Effect of prostaglandin-E1 treatment on pyloric wall thickness in newborns with ductal-dependent critical congenital heart diseases.

BACKGROUND: Prostaglandin E1 (PGE1) is used in the medical treatment of ductal-dependent critical congenital heart disease (CCHD) in neonates. Apnea/bradycardia, hypotension, hypokalemia, and fever are the most important side effects of PGE1. Moreover, gastric outlet obstruction has been reported in a few case reports. A prospective study was conducted to investigate the effect of PGE1 treatment on pyloric wall thickness in newborns with congenital heart diseases. METHODS: A total of 22 newborns with ductal-dependent CCHD having PGE1 infusion longer than a week were included in this study. Ultrasonographic measurements were performed before and one week after the PGE1 infusion to evaluate the pyloric thickness and length. The protocol was registered with ClinicalTrials.govidentifier NCT04496050. RESULTS: A total of 22 neonates with mean gestational age 38 ± 1.8 weeks and birth weight 3105 ± 611 gr were enrolled in the study. The median time of the second ultrasound was seven days. The median cumulative dose of PGE1 given during this period was 108 mcg/kg/min. There was a statistically significant increase in post-treatment pyloric thickness and length compared to pre-treatment measurements (p < 0.001, p < 0.001). None of the patients with increased thickness and pyloric muscle length presented any symptoms. CONCLUSION: PGE1 treatment significantly increased the pyloric thickness and length after at least one-week treatment. PGE1 with its action mechanism is likely to cause gastric outlet obstruction, although not exactly pyloric stenosis on the condition used for a long time.

Lung ultrasonography decreases radiation exposure in newborns with respiratory distress: a retrospective cohort study.

Chest X-ray (CXR) is commonly used as a first-line imaging method to determine the cause of respiratory distress in NICUs. The aim of the study was to retrospectively assess the decrease in the number of CXRs performed due to the use of lung ultrasonography on the first day of life for newborns with respiratory distress. Infants who were admitted to the NICU on the first day of life due to respiratory distress were enrolled in this study (ClinicalTrials.gov identifier NCT04722016) and divided into two groups: the study group (n = 104) included patients born between January 2019 and June 2020, and the historical control group (n = 73) included patients born between June 2017 and December 2018. As a first-line technique for lung imaging, only CXR had been used in the historical control group, whereas ultrasound had been preferred in the study group. The radiation dose to the newborns and the number of CXRs performed in the first day of life were compared between the two groups. Significant reductions in the number of CXRs performed and radiation exposure were observed in the study group. The radiation dose decreased from 5.54 to 4.47 µGy per baby when LUS was routinely used. The proportion of patients who underwent CXR decreased from 100 to 71.2%.Conclusion: We observed that using lung ultrasonography as a first-line evaluation method in neonates with respiratory distress decreased both the number of CXRs performed and radiation exposure. What is Known: • Chest X-ray is commonly used as a first line imaging method to diagnose the reason of respiratory distress in NICUs. • Lung ultrasound is a new diagnostic tool for lung imaging. What is New: • With the use of lung ultrasonography, radiation exposure of both newborns and healthcare workers can be reduced. • This retrospective study revealed that most of the babies with respiratory distress were treated without CXR.

Long-term follow-up of patients after acute kidney injury in the neonatal period: abnormal ambulatory blood pressure findings.

BACKGROUND: Data on the long-term effects of neonatal acute kidney injury (AKI) are limited. METHODS: We invited 302 children who had neonatal AKI and survived to hospital discharge; out of 95 patients who agreed to participate in the study, 23 cases were excluded due to primary kidney, cardiac, or metabolic diseases. KDIGO definition was used to define AKI. When a newborn had no previous serum creatinine, AKI was defined as serum creatinine above the mean plus two standard deviations (SD) (or above 97.5th percentile) according to gestational age, weight, and postnatal age. Clinical and laboratory features in the neonatal AKI period were recorded for 72 cases; at long-term evaluation (2-12 years), kidney function tests with glomerular filtration rate (eGFR) by the Schwartz formula, microalbuminuria, office and 24-h ambulatory blood pressure monitoring (ABPM), and kidney ultrasonography were performed. RESULTS: Forty-two patients (58%) had stage I AKI during the neonatal period. Mean age at long-term evaluation was 6.8 ± 2.9 years (range: 2.3-12.0); mean eGFR was 152.3 ± 26.5 ml/min/1.73 m2. Office hypertension (systolic and/or diastolic BP ≥ 95th percentile), microalbuminuria (> 30 mg/g creatinine), and hyperfiltration (> 187 ml/min/1.73 m2) were present in 13.0%, 12.7%, and 9.7% of patients, respectively. ABPM was performed on 27 patients, 18.5% had hypertension, and 40.7% were non-dippers; 48.1% had abnormal findings. Female sex was associated with microalbuminuria; low birth weight (< 1,500 g) and low gestational age (< 32 weeks) were associated with hypertension by ABPM. Twenty-three patients (33.8%) had at least one sign of microalbuminuria, office hypertension, or hyperfiltration. Among 27 patients who had ABPM, 16 (59.3%) had at least one sign of microalbuminuria, abnormal ABPM (hypertension and/or non-dipping), or hyperfiltration. CONCLUSION: Even children who experienced stage 1 and 2 neonatal AKI are at risk for subclinical kidney dysfunction. Non-dipping is seen in four out of 10 children. Long-term follow-up of these patients is necessary.

Impact of preterm birth on the cellular characteristics of neonatal buccal cells.

OBJECTIVE: To demonstrate the impact of preterm birth on the cytological, cytomorphometrical, and nuclear parameters of neonatal buccal smears. METHODS: This study consisted of Early Preterm Neonates (EPN; ≤34th gestational week [gw]; n = 36), Late Preterm Neonates (LPN; 34th to <37th gw; n = 46), and Term Neonates (control; ≥37th gw; n = 56). Cytological evaluation and buccal cytome assay were performed using Papanicolaou and Feulgen methods, respectively. RESULTS: Cytological evaluation demonstrated that smear background was cleaner (P < .05) and there were less macrophages in the control group (P < .001). Cyto-morphometric analysis showed that the measurements of nuclear diameter, nuclear area, and nucleus-to-cytoplasm ratio were higher in the preterm (EPN and LPN) versus the control groups (P = .016, P < .001, and P < .001, respectively). We also demonstrated that staining intensity of the nucleus and cytoplasm were less intense in the EPN and LPN groups (P < .001). There was no statistically significant difference between the EPN and LPN groups for any parameters (P > .05). Buccal cytome assay showed that nuclear buds were more prevalent in term newborns compared to preterm neonates (P < .001). CONCLUSIONS: Morphological and cytological properties of neonatal buccal cells are influenced by preterm birth status, and buccal smears may be used as a tool to detect biological markers of neonatal health problems.

Impact of Prematurity on the Buccal Epithelial Cells of the Neonates via Wnt/Beta-Catenin Signaling Pathway and Apoptosis.

OBJECTIVE: Understanding the reflections of prematurity is necessary for the management of neonatal complications. We focused on the impact of prematurity and related "maternal risk factors/obstetric complications" on buccal cells of the neonates via evaluation of the Wnt/ß-catenin signaling pathway and apoptosis. STUDY DESIGN: This study consisted of "early preterm neonates (EPN) (≤34th gestational week [gw]) (n = 36)," "late preterm neonates (LPN) (34th- < 37th gw) (n = 46)," and "term neonates (control) (≥37th gw) (n = 56)." Cohort was also subclassified according to the presence of maternal risk factors, obstetric complications, and neonatal complications. Wnt/ß-catenin signaling and caspase-3 activation pathways were studied immunocytochemically. RESULTS: Wnt/ß-catenin signaling positivity was statistically more frequent at buccal smears of the EPN and LPN groups compared with controls (p < 0.001). The cutoff for gestational age at delivery in receiver operating characteristic curve with the best balance of sensitivity (67.4%) and specificity (67.3%) was 35.8th gw for determining the reduction of Wnt/ß-catenin signaling positivity (p < 0.001). The study demonstrated that obstetric complications significantly affected the activity of signaling, while maternal risk factors do not have any effect on Wnt/ß-catenin signaling pathway (p = 0.003 and p = 0.828, respectively). This study also demonstrated a significant relationship between Wnt/ß-catenin signaling pathway and the presence of neonatal complications (p = 0.015). CONCLUSION: Dynamic characteristics of buccal cells are influenced by prematurity and related obstetric and neonatal problems. Buccal smear is a good tool to investigate the impact of prematurity and obstetric problems on perinatal outcome. KEY POINTS: · Neonatal buccal cells are affected by prematurity and related obstetric/neonatal problems.. · 35.8th gw is critical for determining the reduction of Wnt/ß-catenin signaling positivity.. · Obstetric and neonatal complications significantly related to Wnt/ß-catenin signaling activity..

Hypoxic-ischemic enterocolitis: a proposal of a new terminology for early NEC or NEC-like disease in preterm infants, a single-center prospective observational study.

We aimed to investigate the role of hypoxia-ischemia in the pathophysiology of early NEC/NEC like disease (ENEC) and classic NEC/NEC like disease (CNEC) in preterm infants. In this pilot study, preterm infants who developed the clinical symptoms and signs of NEC/NEC like disease were divided into two groups as early (≤ 7 days, ENEC) or late (> 7 days, CNEC) groups. Beside clinical variables, serum L-lactate, endothelin-1 (ET-1), platelet activating factor (PAF), and intestinal fatty acid binding protein (I-FABP) levels were measured from umbilical/peripheric venous blood in the first hour of life and during the clinical presentation in all groups. A total of 86 preterm infants were enrolled in the study. In the ENEC group, the incidences of fetal umbilical artery Doppler velocimetry abnormalities, IUGR, and delayed passage of first meconium were higher. In addition, mean levels of L-lactate, ET-1, PAF, and I-FABP were higher in the first hour of life.Conclusion: Our study firstly showed that the dominant pathophysiological factor of ENEC is prenatal hypoxic-ischemic event where intestinal injury and inflammation begin in-utero and become clinically apparent in the first week of life. Therefore, we propose a new term "Hypoxic-Ischemic Enterocolitis (HIEnt)" for the definition of ENEC in preterm infants with prenatal hemodynamic disturbances and IUGR. This new sight can provide individualized preventive and therapeutic strategies for preterm infants.What is Known:• The pathophysiology of early necrotizing enterocolitis (NEC) or NEC-like disease which is seen in the first week of life seems different than classic necrotizing enterocolitis (CNEC) which is always seen after the first week of life.What is New:• This study suggests that perinatal hypoxic-ischemic process with inflammation is the point of origin of fetal intestinal injury leading to ENEC.• We propose a new term "Hypoxic-Ischemic Enterocolitis (HIEnt)" for the definition and differentiation of this unique clinical entity.

Epidermolysis Bullosa with Pyloric Atresia and Aplasia Cutis in a Newborn Due to Homozygous Mutation in ITGB4.

BACKGROUND: Epidermolysis bullosa with pyloric atresia (EB-PA) is an autosomal recessive disorder due to mutations in ITGA6 and/or ITGB4, resulting in altered expression of α6ß4 integrin. EB-PA can also occur with aplasia cutis. CASE REPORT: We present a newborn with EB-PA and aplasia cutis, born of consanguineous parents, with a homozygous c.3793+1G>A mutation affecting ITGB4, previously described only in the heterozygous state with other mutations. CONCLUSION: The previously unreported homozygous c.3793+1G>A mutation affecting ITGB4 causes a severe form of junctional epidermolysis bullosa with pyloric atresia and aplasia cutis.

Efficacy of new leukocyte parameters versus serum C-reactive protein, procalcitonin, and interleukin-6 in the diagnosis of neonatal sepsis.

BACKGROUND: The aim of this study was to investigate and compare the efficacy of the new leukocyte parameters mean neutrophil and monocyte volume (MNV, MMV), conductivity (MNC, MMC), scattering (MNS, MMS) and volume distribution width (NDW, MDW) with serum C-reactive protein (CRP), procalcitonin (PC) and interleukin (IL)-6 in the diagnosis of neonatal sepsis. METHODS: A total of 227 newborns (132 boys, 95 girls) were analyzed. There were 116 infants in the sepsis group (proven sepsis, n = 40; clinical sepsis, n = 76) and 111 in the control group. Venous blood samples were collected from infants at the time of diagnosis and complete blood count, peripheral blood smear, blood cultures, CRP, PC, IL-6 and MNV, MMV, MNC, MMC, MNS, MMS, NDW, and MDW were analyzed. RESULTS: MNV, NDW, MMV and, MDW were higher in infants with sepsis than in controls (P < 0.05 for all). MNS was lower in the patients with sepsis (P = 0.002). There was no significant difference between the sepsis and control groups in terms of MNC, MMC and MMS. CONCLUSION: Although the predictive value of leukocyte parameters including neutrophil and monocyte volume, conductivity, scattering and volume distribution width in the diagnosis of neonatal sepsis was lower than that of CRP, PC and IL-6, some of these new parameters may be useful in the differential diagnosis of newborn sepsis, along with the other screening tools. In particular, MNV seems to be the most useful parameter with the highest specificity; also, the importance of PC in the diagnosis of early onset sepsis was confirmed.

Neonatal assessment in the delivery room--Trial to Evaluate a Specified Type of Apgar (TEST-Apgar).

BACKGROUND: Since an objective description is essential to determine infant's postnatal condition and efficacy of interventions, two scores were suggested in the past but weren't tested yet: The Specified-Apgar uses the 5 items of the conventional Apgar score; however describes the condition regardless of gestational age (GA) or resuscitative interventions. The Expanded-Apgar measures interventions needed to achieve this condition. We hypothesized that the combination of both (Combined-Apgar) describes postnatal condition of preterm infants better than either of the scores alone. METHODS: Scores were assessed in preterm infants below 32 completed weeks of gestation. Data were prospectively collected in 20 NICU in 12 countries. Prediction of poor outcome (death, severe/moderate BPD, IVH, CPL and ROP) was used as a surrogate parameter to compare the scores. To compare predictive value the AUC for the ROC was calculated. RESULTS: Of 2150 eligible newborns, data on 1855 infants with a mean GA of 28(6/7) ± 2(3/7) weeks were analyzed. At 1 minute, the Combined-Apgar was significantly better in predicting poor outcome than the Specified- or Expanded-Apgar alone. Of infants with a very low score at 5 or 10 minutes 81% or 100% had a poor outcome, respectively. In these infants the relative risk (RR) for perinatal mortality was 24.93 (13.16-47.20) and 31.34 (15.91-61.71), respectively. CONCLUSION: The Combined-Apgar allows a more appropriate description of infant's condition under conditions of modern neonatal care. It should be used as a tool for better comparison of group of infants and postnatal interventions. TRIAL REGISTRATION: clinicaltrials.gov Protocol Registration System (NCT00623038). Registered 14 February 2008.

Oxidant and antioxidant status in neonatal proven and clinical sepsis according to selenium status.

BACKGROUND: Selenium is a trace element required for the functioning of the immune system. Neonatal sepsis is a serious condition leading to morbidity and mortality in neonates worldwide. The purpose of this study was to measure selenium and plasma selenoprotein P (SePP), selenoenzyme activity, and alterations in oxidant/antioxidant status with immune biomarkers in neonates with clinical (n = 27) and proven neonatal sepsis (n = 25). METHODS: Erythrocyte selenium and SePP; plasma lipid peroxidation (LP), protein oxidation and total antioxidant capacity and erythrocyte total glutathione (GSH) concentration; erythrocyte glutathione peroxidase (GPx), thioredoxin reductase (TrxR), catalase (CAT) and total superoxide dismutase (SOD) activity were measured spectrophotometrically/spectrofluorometrically. Plasma interleukin 2 and 6 were also measured. RESULTS: Erythrocyte selenium and SePP were markedly lower both in the clinical and proven sepsis groups versus control. Erythrocyte GPx activity was higher only in the clinical sepsis group. TrxR activity was markedly lower in proven sepsis. SOD activity and GSH were markedly higher both in clinical sepsis and in proven sepsis. CAT activity was significantly higher both in clinical sepsis and in proven sepsis. LP and protein oxidation were significantly higher in both of the sepsis groups. CONCLUSIONS: Both selenium-dependent and selenium-independent blood redox systems were altered in sepsis, suggesting that sepsis causes an imbalance between cellular antioxidant and oxidant states.

A novel mutation in protein C gene (PROC) causing severe phenotype in neonatal period.

Homozygous protein C deficiency is among rare causes of thrombophilia. Herein, we present a neonate with purpura fulminans, disseminated intravascular coagulation and severe intracranial hemorrhage who was found to have plasma protein C level of 4%. The molecular work-up revealed a novel homozygous mutation of T903C (amino acid position Leu 270 Pro) located in a catalytic domain region of PROC gene. Asymptomatic course in patients with low but measurable levels of protein C levels has been reported, which is different than observed in our patient who had a very severe course despite plasma protein C level of 4%.

Lung ultrasound scores within the first 3 days of life to predict respiratory outcomes.

BACKROUND: Lung ultrasound (LUS) is a rapid and simple method to evaluate preterm babies with respiratory distress. Lately, LUS has also been reported as an accurate predictor for bronchopulmonary dysplasia (BPD). OBJECTIVES: The aim of the study was to investigate the relationship between the LUS scores within the first 3 days of life and respiratory outcomes including the need and the duration of invasive mechanical ventilation, and development of BPD. METHODS: It was a retrospective observational study. Preterm infants younger than 32 weeks were included at an academic tertiary Neonatal Intensive Care Unit between 2018 and 2023. LUS was performed within the first 3 days. Each lung was divided into three regions and defined as a score of 0 to 3 points; the total score was obtained by adding the six regional scores. LUS scores were noted in two groups as the highest and lowest scores. Statistical analyses were done to predict respiratory outcomes. RESULTS: Total 218 patients were enrolled; 40, 17, and 18 infants had mild, moderate, and severe BPD, respectively. BPD did not develop in 143 patients. Within the first 3 days, the highest and lowest LUS scores significantly predicted moderate-to-severe BPD (p < .001) (area under receiver operating characteristic [ROC] curve, 0.684-0.913; area under ROC curve 0.647-0.902; respectively). High LUS scores were also related with the need of mechanical ventilation (p < .001). There was not a significant correlation between the duration of mechanical ventilation and the LUS scores. Regression analysis revealed that the highest LUS scores within the first 3 days of life, sepsis, and the presence of hemodynamically significant patent ductus arteriosus (hsPDA) were significantly associated with the severity of BPD. CONCLUSIONS: In preterm babies, the LUS scores were useful to predict BPD and the need of invasive ventilation in long term. However, it was not related with the length of invasive ventilation.

Feeding intolerance in preterm infants fed with powdered or liquid formula: a randomized controlled, double-blind, pilot study.

UNLABELLED: Feeding intolerance (FI) is usually defined as "gastric residual volume of more than 50 % of the previous feeding volume, emesis, abdominal distension or both of these symptoms and a decrease, delay or discontinuation of enteral feedings." We aimed to compare the incidence of FI in preterm infants fed with powdered or liquid infant formula, and in a prospective, double-blind, pilot study, 78 preterm infants were randomized to receive powdered or liquid form of the same preterm infant formula. The primary outcomes were the incidence of FI in both groups. The pH of gastric fluids was measured in the fasting and postprandial periods on the seventh day of life, and gastrointestinal complications were recorded during the hospitalization period. The incidence of FI was significantly higher in infants fed with liquid formula (n = 34) when compared with infants fed with powdered formula (n = 44) [9 (26.5 %) vs 2 (4.5 %), p < 0.01, respectively]. The median fasting gastric fluid pH was significantly lower and postprandial gastric fluid pH was significantly higher than in infants fed with powdered formula (2.9 vs 3.4, p < 0.01 and 6.0 vs 5.9, p < 0.05 respectively). Infants fed with liquid formula regained birth weight significantly later than infants fed with powdered formula (9.5 vs 8.0 days, p < 0.01). CONCLUSION: Although the exact mechanisms are not clear, increased incidence of FI and delayed growth in the first weeks of life in preterm infants fed with liquid formula might be caused by altered gastric acidity or possible disrupted protein bioavailability due to different production and sterilization processes.

Phototherapy rash in newborn infants: does it differ between conventional and light emitting diode phototherapy?

Data comparing the cutaneous side effects of light emitting diode (LED) phototherapy (LP) and conventional phototherapy (CP) devices in jaundiced newborn infants are very limited. We investigated the incidence and extent of skin eruptions caused by different phototherapy devices in preterm infants who are more prone to neonatal jaundice. This prospective, randomized controlled trial was conducted in the neonatal intensive care unit (NICU) of Hacettepe University Ihsan Dogramaci Childrens' Hospital in Ankara, Turkey. Preterm infants without skin lesions before and requiring phototherapy in the first week of life were included in the study. The infants were randomly assigned to receive CP or LP and were monitored closely for skin eruptions during phototherapy. Fifty-eight infants were included in the study: 25 (43.1%) received CP while 33 (56.9%) received LP. The duration of phototherapy was similar in the two groups (30.4 ± 9.6 hours and 31.8 ± 15.6 hours, respectively). Baseline and control bilirubin levels were similar for the two groups (p = 0.101 and p = 0.105, respectively). The frequency of skin eruptions was 36% in the CP group and 33% in the LP group (p = 0.83). The skin eruptions were macules in 13 (22.4%), papules in 5 (8.6%), and maculopapular rashes in 2 (3.4%) infants.There were no differences in the incidence and extent of skin eruptions in preterm infants who received CP or LP.

Successful implantation of an intracardiac defibrillator in an infant with long QT syndrome and isolated noncompaction of the ventricular myocardium.

Congenital long QT syndrome (LQTS) is an inherited disorder characterized by QT prolongation and polymorphic ventricular tachycardia known as torsade de pointes. The underlying cellular mechanism is prolonged ventricular repolarization caused by mutations in genes encoding cardiac ion channels or membrane adaptors. The disease can be diagnosed at any age and, very rarely, it can be diagnosed prenatally or in the neonatal period. Isolated noncompaction of the ventricular myocardium (INCVM) is defined as the presence of prominent ventricular trabeculations and deep intertrabecular recesses within the endomyocardium. This report describes a newborn baby presenting with polymorphic ventricular tachycardia whose diagnosis was LQTS and INCVM. Ventricular tachycardia did not respond to medical treatment, and a transient epicardial pacemaker was inserted surgically on his 30th day of life for atrioventricular block and bradycardia. The transient epicardial pacemaker was upgraded to an epicardial intracardiac defibrillator on his 40th day. The concomitant occurrence of INCVM, LQTS, and atrioventricular block needs to be evaluated further.

Comparison of intensive light-emitting diode and intensive compact fluorescent phototherapy in non-hemolytic jaundice.

In severe and rapidly increasing jaundice, the use of intensive phototherapy provides greater effectiveness and a faster decrement in bilirubin levels compared to conventional phototherapy. The aim of this study was to compare the effectiveness of two types of intensive phototherapy: intensive compact fluorescent tube (CFT) and intensive light-emitting diode (LED) phototherapy. Forty-three infants over 35 weeks of gestation with severe non-hemolytic hyperbilirubinemia were enrolled in the prospective study. All infants received multidirectional (circular-shaped) intensive phototherapy. Of these, 20 infants received CFT while 23 infants received LED phototherapy. Bilirubin levels and body temperatures were measured periodically, and the rates of bilirubin decrement were calculated. Mean serum bilirubin level of the 43 infants was 20.5±1.5 mg/dl at the beginning of the therapy and mean duration of phototherapy was 20.6±1.1 hours. The rate of mean bilirubin decline was 47.2% and the decrease was more prominent in the first four hours (0.84 ± 0.41 mg/dl/h). The rates of bilirubin decrement were comparable between the LED and CFT groups. Slightly elevated mean body temperature (37.1ºC) was determined in the CFT group (p<0.05). Intensive phototherapy units with both LED and CFT were effective, showing a decline of half the initial value of bilirubin during the study period in infants with non-hemolytic jaundice. This study shows that intensive phototherapy with either CFT or LED can provide rapid decrease in bilirubin levels in the first few hours. This rapid decline is important in cases that have high risk of bilirubin encephalopathy.

Implications of serial magnetic resonance imaging in the management of a newborn with vein of Galen aneurysmal malformation and a review of the relevant literature.

BACKGROUND: Despite advanced endovascular methods and comprehensive intensive care in the neonatal vein of Galen aneurysmal malformation, overall mortality ranges between 37-63% in treated patients with 37-50% of survivors possessing poor neurologic outcomes. These findings stress the need for more accurate and timely recognition of the patients who may and may not benefit from aggressive intervention. CASE: This case report presents a newborn with a vein of Galen aneurysmal malformation whom antenatal and postnatal follow-up included serial magnetic resonance imaging (MRI) including diffusion-weighted series. CONCLUSIONS: Given the experience from our current case and in light of the relevant literature, it is plausible that diffusion-weighted imaging studies may widen our perspective on dynamic ischemia and progressive injury occurring within the developing central nervous system of such patients. Meticulous identification of patients may favorably influence the clinical and parental decision on early delivery and prompt endovascular treatment versus aiding avoidance of further futile interventions both antenatally and postnatally.

Impact of clinical pharmacist-led intervention for drug-related problems in neonatal intensive care unit a randomized controlled trial.

Introduction: Drug-related problems (DRPs) incidence is higher in neonatal intensive care units (NICUs), compared to other pediatric wards due to aspects like off-label medications, pharmacokinetic/dynamic variability, or organ dysfunction/immaturity. This study aimed to determine whether and to what extent a clinical pharmacist intervention improves medication safety and prevents DRPs [medication errors (MEs), adverse drug reactions (ADRs), drug-drug interactions (DDIs)]. Methods: A prospective, randomized, double blind, controlled study in NICU-admitted neonates was conducted. NICU patients were randomly assigned to the intervention (clinical pharmacist-led) (IG) or control group (standard care such as clinical diagnosis, pharmacotherapy) (CG). The clinical pharmacist was involved in the IG to identify-prevent-intervene MEs, or identify and monitor ADRs and DDIs. The primary outcome was the number of neonates who developed at least one DRP compared with those seen across IG and CG. Secondary outcomes included length of hospital stay, total number of drugs or DRP type. Results: Neonates were randomly assigned to CG (n = 52) or IG (n = 48). In total, 45%, 42%, and 16% of patients had at least 1 MEs, ADRs, and clinically significant DDIs, respectively. The number of patients with at least 1 ME was 28 (53%) and 17 (35%) in the CG and IG (p>0.05). The median (range) number of ME was higher in CG [1 (0-7)] than in IG [0 (0-4)] (p = 0.003). Applying regression analysis, the CG had 2.849 times more MEs than the IG (p<0.001). Furthermore, the number of patients (CG to IG) with at least one detected ADR or clinical DDI was 19 (36%) to 23 (47%) (p>0.05) and 4 (7%) to 12 (25%), respectively (p = 0.028). Conclusion: Clinical pharmacist availability to systematically and standardized identify, prevent and resolve DRPs among NICU patients is effective. Daily detailed clinical pharmacist observations and interventions enables prevention and monitoring of DRPs. Clinical Trial Registration ClinicalTrials.gov, identifier NCT04899960.

Development and validation of a machine learning-based detection system to improve precision screening for medication errors in the neonatal intensive care unit.

Aim: To develop models that predict the presence of medication errors (MEs) (prescription, preparation, administration, and monitoring) using machine learning in NICU patients. Design: Prospective, observational cohort study randomized with machine learning (ML) algorithms. Setting: A 22-bed capacity NICU in Ankara, Turkey, between February 2020 and July 2021. Results: A total of 11,908 medication orders (28.9 orders/patient) for 412 NICU patients (5.53 drugs/patient/day) who received 2,280 prescriptions over 32,925 patient days were analyzed. At least one physician-related ME and nurse-related ME were found in 174 (42.2%) and 235 (57.0%) of the patients, respectively. The parameters that had the highest correlation with ME occurrence and subsequently included in the model were: total number of drugs, anti-infective drugs, nervous system drugs, 5-min APGAR score, postnatal age, alimentary tract and metabolism drugs, and respiratory system drugs as patient-related parameters, and weekly working hours of nurses, weekly working hours of physicians, and number of nurses' monthly shifts as care provider-related parameters. The obtained model showed high performance to predict ME (AUC: 0.920; 95% CI: 0.876-0.970) presence and is accessible online (http://softmed.hacettepe.edu.tr/NEO-DEER_Medication_Error/). Conclusion: This is the first developed and validated model to predict the presence of ME using work environment and pharmacotherapy parameters with high-performance ML algorithms in NICU patients. This approach and the current model hold the promise of implementation of targeted/precision screening to prevent MEs in neonates. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04899960.