Feasibility and Safety of Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-01): A Randomized, Double-blind, Placebo-controlled Phase Ib Clinical Trial.

OBJECTIVE: To test feasibility and safety of administering sildenafil in neonates with neonatal encephalopathy (NE), developing brain injury despite therapeutic hypothermia (TH). STUDY DESIGN: We performed a randomized, double-blind, placebo-controlled phase Ib clinical trial between 2016 and 2019 in neonates with moderate or severe NE, displaying brain injury on day-2 magnetic resonance imaging (MRI) despite TH. Neonates were randomized (2:1) to 7-day sildenafil or placebo (2 mg/kg/dose enterally every 12 hours, 14 doses). Outcomes included feasibility and safety (primary outcomes), pharmacokinetics (secondary), and day-30 neuroimaging and 18-month neurodevelopment assessments (exploratory). RESULTS: Of the 24 enrolled neonates, 8 were randomized to sildenafil and 3 to placebo. A mild decrease in blood pressure was reported in 2 of the 8 neonates after initial dose, but not with subsequent doses. Sildenafil plasma steady-state concentration was rapidly reached, but decreased after TH discontinuation. Twelve percent of neonates (1/8) neonates died in the sildenafil group and 0% (0/3) in the placebo group. Among surviving neonates, partial recovery of injury, fewer cystic lesions, and less brain volume loss on day-30 magnetic resonance imaging were noted in 71% (5/7) of the sildenafil group and in 0% (0/3) of the placebo group. The rate of death or survival to 18 months with severe neurodevelopmental impairment was 57% (4/7) in the sildenafil group and 100% (3/3) in the placebo group. CONCLUSIONS: Sildenafil was safe and well-absorbed in neonates with NE treated with TH. Optimal dosing needs to be established. Evaluation of a larger number of neonates through subsequent phases II and III trials is required to establish efficacy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT02812433.

Midazolam Prevents the Adverse Outcome of Neonatal Asphyxia.

OBJECTIVE: Birth asphyxia (BA) is the most frequent cause of neonatal death as well as central nervous system (CNS) injury. BA is often associated with neonatal seizures, which only poorly respond to anti-seizure medications and may contribute to the adverse neurodevelopmental outcome. Using a non-invasive rat model of BA, we have recently reported that the potent benzodiazepine, midazolam, prevents neonatal seizures in ~50% of rat pups. In addition to its anti-seizure effect, midazolam exerts anti-inflammatory actions, which is highly relevant for therapeutic intervention following BA. The 2 major aims of the present study were to examine (1) whether midazolam reduces the adverse outcome of BA, and (2) whether this effect is different in rats that did or did not exhibit neonatal seizures after drug treatment. METHODS: Behavioral and cognitive tests were performed over 14 months after asphyxia, followed by immunohistochemical analyses. RESULTS: All vehicle-treated rats had seizures after asphyxia and developed behavioral and cognitive abnormalities, neuroinflammation in gray and white matter, neurodegeneration in the hippocampus and thalamus, and hippocampal mossy fiber sprouting in subsequent months. Administration of midazolam (1 mg/kg i.p.) directly after asphyxia prevented post-asphyctic seizures in ~50% of the rats and resulted in the prevention or decrease of neuroinflammation and the behavioral, cognitive, and neurodegenerative consequences of asphyxia. Except for neurodegeneration in the thalamus, seizures did not seem to contribute to the adverse outcome of asphyxia. INTERPRETATION: The disease-modifying effect of midazolam identified here strongly suggests that this drug provides a valuable option for improving the treatment and outcome of BA. ANN NEUROL 2023;93:226-243.

Enteral plasma supports brain repair in newborn pigs after birth asphyxia.

Newborns exposed to birth asphyxia transiently experience deficient blood flow and a lack of oxygen, potentially inducing hypoxic-ischaemic encephalopathy and subsequent neurological damage. Immunomodulatory components in plasma may dampen these responses. Using caesarean-delivered pigs as a model, we hypothesized that dietary plasma supplementation improves brain outcomes in pigs exposed to birth asphyxia. Mild birth asphyxia was induced by temporary occlusion of the umbilical cord prior to caesarean delivery. Motor development was assessed in asphyxiated (ASP) and control (CON) piglets using neonatal arousal, physical activity and gait test parameters before euthanasia on Day 4. The ASP pigs exhibited increased plasma lactate at birth, deficient motor skills and increased glial fibrillary acidic protein levels in CSF and astrogliosis in the putamen. The expression of genes related to oxidative stress, inflammation and synaptic functions was transiently altered in the motor cortex and caudate nucleus. The number of apoptotic cells among CTIP2-positive neurons in the motor cortex and striatal medium spiny neurons was increased, and maturation of preoligodendrocytes in the internal capsule was delayed. Plasma supplementation improved gait performance in the beam test, attenuated neuronal apoptosis and affected gene expression related to neuroinflammation, neurotransmission and antioxidants (motor cortex, caudate). We present a new clinically relevant animal model of moderate birth asphyxia inducing structural and functional brain damage. The components in plasma that support brain repair remain to be identified but may represent a therapeutic potential for infants and animals after birth asphyxia.

On hidden factors and design-associated errors that may lead to data misinterpretation: An example from preclinical research on the potential seasonality of neonatal seizures.

Unintentional misinterpretation of research in published biomedical reports that is not based on statistical flaws is often underrecognized, despite its possible impact on science, clinical practice, and public health. Important causes of such misinterpretation of scientific data, resulting in either false positive or false negative conclusions, include design-associated errors and hidden (or latent) variables that are not easily recognized during data analysis. Furthermore, cognitive biases, such as the inclination to seek patterns in data whether they exist or not, may lead to misinterpretation of data. Here, we give an example of these problems from hypothesis-driven research on the potential seasonality of neonatal seizures in a rat model of birth asphyxia. This commentary aims to raise awareness among the general scientific audience about the issues related to the presence of unintentional misinterpretation in published reports.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Population pharmacokinetics of vancomycin in term neonates with perinatal asphyxia treated with therapeutic hypothermia.

AIMS: Little is known about the population pharmacokinetics (PPK) of vancomycin in neonates with perinatal asphyxia treated with therapeutic hypothermia (TH). We aimed to describe the PPK of vancomycin and propose an initial dosing regimen for the first 48 h of treatment with pharmacokinetic/pharmacodynamic target attainment. METHODS: Neonates with perinatal asphyxia treated with TH were included from birth until Day 6 in a multicentre prospective cohort study. A vancomycin PPK model was constructed using nonlinear mixed-effects modelling. The model was used to evaluate published dosing guidelines with regard to pharmacokinetic/pharmacodynamic target attainment. The area under the curve/minimal inhibitory concentration ratio of 400-600 mg*h/L was used as target range. RESULTS: Sixteen patients received vancomycin (median gestational age: 41 [range: 38-42] weeks, postnatal age: 4.4 [2.5-5.5] days, birth weight: 3.5 [2.3-4.7] kg), and 112 vancomycin plasma concentrations were available. Most samples (79%) were collected during the rewarming and normothermic phase, as vancomycin was rarely initiated during the hypothermic phase due to its nonempirical use. An allometrically scaled 1-compartment model showed the best fit. Vancomycin clearance was 0.17 L/h, lower than literature values for term neonates of 3.5 kg without perinatal asphyxia (range: 0.20-0.32 L/h). Volume of distribution was similar. Published dosing regimens led to overexposure within 24 h of treatment. A loading dose of 10 mg/kg followed by 24 mg/kg/day in 4 doses resulted in target attainment. CONCLUSION: Results of this study suggest that vancomycin clearance is reduced in term neonates with perinatal asphyxia treated with TH. Lower dosing regimens should be considered followed by model-informed precision dosing.

Predictive Performance of a Gentamicin Pharmacokinetic Model in Term Neonates with Perinatal Asphyxia Undergoing Controlled Therapeutic Hypothermia.

BACKGROUND: Model validation procedures are crucial when population pharmacokinetic (PK) models are used to develop dosing algorithms and to perform model-informed precision dosing. We have previously published a population PK model describing the PK of gentamicin in term neonates with perinatal asphyxia during controlled therapeutic hypothermia (TH), which showed altered gentamicin clearance during the hypothermic phase dependent on gestational age and weight. In this study, the predictive performance and generalizability of this model were assessed using an independent data set of neonates with perinatal asphyxia undergoing controlled TH. METHODS: The external data set contained a subset of neonates included in the prospective observational multicenter PharmaCool Study. Predictive performance was assessed by visually inspecting observed-versus-predicted concentration plots and calculating bias and precision. In addition, simulation-based diagnostics, model refitting, and bootstrap analyses were performed. RESULTS: The external data set included 323 gentamicin concentrations of 39 neonates. Both the model-building and external data set included neonates from multiple centers. The original gentamicin PK model predicted the observed gentamicin concentrations with adequate accuracy and precision during all phases of controlled TH. Model appropriateness was confirmed with prediction-corrected visual predictive checks and normalized prediction distribution error analyses. Model refitting to the merged data set (n = 86 neonates with 935 samples) showed accurate estimation of PK parameters. CONCLUSIONS: The results of this external validation study justify the generalizability of the gentamicin dosing recommendations made in the original study for neonates with perinatal asphyxia undergoing controlled TH (5 mg/kg every 36 or 24 h with gestational age 36-41 and 42 wk, respectively) and its applicability in model-informed precision dosing.

Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia.

OBJECTIVES: Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. METHODS: We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. RESULTS: S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 µg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. CONCLUSIONS: The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE.

Initial lactate levels linked to oliguria in term neonates with perinatal asphyxia.

BACKGROUND: Oliguria is a sign of impaired kidney function and has been shown to be an early predictor of adverse prognoses in patients with acute kidney injury. The relationship between urine output (UOP) and early lactate levels in neonates with perinatal asphyxia (PA) has not been extensively explored. This study aimed to investigate the link between oliguria during the first 24 h of life and early lactate levels in neonates with PA. METHODS: The medical records of 293 term neonates with asphyxia from 9216 hospitalized newborns were retrospectively analyzed, including 127 cases designated as the oliguria group and 166 cases as controls. Peripheral arterial blood gas after PA and UOP within 24 h after birth were analyzed. Logistic regression analyses and receiver operating characteristic curve analysis were conducted. RESULTS: Oliguria occurred in 43.34% of neonates with PA. The median UOP of the oliguria and control groups were 0.65 and 1.46 mL/kg/h, respectively. Elevated lactate levels after PA are an independent risk factor for oliguria in the following 24 h (p = 0.01; OR: 1.19; 95%CI: 1.04-1.35) and show a moderate discriminatory power for oliguria (AUC = 0.62). Using a cut off value of 8.15 mmol/L, the positive and negative predictive values and the specificity were 59.34%, 63.86%, and 78.30%, respectively. CONCLUSION: Neonates with elevated lactate levels after PA face a risk of oliguria in the following 24 h. Based on early elevated lactate levels after resuscitation, especially ≥ 8.15 mmol/L, meticulously monitoring UOP will allow this vulnerable population to receive early, tailored fluid management and medical intervention.

Hearing impairment after asphyxia and neonatal encephalopathy: a Norwegian population-based study.

The purpose of this study is to evaluate the association between perinatal asphyxia, neonatal encephalopathy, and childhood hearing impairment. This is a population-based study including all Norwegian infants born ≥ 36 weeks gestation between 1999 and 2014 and alive at 2 years (n = 866,232). Data was linked from five national health registries with follow-up through 2019. Perinatal asphyxia was defined as need for neonatal intensive care unit (NICU) admission and an Apgar 5-min score of 4-6 (moderate) or 0-3 (severe). We coined infants with seizures and an Apgar 5-min score < 7 as neonatal encephalopathy with seizures. Infants who received therapeutic hypothermia were considered to have moderate-severe hypoxic-ischemic encephalopathy (HIE). The reference group for comparisons were non-admitted infants with Apgar 5-min score ≥ 7. We used logistic regression models and present data as adjusted odds ratios (aORs) with 95% confidence intervals (CI). The aOR for hearing impairment was increased in all infants admitted to NICU: moderate asphyxia aOR 2.2 (95% CI 1.7-2.9), severe asphyxia aOR 5.2 (95% CI 3.6-7.5), neonatal encephalopathy with seizures aOR 7.0 (95% CI 2.6-19.0), and moderate-severe HIE aOR 10.7 (95% CI 5.3-22.0). However, non-admitted infants with Apgar 5-min scores < 7 did not have increased OR of hearing impairment. The aOR for hearing impairment for individual Apgar 5-min scores in NICU infants increased with decreasing Apgar scores and was 13.6 (95% CI 5.9-31.3) when the score was 0.          Conclusions: An Apgar 5-min score < 7 in combination with NICU admission is an independent risk factor for hearing impairment. Children with moderate-severe HIE had the highest risk for hearing impairment. What is Known: • Perinatal asphyxia and neonatal encephalopathy are associated with an increased risk of hearing impairment. • The strength of the association, and how other co-morbidities affect the risk of hearing impairment, is poorly defined. What is New: • Among neonates admitted to a neonatal intensive care unit (NICU), decreased Apgar 5-min scores, and increased severity of neonatal encephalopathy, were associated with a gradual rise in risk of hearing impairment. • Neonates with an Apgar 5-min score 7, but without NICU admission, did not have an increased risk of hearing impairment.

Birth asphyxia and its association with grand multiparity and referral among hospital births: A prospective cross-sectional study in Benin, Malawi, Tanzania and Uganda.

INTRODUCTION: Birth asphyxia is a leading cause of neonatal mortality in sub-Saharan Africa. The relationship to grand multiparity (GM), a controversial pregnancy risk factor, remains largely unexplored, especially in the context of large multinational studies. We investigated birth asphyxia and its association with GM and referral in Benin, Malawi, Tanzania and Uganda. MATERIAL AND METHODS: This was a prospective cross-sectional study. Data were collected using a perinatal e-Registry in 16 hospitals (four per country). The study population consisted of 80 663 babies (>1000 g, >28 weeks' gestational age) delivered between July 2021 and December 2022. The primary outcome was birth asphyxia, defined by 5-minute appearance, pulse, grimace, activity and respiration score <7. A multilevel and stratified multivariate logistic regression was performed with GM (parity ≥5) as exposure, and birth asphyxia as outcome. An interaction between referral (none, prepartum, intrapartum) and GM was also evaluated as a secondary outcome. All models were adjusted for confounders. CLINICAL TRIAL: Pan African Clinical Trial Registry 202006793783148. RESULTS: Birth asphyxia was present in 7.0% (n = 5612) of babies. More babies with birth asphyxia were born to grand multiparous women (11.9%) than to other parity groups (≤7.6%). Among the 76 850 cases included in the analysis, grand multiparous women had a 1.34 times higher odds of birth asphyxia (95% confidence interval [CI] 1.17-1.54) vs para one to two. Grand multiparous women referred intrapartum had the highest probability of asphyxiation (13.02%, 95% CI 9.34-16.69). GM increased odds of birth asphyxia in Benin (odds ratio [OR] 1.37, 95% CI 1.13-1.68) and Uganda (OR 1.29, 95% CI 1.02-1.64), but was non-significant in Tanzania (OR 1.44, 95% CI 0.81-2.56) and Malawi (OR 0.98, 95% CI 0.67-1.44). CONCLUSIONS: There is some evidence of an increased risk of birth asphyxia for grand multiparous women having babies at hospitals, especially following intrapartum referral. Antenatal counseling should recognize grand multiparity as higher risk and advise appropriate childbirth facilities. Findings in Malawi suggest an advantage of health systems configuration requiring further exploration.

Risk factors for neonatal hypoxic ischemic encephalopathy and therapeutic hypothermia: a matched case-control study.

BACKGROUND: Peripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonates, therapeutic cooling can be used to prevent or reduce permanent brain damage. The aim of this study was to assess the significance of different antenatal and delivery related risk factors for moderate and severe HIE and the need for therapeutic hypothermia. METHODS: We conducted a retrospective matched case-control study in Helsinki University area hospitals during 2013-2017. Newborn singletons with moderate or severe HIE and the need for therapeutic hypothermia were included. They were identified from the hospital database using ICD-codes P91.00, P91.01 and P91.02. For every newborn with the need for therapeutic hypothermia the consecutive term singleton newborn matched by gender, fetal presentation, delivery hospital, and the mode of delivery was selected as a control. Odds ratios (OR) between obstetric and delivery risk factors and the development of HIE were calculated. RESULTS: Eighty-eight cases with matched controls met the inclusion criteria during the study period. Maternal and infant characteristics among cases and controls were similar, but smoking was more common among cases (aOR 1.46, CI 1.14-1.64, p = 0.003). The incidence of preeclampsia, diabetes and intrauterine growth restriction in groups was equal. Induction of labour (aOR 3.08, CI 1.18-8.05, p = 0.02) and obstetric emergencies (aOR 3.51, CI 1.28-9.60, p = 0.015) were more common in the case group. No difference was detected in the duration of the second stage of labour or the delivery analgesia. CONCLUSIONS: Smoking, induction of labour and any obstetric emergency, especially shoulder dystocia, increase the risk for HIE and need for therapeutic hypothermia. The decisions upon induction of labour need to be carefully weighed, since maternal smoking and obstetric emergencies can hardly be controlled by the clinician.

Intimate partner violence during pregnancy and its association with birth asphyxia in hospitals of Tigray region, Ethiopia.

BACKGROUND: Birth asphyxia is the main cause of neonatal mortality and morbidity worldwide. Some studies indicate intimate partner violence during pregnancy is a risk factor for birth asphyxia. In Ethiopia, intimate partner violence during pregnancy is reported to be high. Despite this high prevalence, there is a lack of data about the association of birth asphyxia and intimate partner violence. The aim of this study was to assess the prevalence of intimate partner violence during pregnancy and its associated factors with birth asphyxia in health facilities in the Tigray region of northern Ethiopia. METHODS: This was an institutional-based cross-sectional study conducted at select health facilities in the Tigray region of Ethiopia. Random sampling technique was employed to select health facilities and systematic sampling was used to select 648 study participants. Data was entered by using Epi info version 3.5.1 and was analyzed using SPSS version 20. Bivariate and multivariate analysis was done to assess the association between exposure to intimate partner violence during pregnancy and birth asphyxia after adjusting for possible confounders. RESULTS: The prevalence of intimate partner violence during pregnancy was 47(7.3%). Eighty two (12.7%) babies were delivered with birth asphyxia. Intimate partner violence during pregnancy had a significant association with birth asphyxia, AOR (95% CI) = 4.4(2-9.8). In addition to this, other factors that were associated with birth asphyxia include place of residence [ AOR (95% CI) = 2.7(1.55-4.8)], age > 19 [AOR (95% CI) = 2.9(1.29-6.5)], age 20-35 [AOR (95% CI) = 3.1(1.06-9.3)], gestational age < 37 weeks [AOR(95% CI) = 7.2(3.5-14.8)] and low birth weight [AOR(95% CI) = 3.9(2.1-7.3)]. CONCLUSIONS: The prevalence of birth asphyxia in this study is high and is further increased by intimate partner violence during pregnancy. Health care providers and policy makers should take measures aimed at preventing intimate partner violence during pregnancy to reduce harm to the mother and adverse birth outcomes.

Magnitude of neonatal asphyxia and its predictors among newborns at public hospitals of Wolaita Zone in Southern Ethiopia, 2023.

BACKGROUND: Neonatal asphyxia is one of preventable causes of neonatal mortality throughout the world. It could be improved by early detection and control of the underlying causes. However, there was lack of evidence on it in the study setting. Thus, the aim of this study was to assess the magnitude and predictors of neonatal asphyxia among newborns at public hospitals of Wolaita Zone in Southern Ethiopia. METHOD: A facility-based cross-sectional study was done among 330 mothers with neonates in selected public hospitals. A systematic random sampling technique was used to select the study participants. Data were collected through an interviewer-administered questionnaire and checklist. The collected data were entered into EpiData version 4.6 and exported to SPSS version 26 for analysis. Logistic regression was fitted to examine the association between explanatory variables and outcome variable. In multivariable logistic regression, AOR with 95% CI was reported, and p < 0.05 was used to declare statistically significant variables. RESULTS: The magnitude of neonatal asphyxia was 26.4% with 95% CI: (21.8, 30.9). In multivariable logistic regression analysis primiparity (AOR = 2.63 95%CI 1.47, 4.72), low-birth-weight (AOR = 3.45 95%CI 1.33, 8.91), preterm birth (AOR = 3.58 95%CI 1.29, 9.92), and premature rupture of membranes (AOR = 5.19 95%CI 2.03, 13.26) were factors significantly associated with neonatal asphyxia. CONCLUSIONS: In this study, the magnitude of neonatal asphyxia was high. From the factors, premature rapture of the membrane, parity, birth weight of the newborn, and gestational age at birth were significantly associated with neonatal asphyxia. Attention should be given to early detection and prevention of neonatal asphyxia from complicated labor and delivery.

Incidence and development of validated mortality prediction model among asphyxiated neonates admitted to neonatal intensive care unit at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Northwest Ethiopia, 2021: retrospective follow-up study.

INTRODUCTION: Perinatal asphyxia is failure to maintain normal breathing at birth. World Health Organization indicates that perinatal asphyxia is the third major cause of neonatal mortality in developing countries accounting for 23% of neonatal deaths every year. At global and national level efforts have done to reduce neonatal mortality, however fatalities from asphyxia remains high in Ethiopia (24%). And there are no sufficient studies to show incidence and prediction of mortality among asphyxiated neonates. Developing validated risk prediction model is one of the crucial strategies to improve neonatal outcomes with asphyxia. Therefore, this study will help to screen asphyxiated neonate at high-risk for mortality during admission by easily accessible predictors. This study aimed to determine the incidence and develop validated Mortality Prediction model among asphyxiated neonates admitted to the Neonatal Intensive Care Unit at Felege-Hiwot Comprehensive Specialized Hospital, Bahir Dar, Ethiopia. METHOD: Retrospective follow-up study was conducted at Felege-Hiwot Comprehensive Specialized Hospital from September 1, 2017, to March 31, 2021. Simple random sampling was used to select 774 neonates, and 738 were reviewed. Since was data Secondary, it was collected by checklist. After the description of the data by table and graph, Univariable with p-value < 0.25, and stepwise multivariable analysis with p-value < 0.05 were done to develop final reduced prediction model by likelihood ratio test. To improve clinical utility, we developed a simplified risk score to classify asphyxiated neonates at high or low-risk of mortality. The accuracy of the model was evaluated using area under curve, and calibration plot. To measures all accuracy internal validation using bootstrapping technique were assessed. We evaluated the clinical impact of the model using a decision curve analysis across various threshold probabilities. RESULT: Incidence of neonatal mortality with asphyxia was 27.2% (95% CI: 24.1, 30.6). Rural residence, bad obstetric history, amniotic fluid status, multiple pregnancy, birth weight (< 2500 g), hypoxic-ischemic encephalopathy (stage II and III), and failure to suck were identified in the final risk prediction score. The area under the curve for mortality using 7 predictors was 0.78 (95% CI 0.74 to 0.82). With ≥ 7 cutoffs the sensitivity and specificity of risk prediction score were 0.64 and 0.82 respectively. CONCLUSION AND RECOMMENDATION: Incidence of neonatal mortality with asphyxia was high. The risk prediction score had good discrimination power built by rural residence, bad obstetric history, stained amniotic fluid, multiple pregnancy, birth weight (< 2500 g), hypoxic-ischemic encephalopathy (stage II and III), and failure to suck. Thus, using this score chart and improve neonatal and maternal service reduce mortality among asphyxiated neonates.

Predictors of neonatal mortality among neonates admitted to the neonatal intensive care unit at Hawassa University Comprehensive Specialized Hospital, Sidama regional state, Ethiopia.

BACKGROUND: Despite promising efforts, substantial deaths occurred during the neonatal period. According to estimates from the World Health Organization (WHO), Ethiopia is among the top 10 nations with the highest number of neonatal deaths in 2020 alone. This staggering amount makes it difficult to achieve the SDG (Sustainable Development Goals) target that calls for all nations to work hard to meet a neonatal mortality rate target of ≤ 12 deaths per 1,000 live births by 2030. We evaluated neonatal mortality and it's contributing factors among newborns admitted to the Neonatal Intensive Care Unit (NICU) at Hawassa University Comprehensive Specialized Hospital (HUCSH). METHODS: A hospital-based retrospective cross-sectional study on neonates admitted to the NICU from May 2021 to April 2022 was carried out at Hawassa University Comprehensive Specialized Hospital. From the admitted 1044 cases over the study period, 225 babies were sampled using a systematic random sampling procedure. The relationship between variables was determined using bivariate and multivariable analyses, and statistically significant relations were indicated at p-values less than 0.05. RESULTS: The magnitude of neonatal death was 14.2% (95% CI: 0.099-0.195). The most common causes of neonatal death were prematurity 14 (43.8%), sepsis 9 (28.1%), Perinatal asphyxia 6 (18.8%), and congenital malformations 3 (9.4%). The overall neonatal mortality rate was 28 per 1000 neonate days. Neonates who had birth asphyxia were 7.28 times more probable (AOR = 7.28; 95% CI: 2.367, 9.02) to die. Newborns who encountered infection within the NICU were 8.17 times more likely (AOR = 8.17; 95% CI: 1.84, 36.23) to die. CONCLUSION: The prevalence of newborn death is excessively high. The most common causes of mortality identified were prematurity, sepsis, perinatal asphyxia and congenital anomalies. To avert these causes, we demand that antenatal care services be implemented appropriately, delivery care quality be improved, and appropriate neonatal care and treatment be made available.

Determinants of speech and language delay among children aged 12 months to 12 years at Yekatit 12 Hospital, Addis Ababa, Ethiopia: a case-control study.

BACKGROUND: Speech and language delay among children can result in social interaction problems, attention difficulties, decreased writing and reading abilities, and poor cognitive and behavioral development. Despite the mounting prevalence of speech and language delays in Ethiopia, there is a lack of literature addressing the factors contributing to this delay. Consequently, this study aims to identify determinants of speech and language delay among children aged 12 months to 12 years at Yekatit 12 Hospital in Addis Ababa, Ethiopia. METHODS: We conducted an institutional-based at Yekatit 12 Hospital, unmatched case-control study with 50 cases and 100 controls aged 12 months to 12 years. Interviewer-administered questionnaires were used to collect data from the parents or caregivers of the participating children. Epi Info v7 was used for sample calculation, and SPSS v26 was used for analysis. The chi-square test was performed to determine the relationship between speech and language delay and determining factors, which was then followed by logistic regression. The significant determining factors were identified based on the adjusted odds ratio (AOR), with a 95% CI and p-value (< 0.05). RESULTS: Case group constituted 23 males and 27 females, totaling 50 children. Upon completing the multivariate analysis, birth asphyxia [AOR = 4.58, 95CI (1.23-16.99)], bottle-feeding [AOR = 4.54, 95CI (1.29-16.04)], mother-child separation [AOR = 2.6, 95CI (1.05-6.43)], multilingual family [AOR = 2.31, 95CI (1.03-5.18)], and screen time greater than two hours [AOR = 3.06, 95CI (1.29-7.28)] were found to be statistically significant determinants of speech and language delay. CONCLUSIONS: Our study found that birth asphyxia, bottle-feeding, mother-child separation, being from a multilingual family, and excessive screen time contribute significantly to speech and language delay. As a result, it is important to develop interventions that target these modifiable factors, while also ensuring that early diagnosis and treatment options are readily accessible.

Perinatal asphyxia does not influence presepsin levels in neonates: A prospective study.

AIM: To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. METHODS: In this prospective study, we enrolled 25 uninfected full-term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. RESULTS: In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut-off but not those of presepsin. CONCLUSION: In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased.

Risk factors associated with intraventricular hemorrhage in very-low-birth-weight premature infants.

PURPOSE: To analyze the association between risk factors and severe intraventricular hemorrhage (grade II-IV) in PNB under 1500 g. METHODS: Multicenter, retrospective, analytical, case-control study in PNB under 34 weeks and under 1500 g admitted to the NICU. CASE: PNB with severe intraventricular hemorrhage (grade II-IV). Logistic regression analysis was used to adjust for IVH-associated variables and odds ratios (OR). RESULTS: A total of 90 PNB files were analyzed, 45 cases and 45 controls. The highest risk factors for severe IVH were lower gestational age (OR 1.3, p < 0.001), perinatal asphyxia (OR 12, p < 0.001), Apgar < 6 at minute 1 and 5 (OR 6.3, p < 0.001). CONCLUSION: Lower gestational age, birth asphyxia, Apgar score lower of 6, and respiratory-type factors are associated with increased risk for severe IVH.

Qualitative Insights Into Enhancing Neonatal Resuscitation in Post-Pandemic Vietnam: A Stakeholder Perspective on the Helping Babies Breathe Program.

BACKGROUND: The neonatal phase is vital for child survival, with a substantial portion of deaths occurring in the first month. Neonatal mortality rates differ significantly between Vietnam (10.52/1000 live births) and the United States (3.27/1000). In response to these challenges, interventions such as the Helping Babies Breathe (HBB) program have emerged, aiming to enhance the quality of care provided during childbirth, and the postpartum period in low-resource settings. PURPOSE: The purpose of this study was to explore stakeholder perceptions of the HBB program in Vietnam postpandemic, aiming to identify requisites for resuming training. METHODS: Utilizing qualitative content analysis, 19 in-person semistructured interviews were conducted with diverse stakeholders in 2 provinces of Central Vietnam. RESULTS: The content analysis revealed following 5 main themes: (1) the pandemic's impact on HBB training; (2) resource needs for scaling up HBB training as the pandemic abates; (3) participants' perceptions of the pandemic's effect on HBB skills and knowledge; (4) the pandemic's influence on a skilled neonatal resuscitation workforce; and (5) future prospects and challenges for HBB training in a postpandemic era. IMPLICATIONS FOR PRACTICE AND RESEARCH: This research highlights the importance of sustainable post-HBB training competencies, including skill assessment, innovative knowledge retention strategies, community-based initiatives, and evidence-based interventions for improved healthcare decision-making and patient outcomes. Healthcare institutions should prioritize skill assessments, refresher training, and collaborative efforts among hospitals, authorities, non-government organizations, and community organizations for evidence-based education and HBB implementation.