Antiapoptotic Effects of Hydroxychloroquine on Hypoxic-Ischemic Injury in Neonatal Rat Brain: May Hydroxychloroquine Be an Adjuvant Theraphy?

OBJECTIVE: Hydroxychloroquine (HCQ) has immunomodulatory, antithrombotic, cardiovascular, antimicrobial, and antineoplastic effects. In this study, we aimed to investigate the antiapoptotic and immunomodulator effects of intraperitoneal HCQ on hypoxic-ischemic (HI) injury in newborn rats. STUDY DESIGN: Wistar albino rats, 7 to 10 days old, were randomly divided into three groups: hypoxic-ischemic encephalopathy (HIE) group, HIE treated with HCQ group, and Sham group. Left common carotid artery ligation and hypoxia model were performed in HIE and HCQ groups. The HCQ group was treated with 80 mg/kg intraperitoneal HCQ every 24 hours for 3 days, while Sham and HIE groups were given physiological saline. After 72 hours, rats were decapitated and brain tissues were stained with hematoxylin and eosin, TUNEL, and IL-1ß for histopathological grading and neuronal cell injury. RESULTS: Neuronal apoptosis was statistically lower in all neuroanatomical areas in the HCQ group compared with the HIE group. IL-1ß-stained areas were similar in both HCQ and HIE groups but significantly higher compared with the Sham group. Histopathological grading scores were found to be lower in the HCQ group on the left parietal cortex and hippocampus region. CONCLUSION: In this study, we have shown for the first time that HCQ treatment decreased apoptosis in HI newborn rat model in both hemispheres. HCQ may be a promising adjuvant therapy in neonatal HIE. KEY POINTS: · HCQ decreased neuronal apoptosis in the ischemic penumbra of the rat brain.. · HCQ attenuates hypoxia-ischemia-induced brain injury in neonatal rats.. · HCQ has no anti-inflammatory effect on HI injury..

Evaluation of Score for Neonatal Acute Physiology and Perinatal Extension II and Clinical Risk Index for Babies with additional parameters.

BACKGROUND: The aim of this study was to determine mortality risk by calculating Score for Neonatal Acute Physiology and Perinatal Extension II (SNAP-PE-II) and Clinical Risk Index for Babies (CRIB) score, and evaluate prediction of the effects of antenatal corticosteroid and surfactant treatment on mortality. METHODS: This multicenter study was conducted simultaneously in five different centers in four different provinces in Southern Turkey between July 2012 and July 2013. A total of 1668 inborn subjects hospitalized in the neonatal intensive care unit within the first 12 h of delivery, and meeting the selection criteria, were included in the study, and CRIB and SNAP-PE-II were used to determine mortality. RESULTS: The SNAP-PE-II scoring system was applied to all patients, and the CRIB scoring system was used for 310 newborns with gestational age <32 weeks and weighing <1500 g. Of the 1668 patients, 188 died (mortality rate, 11.3%). Cut-off was found to vary with center, which changed specificity and sensitivity of the mortality scores. SNAP-PE-II significantly predicted mortality (P < 0.05) compared with CRIB. SNAP-PE-II also successfully predicted mortality in the group receiving antenatal corticosteroid compared with the group not receiving antenatal corticosteroid. CONCLUSION: SNAP-PE-II was a significant predictor of mortality in newborns with birthweight <1500 g compared with CRIB, and assessment of antenatal corticosteroid use in conjunction with SNAP-PE-II increased the accuracy of the prediction of mortality.

Long-term effect of indomethacin on a rat model of neonatal hypoxia ischemic encephalopathy through behavioral tests.

BACKGROUND: Many medical experts prescribe indomethacin because of its anti-inflammatory, analgesic, tocolytic, and duct closure effects. This article presents an evaluation of the enduring impact of indomethacin on neonatal rats with hypoxic-ischemic (HI) insults, employing behavioral tests as a method of assessment. METHODS: The experiment was conducted on male Wistar-Albino rats weighing 10 to 15 g, aged between seven and 10 days. The rats were divided into three groups using a random allocation method as follows: hypoxic ischemic encephalopathy (HIE) group, HIE treated with indomethacin group (INDO), and Sham group. A left common carotid artery ligation and hypoxia model was applied in both the HIE and INDO groups. The INDO group was treated with 4 mg/kg intraperitoneal indomethacin every 24 h for 3 days, while the Sham and HIE groups were given dimethylsulfoxide (DMSO). After 72 h, five rats from each group were sacrificed and brain tissue samples were stained with 2,3,5-Triphenyltetrazolium chloride (TCC) for infarct-volume measurement. Seven rats from each group were taken to the behavioral laboratory in the sixth postnatal week (PND42) and six from each group were sacrificed for the Evans blue (EB) experiment for blood-brain barrier (BBB) integrity evaluation. The open field (OF) test and Morris water maze (MWM) tests were performed. After behavioral tests, brain tissue were obtained and stained with TCC to assess the infarct volume. RESULTS: The significant increase in the time spent in the central area and the frequency of crossing to the center in the INDO group compared with the HIE group indicated that indomethacin decreased anxiety-like behavior (p < 0.001, p < 0.05). However, the MWM test revealed that indomethacin did not positively affect learning and memory performance (p > 0.05). Additionally, indomethacin significantly reduced infarct volume and neuropathological grading in adolescence (p < 0.05), although not statistically significant in the early period. Moreover, the EB experiment demonstrated that indomethacin effectively increased BBB integrity (p < 0.05). CONCLUSIONS: In this study, we have shown for the first time that indomethacin treatment can reduce levels of anxiety-like behavior and enhance levels of exploratory behavior in a neonatal rat model with HIE. It is necessary to determine whether nonsteroidal anti-inflammatory agents, such as indomethacin, should be used for adjuvant therapy in newborns with HIE.

Effect of whole body massage on pain scores of neonates during venous puncture and comparison with oral dextrose and Kangaroo care, a randomized controlled evaluator-blind clinical study.

OBJECTIVE: Newborns in NICUs experience many painful procedures. The aim of the study was to evaluate the effect of whole body massage therapy on pain scores during venipuncture and to compare with oral 10% dextrose and Kangaroo care. STUDY DESIGN: Newborns with gestational age ≥34 weeks were randomly enrolled to one of three groups: dextrose, massage and Kangaroo care and a blinded investigator scored the pain using NIPS before and during the procedure. RESULTS: There were 25, 26 and 23 newborns in dextrose, massage and Kangaroo care groups, respectively. Pain scores were similar before and during venipuncture in groups (p > 0.05). 36.5% of newborns (27/74) had severe pain scores. Number of newborns with no pain (score 0-2), moderate pain (score 3-4) and severe pain (score 5-7) were similar in each group. CONCLUSION: Massage, Kangaroo and oral 10% dextrose had similar effects on pain scores during venipuncture.

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.

The coincidence of necrotizing enterocolitis and rotavirus infections and potential associations with cytokines.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease in neonatal intensive care units. Although the pathogenesis of NEC remains unclear, evidence suggests that infections, especially bacterial infections, may play an important role. Viral infections may also result in NEC. Several outbreaks of NEC associated with rotaviruses have been described previously. OBJECTIVE: To investigate the association between rotavirus (RV) and serum interleukin (IL)-6 and IL-8 levels in infants with NEC. METHODS: RV infections were prospectively studied using antigen detection in the stools of 31 infants with NEC. Additionally, serum levels of IL-6, IL-8 and tumour necrosis factor-alpha were tested using micro-ELISA at 0 h and 48 h after diagnosis of NEC. RESULTS: Fecal specimens from 13 infants were positive, while fecal specimens from 18 infants were negative for RV according to antigen detection (RV+ and RV- groups, respectively). The mortality rate and the severity of NEC were not significantly different between the RV+ and RV- groups. IL-6 levels at 0 h and 48 h after diagnosis of NEC in RV+ infants were lower compared with RV- infants, while IL-8 levels were greater at 0 h and 48 h after diagnosis of NEC in RV+ infants compared with RV- infants. CONCLUSION: A high prevalence of RV infection in neonates with NEC was found. Decreased IL-6 levels and increased IL-8 and tumour necrosis factor-alpha levels in RV+ neonates with NEC suggests a role for RV in NEC.

HISTORIQUE: L'entérocolite nécrosante (ECN) est la principale maladie gastro-intestinale observée dans les unités de soins intensifs néonatals. Même si la pathogenèse de l'ECN demeure nébuleuse, les données probantes indiquent que les infections, notamment les infections bactériennes, peuvent y jouer un rôle important. Les infections virales peuvent également provoquer une ECN. Plusieurs éclosions d'ECN associées à des rotavirus ont été décrites par le passé. OBJECTIF: Explorer l'association entre le rotavirus (RV) et les taux d'interleukine sérique (IL)-6 et IL-8 chez les nourrissons ayant une ECN. MÉTHODOLOGIE: Les chercheurs ont étudié les infections à RV de manière prospective au moyen de la détection des antigènes dans les selles de 31 nourrissons atteints d'une ECN. Ils ont également testé les taux sériques d'IL-6, d'IL-8 et de facteur de nécrose tumorale alpha au moyen du test micro-ELISA immédiatement après le diagnostic d'ECN, puis 48 heures plus tard. RÉSULTATS: Les échantillons fécaux de 13 nourrissons étaient positifs, tandis que ceux de 18 nourrissons étaient négatifs au RV d'après la détection des antigènes (groupe RV+ et groupe RV−, respectivement). Le taux de mortalité et la gravité de l'ECN ne différaient pas de manière significative entre le groupe RV+ et le groupe RV−. Les taux d'IL-6 immédiatement après le diagnostic d'ECN et 48 heures plus tard chez les nourrissons du groupe RV+ étaient inférieurs à ceux des nourrissons du groupe RV−, tandis que les taux d'IL-8 étaient plus élevés immédiatement après le diagnostic d'ECN et 48 heures plus tard chez les nourrissons du groupe RV+ que chez ceux du groupe RV−. CONCLUSION: Les chercheurs ont décelé une forte prévalence d'infection à RV chez les nouveau-nés ayant une ECN. Les taux d'IL-6 moins élevés et d'IL-8 et de facteur de nécrose tumorale alpha plus élevés chez les nouveau-nés du groupe RV+ ayant une ECN laissent supposer que le RV joue un rôle dans l'ECN.

The effect of different intravenous lipids on free bilirubin levels in premature infants.

BACKGROUND: Intravenous lipid emulsions are commonly used as a part of parenteral nutrition in premature infants. The potential bilirubin-displacing effects of high free fatty acid (FFA) levels during lipid infusions are known. Levels of free bilirubin (FB) predict the risk of bilirubin neurotoxicity more accurately than indirect serum bilirubin levels. In the present study, we decided to compare the effect of two different lipid solutions on free bilirubin and free fatty acids levels in premature infants. METHODS: Infants were grouped into two groups according to intravenous lipid preparations: Infants in Group 1 received lipid emulsion containing olive oil + soybean oil and Group 2 received containing olive oil + soybean oil + fish oil. The blood samples were gained when lipid intake was 3.5 g/kg/day and FFA and FB levels were analyzed. RESULTS: Serum FFA and FB levels were similar in groups (p = 0.26 and 0.69 respectively). There were significant correlation between serum FFA and FB levels in Group 1 (r = 0.74, p < 0.001) and in Group 2 (r = 0.92, p < 0.001). CONCLUSION: Both lipid preparations seem to have similar effects on free bilirubin and free fatty acid levels in premature newborns.

Risk factors for mortality in ICU patients in 10 middle eastern countries: The role of healthcare-associated infections.

PURPOSE: The International Nosocomial Infection Control Consortium (INICC) found a high mortality rate in ICUs of the Middle East (ME). Our goal was to identify mortality risk factor (RF) in ICUs of the ME. MATERIALS: From 08/01/2003 to 02/12/2022, we conducted a prospective cohort study in 236 ICUs of 77 hospitals in 44 cities in 10 countries of ME. We analyzed 16 independent variables using multiple logistic regression. RESULTS: 66,440 patients, hospitalized during 652,167 patient-days, and 13,974 died. We identified following mortality RF: Age (adjusted odds ratio (aOR):1.02;p < 0.0001) rising risk 2% yearly; length of stay (LOS) (aOR:1.02;p < 0.0001) rising the risk 2% per day; central line (CL)-days (aOR:1.01;p < 0.0001) rising risk 1% per day; mechanicalventilator (MV) utilization-ratio (aOR:14.51;p < 0.0001); CL-associated bloodstream infection (CLABSI) acquisition (aOR):1.49;p < 0.0001); ventilator-associated pneumonia (VAP) acquisition (aOR:1.50;p < 0.0001); female gender (OR:1.14;p < 0.0001); hospitalization at a public-hospital (OR:1.31;p < 0.0001); and medical-hospitalization (aOR:1.64;p < 0.0001). High-income countries showed lowest risk (aOR:0.59;p < 0.0001). CONCLUSION: Some identified RF are unlikely to change, such as country income-level, facility ownership, hospitalization type, gender, and age. Some can be modified; LOS, CL-use, MV-use, CLABSI, VAP. So, to lower the mortality risk in ICUs, we recommend focusing on strategies to shorten the LOS, reduce CL and MV-utilization, and use evidence-based recommendations to prevent CLABSI and VAP.

Spontaneously resolved uterine prolapse in a neonate with spina bifida.

Yapicioglu Yildizdas H, Ece Ü, Bilen Yurdakul G, Kolagasigil E. Spontaneously resolved uterine prolapse in a neonate with spina bifida. Turk J Pediatr 2019; 61: 979-981. Neonatal uterine prolapse is rare and mostly due to spina bifida. It is probably due to abnormal innervation of levator ani and subsequent atrophy of the muscle in patients with spina bifida. Here we report a newborn patient with uterine prolapse after meningomyelocele operation. Foley catheter was used to manage uterine prolapse, however rectal prolapse occurred and catheter was pulled out. She was followed in an outpatient clinic without any management. She is now seven months old and had no uterine prolapse since the age of two months.

Non-persistent pesticides in breast milk in an agricultural area in Turkey.

BACKGROUND: Organophosphates, pythyreoids, carbamate pesticides and fungicides are heavily used in agriculture. They may have dangerous effects on newborn health especially on immune system and growth via prenatal transmission by placenta or postnatal transmission by breastfeeding. METHODS: In 2015, 144 non-persistent pesticides in 64 milk samples of 32 mothers were studied by OuEChERS method in liquid chromatography/tandem mass spectrometer in neonatal Intensive Care Unit in Adana, a city in Cukurova region which is an important agricultural area in Turkey. RESULTS: Pesticides were detected in milk samples of 11 mothers (34.3%) and 21 (32.8%) of milk samples. In five mothers, fungicides (in 5/10 samples propicanozole-PP, in 4/10 samples bromucanozole-BM), in five mothers, organophosphates (in 10/10 samples primyphosphomethyl-PPM), in one mother, both organophosphates and fungicide (in 1/2 samples PPM and in 1/2 samples buprimate) were detected. However, the estimated daily intakes (EDI) were less than acceptable daily intakes (ADI) for PPM, PP and BM, respectively. CONCLUSIONS: Although pesticides levels in human milk did not exceed the ADIs, we suggest monitoring pesticides in human breast milk especially for newborn health.

Effects of two different lipid emulsions on antioxidant status, lipid peroxidation and parenteral nutrition- related cholestasis in premature babies, a randomized-controlled study.

BACKGROUND: Olive oil-soybean oil (OO/SO) based lipid emulsions (LE) lack ω-3 PUFAs eicosapentaenoic acid -EPA and docosahexaenoic acid- DHA, which have clinical benefits on inflammatory processes. Fish oil based LEs are good sources of DHA and EPA. Fish oil, MCT, Olive oil and Soya oil (FMOS) lipid is one of the fish oil containing LEs supplemented with high levels of α-tocopherol and lower levels of phytosterol compared to OO/SO lipid emulsions. We investigated the effects of OO/SO and FMOS lipid preparations on cholestasis, levels of antioxidant enzymes and lipid peroxidation. METHODS: Preterm neonates ≤32 gestational weeks age and/or ≤1500 g were randomly assigned to receive either FMOS or OO/SO in the first day of life. Catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS) levels in the first day of life, 7th day of lipid use and 28th day of life were measured and cholestasis during parenteral nutrition was recorded. RESULTS: 34 and 33 patients were in FMOS and OO/SO lipid groups respectively. Although the TBARS levels were higher in the first day of life and 7th day of LEs in OO/SO lipid group (p=0.014 and p=0.022), on the 28th day of life TBARS level was similar and SOD level was higher (p=0.014) in OO/SO group. Cholestasis was significantly lower in FMOS lipid group (0% vs. 18.2%), (p=0.011) and neonates regained birth weight earlier (p=0.006). There was no significant difference in other morbidities. CONCLUSIONS: FMOS and OO/SO lipid emulsions have similar effects on lipid peroxidation on 28th day of life and on morbidities in short term period except for cholestasis.

Turkish Neonatal Society Guideline on fluid and electrolyte balance in the newborn.

Fluid and electrolyte balance and acid-base homeostasis are essential components of normal cellular and organ functions, both in the intrauterine and postnatal developmental period. Knowledge of physiologic changes and appropriate management are important aspects of neonatal intensive care. The aim is to ensure successful transition from the fetal to neonatal period and maintain a normal fluid-electrolyte and acid-base balance. In this paper, fluid and electrolyte requirements in the neonate, treatment of sodium and acid-base disorders on which some controversy exists, and also perioperative fluid-electrolyte management are reviewed.

The effects of umblical cord clamping time on lymphocyte subgroups in term and late preterm infants.

AIM: To evaluate the effect of umblical cord clamping time on lymphocyte subgroups in term and late preterm infants. MATERIAL AND METHODS: Seventy-four infants between 34 and 41 weeks of gestation were included in the study. Of these, 37 were umbilical cord clamped immediately after birth and the remaining 37 were clamped after waiting one minute. Babies were divided into two groups as term and preterm. The prenatal, natal, postnatal characteristics of the infants were recorded. Hematologic and lymphocyte subgroups were investigated in cord blood and venous blood at day 7. Lymphocyte subgroups were evaluated using flow cytometry. RESULTS: With the delay of cord clamping, the leucocytes count and the percentage of CD3+T lymphocytes in cord blood of preterm infants decreased and this decrease continued at day 7. On the contrary, CD19+B lymphocyte levels in the cord blood of preterm infants increased, and this increase continued at day 7. Also, the percentage of CD4+T lymphocytes of preterm infants decreased with the delay of cord clamping at day 7. There was no difference between groups for the rate of sepsis development. CONCLUSION: With the delay of cord clamping, the leucocytes count, the percentage of CD3+T, and CD4+T lymphocytes decreased, and the percentage of CD19+B lymphocytes increased in preterm infants. The delay in cord clamping time in term and preterm infants seems to have no impact on the rate of sepsis development. Larger series of studies are needed to assess the effect of these findings on the development of infection in late preterm infants who have delayed cord clamping.