Respiratory Syncytial Virus Infections in Polish Pediatric Patients from an Expert Perspective.

Respiratory syncytial virus (RSV) is the most common pathogen causing respiratory tract infections in infants, affecting over 90% of children within the first two years of life. It may cause lower respiratory tract infections, which constitute a significant healthcare burden both in the primary and secondary care settings. Meanwhile, the data regarding RSV disease in Poland is scarce, and published data significantly differs from the numbers reported for other countries with longstanding surveillance and reporting systems. A literature review and an expert panel were conducted to (1) understand the healthcare burden of RSV infections in Poland; (2) collect data on infection seasonality, patient pathway, and management patterns; and (3) evaluate RSV infection surveillance in Poland. According to the literature, RSV is the major agent responsible for non-influenza respiratory diseases in Poland. The reported rates of hospitalization for RSV infections are 267.5/100,000 for children under 5 years of age and 1132.1/100,000 for those under 1 year of age. Comparisons with data from other countries suggest that these values may be underestimated, possibly due to insufficient access to microbiological testing and a low awareness of RSV. Infections occur mainly between December and April, however, this pattern has changed following the implementation of preventive measures for coronavirus disease 2019 in the past few years. According to available reports, bronchodilators, antibiotics, corticosteroids, and X-ray imaging have been frequently used. The surveillance system in Poland has limitations, but these may be overcome due to recent changes in healthcare law as well as the availability and reimbursement of diagnostic tests.

Protocol for a multicenter, double-blind, randomized, placebo-controlled phase III trial of the inhaled ß2-adrenergic receptor agonist salbutamol for transient tachypnea of the newborn (the REFSAL trial).

Background: Transient tachypnea of the newborn (TTN), which results from inadequate absorption of fetal lung fluid, is the most common cause of neonatal respiratory distress. Stimulation of ß-adrenergic receptors enhances alveolar fluid absorption. Therefore, the ß2-adrenergic receptor agonist salbutamol has been proposed as a treatment for TTN. This study aims to evaluate the efficacy and safety of salbutamol as supportive pharmacotherapy together with non-invasive nasal continuous positive airway pressure (NIV/nCPAP) for the prevention of persistent pulmonary hypertension of the newborn (PPHN) in infants with TTN. Methods and analysis: This multicenter, double-blind, phase III trial will include infants with a gestational age between 32 and 42 weeks who are affected by respiratory disorders and treated in eight neonatal intensive care units in Poland. A total of 608 infants within 24 h after birth will be enrolled and randomly assigned (1:1) to receive nebulized salbutamol with NIV or placebo (nebulized 0.9% NaCl) with NIV. The primary outcome is the percentage of infants with TTN who develop PPHN. The secondary outcomes are the severity of respiratory distress (assessed with the modified TTN Silverman score), frequency of need for intubation, duration of NIV and hospitalization, acid-base balance (blood pH, partial pressure of O2 and CO2, and base excess), and blood serum ionogram for Na+, K+, and Ca2+. Discussion: The Respiratory Failure with Salbutamol (REFSAL) study will be the first clinical trial to evaluate the efficacy and safety of salbutamol in the prevention of persistent pulmonary hypertension in newborns with tachypnea, and will improve short term outcomes. If successful, the study will demonstrate the feasibility of early intervention with NIV/nCPAP together with nebulized salbutamol in the management of TTN. Ethics and dissemination: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland on November 16, 2020 (decision number KB/190/2020). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. Clinical Trial Registration: It is registered at ClinicalTrials.gov NCT05527704, EudraCT 2020-003913-36; Protocol version 5.0 from 04/01/2022.

Polish growth charts for preterm infants - comparison with reference Fenton charts.

OBJECTIVES: Proper infant classification, particularly a preterm infant, as small or large for gestational age, is crucial to undertake activities to improve postnatal outcomes. This study aimed to assess the usability of the Fenton preterm growth charts to evaluate the anthropometric parameters of Polish preterm neonates. MATERIAL AND METHODS: In this single-center, retrospective study data extracted from the medical documentation of preterm neonates born 2002-2013 were analyzed. Body weight, body length, and head circumference were evaluated and used to develop growth charts, which were compared with the reference Fenton growth charts. RESULTS: This study included 3,205 preterm neonates, of whom 937 were born before 30 weeks of pregnancy. Overall, 11.04%, 3.3%, and 5.2% of neonates were below the 10th percentile on the Fenton charts for birth weight, body length, and head circumference, respectively. Only 26 (6.67%) of 390 analyzed anthropological parameters differed significantly between the study and the Fenton groups. Statistically significant differences between the study and the Fenton populations were found only in body length for both sexes, and in head circumference for female neonates. CONCLUSIONS: The growth charts developed in this study for a population of Polish preterm neonates corresponded to the Fenton charts in terms of birth weight but differed in terms of body length and head circumference. Our findings suggest the need to evaluate growth charts for Polish preterm newborns.

Barley malt-based composition as a galactagogue - a randomized, controlled trial in preterm mothers.

OBJECTIVES: Delayed or insufficient breast milk production, as well as low milk supply, is still a challenging problem to overcome, particularly in the case of preterm delivery. Herbal galactagogues might be a good way to increase milk supply, however, there is a lack of clinical studies confirming their efficacy and safety. The aim of this study was to verify the safety and effectiveness as a galactagogue of the unique galactagogue composition based on barley malt with ß -glucan and lemon balm. MATERIAL AND METHODS: The study included 117 mothers of preterm infants randomly divided into the Galactagogue Group given galactagogue and the Placebo Group. A complete data set was obtained for 80 participants, divided equally between two groups. Volume of milk expressed by mothers during the first two weeks after delivery was the primary outcome and safety of the product was the secondary outcome. RESULTS: Volume of milk recorded on participants' last visit in the Galactagogue Group was significantly higher than in the Placebo Group (95 mL vs 62.5 mL, p = 0.049). The total expressed milk volume during the study was 4209 ± 335 mL in the Placebo Group vs 6036 ± 498 mL (p = 0.003) in the Galactagogue Group. CONCLUSIONS: Supplementation with unique Galactagogue composition was safe and increased milk output which allowed achieving target minimal volume of 500 mL per day in first week of lactation in preterm mothers.

Comparison of the offspring ultrasound thyroid volume in hypothyroid mothers treated with different levothyroxine doses: A cohort study.

PURPOSE: We aimed to determine the volume of the thyroid gland in full-term neonates born to hypothyroid mothers as compared with full-term infants born to healthy mothers and to investigate the association between levothyroxine doses and the thyroid volume of neonates. MATERIALS AND METHODS: This is single center prospective observational study of 245 full-term neonates (96 from hypothyroid and 149 from healthy mothers). Ultrasound examination in both longitudinal and transverse projections was used to calculate the thyroid volume applying the ellipsoid formula. RESULTS: Median (interquartile range) thyroid volume of newborns from hypothyroid mothers was significantly smaller compared to the control group with regard to the total thyroid volume and the left lobe (p < 0.05). We found no statistically significant difference for the right lobe (p > 0.05) and inverse correlation between the thyroid volume and levothyroxine doses taken by mothers. CONCLUSION: Results of the present study indicate that maternal thyroid hormone levels may interfere with the fetal hypothalamic-pituitary axis.

Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia.

BACKGROUND: In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. METHODS: Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(-) groups, according to the development of BPD. RESULTS: Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. CONCLUSIONS: BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD.

Fraction of Inspired Oxygen as a Predictor of CPAP Failure in Preterm Infants with Respiratory Distress Syndrome: A Prospective Multicenter Study.

INTRODUCTION: There are limited data available regarding the fraction of inspired oxygen (FiO2) predictive of the failure of continuous positive airway pressure (CPAP) in preterm infants with respiratory distress syndrome (RDS). Therefore, we investigated factors predictive of CPAP failure in the first 72 h of life, with special attention to the prognostic role of FiO2. METHODS: This multicenter, prospective study enrolled infants <30 weeks gestation in whom CPAP was initiated within the first 15 min after birth. In the univariate and multivariate logistic regression models, demographic, perinatal, and respiratory parameters were analyzed. The FiO2 threshold was determined with ROC curve analysis. RESULTS: Of 389 recruited newborns, CPAP failure occurred in 108 infants (27.8%). In the univariate model, each gestational week reduced the odds of CPAP failure by 19%, and each 100 g of birth weight reduced the odds by 16% (both p < 0.05). The risk was increased by 4.2 and 7.5% for each 0.01 increase in FiO2in the first and second hours of life, respectively. In the final multivariate model, birth weight and FiO2 in the second hour of life were the predictive measures. The prognostic threshold was FiO2 = 0.29 in the second hour of life (AUC 0.7; p < 0.0001), with a sensitivity of 73% and a specificity of 57%. CPAP failure implied a more than 20-fold higher risk of death and pneumothorax and a 2- to 5-fold higher risk of typical complications of prematurity, including bronchopulmonary dysplasia and severe intraventricular hemorrhage. CONCLUSION: FiO2 in the second hour of life is a significantpredictor of CPAP failure. The threshold of 0.29 best discriminates the CPAP outcome. Nonresponders to CPAP have a remarkably higher incidence of complications and a higher mortality rate.

Innovative Techniques of Processing Human Milk to Preserve Key Components.

Human milk not only contains all nutritional elements that an infant requires, but is also the source of components whose regulatory role was confirmed by demonstrating health-related deficiencies in formula-fed children. A human milk diet is especially important for premature babies in the neonatal intensive care unit (NICU). In cases where breastfeeding is not possible and the mother's own milk is insufficient in volume, the most preferred food is pasteurized donor milk. The number of human milk banks has increased recently but their technical infrastructure is continuously developing. Heat treatment at a low temperature and long time, also known as holder pasteurization (62.5 °C, 30 min), is the most widespread method of human milk processing, whose effects on the quality of donor milk is well documented. Holder pasteurization destroys vegetative forms of bacteria and most viruses including human immunodeficiency virus (HIV) herpes and cytomegalovirus (CMV). The macronutrients remain relatively intact but various beneficial components are destroyed completely or compromised. Enzymes and immune cells are the most heat sensitive elements. The bactericidal capacity of heat-pasteurized milk is lower than that of untreated milk. The aim of the study was for a comprehensive comparison of currently tested methods of improving the preservation stage. Innovative techniques of milk processing should minimize the risk of milk-borne infections and preserve the bioactivity of this complex biological fluid better than the holder method. In the present paper, the most promising thermal pasteurization condition (72 °C-75 °C,) and a few non-thermal processes were discussed (high pressure processing, microwave irradiation). This narrative review presents an overview of methods of human milk preservation that have been explored to improve the safety and quality of donor milk.

Echocardiographic analysis of left ventricular function in term and preterm neonates at week 40 of postconceptional life.

BACKGROUND Both gestational and chronological age of the neonate may influence and impair the function of the delicate and immature myocardium. However, the transition from fetal to neonatal circulation in preterm neonates is poorly understood. AIMS This study aimed to compare left ventricular (LV) systolic and diastolic function between premature neonates at expected term and term neonates during the postnatal cardiovascular transitional period. METHODS Using echocardiography, we assessed systolic and diastolic function of the LV in 89 preterm neonates at week 40 of postconceptional age and 29 term neonates after closure of the patent ductus arteriosus (PDA) and on the 28th day of life. Based on M­mode images, we measured myocardial thickness and fractional shortening (FS%). Using pulsed­wave Doppler echocardiography, we estimated cardiac output, myocardial performance index (MPI), and LV diastolic function (E and A waves, E/A ratio). Systolic and diastolic function was also assessed by tissue Doppler imaging. RESULTS Compared with term neonates on the 28th day of life, preterm neonates had reduced myocardial thickness (P ≤0.04), FS% (P = 0.002), and cardiac output (P = 0.01). However, preterm neonates had a lower MPI than term neonates after PDA closure (P <0.001) and on the 28th day of life (P = 0.02). The E/A ratio and S' wave values were similar in preterm and term neonates (P >0.05). CONCLUSIONS Preterm neonates at 40 weeks of postconceptional age have preserved systolic and diastolic function of the LV.

Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

In the version of this article initially published, affiliation 38 incorrectly read "ICNU-Nephrology and Urology Department, Barcelona, Spain"; "Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain" is the correct affiliation. The error has been corrected in the HTML and PDF versions of the article.

Severe bronchopulmonary dysplasia - incidence and predictive factors in a prospective, multicenter study in very preterm infants with respiratory distress syndrome.

BACKGROUND: Severe bronchopulmonary dysplasia (BPD) remains a major complication of prematurity and can have significant impact on long-term pulmonary sequelae and adverse neurodevelopmental outcomes. OBJECTIVE: To assess the incidence and evaluate the predictive factors for severe BPD in very preterm infants with respiratory distress syndrome. METHODS: Of the 846 premature infants born at ≤32-week gestation who developed respiratory distress syndrome (RDS), 707 infants with known oxygen dependency at 36 weeks gestational age were included in the analysis of BPD incidence. With univariate and multiple logistic regression models we evaluated the risk factors for the development of severe BPD and calculated odds ratios (ORs). RESULTS: The overall incidence of BPD was 45.2%. Severe BPD accounted for 6%, with morbidity pertaining mainly to infants <29-week gestation (incidence 10%). The risk factors for severe BPD included male gender (OR 3.02 95%CI 1.30-7.46), intubation in the delivery room (OR 2.57, 95%CI 1.00-7.18), and invasive ventilation >7 days (OR 7.05, 95%CI 2.63-22.4). The protective factors were early continuous positive airway pressure (CPAP) in the univariate analysis and receiving surfactant <15 min after birth in the multivariate model. CONCLUSIONS: Mechanical ventilation >7 days is the most prevalent risk factor for severe BPD. CPAP initiated in the delivery room and early surfactant are key preventive measures.

The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12 and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3 and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

New Achievements in High-Pressure Processing to Preserve Human Milk Bioactivity.

High-pressure processing (HPP) is a non-thermal technology that is being increasingly applied in food industries worldwide. It was proposed that this method could be used as an alternative to holder pasteurization (HoP; 62.5°C, 30 min) in milk banks but its impact on the immunologic, enzymatic and hormonal components of human milk has not yet been evaluated in detail. The aim of our study was to compare the effects of HPP in variants: (1) 600 MPa, 10 min (2) 100 MPa, 10 min, interval 10 min, 600 MPa, 10 min (3) 200 MPa, 10 min, interval 10 min, 400 MPa, 10 min (4) 200 MPa, 10 min, interval 10 min, 600 MPa, 10 min in temperature range 19-21°C and HoP on the leptin, adiponectin, insulin, hepatocyte growth factor (HGF), lactoferrin and IgG contents in human milk. HoP was done at the Regional Human Milk Bank in Warsaw at the Holy Family Hospital on S90 Eco pasteurizer (Sterifeed, Medicare Colgate Ltd). Apparatus U4000/65 (Unipress Equipment, Poland) was used for pascalization. Milk samples were obtained from women during 2-6 weeks of lactation. Post-treatment culture showed no endogenous bacterial contamination in any tested option. Concentrations of selected components were determined using ELISA tests. The level of all analyzed components were significantly decreased by HoP: leptin 77.86%, adiponectin 32.79%, insulin 32.40%, HGF 88.72%, lactoferrin 60.31@.%, IgG 49.04%. All HPP variants caused an increase in leptin concentration, respectively (1) 81.79% (2) 90.01% (3) 86.12% (4) 47.96%. Retention of insulin after HPP was (1) 88.20% (2) 81.98% (3) 94.76% (4) 90.31% HGF (1) 36.15% (2) 38.81% 97.15% (3) 97.15% (4) 43.02%, lactoferrin (1) 55.78% (2) 57.63% (3) 78.77% (4) 64.75%. Moreover, HPP variant as 200 + 400 MPa preserved IgG (82.24%) better than HoP and resulted not statistically significant change of adiponectin level (38.55%) compare to raw milk. Our results showed that HPP leads to preservation of adipokines, growth factor, and lactoferrin, IgG much better or comparable with HoP.

An iTRAQ-Based Quantitative Proteomic Analysis of Plasma Proteins in Preterm Newborns With Retinopathy of Prematurity.

Purpose: Retinopathy of prematurity (ROP) is a vision-threatening complication of a premature birth, in which the etiology still remains unclear. Importantly, the molecular processes that govern these effects can be investigated in a perturbed plasma proteome composition. Thus, plasma proteomics may add new insights into a better understanding of the pathogenesis of this disease. Methods: The cord and peripheral blood of neonates (≤30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (PMA), respectively. Blood samples were retrospectively subdivided into ROP(+) and ROP(-) groups, according to the development of ROP. Results: The quantitative analysis of plasma proteome at both time points revealed 30 protein abundance changes between ROP(+) and ROP(-) groups. After standardization to gestational age, children who developed ROP were characterized by an increased C3 complement component and fibrinogen level at both analyzed time points. Conclusions: Higher levels of the complement C3 component and fibrinogen, present in the cord blood and persistent to 36 PMA, may indicate a chronic low-grade systemic inflammation and hypercoagulable state that may play a role in the development of ROP.

Sequential sonographic features in neonatal renal vein thrombosis.

OBJECTIVES: Renal vein thrombosis in newborns is a rare but serious and acute disease. Clinical representations of RVT can vary from discrete symptoms to life-threatening conditions. Therefore imaging, and in particular sonography, plays an important role in the diagnosis of RVT in neonates. Gray-scale, color and spectral/power Doppler ultrasound are all used in the diagnosis of RVT. MATERIAL AND METHODS: We present retrospective sequential ultrasonic imaging of three patients (two term and one preterm infant) with findings characteristic of RVT. RESULTS: Initial ultrasound diagnostic features include: renal enlargement, echogenic medullary streaks, lack of the flow pattern characteristic of arcuate vessels and subsequently loss of corticomedullary differentiation, reduced echogenicity around pyramids and echogenic band at the extreme apex of the pyramid. Higher resistance index or less pulsatile venous flow on the affected kidney are helpful Doppler signs. CONCLUSIONS: Knowledge and identification of specific features of each phase of the evolution of RTV seems essential to prompt diagnosis. We would like to highlight the evolution of specific sonographic features in each subsequent phase of RVT.

Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland-Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 Update.

INTRODUCTION: Vitamin D deficiency is an important public health problem worldwide. Vitamin D deficiency confers a significant risk for both skeletal and non-skeletal disorders and a number of lifelong negative health outcomes. The objectives of this evidence-based guidelines document are to provide health care professionals in Poland, an updated recommendation for the prevention, diagnosis and treatment of vitamin D deficiency. METHODS: A systematic literature search examining the prevention and treatment strategies for vitamin D deficiency was conducted. Updated recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation system describing the strength of the recommendation and the quality of supporting evidence. Twenty-seven contributors representing different areas of expertise and medical specialties, including pediatricians, geriatricians, endocrinologists, epidemiologists, nephrologists, gynecologists and obstetricians evaluated the available published evidence related to vitamin D, formulated the goals of this document and developed a common consolidated position. The consensus group, representing six national specialist consultants and eight Polish and international scientific organizations/societies, participated in the process of grading evidence and drawing up the general and specific recommendations. RESULTS: The updated recommendations define the diagnostic criteria for the evaluation of vitamin D status and describe the prevention and treatment strategies of vitamin D deficiency in the general population and in groups at increased risk of the deficiency. Age- and weight-specific recommendations for prevention, supplementation and treatment of vitamin D deficiency are presented, and detailed practice guidance is discussed regarding the management in primary and specialized health care. CONCLUSION: Vitamin D deficiency remains still highly prevalent in Poland, in all age groups. Currently, there is a great necessity to implement a regular supplementation with recommended doses and to develop an effective strategy to alleviate vitamin D deficiency in the population. These updated recommendations are addressed to health professionals and the authorities pursuing comprehensive health policies and should also be included in public health programs aimed at preventing a broad spectrum of chronic diseases.

Plasma proteome changes in cord blood samples from preterm infants.

OBJECTIVE: In the presented study, we aimed to systematically analyze plasma proteomes in cord blood samples from preterm infants stratified by their gestational age to identify proteins and related malfunctioning pathways at birth, possibly contributing to the complications observed among preterm infants. STUDY DESIGN: Preterm newborns were enrolled of three subgroups with different gestation age: newborns born ≤26 (group 1), between 27 and 28 (group 2) and between 29 and 30 (group 3) weeks of gestation, respectively, and compared to the control group of healthy, full-term newborns in respect to their plasma proteome composition. RESULT: Preterm delivery is associated with multiple protein abundance changes in plasma related to a plethora of processes, including inflammation and immunomodulation, coagulation, and complement activation as some key features. CONCLUSION: Plasma proteome analysis revealed numerous gestation-age-dependent protein abundance differences between term and preterm infants, which highlight key dysregulated pathways and potential new protein treatment targets.

Prospective plasma proteome changes in preterm infants with different gestational ages.

BACKGROUND: In this study, we aimed to analyze time-resolved plasma proteome changes in preterm neonates stratified by their gestational age to detect malfunctioning pathways that derive from the systemic immaturity of the neonate and to highlight those that are differentially regulated during the early development. METHODS: Preterm newborns were enrolled in three subgroups with different gestational ages: before 26 weeks of gestation (group 1), between 27 and 28 weeks of gestation (group 2), and between 29 and 30 (group 3) weeks of gestation. Plasma protein abundances were assessed at two time points (at preterm delivery and at the 36th week of post-menstrual age) by quantitative proteomics. RESULT: The quantitative analysis of plasma proteome in preterm infants revealed a multitude of time-related differences in protein abundances between the studied groups. We report protein changes in several functional domains, including inflammatory domains, immunomodulatory factors, and coagulation regulators as key features, with important gestational age-dependent hemopexin induction. CONCLUSION: The global trend emerging from our data, which can collectively be interpreted as a progression toward recovery from the perinatal perturbations, highlights the profound impact of gestation duration on the ability to bridge the gap in systemic homeostasis after preterm labor.

Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III.

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families.

Shifting the boundaries for early caffeine initiation in neonatal practice: Results of a prospective, multicenter study on very preterm infants with respiratory distress syndrome.

BACKGROUND: There is growing evidence that supports the benefits of early use of caffeine in preterm neonates with RDS; however, no formal recommendations specifying the exact timing of therapy initiation have been provided. OBJECTIVES: We compared neonatal outcomes in infants receiving early (initial dose on the 1st day of life) and late (initial dose on day 2+ of life) caffeine therapy. METHODS: Using data from a prospective, cohort study, we identified 986 infants ≤32 weeks' gestation with RDS and assessed the timing of caffeine therapy initiation, need for ventilatory support, mortality and incidence of typical complications of prematurity. To adjust for baseline severity, the early and late caffeine groups were propensity score (PS) matched to 286 infants (1:1). Clinical outcomes were compared between the PS-matched groups. RESULTS: Early treatment with caffeine citrate was associated with a significantly reduced need for invasive ventilation (71.3% vs 83.2%; P = 0.0165) and total duration of mechanical ventilation (mean 5 ± 11.1 days vs 10.8 ± 14.6 days; P = 0.0000) and significantly lower odds of intraventricular hemorrhage (IVH) (OR 0.4827; 95% CI 0.2999-0.7787) and patent ductus arteriosus (PDA) (OR 0.5686; 95% CI 0.3395-0.9523). The incidence of bronchopulmonary dysplasia (BPD) (36.4% vs 45.8%) and rates of moderate and severe BPD were not significantly different between the two groups. The mortality rates were comparable between the two groups (8.6% vs 8.5%, P = ns). CONCLUSION: Early caffeine initiation was associated with a decreased need for invasive ventilatory support and lower incidence of IVH and PDA.