Risk of childhood neoplasms related to neonatal phototherapy- a systematic review and meta-analysis.

CONTEXT: Observational studies have shown conflicting results as to whether exposure to neonatal phototherapy is associated with increased rates of childhood cancer. OBJECTIVE: To describe the rates of childhood neoplasms and cancer after neonatal phototherapy. DATA SOURCES: The CENTRAL, PubMed, Scopus, and Web of Science databases. STUDY SELECTION: Observational studies regardless of design were included. DATA EXTRACTION: The data were extracted by one author and validated by another. The risk-of-bias assessment was performed using the ROBINS-E and Joanna Briggs Institute critical appraisal tools. RESULTS: Six cohort and 10 case-control studies were included. The overall risk of bias was high in seven and low in nine studies. In cohort studies, the odds ratio (OR) was increased for hematopoietic cancer (1.44; confidence interval [CI]: 1.16-1.80) and solid tumors (OR: 1.18; CI: 1.00-1.40). In case-control studies, the OR was 1.63 (CI: 0.99-2.67) for hematopoietic cancers and 1.18 (CI: 1.04-1.34) for solid tumors. CONCLUSIONS: Children with a history of neonatal phototherapy had increased risk of hematopoietic cancer and solid tumors. The evidence quality was limited due to the high risk of bias and potential residual confounding. IMPACT STATEMENT: Exposure to neonatal phototherapy increased later risk of hematopoietic cancer and solid tumors. This is the most comprehensive study on the association between phototherapy and cancer, but the evidence quality was limited due risk of bias and residual confounding. Future large scale well conducted studies are still needed to better estimate the association and.

High-flow nasal cannula use in pediatric patients for other indications than acute bronchiolitis-a scoping review of randomized controlled trials.

The objective of the study is to summarize current literature on high-flow nasal cannula (HFNC) use for different indications in pediatric patient excluding acute bronchiolitis and neonatal care. The study design is a systematic scoping review. Pubmed, Scopus, and Web of Science databases were searched in February, 2023. All abstracts and full texts were screened by two independent reviewers. Randomized controlled trials focusing on HFNC use in pediatric patients (age < 18 years) were included. Studies focusing on acute bronchiolitis and neonatal respiratory conditions were excluded. Study quality was assessed by Cochrane risk of bias 2.0 tool. The main outcomes are patient groups and indications, key outcomes, and risk of bias. After screening 1276 abstracts, we included 22 full reports. Risk of bias was low in 11 and high in 5 studies. We identified three patient groups where HFNC has been studied: first, children requiring primary respiratory support for acute respiratory failure; second, perioperative use for either intraprocedural oxygenation or postoperative respiratory support; and third, post-extubation care in pediatric intensive care for other than postoperative patients. Clinical and laboratory parameters were assessed as key outcomes. None of the studies analyzed cost-effectiveness.Conclusion: This systematic scoping review provides an overview of current evidence for HFNC use in pediatric patients. Future studies should aim for better quality and include economic evaluation with cost-effectiveness analysis.Protocol registration: Protocol has been published https://osf.io/a3y46/ .

Pacifier use and breastfeeding in term and preterm newborns-a systematic review and meta-analysis.

The purpose of this study is to assess whether pacifier use is associated with breastfeeding success in term and preterm newborns and whether it influences hospitalization time in preterm newborns. Four databases were searched for randomized controlled trials (RCTs), and a systematic review and meta-analysis were conducted. The risk of bias and evidence quality, according to the GRADE methodology, were analyzed. Risk ratios with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) for continuous outcomes were used. The random effect model was used if heterogeneity was high (I2 over 40%). We screened 772 abstracts, assessed 44 full texts, and included 10 studies, of which 5 focused on term and 5 on preterm newborns. There were a few concerns about the risk of bias in 9 of the 10 studies. Breastfeeding rates were analyzed at 2, 3, 4, and 6 months, and the success rates were similar between the restricted and free pacifier use groups (evidence quality was moderate to high). In preterm neonates, the use of a pacifier shortened the duration of hospitalization by 7 days (MD 7.23, CI 3.98-10.48) and the time from gavage to total oral feeding by more than 3 days (MD 3.21 days, CI 1.19-5.24) (evidence quality was ranked as moderate).   Conclusions: Based on our meta-analysis, pacifier use should not be restricted in term newborns, as it is not associated with lower breastfeeding success rates. Furthermore, introducing pacifiers to preterm newborns should be considered, as it seems to shorten the time to discharge as well as the transition time from gavage to total oral feeding. What is Known: • Observational studies show that infants who use a pacifier are weaned from breastfeeding earlier. • Previous randomized studies have not presented such results, and there have been no differences in the successful breastfeeding rates regardless of the use of pacifier. What is New: • Term and preterm newborns do not have worse breastfeeding outcomes if a pacifier is introduced to them, and additionally preterm newborns have shorter hospitalization times. • The decision to offer a pacifier should depend on the caregivers instead of hospital policy or staff recommendation, as there is no evidence to support the prohibition or restriction.

Homozygosity of a Founder Variant c.1508dupC in DOK7 Causes Congenital Myasthenia With Variable Severity.

Background and Objectives: Description of 15 patients with the same variant in DOK7 causing congenital myasthenic syndrome (CMS). Methods: Nine adult and 6 pediatric patients were studied with molecular genetic and clinical investigations. Results: All patients were identified with the c.1508dupC variant in DOK7, of whom 13 were homozygous and 2 patients compound heterozygous. Only 2 patients had limb girdle phenotype, while all adult patients also had ptosis, ophthalmoplegia, facial weakness, as well as inspiratory stridor. Pediatric patients had severe respiratory insufficiency and feeding difficulties at birth. Discussion: The disease severity in our patients varied extensively from ventilator or wheelchair dependence to mild facial weakness, ptosis, and ophthalmoparesis. Most of the patients had normal transmission in conventional 3 Hz stimulation electrophysiologic studies, making the diagnosis of CMS challenging. Our cohort of adult and pediatric patients expands the phenotype of DOK7 CMS and shows the importance of correct and early diagnosis.

Ursodeoxycholic acid as adjuvant treatment to phototherapy for neonatal hyperbilirubinemia: a systematic review and meta-analysis.

BACKGROUND: Neonatal hyperbilirubinemia is observed in most newborns, and 5-15% of neonates require phototherapy. Phototherapy is effective but often prolongs hospitalization and has both short-term and potential long-term harms. The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid (UDCA) combined with phototherapy in neonatal hyperbilirubinemia. METHODS: A literature search was conducted on September 1, 2021; 590 studies were screened, and 17 full texts were assessed by two authors. We included randomized controlled trials with or without placebo intervention. Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration. We calculated mean differences with 95% confidence intervals (CI). RESULTS: Six studies with 880 neonates were included. Of these studies, only two used a placebo-controlled double-blinded design. The overall risk of bias was high in one and moderate in four of the included studies. The mean decrease in the total bilirubin level during the first 24 hours was 2.06 mg/dL (95% CI 0.82-3.30; six studies) greater in the UDCA treatment group. The phototherapy duration was 19.7 hours (95% CI 10.4-29.1; five studies) shorter in the UDCA treatment group. CONCLUSIONS: We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment. Further studies are needed to confirm the efficacy, acute and long-term outcomes, and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia.

Helium-oxygen in bronchiolitis-A systematic review and meta-analysis.

INTRODUCTION: Bronchiolitis is common reason for infant hospitalization. The aim of our systematic review and meta-analysis was to evaluate helium-oxygen (heliox) in bronchiolitis. METHODS: We screened 463 studies, assessed 22 of them, and included six randomized controlled trials. Primary outcomes were the need for continuous positive airway pressure (CPAP) or intubation, hospitalization duration, and change in the modified Woods Clinical Asthma Scale (M-WCAS). We calculated mean differences with 95% confidence intervals (CIs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. RESULTS: Six studies (five double- and one single-blinded) with 560 infants were included. The risk of bias was high in one, moderate in four, and low in one. The RR for the need for CPAP (three studies) was 0.87 (CI: 0.56-1.35), and for intubation (four studies) was 1.39 (CI: 0.53-3.63), heliox compared to air-oxygen. The hospital stay (four studies) was 0.25 days longer (CI: -0.22 to 0.71) in the heliox group. The mean decrease in M-WCAS from the baseline (three studies) was 1.90 points (CI: 1.46-2.34) greater in the heliox group. CONCLUSION: We found low-quality evidence that heliox does not reduce the need for CPAP, intubation, or length of hospitalization for bronchiolitis. Based on the M-WCAS scores, heliox seems to relieve respiratory distress symptoms rapidly after its initiation. The included studies had high heterogeneity in their methods and included relatively mild cases of bronchiolitis. A larger randomized controlled trial with more severe cases of bronchiolitis with enough power to analyze the need for intubation is needed in the future.

Characterization of articular cartilage by combining microscopic analysis with a fibril-reinforced finite-element model.

Load-bearing characteristics of articular cartilage are impaired during tissue degeneration. Quantitative microscopy enables in vitro investigation of cartilage structure but determination of tissue functional properties necessitates experimental mechanical testing. The fibril-reinforced poroviscoelastic (FRPVE) model has been used successfully for estimation of cartilage mechanical properties. The model includes realistic collagen network architecture, as shown by microscopic imaging techniques. The aim of the present study was to investigate the relationships between the cartilage proteoglycan (PG) and collagen content as assessed by quantitative microscopic findings, and model-based mechanical parameters of the tissue. Site-specific variation of the collagen network moduli, PG matrix modulus and permeability was analyzed. Cylindrical cartilage samples (n=22) were harvested from various sites of the bovine knee and shoulder joints. Collagen orientation, as quantitated by polarized light microscopy, was incorporated into the finite-element model. Stepwise stress-relaxation experiments in unconfined compression were conducted for the samples, and sample-specific models were fitted to the experimental data in order to determine values of the model parameters. For comparison, Fourier transform infrared imaging and digital densitometry were used for the determination of collagen and PG content in the same samples, respectively. The initial and strain-dependent fibril network moduli as well as the initial permeability correlated significantly with the tissue collagen content. The equilibrium Young's modulus of the nonfibrillar matrix and the strain dependency of permeability were significantly associated with the tissue PG content. The present study demonstrates that modern quantitative microscopic methods in combination with the FRPVE model are feasible methods to characterize the structure-function relationships of articular cartilage.

Collagen network primarily controls Poisson's ratio of bovine articular cartilage in compression.

The equilibrium Young's modulus of articular cartilage is known to be primarily determined by proteoglycans (PGs). However, the relation between the Poisson's ratio and the composition and structure of articular cartilage is more unclear. In this study, we determined Young's modulus and Poisson's ratio of bovine articular cartilage in unconfined compression. Subsequently, the same samples, taken from bovine knee (femoral, patellar and tibial cartilage) and shoulder (humeral cartilage) joints, were processed for quantitative microscopic analysis of PGs, collagen content, and collagen architecture. The Young's modulus, Poisson's ratio, PG content (estimated with optical density measurements), collagen content, and birefringence showed significant topographical variation (p < 0.05) among the test sites. Experimentally the Young's modulus was strongly determined by the tissue PG content (r = 0.86, p < 0.05). Poisson's ratio revealed a significant negative linear correlation (r = -0.59, p < 0.05) with the collagen content, as assessed by the Fourier transform infrared imaging. Finite element analyses, conducted using a fibril reinforced biphasic model, indicated that the mechanical properties of the collagen network strongly affected the Poisson's ratio. We conclude that Poisson's ratio of articular cartilage is primarily controlled by the content and organization of the collagen network.

Transient Postnatal Gonadal Activation and Growth Velocity in Infancy.

BACKGROUND AND OBJECTIVE: Transient activation of the hypothalamic-pituitary-gonadal axis with a sex steroid surge is observed in boys and girls during the first months of life. However, the role of sex steroids in the regulation of growth has not been substantiated in infancy. We tested the hypothesis that testosterone (T) surge, known to be higher in infant boys than in girls during the transient postnatal gonadal activation regulates linear growth in infants. METHODS: To characterize in detail the linear growth velocity (GV) differences between genders in the normal population in early infancy, we evaluated growth of 18 570 healthy infants (51.0% boys) with 162 003 height measurements from birth to 12 months of age. GV was monitored and compared with serially measured urinary T and estradiol levels and serum insulin-like growth factor 1 levels in 84 healthy infants (45% boys) during the first 6 months of life. RESULTS: GV was significantly faster from birth to 6 months of age in boys than in girls (P ≤ .01). The greatest GV difference, 4.1 cm per year, was observed at 1 month of age, simultaneously with the peak of postnatal gonadal activation. In the mixed model analysis, GV showed a significant positive association with T in both genders (parameter estimate up to 0.62, 95% confidence interval 0.44-0.81). CONCLUSIONS: These results provide a new insight into the regulation of growth in infants and elucidate a novel biological role of the transient postnatal gonadal activation in growth regulation.

2-D finite difference time domain model of ultrasound reflection from normal and osteoarthritic human articular cartilage surface.

Quantitative high-frequency ultrasonic evaluation of articular cartilage has shown a potential for the diagnosis of osteoarthritis, where the roughness of the surface, collagen and proteoglycan contents, and the density and mechanical properties of cartilage change concurrently. Experimentally, these factors are difficult to investigate individually and thus a numerical model is needed. The present study is the first one to use finite difference time domain modeling of pulse-echo measurements of articular cartilage. Ultrasound reflection from the surface was investigated with varying surface roughness, material parameters (Young's modulus, density, longitudinal, and transversal velocities) and inclination of the samples. The 2-D simulation results were compared with the results from experimental measurements of the same samples in an identical geometry. Both the roughness and the material parameters contributed significantly to the ultrasound reflection. The angular dependence of the ultrasound reflection was strong for a smooth cartilage surface but disappeared for the samples with a rougher surface. These results support the findings of previous experimental studies and indicate that ultrasound detects changes in the cartilage that are characteristic of osteoarthritis. In the present study there are differences between the results of the simulations and the experimental measurements. However, the systematic patterns in the experimental behavior are correctly reproduced by the model. In the future, our goal is to develop more realistic acoustic models incorporating inhomogeneity and anisotropy of the cartilage.

Differences in acoustic properties of intact and degenerated human patellar cartilage during compression.

Ultrasound indentation measurements have been shown to provide means to assess cartilage integrity and mechanical properties. To determine cartilage stiffness in the ultrasound indentation geometry, cartilage is compressed with an ultrasound transducer to determine the induced strain from the ultrasound signal using the time-of-flight principle. As the ultrasound speed in cartilage has been shown to vary during compression, the assumption of constant speed generates significant errors in the values of mechanical parameters. This variation in ultrasound speed has been investigated in intact cartilage, however, its existence and significance in degenerated tissue is unknown. In the present study, we investigate this issue with both intact and spontaneously degenerated human tissue. To accomplish this aim, we determined ultrasound speed and attenuation in human patellar cartilage (n=68) during mechanical loading. For reference, cartilage mechanical properties and proteoglycan, collagen and water contents were determined. The acoustic properties were related to the composition and mechanical properties of the samples. Ultrasound speed showed significant, site-dependent variation and it was significantly associated (r=0.79-0.81, p<0.01) with the mechanical properties of cartilage. The compression related decrease in ultrasound speed showed statistically significant variation between different stages of degeneration. Error simulations revealed that changes in ultrasound speed during 2% compression could generate errors up to 15% in the values of elastic moduli of samples with early degeneration, if determined with the ultrasound indentation technique. In samples with advanced degeneration, the error was significantly (p<0.05) smaller being 2% on average. As the compression related variation in ultrasound speed was lower in more degenerated samples, the mechanical parameters could be diagnosed more reliably in tissue showing advanced degeneration. The present results address the need to consider possible uncertainties in mechano-acoustic measurements of articular cartilage and call for methods to correct the effect of variable sound speed during compression.