The ethics and practice of neonatal resuscitation at the limits of viability: an international perspective

Premature infants at the limits of viability raise difficult ethical, legal, social and economic questions. Neonatologists attending an international Collegium were surveyed about delivery room behaviour, and the approach taken by selected countries practicing 'modern' medicine was explored. Conclusion There were strong preferences for comfort care at 22 weeks and full resuscitation at 24 weeks. Resuscitation was a grey area at 23 weeks. Cultural, social and legal factors also had a considerable impact on decision-making. ©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd

Simultaneous determination of selective serotonin reuptake inhibitors and their main metabolites in human breast milk by liquid chromatography-electrospray mass spectrometry.

A bioanalytical method by high performance liquid chromatography coupled to electrospray mass spectrometry (HPLC-ESI-MS), adapted from a previously published method in plasma, was validated in breast milk for the simultaneous quantification of all antidepressants belonging to the class of selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their major metabolites (desmethylcitalopram and norfluoxetine). Milk samples (250μl) first underwent protein precipitation followed by solid-phase extraction on a reversed phase/cation exchange sorbent. Analytes were thereafter separated on a XBridge C18 column (2.1mm×100mm; 3.5μm) using a mobile phase composed of ammonium acetate buffer (pH 8.1; 50mM) and acetonitrile in gradient mode. Detection was performed by a single quadrupole mass spectrometer running in selected ion monitoring in positive ionization mode. Method validation covered a wide concentration range of 2-500ng/ml for citalopram, desmethylcitalopram and paroxetine, 5-500ng/ml for sertraline, and 2-1000ng/ml for fluoxetine, norfluoxetine and fluvoxamine. Validation performances such as trueness (90.3-111.6%), repeatability (0.8-9.3%) and intermediate precision (0.9-9.5%) were in agreement with criteria from international guidelines and matrix effects for the analyte/internal standard ratios ranged from 92% to 110% (relative standard deviation <15%). Accuracy profiles (total error of trueness and precision) were lying within the limits of ±30% accepted in bioanalysis. Finally, the method was successfully applied to patient samples collected in a clinical pharmacokinetic study of nursing mothers taking an antidepressant treatment

Stereoselective determination of citalopram and desmethylcitalopram in human plasma and breast milk by liquid chromatography tandem mass spectrometry.

A high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS) method was developed for the simultaneous, stereoselective quantification of the antidepressant citalopram and its active metabolite desmethylcitalopram in human plasma and breast milk. Sample preparation was performed by a two-step approach, including generic protein precipitation with acetonitrile followed by solid phase extraction. Enantiospecific separation of analytes was achieved on a Phenomenex(®) Lux Cellulose-2 column (4.6mm×150mm; 5μm), using reversed phase chromatography conditions characterized by a gradient elution of ammonium acetate buffer (pH 9.0; 20mM) and acetonitrile at a flow rate of 0.6ml/min. The compounds were detected by a tandem quadrupole mass spectrometer equipped with an electrospray ionization source and operating in multiple reaction monitoring mode. The method was fully validated in both biological fluids over a large concentration range of 0.1-100ng/ml for S-(+)- and R-(-)-citalopram, and 0.3-100ng/ml for S-(+)- and R-(-)-desmethylcitalopram. Trueness (90.0-113.3% and 97.1-103.6%), repeatability (0.9-15.9% and 0.9-8.4%) and intermediate precision (1.3-17.8% and 0.9-9.6%) in plasma and breast milk, respectively, meet international guidelines for method validation. Internal standard-normalized matrix effects ranged between 99 and 101% and 98-105%, respectively. The accuracy profiles (total error of trueness and precision) were mostly within the acceptance limits for biological samples defined as ±30%. The method was successfully applied to patient samples in a clinical trial setting

Risk factors for bronchiolitis hospitalization in infants: A French nationwide retrospective cohort study over four consecutive seasons (2009-2013)

International audienceObjectives: Large studies are needed to update risk factors of bronchiolitis hospitalization. We performed a nationwide analysis of hospitalization rates for bronchiolitis over four consecutive bronchiolitis seasons to identify underlying medical disorders at risk of bronchiolitis hospitalization and assess their frequency.Methods: Data were retrieved from the French National Hospital Discharge database. Of all infants discharged alive from maternity wards from January 2008 to December 2013 in France (N = 3,884,791), we identified four consecutive cohorts at risk of bronchiolitis during the seasons of 2009–2010 to 2012–2013. The main outcome was bronchiolitis hospitalization during a season. Individual risk factors were collected.Results: Among infants, 6.0% were preterm and 2.0% had ≥1 chronic condition including 0.2% bronchopulmonary dysplasia (BPD) and 0.2% hemodynamically significant congenital heart disease (HS-CHD). Bronchiolitis hospitalization rates varied between seasons (min: 1.26% in 2010–2011; max: 1.48% in 2012–2013; p<0.001). Except omphalocele, the following conditions were associated with an increased risk for bronchiolitis hospitalization: solid organ (9.052; 95% CI, 4.664–17.567) and stem cell transplants (6.012; 95% CI, 3.441–10.503), muscular dystrophy (4.002; 95% CI, 3.1095–5.152), cardiomyopathy (3.407; 95% CI, 2.613–4.442), HS-CHD (3.404; 95% CI, 3.153–3.675), congenital lung disease and/or bronchial abnormalities, Down syndrome, congenital tracheoesophageal fistula, diaphragmatic hernia, pulmonary hypertension, chromosomal abnormalities other than Down syndrome, hemodynamically non-significant CHD, congenital abnormalities of nervous system, cystic fibrosis, cleft palate, cardiovascular disease occurring during perinatal period, and BPD.Conclusion: Besides prematurity, BPD, and HS–CHD, eighteen underlying conditions were associated with a significant increased risk for bronchiolitis hospitalization in a nationwide population

Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota:A Randomized Clinical Trial

International audienceBackground: Post-natal gut maturation in infants interrelates maturation of the morphology, digestive, and immunological functions and gut microbiota development. Here, we explored both microbiota development and markers of gut barrier and maturation in healthy term infants during their early life to assess the interconnection of gut functions during different infant formulae regimes.Methods: A total of 203 infants were enrolled in this randomized double-blind controlled trial including a breastfed reference group. Infants were fed starter formulae for the first four weeks of life, supplemented with different combination of nutrients (lactoferrin, probiotics (Bifidobacterium animal subsp. Lactis) and prebiotics (Bovine Milk-derived Oligosaccharides-BMOS)) and subsequently fed the control formula up to eight weeks of life. Stool microbiota profiles and biomarkers of early gut maturation, calprotectin (primary outcome), elastase, α-1 antitrypsin (AAT) and neopterin were measured in feces at one, two, four, and eight weeksResults: Infants fed formula containing BMOS had lower mean calprotectin levels over the first two to four weeks compared to the other formula groups. Elastase and AAT levels were closer to levels observed in breastfed infants. No differences were observed for neopterin. Global differences between the bacterial communities of all groups were assessed by constrained multivariate analysis with hypothesis testing. The canonical correspondence analysis (CCA) at genus level showed overlap between microbiota profiles at one and four weeks of age in the BMOS supplemented formula group with the breastfed reference, dominated by bifidobacteria. Microbiota profiles of all groups at four weeks were significantly associated with the calprotectin levels at 4 (CCA, p = 0.018) and eight weeks of age (CCA, p = 0.026).Conclusion: A meaningful correlation was observed between changes in microbiota composition and gut maturation marke

Effect of Intra- and Extrauterine Growth on Long-Term Neurologic Outcomes of Very Preterm Infants

International audienc