The Level of Protein in Milk Formula Modifies Ileal Sensitivity to LPS Later in Life in a Piglet Model

Background: Milk formulas have higher protein contents than human milk. This high protein level could modify the development of intestinal microbiota, epithelial barrier and immune functions and have long-term consequences. Methodology/Principal findings: We investigated the effect of a high protein formula on ileal microbiota and physiology during the neonatal period and later in life. Piglets were fed from 2 to 28 days of age either a normoprotein (NP, equivalent to sow milk) or a high protein formula (HP, +40% protein). Then, they received the same solid diet until 160 days. During the formula feeding period ileal microbiota implantation was accelerated in HP piglets with greater concentrations of ileal bacteria at d7 in HP than NP piglets. Epithelial barrier function was altered with a higher permeability to small and large probes in Ussing chambers in HP compared to NP piglets without difference in bacterial translocation. Infiltration of T cells was increased in HP piglets at d28. IL-1b and NF-kappa B sub-units mRNA levels were reduced in HP piglets at d7 and d28 respectively; plasma haptoglobin also tended to be reduced at d7. Later in life, pro-inflammatory cytokines secretion in response to high doses of LPS in explants culture was reduced in HP compared to NP piglets. Levels of mRNA coding the NF-kappa B pathway sub-units were increased by the challenge with LPS in NP piglets, but not HP ones. Conclusions/Significance: A high protein level in formula affects the postnatal development of ileal microbiota, epithelial barrier and immune function in piglets and alters ileal response to inflammatory mediators later in life

Research priorities for European paediatric emergency medicine

Objective Research in European Paediatric Emergency Medicine (REPEM) network is a collaborative group of 69 paediatric emergency medicine (PEM) physicians from 20 countries in Europe, initiated in 2006. To further improve paediatric emergency care in Europe, the aim of this study was to define research priorities for PEM in Europe to guide the development of future research projects. Design and Setting We carried out an online survey in a modified three-stage Delphi study. Eligible participants were members of the REPEM network. In stage 1, the REPEM steering committee prepared a list of research topics. In stage 2, REPEM members rated on a 6-point scale research topics and they could add research topics and comment on the list for further refinement. Stage 3 included further prioritisation using the Hanlon Process of Prioritisation (HPP) to give more emphasis to the feasibility of a research topic. Results Based on 52 respondents (response rates per stage varying from 41% to 57%), we identified the conditions 'fever', 'sepsis' and 'respiratory infections', and the processes/interventions 'biomarkers', 'risk stratification' and 'practice variation' as common themes of research interest. The HPP identified highest priority for 4 of the 5 highest prioritised items by the Delphi process, incorporating prevalence and severity of each condition and feasibility of undertaking such research. Conclusions While the high diversity in emergency department (ED) populations, cultures, healthcare systems and healthcare delivery in European PEM prompts to focus on practice variation of ED conditions, our defined research priority list will help guide further collaborative research efforts within the REPEM network to improve PEM care in Europe.publishersversionPeer reviewe

Umbilical cord blood procalcitonin and C reactive protein concentrations as markers for early diagnosis of very early onset neonatal infection

Procalcitonin (PCT) and C reactive protein (CRP) concentrations in umbilical cord blood of 197 neonates were measured to evaluate their value as markers of infection. Sixteen of the neonates were infected. The sensitivity, specificity, and negative and positive predictive values were respectively 87.5%, 98.7%, 87.5%, and 98.7% for PCT and 50%, 97%, 67%, and 94% for CRP. Serum PCT in cord blood seems to be a useful and early marker of antenatal infection

Umbilical cord blood procalcitonin level in early neonatal infections: a 4-year university hospital cohort study

International audienceThis article describes a study of procalcitonin (PCT) measured in cord blood as a discriminating marker of early-onset neonatal infection. This was a monocenter retrospective study with prospective collection of data including all babies born during the study period. Those presenting infection risk factors had PCT measurement. Three groups were defined: certainly infected, probably infected, and non-infected. A total of 12,485 newborns were included, 2151 had PCT measurement, and 26 were infected. Receiver operating curves of PCT determined 0.6 ng/ml as the best cut-off, with an area under the curve of 0.96 (CI 95% 0.95-0.98). Sensitivity, specificity, positive and negative predictive value and positive and negative likelihood ratios were 0.92 (range, 0.75-0.98), 0.97 (0.96-0.98), 0.28 (0.20-0.36), 0.99 (0.99-0.99), 32 (24-41) and 0.08 (0.02-0.3), respectively. Post-test probabilities were 28% (23-33) if the test was positive, and less than 0.001% (0-1.10) if the test was negative. Gestational age between 28 and 32 weeks (OR 4.4; range, 1.2-16.2) and pH at birth < 7.10 (OR 2.9; 1.1-7.4) were other independent factors of increasing PCT ( < 0.05). PCT measured in umbilical cord blood is reliable to detect early infected and non-infected newborns

Non-immunization associated with increased risk of sudden unexpected death in infancy: A national case–control study

International audienceObjective: In the context of vaccine scepticism, our study aimed to analyse the association between immunization status and the occurrence of sudden unexpected death in infancy (SUDI). Study design: A multi-centre case–control study was conducted between May 2015 and June 2017 with data from the French national SUDI registry (OMIN) for 35 French regional SUDI centres. Cases were infants under age 1 year who died from SUDI and who were registered in OMIN. Controls, matched to cases by age and sex at a 2:1 ratio, were infants admitted to Nantes University Hospital. All immunization data for diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), Haemophilus influenzae b (Hib), hepatitis B (HB) and 13-valent pneumococcal conjugate vaccine (PCV13) were collected by a physician. Cases and controls were considered immunized if at least one dose of vaccine was administered. Results: A total of 91 cases and 182 controls were included. The median age was 131 days (interquartile range 98–200.0) and the sex ratio (M/F) was about 1.1. For all vaccines combined (D-T-aP-IPV-Hib and PCV13), 22 % of SUDI cases versus 12 % of controls were non-immunized, which was significantly associated with SUDI after adjustment for potential adjustment factors (adjusted odds ratio 2.01 [95 % confidence interval 1.01–3.98, p = 0,047]). Conclusions: Non-immunization for D-T-aP-IPV-Hib-HB and PCV13 was associated with increased risk of SUDI. This result can be used to inform the general public and health professionals about this risk of SUDI in case of vaccine hesitancy

Validation of the PECARN clinical decision rule for children with minor head trauma: a French multicenter prospective study

International audienceBackground: To date, the Pediatric Emergency Care Applied Research Network (PECARN) rule for identifying children who are at very low risk of clinically-important traumatic brain injuries after minor head trauma has not been validated prospectively in an independent population. Our goal was to evaluate the diagnostic performance of the PECARN clinical decision rule in a French pediatric population in multiple clinical settings. Methods: We conducted a multicenter, prospective, non-interventional cohort study of patients with minor head trauma who presented to three emergency departments in France. We enrolled patients younger than 16 years of age seeking a consultation within 24 h of head trauma with Glasgow Coma Scale scores of 14-15. Results: During the study period, we included 1499 children of which 421 (28 %) were under 2 years of age, and 955 (64 %) were male. A cranial computed tomography (CT) scan was performed on 76 patients (5.1 %). Of the 1499 included patients, 9 children (0.6 %) had a clinically-important traumatic brain injury, and none were classified as very low risk by the PECARN rule. In our study, the sensitivity of this clinical decision rule was 100 % (95 % CI 66.4 to 100 %), the specificity was 69.9 % (95 % CI 67.5 to 72.2 %) and the negative predictive value was 100 % (95 % CI 99.7 to 100 %). Discussion: Our study confirmed the good predictive performances of the PECARN clinical decision rule for minor head trauma in children. The PECARN rule performed similarly to our study and to its internal validation study. Conclusions: We conducted an external validation study of the PECARN clinical decision rule for the detection of clinically-important traumatic brain injuries in children with minor head trauma, according to the methodological standards. The PECARN rule successfully identified all patients with clinically-important traumatic brain injuries, with a limited use of CT scans. Conducting a broad validation study with a large cohort is a prerequisite to provide sufficient statistical power before authorizing its implementation and generalization. Trial registration: This study has been registered in ClinicalTrials.gov with identifier number: NCT02752711 on April 27, 2016

Persistent Bacteremia in Rabbit Fetuses despite Maternal Antibiotic Therapy in a Novel Intrauterine-Infection Model

The effect of optimized maternal therapy by bactericidal agents was evaluated in a reproducible rabbit model of Escherichia coli maternofetal infection simulating human pharmacokinetics. Intravenous antibiotic therapy was begun in the pregnant rabbit 12 h after bacterial intrauterine inoculation, using a computer-controlled pump to simulate human pharmacokinetics of ceftriaxone (1 g/day) associated or not with gentamicin (3 mg/kg of body weight/day). Data were compared for fetal survival, quantitative blood cultures, fetal histology in treated versus untreated groups, and maternal and fetal antibiotic concentrations in plasma in treated animals. Antibiotic therapy led to dramatic improvement in maternal outcome (100% survival versus 100% death in the untreated group in association with maternal septicemia). Fetal survival also improved, with the two-drug combination providing a more potent effect. After 3 days of treatment, 32% of fetuses survived with one-drug therapy and 62% with two-drug therapy (Yates corrected χ(2), P < 0.05). In untreated animals, bacterial counts in blood cultures increased rapidly during the first 24 h up to 8.1 ± 0.5 log CFU/ml, but remained relatively constant at all times with antibiotic treatment: 4.5 ± 0.7 log CFU/ml at the start of treatment and 6.2 ± 0.4 and 5.2 ± 0.9 log CFU/ml after 72 h for one- and two-drug therapy, respectively (data are means ± standard deviations). The failure of animals to be cured after 3 days of treatment was not due to an inadequate concentration of ceftriaxone, as the residual level in fetal serum at sacrifice was more than 1,000 times the MIC of the microbe. Unexpectedly, inflammation in fetal lung decreased in the treated group after as little as 24 h of antibiotic therapy, despite persistent bacteremia. Although maternal outcome improved and drug concentrations were above the MIC, the treatment did not achieve sterilization of fetuses in utero for this rabbit E. coli maternofetal infection. However, fetal survival showed some improvement, and the histologic features of lung inflammation were reduced