Lower plasma melatonin levels in non-hypoxic premature newborns associated with neonatal pain.

We analyzed plasma melatonin levels in different groups of preterm newborns without hypoxia and their relationship with several perinatal variables like gestational age or neonatal pain. Prospective cohort study of preterm newborns (PTNB) without perinatal hypoxia, Apgar > 6 at 5 min, and oxygen needs on the third day of life. We compared melatonin levels at day 3 of life in different groups of non-hypoxic preterm infants (Student's t-tests, Mann-Whitney U, and chi2) and analyzed the relationship of melatonin with GA, birth weight, neonatal pain (Premature Infant Pain Profile (PIPP) scale), caffeine treatment, parenteral nutrition, or the development of free radical diseases (correlation study, linear regression) and factors associated with moderate/intense pain and free radical diseases (logistic regression analysis). Sixty-one preterm infants with gestational age (GA) of 30.7 ± 2.0 weeks with no oxygen requirements at day 3 of life were studied with plasma melatonin levels of 33.8 ± 12.01 pg/ml. Preterm infants weighing < 1250 g at birth had lower plasma melatonin levels (p = 0.05). Preterm infants with moderate or severe pain (PPIPP > 5) have lower melatonin levels (p = 0.01), and being preterm with PIPP > 5 is associated with lower plasma melatonin levels (p = 0.03). Being very preterm (GA < 32 GS), having low weight for gestational age (LWGA), receiving caffeine treatment, or requiring parenteral nutrition did not modify melatonin levels in non-hypoxic preterm infants (p = NS). Melatonin on day 3 of life in non-hypoxic preterm infants is not associated with later development of free radical diseases (BPD, sepsis, ROP, HIV, NEC). CONCLUSION: We observed that preterm infants with moderate to severe pain have lower melatonin levels. These findings are relevant because they reinforce the findings of other authors that melatonin supplementation decreases pain and oxidative stress in painful procedures in premature infants. Further studies are needed to evaluate whether melatonin could be used as an analgesic in painful procedures in preterm infants. TRIAL REGISTRATION: Trial registration was not required since this was an observational study. WHAT IS KNOWN: • Melatonin is a potent antioxidant and free radical scavenger in newborns under stress conditions: hypoxia, acidosis, hypotension, painful procedures, or parenteral nutrition. • Pain stimulates the production of melatonin. • Various studies conclude that melatonin administration decreases pain during the neonatal period. WHAT IS NEW: • Non-hypoxic preterm infants with moderate to severe pain (PIPP>5) have lower levels of melatonin. • Administration of caffeine and treatment with parenteral nutrition do not modify melatonin levels in non-hypoxic preterm infants.

Mineralizing angiopathy as a rare cause of pediatric stroke: review and report of two cases.

In the Indian subcontinent, traumatic brain injury stands as the leading cause of pediatric stroke, whereas in Europe, it is considered a rare or potentially underdiagnosed factor. The etiology of post-traumatic stroke is unknown, although it has been associated with the presence of calcification in the lenticulostriate arteries, a condition known as "mineralizing angiopathy." The theory suggests that calcified lenticulostriate vessels in a brain with inadequate myelination could have an increased vulnerability to mechanical injuries, which may result in their obstruction. This ischemic stroke associated with mineralizing angiopathy usually occurs after mild traumatic brain injury, with an asymptomatic interval following the trauma. The typical age of presentation is between 6 and 24 months. Children with mineralizing lenticulostriate vasculopathy generally experience a favorable outcome after stroke, with the majority achieving complete or nearly complete recovery of their motor functions. Despite aspirin treatment, a small proportion of children may still face stroke recurrence following repeat head trauma. We present the cases of two male patients with clinical features compatible with childhood stroke after a mild traumatic brain injury.

Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy.

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.

Prevalence and associated factors of iron deficiency in Spanish children aged 1 to 11 years.

Iron deficiency (ID) is the most common nutritional deficiency affecting children worldwide. Most traditional laboratory parameters to assess ID can be altered by infections or other inflammatory states, including obesity. The aims of this study were to determine the prevalence of ID in healthy children and to analyse associated factors, avoiding potential confounding factors through the use of serum transferrin receptor (sTfR), reticulocyte haemoglobin content and sTfR/log ferritin index. A cross-sectional population-based study was conducted on 951 children aged 1 to 11 years in Almería (Spain). ID was detected in 7.7% of children and iron deficiency anaemia in 0.9%. Multivariate analysis identified the following as independent risk factors: age under 5 years (OR: 2.2, 95% CI: 1.35-3.6); excessive consumption of cow's milk and dairy products (OR: 1.87, 95% CI: 1.13-3.1); and insufficient consumption of vegetables (OR: 2.7, 95% CI: 1.2-6.1).Conclusions: Using a combination of iron status parameters with greater discriminatory power than classical measures, this study detected a considerable iron deficiency prevalence in Spanish children. Younger children and specific dietary habits exhibit a particular risk for ID, so special attention should be paid to this population. What is Known: • Iron deficiency remains the most prevalent nutritional deficit worldwide, and children aged under 3 years are the most vulnerable to this condition. • Accurate assessment of iron status, based on a combination of biochemical indicators, can often be complicated. What is New: • Iron deficiency continues to present a health problem in Spanish children aged 1 to 11 years, considering the serum transferrin receptor and reticulocyte haemoglobin content for diagnosis. • Excessive consumption of dairy products and low consumption of vegetables are independent risk factors for iron deficiency.

Status of folate in healthy children in Almeria.

The objective of this study is to establish reference values for folic acid in a healthy population of children aged 4-11 years and to examine related epidemiological, dietary and analytical factors. A cross-sectional study of 658 healthy children aged 4-11 years was made. Epidemiological, socioeconomic and dietary variables were analysed, the BMI Z-score was obtained, levels of serum folate and serum vitamin B12 were determined and haematological, iron status and erythropoietic activity parameters were examined. The study data were analysed by non-parametric tests and linear multiple regression. The mean folate value was 8.6 ± 4.6 ng/mL (95% reference interval: 2.8-20 ng/mL). A level < 3 ng/mL (5th percentile) was considered as folate deficiency (4.6% of subjects). No child reported symptoms related to this deficiency. Folate values were significantly lower with age (p < 0.01), low NSE and low parental educational level (p: 0.0001). No relationship was found between folates and the analytical variables. According to multivariate linear regression, the variables significantly associated with serum folate were age, socioeconomic level and vitamin B12.Conclusions: Serum folate levels in healthy school children are described. Age, socioeconomic level and serum vitamin B12 are factors associated with folate status. Specific cut-off values for a paediatric population should be defined. What is Known: • Folic acid is an essential micronutrient for optimal growth and development; its deficit is associated with adverse health effects. • The studies on their status and deficit are not comparable due to a lack of agreement on appropriate indicators and reference values. What is New: • This study reports the levels of serum folate in a large population of healthy schoolchildren, with strict inclusion criteria in a developed country and identifies the associated sociodemographic, dietary and analytical (vitamin B12, iron parameters and erythropoietic activity) factors, avoiding potential confusion.

Prevalence of iron deficiency and related factors in Spanish adolescents.

Iron deficiency anaemia continues to be the world's most important cause of years lived with disability in children and adolescents. Assessment of iron deficiency traditionally depended on laboratory parameters that may be modified by inflammation states, including obesity, which is nowadays a current condition in adolescent population of high-income countries. The present study ascertains the prevalence of iron deficiency and its related factors in adolescents, using the serum transferrin receptor and the reticulocyte haemoglobin content, in order to avoid this confusing effect of classical parameters. A cross-sectional study was conducted on a population-based representative sample for teenagers in Almería (Spain), of 405 subjects aged 12 to 16 years. Iron deficiency was present in 13.3% of adolescents, but iron deficiency anaemia only in 1.2%. Multivariate logistic regression analyses showed that being part of an immigrant family, a low iron bioavailability diet, meat consumption below four times a week and fish consumption below twice a week, were independent risk factors for iron deficiency.Conclusion: This study provides an estimate iron deficiency prevalence of 13.3% in Spanish healthy adolescents, avoiding potential confounding factors through the use of new iron status parameters, based on a wide representative sample of adolescents from the city of Almería. What is Known: • For children and adolescents, iron deficiency anaemia continues to be the world's most important cause of years lived with disability. • Assessment of iron deficiency has traditionally depended on laboratory parameters that may be modified by inflammatory states, including obesity. What is New: • Iron deficiency prevalence and their related factors were analysed in Spanish adolescents, avoiding potential confounding factors through the use of sTfR and CHr. • Being part of an immigrant family and consuming a low iron bioavailability diet are independent risk factors for iron deficiency.

The usefulness of reticulocyte haemoglobin content, serum transferrin receptor and the sTfR-ferritin index to identify iron deficiency in healthy children aged 1-16 years.

This cross-sectional study, conducted on a population-based representative sample, evaluates the usefulness of reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) to recognise iron deficiency (ID) without anaemia, provides specific cut-off points for age and gender, and proposes a new definition of ID. A total of 1239 healthy children and adolescents aged 1-16 years were included. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, CHr, sTfR, and sTfR-F index were determined. ROC curves were obtained and sensitivity, specificity, predictive values, likelihood ratios, and accuracy for each specific cut-off points were calculated. Seventy-three had ID without anaemia. Area under the curve for sTfR-F index, sTfR and CHr were 0.97 (CI95% 0.95-0.99), 0.87 (CI95% 0.82-0.92) and 0.68 (CI95% 0.61-0.74), respectively. The following cut-off points defined ID: sTfR-F Index > 1.5 (1-5 years and 12-16 years boys) and > 1.4 (6-11 years and 12-16 years girls); sTfR (mg/L) > 1.9 (1-5 years), > 1.8 (6-11 years), > 1.75 (12-16 years girls) and > 1.95 (12-16 years boys); and CHr (pg) < 27 (1-5 years) and < 28.5 (6-16 years).Conclusions: CHr, sTfR and the sTfR-F index are useful parameters to discriminate ID without anaemia in children and adolescents, and specific cut-off values have been established. The combination of these new markers offers an alternative definition of ID with suitable discriminatory power. What is Known: • In adults, reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) have been evaluated and recognised as reliable indicators of iron deficiency (ID). • Clinical manifestations of ID may be present in stages prior to anaemia, and the diagnosis of ID without anaemia continues to pose problems. What is New: • CHr, sTfR and the sTfR-F index are useful parameters in diagnosis of ID in childhood and adolescence when anaemia is not present. • We propose a new strategy for the diagnosis of ID in childhood and adolescence, based on the combination of these measures, which offer greater discriminatory power than the classical parameters.

Insulinaemia and insulin resistance in Caucasian general paediatric population aged 2 to 10 years: Associated risk factors.

BACKGROUND: The aim of this study is to determine values of insulinaemia, homeostasis model assessment (HOMA) index and quantitative insulin sensitivity check index (QUICKI) among a population of prepubertal Caucasian children, to analyse factors associated with insulin resistance (IR), and to study its association with cardiovascular risk factors. MATERIALS AND METHODS: Population-based study conducted on a randomly selected sample of prepubescent Caucasian subjects aged 2.00 to 9.99 years old. Anthropometric measurements, blood pressure, and fasting blood samples were obtained, including fasting glucose, triglycerides, High Density Lipoprotein (HDL)-cholesterol, and insulin. In addition, QUICKI and HOMA indices were calculated. Generalised additive models for location, scale and shape (GAMLSS) was used to calculate centiles curves and multivariate logistic regression analysis to assess factors associated with IR. RESULTS: A total of 654 subjects were included. Mean values obtained for insulinaemia, HOMA index, and QUICKI were 3.74 µIU/mL, 0.73, and 0.44, respectively, in the overall population and 3.32 µIU/mL, 0.64 and 0.46, respectively, in normal weight subjects. The main factor associated with IR was abdominal obesity (odds ratio [OR] 3.38 [95% CI 1.44-7.94] in the subgroup aged 2.00-5.99 years and OR 9.14 [3.42-24.41] for those aged 6.00-9.99 years). An increased risk of hyperglycaemia (P = 0.043), hypertriglyceridaemia (P < .001), and HDL < p10 (P = 0.021) was described among children aged 2.00 to 5.99 years with IR, and among those aged 6.00 to 9.99 years, IR was associated with an increased risk of hypertriglyceridaemia (P < .001). CONCLUSION: Abdominal obesity was the main factor associated with IR. Metabolic changes associated with IR seem to be present from early stages of life, which highlights the importance of the prevention, early diagnosis and treatment of obesity.

Reference Values of Reticulocyte Hemoglobin Content in Healthy Adolescents.

Assessing iron status in a pediatric population is not easy, as it is based on parameters that undergo physiological variations in childhood and adolescence. Analysis of the reticulocyte hemoglobin content (CHr) to screen for iron deficiency may increase the accuracy of diagnosis, but, to date, reference values in healthy adolescents have not been adequately determined. A cross-sectional study was conducted on a population-based representative sample in the city of Almería (Spain), with 253 healthy non-iron-deficient (ID) subjects, aged 12 to 16 years. The mean CHr value was 31.6±1.3 pg. The CHr 2.5 percentile was 28.7 pg. There were no significant differences as regards age or sex. In the multivariate linear regression analysis, sex did not influence the variability of CHr, but it was related to age. CHr was influenced by hemoglobin and the Mentzer index, as well as by functional iron indicators such as erythrocyte protoporphyrin and serum transferrin receptor. These independent variables predicted two thirds of the variability in healthy adolescents (R=0.55). This study provides CHr reference ranges in healthy adolescents for use in clinical practice for the early detection of ID states. In populations with similar sociodemographic characteristics, values above the 2.5 percentile rule out ID, as values under the 2.5 percentile could be suggestive of functional ID.

Objective and Subjective Sleep Efficiency in Adult Patients with Cystic Fibrosis and Impact on Quality of Life.

INTRODUCTION: Poor sleep quality and excessive daytime sleepiness are common in patients with cystic fibrosis (CF), and both are negatively correlated with health-related quality of life (HRQoL). The objective of our study was to evaluate subjective and objective sleep quality in adult CF patients and its effect on HRQoL. MATERIALS AND METHODS: This was a descriptive, prospective, cross-sectional study of CF patients > 18 years of age. Patients underwent nocturnal polysomnography (PSG) and were administered the Pittsburgh Sleep Quality Index questionnaire (PSQI) and the Cystic Fibrosis Quality of Life Questionnaire (CFQR 14 + Spain). RESULTS: The study included 23 patients, 14 women (61%). The mean age of the participants was 32 + 18 years. The mean PSQI score was 5.57 + 3.55; 13 (56.5%) of the patients were poor sleepers, and 13% reported poor sleep quality; seven (30%) had sleep latency > 30 min, 10 (43.5%) had sleep efficiency < 85%. Nineteen underwent polysomnography. According to PSG measurements, sleep efficiency was less than 90% in 61% of the patients. Pathological values were found for the following parameters: intra-sleep wakefulness in 12 patients (63%); microarousal index in 12 patients (63%); and apnea-hypopnea index (AHI) in 2 patients. The desaturation time with SpO2 < 90% (T90) was > 30% in 3 patients. We observed a significant correlation between PSQI and all dimensions of CFQR 14. CONCLUSIONS: Subjective and objective sleep efficiency decreases in adult CF patients. Sleep quality has an impact on HRQoL. The PSQI questionnaire was able to discriminate sleep quality.