Blood lactate level and meconium aspiration syndrome

Purpose: Approximately 5 % of infants born with a meconium-stained amniotic fluid (MSAF) develop meconium aspiration syndrome (MAS). Early recognition of infants at highest risk for the development of MAS and the prediction of disease severity are important for optimizing the clinical strategies for prevention and treatment. The aim of the present study was to identify the risk factors for MAS and to investigate the effect of blood lactate level on the development of MAS. Methods: Between January 2011 and January 2012, data were recorded with regard to gender, mode of delivery, gestational week, birth weight, 5-min Apgar score, and need for resuscitation of the meconium-stained depressed infants who underwent tracheal aspiration. Moreover, the number of cases developing MAS, blood pH value, and lactate level in capillary blood gases obtained during the first hour after delivery, duration of oxygen supplementation, the number of cases receiving mechanical ventilation and surfactant therapy, duration of hospital stay, and outcomes of the infants were recorded. Results: The number of live births during the study period was 17,202, and of them, 1,341 (7.8 %) infants were born through MSAF. Of 195 infants who were meconium-stained depressed, 90 were girls and 105 were boys. Their mean gestational week was 39.37 ± 0.89 weeks and mean birth weight was 3,426 ± 634 g. Eighty-four of them were born through cesarean section (C/S), and 111 were born via normal spontaneous labor. For 40 infants, Apgar score at fifth minute was less than 6. In total, resuscitation was performed on 43 (22.9 %) infants. Of the infants, 141 did not develop MAS and 54 developed MAS. While there were no significant differences between infants with and without MAS with regard to gender, delivery route, gestational week, and birth weight, a significant difference was observed regarding the Apgar score (p = 0.0001). The blood pH value in capillary blood gas analysis was less than 7.25 in 18 (28.5 %) cases with MAS and four (3.2 %) cases without MAS. There was no significant difference between infants with and without MAS with regard to blood pH levels (p = 0.031). The mean blood lactate level was 8.5 ± 3.4 mmol/L in the patients with MAS, and there was a significant difference between infants with and without MAS regarding blood lactate level (p = 0.0001). The mean duration of oxygen supplementation was 86.62 ± 66.52 and 44.36 ± 19.03 h in patients with MAS and without MAS, respectively. In total, 30 infants required mechanical ventilation (24 infants with MAS and 6 infants without MAS). In addition to mechanical ventilation, 16 infants with MAS were administered surfactant therapy. The mean duration of hospital stay of infants with MAS was significantly higher than infants without MAS (p = 0.0001). There was a correlation between blood lactate levels, blood pH value, and hospitalization duration (p < 0.05). All of the infants, except one patient, were discharged from the NICU. Conclusion: In addition to the blood pH value and 5-min Apgar score, increased blood lactate level may be a risk factor for the development of MAS in infants born with MSAF. This may aid in the early detection of MAS and, with appropriate measures taken sooner, reduce morbidity and mortality. Further studies are needed to elucidate the role of lactate level, which is an important indicator of hypoxia during the development of MAS

The potential of the Mediterranean diet to improve metabolic control and body composition in youths with Type 1 Diabetes Mellitus

Abstract Background A chronic autoimmune disease with an increasing incidence rate, type 1 diabetes mellitus (T1DM) is typified by the degeneration of the pancreatic beta cells. Diabetes management is significantly impacted by nutrition. Although it has been demonstrated that following the Mediterranean diet (MD) improves metabolic control with type 2 diabetes in children and adults, its effects on children with T1DM have not received much attention. Objective Therefore, the purpose of this study was to assess whether adherence to Mediterranean diet is associated with better metabolic control and body composition in youths with Type 1 Diabetes Mellitus. The study recruited T1DM patients aged 6-18 years at İstanbul University Cerrahpaşa Medical Faculty Hospital's Pediatric Endocrinology and Diabetes Outpatient Clinic for follow-up. Methods In addition to demographic variables, some anthropometric measurements, body composition and biochemical parameters such as: Trygliceride(TG), Total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Low density lipoprotein cholesterol (LDL-C), (Aspartate aminotransferase) AST, Alanine transaminase (ALT) and glycated hemoglobin (HbA1c) was analyzed. The time in range (TIR) is a value obtained from continuous glucose monitoring. KIDMED was used to assess the participants' adherence with the MD. Results Good adherence to the MD resulted in much larger height SDS than poor adherence. Poor adherence to MD resulted in higher body fat than moderate and good adherence. There is positivite correlation between TIR and KIDMED score. Adherence to MD is negatively associated with HbA1c. The regression anaylsis showed that a one-point rise in the KIDMED score would result in a 0.314-unit reduction in the HbA1c value (p < 0.01). Conclusions In conclusion, this study found that adhering to MD led to improved anthropometric measurements, biochemistry, and diabetes outcomes. Awareness among children, adolescents with T1DM, and their parents about the benefits of MD compliance for glycemic and metabolic control should be raised

Seroprotection status of hepatitis B and measles vaccines in children with type 1 diabetes mellitus

WOS: 000384418000002PubMed ID: 27658137Background: Type 1 diabetes mellitus (T1DM) is speculated to have an impaired immunological response to vaccines. This paper aimed to investigate the presence of specific antibodies against hepatitis B virus (HBV) and measles in diabetic children who had been immunized according to the standard national calendar of immunization. Methods: Two hundred and one diabetic children and 140 healthy controls were prospectively evaluated. Antibodies against hepatitis B (anti-HBs) and measles were detected in all individuals who completed the vaccination schedule. We noted onset of T1DM, duration of the disease, diabetes-related autoantibodies and mean HbA(1c) levels. Results: Some 72.6% of diabetics and 82.1% of controls had anti-HBs (+) (p=0.04). We found a reduced efficacy of measles vaccination in anti-HBs (-) diabetic children (p=0.009), even though there was no significant difference between the study and control groups. Onset of the disease was earlier in anti-HBs (-) diabetics than in controls (p=0.038). No difference with respect to other parameters was found. Conclusions: Our data showed a reduced seroprotection rate for HBV vaccination in diabetic children and for measles with anti-HBs (-) diabetics. Larger studies should be encouraged to confirm the vaccine efficacy in diabetic children and to elucidate possible pathogenic mechanisms

Management of Thyrotoxicosis in Children and Adolescents: A Turkish Multi-center Experience

esen, ihsan/0000-0003-1700-6778; AYDIN, MURAT/0000-0001-7374-229X; bayramoglu, elvan/0000-0002-6732-8823; Buyukinan, Muammer/0000-0002-2937-823X; bolu, semih/0000-0002-8183-2188; Kor, Yilmaz/0000-0003-1645-5416WOS: 000469271100008PubMed: 30488822Objective: To determine the demographic and biochemical features of childhood and juvenile thyrotoxicosis and treatment outcome. Methods: We reviewed the records of children from 22 centers in Turkey who were diagnosed with thyrotoxicosis between 2007 to 2017. Results: A total of 503 children had been diagnosed with thyrotoxicosis at the centers during the study period. Of these, 375 (74.6%) had been diagnosed with Graves' disease (GD), 75 (14.9%) with hashitoxicosis and 53 (10.5%) with other less common causes of thyrotoxicosis. The most common presenting features in children with GD or hashitoxicosis were tachycardia and/or palpitations, weight loss and excessive sweating. The cumulative remission rate was 17.6% in 370 patients with GD who had received anti-thyroid drugs (ATDs) for initial treatment. The median (range) treatment period was 22.8 (0.3-127) months. No variables predictive of achieving remission were identified. Twenty-seven received second-line treatment because of poor disease control and/or adverse events associated with ATDs. Total thyroidectomy was performed in 17 patients with no recurrence of thyrotoxicosis and all became hypothyroid. Ten patients received radioiodine and six became hypothyroid, one remained hyperthyroid and restarted ATDs and one patient achieved remission. TWo patients were lost to follow up. Conclusion: This study has demonstrated that using ATDs is the generally accepted first-line approach and there seems to be low remission rate with ATDs in pediatric GD patients in Turkey

Reclassification of two germline DICER1 splicing variants leads to DICER1 syndrome diagnosis

DICER1 syndrome is an inherited condition associated with an increased risk of developing hamartomatous and neoplastic lesions in diverse organs, mainly at early ages. Germline pathogenic variants in DICER1 cause this condition. Detecting a variant of uncertain significance in DICER1 or finding uncommon phenotypes complicate the diagnosis and can negatively impact patient care. We present two unrelated patients suspected to have DICER1 syndrome. Both females (aged 13 and 15 years) presented with multinodular goiter (thyroid follicular nodular disease) and ovarian tumours. One was diagnosed with an ovarian Sertoli-Leydig cell tumour (SLCT) and the other, with an ovarian juvenile granulosa cell tumour, later reclassified as a retiform variant of SLCT. Genetic screening showed no germline pathogenic variants in DICER1. However, two potentially splicing variants were found, DICER1 c.5365-4A>G and c.5527+3A>G. Also, typical somatic DICER1 RNase IIIb hotspot mutations were detected in the thyroid and ovarian tissues. In silico splicing algorithms predicted altered splicing for both germline variants and skipping of exon 25 was confirmed by RNA assays for both variants. The reclassification of the ovarian tumour, leading to recognition of the association with DICER1 syndrome and the characterization of the germline intronic variants were all applied to recently described DICER1 variant classification rules. This ultimately resulted in confirmation of DICER1 syndrome in the two teenage girls

Adrenocortical hormone profiles do not predict the molecular etiology in non-CAH primary adrenal insufficiency

Background: Primary adrenal insufficiency other than congenital adrenal hyperplasia (non-CAH PAI) is very uncommon in children but associated with a variety of molecular defects. Biosynthesis of adrenocortical hormones is reduced although the relation of steroid profiles with underlying molecular etiology is not yet studied. Objective: Investigation of clinical and steroid hormone profiles of a multicenter cohort of children with non-CAH PAI. Design: Patients with CAH, adrenoleukodystrophy, autoimmune adrenal insufficiency or obvious syndromic PAI on clinical and biochemical assessment were excluded. Genetic analysis was performed using either targeted gene panel or whole-exome sequencing. Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. Setting: Sixteen tertiary pediatric endocrinology clinics. Patients: Forty-one children (19 females, median age: 3 months, range: 0-8 years) with non-CAH PAI of unknown etiology. Results: A genetic diagnosis was obtained in 29 (68%) patients by targeted gene panel. Further molecular diagnosis could not be achieved by WES. The range of etiologies was: MC2R (n = 6), StAR (n = 6), NNT (n = 3), NR0B1 (n = 3), CYP11A1 (n = 2), MRAP (n = 2), SGPL1 (n = 2), ABCD1 (n = 1), AIRE (n = 1), AAAS (n = 1), HSD3B2 (n = 1). Steroid profiling demonstrated low levels in all adrenocortical steroid hormones irrespective of age and not varied among the genetic etiologies except two patients with new-onset symptoms of PAI due to homozygous c.518T>A(p.Leu173Gln) SGPL1, and hemizygous c.1772G>T(p.Arg591Leu) ABCD1 defects, and another patient with non-classic non-CAH PAI due to homozygous c.1351C>T (p.Arg451Trp) variant in CYP11A1. Compared to age-matched healthy control group in whom steroid hormone concentrations are physiologically low, the patient group had even lower steroid concentrations, most significantly in cortisone, cortisol, and corticosterone (P 95% specificity to segregate non-CAH PAI patients compared to control groups. Conclusion: Adrenocortical hormone profiles are highly sensitive for the diagnosis of non-CAH PAI, while, in contrast to CAH, they are unlikely to point out a specific molecular diagnosis. Targeted gene panel sequencing is an undisputed optimal approach in the molecular diagnosis of non-CAH PAI with low cost and high efficacy, while little additional benefit is expected from whole-exome sequencing. Further progress can be made, mainly by more collaboration and exchanging knowledge for delineation of rare causes of primary adrenal insufficiency

Steroid hormone profiles and molecular diagnostic tools in pediatric patients with non-CAH primary adrenal insufficiency

CONTEXT: There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. OBJECTIVE: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. METHODS: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. RESULTS: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. CONCLUSION: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES