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.

Turkish Neonatal Society guideline on neonatal infections-diagnosis and treatment.

Neonatal infections are a major cause of morbidity and mortality in the first month of life, especially in developing countries. Despite advances in neonatology, neonatal infections still haves clinical importance because of nonspecific signs and symptoms, no perfect diagnostic marker, and interference with non-infectious diseases of newborns. Diagnosis is typically made by clinical and laboratory findings. Empiric antibiotic therapy should be started in a newborn with signs and symptoms of infection after cultures are taken according to the time of the signs and symptoms, risk factors, admission from community or hospital, focus of infection, and antibiotic susceptibility estimation. Treatment should be continued according to clinical findings and culture results. Intrapartum antibiotic prophylaxis, proper hand washing, aseptic techniques for invasive procedures, appropriate neonatal intensive care unit design, isolation procedures, and especially breast milk use are needed to prevent infections. The use of diagnosis and treatment protocols increases clinical success.

Management of hypoglycemia in newborn: Turkish Neonatal and Pediatric Endocrinology and Diabetes Societies consensus report.

Hypoglycemia is one of the most important and most common metabolic problems of the newborn because it poses a risk of neurological injury, if it is prolonged and recurs. Therefore, newborns who carry a risk of hypoglycemia should be fed immediately after delivery and the blood glucose level should be measured with intervals of 2-3 hours from the 30th minute after feeding. The threshold value for hypoglycemia is 40 mg/dL for the first 24 hours in symptomatic babies. In asymptomatic babies, this value is considered 25 mg/dL for 0-4 hours, 35 mg/dl for 4-24 hours, 50 mg/dL after 24 hours and 60 mg/dL after 48 hours. Screening should be performed with bed-side test sticks. When values near the limit value are obtained, confirmation with laboratory method should be done and treatment should be initiated, if necessary. The level targeted with treatment is considered 50 mg/dL in the postnatal first 48 hours before feeding, 60 mg/dL after 48 hours in babies with high risk and above 70 mg/dL in babies with permanent hypoglycemia. In cases in which the blood glucose level is below the threshold value and can not be increased by feeding, a glucose infusion of 6-8 mg/kg/min should be initiated. If symptoms accompany, a mini bolus of 10% dextrose (2 ml/kg/min) should accompany. Incements (2 mg/kg/min) should be performed, if the target level can not be achieved and decrements (2 ml/kg/ min) should be performed, if nutrition and stabilization is provided. The infusion should be discontinued, if the infusion rate decreases to 3-5 mg/ kg/min. If necessary, blood samples should be obtained during hypoglycemia in terms of differential diagnosis and the investigation should be performed following a 6-hour fasting period in babies fed enterally and at any time when the plasma glucose is <50 mg/dL in babies receiving parenteral infusion. The hypoglycemic babies in the risk group whose infusions have been terminated can be discharged, if the plasma glucose level is found to be at the target level for two times before feeding and babies with permanent, severe or resistant hypoglycemia can be discharged, if the plasma glucose level is >60 mg/dL following a 6-hour fast.

Neonatal Hyperglycemia, which threshold value, diagnostic approach and treatment?: Turkish Neonatal and Pediatric Endocrinology and Diabetes Societies consensus report.

Hyperglycemia has become an important risk factor for mortality and morbidity in the neonatal period, especially with increased survival rates of very low birth weight neonates. Hyperglycemia in the neonatal period develops as a result of various mechanisms including iatrogenic causes, inability to supress hepatic glucose production, insulin resistance or glucose intolerance, specifically in preterm neonates. Initiation of parenteral or enteral feeding in the early period in preterm babies increases insulin production and sensitivity. The plasma glucose is targeted to be kept between 70 and 150 mg/dL in the newborn baby. While a blood glucose value above 150 mg/dL is defined as hyperglycemia, blood glucose values measured with an interval of 4 hours of >180-200 mg/dL and +2 glucosuria require treatment. Although glucose infusion rate is reduced in treatment, use of insulin is recommended, if two blood glucose values measured with an interval of 4 hours are >250 mg/dL and glucosuria is present in two separate urine samples.

Evaluation of pulmonary functions in preschool children born late-preterm.

AIM: The aim of this study was to evaluate the pulmonary functions of preschool children born late-preterm. MATERIAL AND METHODS: Children aged between 3-7 years who were born at 340/7-366/7 weeks' gestation represented the target sample. Patients with a diagnosis of congenital cardiac, pulmonary and/or muscle diseases were excluded. Respiratory symptoms were evaluated using the modified asthma predictive index and International Study of Asthma and Allergies in Childhood criteria for children aged under and over 6 years, respectively. Skin prick tests were performed. Age-matched healthy controls were chosen according to the criteria proposed by the American Thoracic Society. Lung functions were evaluated using impulse oscillometry study in both groups. Data were recorded in the SPSS program. RESULTS: A total of 139 late-preterms and 75 healthy controls participated in the study. The mean gestational week of the late-preterms was 35.3±0.9 weeks. The main admission diagnosis to neonatal intensive care unit was respiratory distress. In the postdischarge period, 54.1% were hospitalized for pulmonary infections at least once, and 57.8% were passive smoking currently. Aeroallergen sensitivity was detected as 25.8% in the late-preterm group; 34.5% and 15.1% were diagnosed as having asthma and non-asthmatic atopy, respectively. Impulse oscillometry study parameters of R5, R10, and Z5 were higher and X10 and X15 were lower in late-preterms than in controls (p<0.05). Late-preterms with and without respiratory distress in the postnatal period revealed no statistical differences for any parameters. CONCLUSIONS: Our findings suggest that presence of increased peripheral airway resistance in late-preterms as compared to term-born controls.

Neonatal sepsis and simple minor neurological dysfunction.

BACKGROUND: This study examined potential risk factors for and consequences of simple minor neurological dysfunction (SMND), in a group of very low-birthweight newborns followed until preschool age. METHODS: This was a prospective longitudinal study. Children with birthweight <1500 g were assessed at 4-6 years of age. Twenty-eight children with normal neurological examination and 35 children with SMND were included in the final analysis. Risk factors for the development of SMND and its association with certain neuropsychiatric conditions were studied. RESULTS: Based on neonatal data, in children with SMND, Apgar score at 1 min (6.13 ± 2.37 vs 7.66 ± 1.04, P = 0.008) and at 5 min (8.63 ± 1.29 vs 9.45 ± 0.65, P = 0.019) was lower, duration of hospital stay was longer (45.8 ± 21.8 vs 35.1 ± 18.2 days, P = 0.037), and the frequency of sepsis was higher (73.5 vs 25%, P < 0.001). Sepsis was found to be an independent risk factor for SMND (OR, 7.6; 95% CI: 2.2-26.0; P = 0.001). The children with SMND had lower intelligence quotient and higher prevalence of hyperactivity and refraction error. CONCLUSION: Postnatal sepsis was the single most important risk factor for the development of SMND, and these children with SMND are at great risk for certain neuropsychiatric conditions. Preventive strategies, particularly for sepsis in the neonatal period, and early diagnosis and rehabilitation of future neuropsychiatric disorders are needed for better management of these cases.

Evaluation of lung function on impulse oscillometry in preschool children born late preterm.

BACKGROUND: There is a paucity of data on lung physiology in late-preterm children, who may be exposed to a risk of decline in lung function during childhood. In this study, we evaluated lung function in preschool children born late preterm using impulse oscillometry (IOS), and compared the results with those obtained in healthy term-born children. METHODS: Children between 3 and 7 years of age who were born late preterm and who were being followed up at the outpatient clinic were included as the late-preterm group. Age-matched healthy term-born children served as controls. A total of 90 late-preterm and 75 healthy children were included in the study. At 5-20 Hz, resistance (R5-R20), reactance (X5-X20), impedans (Z5) and resonant frequency were measured on IOS. RESULTS: Mean IOS R5 and R10 were significantly higher in the late-preterm group than in the control group (P < 0.05). Mean R5, R10 and Z5 were statistically higher in late-preterm children who had been hospitalized for pulmonary infection compared with the control group (P < 0.05). Mean R5, R10, R15, R20 and Z5 were significantly higher, and mean X10 and X15 significantly lower in late-preterm children with passive smoking compared with late-preterm children without passive smoking and controls (P < 0.05). CONCLUSION: Children born late preterm had signs of peripheral airway obstruction on IOS-based comparison with healthy term-born controls. Besides the inherent disadvantages of premature birth, hospitalization for pulmonary infection and passive smoking also seemed to adversely affect lung function in children born late preterm.

Functional pulmonary atresia in newborn with normal intracardiac anatomy: Successful treatment with inhaled nitric oxide and pulmonary vasodilators.

Functional pulmonary atresia is characterized by a structurally normal pulmonary valve that does not open during right ventricular ejection. It is usually associated with Ebstein's anomaly, Uhl's anomaly, neonatal Marfan syndrome and tricuspid valve dysplasia. However, functional pulmonary atresia is rarely reported in newborn with anatomically normal heart. We report a newborn with functional pulmonary atresia who had normal intracardiac anatomy, who responded to treatment with nitric oxide and other vasodilator therapy successfully.

The effect of IVF pregnancies on mortality and morbidity in tertiary unit.

BACKGROUND: There are several studies that have shown an increased risk of premature birth and developmental abnormalities with in vitro fertilization (IVF); however, the data on preterm mortality and morbidity are limited. AIM: Our aim is to investigate whether IVF had an effect on the mortality and morbidity in neonates admitted to the neonatal intensive care unit. METHODS: A total of 940 term and preterm babies who were admitted to the intensive care unit over a period of 2 years were enrolled. Of these, 121 babies were born after IVF and 810 were born after a natural conception and 9 were born after ovulation induction. Of these, 112 preterm babies were born after IVF and 405 preterm babies were born after a natural conception. RESULTS: In the IVF group, the gestational age and birth weight were significantly lower than in the non-IVF group. Additionally, in the IVF group, multiple births were significantly higher than in the non-IVF group. IVF pregnancies increase preterm delivery but did not increase preterm mortality, and preterm morbidity did not differ among groups, except for intraventricular hemorrhage (IVH). Gestational age was shown to be the primary risk factor for IVH using a logistic regression analysis. Also when newborns at gestational age <32 weeks were compared using regression analysis, gestational age was the major risk factor for IVH. CONCLUSION: IVF appears to be associated with premature delivery and the known risks associated with prematurity.

Acute effects of gentamicin on glomerular and tubular functions in preterm neonates.

It has been reported that gentamicin causes natriuresis, magnesuria and calciuria in neonates. The aim of this study was to determine the acute effects of trough and peak levels of gentamicin on the values of serum creatinine (SCr), urine albumin/urine creatinine (UA/UCr), fractional excretion of sodium and potassium (FENa, FEK) and urine calcium/urine creatinine (UCa/UCr) in preterm neonates treated with gentamicin for suspected infection. Baseline levels of serum and urine Cr, Na and K and urine albumin and Ca levels together with trough and peak gentamicin levels were measured in 61 preterm neonates at the start of the therapy, on the day of the third gentamicin dose and 48-72 h after the cessation of the gentamicin therapy. Therapeutic trough and peak levels were recorded in 56 (91.8%) and 39 (63.9%) of the preterm neonates, respectively, whereas high trough (>2 mg/dl) and peak (>9.99 mg/dl) levels were recorded in five (8.1%) and 11 (18%) of the 61 preterm neonates, respectively. Trough and peak levels of gentamicin were positively correlated with SCr, UA/UCr, FENa, FEK and UCa/UCr values. The UA/UCr, FENa and UCa/UCr values recorded during treatment were statistically significantly different from sub-therapeutic, therapeutic and high peak gentamicin levels. Gentamicin was found to have a serum peak level-dependent microalbuminuric, natriuric and calciuric effect in preterm neonates. Based on these results, we suggest that when the monitoring of serum gentamicin levels is not possible, the monitoring of UA/UCr, FENa and UCa/UCr can be useful as a noninvasive alternative.

Concentrations of toxic metals and trace elements in the meconium of newborns from an industrial city.

OBJECTIVE: To investigate fetal exposure to toxic metals [lead (Pb), cadmium (Cd)] and fetal levels of trace elements [zinc (Zn), copper (Cu), and iron (Fe)] in newborns from an industrial city. Relationships between meconium mineral contents and parental occupation and location of residence were also tested. METHOD: The meconium mineral contents of 117 healthy newborn infants were measured by flame atomic absorption spectrophotometer. RESULTS: The median concentrations (interquartile range) of toxic metals and trace elements in the meconium were as follows: Pb: 46.5 (1,399) microg/g dry weight (wt), Cd: 2.3 (55.6) microg/g dry wt; Zn: 234 (3,049) microg/g dry wt; Cu: 11.8 (818.7) microg/g dry wt, and Fe 105 (2,980) microg/g dry wt. All the meconium samples contained both toxic metals and trace elements. The proportions of trace elements in the meconium samples with concentration higher than 100 microg/g dry wt of the substances tested were Zn 90%, Cu 64%, and Fe 53%. There were significantly positive correlations between the concentrations of toxic metals and trace elements. Also there were positive correlations between the levels of Zn, Fe, and parental occupations, and between the level of Fe and location of residence of the parents (proximity to the petroleum refinery or the dye industries). CONCLUSION: All the meconium samples were positive for toxic metals, and thus may reflect environmental pollution in the city. The occupation environments and the location of the family residence are linked with levels of trace elements in meconium.

An outbreak of SHV-5 producing Klebsiella pneumoniae in a neonatal intensive care unit; meropenem failed to avoid fecal colonization.

An outbreak of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae (ESBL-Kp) in a neonatal intensive care unit prompted a prospective surveillance study between 12th September and 6th October 2003. Surveillance was carried out by obtaining stool samples twice a week. The DNA relatedness of the isolates was shown by random amplified polymorphic DNA comparison (ERIC-PCR). ESBL production was identified by clavulanate synergy, isoelectric focusing, PCR and sequence analysis. During the study period, 49 neonates were hospitalized in the neonatal intensive care unit (NICU). In the first 20-day period, five neonates were infected with ESBL-Kp. The first patient treated with third generation cephalosporin and the second patient treated with meropenem died. While all three infected survivors were clinically improving, the digestive tracts were being colonized by SHV-5 producing Klebsiella. In the next period of the study, five neonates were colonized by ESBL-Kp as well. Univariate comparison of risk factors between colonized and non-colonized neonates was not significant. A total of 24 colonally related ESBL-Kp have been recovered from clinical materials and stool samples. This study demonstrated that parenterally applied meropenem, though successful in treating the systemic illness, might fail to protect the digestive tract from colonization of ESBL-Kp.

The effect of blood gas and Apgar score on cord blood cardiac troponin I.

OBJECTIVES: The aims of this study were to (a) establish a reference range for cardiac troponin I (cTnI) in the cord blood of healthy infants, and (b) investigate the effect of Apgar score, cord blood gas, gestational age, and creatine kinase (CK) and creatine kinase MB (CK-MB) fraction levels on cord blood cTnI levels. METHODS: 112 perinatal hypoxic and 84 control newborns without perinatal hypoxia were enrolled in this study. Cord blood samples were collected from the babies for arterial blood gas analysis, cTnI, CK and CK-MB measurements. Gestational age, birth weight, sex, Apgar score and history of fetal distress were recorded. Hypoxic ischemic encephalopathy (HIE) group, hypoxic but without HIE group and control groups were identified according to clinical observations during the first 72 h in the newborn unit. RESULTS: HIE and perinatal hypoxic without HIE groups had a significantly higher cord blood cTnI level according to the control group (1.8 ng/mL (0-13), 0 ng/ml (0-1.1) and 0 ng/ml (0-0.3) respectively). Cord blood cTnI level did not have a correlation with birth weight and gestational age (r = -0.02, p > 0.05 and r = 0.08, p > 0.05 respectively). Cord blood cTnI level also had a negative correlation with pH, bicarbonate, base deficit, and Apgar score (r = -0.40, p < 0.001; r = -0.39 p < 0.001; r = -0.45 p < 0.001; r = -0.41, p < 0.001) respectively). Cord blood cTnI level showed a positive correlation with CK and CK-MB levels (r = 0.45, p < 0.001 and r = 0.37, p < 0.001 respectively). Receiver operator curve analysis revealed that the most sensitive factor for prediction of perinatal hypoxia is cord cTnI value [area under curve = 0.929]. The optimal cut-off value of cord cTnI was 0.35 ng/ml for hypoxia. CONCLUSION: cTnI levels in the cord blood are not affected by gestational age and birth weight. cTnI together with CK and CK-MB has been found to be elevated in hypoxic infants compared to normal infants. Therefore cTnI may be an indicator for perinatal hypoxia in neonates.

Serum leptin levels of premature and full-term newborns in early infancy: metabolic catch-up of premature babies.

Leptin is secreted from the edipose tissue and has an important role in the regulation of energy metabolism. This study aimed to compare serum leptin levels of preterm and full-term infants during the first three months of their life and to define the roles of sex, weight, thickness of subcutaneous adipose tissue, gestational age and maternal leptin in the determination of serum leptin levels. Forty-four full-term and 32 preterm infants were included in the study. Weight, thickness of subcutaneous adipose tissue, serum glucose, cortisol, insulin and leptin levels were compared between preterm and full-term infants at 7th, 30th and 90th days. ELISA method was used in determining serum leptin levels. Weight, thickness of subcutaneous adipose tissue and serum leptin levels were significantly increased in full-term infants compared to preterm infants at days 7 and 30. At 90th day weight and thickness of subcutaneous adipose tissue were significantly increased in full-term infants, but the difference in serum leptin levels did not reach statistical significance (p=0.56). Weight was the most important factor predicting serum leptin levels at the 7th day. On the other hand, the thickness of subcutaneous adipose tissue was the most important determinant at days 30 and 90. Maternal serum leptin level was a determinant of serum leptin level at day 7. Sex was a determinant of serum leptin level of the infant at days 7 and 30. The differences in weight gain, increase in thickness of subcutaneous adipose tissue and increase of serum leptin levels were not significant between groups. But the increase in serum leptin levels was correlated in both preterm and full-term infants with weight gain and increase in thickness of subcutaneous adipose tissue. At three months of age, in the catch-up growth period, preterm infants reach serum leptin levels near those of full-term infants. The thickness of subcutaneous adipose tissue has a role in the determination of serum leptin levels after 30 days of life.

Cord blood cardiac troponin I as an early predictor of short-term outcome in perinatal hypoxia.

BACKGROUND: In most perinatal-hypoxia survivors, myocardial dysfunction can be reversed with appropriate inotropic support and oxygenation. The main problem related to outcome is cerebral damage. OBJECTIVE: We tested the hypothesis that cardiac troponin I (cTnI), a known marker of myocardial injury, is also an early predictor of severity of cerebral damage and mortality in intrauterine hypoxia. METHODS: Venous and arterial cord blood samples were collected at delivery from 54 consecutive newborns with hypoxic-ischemic encephalopathy and from 50 consecutive healthy controls. Arterial blood gas analysis was performed and levels of cTnI, creatine kinase and creatine kinase-MB in venous cord blood were measured. The same serum parameters were also measured on the 3rd and 7th day of life. RESULTS: Infants with hypoxia had a significantly higher cord blood cTnI levels than controls (p < 0.0001). Cord blood and 3rd and 7th day serum cTnI values showed a significant increase with severity of HIE (p < 0.0001). In non-survivors cord blood cTnI levels were significantly higher than the survivors (5.9 ng/ml, range 2.1-12.8, and 1.6 ng/ml, range 0.4-5.8, respectively; p < 0.0001). Receiver-operator curve analysis revealed cord cTnI as the most sensitive factor for predicting early death (area under curve = 0.956; SE: 0.028; 95% CI: 0.9-1.01). Cord blood cTnI of 4.6 ng/ml was identified as the optimal cut-off level for predicting serious risk of early mortality. CONCLUSION: The results suggest that significant elevation of cord cTnI is an excellent early predictor of severity of hypoxic-ischemic encephalopathy and mortality in term infants.