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AbstractObjectivesMethodsResultsConclusionsThis study investigated the mechanisms underlying myocardial damage after perinatal hypoxia.An intrauterine hypoxia-ischemia model (I/U HI) and a hypoxia/reoxygenation (H/R) model were established. Myocardial damage, mitochondrial function, and mitochondria permeability transition pore (MPTP) opening were determined. The results, presented as means ± SD, were analyzed using SPSS.Intrauterine hypoxia induced cardiac damage, mitochondrial dysfunction, and MPTP opening in neonatal rats. H/R led to apoptosis and MPTP opening. cTnI and apoptosis-inducing factor (AIF) levels were positively correlated with the degree of MPTP opening. The larger degree of MPTP opening combined with the significant increases in the Ca2+, ROS, and decreases in mitochondrial membrane potential and ATP levels. The larger degree of MPTP opening combined with the stronger release of cytochrome c and AIF.Increased MPTP opening may play a crucial role in perinatal asphyxia-induced myocardial damage in neonatal rats. [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia in neonates with perinatal asphyxia may increase the risk of PPHN. This potentially affects outcome. Objectives: (1) To investigate whether neonates with perinatal asphyxia and therapeutic hypothermia more often developed PPHN compared to a control group with perinatal asphyxia not treated with hypothermia; (2) To identify risk factors for severe PPHN during hypothermia and evaluate short-term outcome. Methods: This single-center retrospective cohort study included (near-)term neonates with perinatal asphyxia admitted between 2004 and 2016. Neonates with perinatal asphyxia and hypothermia were compared to a historical control group without hypothermia. Primary outcome was PPHN, defined as severe hypoxemia requiring mechanical ventilation and inhaled nitric oxide, confirmed by echocardiography. Short-term adverse outcome was defined as mortality within one month and/or severe brain injury on MRI. Results: Incidence of PPHN was 23% (26/114) in the hypothermia group and 11% (8/70) in controls. In multivariate analysis, PPHN was 2.5 times more common among neonates with hypothermia. Neonates developing PPHN during hypothermia often had higher fraction of inspired oxygen at baseline. PPHN was not associated with a higher risk of severe brain injury. However, early mortality was higher and three infants died due to severe refractory PPHN during hypothermia. Conclusions: In this study PPHN occurred more often since the introduction of therapeutic hypothermia. This was usually reversible and did not lead to overall increased adverse outcome. However, in individual cases with PPHN deterioration occurred rapidly. In such cases the benefits of hypothermia should be weighed against the risk of a complicated, fatal course. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE) has a high risk of mortality in addition to serious neurological damage. In this study, we investigated the values of umbilical cord netrin-1 (NT-1) and neuron specific enolase (NSE) levels in the early diagnosis of HIE stage II/III induced by neonatal asphyxia. In the study group, infants with gestational age ≥ 36 weeks who were diagnosed with HIE II/III were included. NT-1 and NSE levels were measured from the umbilical cord immediately after birth. Results were compared between HIE II/III and the healthy control group. Cutoff values for serum NT-1 and NSE were determined with receiver-operating characteristics curves and the area under the curve (AUC) was used to determine the diagnostic value of NT-1 and NSE levels in infants diagnosed with HIE II/III. NT-1 (358.3 ± 108.3 pg/mL) and NSE (52.97 ± 17.8 ng/mL) levels in the cord blood in the HIE group were significantly higher (p =.030, p =.001, respectively) than cord blood values in the control group (NT-1 (275.1 ± 84.6 pg/mL) and NSE (28.7 ± 16.3 ng/mL)). NT-1 cutoff value for HIE was 292.3 pg/mL and 34.7 ng/mL for NSE (AUC: 990, sensitivity: 94%, specificity 100% and AUC: 1.0, sensitivity: 100% vs. specificity 100%, respectively). NT-1 and NSE represent candidate biomarkers with high reliability in the prediction in newborns with moderate-to-severe HIE. [ABSTRACT FROM AUTHOR]

In this study, the effect of applying wharton jelly mesenchymal stromal cells (WJ-MSC) isolated from the human umbilical cord tissue on the neonatal mouse model caused experimental asphyxia in mice was investigated. WJ-MSC surface markers (CD44, CD90, CD105) were characterised by immunofluorescence staining, and pluripotency genes (Nanog, Oct-4, Sox-2) were characterised by qPCR. Blood, prefrontal cortex, cerebellum, hippocampus, lung, heart, kidney, and liver tissues were analysed twenty days after subcutaneously administered WJ-MSC. WJ-MSC administration significantly decreased serum TNF-α, NSE, GFAP, and IL-6 levels in the asphyxia mice. It was determined that WJ-MSC application in tissues accelerated cell regeneration and decreased oxidative stress. In conclusion, this study showed that multiorgan damage in asphyxia could be prevented by applying WJ-MSC at an early stage. Therefore, WJ-MSC application in infants with neonatal asphyxia in the clinic may be an innovative method in the future. What is already known on this subject? Perinatal asphyxia is a serious condition that generates progressive neurological defects and systemic multi-organ failure because of the absence of blood flow or gas exchange in the fetusfoetus during birth. There is no clinical application to reduce damage except for hypothermia treatment in asphyxia. What do the results of this study add? This study showed that WJ-derived mesenchymal stromal cell administration could be used to treat hypoxia-induced asphyxia in newborns. In addition, it can be effective against multi-organ damage caused by asphyxia by evaluating the rich content of the UC tissue expelled during birth. What are the implications of these findings for clinical practice and/or further research? In treating asphyxia, the need to develop new strategies emerges as these are not effective in reducing the damage adequately. This WJ-MSC will be new hope for treating asphyxia and guide clinical applications. [ABSTRACT FROM AUTHOR]

Although shown to reduce death or disability in moderate-to-severe hypoxic ischaemic encephalopathy (HIE), therapeutic hypothermia (TH) has recently been associated with an increase in adverse events in low- and middle-income countries (LMIC). To determine the clinical characteristics, complications and short-term outcome in neonates receiving TH in King Edward Memorial Hospital, Mumbai, India. A retrospective single-centre study of neonates with moderate-to-severe HIE who received TH from 1 January 2018 to 31 December 2021 was undertaken. TH was provided as per the unit's protocol using either a servo-controlled device or a phase-changing material (PCM). One hundred and fifty-five neonates were included with 94.2% intramural births. Mean gestation and birthweight were 38.6 (1.5) weeks and 2776.7 (431) g, respectively. HIE staging was moderate in 87.1% and severe in 12.9%, with a mean cord pH of 6.93 (0.14) and seizures in 38.7%. Adverse events included shock (50.3%), clinically significant bleeding (16%), acute kidney injury (6.7%), culture-positive sepsis (11.6%), persistent pulmonary hypertension (9%), bradycardia (9%), food intolerance (14.9%) and premature termination (7.1%). A servo-controlled device (15.5%) or PCM (84.5%) was used, with comparable adverse events. 84.5% of the neonates were discharged, 7.1% discharged against medical advice and 8.4% died. Detailed neurological assessment at discharge/discharge against medical advice suggested neurological impairment in 128 (87.1%) neonates. Adverse events during TH range from asymptomatic laboratory abnormalities to life-threatening complications, which are manageable in well equipped units. Neurological impairment at discharge in neonates who received cooling mandates strict neurological follow-up. Abbreviations: aEEG: amplitude-integrated EEG; AKI: acute kidney injury; BW: birthweight; EEG: electro-encephalogram; GA: gestational age; HELIX: hypothermia for encephalopathy in low- and middle-income countries; HIE: hypoxic ischaemic encephalopathy; IVH: intraventricular haemorrhage; LMIC: low- and middle-income countries; NICHD: National Institute of Child Health and Human Development; NICU: neonatal intensive care unit; PPHN: persistent pulmonary hypertension of newborn; PCM: phase-changing material; SGA: small-for-gestational age; TH: therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

The outcome of perinatal hypoxic-ischaemic encephalopathy (HIE) in middle-to-low-income countries varies between regions. To determine the mortality and morbidity, and factors influencing the deaths of infants with perinatal HIE. A retrospective study was conducted at Chiang Mai University Hospital, Thailand. Perinatal HIE infants of >35 weeks gestation, birthweight ≥2000 g and admitted during 2005-2019 were reviewed. Baseline Characteristics, clinical course and outcome at discharge were compared between the period before and after initiation of therapeutic hypothermia (TH). Risk of death in HIE infants who underwent TH was identified A total of 162 HIE infants were included. Compared to the period before TH initiation, the mortality rate was significantly decreased in the TH period. (27% vs. 12.8%, p=0.04) Among 100 HIE infants who underwent TH, the mortality rates was 14%(14/100), of whom 2.5% (2/76) and 50% (12/24) were in the moderate and severe HIE groups. Apgar score at 5 mins ≤1, severe HIE, seizures, hypoglycaemia, organ involvement ≥ five sites, ammonia ≥100 umol/L, lactate ≥14 mmol/L, and requirement for two or more inotropic drugs were risks of death. Multivariate analysis demonstrated that severe HIE (aOR 732.8, 95% CI 4.7–114643, p=0.01) and a need for two or more inotropic drugs (aOR 45.7, 95% CI 1.5–1040, p=0.029) were significant factors for mortality. In the period of TH, perinatal HIE infants had decreased mortality. Severe HIE and a need for two or more inotropic drugs were associated with death in the infant with HIE who underwent TH. Abbreviations: AED: anti-epileptic drug; BW, birthweight; CI: confidence interval; CMU: Chiang Mai University; EEG: electro-encephalogram; GA: gestational age; HIE: hypoxic-ischaemic encephalopathy; IQR: interquartile range; NICU: neonatal intensive care unit; SD: standard deviation; TH: therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal asphyxia remains a frequent cause of neonatal mortality and long-term neurodevelopmental sequelae, despite the introduction of therapeutic hypothermia. Specific maternal characteristics may predispose asphyxiated newborns treated with hypothermia to worse outcome.Objective: To investigate the possible association between specific maternal factors and adverse outcome in asphyxiated newborns treated with hypothermia.Methods: We conducted a retrospective review of our database of 215 asphyxiated newborns treated with hypothermia from 2008 to 2015. We collected maternal characteristics including parity and labor duration, and we defined adverse outcome as death and/or brain injury. We compared the maternal characteristics between the asphyxiated newborns who developed adverse outcome and those who did not.Results: Asphyxiated newborns born to nulliparous mothers had a significantly higher risk of adverse outcome (61%), compared to asphyxiated newborns born from primiparous (19%) and multiparous (20%) mothers (p = .002). Labor duration was longer in nulliparous mothers (p = .04). Among mothers who delivered vaginally, labor duration was significantly longer in newborns developing adverse outcome (p = .04). In multivariable analysis, parity was confirmed as an independent predictor of adverse outcome in all newborns, but labor duration showed a borderline non-significant association with adverse outcome (p = .051) only in newborns born vaginally. Labor duration beyond 12 h of life was associated with maximal sensitivity and specificity in detecting asphyxiated newborns at an increased risk of adverse outcome despite hypothermia treatment (AUC 0.62, p = .044).Conclusions: Newborns with evidence of perinatal asphyxia, born to nulliparous mothers, and especially to those in whom the duration of labor has been prolonged, might be at higher risk of death or brain injury despite the use of therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of prophylactic theophylline in renal function and survival rates of asphyxiated newborns.Methods: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and Google Scholar databases were systematically searched. All randomized controlled trials evaluating the efficacy of theophylline in the prevention of perinatal asphyxia were selected.Results: A total of seven studies were included with a total of 458 asphyxiated neonates. Incidence of acute kidney injury was significantly lower in neonates receiving theophylline (OR: 0.24, 95% CI: [0.16, 0.36]), while mortality rates were similar between the two groups (OR: 0.86, 95% CI: [0.46, 1.62]). Theophylline administration was associated with significantly decreased serum creatinine levels (MD: -0.57 mg/dl, 95% CI: [-0.68, -0.46]) and elevated glomerular filtration rate (MD: 13.79 ml/min/1.73 m2, 95% CI: [11.91, 15.68]) in the third day of life. Theophylline also lead to lower β2-microglobulin levels, higher urine output and negative fluid balance.Conclusions: The present findings suggest the effectiveness of theophylline in ameliorating renal function of asphyxiated neonates. Future large-scale trials should assess potential long-term adverse outcomes in clinical practice.KeynotesAsphyxia is a major cause of acute kidney injury in neonatesAcute kidney injury is associated with adverse clinical outcomes in asphyxiated neonates.Theophylline administration leads to significantly lower incidence of acute kidney injury in asphyxiated neonates. [ABSTRACT FROM AUTHOR]

To prepare and characterise lutein-loaded polylactide-co-glycolide–polyethylene glycol–folate (PLGA-PEG-FOLATE) nanoparticles and evaluate enhanced uptake in SK-N-BE(2) cells. Nanoparticles were prepared using O/W emulsion solvent evaporation and characterised using DLS, SEM, DSC, FTIR and in-vitro release. Lutein-uptake in SK-N-BE(2) cells was determined using flow-cytometry, confocal-microscopy and HPLC. Control was lutein PLGA nanoparticles. The size of lutein-loaded PLGA and PLGA-PEG-FOLATE nanoparticles were 189.6 ± 18.79 nm and 188.0 ± 4.06 nm, respectively. Lutein entrapment was ∼61%(w/w) and ∼73%(w/w) for PLGA and PLGA-PEG-FOLATE nanoparticles, respectively. DSC and FTIR confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies showed ∼1.6 and ∼2-fold enhanced uptake of lutein from PLGA-PEG-FOLATE nanoparticles compared to PLGA nanoparticles and lutein, respectively. Cumulative release of lutein was higher in PLGA nanoparticles (100% (w/w) within 24 h) compared to PLGA-PEG-FOLATE nanoparticles (∼80% (w/w) in 48 h). Lutein-loaded PLGA-PEG-FOLATE nanoparticles could be a potential treatment for hypoxic ischaemic encephalopathy. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the present review is to evaluate whether urine uric acid to creatinine ratio is increased in perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE), as well as to assess its predictive accuracy in the disease. Methods: We used the Medline (1966–2017), Scopus (2004–2017), Clinicaltrials.gov (2008–2017), Embase (1980–2017), Cochrane Central Register of Controlled Trials CENTRAL (1999–2017), and Google Scholar (2004–2017) databases in our primary search along with the reference lists of electronically retrieved full-text papers. The hierarchical summary receiver operating characteristic (HSROC) model was used for the meta-analysis of diagnostic accuracy. Results: Fourteen studies were finally included in the present review, that investigated 1226 neonates. Urinary uric acid to creatinine ratio was significantly higher in neonates with perinatal asphyxia than in healthy controls (mean differences (MD): 1.43 95%CI [1.17, 1.69]). Specifically, the mean difference for Sarnat stage 1 was 0.70 (95%CI [0.28, 1.13]), for stage 2 1.41 (95%CI [0.99, 1.84]), and for stage 3 2.71 (95%CI [2.08, 3.35]). The estimated sensitivity for the summary point was 0.90 (95%CI (0.82–0.95)), the specificity was 0.88 (95%CI (0.73–0.95)) and the diagnostic odds ratio was calculated at 63.62 (95%CI (17.08–236.96)). Conclusions: Urinary uric acid to creatinine ratio is a rapid and an easily detected biomarker that may help physicians identify neonates at risk of developing perinatal asphyxia and HIE. However, large-scale prospective studies are still needed to determine its value in predicting mortality, as well as short- and long-term adverse neurological outcomes. [ABSTRACT FROM AUTHOR]

Background: In perinatal asphyxia, hypoxia often leads to myocardial ischaemia. Few studies have assessed the degree of myocardial dysfunction in severely asphyxiated term neonates. Aim: To assess the extent of myocardial damage in newborns with severe perinatal asphyxia. Methods: A case–control study was conducted in asphyxiated newborns with hypoxic ischaemic encephalopathy (HIE) and in controls who were term non-asphyxiated newborns. Total (T) creatinine kinase (CK), CK-MB, troponin-T and 12-lead electrocardiography (ECG) and echocardiography were performed in both groups within 24–48 h after birth. The proportions of asphyxiated neonates with myocardial dysfunction and its relationship between severity of HIE and immediate outcome was compared. Results: Five of 23 asphyxiated neonates developed stage I, 10 stage II and eight stage III HIE. Serum levels of CK-T and CK-MB were raised in all 23 cases and troponin-T was raised in 13 (56.5%) HIE cases. ECG was abnormal in all cases and echocardiography in three (13%). Left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) were significantly decreased in all asphyxiated neonates. Eight (35%) patients died. Enzyme levels were higher and ECG and echocardiography abnormalities were common in infants with more severe HIE (p <0.05). Mean serum levels of CK-T and MB (p <0.001) and troponin-T (p =0.002) were higher in non-survivors. Mean LVEF and RVEF values were higher in survivors (p <0.001). All the controls had normal enzyme levels and echocardiography. ECG was abnormal in one control. Conclusion: Cardiac enzymes, ECG and echocardiography changes were associated with increasing severity of HIE and mortality. [ABSTRACT FROM AUTHOR]

Purpose: To identify risk factors and predictors of severity associated with meconium aspiration syndrome (MAS) in the patients admitted to the neonatal intensive care unit (NICU).Materials and Methods: Retrospective study including newborns admitted, between 2005 and 2015, with a diagnosis of MAS.Results: Of the newborns admitted to the NICU, 0.66% were diagnosed with MAS. These had higher prevalence of caesarean delivery (p < .001), nonreassuring or abnormal cardiotocography (CTG) (p < .001), intrapartum maternal fever (p = .002), Apgar scores at the first minute <7 (p < .001) and need of endotracheal intubation at birth (p < .001). Newborns with severe MAS had higher median reactive C protein (86.9 versus 9.65, p = .001) and 73.3% had pulmonary hypertension (p = .027). They required significantly more days of oxygen therapy, mechanical ventilation, nitric oxide, inotropic, and surfactant therapy, as well as longer hospital stay.Conclusions: Nonreassuring or abnormal CTG and low Apgar score at the first minute were established as risk factors for MAS and need of surfactant therapy as a predictor of severity. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of therapeutic hypothermia on myocardial dysfunction in term neonates with perinatal asphyxia.Material and Methods: This randomized controlled trial (RCT) conducted in a tertiary care teaching hospital, south India included 120 newborns with perinatal asphyxia that were randomized to two groups (therapeutic hypothermia and normothermia). Cardiac enzyme profile changes between groups were assessed at 0, 24, 72 h CPK-MB and troponin I levels were estimated by immune inhibition and quantitative immunochromatography methods, respectively. Electrocardiography (ECG) and Echocardiography (ECHO) were done at 0 and 72 h to evaluate the cardiac function and pulmonary hypertension. Neurodevelopment was assessed at 6 months of age in both groups using Developmental Assessment Scales for Indian Infants.Results: The median values of CPK-MB in the normothermia and hypothermia groups at 0, 24, and 72 h were 198, 127, and 92 IU/L and 202, 111 and 64 IU/L, respectively. The median values of troponin I in normothermia and hypothermia groups at 0, 24, and 72 hrs were 2.45, 1.53, and 0.9 ng/mL and 1.97, 0.93, and 0.01 ng/mL, respectively. ECG and ECHO findings also suggest lesser myocardial dysfunction in therapeutic hypothermia group compared with the normothermia group.Conclusions: Therapeutic hypothermia significantly decreases the myocardial damage in term asphyxiated neonates. [ABSTRACT FROM AUTHOR]

Introduction: Multi-organ injury causes leakage of several intracellular enzymes into the circulation. We evaluated the correlation between the serum-leaked intracellular enzyme levels at the beginning of treatment and the outcome in perinatally stressed neonates. Materials and methods: We retrospectively studied neonates whose 1 minute Apgar score was < 7. We collected initial venous blood sample data, including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, and correlated these with patient short-term outcomes. Results: Of 60 neonates, nine patients were treated with therapeutic hypothermia, and 32 needed mechanical ventilation. The therapeutic hypothermia group showed significantly larger base deficit, and higher lactate, AST, ALT, LDH, and CK (all p < 0.01). The duration of mechanical ventilation significantly correlated with AST, ALT, LDH, and CK levels (all p < 0.01). Conclusion: Initial enzyme levels are useful for predicting the duration of mechanical ventilation in stressed neonates. [ABSTRACT FROM AUTHOR]

Introduction: Temperature, glycemia and respiration make neonatal energy triangle (NET). In growth retardation (IUGR) neonates pathological metabolic adaptation exists in transient neonatal period.Aim: The of this study was to examine the occurrence of pathological NET and check its impact on perinatal asphyxia during the transient period in IUGR neonates.Material and Methods: One hundred and fifty-nine neonates with IUGR were classified into - early preterm, late preterm and term neonates. By the presence of hypothermia, hypoglycemia and hypoxia in the first hour after birth neonates were classified into: group of pathological NET, group of unstable NET and group of stable NET. We analyzed distribution per body mass, gestational age, type of IUGR, gender and the frequency of perinatal asphyxia between the groups.Results: The late preterm neonates were the most frequent in the group of pathological NET. Perinatal asphyxia was diagnosed in 52 (32.7%) neonates, with highest frequency in the group of pathological NET. Univariate binary logistic regression analysis showed that pathological NET in neonates with IUGR is significant predictor for perinatal asphyxia occurrence (OR = 8.57; CI = 4.05-18.12; p < 0.001 R2 = 0.27).Conclusion: Poor metabolic adaptation in neonates with IUGR in the first hour after birth is significant risk factor for the perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Subamniotic hemorrhage results from rupture of chorionic vessels near the cord insertion. In the literature, it has never been a major cause for severe intrapartum complications. We report the first case of acute massive subamniotic hemorrhage intrapartum resulting in severe perinatal asphyxia. [ABSTRACT FROM PUBLISHER]

Fetal scalp blood sampling (FSBS) is used to provide information regarding fetal acid–base status during labour. This study assessed the interval between the decision to perform the procedure and obtaining the result and evaluated whether it is affected by cervical dilatation or the experience of the doctor. The median time for FSBS was 10 min. When cervical dilatation was ≤4 cm samples took approximately 30% longer to obtain. After adjustment for dilation, there were no significant differences between different grades of doctors. FSBS is shorter than previously reported; clinicians should be aware that procedures in early labour take longer to complete. [ABSTRACT FROM PUBLISHER]

Objective: The objective of this study is to evaluate whether therapeutic hypothermia reduces the incidence of acute kidney injury (AKI) among term neonates perinatal asphyxia. Methods: This randomized controlled trial conducted in a tertiary care teaching hospital, south India included 120 term neonates with perinatal asphyxia who were randomized to receive either therapeutic hypothermia or standard supportive care. Renal parameters of neonates in both the groups were monitored and AKI was ascertained as per Acute Kidney Injury Network criteria. Results: The incidence of AKI was less in therapeutic hypothermia group compared to standard treatment group (32% versus 60%, p < 0.05). The incidence of Stages 1, 2, and 3 AKI was 22%, 5%, and 5% in therapeutic hypothermia group compared with 52%, 5%, and 3%, respectively, in the standard treatment group. The mortality was less in therapeutic hypothermia group compared with the standard treatment group (26% versus 50%, p < 0.05). Conclusion: Therapeutic hypothermia reduces the incidence and severity of AKI among term neonates with perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA).Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria.Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p < 0.001,p <0.001,p  <0.02,p  <0.001, respectively). In patients with AKI, the levels of NGAL and IL-18 were higher when compared to patients without AKI (p = 0.002,p  <0.001, respectively). The levels of NTN-1 and NHE3 were similar in both groups. For the samples obtained on postnatal day 4, only NGAL levels were significantly higher in patients with AKI (p = 0.004) compared to those without AKI.Conclusion: To our knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with PA. First day, urine NGAL and IL-18 levels have an important diagnostic power in such patients. [ABSTRACT FROM PUBLISHER]

Perinatal asphyxia is a clinical condition which results from oxygen deprivation of the fetus or newborn and the breakdown of perfusion in various organs. The aim of this study was to evaluate and compare troponin T levels over time as a marker of cardiac injury in cases of perinatal asphyxia and healthy newborns. The study included a total of 30 newborns diagnosed with perinatal asphyxia with a gestational age of 32–41 weeks, based on the last menstruation date, and 30 healthy newborns with a gestational age of 34–40 weeks, as the control group. Levels of troponin T and creatinin kinase MB were recorded for all participants. No difference was determined between the groups in terms of gestational age, manner of birth, electrocardiographic findings, and PaO2and PaCO2values. The umbilical artery pH levels and bicarbonate levels in the study group were found to be statistically lower than those in the control group (p< 0.001). The troponin T and creatinin kinase MB levels in the patients in the study group were higher than those within the control group, at all times. The periods when specificity and sensitivity were highest together for troponin T were the 12th and 24th h. Specificity for troponin T reached the highest value at the 24th h and sensitivity reached the highest value in the cord blood. A positive correlation was found between the troponin T and creatinin kinase MB values at the 6th and 12th h. However, no correlation could be found in the blood between the serum troponin T and creatinin kinase MB levels at the 3rd and 24th h. The troponin T level is a useful test for showing cardiac damage in hypoxic patients in the neonatal period. The sensitivity and specificity of cardiac specific troponin T levels in detecting cardiac damage are much higher according to telecardiography and electrocardiography, while the implementation of the method is simple. [ABSTRACT FROM PUBLISHER]

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a highly sensitive and specific marker of acute kidney injury (AKI). The aim of this study was to assess the factors affecting serum and urine total NGAL in preterm newborns, limiting the role of this new potential marker of AKI. Methods: Serum and urinary total NGAL concentrations were determined in 57 preterm infants admitted to the Neonatal Intensive Care Unit in the following points of time: first week of life, between 8 and 14 days of life, and after the fourth week of life. Patients' clinical conditions were evaluated based on NTISS (Neonatal Therapeutic Intervention Scoring System). Two gestational age subgroups were distinguished: ≤29 and 30 to 35 weeks of gestation. We sought correlation between total NGAL values and gestational age, birth weight, Apgar score and severity of clinical condition, with particular interest in inflammatory status. Results: Serum and urinary total NGAL concentration correlated with inflammatory markers, such as CRP and procalcitonin, as well as with NTISS values. Birth weight and gestational age influence urinary NGAL (uNGAL) values in the first two weeks of life. In AKI ( N = 8) patients uNGAL values were significantly higher than in non-AKI newborns. Conclusions: We conclude that inflammatory status and prematurity limits the specificity of total NGAL measurement as a marker of AKI. [ABSTRACT FROM AUTHOR]

Objective: Preeclampsia may result in uteroplacental insufficiency and chronic intrauterine fetal distress. The aim of this study is to address this issue investigating neuronal apoptosis in an experimental model of preeclampsia and to evaluate the neurological outcome of the perinatal asphyxia in the neonates born to preeclamptic mother. Materials and methods: Two out of four pregnant Sprague-Dawley rats (preeclamptic group) were given water containing 1.8% NaCl on gestation day 15 and 22 in order to establish the model of preeclampsia whereas other two (non-preeclamptic group) received normal diet. A model of perinatal asphyxia was established on the postnatal 7th day to one preeclamptic and one non-preeclamptic dam. Overall 23 pups born to overall four dams were decapitated to assess neuronal apoptosis by the TUNEL assay. Results: The number of apoptotic neuronal cells was significantly higher in the preeclampsia groups in comparison with the control group ( p = 0.006 and p = 0.006, respectively). It was also significantly higher in the asphyctic/non-preeclamptic group than the count in the control group ( p = 0.01). There was also significant difference between both asphyctic groups ( p = 0.003). Conclusion: We conclude that preeclampsia causes small babies for the gestational age and cerebral hypoplasia. Both preeclampsia and perinatal asphyxia can cause increased neuronal apoptosis in the neonatal brains. However, the prognosis for neurological outcome is much worse when the perinatal asphyxia occurs in newborns born to preeclamptic mothers. [ABSTRACT FROM AUTHOR]

Although moderate therapeutic hypothermia is the only proven neuroprotective therapy in neonatal hypoxic ischemic encephalopathy secondary to perinatal asphyxia (PA), there is lack of data for its effect on hemostasis. To investigate the effect of neonatal asphyxia on hemostasis and to evaluate the effect of whole body cooling on hematological parameters. Hematological parameters evaluated on the first day of patients with PA before start of hypothermia were compared with those of healthy controls. The effects of whole body cooling on the same parameters were also evaluated on the fourth day. A total of 17 neonates with PA and 15 healthy controls were included. Mean values for prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and d-dimer obtained on the first day were significantly higher in the PA group compared to healthy controls ( P ≤ .001 for all comparisons), whereas platelet count, levels of fibrinogen, factors II, V, VII, IX, X, and XI were significantly lower ( P ≤ .005 for all comparisons). Levels of factor XIII were normal in both groups. In the study group, mean values for PT, INR, aPTT, and d-dimer evaluated on postnatal day 4 were significantly lower compared to values obtained on the first day of birth in PA group ( P < .05 for all comparisons), with statistically significant increases in mean levels of fibrinogen, factor II, V, VII, IX, X, and XII ( P < .05 for all comparisons). PA results in significant reductions in levels of factors of the extrinsic pathway and has been associated with thrombocytopenia and disseminated intravascular coagulation. Hypothermia may actually improve the clinical picture in such patients rather than aggravating the hemostatic disturbance, particularly with the implementation of supportive treatment. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia is a significant cause of perinatal morbidity and mortality worldwide. It is estimated that around 23% of all newborn deaths are caused by birth asphyxia. Each year, between four and nine million newborns develop birth asphyxia worldwide, according to the World Health Organization (WHO). Therefore, despite major advances in monitoring and knowledge of fetal and neonatal physiology and development, perinatal asphyxia remains a serious condition that causes significant mortality and long-term morbidity. However, to date no single marker of perinatal asphyxia has shown good predictive efficacy in prediction and early diagnosis of perinatal asphyxia. On the other hand, ischemia-modified albumin (IMA) is a new biomarker in identification of myocardial ischemia of myocardial necrosis. IMA may also increase in the ischemia of liver, brain, kidney and bowel. Ischemia of these organs may also seen in perinatal asphyxia as well. Reactive oxygen species, produced during ischaemia/reperfusion which is essential steps of perinatal asphyxia, may generate the highly reactive hydroxyl radicals. These hydroxyl radicals modify the albumin and transforms it into IMA. Therefore, IMA might be useful for the prediction and diagnosis of perinatal asphyxia. Further studies are urgently needed to determine the role of IMA in the prediction of perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Background: In caucasian newborns, troponin T (cTnT) is a specific marker for myocardial injury in perinatal asphyxia. This is the first such study in negroid neonates. Aims: To evaluate myocardial injury in a group of asphyxiated African newborns and determine the influence of mode of delivery on cTnT levels. Methods: Serum cTnT and clinical parameters in 40 asphyxiated and 40 healthy negroid neonatal controls were measured within the first 72 hours of life by chemiluminescence immune-assay. Perinatal asphyxia was assessed by APGAR score. The infants were followed up until discharge or death. Results: Mean (SD) cTnT values were significantly higher in asphyxiated infants [0·03 (0·04) ng/ml] than in healthy controls [0·01 (0·006) ng/ml, P = 0·002]. Asphyxiated infants delivered by forceps and vacuum extraction had significantly higher levels of cTnT [0·04 (0·018) ng/ml] than those born by caesarian section [0·02 (0·008) ng/ml] and by normal delivery [0·03 (0·01) ng/ml, P = 0·003]. cTnT levels were higher in infants who died (P = 0·037). Conclusion: In the asphyxiated infants, mean cTnT levels were significantly higher than in controls. They were also significantly higher in those born by vacuum and forceps delivery and asphyxiated infants who died. [ABSTRACT FROM AUTHOR]

Objective. To provide recent figures on the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE) from a Teaching Hospital. Study Design. A retrospective case–control study was conducted in a tertiary level university hospital with more than 3000 deliveries annually. Twenty-four cases of NHIE that occurred in apparently low-risk pregnancies were analysed and compared to a group of controls for the most common labor variables. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results. Of 15,371 apparently low-risk deliveries, 24 cases of NHIE were observed (0.16%), with perinatal death or cerebral palsy occurring in nine of these cases (0.06%). The following intra-partum variables were significantly more common in cases than in controls: stained amniotic fluid (OR: 7.50; 95% CI:1.77–31.79), maternal fever (none in the control group), abnormal CTG (OR: 253.0; 95% CI: 26.70–2397), persistent occiput posterior (OR: 15.67; 95% CI: 2.25–104.53) and operative delivery (OR: 3.98; 95% CI: 1.39–11.33). Conclusion. The incidence of NHIE is considerably low in a Tertiary care Centre. [ABSTRACT FROM AUTHOR]

Objective. To identify during the first hour of life the asphyxiated term neonates who further develop moderate or severe neonatal encephalopathy. Methods. In 75 asphyxiated term infants, we measured postnatal arterial base deficit (BD30), assigned an early neurological score (ENS) according to their level of consciousness, respiration pattern and neonatal reflexes at 30 min of life and calculated the logistic score (LS) = (0.33 × BD30) – ENS. The receiver operating characteristics (ROC) methodology was applied to analyze the ability of the LS to correctly classify patients into two groups: normal or mild encephalopathy (60 patients) versus moderate or severe encephalopathy (15 patients). Results. The area under the ROC curve of the LS for moderate or severe encephalopathy (± standard error) was 94.4 ± 3.6%. At the threshold value of 1.2, the LS provided 87.5% sensitivity and 73.7% positive predictive value (PPV). The PPV of LS reaches 100% for a value >3.2, but this threshold allowed only 53.3% sensitivity. Conclusions. The LS is predictive of the neonatal neurological evolution after birth asphyxia and may help to select the high risk patients who are potential candidates for hypothermia therapy. [ABSTRACT FROM AUTHOR]

Brain hypothermic therapy (BHT) is becoming a frequently used standard of care for perinatal asphyxia. Although cardiovascular side effects, coagulation disorders, renal impairment, electrolyte abnormalities, impaired liver function, opportunistic infections, and skin lesions are well-known adverse effects of BHT in newborns, little information is available on the clinical features of intestinal perforation-related BHT. We herein report a case of therapeutic brain cooling for perinatal asphyxia complicated by localized intestinal perforation. In practice, the neonatologist should be aware that intestinal perforation in an infant with perinatal asphyxia is possible, particularly following BHT. [ABSTRACT FROM AUTHOR]

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular auto-regulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present review is aimed at investigating the role of biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein, in the cascade of events leading to I-R injury in newborns complicated by perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Today, the fetal bioprofile generated during labor and delivery consists of a static assessment of fetal heart rate (FHR). The stress generated by uterine activity provides a means of testing the ability of the fetus to meet the challenges of being born. FHR patterns are valuable for identifying normality, and patterns identifying fetal reactivity (variability and accelerations) are most useful for immediate fetal surveillance. Complexity becomes vast when abnormality is detected, owing to active fetal adaptation to stress and variations in the ability to cope. Thus, each fetus has its own pattern of reactions and bioprofile to be considered. The fetal ECG, forming the basis for FHR monitoring, has been shown to be a clinically useful source of information reflecting both autonomic nervous system (FHR patterns, beat-to-beat variation) and heart muscle reactivity (ST waveform changes). Automatic assessment of the ST forms the basis for the new STAN® fetal surveillance methodology, and additional decision support is being developed in order to optimize the use of the fetal ECG in general and fetal reactivity measures in particular. This article presents the current basis for ST analysis of the fetal ECG as an adjunct to standard electronic fetal monitoring and discusses new developments in the automatic quantification of beat-to-beat variations. [ABSTRACT FROM AUTHOR]

Objectives. Long-chain polyunsaturated fatty acids (LC-PUFA) are important for fetal and infant growth and development. The effects of prematurity and perinatal asphyxia on the levels of linoleic acid (LA) and arachidonic acid (AA) in plasma and red blood cell (RBC) membranes were investigated. Methods. Fifty-five neonates were studied: 18 full term neonates with perinatal asphyxia (group A), nine preterm neonates (group B), and 28 healthy term neonates (group C). Non-esterified and total levels of LA and AA in plasma and RBC membranes were estimated using gas chromatography within the first day of life. Malondialdehyde (MDA) levels were measured using the thiobarbituric acid (TBA) reactivity method. Results. Compared to group C, statistically significant lower levels of plasma free and total AA and free LA were observed in group A, whereas statistically significant higher levels of RBC total LA and AA were observed in RBC membranes of group B. A negative correlation between MDA and LC-PUFA levels was found. Conclusion. Perinatal asphyxia is associated with a reduction in LC-PUFA levels, most likely as a result of increased oxidative stress. Premature infants soon after birth have higher LC-PUFA levels than term neonates, probably reflecting the overall metabolic activity and/or intrauterine transport of LC-PUFA. [ABSTRACT FROM AUTHOR]

Long-term changes of different types of neurofilaments (NF) and glial fibrilar acid protein (GFAP) were studied in neostriatal rat subjected to perinatal asphyxia (PA) under normothermic and hypothermic (15°C) conditions, using immunohistochemistry for light and electron microscopy. Neostriatal neurons of 6-month-old rats that were subjected to 19 and 20 min of PA, showed an increase of NF 200 kDa immunostaining mainly in the axon fascicles in comparison with the control and hypothermia groups. In contrast, no alterations were seen with NF68 and NF160 neurofilament antibodies. Furthermore, the same PA groups showed astroglial cells with enhanced GFAP immunoreactivity, evidencing a typical astroglial reaction with a clear hypertrophy of these cells. A quantitative image analysis confirmed these observations. Hypothermic treated animals did show neither astroglial nor neuronal cytoskeletal changes in comparison to the control group. These findings showed that PA produces chronic cytoskeletal alterations in the neostriatum cells that can be prevented by hypothermia. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to develop a piglet model of neonatal hypoxic-ischemic encephalopathy, which would allow for serial assessments of long-term neurodevelopmental impairment. Methods: In 12 newborn piglets, we produced hypoxia by 8% oxygen breathing for 5–91 minutes. We combined ischemia by reversible bilateral common carotid artery occlusion for varying times. Outcome measures were clinical neurological evaluation, magnetic resonance spectroscopy studies and brain histology. Results: Those animals which received intravenous sedation and no mechanical ventilation showed poor tolerance to hypoxia-ischemia and died early in the course of the experiments. The use of inhalation anesthesia during surgical procedures and mechanical ventilation during hypoxia-ischemia was associated with long-term survival. Seven of eight animals that survived ≥ 48 hr showed clinical neurological abnormalities, that later resolved. Magnetic resonance spectroscopy measurements did not change significantly following hypoxia-ischemia. None of the animals had histopathological brain lesions. Conclusion: When subjected to acute hypoxia-ischemia, piglets were likely to survive only if they were given such supportive measures as anesthesia and mechanical ventilation. Even with hypoxic-ischemic injury sufficient to produce acute signs of neurological dysfunctions, longterm, stable survival with no evident brain histopathological abnormalities was possible. [ABSTRACT FROM AUTHOR]

Acute renal failure (ARF) is a common problem in the neonatal intensive care unit (NICU). In most cases, ARF is associated with a primary condition such as sepsis, metabolic diseases, perinatal asphyxia and/or prematurity. This retrospective study investigated the course of illness, therapeutic interventions, early prognosis and risk factors associated with development of ARF in the neonatal period. A total of 1311 neonates were treated in our NICU during the 42-month study period, and 45 of these babies had ARF. This condition was defined as serum creatinine level above 1.5 mg/dL despite normal maternal renal function. The data collected for each ARF case were contributing condition, cause and clinical course of ARF, gestational age and birth weight, age at the time of diagnosis, treatment, presence of perinatal risk factors and need for mechanical ventilation. The frequency of ARF in the NICU during the study period was 3.4%. Premature newborns constituted 31.1% of the cases. The mean birth weight in the group was 2863 ± 1082 g, and the mean age at diagnosis was 6.2 ± 7.4 days. The causes of ARF were categorized as prerenal in 29 patients (64.4%), renal in 14 patients (31.1%) and postrenal in 2 patients (4.4%). Forty-seven percent of the cases were nonoliguric ARF. Asphyxia was the most common condition that contributed to ARF (40.0%), followed by sepsis/metabolic disease (22.2%) and feeding problems (17.8%). Therapeutic interventions were supportive in 77.8% of the cases, and dialysis was required in the other 22.2%. The mortality rate in the 45 ARF cases was 24.4%. Acute renal failure of renal origin, need for dialysis, and need for mechanical ventilation were associated with significantly increased mortality (p < 0.05). There were no statistical correlations between mortality rate and perinatal risk factors, oliguria, prematurity or blood urea nitrogen and creatinine levels. The study showed that, at our institution, ARF in the neonatal period is frequently associated with preventable conditions, specifically asphyxia, sepsis and feeding problems. Supportive therapy is effective in most cases of neonatal ARF. Acute renal failure of renal origin, need for dialysis, and need for mechanical ventilation were identified as indicators of poor prognosis in these infants. Early recognition of risk factors and rapid effective treatment of contributing conditions will reduce mortality in neonatal ARF. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic brain injury and hypoxic-ischemic encephalopathy (HIE) remain a serious problem for both preterm and term neonates with the spectrum of injury ranging from neuronal injury to encephalopathy and death. Neonatal encephalopathy due to such injury occurs in 3-9 of every 1000 term infants. Of these, it is estimated that nearly a third to a half will either have severe adverse outcomes or die. Treatment of infants with HIE remains generally supportive with attention to resuscitation, fluid and electrolyte homeostasis, maintenance of acid-base balance, nutrition and feeding issues and treatment of seizures. [ABSTRACT FROM AUTHOR]

Sinovenous thrombosis is a definite cause of mortality or morbidity in newborns. Perinatal hypoxia is one of the well known risk factors. Two term newborns were diagnosed to have cerebral venous thrombosis after a hypoxic-ischemic insult. They were later found to have carnitine deficiency. Both of the patients died. Carnitine was previously shown to have inhibitory effects on thrombogenesis in experimental studies. The possible contribution of carnitine in thrombogenesis was discussed. [ABSTRACT FROM AUTHOR]

Cardiac troponins can be useful in monitoring cardiac injury following perinatal distress. We report here an increase of cardiac troponin I (cTnI) to 2.84 microg/l at 3 weeks (age-related median: 0.07 microg/l) followed by normalization in a newborn with an uneventful clinical course after resuscitation at birth. Serial echocardiographs showed normal cardiac function. Such a time course of cTnI, not previously reported, could be due to either a greater sensitivity of biochemical markers than of instrumental tools or birth asphyxia. Larger studies are needed [ABSTRACT FROM AUTHOR]