Source of human milk (mother or donor) is more important than fortifier type (human or bovine) in shaping the preterm infant microbiome.

Milk fortifiers help meet the nutritional needs of preterm infants receiving their mother's own milk (MOM) or donor human milk. We conducted a randomized clinical trial (NCT03214822) in 30 very low birth weight premature neonates comparing bovine-derived human milk fortifier (BHMF) versus human-derived fortifier (H2MF). We found that fortifier type does not affect the overall microbiome, although H2MF infants were less often colonized by an unclassified member of Clostridiales Family XI. Secondary analyses show that MOM intake is strongly associated with weight gain and microbiota composition, including Bifidobacterium, Veillonella, and Propionibacterium enrichment. Finally, we show that while oxidative stress (urinary F2-isoprostanes) is not affected by fortifier type or MOM intake, fecal calprotectin is higher in H2MF infants and lower in those consuming more MOM. Overall, the source of human milk (mother versus donor) appears more important than the type of milk fortifier (human versus bovine) in shaping preterm infant gut microbiota.

La prise en charge de la persistance du canal artériel chez les nouveau-nés prématurés.

La prise en charge de la persistance du canal artériel est l'un des aspects les plus litigieux des soins aux nouveau-nés prématurés. On peut la classer en deux grandes catégories : la prophylaxie et le traitement en cas de symptômes. L'administration prophylactique d'indométacine par voie intraveineuse chez les nouveau-nés d'extrême petit poids à la naissance peut limiter les graves hémorragies intraventriculaires. L'échocardiographie est systématiquement recommandée pour confirmer une persistance du canal artériel avant d'envisager le traitement en cas de symptômes, qui peut prendre la forme d'un traitement conservateur, d'une pharmacothérapie ou d'une fermeture invasive. L'ibuprofène doit être considéré comme le traitement pharmacologique de première intention dans cette situation. Une forte dose peut être à privilégier, particulièrement chez les nouveau-nés prématurés de plus de trois à cinq jours de vie. Si deux traitements pharmacologiques consécutifs échouent ou si la pharmacothérapie est contre-indiquée, on peut envisager une fermeture invasive en cas de symptômes marqués lorsque l'échocardiographie révèle des signes de shunt à fort volume à travers le canal artériel et de circulation pulmonaire excessive.

Management of the patent ductus arteriosus in preterm infants.

Management of the patent ductus arteriosus (PDA) is one of the most contentious topics in the care of preterm infants. PDA management can be broadly divided into prophylactic and symptomatic therapy. Prophylaxis with intravenous indomethacin in extremely low birth weight infants may reduce severe intraventricular hemorrhage. Echocardiography should be routinely used to confirm the presence of a PDA before considering symptomatic therapy. A symptomatic PDA can be managed conservatively, using pharmacotherapy or with procedural closure. Ibuprofen should be considered as the pharmacotherapy of choice for a symptomatic PDA. High-dose ibuprofen may be preferable, especially for preterm infants beyond the first 3 to 5 days of age. If pharmacotherapy fails (after two courses) or is contraindicated, procedural closure may be considered for infants with a persistent PDA with significant clinical symptoms in addition to echocardiographic signs of a large PDA shunt volume and pulmonary over-circulation.

A pharmacogenomic investigation of the cardiac safety profile of ondansetron in children and pregnant women.

BACKGROUND: Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication. METHODS: Three patient groups receiving ondansetron were recruited and followed prospectively (pediatric post-surgical patients n = 101; pediatric oncology patients n = 98; pregnant women n = 62). Electrocardiograms were conducted at baseline, and 5- and 30-min post-ondansetron administration, to determine the effect of ondansetron treatment on QT interval. Pharmacogenomic associations were assessed via analyses of comprehensive CYP2D6 genotyping and genome-wide association study data. RESULTS: In the entire cohort, 62 patients (24.1%) met the criteria for prolonged QT, with 1.2% of the cohort exhibiting unsafe QT prolongation. The most significant shift from baseline occurred at five minutes post-ondansetron administration (P = 9.8 × 10-4). CYP2D6 activity score was not associated with prolonged QT. Genome-wide analyses identified novel associations with a missense variant in TLR3 (rs3775291; P = 2.00 × 10-7) and a variant linked to the expression of SLC36A1 (rs34124313; P = 1.97 × 10-7). CONCLUSIONS: This study has provided insight into the genomic basis of ondansetron-induced cardiac changes and has emphasized the importance of genes that have been implicated in serotonin-related traits. These biologically-relevant findings represent the first step towards understanding this adverse event with the overall goal to improve the safety of this commonly used antiemetic medication.

The use of oral opioids to control children's pain in the post-codeine era.

Pain is a common problem for children, and pain management comprises both pharmacologic and nonpharmacologic measures. For moderate to severe pain, oral opioids have been a popular choice for the last few decades. Codeine has historically been the best-known oral opioid for use in children. However, availability and use of codeine have sharply declined due to safety concerns. A variety of other opioids have been used in place of codeine, but data are limited regarding their efficacy and safety in children. While the same pathways metabolize oral oxycodone as codeine, oxycodone's pharmacokinetics varies widely. There are also limited data on the safety and efficacy of oral hydromorphone and tramadol use for children. Oral morphine is the opiate alternative to codeine for which there is the most evidence of safety and efficacy in children. Research is needed to investigate both other opioids and non-opioid approaches to guide evidence-based analgesic therapy and treatment for moderate-to-severe pain in children.

Les opioïdes par voie orale en remplacement de la codéine pour contrôler la douleur chez les enfants.

La douleur est un problème courant chez les enfants. Des mesures pharmacologiques et non pharmacologiques sont utilisées pour la prendre en charge. Depuis quelques décennies, les opioïdes par voie orale sont populaires pour soulager la douleur modérée à grave. La codéine a longtemps été l'opioïde par voie orale le plus connu pour les enfants. Pour des raisons de sécurité, elle est désormais nettement moins accessible et moins employée. Divers autres opioïdes la remplacent, mais les données sur leur efficacité et leur sécurité sont limitées chez les enfants. L'oxycodone par voie orale emprunte les mêmes voies métaboliques que la codéine, mais sa pharmacocinétique est très variable. Les données sur la sécurité et l'efficacité de l'hydromorphone et du tramadol par voie orale chez les enfants sont également limitées. Lorsqu'on y recourt au lieu de la codéine, la morphine par voie orale est l'opiacé dont la sécurité et l'efficacité sont les mieux démontrées chez les enfants. Des recherches devront être réalisées pour explorer d'autres approches relatives aux médicaments opioïdes et non opioïdes, afin d'orienter les traitements analgésiques fondés sur des données probantes qui soulageront la douleur modérée à grave chez les enfants.

Teens Taking Charge: A Randomized Controlled Trial of a Web-Based Self-Management Program With Telephone Support for Adolescents With Juvenile Idiopathic Arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a serious and potentially debilitating pediatric illness. Improved disease self-management may help to improve health outcomes. OBJECTIVE: This study aimed to evaluate the effectiveness of the Teens Taking Charge Web-based self-management intervention in reducing symptoms and improving health-related quality of life (HRQL) in adolescents with JIA compared with a Web-based education control condition. METHODS: Adolescents with JIA aged 12 to 18 years were recruited from 11 Canadian pediatric rheumatology centers. Caregivers were invited to participate along with their child. In addition to standard medical care, participants were randomized to receive either (1) the Teens Taking Charge self-management intervention or (2) a Web-based education control condition for a period of 12 weeks. Adolescents in the intervention group completed website modules addressing cognitive behavioral coping skills, stress management, and other self-management topics, while also receiving monthly telephone calls from a trained health coach. Adolescents in the education control group were instructed to view a series of preselected public JIA educational websites and received monthly calls from a coach who asked about their own best efforts at managing JIA. Caregivers in the intervention group completed website modules related to promoting independence and disease self-management in their child. Caregivers in the education control group were instructed to view a series of preselected public JIA educational websites. Outcome assessment occurred at baseline, 12 weeks (posttreatment), and at 6 and 12 months postrandomization. The primary outcomes were pain intensity, pain interference, and HRQL. Secondary outcomes were emotional symptoms, adherence, coping, knowledge, and self-efficacy. RESULTS: In total, 333 adolescents and 306 caregivers were enrolled. Significant overall reductions in pain intensity (P=.02) and pain interference (P=.007) were observed for intervention group participants compared with those in the education control group, after adjusting for baseline levels. There was a significant overall improvement in HRQL related to problems with pain (P=.02) and problems with daily activities (P=.01). There was also a significant difference in the intervention group over time (P=.008) for HRQL related to treatment problems, with the intervention group participants demonstrating improved HRQL by 12 months compared with education control group participants. Both groups showed nonsignificant improvements compared with baseline in other primary outcomes. There were no significant differences between the groups in any secondary outcomes or caregiver-reported outcomes. CONCLUSIONS: The results of this randomized trial suggest that the Teens Taking Charge Web-based intervention is effective at reducing both pain intensity and pain interference, as well as improving HRQL in adolescents with JIA, compared with education control. These effects are sustained for up to 12 months following program completion. The Teens Taking Charge program is now publicly available at no cost. TRIAL REGISTRATION: ClinicalTrials.gov NCT01572896; https://clinicaltrials.gov/ct2/show/NCT01572896.

Pharmacare in Canada: The paediatric perspective.

Canada's drug insurance system is one of the most expensive in the world, yet millions of Canadians still struggle to access necessary medications. As a result, provincial, territorial, and federal governments are considering public pharmacare policy proposals to ensure that all Canadians can access the medications they need. Pharmacare policies offer an opportunity to prioritize children and youth, whose unique drug needs have long been neglected. Prescription drug use is common in this population, with approximately half of Canadian children and youth requiring at least one prescription in any given year. Drug use remains concentrated, however, among those with complex, chronic, and serious diseases. Children and youth rely heavily on compounded and off-label prescription drugs, which impacts safety, efficacy, palatability, and cost. Reimbursement decision-making bodies do not appropriately value the unique benefits of paediatric drugs, including child-friendly formulations, improved quality of life for children and families, and cost-savings outside the healthcare system. Regardless of the pharmacare model ultimately implemented, ensuring universal, comprehensive, and portable prescription drug coverage for all children and youth is essential. To accomplish this, paediatric drug experts should develop a national, evidence-informed formulary of paediatric drugs. Health Canada should also improve processes to make commercial paediatric drugs and child-friendly formulations more available and accessible. The federal government must also support paediatric drug research and development to this end.

Access to Multidisciplinary Care for Pediatric Weight Management: Exploring Perspectives of the Health Care Team within Canada and the United States.

Background: In Canada and the United States, most families referred for pediatric weight management services do not start treatment. Of families who initiate care, many discontinue before the program ends. Parents and youth have reported difficulties in accessing services as an important barrier to starting or completing programming. The purpose of this study was to understand barriers and identify potential solutions related to access to care from the perspective of health care team members from Canada and the United States. Methods: Qualitative description method guided the study design. Participants were health care team members, purposefully recruited through Canadian and US-based pediatric weight management program registries. Telephone interviews were conducted with participants between February and May 2017. Interviews were transcribed verbatim and analyzed using content analysis. Results: Eighteen individuals from 16 sites participated (n = 8 Canada, n = 8 United States). Access barriers and potential solutions were related to: (1) referral and eligibility, (2) wait lists and program capacity, (3) logistics and costs, and (4) stigma and weight bias. Barriers were similar between Canadian and US sites, with the exception of cost-related barriers. Conclusions: Health care providers from Canada and the United States reported multiple societal, organizational, service, and family-level barriers to accessing multidisciplinary pediatric weight management care. Proposed solutions suggest that service providers can play a key role alongside families to improve access to appropriate care. Further research is needed to demonstrate the feasibility and effectiveness of proposed solutions.

The fetal safety of Levetiracetam: a systematic review.

OBJECTIVE: To systematically review the available published evidence on the fetal safety of Levetiracetam with focus on birth defects. RESULTS: Eight studies met the inclusion criteria; five pregnancy registries and one population based cohort study. A total of 27 major congenital malformations were reported among 1213 Levetiracetam monotherapy - exposed pregnant women, yielding an overall major malformation rate of 2.2% (27/1213) [95% confidence interval of 1.53-3.22]. In contrast, Levetiracetam polytherapy was associated with significantly higher malformation rate of 6.3% (34/541) [95% CI of 4.53-8.65] (P<0.001). Additionally 2 studies investigating child neurodevelopment in Levetiracetam - exposed children revealed that the measured achievements were well above those children exposed to valproic acid, and similar to unexposed controls. CONCLUSIONS: The current evidence suggests that the overall risk of major malformation after first trimester exposure to Levetiracetam is within the population baseline risk of 1-3%, with no apparent adverse effects on long term child development.