compare remifentanil and morphine-midazolam for use in nonurgent endotracheal intubation in neonates. STUDY DESIGN: In this prospective noninferiority randomized trial, newborns of gestational age ≥28 weeks admitted in the neonatal intensive care unit requiring an elective or semielective endotracheal intubation were divided into 2 groups. One group (n = 36) received remifentanil (1 µg/kg), and the other group (n = 35) received morphine (100 µg/kg) and midazolam (50 µg/kg) at a predefined time before intubation (different in each group), to optimize the peak effect of each drug. Both groups also received atropine (20 µg/kg). The primary outcome was to compare the conditions of intubation, and the secondary outcome was to compare the duration of successful intubation, physiological variables, and pain scores between groups for first and second intubation attempts. Adverse events and neurologic test data were reported. RESULTS: Intubation with remifentanil was not inferior to that with morphine-midazolam. At the first attempted intubation, intubation conditions were poor in 25% of the remifentanil group and in 28.6% of the morphine-midazolam group (P = .471). For the second attempt, conditions were poor in 28.6% of the remifentanil group, compared with 10% of the morphine-midazolam group (P = .360). The median time to successful intubation was 33 seconds (IQR, 24-45 seconds) for the remifentanil group versus 36 seconds (IQR, 25-59 seconds) for the morphine-medazolam group (P = .359) at the first attempt and 45 seconds (IQR, 35-64 seconds) versus 56 seconds (IQR, 44-68 seconds), respectively, for the second attempt (P = .302). No significant between-group difference was reported for hypotension, bradycardia, or adverse events. CONCLUSION: In our cohort, remifentanil was at least as effective as the morphine-midazolam regimen for endotracheal intubation. Thus, premedication using this very-short-acting opioid can be considered in urgent intubations and is advantageous in rapid extubation.

Use of the "Sepsis Risk Calculator" in Belgian Newborns: A Retrospective Cohort Study.

BACKGROUND: Prevention of early-onset neonatal sepsis (EONS) is a frequent reason why many newborns receive unnecessary antibiotics. The Sepsis Risk Calculator (SRC) was developed by the Kaiser Permanente Institute as a multivariate risk assessment of EONS, aiming to reduce laboratory testing and empiric neonatal antibiotic therapy. Our objective was to assess the potential of the SRC in reducing antibiotic use in our setting. METHODS: Late preterm and term newborns who received antibiotics from 2019 to 2020 in a tertiary Belgian hospital were included. Newborn-specific data were collected and entered into the online SRC, retrospectively calculating a sepsis risk score and providing recommendations for antibiotic administration. False-positive indications for treatment by the SRC were estimated based on previously published data. Antibiotic therapy rates according to the SRC recommendations were compared to the actual rate of antibiotic therapy. RESULTS: Of 5891 births, 414 newborns received antibiotics and were eligible for this study, representing a rate of 7.6% of newborns receiving antibiotics following our current guidelines. The SRC would have recommended antibiotic administration for 2.7%, reducing antibiotic therapy by 64.5%. Of 5 possible cases of EONS, 3 would have received antibiotics in the first 24 hours according to the SRC. CONCLUSIONS: In this Belgian cohort, use of the SRC has the potential to significantly decrease by 64.5% the newborns that receive antibiotics. This reduction would primarily concern asymptomatic newborns. If use of the SRC was to be implemented in Belgian maternities, strict clinical surveillance practices should be ensured.

Hemodynamic effects of fluid restriction in preterm infants with significant patent ductus arteriosus.

OBJECTIVE: To determine the hemodynamic impact of fluid restriction in preterm newborns with significant patent ductus arteriosus. STUDY DESIGN: Newborns ≥24 and <32 weeks' gestational age with significant patent ductus arteriosus were eligible for this prospective multicenter observational study. We recorded hemodynamic and Doppler echocardiographic variables before and 24 hours after fluid restriction. RESULTS: Eighteen newborns were included (gestational age 24.8 ± 1.1 weeks, birth weight 850 ± 180 g). Fluid intake was decreased from 145 ± 15 to 108 ± 10 mL/kg/d. Respiratory variables, fraction of inspired oxygen, blood gas values, ductus arteriosus diameter, blood flow-velocities in ductus arteriosus, in the left pulmonary artery and in the ascending aorta, and the left atrial/aortic root ratio were unchanged after fluid restriction. Although systemic blood pressure did not change, blood flow in the superior vena cava decreased from 105 ± 40 to 61 ± 25 mL/kg/min (P < .001). The mean blood flow-velocity in the superior mesenteric artery was lower 24 hours after starting fluid restriction. CONCLUSIONS: Our results do not support the hypothesis that fluid restriction has beneficial effects on pulmonary or systemic hemodynamics in preterm newborns.

Irritability, Poor Feeding and Respiratory Alkalosis in Newborns: Think about Metabolic Emergencies. A Brief Summary of Hyperammonemia Management.

The urea cycle is a series of metabolic reactions that convert ammonia into urea in order to eliminate it from the body. Urea cycle disorders are characterized by hyperammonemia, which can cause irreversible damages in central nervous system. We report a series of three newborns presenting irritability, poor feeding and tachypnea. Their first gas analysis revealed respiratory alkalosis. Hyperammonemia was confirmed, and three different enzymatic blocks in the urea cycle were diagnosed. Immediate treatment consisted in the removal of ammonia by reduction of the catabolic state, dietary adjustments, use of nitrogen scavenging agents and ultimately hemodiafiltration. Hyperammonemia is a medical emergency whose treatment should not be delayed. This report aims to highlight the importance of suspecting urea cycle disorders in newborns with aspecific signs of hyperammonemia and respiratory alkalosis, and to sum up the broad lines of hyperammonemia management.

Comprehensive management of congenital choanal atresia.

OBJECTIVES: To present results of a one-stage minimally invasive surgical procedure for congenital choanal atresia (CCA). Seven outcome measures were applied. MATERIALS AND METHODS: Retrospective study conducted between 1999 and 2015. The same endonasal endoscopic approach with multiflaps and no stenting was used on 36 children. The flaps were attached with fibrine glue. There were 50% unilateral and 50% bilateral cases, 70% primary and 30% secondary surgery. The mean age at primary surgery for bilateral atresia was 10 days and for unilateral atresia 4 years. Associated loco-regional disorders were: hypoplasia of the inferior turbinate, rhinopharyngeal stenosis and rhinopharyngeal web. RESULTS: The average follow-up time was 6 years, ranging from 1 to 14 years. There was a functionally patent choanae in 94% of children, and 6% showed severe restenosis with a diameter less than 4 mm, which needed one revision surgery each. Charge patients were not associated with worse outcome. There was no external nasal valve stenosis and no permanent Eustachian tube dysfunction. Synechiae occurred in 3 patients with hyperplastic inferior turbinate. No patients showed any disharmonious nasal growth. In neonates with isolated bilateral CCA, breast-suction could be started within 1 day (range 1-2 days), and pain-killers were needed on average for 1.5 days (range 1-4 days). The hospital stay for unilateral isolated CCA was on average 1.5 days (range 1-2 days) and for bilateral isolated CCA, 8 days (range 3-20 days). Postoperative procedures under a short general anesthesia were necessary in 12 cases, 10 of them were infants under 6 months of age. CONCLUSION: Surgery could be performed safely in the newborn in the early stage of life, even for unilateral atresia. Tendency for restenosis can be minimized by: 1. the construction of an as large as possible uni-neochoanae by removing the posterior part of the vomer and by drilling away the medial pterygoid; 2. in case of rhinopharyngeal stenosis, part of the endochondral clivus bone should be resected; 3. all raw surfaces should be covered by multiple mucosal flaps secured with fibrin glue; 4. no stenting; 5. appropriate postoperative care.

The use of human milk in the neonatal intensive care unit: practices in Belgium and Luxembourg.

BACKGROUND: Human milk remains the preferred feeding for all infants, including premature and sick newborns. However, mother's milk is not sterile, and expressed milk can be a source of commensal and pathogenic microorganisms. Microbiological quality standards for the use of expressed human milk in hospitals are not available, unlike for donor or formula milk. METHODS: To document current practices for the use of human milk in the neonatal intensive care units (NICU) in Belgium and Luxembourg, both for mother's own milk and donor milk, a questionnaire was sent to all 20 neonatal units. RESULTS: Of the 19 units that completed the survey, 47% perform bacteriological testing of expressed milk. Applied bacterial count limits for the acceptable level of contamination differ among units, for both commensals and pathogens. Only six units have a device for pasteurizing milk at their disposal. Storage time in the refrigerator for fresh milk varies between 24 hours to 7 days before use. Access to donor milk is limited. CONCLUSIONS: Routines for handling of human milk differ widely among NICUs in Belgium and Luxembourg. An assessment of current issues through a structured survey is a useful tool in the development of best practice guidelines.

Relationship between the presence of newborn and the house dust endotoxin.

BACKGROUND: Exposure to house dust endotoxin induces of airways' inflammation. Endotoxin are produced by the Gram-negative bacteria, which are released into the stools and could contaminate domestic environment. OBJECTIVE: The newborn could contaminate his mattress by endotoxin. METHODS: The dusts of mattress and carpets of 97 newborn' dwellings were sampled at birth and after six months of life. Samplings were made in the bedroom from the baby and in the second place where the baby spent the longer time. The endotoxin concentration was measured by a quantitative Limulus assay and the bacterial contamination was evaluated using 3 selective agar media. RESULTS: Endotoxin concentration at birth was positively associated with the presence of both sibling and the number of inhabitants (p<0.01). At 6 months of life, the endotoxin concentration raised significantly not only in the mattresses (from a median of 17.6 (ranges: 0.4-346.7) to 79.6 (3.8-518.8) EU/mg) (p<0.0001), but also in the dust from the second place where the baby is sleeping (from 20.4 (0.8-226.3) to 101.8 (6.5-634.3) EU/mg) (p<0.001). Importantly, there was no change in endotoxin concentration from the carpets dust, and the environmental dwelling characteristics remained unchanged. The total bacterial contamination was also positively associated with endotoxin concentration in newborn mattress at birth (p<0.01) and showed a significant increase at 6 months of life of the newborn (p<0.01). CONCLUSION: The newborn is a significant source of house dust's endotoxin.

Methylergometrine poisoning in children: review of 34 cases.

Methylergometrine is often used in the management of the third stage of labor and for treatment of prevention of puerperal hemorrhage. Intoxication in newborns is rare but may lead to severe complications. We reviewed 34 cases of methylergometrine poisoning that occurred in Belgium between 1969 and 1999. Fourteen patients were newborns and 20 were older children. Twenty-nine patients were exposed by the oral route, 3 by the intranasal route, and 2 by the intramuscular route. Oral exposure was associated mostly with gastrointestinal symptoms, but one newborn required mechanical ventilation for apnea. Intramuscular exposure was associated with severe complications, including apnea, coma, and convulsions. We describe the first case of oral methylergometrine poisoning requiring mechanical ventilation and alert physicians that oral exposure to methylergometrine may lead to severe complications.