An observational, multicenter, registry-based cohort study of Turkish Neonatal Society in neonates with Hypoxic ischemic encephalopathy.

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) is a significant cause of mortality and short- and long-term morbidities. Therapeutic hypothermia (TH) has been shown to be the standard care for HIE of infants ≥36 weeks gestational age (GA), as it has been demonstrated to reduce the rates of mortality, and adverse neurodevelopmental outcomes. This study aims to determine the incidence of HIE in our country, to assess the TH management in infants with HIE, and present short-term outcomes of these infants. METHODS: The Turkish Hypoxic Ischemic Encephalopathy Online Registry database was established for this multicenter, prospective, observational, nationally-based cohort study to evaluate the data of infants born at ≥34 weeks GA who displayed evidence of neonatal encephalopathy (NE) between March, 2020 and April 2022. RESULTS: The incidence of HIE among infants born at ≥36 weeks GA (n = 965) was 2.13 per 1000 live births (517:242440), and accounting for 1.55% (965:62062) of all neonatal intensive care unit admissions. The rates of mild, moderate and severe HIE were 25.5% (n = 246), 58.9% (n = 568), and 15.6% (n = 151), respectively. Infants with severe HIE had higher rates of abnormal magnetic resonance imaging (MRI) findings, and mortality (p<0.001). No significant difference in mortality and abnormal MRI results was found according to the time of TH initiation (<3 h, 3-6 h and >6 h) (p>0.05). TH was administered to 85 (34.5%) infants with mild HIE, and of those born of 34-35 weeks of GA, 67.4% (n = 31) received TH. A total of 58 (6%) deaths were reported with a higher mortality rate in infants born at 34-35 weeks of GA (OR 3.941, 95% Cl 1.446-10.7422, p = 0.007). CONCLUSION: The incidence of HIE remained similar over time with a reduction in mortality rate. The timing of TH initiation, whether <3 or 3-6 h, did not result in lower occurrences of brain lesions on MRI or mortality. An increasing number of infants with mild HIE and late preterm infants with HIE are receiving TH; however, the indications for TH require further clarification. Longer follow-up studies are necessary for this vulnerable population.

Effect of partially hydrolyzed synbiotic formula milk on weight gain of late preterm and term infants-a multicenter study.

Introduction: Data on the effectiveness of hydrolyzed infant formula containing both pre- and probiotics (synbiotic formula) on the growth of infants is still scarce. This retrospective study was designed to evaluate the effect of a partially hydrolyzed synbiotic formula on growth parameters and the possible occurrence of major gastrointestinal adverse events or morbidities in infants born via cesarean section (C-section) delivery. Methods: C-section-delivered term and late preterm infants who received either partially hydrolyzed synbiotic formula, standard formula, or maternal milk and followed at seven different hospitals from five different regions of Turkey, during a 1-year period with a minimum follow-up duration of 3 months were evaluated retrospectively. All the included infants were evaluated for their growth patterns and any kind of morbidity such as diarrhea, constipation, vomiting, infection, or history of hospitalization. Results: A total of 198 infants (73 in the human milk group, 61 in the standard formula group, and 64 in the partially hydrolyzed synbiotic formula group) reached the final analysis. The groups were similar regarding their demographic and perinatal characteristics. No difference was observed between the three groups regarding gastrointestinal major side effects. Growth velocities of the infants in the human milk and partially hydrolyzed synbiotic formula groups during the first month of life were similar whereas the weight gain of infants in the standard formula group was significantly less than these two groups (p < 0.001). Growth velocities were similar among the three groups between 1st and 3rd months of age. Discussion: A partially hydrolyzed synbiotic formula provided better weight gain in late-preterm and term infants who were delivered via C-section delivery compared to the standard formula during the first month of life. This weight gain was similar to the infants receiving exclusively human milk. This difference was not observed in length and head circumference gain. No difference was observed in any of the parameters during the 1st-3rd months of age. Specially formulated partially hydrolyzed synbiotic formulas may reverse at least some of the negative impacts of C-section delivery on the infant and help to provide better growth, especially during the early periods of life.

Association Between Umbilical Cord Levels of Glypican-1, Glypican-3, Syndecan-1, WISP1, Leptin and Birth Weight of Small, Appropriate, and Large for Gestational Age Infants.

BACKGROUND: Many factors are affecting intrauterine growth. The role of Wingless-type (Wnt) inducible signaling pathway protein-1 (WISP1), a novel adipokine and placental proteoglycans in intrauterine growth, is not known. We aimed to measure umbilical cord blood levels of glucose, insulin, leptin, WISP1, and placental proteoglycans [glypican-1 (GPC1), glypican-3 (GPC3), and syndecan-1 (SDC1)] which are thought to have an important role in fetal growth and investigate their relation with birth weight. METHODS: Full-term neonates were included in this prospective, cross-sectional study and classified as appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA) according to their birth weight. Umbilical cord blood levels of glucose, insulin, leptin, WISP1, GPC1, GPC3, and SDC1 were measured. RESULTS: Leptin levels were higher in LGA newborns compared to AGA and SGA newborns, while WISP1, GPC1, GPC3, and SDC1 levels were not different between the three groups. Leptin and GPC1 levels were higher in infants of mothers with gestational diabetes mellitus compared to infants of non-diabetic mothers, while WISP1, GPC3, and SDC1 were not different between the groups. Leptin was positively correlated with insulin, birth weight, and maternal weight. While there was a strong correlation between the WISP1, GPC1, GPC3, and SDC1 levels; there was no correlation between the birth weight, maternal weight, glucose, insulin, and WISP1, GPC1, GPC3, and SDC1 levels. CONCLUSION: Umbilical cord blood levels of GPC1, GPC3, SDC1, and WISP1 were not different between SGA, AGA, and LGA infants. The significance of serum levels of these adipokines and proteoglycans remains to be elucidated.

School-age obese asthmatic children have distinct lung function measures from lean asthmatics and obese children.

BACKGROUND: The lung functions of children with obese asthma seem to be distinct from those of obese children or lean asthmatics. AIM: To measure baseline lung function, exercise-induced bronchoconstriction (EIB), and bronchial hyperreactivity (BHR) in school-age obese asthmatics (OA group) and to compare the data with obese children (O group), lean asthmatics (A group), and healthy controls (H group). METHODS: One hundred seventy school-age children were enrolled in this prospective cross-sectional study. Baseline fractionated exhaled nitric oxide (FeNO), and baseline, post-exercise (post-E), and post-bronchodilation (post-BD) impulse oscillometry (IOS) and spirometry tests were performed. EIB and BHR were evaluated based on the difference (Δ) in post-E - baseline, and post-BD - baseline values. RESULTS: The mean FeNO level was higher in the OA group than in the other groups (p = 0.002). Baseline zR5 and R5-20 were higher (p = 0.013 and p = 0.044), but zFEF25-75 was lower (p < 0.01), in the OA group. ΔPost-E - baseline zFEV1 was lower in the A group (p = 0.003) but was higher in the OA group (p = 0.014) than the other groups. ΔPost-BD - baseline zFEV1 was lower in the H group compared to the other three groups (p = 0.004), but no significant difference was observed among the O, A, and OA groups (p > 0.05). CONCLUSION: Higher airway inflammation (high FeNO), peripheral airway resistance (high zR5 and zR5-20) and a lower peripheral airway flow (low FEF25-75) were observed at baseline measurement in school-age obese asthmatics compared to lean asthmatics and obese children. Obese asthmatics had no EIB but exhibited a similar BHR to that of asthmatics.

Human wharton-jelly mesenchymal stromal cells reversed apoptosis and prevented multi-organ damage in a newborn model of experimental asphyxia.

In this study, the effect of applying wharton jelly mesenchymal stromal cells (WJ-MSC) isolated from the human umbilical cord tissue on the neonatal mouse model caused experimental asphyxia in mice was investigated. WJ-MSC surface markers (CD44, CD90, CD105) were characterised by immunofluorescence staining, and pluripotency genes (Nanog, Oct-4, Sox-2) were characterised by qPCR. Blood, prefrontal cortex, cerebellum, hippocampus, lung, heart, kidney, and liver tissues were analysed twenty days after subcutaneously administered WJ-MSC. WJ-MSC administration significantly decreased serum TNF-α, NSE, GFAP, and IL-6 levels in the asphyxia mice. It was determined that WJ-MSC application in tissues accelerated cell regeneration and decreased oxidative stress. In conclusion, this study showed that multiorgan damage in asphyxia could be prevented by applying WJ-MSC at an early stage. Therefore, WJ-MSC application in infants with neonatal asphyxia in the clinic may be an innovative method in the future.

Ileal atresia and severe cerebral injury after fetoscopic laser photocoagulation treatment for twin-to-twin transfusion syndrome.

BACKGROUND: Twin-to-twin transfusion syndrome (TTTS) is a significant cause of perinatal morbidity and mortality. Fetoscopic laser photocoagulation (FLP) is the optimal treatment option for twin-to-twin transfusion syndrome; but can cause central nervous system, extremity and intestinal system injury. CASE: We report the case report of ileal atresia and severe cerebral infarction co-occurrence after fetoscopic laser photocoagulation treatment. It is uncertain as to whether ileal atresia occurred due to ischemia associated with TTTS, the treatment with FLP, or a combination of both. CONCLUSIONS: Cases with prenatal ultrasonographic abnormalities after FLP should have a close assessment to detect bowel complications. Despite many developments in its management, TTTS remains an important risk factor for cerebral injury.

The association of lactating mothers' urinary and breast milk iodine levels with iodine nutrition status and thyroid hormone levels of newborns.

OBJECTIVE: To explore the iodine status of lactating mother-newborn pairs, and whether neonatal serum thyroid-stimulating hormone (TSH) can be used for estimation of iodine status of the population. MATERIALS AND METHODS: A total of 334 mothers and their healthy neonates were included. Urine, serum, and breast milk samples were obtained at 4th and 6th days of delivery. Urinary iodine concentration (UIC) was measured in urine samples of mothers and their neonates, as well as breast milk iodine concentration (BMIC) and serum thyroid hormone levels of neonates, were measured from the samples taken between the 4th and 6th days after birth. RESULTS: Median age of the mothers was 27 years (23-30). The median UIC of mothers and their newborns were 125 µg/L and 142 µg/L, respectively. The median BMIC was 138,0 µg/L. There was a significant positive correlation between the BMIC and UIC of neonates (r=0.276, p<0.001). The prevalence of neonatal serum TSH >10 mIU/L, which is suggestive of mild iodine deficiency (i.e. 3.0-19.9%), was 19.0%. However, there were no participants with iodine deficiency in lactating mothers and neonates according to UIC. CONCLUSION: By previous reports, Aydin is iodine sufficient. Although 19% of the neonates had serum TSH levels >10 mU/L, which is suggestive of a mild iodine deficiency, iodine deficiency was observed in none of the neonates and their mothers. Therefore, it will be appropriate to investigate the role of neonatal TSH levels in a larger sample to assess the iodine status of the population.

Experience with Real-Time Continuous Glucose Monitoring in Newborns with Congenital Hyperinsulinemic Hypoglycemia.

BACKGROUND: Effective treatment and close monitoring of hypoglycemia in children with congenital hyperinsulinemic hypoglycemia (CHH) is vital to prevent brain damage. The current use of capillary sampling schedules does not provide a comprehensive assessment of glycemic status and fails to detect asymptomatic hypoglycemia episodes. AIM: To investigate the efficacy and accuracy of a real-time continuous glucose monitoring system (RT-CGMS) in neonates with CHH. METHODS: A sensor connected to RT-CGMS was inserted into the newborn patients and maintained for at least 6 days during their stay in the hospital. We compared the readings of CGMS with capillary blood glucose values using Bland-Altman analysis. RESULTS: A total of 110 blood glucose values were compared to readings from the CGMS. All results were calculated and plotted for CGMS values at 0-4, 5-9, 10-14, 15-19, 20-24, and 25-29 min after capillary blood glucose sampling. CGMS readings were highly correlated with blood glucose values, especially during normoglycemia. In case of hypoglycemia, the mean difference between the CGMS and capillary glucose values was higher. Although the false positive rate for hypoglycemia was relatively high in CGMS, RT-CGMS may show some episodes of hypoglycemia earlier than blood measurement. CONCLUSION: RT-CGMS is accurate during normoglycemia, and it can reduce the number of capillary blood samples in children with CHH.

Tidal breath in healthy term newborns: An analysis from the 2nd to the 30th days of life.

BACKGROUND: Few data are available concerning normative lung function parameters measured in unsedated neonates. AIM: To evaluate lung function changes in neonates. METHODS: In this prospective cohort study, tidal breath parameters were measured using the MasterScreen PAED system and standardized protocols. Measurements were performed on 60 (30 male) term, healthy, unsedated neonates on the postnatal 2nd and 30th days. RESULTS: Expiratory time (TE; p < .001; Cohen's d = 0.561), exhaled volume to peak tidal expiratory flow (VPTEF; p < .001; Cohen's d = 0.789), minute ventilation (p < .001; Cohen's d = 0.926), tidal volume (VT; p < .001; Cohen's d = 1.835), expiratory flow when 75%, 50%, and 25% of tidal volume remaining in the lungs (TEF75 [p < .001; Cohen's d = 1.070], TEF50 [p < .001; Cohen's d = 0.824], TEF25 [p < .001; Cohen's d = 0.568]), and inspiratory time (Ti; p < .001; Cohen's d = 0.654) were higher on Day 30 compared to Day 2, while time to reach peak tidal expiratory flow to total expiratory time (TPTEF/TE; p = .006; Cohen's d = 0.371), the volume until peak tidal expiratory flow to total expiratory volume (VPTEF/VE; p = .001; Cohen's d = 0.447), and respiration rate (RR; p = .001; Cohen's d = 0.432) were lower, and Ti/TE was unchanged. Positive correlation was observed between length and VT (r = .347; p = .008) on Day 2 and (r = .338; p = .008) on Day 30. CONCLUSIONS: The present study reveals the physiological changes occurring in lung functions in healthy term neonates during the neonatal period.

Assessment of pulmonary function by impulse oscillometry and spirometry in children with type 1 diabetes mellitus.

AIM: To assess the lung functions with impulse oscillometry (IOS) and spirometry in children with type 1 diabetes mellitus (T1DM). METHODS: Fifty-one children with T1DM, and sex- and age-matched 53 healthy control (HC) subjects were included in this study. Demographic, clinical, and laboratory characteristics of the subjects were recorded and their pulmonary functions were analyzed by IOS and spirometry. RESULTS: In IOS, zR5, zR10, and zR20 levels were higher in children with T1DM compared with HCs (P = .019, P = .017, and P = .002, respectively). In spirometry, zFEF75 and zFEF25-75 were lower in children with T1DM compared with HCs (P = .025, P = .001, respectively). In IOS, zR5-20 (P = .008, P = .005, respectively) and zAX (P = .013, P = .009, respectively) were significantly lower in good-controlled group compared with moderate- and poor-controlled group. In spirometry, zFEF25-75 was significantly higher in good-controlled group compared with moderate- and poor-controlled group (P = .005, P = .009, respectively). HbA1c was positively correlated with zR5-20 value (r = .339; P = .017) in male children with T1DM. The duration of the disease was positively correlated with zR5-20 (r = .290; P = .043) and zFres (r = .358; P = .010). According to the receiver operating characteristic curve analysis to estimate optimal cut-offs to discriminate good control level of T1DM (HbA1c < 7%), a zR5-20 ≤ 2.28 demonstrated a 75.0% sensitivity and 82.9% specificity, with an area under the curve of 0.805 ([confidence interval, 0.615-0.995]; P = .007). CONCLUSIONS: This study showed subclinical impairment of lung functions which is associated with disease duration and the degree of metabolic control in children with T1DM.

The relation of serum endocan and soluble endoglin levels with metabolic control in children and adolescents with type 1 diabetes mellitus.

Objectives Endothelial dysfunction is an early marker of vascular disease in Type 1 diabetes mellitus (T1DM). In the present study, we aimed to investigate serum endocan and soluble endoglin (S-endoglin) levels, and their relation with metabolic control in children with T1DM, which was not previously assessed. Methods A total of 64 T1DM subjects and 64 healthy subjects were included in this study. Their anthropometric features, arterial blood pressures, pubertal status, insulin doses were recorded. Glycated hemoglobin, serum endocan and S-endoglin levels were measured and compared to each other. Results Serum endocan and S-endoglin levels were higher in children with T1DM than those of healthy group (p<0.01). Significant positive correlation was detected between both endocan and S-endoglin (r=0.579, p<0.001); and HbA1c and endocan (r=0.296, p=0.01). Compared to patients with good metabolic control, those with poorer metabolic control (HbA1c > 8%) had an older age, longer duration of diabetes, higher number of pubertal children. Also, patients with poorer metabolic control had higher endocan and S-endoglin levels than those of healthy group, but this finding did not reach statistical significance. There was no correlation between the endocan/S-endoglin levels and age, duration of diabetes and insulin dose. Conclusion Serum levels of endocan and S-endoglin which are novel biomarkers of endothelial dysfunction are high in children with T1DM. Elevated serum endocan and endoglin levels in children with T1DM without microvascular complications indicates endothelial damage in very early stages of the disease.

Can Complete Blood Count Parameters Predict Retinopathy of Prematurity?

Objectives: To predict the risk of retinopathy of prematurity (ROP) development according to routine complete blood count (CBC) parameters. Materials and Methods: The medical records and CBC results of 150 premature neonates were retrospectively evaluated. As ROP develops 1 month after birth, first month CBC profiles of neonates without ROP (non-ROP), with ROP (ROP group), and those with Type 1, Type 2, and Stage 1+2 ROP were compared. Besides known statistical methods like Student's t-test, logistic regression and classification & regression tree (C&RT) analysis were also done to identify a reliable quantitative predictive parameter. Results: Mean gestational age and birth weight of the ROP group (n=99) and non-ROP (n=43) group were 29.39±3.43 and 32.05±2.20 weeks and 1382.44±545.30 and 1691.51±360.84 grams, respectively (p<0.001, p<0.001). Average hemoglobin (Hb) (p<0.001), hematocrit (HCT) (p<0.001), erythrocyte (p=0.005), mean corpuscular hemoglobin (MCH) (p=0.020), and MCH concentration (p=0.019) values of the ROP group were lower than those of the non-ROP group. Leukocyte was higher in the ROP group (p=0.018). Hb [odds ratio (OR)=0.668, 95% confidence interval (CI)=0.555-0.804, p<0.001], red cell distribution width (RDW) (OR=1.282, 95% CI=1.012-1.624, p=0.040), leukocyte (OR=1.157, 95% CI=1.053-1.271, p=0.002), and platelet (OR=0.997, 95% CI: 0.994-0.999, p=0.036) values differed significantly between the two groups. Platelet, MCV, and MCH parameters were found to be lower in the Type 1 ROP group compared to the Stage 1+2 ROP group (p<0.005). MCH was the most prominent predictor (cut-off: 34.43 pg) according to the results of C&RT analysis. Conclusion: As Hb plays an important role in oxygen transport, low levels of Hb and especially MCH may cause increased vascular endothelial growth factor secretion from the hypoxic retina, thereby causing ROP. Therefore, the results of this study are encouraging regarding the use of the abovementioned CBC parameters as a simple screening test to predict ROP.

Gingival crevicular fluid levels of interleukin-18 and tumor necrosis factor-alpha in type 1 diabetic children with gingivitis.

OBJECTIVE: This study aimed to evaluate the levels of interleukin-18 and tumor necrosis factor-alpha in gingival crevicular fluid of diabetic children with gingivitis. METHODOLOGY: Eighty-eight children (44 with type 1 diabetes mellitus and 44 systemically healthy) were recruited for the study. The children were divided into four subgroups based on their periodontal and systemic condition: (1) systemically and periodontally healthy children (H), (2) systemically healthy children with gingivitis (G), (3) periodontally healthy children with T1DM (T1DM + H), and (4) children with T1DM and gingivitis (T1DM + G). The plaque index, gingival index, probing pocket depth, and GCF volume were recorded. The IL-18 and TNF-α levels in GCF were determined by ELISA. RESULTS: The clinical periodontal parameters, GCF IL-18 level, and TNF-α level were similar between diabetic and systemically healthy children (p > 0.05). The gingivitis subgroups had a significantly higher GI, PI, PPD, GCF volume, and TNF-α total amounts than the H subgroups (p < 0.0001). The IL-18 concentrations in the gingivitis subgroups were significantly lower than in the periodontally healthy subgroups. CONCLUSIONS: In diabetic children with good metabolic control, T1DM did not affect the GCF levels of IL-18 and TNF-α in the presence of gingivitis. However, increased GCF TNF-α levels in children with gingivitis confirm that TNF-α is closely related to gingival inflammation. CLINICAL RELEVANCE: Type 1 diabetes mellitus is not associated with GCF interleukin-18 and tumor necrosis factor-alpha levels in children with gingivitis.

Retinopathy of prematurity risk factors: Does human milk prevent retinopathy of prematurity?

Akyüz-Ünsal AI, Key Ö, Güler D, Bekmez S, Sagus M, Akcan AB, Kurt-Omurlu I, Anik A, Oruç-Dündar S, Türkmen M. Retinopathy of prematurity risk factors: Does human milk prevent retinopathy of prematurity? Turk J Pediatr 2019; 61: 13-19. The aim of this study was to investigate the risk factors for Retinopathy of Prematurity (ROP) development and the potential effect of human breast milk among these factors. For this purpose, infants admitted to a tertiary referral clinic for ROP screening and treatment between April 2013 and May 2015, were included in this retrospective study. The demographic data, accompanying diseases, previous surgery, type of feeding and duration of human breast milk intake were recorded. According to the ROP screening examination results, infants were divided into two groups as those with ROP (infants at any stage of ROP) and those without ROP. Relationship between the risk factors and ROP were evaluated. The comparison of 221 infants without ROP and 99 infants with ROP; revealed that gestational age at birth, birth weight, mechanical ventilation support, bronchopulmonary and cardiac diseases, hydrocephaly, any previous surgery, infections, steroid treatment percentages were high and human breast milk intake percentage was low among infants with ROP. Mean breast feeding time for infants with ROP (3.81 ± 2.33 month) was shorter than the infants without ROP (5.51 ± 1.43 month) (p < 0.001). In logistic regression analysis, the duration of breast feeding was inversely related with ROP (OR 0.744; 95% CI 0.621-0.891; p < 0,001). These results suggest that gestational age at birth and accompanying diseases are the main risk factors for the development of ROP. As the duration of the breast feeding of the infants without ROP was longer than the infants with ROP; breast feeding may have a preventive effect on ROP development.