Survivors Of Hypoxic-ischemic Encephalopathy Research Articles

Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy

BackgroundInfants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE. MethodsInfants with HIE enrolled in a phase III trial underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years. ResultsOf 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 7%) were diagnosed with a genetic (n = 15) or congenital (n = 14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have death or NDI (75% vs 50%, P = 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs 13%, P = 0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies. ConclusionsAmong infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.

Patterns of neurobehavioral functioning in school-aged survivors of neonatal jaundice and hypoxic-ischemic encephalopathy in Kilifi, Kenya: A cross-sectional study

Background: Studies in high-income countries have reported that school-aged children who survive neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) develop long-term neurocognitive problems. However, less is known about the patterns of functioning in school-aged survivors of NNJ and HIE in sub-Saharan Africa. This study examined patterns of functioning in school-aged children who survived NNJ and HIE in Kilifi, Kenya. Methods: This is a cross-sectional study that included 107 survivors of NNJ/HIE (64 with NNJ, 43 with HIE), aged 6-12 years, admitted to Kilifi County Hospital on the Kenyan Coast. The Gross Motor Function Classification System (GMFCS), Adapted Communication Profile, Raven’s Coloured Progressive Matrices (RCPM) and an epilepsy screening tool were used to assess gross motor function, communication function, intellectual functioning, and epilepsy, respectively. Results: Most of the survivors of NNJ (95.2%) and HIE (95.3%) had no impairments in gross motor functioning. A small percentage of the children in the NNJ and HIE groups had profound problems in their communication (4.7% and 4.7%); expressive communication function (4.7% and 4.7%); social functions (3.1% and 2.3%); receptive communication (4.7% and 2.3%); and communicative effectiveness (4.7% and 2.3%). Cognitive impairment was reported in 10.9% and 11.9% for NNJ and HIE survivors, respectively. Active epilepsy was detected in 1.6% of survivors of NNJ and 2.3% of survivors of HIE. A subgroup of severe NNJ and HIE survivors without co-occurring conditions had the worst intellectual and active epilepsy outcomes. All children had normal hearing and visual functioning except one participant who presented with mild visual acuity problems. Conclusions: Most school-aged children who survive with NNJ and HIE have normal motor and communication function; however, one in ten are likely to present with lowered intellectual functioning compared to the normative sample.

The efficacy and safety of massage therapy as an adjuvant in the treatment of hypoxic ischemic encephalopathy in neonates: A protocol for systematic review and meta-analysis.

Background:Neonatal hypoxic-ischemic encephalopathy (HIE) has become a major problem that endangers the life and health of newborns. It is the most serious complication after neonatal asphyxia with a high mortality rate. Even survivors of HIE would suffer permanent neurological developmental impairment that seriously affects the growth and development in the future. Previous studies have shown that massage therapy can improve the prognosis of neonatal HIE. However, the efficacy of massage therapy on the growth, development, and sleep in neonates with HIE reported by various studies is inconsistent, which will be thoroughly assessed in this meta-analysis.Methods:Randomized controlled trials of massage therapy on the growth, development, and sleep neonates with HIE published before February 2022 will be retrieved from the PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Database, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, and Clinical Trial Register. Literature selection, data extraction, risk of bias assessment, and meta-analyses will be independently completed by 2 researchers. Meta-analysis will be performed by using RevMan5.4.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This systematic review provides a high-quality synthesis to assess the effect of massage therapy on growth, development, and sleep in neonates with HIE.OSF registration number:DOI 10.17605/OSF.IO/G9WXN.

Long-term neurocognitive and educational outcomes of neonatal insults in Kilifi, Kenya

BackgroundThere is little data on the long-term neurocognitive and educational outcomes among school-aged survivors of neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) in Africa.This study investigates the long-term neurocognitive and educational outcomes and the correlates of these outcomes in school-aged survivors of NNJ or HIE in Kilifi, Kenya.MethodsWe conducted a cross-sectional study on neurocognitive and educational outcomes among school-aged survivors (6–12 years) of NNJ (n = 134) and HIE (n = 107) and compared them to a community comparison group (n = 134). We assessed nonverbal intelligence, planning, working memory, attention, syntax, pragmatics, word-finding, memory, perceptual-motor, mathematical, and reading abilities. We also collected information on medical history, caregivers’ mental health, and family environment.ResultsThe survivors of NNJ had lower mean total scores in word-finding [F (1, 250) = 3.89, p = 0.050] and memory [F (1, 248) = 6.74, p = 0.010] than the comparison group. The survivors of HIE had lower mean scores in pragmatics [F (1, 230) = 6.61, p = 0.011] and higher scores higher scores in non-verbal reasoning [F (1, 225) =4.10, p = 0.044] than the comparison group. Stunted growth was associated with almost all the outcomes in HIE.ConclusionSurvivors of NNJ and HIE present with impairment in the multiple domains, which need to be taken into consideration in the planning of educational and rehabilitative services.

Cerebral Pulsed Arterial Spin Labeling Perfusion Weighted Imaging Predicts Language and Motor Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.

Rationale and Objectives: To compare cerebral pulsed arterial spin labeling (PASL) perfusion among controls, hypoxic ischemic encephalopathy (HIE) neonates with normal conventional MRI(HIE/MRI⊕), and HIE neonates with abnormal conventional MRI(HIE/MRI⊖). To create a predictive machine learning model of neurodevelopmental outcomes using cerebral PASL perfusion.Materials and Methods: A total of 73 full-term neonates were evaluated. The cerebral perfusion values were compared by permutation test to identify brain regions with significant perfusion changes among 18 controls, 40 HIE/MRI⊖ patients, and 15 HIE/MRI⊕ patients. A machine learning model was developed to predict neurodevelopmental outcomes using the averaged perfusion in those identified brain regions.Results: Significantly decreased PASL perfusion in HIE/MRI⊖ group, when compared with controls, were found in the anterior corona radiata, caudate, superior frontal gyrus, precentral gyrus. Both significantly increased and decreased cerebral perfusion changes were detected in HIE/MRI⊕ group, when compared with HIE/MRI⊖ group. There were no significant perfusion differences in the cerebellum, brainstem and deep structures of thalamus, putamen, and globus pallidus among the three groups. The machine learning model demonstrated significant correlation (p < 0.05) in predicting language(r = 0.48) and motor(r = 0.57) outcomes in HIE/MRI⊖ patients, and predicting language(r = 0.76), and motor(r = 0.53) outcomes in an additional group combining HIE/MRI⊖ and HIE/MRI⊕.Conclusion: Perfusion MRI can play an essential role in detecting HIE regardless of findings on conventional MRI and predicting language and motor outcomes in HIE survivors. The perfusion changes may also reveal important insights into the reperfusion response and intrinsic autoregulatory mechanisms. Our results suggest that perfusion imaging may be a useful adjunct to conventional MRI in the evaluation of HIE in clinical practice.

Abnormal heart rate variability at school age in survivors of neonatal hypoxic-ischemic encephalopathy managed with therapeutic hypothermia.

Major deficits in the autonomic nervous system function, detected by measuring heart rate variability (HRV), are reported in neonatal hypoxic-ischemic encephalopathy (HIE)). However, it is unknown if they will recover in the long-term. Because of the possible implications for the neurological outcome, this study aimed to evaluate the HRV at school age, in a cohort of children who survived HIE managed with therapeutic hypothermia. A cross-sectional study of HRV in 40 children: 20 HIE survivors and 20 healthy peers. All underwent 5-min plethysmography using the PPG Stress Flow device (BioTekna Italy). Absolute and normalized HRV spectral power in the very low frequency (VLF), low frequency (LF), and high frequency (HF) bands and total power were compared between patients and healthy children. The outcome evaluation included neurological, cognitive (WISC-IV), and psychosocial (Parent Stress Index-Short Form-PSI-SF and psychosocial interview) measures. All mean HRV values were significantly higher in survivors of HIE, compared to healthy peers, with the larger effect size for the HF band (Total Power 8.57±0.59 vs 7.82±0.77ms2, p .003 ES 0.21; HF 7.82+0.77 vs 8.57+0.59ms2, p .001EF 0.24). None of the children had major health, neurological and psychosocial (PSI-SF/interview) problems. The IQ (WISC-IV) was normal in 17/20 patients, borderline in 2, and <70 in 1. HRV measures highlight autonomic dysfunction at school age in survivors of neonatal HIE, in the absence of major neurodevelopmental and psychosocial problems. The significance of this finding for children's future life needs further neuropsychiatric investigations and longer follow-up.

Patterns of neurobehavioral functioning in school-aged survivors of neonatal jaundice and hypoxic-ischemic encephalopathy in Kilifi, Kenya: A cross-sectional study

Background: Studies in high-income countries have reported that school-aged children who survive neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) develop long-term neurocognitive problems. However, less is known about the patterns of functioning in school-aged survivors of NNJ and HIE in sub-Saharan Africa. This study examined patterns of functioning in school-aged children who survived NNJ and HIE in Kilifi, Kenya. Methods: This is a cross-sectional study that included 107 survivors of NNJ/HIE (64 with NNJ, 43 with HIE), aged 6-12 years, admitted to Kilifi County Hospital on the Kenyan Coast. The Gross Motor Function Classification System (GMFCS), Adapted Communication Profile, Raven’s Coloured Progressive Matrices (RCPM) and an epilepsy screening tool were used to assess gross motor function, communication function, intellectual functioning, and epilepsy, respectively. Results: Most of the survivors of NNJ (95.2%) and HIE (95.3%) had no impairments in gross motor functioning. A small percentage of the children in the NNJ and HIE groups had profound problems in their communication (4.7% and 4.7%); expressive communication function (4.7% and 4.7%); social functions (3.1% and 2.3%); receptive communication (4.7% and 2.3%); and communicative effectiveness (4.7% and 2.3%). Cognitive impairment was reported in 10.9% and 11.9% for NNJ and HIE survivors, respectively. Active epilepsy was detected in 1.6% of survivors of NNJ and 2.3% of survivors of HIE. All children had normal hearing and visual functioning except one participant who presented with mild visual acuity problems. Conclusions: Most school-aged children who survive with NNJ and HIE have normal motor and communication function; however, one in ten are likely to present with lowered intellectual functioning compared to the normative sample.

Patterns of neurobehavioral functioning in school-aged survivors of neonatal jaundice and hypoxic-ischemic encephalopathy in Kilifi, Kenya: A cross-sectional study

Background: Studies in high-income countries have reported that school-aged children who survive neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) develop long-term neurocognitive problems. However, less is known about the patterns of functioning in school-aged survivors of NNJ and HIE in sub-Saharan Africa. This study examined patterns of functioning in school-aged children who survived NNJ and HIE in Kilifi, Kenya. Methods: This is a cross-sectional study that included 107 survivors of NNJ/HIE (64 with NNJ, 43 with HIE), aged 6-12 years, admitted to Kilifi County Hospital on the Kenyan Coast. The Gross Motor Function Classification System (GMFCS), Adapted Communication Profile, Raven’s Coloured Progressive Matrices (RCPM) and an epilepsy screening tool were used to assess gross motor function, communication function, intellectual functioning, and epilepsy, respectively. Results: Most of the survivors of NNJ (95.2%) and HIE (95.3%) had no impairments in gross motor functioning. A small percentage of the children in the NNJ and HIE groups had profound problems in their communication (4.7% and 4.7%); expressive communication function (4.7% and 4.7%); social functions (3.1% and 2.3%); receptive communication (4.7% and 2.3%); and communicative effectiveness (4.7% and 2.3%). Cognitive impairment was reported in 10.9% and 11.9% for NNJ and HIE survivors, respectively. Active epilepsy was detected in 1.6% of survivors of NNJ and 2.3% of survivors of HIE. All children had normal hearing and visual functioning except one participant who presented with mild visual acuity problems. Conclusions: Most school-aged children who survive with NNJ and HIE have normal motor and communication function; however, one in ten are likely to present with lowered intellectual functioning compared to the normative sample.

Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy.

Background: Therapeutic hypothermia (TH) is the standard therapy for hypoxic-ischemic encephalopathy (HIE) and is associated with a wide range of physiological changes. Objective: We re-evaluated the effects of HIE and TH on bilirubin measurements following HIE in a center involved in the China cooling randomized controlled trial (RCT). Methods: Serial serum bilirubin concentrations measured during the first week of life were compared among the HIE + NT (normothermia) group, HIE + TH treatment group and control group (without HIE). Survivors of HIE were followed and assessed at approximately 2 years of age, and the results were correlated with peak bilirubin levels during the first week of life. Results: One hundred and thirty-eight infants were available for analysis. Significantly lower bilirubin levels were recorded in the HIE + NT group than in the controls (P<0.05). Significant differences were not observed among the patients in the HIE + NT group (mild to severe) or between the HIE + TH group and the HIE + NT group at any time point (P>0.05). The peak serum bilirubin concentrations recorded at 96 h of age showed a good correlation with the results of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) (P=0.02). Conclusion: Bilirubin potentially exerts a neuroprotective effect during the first week of life, and low temperature does not affect the possible antioxidant function of bilirubin during TH following HIE.

Early detection of neonatal hypoxic-ischemic white matter injury: an MR diffusion tensor imaging study.

The purpose of this study was to compare diffusion tensor metrics in normal age-matched neonates with survivors of hypoxic–ischemic encephalopathy (HIE) and extracorporeal membrane oxygenation (ECMO). Thirty-five normal, 27 HIE, and 13 ECMO infants underwent MRI at 3 T. Neurodevelopmental assessments were performed. Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) of the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, anterior commissure, genu corpus callosum and splenium of the corpus callosum, anterior and posterior limb of the internal capsule, superior longitudinal fasciculus, and the centrum semiovale were analyzed with tract-based spatial statistics modified for use in neonates. Linear regression analysis was performed, and 95% confidence intervals were created for age effects on the tensor metrics with the control patients. Two-sample t-test was done to determine whether there was a difference in the tensor metrics between the normal and patient cohort. There was a statistically significant age effect on the FA and RD in the selected regions of the brain (F<0.05) and a group difference in the FA and RD between the normal and the HIE group (P<0.05). The group difference in the FA and RD between the normal and ECMO groups was seen in the anterior commissure, genu corpus callosum, right inferior longitudinal fasciculus, fronto-occipital fasciculus, centrum semiovale, and superior longitudinal fasciculus (P<0.05). Patients who were outside the 95% confidence intervals of the FA, AD, and RD overlapped with those with abnormalities clinically and on the conventional MRI. In conclusion, diffusion tensor imaging can play a significant role in detecting infants with early indications of hypoxic–ischemic brain injury.