The Limitations of Cytomegalovirus DNA Detection in Cerebrospinal Fluid of Newborn Infants With Congenital CMV Infection: A Tertiary Care Neonatal Center Experience.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection of the central nervous system (CNS) can cause ventriculomegaly, gliosis, calcifications and cortical defects. Detection of CMV DNA in cerebrospinal fluid by PCR (CSF-CMV-PCR) is a marker of CNS involvement. OBJECTIVE: To evaluate a diagnostic value of the positive CSF-CMV-PCR in cCMV. METHODS: Analysis of clinical, laboratory, neuroimaging and single-nucleotide polymorphisms (SNPs) data according to the results of CSF-CMV-PCR were performed in infants with cCMV. RESULTS: A total of 168 infants were included; 145 (86.3%) had negative and 23 (13.7%) had positive CSF-CMV-PCR results. Associations between the positive CSF-CMV-PCR results and prematurity (odds ratio [OR] = 3.24; 95% confidence interval [CI]: 1.30-8.07), microcephaly (OR = 5.67; 95% CI: 2.08-15.41), seizures (OR = 4.15; 95% CI: 1.10-15.67), sensorineural hearing loss (OR = 6.6; 95% CI: 2.49-17.46), splenomegaly (OR = 8.13; 95% CI: 3.12-21.16), hepatitis (OR = 10.51; 95% CI: 3.31-33.35), petechiae (OR = 10.21; 95% CI: 3.78-27.57) and heterozygous T/C genotype at TLR4rs4986791 (OR = 7.88; 95% CI: 1.55-40.12) were observed. When using a multivariate logistic regression analysis, only the presence of severe sensorineural hearing loss (OR = 7.18; 95% CI: 1.75-29.34, P = 0.006), cystic lesions on MRI (OR 5.29; 95% CI: 1.31-21.36, P = 0.02), and calcifications on MRI (OR = 7.19; 95% CI: 1.67-30.97, P = 0.008) remained as the significant independent predictors of the positive CSF-CMV-PCR results. CONCLUSIONS: The detection of CMV DNA in CSF is associated with a higher rate of CNS damage including abnormal MRI neuroimaging and severe hearing loss. Therefore, detection of CMV DNA in CSF may be considered as a marker of severe CNS injury in cCMV infection. However, the very low prevalence of the positive CSF-CMV-PCR results, even in infants with proven CNS involvement, may imply its limited role in clinical practice.

Association between single nucleotide polymorphisms and viral load in congenital cytomegalovirus infection.

BACKGROUND: There are limited data on factors that determine viral load (VL) in congenital cytomegalovirus (cCMV) infection. Single nucleotide polymorphisms (SNPs) might influence individual host response to infection. This study aimed to investigate the association between SNPs in genes encoding cytokines or cytokine receptors and VL in newborns with cCMV. MATERIAL AND METHODS: Eight polymorphisms (IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791 and TLR9 rs352140) were analyzed in study population of 233 newborns, including 92 cCMV-infected newborns (73 symptomatic and 19 asymptomatic) by TaqMan SNP Predesigned Genotyping Assays. The association analysis was performed using SNPStats software and STATISTICA10. RESULTS: The association between IL12B polymorphism and viruria was observed (p = 0.029). In multiple comparison tests, heterozygous T/G genotype of IL12B was associated with higher viruria than T/T genotype (p = 0.041) in cCMV-infected newborns. In allele analysis, T allele of IL12B was associated with higher viremia (p = 0.037) in symptomatic newborns. We observed higher VL in symptomatic newborns in comparison to asymptomatic (median viremia: 1.7 × 104 copies/mL vs. 2.0 × 103 copies/mL (p = 0.002), median viruria: 1.0 × 107 copies/mL versus 6.9 × 105 copies/mL (p = 0.001), respectively). CONCLUSIONS: IL12B rs3212227 was associated with VL in cCMV. Symptomatic newborns had significantly higher viremia and viruria. The role of SNPs in pathogenesis of cCMV warrants further investigations.

Antiviral treatment in congenital HCMV infection: The six-year experience of a single neonatal center in Poland.

BACKGROUND: Antiviral treatment is recommended for symptomatic newborns with congenital cytomegalovirus infection (cCMV). OBJECTIVES: To compare 2 treatment methods in neonates with cCMV - ganciclovir-based therapy (intravenous ganciclovir (GCV) or sequential GCV + valganciclovir (VGCV) therapy) with oral VGCV-based therapy - in Polish neonates. MATERIAL AND METHODS: A total of 98 symptomatic infants with cCMV (positive HCMV DNA in urine ≤21st day of life) hospitalized in the neonatal intensive care unit (NICU) between 2012 and 2017 were enrolled. Clinical characteristics, the viral load in blood and urine, hematological and biochemical tests, neuroimaging results, and the length of hospitalization were compared between the study groups at baseline and at the 2nd hospitalization. RESULTS: In 2012, GCV was used in 57% of the cases, sequential therapy in 33% and VGCV in 10%. In 2017, VGCV monotherapy was used in 83% of the infants treated. Valganciclovir treatment allowed the length of hospitalization to be shortened over 2.5 times during the six-year observation period. Infants treated intravenously had lower birth weights and head circumferences, and more frequently presented splenomegaly, petechiae, thrombocytopenia, and hepatitis. The baseline viral load in the blood and urine were similar in both groups, but at follow-up visits 4-6 weeks later, a viral load about 70 times lower was observed in the blood of the VGCV-based group (1029 viral copies/mL compared to 72,188 viral copies/mL in the GCV-based group; p = 0.04). The prevalence of neutropenia was similar in both groups at the follow-up visits. CONCLUSIONS: Valganciclovir became the first line of antiviral therapy in cCMV in the study population. Compared to GCV-based therapy, VGCV monotherapy allowed shorter hospital stays and reduced the viral load in blood due to continuing treatment at home. Valganciclovir monotherapy did not provoke more side effects such as neutropenia. Intravenous GCV is still suitable for patients with severe disseminated disease, born prematurely, with low birth weights, or not tolerating enteral feeding. In those infants, the sequential therapy seems to be optimal.

Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection.

Congenital cytomegalovirus (cCMV) infection is the most common intrauterine infection. A non-specific immune response is the first line of host defense mechanism against human cytomegalovirus (HCMV). There is limited data on associations between Single Nucleotide Polymorphisms (SNPs) in genes involving innate immunity and the risk and clinical manifestation of cCMV infection. The aim of the study was to investigate association between selected SNPs in genes encoding cytokines and cytokine receptors, and predisposition to cCMV infection including symptomatic course of disease and symptoms. A panel of eight SNPs: IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140 was analyzed in 233 infants (92 cCMV-infected and 141 healthy controls). Associations between genotyped SNPs and predisposition to cCMV infection and symptoms were analyzed. The association analysis was performed using SNPStats software. No statistically significant association was found between any genotyped SNPs and predisposition to cCMV infection and symptomatic course of disease. In relation to particular symptoms, polymorphism of IL12B rs3212227 was linked to decreased risk of prematurity (OR = 0.37;95%CI,0.14-0.98;p = 0.025), while polymorphism of IL1B rs16944 was linked to reduced risk of splenomegaly (OR = 0.36;95%CI,0.14-0.98; p = 0.034) in infants with cCMV infection. An increased risk of thrombocytopenia was associated with IL28B rs12979860 polymorphism (OR = 2.55;95%CI,1.03-6.32;p = 0.042), while hepatitis was associated with SNP of TLR4rs4986791 (OR = 7.80;95%CI,1.49-40,81; p = 0.024). This is the first study to demonstrate four new associations between SNPs in selected genes (IL1B, IL12B, IL28B, TLR4) and particular symptoms in cCMV disease. Further studies on the role of SNPs in the pathogenesis of cCMV infection and incorporation of selected SNPs in the clinical practice might be considered in the future.

A case of severe trichothiodystrophy 3 in a neonate due to mutation in the GTF2H5 gene: Clinical report.

Trichothiodystrophy (TTD) is a group of predominantly autosomal recessive disorders characterized by sulfur-deficient brittle hair. Clinical features of TTD consist of variable neuroectodermal symptoms including ichthyosis, nail abnormalities, mental retardation, short stature, decreased fertility and proneness to infections. Approximately half of the reported patients with TTD have clinical and cellular photosensitivity associated with mutations in three subunits (ERCC3, ERCC2, GTF2H5) of the basal transcription factor TFHII, which is involved in transcription and nucleotide excision repair. We report on a case of a male neonate with a novel GTF2H5 gene mutation, detected by whole exome sequencing. The GTF2H5 gene's role is to provide stability to the entire TFHII complex. The reported patient was born at 33 weeks' gestation from a pregnancy complicated by intrauterine growth restriction and premature rupture of membranes. His main clinical problems included severe congenital ichthyosis and proneness to infections with episodes of multiorgan failure. The infant's history displays the most severe clinical manifestations among patients with GTF2H5 gene mutations that have so far been reported.

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.

Assessment of continuous pain in newborns admitted to NICUs in 18 European countries.

AIM: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown. METHODS: A prospective cohort study in 243 neonatal intensive care units (NICUs) from 18 European countries recorded the frequency of pain assessments, use of mechanical ventilation, sedation, analgesia or neuromuscular blockade for each neonate for up to 28 days after NICU admission. RESULTS: Only 2113 of 6648 (31.8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46.0%), noninvasive ventilation (NiV, 35.0%) and no ventilation (NoV, 20.1%) groups (p < 0.001). Daily assessments for continuous pain occurred in only 10.4% of all neonates (TrV: 14.0%, NiV: 10.7%, NoV: 7.6%; p < 0.001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions and surgical admissions (all p < 0.01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives-hypnotics, general anaesthetics (O-SH-GA) (all p < 0.001), or surgery (p = 0.028). Use of O-SH-GA drugs increased the odds for pain assessment in the TrV (OR:1.60, p < 0.001) and NiV groups (OR:1.40, p < 0.001). CONCLUSION: Assessments of continuous pain occurred in less than one-third of NICU admissions and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.

The Clinical and Biochemical Predictors of Bone Mass in Preterm Infants.

BACKGROUND: Metabolic bone disease of prematurity still occurs in preterm infants, although a significant improvement in neonatal care has been observed in recent decades. Dual-energy X-ray absorptiometry (DXA) is the precise technique for assessing bone mineral content (BMC) in preterm infants, but is not widely available. AIM: To investigate the clinical and biochemical parameters, including bone metabolism markers as potential predictors of BMC, in preterm infants up to 3 months corrected age (CA). MATERIALS AND METHODS: Ca-P homeostasis, iPTH, 25-hydroxyvitamin D, osteocalcin, N-terminal propeptide, cross-linked C-telopeptide and amino-terminal pro C-type natriuretic peptide and the DXA scans were prospectively performed in 184 preterm infants (≤ 34 weeks' gestation) between term age and 3 mo CA. Lower bone mass was defined as BMC below or equal to respective median value for the whole study group, rounded to the nearest whole number. RESULTS: The appropriate quality DXA scans were available for 160 infants (87%) examined at term and for 130 (71%) tested at 3 mo CA. Higher iPTH level was the only independent predictor of lower BMC at term, whereas lower BMC at 3 mo CA was associated both with lower urinary phosphate excretion and higher serum osteocalcin level. ROC analysis showed that iPTH >43.6 pg/mL provided 40% sensitivity and 88% specificity in identification of preterm infants with lower BMC at term. In turn, urinary phosphate excretion (TRP>97% or UP/Cr ≤0.74 mg/mg) and serum osteocalcin >172 ng/mL provided 40% sensitivity and 93% specificity in identification of infants with decreased BMC at 3 mo CA. CONCLUSION: Serum iPTH might to be a simple predictor of reduced BMC in preterm infants at term age, but urinary phosphate excretion and serum osteocalcin might predict reduced BMC at 3 mo CA. These results represent a promising diagnostic tool based on simple, widely available biochemical measurements for bone mass assessment in preterm infants.

Recommendations for the diagnosis and treatment of CMV infections. Polish Society of Epidemiology and Infectious Diseases

Cytomegalovirus (CMV) infections are common and their incidence increases with age. In immunocompetent people they are usually asymptomatic or manifest as a mild, self-limiting mononucleosis syndrome. CMV infection in patients with immune deficiency as well as congenital infections may cause a considerable problem. A group of experts designated by the Polish Society of Epidemiology and Infectious Diseases has prepared recommendations on the diagnosis and treatment of CMV infections, with particular emphasis on the management of patients with immunodeficiencies and congenital infections.

Sedation and analgesia practices in neonatal intensive care units (EUROPAIN): results from a prospective cohort study.

BACKGROUND: Neonates who are in pain or are stressed during care in the intensive care unit (ICU) are often given sedation or analgesia. We investigated the current use of sedation or analgesia in neonatal ICUs (NICUs) in European countries. METHODS: EUROPAIN (EUROpean Pain Audit In Neonates) was a prospective cohort study of the management of sedation and analgesia in patients in NICUs. All neonates admitted to NICUs during 1 month were included in this study. Data on demographics, methods of respiration, use of continuous or intermittent sedation, analgesia, or neuromuscular blockers, pain assessments, and drug withdrawal syndromes were gathered during the first 28 days of admission to NICUs. Multivariable linear regression models and propensity scores were used to assess the association between duration of tracheal ventilation (TV) and exposure to opioids, sedatives-hypnotics, or general anaesthetics in neonates (O-SH-GA). This study is registered with ClinicalTrials.gov, number NCT01694745. FINDINGS: From Oct 1, 2012, to June 30, 2013, 6680 neonates were enrolled in 243 NICUs in 18 European countries. Mean gestational age of these neonates was 35.0 weeks (SD 4.6) and birthweight was 2384 g (1007). 2142 (32%) neonates were given TV, 1496 (22%) non-invasive ventilation (NIV), and 3042 (46%) were kept on spontaneous ventilation (SV). 1746 (82%), 266 (18%), and 282 (9%) neonates in the TV, NIV, and SV groups, respectively, were given sedation or analgesia as a continuous infusion, intermittent doses, or both (p<0.0001). In the participating NICUs, the median use of sedation or analgesia was 89.3% (70.0-100) for neonates in the TV group. Opioids were given to 1764 (26%) of 6680 neonates and to 1589 (74%) of 2142 neonates in the TV group. Midazolam was given to 576 (9%) of 6680 neonates and 536 (25%) neonates of 2142 neonates in the TV group. 542 (25%) neonates in the TV group were given neuromuscular blockers, which were administered as continuous infusions to 146 (7%) of these neonates. Pain assessments were recorded in 1250 (58%) of 2138, 672 (45%) of 1493, and 916 (30%) of 3017 neonates in the TV, NIV, and SV groups, respectively (p<0.0001). In the univariate analysis, neonates given O-SH-GA in the TV group needed a longer duration of TV than did those who were not given O-SH-GA (mean 136.2 h [SD 173.1] vs 39.8 h [94.7] h; p<0.0001). Multivariable and propensity score analyses confirmed this association (p<0.0001). INTERPRETATION: Wide variations in sedation and analgesia practices occur between NICUs and countries. Widespread use of O-SH-GA in intubated neonates might prolong their need for mechanical ventilation, but further research is needed to investigate the therapeutic and adverse effects of O-SH-GA in neonates, and to develop new and safe approaches for sedation and analgesia. FUNDING: European Community's Seventh Framework Programme.

Determinants of Postpartum Vitamin D Status in the Caucasian Mother-Offspring Pairs at a Latitude of 52°N: A Cross-Sectional Study.

BACKGROUND: High prevalence of vitamin D deficiency in pregnancy is recorded. AIM: To establish determinants of postpartum 25-hydroxyvitamin D (25(OH)D) levels on mothers and offspring. METHODS: 25(OH)D level was measured in cord blood and maternal blood collected ≤3 weeks postpartum. Maternal socioeconomic status, vitamin D intake, sun exposure during pregnancy and maternal and neonatal fat mass (FM; dual X-ray absorptiometry) were assessed within 3 weeks postpartum. RESULTS: A total of 174 mother-offspring pairs were enrolled. Maternal 25(OH)D <20 ng/ml was seen in 32 (51%) of summer and 82 (74%) of winter deliveries. Women with 25(OH)D <20 ng/ml had a 2-fold lower percentage of vitamin D intake of ≥800 IU/day than women with 25(OH)D ≥20 ng/ml (p = 0.02). FM (%) was comparable between groups (p > 0.05). Multiple regression analysis revealed the delivery season, prenatal vitamin D intake ≥800 IU/day and duration of supplementation to be the determinants of maternal 25(OH)D level (R(2) = 0.26, p < 0.001). Maternal 25(OH)D level, season of birth and duration of maternal supplementation explained 83% of the variance in cord blood 25(OH)D level (R(2) = 0.83, p < 0.001). CONCLUSIONS: The key determinants of higher maternal vitamin D status were the summer-autumn season of delivery and prenatal use of ≥800 IU/day of vitamin D. The cord blood 25(OH)D level was mainly determined by maternal 25(OH)D level and season of birth.

Protein intake in infancy and carotid intima media thickness at 5 years--a secondary analysis from a randomized trial.

BACKGROUND: Nutrition in childhood has an influence on the cardiovascular function later on in life. European Childhood Obesity Project is a multicenter, randomized clinical intervention trial examining the effect of early protein intake on later health outcomes, particularly adiposity and related disorders. The aim of the study was to examine the effect of nutritional intervention--different protein intake in infancy on carotid intima-media thickness (cIMT) at 5 years. The association of cardiovascular risk factors with cIMT was also assessed. METHODS: Healthy term formula-fed infants in five European countries were enrolled either to the higher (HP) or to the lower (LP) protein group. Observational group consisted of breastfed infants. Plasma insulin, glucose, lipid profile, IGF-1, apolipoprotein A1 and B were measured as well as anthropometric parameters of parents and a child, blood pressure and physical activity. RESULTS: No difference in cIMT between HP and LP group was observed. Insulin, HOMA-IR index and total IGF-1 were positively associated with cIMT but after adjustment for confounders only an inverse association between ApoA1 and positive between ApoB/ApoA1 and cIMT were significant. CONCLUSION: High versus low protein intake in infancy does not influence cIMT at 5 years. cIMT in healthy children at 5 years is associated with their apolipoprotein profile.

Impact of vitamin D supplementation during lactation on vitamin D status and body composition of mother-infant pairs: a MAVID randomized controlled trial.

OBJECTIVE: The optimal vitamin D intake for nursing women is controversial. Deterioration, at least in bone mass, is reported during lactation. This study evaluated whether vitamin D supplementation during lactation enhances the maternal and infant's vitamin D status, bone mass and body composition. DESIGN AND METHODS: After term delivery, 174 healthy mothers were randomized to receive 1200 IU/d (800 IU/d+400 IU/d from multivitamins) or 400 IU/d (placebo+400 IU/d from multivitamins) of cholecalciferol for 6 months while breastfeeding. All infants received 400 IU/d of cholecalciferol. Serum 25-hydroxyvitamin D [25(OH)D], iPTH, calcium, urinary calcium, and densitometry were performed in mother-offspring pairs after delivery, and at 3 and 6 months later. RESULTS: A total of 137 (79%) (n = 70; 1200 IU/d, n = 67; 400 IU/d) completed the study. 25(OH)D was similar in both groups at baseline (13.7 ng/ml vs. 16.1 ng/ml; P = 0.09) and at 3 months (25.7 ng/ml vs. 24.5 ng/ml; P = 0.09), but appeared higher in the 1200 IU/d group at 6 months of supplementation (25.6 ng/ml vs. 23.1 ng/ml; P = 0.009). The prevalence of 25(OH)D <20 ng/ml was comparable between groups at baseline (71% vs. 64%, P = 0.36) but lower in the 1200 IU/d group after 3 months (9% vs. 25%, P = 0.009) and 6 months (14% vs. 30%, P = 0.03). Maternal and infants' iPTH, calciuria, bone mass and body composition as well as infants' 25(OH)D levels were not significantly different between groups during the study. Significant negative correlations were noted between maternal 25(OH)D and fat mass (R =  -0.49, P = 0.00001), android fat mass (R = -0.53, P = 0.00001), and gynoid fat mass (R = -0.43, P = 0.00001) after 6 months of supplementation. CONCLUSIONS: Vitamin D supplementation at a dose of 400 IU/d was not sufficient to maintain 25(OH)D >20 ng/ml in nursing women, while 1200 IU/d appeared more effective, but had no effect on breastfed offspring vitamin D status, or changes in the bone mass and the body composition observed in both during breastfeeding. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506557.

Management of familial hypercholesterolemia in children and adolescents. Position paper of the Polish Lipid Expert Forum.

Familial hypercholesterolemia (FH) affects on average 1 in 500 individuals in European countries, and it is estimated that FH in Poland may affect more than 80,000 people. However, in Poland, only about 20% of the population is estimated to have been diagnosed with FH, of which only a small number receive adequate treatment. FH results in more rapid development of atherosclerosis and is associated with a high risk of cardiovascular events. Atherosclerosis develops beginning in childhood in patients with FH and reaches advanced stages before clinical manifestations develop. Inadequate diagnostics and treatment of FH in Polish children suggests a need for raising the level of awareness and understanding of the condition in both society and among health professionals. These recommendations present the current epidemiological status, guidelines for diagnosing FH in Polish children and adolescents, and effective treatment options.

Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency.

INTRODUCTION: Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium-phosphate metabolism as well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activity appear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest that Vitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conference focused on overcoming Vitamin D deficiency. METHODS: After reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses on recommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to Scientific Committee members of the 'Vitamin D - minimum, maximum, optimum' conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting 'Vitamin D - minimum, maximum, optimum' was held on October 19-20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists' voting were reviewed and discussed during eight plenary sessions and two workshops. RESULTS: Based on many polemical discussions, including post-conference networking, the key opinion leaders established ranges of serum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20-30 ng/mL(50-75 nmol/L)], and target concentration for optimal Vitamin D effects [30-50 ng/mL (75-125 nmol/L)]. General practical guidelines regarding supplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, children and adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed. CONCLUSIONS: Improving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementation guidance and population strategies for Vitamin D in Central Europe.

Clinical and radiological pictures of two newborn babies with manifestations of chondrodysplasia punctata and review of available literature.

BACKGROUND: Chondrodysplasia punctata (CDP) is a rare, heterogeneous congenital skeletal dysplasia, characterized by punctate or dot-like calcium deposits in cartilage observed on neonatal radiograms. A number of inborn metabolic diseases are associated with CDP, including peroxisomal and cholesterol biosynthesis dysfunction and other inborn errors of metabolism such as: mucolipidosis type II, mucopolysacharidosis type III, GM1 gangliosidosis. CDP is also related to disruption of vitamin K-dependent metabolism, causing secondary effects on the embryo, as well as fetal alcohol syndrome (FAS), chromosomal abnormalities that include trisomies 18 and 21, Turner syndrome. CASE REPORT: This article presents clinical data and diagnostic imaging findings of two newborn babies with chondrodysplasia punctata. Children presented with skeletal and cartilage anomalies, dysmorphic facial feature, muscles tone abnormalities, skin changes and breathing difficulties. One of the patients demonstrated critical stenosis of spinal canal with anterior subluxation of C1 vertebra relative to C2. The aim of this article is to present cases and briefly describe current knowledge on etiopathogenesis as well as radiological and clinical symptoms of diseases coexisting with CDP. CONCLUSIONS: Radiological diagnostic imaging allows for visualization of punctate focal mineralization in bone epiphyses during neonatal age and infancy. Determining the etiology of chondrodysplasia punctata requires performing various basic as well as additional examinations, including genetic studies.

[Nutritional guidelines for healthy children aged 1-3 years - Polish Expert Group statement. Part I- energy and nutritional components demand]. / Normy zywienia zdrowych dzieci w 1-3. Rokuzycia . stanowisko polskiej grupy ekspertów.czesc i - zapotrzebowanie na energiei skladniki odzywcze.

Updating of the nutritional guidelines for the Polish population requires updates of the nutritional norms for children. We present the Polish Expert Group statement (2012) on intake of selected nutrients (protein, lipids, carbohydrates, vitamin D and E) essential in nutrition of children aged 1-3 years. For this purpose the Expert Group reviewed available scientific data: the recent guidelines, nutritional norms and recommendations, systematic reviews and expert opinions as well as original publications, in relation to the specific requirements of the Polish population.

Left ventricular noncompaction (LVNC) and low mitochondrial membrane potential are specific for Barth syndrome.

Barth syndrome (BTHS) is an X-linked mitochondrial defect characterised by dilated cardiomyopathy, neutropaenia and 3-methylglutaconic aciduria (3-MGCA). We report on two affected brothers with c.646G > A (p.G216R) TAZ gene mutations. The pathogenicity of the mutation, as indicated by the structure-based functional analyses, was further confirmed by abnormal monolysocardiolipin/cardiolipin ratio in dry blood spots of the patients as well as the occurrence of this mutation in another reported BTHS proband. In both brothers, 2D-echocardiography revealed some features of left ventricular noncompaction (LVNC) despite marked differences in the course of the disease; the eldest child presented with isolated cardiomyopathy from late infancy, whereas the youngest showed severe lactic acidosis without 3-MGCA during the neonatal period. An examination of the patients' fibroblast cultures revealed that extremely low mitochondrial membrane potentials (mtΔΨ about 50 % of the control value) dominated other unspecific mitochondrial changes detected (respiratory chain dysfunction, abnormal ROS production and depressed antioxidant defense). 1) Our studies confirm generalised mitochondrial dysfunction in the skeletal muscle and the fibroblasts of BTHS patients, especially a severe impairment in the mtΔΨ and the inhibition of complex V activity. It can be hypothesised that impaired mtΔΨ and mitochondrial ATP synthase activity may contribute to episodes of cardiac arrhythmia that occurred unexpectedly in BTHS patients. 2) Severe lactic acidosis without 3-methylglutaconic aciduria in male neonates as well as an asymptomatic mild left ventricular noncompaction may characterise the ranges of natural history of Barth syndrome.