Observational studies demonstrating reduced rates of infections, necrotizing enterocolitis (NEC), and mortality in preterm infants fed their own mother's milk, as opposed to formula, have prompted ...endeavors to achieve similar effects with the right choice of food and food additives. In a systematic review of meta-analyses and randomized controlled trials (RCTs), we considered nutritional interventions aimed at reducing the rates of infections, NEC, or mortality in very preterm infants. The overall effects of particular interventions were presented as risk ratios with 95% confidence intervals. In RCTs, pasteurized human donor milk, as opposed to formula, reduced NEC but not infections or mortality. No differences emerged between infants receiving human or bovine milk-based fortifiers. Pooled data of small trials and a recent large RCT suggested that bovine lactoferrin reduced rates of fungal sepsis without impact on other infections, NEC, or mortality. Pooled data of RCTs assessing the use of prebiotic oligosaccharides found reduced infection but not mortality. Enteral L-glutamine (six RCTs) lowered infection rates, and enteral L-arginine (three RCTs) reduced NEC. A meta-analysis sensitivity approach found multiple-strain (but not single-strain) probiotics to be highly effective in reducing NEC and mortality. Thus, selected food components may help to improve outcomes in preterm infants.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Clinical pharmacology is a multidisciplinary data sciences field that utilizes mathematical and statistical methods to generate maximal knowledge from data. Pharmacometrics (PMX) is a well‐recognized ...tool to characterize disease progression, pharmacokinetics, and risk factors. Because the amount of data produced keeps growing with increasing pace, the computational effort necessary for PMX models is also increasing. Additionally, computationally efficient methods, such as machine learning (ML) are becoming increasingly important in medicine. However, ML is currently not an integrated part of PMX, for various reasons. The goals of this article are to (i) provide an introduction to ML classification methods, (ii) provide examples for a ML classification analysis to identify covariates based on specific research questions, (iii) examine a clinically relevant example to investigate possible relationships of ML and PMX, and (iv) present a summary of ML and PMX tasks to develop clinical decision support tools.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hypoxic ischemia (HI) is an acute brain threat across all age groups. Therapeutic hypothermia ameliorates resulting injury in neonates but its side effects prevent routine use in adults. Hypothermia ...up-regulates a small protein subset that includes RNA-binding motif protein 3 (RBM3), which is neuroprotective under stressful conditions. Here we show how RBM3 stimulates neuronal differentiation and inhibits HI-induced apoptosis in the two areas of persistent adult neurogenesis, the subventricular zone (SVZ) and the subgranular zone (SGZ), while promoting neural stem/progenitor cell (NSPC) proliferation after HI injury only in the SGZ. RBM3 interacts with IGF2 mRNA binding protein 2 (IMP2), elevates its expression and thereby stimulates IGF2 release in SGZ but not SVZ-NSPCs. In summary, we describe niche-dependent regulation of neurogenesis after adult HI injury via the novel RBM3-IMP2-IGF2 signaling pathway.
Machine learning models may enhance the early detection of clinically relevant hyperbilirubinemia based on patient information available in every hospital.
We conducted a longitudinal study on ...preterm and term born neonates with serial measurements of total serum bilirubin in the first two weeks of life. An ensemble, that combines a logistic regression with a random forest classifier, was trained to discriminate between the two classes phototherapy treatment vs. no treatment.
Of 362 neonates included in this study, 98 had a phototherapy treatment, which our model was able to predict up to 48 h in advance with an area under the ROC-curve of 95.20%. From a set of 44 variables, including potential laboratory and clinical confounders, a subset of just four (bilirubin, weight, gestational age, hours since birth) suffices for a strong predictive performance. The resulting early phototherapy prediction tool (EPPT) is provided as an open web application.
Early detection of clinically relevant hyperbilirubinemia can be enhanced by the application of machine learning. Existing guidelines can be further improved to optimize timing of bilirubin measurements to avoid toxic hyperbilirubinemia in high-risk patients while minimizing unneeded measurements in neonates who are at low risk.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Arginine vasopressin (AVP) plays a major role in the homeostasis of fluid balance, vascular tonus, and the regulation of the endocrine stress response. The measurement of AVP levels is difficult due ...to its short half-life and laborious method of detection. Copeptin is a more stable peptide derived from the same precursor molecule, is released in an equimolar ratio to AVP, and has a very similar response to osmotic, hemodynamic, and stress-related stimuli. In fact, copeptin has been propagated as surrogate marker to indirectly determine circulating AVP concentrations in various conditions. Here, we present an overview of the current knowledge on AVP and copeptin in perinatology with a particular focus on the baby's transition from placenta to lung breathing. We performed a systematic review of the literature on fetal stress hormone levels, including norepinephrine, cortisol, AVP, and copeptin, in regard to birth stress. Finally, diagnostic and therapeutic options for copeptin measurement and AVP functions are discussed.
A COVID-19 vaccine can be an important key for mitigating the spread of the pandemic, provided that it is accepted by a sufficient proportion of the population. This study investigated parents’ ...intention to get vaccinated and to have one’s child vaccinated against COVID-19. In May 2020, 612 parents participating with their child in the KUNO-Kids health study completed an online survey. Multivariable logistic regression models were calculated to analyze predictors of intention to vaccinate. Fifty-eight percent of parents intended to get vaccinated against COVID-19, and 51% intended to have their child vaccinated. Significant predictors for the intention to get vaccinated and for having the child vaccinated included stronger parental confidence in one’s knowledge about prevention measures and lower beliefs that policy measures were exaggerated.
Conclusion:
COVID-19 vaccination hesitancy was considerable in our sample of parents in Germany. However, our study revealed some potentially modifiable factors which should be addressed by a comprehensive and tailored communication and education strategy.
What is Known?
• A COVID-19 vaccine can mitigate the spread of the pandemic.
• Many parents are skeptical about vaccinations in general.
What is New?
• COVID-19 vaccination hesitancy was considerable in our sample of parents from Germany, not only for getting vaccinated but also for having the child vaccinated.
• Negative parental attitudes regarding policy measures to contain the pandemic were associated with a lower intention to vaccinate.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Background To assess the prognostic value of early echocardiographic indices of right ventricular function and vasoactive peptides for prediction of bronchopulmonary dysplasia (BPD) or death in very ...preterm infants. Methods Prospective study involving 294 very preterm infants (median IQR gestational age 28.4 26.4-30.4 weeks, birth weight 1065 800-1380 g), of whom 57 developed BPD (oxygen supplementation at 36 weeks postmenstrual age) and 10 died. Tricuspid annular plane systolic excursion (TAPSE), right ventricular index of myocardial performance (RIMP), plasma concentrations of mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) were measured on day 7 of life. Results RIMP was significantly increased (median IQR 0.3 0.23-0.38 vs 0.22 0.15-0.29), TAPSE decreased (median IQR 5.0 5.0-6.0 vs 6.0 5.4-7.0 mm), MR-proANP increased (median IQR 784 540-936 vs 353 247-625 pmol/L), and CT-proET1 increased (median IQR 249 190-345 vs 199 158-284 pmol/L) in infants who developed BPD or died, as compared to controls. All variables showed significant but weak correlations with each other (r.sub.S -0.182 to 0.359) and predicted BPD/death with similar accuracy (areas under receiver operator characteristic curves 0.62 to 0.77). Multiple regression revealed only RIMP and birth weight as independent predictors of BPD or death. Conclusions Vasoactive peptide concentrations and echocardiographic assessment employing standardized measures, notably RIMP, on day 7 of life are useful to identify preterm infants at increased risk for BPD or death.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The first medical examination of the newborn after birth plays an essential role in identifying congenital malformations and life-threatening conditions. Currently, no Europe-wide guidelines or ...standards for performing the first neonatal examination exist. It is unclear which professional group carries out this examination in different European countries. Additionally, there are no requirements for an examination accepted throughout Europe. The objective of this cross-sectional study was to identify the status quo of medical guidelines and legal requirements in place as well as to determine which profession carries out the first neonatal examination in European countries.INTRODUCTIONThe first medical examination of the newborn after birth plays an essential role in identifying congenital malformations and life-threatening conditions. Currently, no Europe-wide guidelines or standards for performing the first neonatal examination exist. It is unclear which professional group carries out this examination in different European countries. Additionally, there are no requirements for an examination accepted throughout Europe. The objective of this cross-sectional study was to identify the status quo of medical guidelines and legal requirements in place as well as to determine which profession carries out the first neonatal examination in European countries.By means of a structured questionnaire, one expert survey at two international medical specialist conferences in Europe in 2019 were carried out. Participants were asked whether medical guidelines or legal requirements exist in their home country and which medical profession is recommended to perform the neonatal examination. Survey participants were delegates of national neonatal or perinatal societies. To verify statements, further neonatal experts at European level were contacted.METHODSBy means of a structured questionnaire, one expert survey at two international medical specialist conferences in Europe in 2019 were carried out. Participants were asked whether medical guidelines or legal requirements exist in their home country and which medical profession is recommended to perform the neonatal examination. Survey participants were delegates of national neonatal or perinatal societies. To verify statements, further neonatal experts at European level were contacted.A total of 51 participants from 35 countries in Europe were interviewed. Overall, 28 of 35 participating countries (80%) have published medical guidelines and 24 (69%) have legal requirements in place for the first neonatal examination. A wide range of professional groups (midwives, neonatologists, pediatricians, obstetricians, general practitioners, nurse practitioners and advanced neonatal nurse practitioners) performs the first neonatal exam. In 27 (77%) countries, midwives are the main group of examiners.RESULTSA total of 51 participants from 35 countries in Europe were interviewed. Overall, 28 of 35 participating countries (80%) have published medical guidelines and 24 (69%) have legal requirements in place for the first neonatal examination. A wide range of professional groups (midwives, neonatologists, pediatricians, obstetricians, general practitioners, nurse practitioners and advanced neonatal nurse practitioners) performs the first neonatal exam. In 27 (77%) countries, midwives are the main group of examiners.Currently a European patchwork of different medical guidelines and legal requirements in regard to the first medical examination of the newborn after birth exists. In addition, a variety of professional groups perform the first neonatal examination. There is great potential for standardization and an expert committee could establish common European guidelines in order to ensure the best possible neonatal care throughout Europe.CONCLUSIONSCurrently a European patchwork of different medical guidelines and legal requirements in regard to the first medical examination of the newborn after birth exists. In addition, a variety of professional groups perform the first neonatal examination. There is great potential for standardization and an expert committee could establish common European guidelines in order to ensure the best possible neonatal care throughout Europe.
The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers.
Care providers from ...neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies.
Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance.
At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus.
At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions. A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted. We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Primary blood coagulation and wound sealing are orchestrated by von Willebrand factor (VWF), a large multimeric glycoprotein. Upon release of arginine vasopressin (AVP), VWF containing high molecular ...weight multimers is secreted. By measuring copeptin, the C-terminal part of the AVP prohormone, we recently found strongly increased AVP levels in children with febrile seizures (FS) as compared to children with fever but without seizures. It is unknown if increased AVP levels in FS are of any biological function. Therefore, our a priori hypothesis was that children with FS have increased VWF parameters in parallel with higher AVP levels.
We conducted a prospective, cross-sectional study of children aged between 6 months and 5 years. Children that presented at our emergency department with fever or a recent FS (within four hours) were evaluated to be included to the study. We measured serum copeptin and VWF parameters, including analyses of VWF:Antigen (WVF:Ag), VWF:collagen binding activity (VWF:CB) and VWF multimers in children with FS, febrile infections without seizures and additionally, in a non-febrile control group.
We included 54 children in our study, 30 with FS, 10 in the febrile control group, and 14 in the non-febrile control group. Serum copeptin levels were significantly higher in children with FS (median IQR 24.73 pmol/l 13.65-68.65) compared to the febrile control group (5.66 pmol/l 4.15-8.07, p = 0.002) and the non-febrile control group (4.78 pmol/l 3.33-5.3, p<0.001). VWF:CB levels were also significantly higher in children with FS (VWF:CB 2.29 U/ml 1.88-2.97) as compared to the febrile (VWF:CB 1.41 U/ml 1.27-1.93, p = 0.048) and the non-febrile control group (VWF:CB 1.15 U/ml 0.98-1.21, p<0.001). VWF:Ag tended to be higher in children with FS compared to both control groups. Multivariate regression analysis revealed FS and copeptin as major determinants of VWF:CB.
Our results suggest that increased secretion of AVP in children with FS is associated with higher plasma levels of VWF parameters. Especially VWF:CB may serve as additional biomarker in the diagnosis of FS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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