Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples.

BACKGROUND: Many drugs are used off-label or unlicensed in neonates. This does not mean they are used without evidence or knowledge. We aimed to apply and evaluate the Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies (GAPPS) scoring system for the level of evidence of two commonly used anti-epileptic drugs. METHODS: Midazolam and phenobarbital as anti-epileptics were evaluated with a systematic literature search on neonatal pharmacokinetic (PK) and/or pharmacodynamic [PD, (amplitude-integrated) electroencephalography effect] studies. With the GAPPS system, two evaluators graded the current level of evidence. Inter-rater agreement was assessed for dosing evidence score (DES), quality of evidence (QoE), and strength of recommendation (REC). RESULTS: Seventy-two studies were included. DES scores 4 and 9 were most frequently used for PK, and scores 0 and 1 for PD. Inter-rater agreements on DES, QoE, and REC ranged from moderate to very good. A final REC was provided for all PK studies, but only for 25% (midazolam) and 33% (phenobarbital) of PD studies. CONCLUSIONS: There is a reasonable level of evidence concerning midazolam and phenobarbital PK in neonates, although using a predefined target without integrated PK/PD evaluation. Further research is needed on midazolam use in term neonates with therapeutic hypothermia, and phenobarbital treatment in preterms. IMPACT: There is a reasonable level of evidence concerning pharmacotherapy of midazolam and phenobarbital in neonates. Most evidence is however based on PK studies, using a predefined target level or concentration range without integrated, combined PK/PD evaluation. Using the GAPPS system, final strength of recommendation could be provided for all PK studies, but only for 25% (midazolam) to 33% (phenobarbital) of PD studies. Due to the limited PK observations of midazolam in term neonates with therapeutic hypothermia, and of phenobarbital in preterm neonates these subgroups can be identified for further research.

Should Ocular Hemorrhage Screening be Conducted in Newborns with Acidosis?

OBJECTIVE: Ocular hemorrhages (OHs) may cause visual disturbances and incidence vary from 18 to 39% in newborns. Precipitated/instrumental delivery and perinatal asphyxia were predefined risk factors. Acidosis can interfere with coagulation and disrupt the pressure of ocular capillaries and put infants with moderate acidosis with or without hypoxic-ischemic encephalopathy at risk for OH. We aimed to evaluate the OH in neonates with fetal acidosis. STUDY DESIGN: Neonates >34 weeks are included if pH < 7.10 and BE < -12 mmol/L within the first hour. Ophthalmologic examinations for retinal (RH), vitreous, and anterior chamber (hyphema) hemorrhage were done within the third day. RH was staged according to Egge's classification. Follow-up of the patients was continued until the age of 2. Clinical characteristics of newborns were analyzed. RESULTS: Sixty-two neonates (38 ± 2.3 weeks, 2,971 ± 612 g) were included. pH = 6.91 ± 0.16, BE = - 17.2 ± 5.3 mmol/L. OH was found in 22 (36.7%) neonates (hyphema n = 2, vitreous n = 2, RH n = 21). Thirty-eight eyes with RH were staged (Stage 3: n = 15 [39.5%]; Stage 2: n =11 [28.9%]; Stage 1: n = 12 [31.6%]). Vaginal delivery (OR: 4.9, 95% CI [1.4-17.8]) and advanced resuscitation at the delivery room (OR: 8.8; 95% CI [1.9-41.7]) were found to increase the risk of RH. CONCLUSION: Approximately one-third of neonates with moderate to severe acidosis exhibited RH when examined on the third day. Contrary to previous studies that reported mild RH in otherwise healthy neonates, our findings revealed that neonates with moderate to severe acidosis predominantly presented with Stage 3 RH. While the higher incidence of RH in vaginally delivered infants is consistent with previous studies, the identification of advanced resuscitation as a risk factor is a new addition to the literature. The findings in our study highlight the importance of retinal examination in neonates with acidosis in the presence of intubation during resuscitation. KEY POINTS: · One-third of neonates with moderate to severe acidosis exhibited RH.. · Stage 3 RH was identified as the most prevalent.. · Advanced resuscitation was identified as an independent risk factor for RH..

The effect of oscillometric blood pressure measurement on pain response in preterm infants.

AIM: Preterm neonates are exposed to many painful procedures in neonatal intensive care units. This study aims to evaluate the effect of oscillometric blood pressure (BP) measurement on pain response in preterm infants. METHODS: This prospective study was performed over 4 months in a level III neonatal intensive care unit. Premature neonates whose gestational age was <34 weeks and postmenstrual age <36 weeks were included if they had no systemic diseases. BP measurement was performed on the right arm. The Premature Infant Pain Profile-Revised (PIPP-R) scores were evaluated three times before, during, and 10 min after BP measurement. RESULTS: During the 5-month period, 100 preterm neonates (53 male infants) were included in the study. Median birth weight and gestational age of the infants were 1148 (IQR: 1015-1300) g and 28 (IQR: 27-30) weeks, respectively. PIPP-R scores were found to be ≥7 in 34% of neonates. PIPP-R scores increased during BP measurement and decreased after. CONCLUSION: Our results demonstrated that oscillometric BP measurement which is generally accepted as a non-invasive tool for monitoring can produce mild pain in premature neonates of postmenstrual age <36 weeks.

In-Hospital Newborn Falls and Near Miss Events: A Need to Report.

OBJECTIVE: This study aimed to evaluate the clinical characteristics of the neonates who fell in the maternity ward and identify the incidence of near miss events during the immediate postpartum period. STUDY DESIGN: The study consisted of two steps. The retrospective part included the evaluation of admissions due to the in-hospital newborn fall for 6 years. The prospective part included the assessment of the near miss events (any probability of falling of the newborn; either cosleeping or an incident with a possible consequence of falling of the newborn) in the postpartum clinic (<72 hours after delivery) for a period of 4 weeks. The details of the events and clinical outcomes were recorded. A questionnaire about fatigue was administered to mothers who experienced near miss event. RESULTS: Seventeen in-hospital newborn falls were recorded: 1.8 to 2.4/10,000 live births. The median age of the neonates when the fall occurred was 22 (16-34) postnatal hours. Fourteen events (82%) occurred between 10 p.m. and 6 a.m. All neonates who experienced a fall were discharged without any known adverse outcomes. Twelve mothers (71%) had experienced a near miss event before. In the prospective arm of the study, 67 out of 804 mothers (8.3%) were found to experience a near miss event (44/1,000 days of postpartum hospitalization). Thirty-two events (49%) occurred in the first postpartum day. Fifty-two events (78%) occurred between 10 p.m. and 6 a.m. Fifty-eight mothers (86%) had no companion. Sixty-three percent of the mothers expressed intense fatigue after delivery. CONCLUSION: In-hospital newborn fall may occur in the postpartum period, and near miss events should warn clinicians for a probable fall event. The nighttime shift requires more attention regarding the prevention of both the fall and the near miss events. Immediate postpartum mothers are needed to be observed carefully. KEY POINTS: · In-hospital newborn falls occurred mainly during the night shift.. · Nearly two-third of the mothers whose newborn was fallen experienced a previous near miss event.. · Any near miss event in the hospital was detected in 8.3% of mothers..

Umbilical Cord Separation Time and Influencing Factors in Very-Low-Birth-Weight Preterm Neonates.

OBJECTIVE: The average time for umbilical cord separation in term neonates is 7 to 10 days. Prematurity, phototherapy, prolonged duration of antibiotic treatment, and parenteral nutrition are other factors which were demonstrated to delay cord separation. In the previous studies including greater premature infants, the time of separation of the umbilical cord was shown to vary 2 to 3 weeks. We aimed to determine the cord separation time and associated factors in very-low-birth-weight (VLBW) infants. STUDY DESIGN: In this retrospective study, VLBW infants (birth weight [BW] <1,500 g, gestational age [GA] < 32 weeks) without umbilical catheterization were included. Specific cord care was not applied. The cord separation time, gender, mode of delivery, presence of sepsis, duration of antibiotic treatment, serum free thyroxine, free triiodothyronine (FT3), thyroid-stimulating hormone, lowest leukocyte, polymorphonuclear leukocytes (PMNLs), and platelet counts were recorded. RESULTS: The study included 130 infants (GA: 29 ± 2 weeks, BW: 1,196 ± 243 g). Mean cord separation time was 14 ± 5 days, while 95th percentile was 22nd day of life. A positive correlation was demonstrated between duration of antibiotic treatment and cord separation time (p < 0.001, r: 0.505). Cord separation time did not differ regarding gender or mode of delivery. Corrected leukocyte count (p = 0.031, r: -0.190) and PMNL count (p = 0.022, r: -0.201), and serum FT3 level (p = 0.003, r: -0.261) were found to be negatively correlated with cord separation time. The cord separation time was found to be delayed in the presence of sepsis (with sepsis: 18 ± 7 days and without sepsis: 13 ± 3 days; p = 0.008). Sepsis was found to delay the cord separation time beyond second week (odds ratio = 6.30 [95% confidence interval: 2.37-15.62], p < 0.001). CONCLUSION: The 95th percentile for cord separation time was 22nd day. Sepsis might be either the reason or the consequence of delayed cord detachment. The exact contribution of low serum FT3 levels to the process of cord separation should be investigated in further studies. KEY POINTS: · Mean cord separation time was 14 ± 5 days, while 95th percentile was 22nd day, in VLBW infants.. · Sepsis was found to delay the cord separation time by sixfold beyond second week.. · Serum free triiodothyronine level was negatively correlated with cord separation time..

Effects of blood transfusion on regional tissue oxygenation in preterm newborns are dependent on the degree of anaemia.

AIM: Most of the preterm infants are transfused at least once during their stay in the neonatal intensive care unit (NICU). The aims of this study were to demonstrate if packed red blood cell (pRBC) transfusion modulates regional (cerebral, abdominal, renal) tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) and to demonstrate if we can use NIRS to guide transfusion decisions in neonates. METHODS: A multi-probe NIRS device was applied to anaemic preterm infants of gestational age <33 weeks for 30-60 min before and 24 h after pRBC transfusion. We evaluated the results separately in the subgroup with a pre-transfusion haemoglobin (Hb) < 8 g/dL. Cerebral, abdominal and renal tissue oxygen saturation (rSO2 ) and abdominal/cerebral, abdominal/renal and renal/cerebral rSO2 ratios before and 24 h after transfusion were compared. RESULTS: There was no significant difference in cerebral rSO2 and abdominal/renal rSO2 ratios before and 24 h after transfusion, but abdominal and renal rSO2 and abdominal/cerebral and renal/cerebral rSO2 ratios at the 24th h following transfusion increased significantly. This increase was observed in the subgroup with pre-transfusion Hb < 8 g/dL. Although statistically significant, the increase in renal oxygenation was within the limits of variability. CONCLUSIONS: The increase in tissue oxygenation in abdominal region after pRBC transfusion suggests decreased tissue oxygenation of intestines during severe anaemia despite cerebral oxygenation being maintained at that particular Hb level. The impact of the increase on renal oxygenation with pRBC transfusion is unclear and might need further investigation. Increase in abdominal rSO2 may cause reperfusion injury, oxidative damage and trigger necrotising enterocolitis.

Hepatic Complications of Umbilical Venous Catheters in the Neonatal Period: The Ultrasound Spectrum.

OBJECTIVES: Umbilical venous catheterization is commonly used in the neonatal period; however, it has some complications. In this study, we evaluated neonates who underwent umbilical venous catheterization and developed hepatic complications. Furthermore, we aimed to define all of the possible lesions and to clarify the imaging findings of umbilical venous catheter-induced hepatic injury. METHODS: Two hundred forty-four neonates who underwent umbilical venous catheterization between March 2013 and September 2015 in a single tertiary care referral center were included in this study. To determine whether they had any hepatic complications, all patients underwent abdominal grayscale and Doppler ultrasound examinations, and their clinical data were recorded. RESULTS: The frequency of liver-related complications from umbilical venous catheterization was 33.6% (82 of 244). Air in the portal venous system was the most frequent complication (20.1% [49 of 244]). Left portal venous thrombosis was noted in 6.1% (15 of 244). Parenchymal lesions in the liver related to umbilical venous catheterization were seen in 7.4% of patients (18 of 244) as follows: single nodular echogenic lesions (4.1% [10 of 244]), branching small nodular echogenic lesions (2.1% [5 of 244]), and large irregular heterogeneous lesions with laceration and perihepatic fluid (1.2% [3 of 244]). There was no statistical significance for any type of complication according to the gestational age (P > .05). CONCLUSIONS: Hepatic complications due to umbilical venous catheters are not uncommon in the neonatal period. Ultrasound is the best imaging modality for confirming the diagnosis and for follow-up.

Perfusion index assessment during transition period of newborns: an observational study.

BACKGROUND: Perfusion index (PI) is becoming a part of clinical practice in neonatology to monitor peripheral perfusion noninvasively. Hemodynamic and respiratory changes occur in newborns during the transition period after birth in which peripheral perfusion may be affected. Tachypnea is a frequent symptom during this period. While some tachypneic newborns get well in less than 6 h and diagnosed as "delayed transition", others get admitted to intensive care unit which transient tachypnea of newborn (TTN) being the most common diagnosis among them. We aimed to compare PI of neonates with TTN and delayed transition with controls, and assess its value on discrimination of delayed transition and TTN. METHODS: Neonates with gestational age between 37 and 40 weeks who were born with elective caesarian section were included. Eligible neonates were monitored with Masimo Set Radical7 pulse-oximeter (Masimo Corp., Irvine, CA, USA). Postductal PI, oxygen saturation and heart rate were manually recorded every 10 s for 3 min for two defined time periods as 10th minute and 1st hour. Axillary temperature were also recorded. Newborn infants were grouped as control, delayed transition, and TTN. RESULTS: Forty-nine tachypneic (TTN; 21, delayed transition; 28) and 30 healthy neonates completed the study. PI values were similar between three groups at both periods. There were no correlation between PI and respiratory rate, heart rate, and temperature. CONCLUSION: PI assessment in maternity unit does not discriminate TTN from delayed transitional period in newborns which may indicate that peripheral perfusion is not severely affected in either condition.

Nasal HFOV with Binasal Cannula Appears Effective and Feasible in ELBW Newborns.

Non-invasive ventilation has been used increasingly in recent years to reduce the duration of endotracheal ventilation and its complications, especially bronchopulmonary dysplasia. Nasal continuous positive airway pressure and nasal intermittent positive pressure ventilation are the most common non-invasive modalities, and nasal high-frequency oscillatory ventilation (n-HFOV) is relatively new but it seems effective and feasible. We present three premature cases who were ventilated with n-HFOV with Neotech RAM Cannula as interphase. In two cases, we used n-HFOV with good results to prevent extubation failure, and in one case, we used it to avoid intubation with success. n-HFOV may be useful both in early times of respiratory failure and also to facilitate extubation particularly in patients with prolonged intubation.

Neurocutaneous melanocytosis, hemimegalencephaly and large ovarian cyst in a newborn.

We report a case of a newborn girl with neurocutaneous melanocytosis, hemimegalencephaly and a large ovarian cyst. She also had melanocyte deposition in the filum terminale. The ultrasound and the magnetic resonance imaging findings are discussed.

Expanding the mutational spectrum of CRLF1 in Crisponi/CISS1 syndrome.

Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis, and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia associated with death in most cases in the first years of life. To date, 24 distinct CRLF1 mutations have been found either in homozygosity or in compound heterozygosity in CS/CISS1 patients, with the highest prevalence in Sardinia, Turkey, and Spain. By reporting 11 novel CRLF1 mutations, here we expand the mutational spectrum of CRLF1 in the CS/CISS1 syndrome to a total of 35 variants and present an overview of the different molecular and clinical features of all of them. To catalog all the 35 mutations, we created a CRLF1 mutations database, based on the Leiden Open (source) Variation Database (LOVD) system (https://grenada.lumc.nl/LOVD2/mendelian_genes/variants). Overall, the available functional and clinical data support the fact that both syndromes actually represent manifestations of the same autosomal-recessive disorder caused by mutations in the CRLF1 gene. Therefore, we propose to rename the two overlapping entities with the broader term of Crisponi/CISS1 syndrome.

Analysis of serum γ-glutamyl transferase levels in neonatal intensive care unit patients.

OBJECTIVES: Gamma-glutamyl transferase (GGT) is commonly measured in newborn infants as a sensitive liver function test; however, reference ranges are mostly based on early studies, including relatively small number of patients. The aim of this study was to emphasise recently changed GGT values because of changed newborns profile admitted to neonatal intensive care units (NICUs) and establish new cross-sectional reference ranges for the serum GGT levels in a cohort of neonates between 26 and 42 weeks' gestational age in 1 centre. METHODS: From January 1, 2010 to December 31, 2012, liver function tests including serum GGT measurements were performed in 705 newborns who were admitted to NICUs because of different aetiologies at Gazi University School of Medicine Hospital, Ankara, Turkey. Infants with Apgar score <8 at the fifth minute, any metabolic or liver disease, cholestasis, congenital infection, culture-proven sepsis, elevated serum aminotransferases, and who were treated with phenobarbital were excluded. Clinical and laboratory data of 583 neonates were analysed retrospectively. GGT was measured by enzymatic method using the Abbott Architect C16000 autoanalyser. Mean, 2.5th, and 97.5th percentiles were used to express the reference range data. RESULTS: Four hundred sixty-one GGT values of 200 preterm infants and 501 GGT values of 383 term infants during the first 28 days after birth were analysed. Serum GGT levels of preterm infants in the first 7 days and between 8 and 28 days after delivery were (mean±standard deviation; 141.81±88.56 U/L and 131.17±85.53 U/L) similar to term infants (139.90±86.46 U/L and 144.56±86.51 U/L), respectively (P=0.649 and P=0.087). Serum GGT levels were found to be significantly higher in male infants (no need of query) (145.98±93.68 U/L) than female infants (132.18±78.97 U/L) (P=0.035), and infants born vaginally (152.24±90.71 U/L) also had higher serum GGT activity than those born by caesarean section (135.38±85.37 U/L) (P=0.005). CONCLUSIONS: A new reference range for serum GGT levels that is higher than previous reference values can identify neonates with truly abnormal results and prevent unnecessary interventions.

The risk assessment study for hemolytic disease of the fetus and newborn in a University Hospital in Turkey.

Maternal red-cell alloimmunization occurs when a woman's immune system is sensitized to foreign red-blood cell surface antigens, leading to the production of alloantibodies. The resulting antibodies often cross the placenta during pregnancies in sensitized women and, if the fetus is positive for red-blood-cell surface antigens, this will lead to hemolysis of fetal red-blood cells and anemia. The most severe cases of hemolytic disease in the fetus and newborn baby are caused by anti-D, anti-c, anti-E and anti-K antibodies. There are limited data available on immunization rates in pregnant women from Turkey. The aim of the present study was to provide data on the frequency and nature of maternal RBC alloimmunization in pregnant women in a tertiary care hospital. In this study, we retrospectively evaluated the indirect antiglobulin test results of Rh-negative pregnant women performed in our Blood Bank between 2006 and 2012. Indirect antiglobulin test positive women also underwent confirmatory antibody screening and identification. During the study period, 4840 women admitted to our antenatal clinics. With regards to the major blood group systems (ABO and Rh), the most common phenotype was O positive (38.67%). There were 4097 D-antigen-positive women (84.65%) and 743 women with D-antigen-negative phenotype (15.35%). The prevalence of alloimmunization was found to be 8.74% in D-antigen negative group. Despite prophylactic use of Rh immunglobulins, anti-D is still a common antibody identified as the major cause of alloimmunization in our study (anti-D antibody 68.57%, non-D antibody 31.42%). While alloimmunization rate to D antigen was 6.46%, non-D alloimmunization rate was 2.69% among Rh-negative pregnant women. Moreover, detailed identification facilities for antibodies other than anti-D are not available in most of centers across Turkey. However, large-scale studies on pregnant women need to be done in order to collect sufficient evidence to formulate guidelines and to define indications for alloantibody screening and identification.

Multi-organ dysfunction in infants with acidosis at birth in the absence of moderate to severe hypoxic ischemic encephalopathy.

INTRODUCTION: Infants with perinatal asphyxia are at risk for organ failure aside from the brain, regardless of the severity of the asphyxial insult. We aimed to evaluate the presence of organ dysfunction other than the brain in newborns with moderate to severe acidosis at birth, in the absence of moderate to severe hypoxic ischemic encephalopathy. MATERIALS AND METHODS: Data of 2 years were retrospectively recorded. Late preterm and term infants admitted to the intensive care unit with ph < 7.10 and BE < -12 mmol/l in the first hour were included in the absence of moderate to severe hypoxic ischemic encephalopathy. Respiratory dysfunction, hepatic dysfunction, renal dysfunction, myocardial depression, gastrointestinal problems, hematologic system dysfunction, and circulatory failure were evaluated. RESULTS: Sixty-five infants were included [39 (37-40) weeks, 3040 (2655-3380) grams]. Fifty-six (86 %) infants had one or more dysfunction in any system [respiratory: 76.9 %, hepatic: 20.0 %, coagulation: 18.5 %, renal: 9.2 %, hematologic: 7.7 %, gastrointestinal: 3.0 %, and cardiac: 3.0 %]. Twenty infants had at least two affected systems. The incidence of coagulation dysfunctions was higher in the infants with severe acidosis (n = 25, ph < 7.00) than the infants with moderate acidosis (n = 40: pH = 7.00-7.10); 32 % vs 10 %; p = 0.03. CONCLUSIONS: Moderate to severe fetal acidosis is associated with the development of extra-cranial organ dysfunctions in infants who do not require therapeutic hypothermia. A monitoring protocol is needed for infants with mild asphyxia in order to identify and manage potential complications. Coagulation system should be carefully evaluated.

Neonatal Resuscitation Practices in Turkey: A Survey of the Turkish Neonatal Society and the Union of European Neonatal and Perinatal Societies.

OBJECTIVE: Optimal care in the delivery room is important to decrease neonatal morbidity and mortality. We aimed to evaluate neonatal resuscitation practices in Turkish centers. MATERIALS AND METHODS: A cross-sectional survey consisted of a 91-item questionnaire focused on delivery room practices in neonatal resuscitation and was sent to 50 Turkish centers. Hospitals with <2500 and those with ≥2500 births/year were compared. RESULTS: In 2018, approximately 240 000 births occurred at participating hospitals with a median of 2630 births/year. Participating hospitals were able to provide nasal continuous-positiveairway-pressure/high-flow nasal cannula, mechanical ventilation, high-frequency oscillatory ventilation, inhaled nitric oxide, and therapeutic hypothermia similarly. Antenatal counseling was routinely performed on parents at 56% of all centers. A resuscitation team was present at 72% of deliveries. Umbilical cord management for both term and preterm infants was similar between centers. The rate of delayed cord clamping was approximately 60% in term and late preterm infants. Thermal management for preterm infants (<32 weeks) was similar. Hospitals had appropriate equipment with similar rates of interventions and management, except conti nuous-positive-airway-pressure and positive-end-expiratory-pressure levels (cmH2O) used in preterm infants (P = .021, and P = .032). Ethical and educational aspects were also similar. CONCLUSIONS: This survey provided information on neonatal resuscitation practices in a sample of hospitals from all regions of Turkey and allowed us to see weaknesses in some fields. Although adherence to the guidelines was high among centers, further implementations are required in the areas of antenatal counseling, cord management, and circulation assessment in the delivery room.

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.

Evaluation of radiologic evidence of metabolic bone disease in very low birth weight infants at fourth week of life.

AIM: The aim of this study is to determine the incidence of metabolic bone disease (MBD) and assess the risk factors for development radiologic evidence of MBD. METHODS: Preterm infants with gestational age ≤32 weeks and birth weight ≤1500 g were included in this prospective study. Metabolic bone disease was defined as hypophosphatemia (phosphorus levels <4 mg/dl), ALP levels >450 U/L, or radiologic findings of MBD at four weeks of age. RESULTS: The study included 254 infants (gestational age: 29 (27-30) weeks, birth weight: 1130 g (960-1300)). Metabolic bone disease was diagnosed in 96 patients (37%); 48 infants had only radiologic evidence of MBD, 24 infants had only biochemical diagnosis of MBD, and 24 infants had both radiologic evidence of MBD and biochemical diagnosis of MBD. CONCLUSIONS: Our results showed that radiologic evidence of MBD existed in some infants with normal biochemical results. That finding may guide further development of screening programs for MBD.

The prevalence and diagnostic criteria of health-care associated infections in neonatal intensive care units in Turkey: A multicenter point- prevalence study.

BACKGROUND: Healthcare-acquired infections (HAIs) in the neonatal period cause substantial morbidity, mortality, and healthcare costs. Our purpose was to determine the prevalence of HAIs, antimicrobial susceptibility of causative agents, and the adaptivity of the Centres for Disease Control and Prevention (CDC) criteria in neonatal HAI diagnosis. METHODS: A HAI point prevalence survey was conducted in the neonatal intensive care units (NICUs) of 31 hospitals from different geographic regions in Turkey. RESULTS: The Point HAI prevalence was 7.6%. Ventilator-associated pneumonia (VAP) and central line-associated bloodstream infections (CLABSI) and late onset sepsis were predominant. The point prevalence of VAP was 2.1%, and the point prevalence of CLABSI was 1.2% in our study. The most common causative agents in HAIs were Gram-negative rods (43.0%), and the most common agent was Klebsiella spp (24.6%); 81.2% of these species were extended spectrum beta-lactamase (ESBL) (+). Blood culture positivity was seen in 33.3% of samples taken from the umbilical venous catheter, whereas 0.9% of samples of peripherally inserted central catheters (PICCs) were positive. In our study, 60% of patients who had culture positivity in endotracheal aspirate or who had purulent endotracheal secretions did not have any daily FiO2 change (p = 0.67) and also 80% did not have any increase in positive end-expiratory pressure (PEEP) (p = 0.7). On the other hand, 18.1% of patients who had clinical deterioration compatible with VAP did not have endotracheal culture positivity (p = 0.005). CONCLUSIONS: Neonatal HAIs are frequent adverse events in district and regional hospitals. This at-risk population should be prioritized for HAI surveillance and prevention programs through improved infection prevention practices, and hand hygiene compliance should be conducted. CDC diagnostic criteria are not sufficient for NICUs. Future studies are warranted for the diagnosis of HAIs in NICUs.

Effect of long-term glucocorticoid therapy on bone mineral density of the patients with congenital adrenal hyperplasia.

BACKGROUND AND OBJECTIVES: Congenital adrenal hyperplasia (CAH) is characterized by androgen excess which should be treated with life-long glucocorticoid therapy, thus can affect bone mineralization. We aimed to evaluate the bone mineral density (BMD) and determine the factors affecting bone mineralization in patients with CAH. METHOD: This prospective case-control study was conducted in children, adolescents and young adults with classical 21-hydroxylase CAH, and age-, sex-, and pubertal stage matched healthy controls. Lumbar1-4 BMD was determined by dual-energy X-ray absorptiometry. BMD z-score was calculated using national standards with respect to height age and was referred as `low BMD` if z-score < -1 SD. Univariate analyses were performed between low BMD and normal BMD groups, and multivariate logistic regression analysis was performed to assess the independent predictors of low BMD. Correlations of Body Mass Index (BMI)-z-score, average serum 17-hydroxyprogesterone level, duration of treatment, average and cumulative glucocorticoid doses with BMD z-score were evaluated with Spearman analyses. RESULTS: Each group included 37 cases. BMD z-score of patients with CAH [0.47 (-0.04 - 1.56)] was higher than control group [-0.43 (-0.82 -0.05)]; p= < 0.001. Number of patients with low BMD was similar in both groups; [CAH: 6(16.2%), control: 5(13.5%); p= 0.744]. BMI- z-score was higher in patients with CAH when compared to control group; p= < 0.001. BMI z-score was lower in low BMD group as comparison to normal BMD group; p= 0.041. Each 1.0 decrease in BMI z-score, risk of having low BMD was found to increase by 1.79 (%95 CI: 1.03- 3.12, p= 0.040). BMI-z-score, average serum 17-hydroxyprogesterone level, duration of treatment, average and cumulative glucocorticoid doses were not found to be correlated with BMD z-score. CONCLUSION: Long-term glucocorticoid therapy did not have negative effect on BMD of patients with CAH. Higher BMI z-score in patients with CAH may have a positive effect on preserving bone health. Precautions should be taken for increased risk of obesity.