Search

Objective: In this study, we aimed to evaluate the relationship between the level of improvement in blood gas parameters in the first hours of age and normal and diffusion-restriction brain magnetic resonance imaging (MRI). Materials and Methods: The study is a retrospective cohort study. Cases of the diagnosis of hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia in our unit between January 2022 and January 2024 were included in the study. Clinical findings, blood gas values (first, cord; second, first hours of age; third, 24th hour of age), and MRI results were recorded from the case files and compared between normal and diffusion-restricted brain MRI groups. Results: Diffusion-restricted brain MRI was detected in 10 out of a total of 19 cases. The 5-minute Apgar score was lower (p=0.038) and mechanical ventilator support was higher (P=.003) in the diffusion-restricted MRI group than in the normal MRI group. The relationship was shown between high base excess (P=.022) in cord blood gas, low HCO3 (p=0.025) in the 24th hour blood gas, and convulsion (P=.033) in the diffusion-restricted MRI group. Additionally, it was found that only the improvement level of the pH value in the first hour of age was significant (P=.025) in the diffusion-restricted brain MRI group than in the normal MRI group. Conclusion: We showed that there was a relationship between diffusion-restricted brain MRI and the improvement level in the pH value in the first hours of age of patients diagnosed with HIE who received treatment for therapeutic hypothermia [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoxic ischemic encephalopathy (HIE) leads to different degrees of neurological sequelae. The incidence of HIE is relatively high, and the causal pathways leading to HIE are still controversial. This study aimed to investigate the risk factors associated with HIE comparing differences between genders. Methods: A cross-sectional study of 196 neonates diagnosed with HIE was conducted. Based on the severity of clinical findings, HIE was classified as mild, moderate or severe. For mild HIE, the outcomes were relatively less severe, whereas moderate to severe HIE could suffer serious consequences, including death, cerebral palsy, epilepsy. T-test, chi-square test and logistic regression were used to analyze data. Results: Among the 196 neonatal HIE, 39 (19.9%) had mild HIE,157 (80.1%) had moderate or severe HIE. The logistic regression analysis showed that gender was a specific stratified characteristic of moderate or severe HIE. In the male neonates group, emergency cesarean section, abnormal labor stage and amniotic fluid contamination were associated with an increased risk of moderate or severe HIE, where the adjusted odds ratios (ORs) were 4.378 (95% confidence intervals (CI):2.263–6.382), 2.827 (95% CI:1.743–5.196) and 2.653 (95%CI:1.645–3.972), respectively. As expected, a significant additive effect was found in the interactions between emergency cesarean section and abnormal labor stage, as well as between emergency cesarean section and amniotic fluid contamination, where the relative excess risk of interaction was 2.315(95%CI:1.573–3.652) and 1.896(95%CI: 1.337–3.861) respectively. Conclusion: Emergency cesarean section, abnormal labor stage and amniotic fluid contamination were risk factors of moderate or severe HIE in neonates, and the associations were significantly correlated with male gender. Notably, coinciding incidences of emergency cesarean section with abnormal labor stage, or emergency cesarean section with amniotic fluid contamination were possibly synergistic in increasing the risk of moderate or severe HIE. These findings may assist clinicians in strengthening their awareness on risks affecting HIE and help reduce the incidence of moderate or severe HIE in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. Methods: A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. Results: Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. Conclusions: AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH. [ABSTRACT FROM AUTHOR]

Abstract Background Neonatal hypoxic ischemic encephalopathy (HIE) leads to different degrees of neurological sequelae. The incidence of HIE is relatively high, and the causal pathways leading to HIE are still controversial. This study aimed to investigate the risk factors associated with HIE comparing differences between genders. Methods A cross-sectional study of 196 neonates diagnosed with HIE was conducted. Based on the severity of clinical findings, HIE was classified as mild, moderate or severe. For mild HIE, the outcomes were relatively less severe, whereas moderate to severe HIE could suffer serious consequences, including death, cerebral palsy, epilepsy. T-test, chi-square test and logistic regression were used to analyze data. Results Among the 196 neonatal HIE, 39 (19.9%) had mild HIE,157 (80.1%) had moderate or severe HIE. The logistic regression analysis showed that gender was a specific stratified characteristic of moderate or severe HIE. In the male neonates group, emergency cesarean section, abnormal labor stage and amniotic fluid contamination were associated with an increased risk of moderate or severe HIE, where the adjusted odds ratios (ORs) were 4.378 (95% confidence intervals (CI):2.263–6.382), 2.827 (95% CI:1.743–5.196) and 2.653 (95%CI:1.645–3.972), respectively. As expected, a significant additive effect was found in the interactions between emergency cesarean section and abnormal labor stage, as well as between emergency cesarean section and amniotic fluid contamination, where the relative excess risk of interaction was 2.315(95%CI:1.573–3.652) and 1.896(95%CI: 1.337–3.861) respectively. Conclusion Emergency cesarean section, abnormal labor stage and amniotic fluid contamination were risk factors of moderate or severe HIE in neonates, and the associations were significantly correlated with male gender. Notably, coinciding incidences of emergency cesarean section with abnormal labor stage, or emergency cesarean section with amniotic fluid contamination were possibly synergistic in increasing the risk of moderate or severe HIE. These findings may assist clinicians in strengthening their awareness on risks affecting HIE and help reduce the incidence of moderate or severe HIE in clinical practice.

Background: Vasoactive drugs such as low dosage dopamine are often used in the intensive care of asphyxiated term neonates but there is insufficient evidence to support the practice. Aims: To evaluate the impact of low dose dopamine on the clinical course and outcome of newborns with severe perinatal asphyxia and to determine factors that predict survival. Methods: This was a randomized controlled trial. Term asphyxiated newborns were alternately recruited into ‘dopamine’ and ‘no- dopamine’ sub groups. Asphyxia was defined as Apgar score ≤3 at one minute or ≤5 at five minutes, and/or clinical evidence of hypoxic ischemic encephalopathy (HIE). The intervention comprised dopamine infusion at 3.0mcg/kg/minute. Primary outcome was death or survival till discharge while secondary measures were apnoea, oliguria, seizures and other clinical morbidities. The Student t-test was used to compare outcomes between the subgroups. Results: A total of fifty five asphyxiated infants took part in the study: 27 in the intervention group while 28 were in the control group. The subgroups were similar in mean gestational age, Apgar scores, age at admission and modes of delivery (p>0.05). HIE occurred in over a half of the subjects. The frequency of apnoea, oxygen requirement, duration of anticonvulsant treatment and urine outputs were similar between the subgroups(p > 0.05).The mean durations of admission (days) were 5.13±3.0 and 5.3±3.0 for the intervention and non-intervention subgroups respectively (t=0.183, p=0.856). Likewise, survival rates were similar (x2 = 1.261, p = 0.948). Selected perinatal events did not influence outcome (p>0.05). Conclusion: Low-dosedopamine has no impact on the short term outcome of asphyxiated infants.

• Congenital myotonic dystrophy type 1 (CMD1) is a rare neuromuscular disease. • CDM1 is characterized by neonatal hypotonia, weakness, feeding and respiratory difficulties. • Many CMD1 patients suffer from hypoxic ischemic encephalopathy (HIE). • HIE, preterm delivery, resuscitation and hypothermia treatment are poor prognostic factors for survival. • Respiratory insufficiency is the main life-threatening factor in CDM1. Congenital myotonic dystrophy type 1 (CDM1) is a rare neuromuscular disease. The aim of our study was to evaluate clinical variability of CDM1 and factors that may influence survival in CDM1. Research included 24 pediatric patients with CDM1. Most of our patients had some form of hypoxic ischemic encephalopathy (HIE) (74 %), from mild to severe. Prolonged and complicated deliveries (75 %), high percentage of children resuscitated at birth (57 %) and respiratory insufficiency (46 %) with consequent hypoxia were the main reasons that could explain high percentage of HIE. Therapeutic hypothermia was applied in three children with poor outcome. Median survival of all CDM1 was 14.2 ± 1.5 years. Six patients had a fatal outcome (25 %). Their mean age of death was 3.0 ± 2.8 years. Poor prognostic factors for the survival of our CDM1 patients were: preterm delivery, resuscitation at birth, severe HIE, hypothermia treatment and permanent mechanical ventilation. Respiratory insufficiency was the main life-threatening factor. Our data clearly indicates the need to develop natural history studies in CDM1 in order to enhance the standards of care and to develop clinical trials investigating causative therapies in pediatric patients with CDM1. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal portal vein thrombosis (PVT) is frequently related to umbilical venous catheterization (UVC), but risk factors remain unclear. This study aims to analyze the variables associated to PVT in near- to full-term newborns with UVC, with a focus on newborns exposed to controlled therapeutic hypothermia (CTH) for hypoxic ischemic encephalopathy (HIE). Methods: This is retrospective cohort study of infants delivered at or after 36 weeks and with a birthweight over 1,500 g. All infants were assessed for UVC location and PVT using ultrasonography performed between day 5 and day 10 after catheterization. Results: Among 213 eligible patients, PVT was diagnosed in 57 (27%); among them, 54 (95%) were localized in the left portal vein branch. With all significant factors in univariate analysis considered, higher gestational age at birth (adjusted OR 1.35; 95% CI: 1.12–1.64, p = 0.002) and duration of UVC placement (adjusted OR 1.36; 95% CI: 1.11–1.67, p = 0.004) were the main risk factors of PVT. Among 87 infants who were cooled for HIE, 31 (36%) had PVT compared to 26 (21%) in infants without CTH. Using a multivariate model including variables linked to treatment procedures only, an increased PVT incidence was statistically associated with UVC duration (adjusted OR 1.33; 95% CI: 1.08; 1.63, p = 0.01) and CTH (adjusted OR 1.94; 95% CI: 1.04–3.65, p = 0.04). Conclusion: Left PVT was frequently observed in near- to full-term neonates with UVC. Among factors linked to treatment procedures, both duration of UVC and CTH exposure for HIE were found to be independent risk factors of PVT. [ABSTRACT FROM AUTHOR]

Objective Safety and efficacy data on controlled hypothermia (CH) for neonates with moderate to severe hypoxic ischemic encephalopathy has been extrapolated to a subgroup of these patients who also require extracorporeal membrane oxygenation for refractory persistent pulmonary hypertension of the newborn (PPHN). However, safety data on the concomitant use of CH and extracorporeal membrane oxygenation (ECMO) are lacking. Methods This is a single-center retrospective study of neonates ≥35 weeks' gestation with refractory PPHN who required ECMO between January 2010 and December 2020. Study groups were divided into those receiving CH/ECMO versus ECMO only. Baseline characteristics, short-term outcomes, and brain magnetic resonance imaging (MRI) data were compared. Results A total of 36 neonates who received ECMO for refractory PPHN were included. Of these, 44.4% (n = 16) received CH/ECMO and 55.6% (n = 20) received ECMO only. Bleeding complications were more common in CH/ECMO group 50% (n = 8) versus ECMO only 15% (n = 3, p = 0.023). T1 brain MRI severity scores were higher in CH/ECMO group versus ECMO only group, however, there were no statistical difference in T2 and diffusion-weighted image scores. Functional status and survival to discharge were comparable between groups. Conclusion In our cohort, neonates who received CH/ECMO had higher bleeding complications than ECMO only group with comparable functional status and survival at discharge. Key Points Safety data on the concomitant use of CH and ECMO are lacking in neonates. In our cohort, neonates who received CH/ECMO had higher bleeding complications than ECMO only group. Functional status and survival to discharge were no differences between the two groups. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the hemodynamic safety and efficacy of umbilical cord milking (UCM) compared with early cord clamping (ECC) in nonvigorous newborn infants enrolled in a large multicenter randomized cluster-crossover trial. STUDY DESIGN: Two hundred twenty-seven nonvigorous term or near-term infants who were enrolled in the parent UCM vs ECC trial consented for this substudy. An echocardiogram was performed at 12 ± 6 hours of age by ultrasound technicians blinded to randomization. The primary outcome was left ventricular output (LVO). Prespecified secondary outcomes included measured superior vena cava (SVC) flow, right ventricular output (RVO), peak systolic strain, and peak systolic velocity by tissue Doppler examination of the RV lateral wall and the interventricular septum. RESULTS: Nonvigorous infants receiving UCM had increased hemodynamic echocardiographic parameters as measured by higher LVO (225 ± 64 vs 187 ± 52 mL/kg/min; P

OBJECTIVE: A large, randomized cluster cross-over trial (N = 1730) comparing intact umbilical cord milking (UCM) to early cord clamping (ECC) in non-vigorous near-term/term newborns demonstrated a reduction in cardiorespiratory interventions at birth and less moderate to severe hypoxic ischemic encephalopathy. We evaluated changes in cerebral tissue oxygenation (StO2), pulse oximetry (SpO2), pulse rate and fraction of inspired oxygen (FiO2) during the first 10 min of life in a subset of infants enrolled in the parent trial. STUDY DESIGN: Infants enrolled in the Milking in Non-Vigorous Infants trial that had StO2 monitoring at birth were included in the sub-study conducted at 3 hospitals the US and Canada. A near-infrared spectroscopy sensor, pulse oximeter and electrocardiogram electrodes were placed. Pulse rate, StO2, SpO2, and FiO2 were collected for the first 10 min after birth. Longitudinal models were used to compare effects of UCM and ECC. RESULTS: Thirty-four infants had StO2 data. Fifteen of these infants received UCM and 19 had ECC. Infants receiving UCM had similar heart rates, SpO2, and StO2 values, but were exposed to less FiO2 over the first 10 min of life than infants with ECC (0.26 ± 0.12 vs. 0.81 ± 0.05 at 10 min). CONCLUSION: Non-vigorous term/near term infants who received UCM at birth required lower FiO2 after delivery when compared to infants who umbilical cords were clamped soon after birth while achieving similar peripheral and cerebral oxygenation. Cord milking may be a potential option for placental transfusion in non-vigorous near term/term infants when delayed cord clamping cannot be performed.

Zachary A Vesoulis,1 Danielle P Sharp,2 Natasha Lalos,1 Devon P Swofford,1 Valerie Y Chock2 1Department of Pediatrics, Washington University, St. Louis, MO, USA; 2Department of Pediatrics, Stanford University, Palo Alto, CA, USACorrespondence: Zachary A Vesoulis, 660 S. Euclid Ave, Campus Box 8116, St. Louis, MO, 63110, USA, Tel +1 314-454-6148, Email vesoulis_z@wustl.eduAbstract: Conventional clinical practice in the neonatal intensive care unit (NICU) often fails to actively monitor the brain, relying on reactive strategies and imprecise risk indicators. The introduction of Near-Infrared Spectroscopy (NIRS) enhances current approaches to brain monitoring, offering non-invasive, real-time, continuous, and tissue-specific measures of oxygen saturation. NIRS leverages the physics of light to provide a comprehensive evaluation of oxygen delivery and consumption. This review covers the principles of NIRS, normative values for cerebral oximetry, and its applications in various clinical scenarios. Current clinical applications of NIRS span diverse areas, including intraventricular hemorrhage, white matter injury, anemia, congenital heart disease, and hypoxic-ischemic encephalopathy (HIE). NIRS demonstrates its potential in predicting and preventing adverse outcomes, particularly in optimizing cerebral oxygenation during cardiac surgery and guiding respiratory support in neonates. Key highlights of this review include the role of NIRS for the detection of cerebral hypoxia, even when other monitors do not show signs of clinical deterioration, a discussion of new methods for quantifying cerebral autoregulation and the connection to brain injury, and the potential utility NIRS monitoring offers for critically ill infants, such as those with congenital heart disease. The comprehensive insights provided by NIRS, if translated effectively into clinical practice, have the potential to improve the care and outcomes of neonates in the NICU.Keywords: NIRS, neonatal, brain injury, intraventricular hemorrhage, white matter injury, hypoxic ischemic encephalopathy, seizures, congenital heart disease

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, environmental enrichment (EE) is strictly considered a form of sensory intervention. However, limited research uses EE as a single sensory input intervention to validate outcomes postintervention. A Sprague–Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions is used in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The Western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. In addition, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared with the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment. NEW & NOTEWORTHY: Rarely does literature assess motor function, even though it is common after hypoxia ischemic encephalopathy (HIE). Previously used environmental enrichment (EE) components have not been solely used as sensory inputs. Physical factors were minimized in our study to observe the effects of purely sensory inputs. [ABSTRACT FROM AUTHOR]

Early biomarkers of cerebral damage are essential for accurate prognosis, timely intervention, and evaluation of new treatment modalities in newborn infants with hypoxia and ischemia at birth. Hyperpolarized 13C magnetic resonance imaging (MRI) is a novel method with which to quantify metabolism in vivo with unprecedented sensitivity. We aimed to investigate the applicability of hyperpolarized 13C MRI in a newborn piglet model and whether this method may identify early changes in cerebral metabolism after a standardized hypoxic–ischemic (HI) insult. Six piglets were anesthetized and subjected to a standardized HI insult. Imaging was performed prior to and 2 h after the insult on a 3‐T MR scanner. For 13C studies, [1‐13C]pyruvate was hyperpolarized in a commercial polarizer. Following intravenous injection, images were acquired using metabolic‐specific imaging. HI resulted in a metabolic shift with a decrease in pyruvate to bicarbonate metabolism and an increase in pyruvate to lactate metabolism (lactate/bicarbonate ratio, mean [SD]; 2.28 [0.36] vs. 3.96 [0.91]). This is the first study to show that hyperpolarized 13C MRI can be used in newborn piglets and applied to evaluate early changes in cerebral metabolism after an HI insult. [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to evaluate the association between the amount of proteinuria at the time of diagnosis of preeclampsia with severe features (severe preeclampsia [SPE]) and duration of expectant management (EM) and other perinatal outcomes. Study Design This is a retrospective cohort study of patients with SPE delivering live, non-anomalous singletons at 23 0/7 to 34 2/7 weeks' estimated gestational age (EGA) at a single tertiary center 2016 to 2018. Patients with proteinuria assessment (24-hour total urine protein or urine protein-to-creatinine ratio extrapolation) within 3 days of SPE diagnosis were included. Patients delivered for an indication other than SPE were excluded. Patients were categorized by amount of proteinuria (mg): none (≤300), mild (301–1,000), moderate (1,001–3,000), and massive (≥3,001). The primary outcome was the proportion of potential EM time achieved (%EM), i.e., days of EM divided by days from SPE diagnosis to 34 weeks. Secondary outcomes included delivery EGA, days of EM, and perinatal outcomes. Bivariable and multivariable analyses compared outcomes across groups. Results Of 295 patients included, 21% had no proteinuria, 33% mild, 19% moderate, and 27% massive. Groups differed by EGA at diagnosis, age, parity, chronic hypertension, and renal disease. %EM was not significantly different between groups (adjusted β coefficient 4.1 [95% CI −5.3, 13.5] for mild proteinuria vs. none, −4.1 [95% CI −14.9, 6.6] for moderate proteinuria vs. none, and −5.6 [95% CI −16.0, 4.7] for massive proteinuria vs. none). Increasing proteinuria was associated with earlier delivery EGA but only days of EM in the mild versus no proteinuria groups. There was no significant association between proteinuria and maternal composite morbidity, but patients with mild and massive proteinuria had higher odds of neonatal composite morbidities compared with no proteinuria. Conclusion Among patients with SPE, proteinuria level was not consistently associated with duration of EM. However, patients with the greatest amounts of proteinuria may have worse neonatal and selected maternal outcomes. Key Points Amount of proteinuria was not associated with the duration of expectant management. Greater proteinuria was associated with earlier delivery in severe preeclampsia. Massive proteinuria in preeclampsia was associated with select adverse maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE The objective of this study was to evaluate and compare the effectiveness and safety of dexmedetomidine as monotherapy between neonates with mild hypoxic ischemic encephalopathy (HIE) and moderate to severe HIE treated with therapeutic hypothermia (TH). METHODS This retrospective study included neonates of gestational age ≥36 weeks with a diagnosis of HIE and undergoing TH between January 2014 and December 2021. Patients were included if they received at least 6 hours of continuous sedation with dexmedetomidine. Baseline characteristics, dose and duration of medication, adverse events, liver and kidney function tests, and hospital course were reviewed. RESULTS Of the 97 neonates included, 46 had mild, 42 had moderate, and 9 had severe HIE. Dexmedetomidine was initiated at a median 5 hours of life, and the median infusion duration was 77 (46-87) hours. Fifty-two (53.6%) required at least 1 breakthrough opioid or sedative during the first 24 hours of dexmedetomidine infusion. Overall, 40 patients (41.2%) had at least 1 bradycardia episode with heart rate <80 beats/ min and 14 patients (14.4%) had heart rate <70 beats/min. Hypotension was experienced by 7 patients (7.2%). Fifty-two patients (53.6%) were intubated in the delivery room and 33/52 (63.5%) were extubated on day of life 1 during dexmedetomidine infusion. CONCLUSIONS Dexmedetomidine as monotherapy was effective and safe sedation for infants with HIE undergoing hypothermia. The most common side effect of dexmedetomidine was bradycardia. Dexmedetomidine may be considered as first and single agent for neonates with HIE undergoing TH. [ABSTRACT FROM AUTHOR]

There are some factors that leads to hypoxic ischemic encephalopathy, like maternal age = 35 years, social factors, family history of seizures or neurologic disease, infertility treatment, previous neonatal death, severe preeclampsia, multiple gestation, intrauterine growth restriction, trauma, breech presentation and antepartum hemorrhage. The aim of current study was to identify the associated risk factors which can lead to hypoxic ischemic encephalopathy. A descriptive cross-sectional study was conducted at Paediatrics Ward Unit-II of Civil Hospital, Karachi. All laboratory tests were done from the central laboratory of the civil hospital. The presence of hypoxic ischemic encephalopathy was staged using the Sarnat criteria at the time of admission. Data was collected on predesigned proforma consisting of demographic variables and the risk factors leading to HIE. Data was entered and analyzed in Statistical Package for Social Science (SPSS) version 20. The mean ± SD age of mother of neonates enrolled in this study was 27.41 ± 5.44 years. Mean ± SD gestational age was 34.63 ± 3.87 weeks. Risk factors for hypoxic ischemic encephalopathy include inadequate antenatal care (33.8%), maternal anemia (35.9%), history of hypertension (35.2%), prolonged second stage of labor (29%), vacuum extraction (23.4%), premature delivery (25.5%) and intrauterine growth retardation (16.6%). Overall, 95.2% neonates were identified to have one or more of these contributing factors. Stratified analysis showed that over all neonates of female gender were associated with having more frequency of HIE. Maternal anemia was found to be significantly associated with the occurrence of HIE. The frequency of HIE risk increased with increasing maternal age. Lowest the serum pH level, highest was the frequency of HIE risk factors. Prolonged 2nd stage of labor was significantly associated with lower neonatal weight, overall, very low and very high birth weight neonates were having higher frequency of HIE risk. To conclude the risk factors like insufficient antenatal care, high rates of maternal anemia, other maternal comorbid like history of hypertension, complications of delivery process and its management, prolonged second stage labor, vacuum extraction and fetus related factors like premature delivery and IUGR are quite common which prone the neonates to develop HIE. [ABSTRACT FROM AUTHOR]

Abstract Background Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of $$\text{ER}\alpha$$ ER α . These findings demonstrated that TrkB activation in the presence of $$\text{ER}\alpha$$ ER α comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of $$\text{ER}\alpha$$ ER α -dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period. Methods In this study, we used a unilateral hypoxic ischemic (HI) mouse model. $$\text{ER}\alpha$$ ER α +/+ or $$\text{ER}\alpha$$ ER α −/− mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for 7 days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety-like behavior. The brains were then assessed for tissue damage using immunohistochemistry. Results Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking $$\text{ER}\alpha$$ ER α . The female-specific improved recognition and location memory outcomes in adulthood conferred by DHF therapy after neonatal HI tended to be or were $$\text{ER}\alpha$$ ER α -dependent, respectively. Interestingly, DHF triggered anxiety-like behavior in both sexes only in the mice that lacked $$\text{ER}\alpha$$ ER α . When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of $$\text{ER}\alpha$$ ER α significantly reduced overall HI-associated mortality in both sexes. Conclusions These observations provide evidence for a therapeutic role for DHF in which TrkB-mediated sustained recovery of recognition and location memories in females are $$\text{ER}\alpha$$ ER α -associated and dependent, respectively. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner.

Background: Oxidative stress-related diseases in newborns arise from pro-oxidant/antioxidant imbalance in both term and preterm neonates. Pro-oxidant/antioxidant imbalance has shown to be present in different pathological conditions such as hypoxic ischemic encephalopathy (HIE), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA). Methods and Results: We performed a narrative review according to the most recent available literature (2012–2024), using Scopus and PubMed as electronic databases. Many observational and experimental studies in vitro and in vivo have evaluated the effectiveness of antioxidant therapies such as melatonin, erythropoietin (EPO), allopurinol, N-acetylcisteine (NAS), and nitric oxide synthase (NOS) inhibitors in these diseases. Perinatal asphyxia is one of the most important causes of mortality and morbidity in term and near-term newborns. Therapeutic hypothermia (TH) is the gold standard treatment for neonates with moderate-severe perinatal asphyxia, resulting in a reduction in the mortality and neurodevelopmental disability rates. Conclusions: According to the most recent literature and clinical trials, melatonin, allopurinol, NAS, NOS inhibitors, magnesium sulfate, and stem cells stand out as promising as both adjuvants and future probable alternatives to TH in the treatment of HIE.

Background/Objective: It is difficult to predict perinatal brain injury, and performing brain magnetic resonance imaging (MRI) based on suspected injury remains a clinical challenge. Therefore, we aimed to develop a reliable method for predicting perinatal brain injury using a machine learning model with early birth data. Methods: Neonates admitted to our institution from January 2017 to June 2024 with a gestational age of ≥36 weeks, a birth weight of ≥1800 g, admission within 6 h of birth, and who underwent brain MRI to confirm perinatal brain injury were included. Various machine learning models, including gradient boosting, were trained using early birth data to predict perinatal brain injury. Synthetic minority over-sampling and adaptive synthetic sampling (ADASYN) were applied to address class imbalance. Model performance was evaluated using accuracy, F1 score, and ROC curves. Feature importance scores and Shapley additive explanations (SHAP) values were also calculated. Results: Among 179 neonates, 39 had perinatal brain injury. There were significant differences between the injury and non-injury groups in mode of delivery, Apgar scores, capillary pH, lactate dehydrogenase (LDH) levels, and whether therapeutic hypothermia was performed. The gradient boosting model with the ADASYN method achieved the best performance. In terms of feature importance scores, the 1 min Apgar score was the most influential predictor. Additionally, SHAP analysis showed that LDH levels had the highest SHAP values. Conclusion: the gradient boosting model with ADASYN oversampling effectively predicts perinatal brain injury, potentially improving early detection for predicting long-term outcomes, reducing unnecessary MRI scans, and lowering healthcare costs.

Background When the newborn brain is exposed to hypoxia, as in hypoxic ischemic encephalopathy (HIE), it causes an inflammatory response. A wide variety of inflammatory markers are therefore used in the diagnosis of HIE. Objective We aimed to determine the diagnostic role of systemic inflammatory indices in infants with moderate-to-severe HIE. We have also investigated the effect of hypothermia treatment over those indices. Study Design A retrospective cohort study of infants suffering from moderate-to-severe HIE was conducted in a tertiary-level neonatal intensive care unit between September 2019 and March 2021. Systemic inflammatory indices including systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated for infants with HIE and controls at baseline, and after therapeutic hypothermia in those with HIE. Results A total of 103 infants (53 in the HIE group and 50 in the control group) were included in the study. Median gestational ages (GA) were 39 (37–40) and 38 (37–39) weeks, and median birth weights (BW) were 3,165 (2,890–3,440) and 3,045 (2,850–3,460) g in the HIE and control groups, respectively. GA, BW, mode of delivery, and gender of infants were similar between the groups. Infants in the HIE group had significantly higher NLR (p = 0.001), SII (p = 0.001), PIV (p = 0.001), and SIRI (p = 0.004) values when compared with the control group. Those indices decreased significantly after hypothermia treatment in the HIE group. Areas under curve for NLR, PLR, MLR, SII, SIRI, and PIV to predict HIE were found to be 0.808, 0.597, 0.653, 0.763, 0.686, and 0.663, respectively. Cutoff values having a good ability to predict HIE for SII and NLR were 410 and 1.12. Elevated NLR level above 1.12 was found to be an independent predictor for HIE, as revealed by multivariate analyses. No associations were found between systemic inflammatory indices and amplitude-integrated electroencephalography (aEEG) patterns, presence of seizures, and death. Conclusion Systemic inflammatory indices may represent reliable and readily available predictors of HIE risk. NLR seems to be an independent factor in diagnosing moderate-to-severe HIE. Key Points Systemic inflammatory incides are readily calculated from the peripheral blood count. NLR is an independent and valuable factor in diagnosing moderate-to-severe hypoxic-ischemic encephalopathy. Systemic inflammatory incides might be feasible for diagnosing hypoxic-ischemic encephalopathy. [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of ER α . These findings demonstrated that TrkB activation in the presence of ER α comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of ER α -dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period. Methods: In this study, we used a unilateral hypoxic ischemic (HI) mouse model. ER α +/+ or ER α −/− mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for 7 days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety-like behavior. The brains were then assessed for tissue damage using immunohistochemistry. Results: Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking ER α . The female-specific improved recognition and location memory outcomes in adulthood conferred by DHF therapy after neonatal HI tended to be or were ER α -dependent, respectively. Interestingly, DHF triggered anxiety-like behavior in both sexes only in the mice that lacked ER α . When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of ER α significantly reduced overall HI-associated mortality in both sexes. Conclusions: These observations provide evidence for a therapeutic role for DHF in which TrkB-mediated sustained recovery of recognition and location memories in females are ER α -associated and dependent, respectively. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner. Plain language summary: Periods of low oxygen delivery and blood flow to the brains of newborns are known to cause life-long impairments to their cognitive ability as adults. Interestingly, male newborns are more susceptible to this injury than females. The mechanisms causing this sex difference are poorly understood. Here we test the role of the nerve growth factor receptor tyrosine kinase B (TrkB) in providing long-term neuroprotection following neonatal hypoxia–ischemia (HI) in mice. We have previously shown that when mice are treated with the TrkB agonist 7,8-dihydroxyflavone (DHF) in the days following neonatal HI, the result is short-term neuroprotection only in females and this protection is dependent on the presence of the estrogen receptor alpha receptor ( ER α ). In this study, we extend these observations by subjecting mice either with or without ER α to HI. Some of the mice were then treated with DHF immediately after HI. As adults, we performed tests to assess the mice's memory and anxiety-like behavior. At the end of these tests, we assessed the brains for tissue loss. Our results show that as adults the DHF treatment following HI in neonatal mice preserved memory only in females and this effect was dependent on the presence of ER α . In addition, DHF therapy triggered anxiety-like behavior in mice lacking ER α . We also show that this neuroprotection is not dependent on preservation of brain tissue following the injury. These results provide insight into the mechanisms behind the female resistance to hypoxic ischemic episodes as newborns. Highlights: Female neonates are more resistant to the long-term effects of hypoxic ischemic encephalopathy. The mechanism behind female-specific neuroprotection is poorly understood. The preservation of location memory in adult mice subjected to HI as neonates and treated with DHF is specific to females and requires ER α . DHF therapy in mice lacking ER α predisposes both male and female mice to increased anxiety-like behavior. This neuroprotection in females does not correlate with the extent of brain tissue damage. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the neonatal outcomes in normal vs abnormal cardiotocograhy in term pregnancy. MATERIALS AND METHODS: This was a prospective analytical study carried out in A unit of obstetrics and Gynaecology department of Khyber Teaching Hospital Peshawar from 15th April 2022 to 15th October 2022. A total 224 patients meeting inclusion criteria were included in study. In Group A (normal CTG) there were 111 patients and 113 were in Group B (abnormal CTG). Patients with known fetal congenital abnormalities, intrauterine growth restriction, and fetal mal presentations were excluded from the study. RESULTS: The mean age of sample population was 26.02+4.497. Multigravidae were more than primigravidae in both groups (86.4% vs 13.6% in Group A and 72.5% vs 27.5% in Group B). In Group B, caesarean section rate was higher (82.3%) than Group A (9%). From Group B, 26 (23%) newborns went to NICU for admission, whereas only 8 (7.2%) newborns from Group A needed NICU admission. Hypoxic ischemic encephalopathy was also observed more in newborns in Group B compared to Group A (10 vs 1). In Group A 12 babies had APGAR score <7 at 1 minute while in Group B 18 babies had APGAR score < 7 at 1 minute. In Group A 2 babies had APGAR score <7 at 5 minutes whereas in Group B 7 babies had APGAR score < 7. CONCLUSION: The caesarean section rate, NICU admission and hypoxic ischemic encephalopathy were more in Group B than in Group A and this difference was statistically significant (p-value 0.000, 0.000 and 0.006 respectively). Whereas there was no statistically significant difference in APGAR Score at 1 and 5 minutes in both groups (p-value 0.26 and 0.094 respectively). [ABSTRACT FROM AUTHOR]

A late preterm female neonate, born to a consanguineously married couple by normal vaginal delivery and unremarkable family history, was admitted to our NICU soon after birth for management of respiratory distress secondary to meconium aspiration syndrome and persistent pulmonary hypertension of newborn. She required intensive ventilatory and hemodynamic support and was encephalopathic since birth but did not fulfill the criteria for therapeutic hypothermia. Extensive metabolic workup revealed no diagnosis, but neuroimaging showed characteristic findings consistent with the diagnosis of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. This was supported by the result of whole exome sequence that identified a novel homozygous mutation, c.1191 + 11A>C, for DARS2 gene confirming the diagnosis.

Background: The survival rate of very low birth weight (VLBW) infants has recently improved. However, the occurrence of and factors associated with epilepsy in VLBW infants remain unknown. This study aimed to clarify the incidence, characteristics, and factors associated with epilepsy development in VLBW infants. Methods: All VLBW infants admitted to our hospital between 2012 and 2017 were included in this study. VLBW infants with a follow-up period of

BackgroundTo determine whether restricted diffusion of the callosal splenium is specific for seizure activity in neonates.MethodsWe performed a retrospective chart review of 123 neonates who had a diagnosis of hypoxic ischemic encephalopathy (HIE) who underwent therapeutic cooling and had magnetic resonance imaging (MRI) within the first 10 days of life. The regions examined for injury include the callosal splenium, cortex, deep gray matter, and subcortical white matter. Neurodevelopmental outcomes were secondarily assessed using the Bayley Scales of Infant Development at 12 to 18 months of age and > 18 months of age. APGAR scores and pH, two important markers of hypoxia/ischemia and encephalopathy, were also analyzed in relation to these outcomes.ResultsApproximately 41% of the neonates had at least one abnormal region on brain MRI, and 21% had abnormal signal in the splenium. Clinical and/or electrographic seizures were documented in 32%. Changes in the splenium had a sensitivity of 54%, specificity of 94%, and positive predictive value of 81% for seizure presence. The presence of seizures and splenium lesion was associated poor developmental outcomes at 12 to 18 months of age. APGAR scores at 10 minutes, but not lowest pH was associated with splenial changes.ConclusionsRestricted diffusion of the callosal splenium is specific for recent seizures in neonates with HIE. Seizures and splenial lesion represent risk factors for poor neurodevelopmental outcomes. Child neurologists and neonatologists should consider splenial signal abnormality in their assessment of neonates at risk for seizures and counsel families about likely outcomes accordingly.

Background: Since a high incidence of mortality and morbidity is induced by preterm birth, it is important to understand how hypoxic ischemic encephalopathy (HIE) in preterm infants alters gut microbiota development. Methods: We analyzed 89 stools from 30 term newborns (NNG), 30 preterm infants without apnea (PG) and 29 preterm infants with definite diagnosis of apnea (PAG) by 16S rRNA gene sequencing in this study. Results: The data showed that species richness and diversity in PG and PAG were significantly lower compared with NNG. This study investigated the difference in bacteria and relative abundance between NNG, PG and PAG. The abundance of Klebsiella and Streptococcus strains were markedly increased, while Clostridium was significantly decreased in PAG compared with PG. The most notable exceptions included Klebsiella pneumoniae and Escherichia coli, which were markedly increased in PG and PAG, and these provide the main bacterial source of dopamine and serotonin production. This study also revealed that Lactobacillus and Bifidobacterium were markedly increased in PG and PAG, and these are the main source of GABA production for bacteria. Conclusion: The present study confirmed that apnea had a uniform effect on species richness and diversity. However, it cannot be established whether the abundance and difference of these bacterial genera and species directly affect the occurrence and development of preterm infants with HIE by secreting intestinal neurotransmitters.

Background: When a neonate is born under a hypoxic state, there is increased production of uric acid due to hypoxic tissue damage, which is excreted via the kidney, and the ratio of uric acid and creatinine (UA/Cr) in urine is used as an early predictor of perinatal hypoxia. Objectives: We conducted this study to compare urine UA/Cr ratio between normal and asphyxiated newborns and between different stages of HIE to evaluate its usefulness as a diagnostic and prognostic marker of perinatal asphyxia. Patients and method: This observational cross-sectional study is conducted for one year with 75 asphyxiated neonates in different stages of HIE and 75 healthy neonates as control. Uric acid and creatinine values are measured with an auto-analyzer from a single urine sample taken between 6 to 24 hours of birth. Results: We found urine UA(38 ±2.81 mg/dl vs 19.24±0.75 mg/dl ) and urine UA/Cr value (2.81±0.32 vs 1.40±0.13 ) significantly high in cases compared to control. Also, the urine UA and UA/Cr values are increasing with advanced stages of HIE (p 2.45 with an AUC of 0.96, accuracy of 90%, sensitivity of 98.07% , specificity of 85.70% , PPV 78.46%, and NPV 98.82%. Conclusion: Urine UA/Cr appears to be a simple, inexpensive and reliable indicator of perinatal hypoxia for risk stratification based on functional impairment in the HIE babies.

BackgroundHypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants.MethodsThis is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system.ResultsA total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069–2.117).ConclusionsInfants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.

Objectives This study aimed to explore the relationship between varying HIE grades in newborns and levels of reduced glutathione and superoxide dismutase in cerebrospinal fluid, investigating their potential as predictive markers for mortality. The goal was to assess the utility of CSF-based free radical scavengers and antioxidants in predicting mortality in newborns with HIE. Methods A 3-year cross-sectional study at Patna Medical Collage and Hospital in Patna, Bihar, India included 86 newborns with hypoxic ischemic encephalopathy. Standard treatments were administered, and CSF analysis for superoxide dismutase and reduced glutathione followed exclusion criteria. Results In the study of 140 neonates, 54 were excluded due to consent issues, leaving 86 examined by Sarnat staging. Cerebrospinal fluid superoxide dismutase significantly decreased with HIE severity (81.8, 53.2, 31.6 U/ml, P < 0.001). Reduced glutathione exhibited a negative correlation (1354.6, 1041.9, 692.7 ng/ml, P < 0.001). Deceased neonates showed significantly lower SOD (61.43 U/ml, P < 0.001) and GSH (22.45 U/ml, P < 0.001) compared to survivors (1104.32 ng/ml, 584.68 ng/ml, respectively). Conclusion The current study reveals that diminished levels of reduced glutathione (GSH) and superoxide dismutase (SOD) in cerebrospinal fluid indicate the intensity of hypoxic ischemic encephalopathy (HIE) and correlate with newborn mortality, highlighting the critical role of oxidative stress. Establishing cut-off values for these antioxidants in CSF may serve as markers for HIE staging and prognosis, guiding the development of targeted neuroprotective therapies for neonates. Recommendation The study recommends conducting larger, prospective investigations to address limitations like the small sample size and retrospective design. Furthermore, exploring interventions targeting oxidative stress is advised to enhance outcomes in newborns with HIE.

Aim and Objective: Study of the Impact of birth asphyxia on thyroid hormone in newborns. Methods: It was a prospective case-control study conducted at SCB Medical College, Department of Pediatrics. For the study, a total of 200 full-term newborns were assigned of which 100 asphyxiated newborns were taken as cases and 100 healthy newborns as a control group. Sarnat and Sarnat staging is used to classify the severity of birth asphyxia. Blood samples were collected at 18 to 24 hours of age for thyroid hormone level estimation. Results: Out of 100 cases, 33% were HIE stage 1, 43% were HIE stage 2, and 24% were HIE stage 3. The mean value of T3, T4, and TSH was lower at 18 to 24 hours of age. Conclusion: The mean T3, T4, and TSH level at 18 to 24 hours of asphyxiated newborn was significantly lower than the control group. Recommendation: More studies need to be done with a larger sample size in different regions of India and investigate the prevalence of thyroid hypoxic-ischemic encephalopathy and its association with morbidity.

Background/aim: Hypoxic ischemic encephalopathy (HIE) is one of the common causes of mortality and morbidity in newborns. Despite therapeutic hypothermia, an important treatment with proven efficacy, the morbidity and mortality rates remain high. The aim of this study was to neurodevelopmentally evaluate patients who underwent therapeutic hypothermia. Material and method: Included herein were patients who underwent hypothermia between 2018 and 2020. Their medical files were reviewed retrospectively, and their demographic and clinical information was recorded. Patients whose contact information was available were called to the developmental pediatrics outpatient clinic for a neurodevelopmental evaluation. The Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) was used as the evaluation tool. Laboratory values and clinical parameters of the patients were further analyzed. Results: It was found that 42 patients underwent hypothermia in 3 years, of whom 14 (33.3%) had died. Of the 28 patients who were discharged, 20 children could be reached, and a neurodevelopmental evaluation was performed. Developmental delay in the cognitive area was detected in 11 (55%) patients, delay in the language area was found in 9 (45%) patients, and delay in the motor area was found in 11 (55%) patients. The correlation and regression analysis results determined that the time to start cooling was the most effective common factor in all 3 fields of scoring. Conclusion: The time to start cooling is related to the neurodevelopmental outcomes of patients with HIE. The earlier cooling is started, the better the neurodevelopmental results. Despite therapeutic hypothermia, the neurodevelopmental development of infants may be adversely affected. These patients should be followed-up neurodevelopmentally for a long time. [ABSTRACT FROM AUTHOR]

Children who experience adversities in the pre-perinatal period are at increased risk of developing impairment later in life, despite the absence of overt brain and neurological abnormalities. However, many of these children exhibit sequelae several years after a period of normal appearance. As a result, the need for reliable developmental assessments for the early detection of infants at high risk of adverse neurodevelopmental outcomes has emerged. The Griffiths Mental Developmental Scales have a promising but poorly explored prognostic ability. This longitudinal study evaluated the predictive power of the Griffiths Mental Developmental Scales at 12 and 24 months on the cognitive and neuropsychological profile at 6 years of age in a sample of 70 children with a history of prematurity or perinatal asphyxia but without brain and neurological abnormalities. We found that the Griffiths Mental Developmental Scales at 24 months had good predictive ability on the intelligence quotient at 6 years and the capacity to predict some neuropsychological performances. On the other hand, the Griffiths Mental Developmental Scale at 12 months was not associated with the performance at 6 years or 24 months. Conclusion: Data on brain development converge to indicate that the first two years of age represent a critical stage of development, particularly for children experiencing mild pre-perinatal adversities who are thought to exhibit white matter dysmaturity. For this reason, this age is crucial for identifying which children are at major risk, leaving enough time to intervene before overt deficits become apparent. Brain development in the first 2 years could explain the limited reliability of early neurodevelopmental testing. What is Known: • Pre-perinatal adversities increase the risk of developing neurodevelopmental disorders. • The predictive ability of the Griffith scale is poorly explored in low-grade conditions. What is New: • The predictive ability of the Griffith scale has been investigated in low-risk children. • A complete neuropsychological profile could offer a more accurate prediction than the intellectual quotient. [ABSTRACT FROM AUTHOR]

Background. Feeding difficulties continue to be a serious problem in newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). The aim of this study was to investigate the efficacy of oral motor interventions (OMI) on feeding outcomes in neonates with HIE/TH. Methods. This was a prospective randomised control study conducted between January 2022 and September 2022. Premature Infant Oral Motor Intervention (PIOMI) was used as OMI. Newborns with HIE/TH, who underwent PIOMI, constituted the study group, and newborns, who did not receive any feeding exercise, constituted the control group. Transition time to full oral feeding (FOF) was determined as the time between initiation of tube feeding and full oral breastfeeding or bottle feeding. The day per oral (PO) feeding was started was specified as PO first, the day the infants could take half of the volume of the feedings by mouth was PO half, and the day the infants could take all the feedings by mouth was PO full. Results. There were 50 neonates in each group. Time to FOF was significantly shorter in the study group than in the control group in all stages of HIE/TH (P= 0.008 for stage 1, and <0.001 for stage 2 and 3 HIE). However, times to PO first, PO half, PO full and discharge were shorter in the study group than in the control group only in the neonates with stage 3 HIE (P= 0.003, 0.014, 0.013, 0.042, respectively). Conclusions. The PIOMI, which could be named as "HIE-OMI" in our study, is an effective intervention in shortening the transition time to FOF in neonates with all stages of HIE undergoing TH. In addition, "HIEOMI" shortens the length of hospital stay, and improves feeding outcomes in neonates with severe HIE/TH. [ABSTRACT FROM AUTHOR]

The survival rate of very low birth weight (VLBW) infants has recently improved. However, the occurrence of and factors associated with epilepsy in VLBW infants remain unknown. This study aimed to clarify the incidence, characteristics, and factors associated with epilepsy development in VLBW infants. All VLBW infants admitted to our hospital between 2012 and 2017 were included in this study. VLBW infants with a follow-up period of <1 year were excluded. Chromosomal abnormalities, brain anomalies, severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and hypoxic ischemic encephalopathy (HIE) were considered to be risk factors. Epilepsy occurred in 21/526 (4.0%) VLBW infants. Chromosomal abnormalities, brain anomalies, severe IVH, cystic PVL, HIE, neonatal seizures, advanced maternal age, maternal diabetes mellitus, no administration of antenatal corticosteroids, and low Apgar scores at 1 and 5 min were associated with a risk of epilepsy. The median time to epilepsy onset was 8 months (range: 0–59 months), and the onset occurred within 2 years in 15/21 patients (71.4%) and within 4 years in 18/21 patients (85.7%). VLBW infants with risk factors developed epilepsy earlier and at a significantly higher rate than those without risk factors. Among infants who had risk factors and who developed epilepsy, 86.7% did so within 2 years of age, compared to 33.3% of those who developed epilepsy but did not have risk factors. These findings regarding factors associated with a risk of development of epilepsy and temporal feature of epilepsy may contribute to the development of monitoring and treatment protocols for epilepsy in VLBW infants. [ABSTRACT FROM AUTHOR]

BACKGROUND: Late preterm (LPT) infants are increasingly treated for hypoxic-ischemic encephalopathy (HIE). However, neurodevelopmental differences of LPT infants may independently influence the neurologic exam and confound care. METHODS: Perinatal and outcome characteristics were extracted along with the worst autonomic and state/neuromuscular/reflex Sarnat components in a cross-section of infants with moderate/severe HIE. Infants were classified as late preterm (LPT, 34–36 weeks) or term (>36 weeks). RESULTS: 250 infants were identified, 55 were late preterm. LPT infants had lower mean gestational age and birthweight and greater length of stay (LOS). LPT infants had higher median scores for the Moro and respiratory autonomic components, but no difference in total score. CONCLUSIONS: LPT infants had increased LOS, worse Moro reflex, and respiratory status, but no clinically or statistically significant differences in total Sarnat scores. Although it is important to note the impact of immaturity on the exam, it is unlikely to independently alter management. [ABSTRACT FROM AUTHOR]

Objective Describe the association between cardiac dysfunction and death or moderate-to-severe abnormalities on brain magnetic resonance imaging (MRI) in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE). Study Design Retrospective study in neonates with moderate or severe HIE undergoing therapeutic hypothermia between 2008 and 2017. Primary outcome was death or moderate-to-severe brain injury using the Barkovich score. Conventional and speckle-tracking echocardiography measures were extracted from available echocardiograms to quantify right (RV) and left (LV) ventricular functions. Results A total of 166 newborns underwent therapeutic hypothermia of which 53 (36.5%) had echocardiography performed. Ten (19%) died prior to hospital discharge, and 11 (26%) had moderate-to-severe brain injury. There was no difference in chronologic age at echocardiography between the normal and adverse outcome groups (22 [±19] vs. 28 [±21] hours, p = 0.35). Cardiac findings in newborns with abnormal outcome included lower systolic and diastolic blood pressure (BP) at echocardiography (p = 0.004) and decreased tricuspid annular plane systolic excursion (a marker of RV systolic function; p = 0.01), while the ratio of systolic pulmonary artery (PA) pressure to systolic BP indicated isosystemic pressures (>2/3 systemic) in both groups. A multilogistic regression analysis, adjusting for weight and seizure status, indicated an association between abnormal outcome and LV function by longitudinal strain, as well as by ejection fraction. Conclusion Newborns who died or had moderate–to-severe brain injury had a higher incidence of cardiac dysfunction but similar PA pressures when compared with those who survived with mild or no MRI abnormalities. Key Points Newborns with HIE with functional LV/RV dysfunction are at risk for death or brain injury. All neonates with HIE had elevated pulmonary pressure, but neonates with poor outcome had RV dysfunction. When evaluating newborns with HIE by echocardiography, beyond estimation of pulmonary pressure, it is important to assess biventricular function. [ABSTRACT FROM AUTHOR]

Abstract Background Hypoxic-ischemic encephalopathy (HIE) is one of the major complications that can lead to death or disability in neonates. We assessed the effect of citicoline as a neuroprotector in neonates with moderate and severe HIE. Methods This clinical trial was carried on 80 neonates with moderate to severe HIE who were not candidates for therapeutic cooling. They were subdivided randomly into two groups; citicoline treatment group which included 40 neonates who received citicoline 10 mg / kg /12 h IV for 4 weeks plus other supportive measures and the control group which included 40 neonates who were managed with placebo and the same supportive measures. All patients were evaluated for duration of mechanical ventilation (MV), need for inotropes, seizures (type, frequency, and duration), and duration of NICU. Cranial ultrasounds and brain magnetic resonance image (MRI) were performed for all included neonates after 4 weeks of treatment. Follow- ups of all neonates for the neurodevelopmental outcomes were done at 3, 6, 9, and 12 months. Results There was a significant reduction in the number of neonates having seizures after discharge in the citicoline-treated group (2 neonates) compared to the control group (11 neonates). Cranial ultrasound and MRI findings at 4 weeks were significantly better in the treatment group compared to the control group. Moreover, neurodevelopmental outcome showed significant improvement at 9 and 12 months in the citicoline treated neonates compared to the control group. There was statistically significant reduction in the duration of seizures, NICU stay, inotrope use, and MV in the treatment group compared to the control group. Citicoline was well tolerated with no remarkable side effects. Conclusion Citicoline could be a promising neuroprotector drug in neonates with HIE. Trial registration The study was registered at ClinicalTrials.gov (NCT03949049). Registered at 14 May 2019, https://clinicaltrials.gov/ct2/show/NCT03949049

Background: Neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia are at high risk of acute kidney injury (AKI). Methods: We performed a two-site prospective observational study from 2018 to 2019 to evaluate the utility of renal near-infrared spectroscopy (NIRS) in detecting AKI in 38 neonates with HIE receiving therapeutic hypothermia. AKI was defined by a delayed rate of serum creatinine decline (< 33% on day 3 of life, < 40% on day 5, and < 46% on day 7). Renal saturation (Rsat) and systemic oxygen saturation (SpO2) were continuously measured for the first 96 h of life (HOL). Renal fractional tissue oxygen extraction (RFTOE) was calculated as (SpO2 − Rsat)/(SpO2). Using renal NIRS, urine biomarkers, and perinatal factors, logistic regression was performed to develop a model that predicted AKI. Results: AKI occurred in 20 of 38 neonates (53%). During the first 96 HOL, Rsat was higher, and RFTOE was lower in the AKI group vs. the no AKI group (P < 0.001). Rsat > 70% had a fair predictive performance for AKI at 48–84 HOL (AUC 0.71–0.79). RFTOE ≤ 25 had a good predictive performance for AKI at 42–66 HOL (AUC 0.8–0.83). The final statistical model with the best fit to predict AKI (AUC = 0.88) included RFTOE at 48 HOL (P = 0.012) and pH of the infants' first postnatal blood gas (P = 0.025). Conclusions: Lower RFTOE on renal NIRS and pH on infant first blood gas may be early predictors for AKI in neonates with HIE receiving therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Accurate identification and characterization of the severity, extent, and location of brain injury is essential to predict the neurodevelopmental outcome of newborns. The pattern of brain injury depends on the severity and duration of hypoxia and degree of brain maturation. Various neuroimaging modalities such as neurosonogram, CT, MRI are available which help in identification of severity of brain injury. Initial scans were obtained within 72 hrs of birth and subsequent follow up scans were done on 8-10th day and 30th day so as not to miss the relatively late developing intracranial changes. The infants were then followed up after 6-12 months for a detailed neurological assessment for correlation of clinical outcome with NSG findings using statistical analysis. In our study 66% newborns were term and 34% were preterm where as in a study by Sushmita et al., it was 76% term and 24% preterms. In our study 26% neonates had HIE I, 58% were HIE II, 16% were HIE III as compared to another study by Behere A et al., in which 11.3% were HIE I, 72.8% were HIE II and 15.95% were HIE III. In our study 90% of cases had abnormal neurosonogram findings and 10% cases had normal neurosonogram. [ABSTRACT FROM AUTHOR]

Since a high incidence of mortality and morbidity is induced by preterm birth, it is important to understand how hypoxic ischemic encephalopathy (HIE) in preterm infants alters gut microbiota development. We analyzed 89 stools from 30 term newborns (NNG), 30 preterm infants without apnea (PG) and 29 preterm infants with definite diagnosis of apnea (PAG) by 16S rRNA gene sequencing in this study. The data showed that species richness and diversity in PG and PAG were significantly lower compared with NNG. This study investigated the difference in bacteria and relative abundance between NNG, PG and PAG. The abundance of Klebsiella and Streptococcus strains were markedly increased, while Clostridium was significantly decreased in PAG compared with PG. The most notable exceptions included Klebsiella pneumoniae and Escherichia coli , which were markedly increased in PG and PAG, and these provide the main bacterial source of dopamine and serotonin production. This study also revealed that Lactobacillus and Bifidobacterium were markedly increased in PG and PAG, and these are the main source of GABA production for bacteria. The present study confirmed that apnea had a uniform effect on species richness and diversity. However, it cannot be established whether the abundance and difference of these bacterial genera and species directly affect the occurrence and development of preterm infants with HIE by secreting intestinal neurotransmitters. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether an association exists between deceleration and acceleration areas on continuous fetal cardiotocography (CTG) and neonatal encephalopathy (NE). Methods: A single center, retrospective case–control study was conducted to compare CTG characteristics of low‐risk pregnancies (35 weeks of gestation or more), complicated by moderate to severe NE with two matched controls for every case. Controls were matched by gestational age and cord blood pH. We analyzed the intrapartum CTG recordings by calculation of the deceleration and acceleration areas and the ratio between the two. Results: During the period between 2013 and 2019, we identified 95 cases of low‐risk pregnancies that were complicated by moderate to severe NE in our center. Thirty‐three (34.7%) deliveries were excluded, mostly because of an insufficient duration of the CTG recordings. The remaining 62 cases were matched with 123 controls. We found that NE was significantly associated with an increased total deceleration area, a decreased total acceleration area, and a lower acceleration‐to‐deceleration ratio. Conclusions: NE was significantly associated with increased total deceleration area, decreased total acceleration area, and a lower acceleration‐to‐deceleration ratio, independent of cord blood pH. Development of a computerized real‐time analysis of fetal heart rate tracings may contribute to making these measurements a more valid clinical tool. Synopsis: Neonatal encephalopathy was associated with the total area of decelerations and accelerations. [ABSTRACT FROM AUTHOR]

Aim: Hypoxic ischemic encephalopathy (HIE); It is a clinical condition that can progress with abnormal consciousness, seizures, and multi-organ failure. In this retrospective study, it was aimed to evaluate the cord blood gas pH value and cardiac markers, as well as diffusion magnetic resonance imaging (MRI), neurological examinations and developmental results of newborns diagnosed with HIE who underwent therapeutic hypothermia (TH). Materials-Methods: Patients who were hospitalized in the Neonatal Intensive Care Unit of Hacettepe University İhsan Doğramacı Children's Hospital between January 2015 and January 2021 and received TH treatment with the diagnosis of HIE stage 2-3 and were followed up in the outpatient clinic were included in the study. Umbilical cord blood gas pH, Troponin-I, CK-MB values, diffusion MRI findings and Bayley Developmental Assessment Scale for Infants and Young Children-lll (BSID-III) results werecompared. Results: Mean gestational week of 17 patients included in the study was 39 weeks (37-41), mean birth weight was 3360 ± 325 g, 13 (59%) were male. Seizures were not detected in 10 (59%) of the patients in aEEG/EEG follow-up. There was no statistical difference between the median cord blood gas pH value and abnormal diffusion MRI results. Between the BSID-III scoresand the median ofthe cord blood gas pH; There was no statistical difference between heart markers and diffusion MRI and BSID-III results. Conclusion: Cord blood gas values used for TH indication in infants with hypoxic ischemic encephalopathy are not sufficient to predict long-term neurodevelopmental prognosis. If the number of patients is increased, we can say that cardiac enzymes, which show that the heart muscle is affected by hypoxia in these patients, may be useful in predicting the neurological-developmental problems that the baby may presence in long-term follow-up. [ABSTRACT FROM AUTHOR]

Hypoxic ischemic encephalopathy (HIE) remains a significant cause of disability despite treatment with therapeutic hypothermia (TH). Many survive with more subtle deficits that affect daily functioning and school performance. We have previously shown an early indication of hippocampal changes in infants with HIE despite TH. The aim of this study was to evaluate the hippocampal volume via MRI and memory function at 5 years of age. A cohort of children followed from birth returned for a 5-year follow-up (n = 10 HIE treated with TH, n = 8 healthy controls). The children underwent brain MRI and neurodevelopmental testing to assess their brain volume, general development, and memory function. Children with HIE had smaller hippocampal volumes than the controls despite no differences in the total brain volume (p = 0.02). Children with HIE generally scored within the average range on developmental testing. Though there was no difference in the memory scores between these groups, there was a positive within-group correlation between the hippocampal volume and memory scores in children with HIE (sentence recall r = 0.66, p = 0.038). There was no relationship between newborn memory function and 5-year hippocampal size. Children with HIE treated with TH experienced significant and lasting changes to the hippocampus despite improvements in survival and severe disability. Future studies should target diminishing injury to the hippocampus to improve overall outcomes. [ABSTRACT FROM AUTHOR]

This article provides a correlation of the pathophysiology and magnetic resonance imaging (MRI) patterns identified on imaging of children with hypoxic ischemic brain injury (HIBI). The purpose of this pictorial review is to empower the reading radiologist with a simplified classification of the patterns of cerebral injury matched to images of patients demonstrating each subtype. A background narrative literature review was undertaken of the regional, continental and international databases looking at specific patterns of cerebral injury related to perinatal HIBI. In addition, a database of MRI studies accumulated over a decade (including a total of 314 studies) was analysed and subclassified into the various patterns of cerebral injury. Selected cases were annotated to highlight the areas involved and for ease of identification of the affected substrate in daily practice.KeywordsHypoxic ischemic encephalopathy; Magnetic resonance imaging; Acute profound; Partial prolonged; Hypoxic ischemic brain injury; Ulegyria; Multicystic; Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in newborns. Our study aimed to determine the neurodevelopmental outcomes, risk factors, and the relationship between risk factors and prognosis of cases followed up with HIE diagnosis and who were treated with hypothermia treatment. Medical records of 23 patients who were followed up with HIE diagnosis in the pediatric neurology outpatient clinic between January 1, 2018, and December 31, 2021, and treated with therapeutic hypothermia in the newborn period were retrospectively reviewed. Denver Developmental Screening Test II was used in the developmental evaluation. Neurodevelopment was normal in 12 (52.2%) of 23 cases and retarded for age in 11 (47.8%) cases. Variables such as Sarnat encephalopathy score in the neonatal period, need for prolonged ventilation, presence of severe acidosis at birth, Apgar scores at the 1st and 5th minutes, and abnormal cranial magnetic resonance (Mrg) findings were determined to be major factors in determining neurodevelopmental prognosis in asphyxic cases. The male gender was found to be riskier in terms of prognosis. Of the patients with HIE, retardation was determined for fine motor skills in 52.2%, speaking in 39.1%, gross motor skills in 26.1%, and personal development in 21.7%. Epilepsy, cerebral palsy, and speech disorders were the most common chronic period problems in patients with HIE. Despite therapeutic hypothermia treatment, neurodevelopmental problems are still observed in newborns with HIE. We found that male gender, low Apgar score, severe acidosis, and abnormal cranial Mrg findings in the neonatal period are risk factors in determining the neurodevelopmental prognosis of newborns with HIE. Monitoring and supporting the development of HIE cases with risk factors from the first months of life and intervening in developmental problems promptly are crucial in order to improve long-term outcomes.