Serum neuron-specific enolase, magnetic resonance imaging, and electrophysiology for predicting neurodevelopmental outcomes of neonates with hypoxic-ischemic encephalopathy: a prospective study.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality and morbidity. Effective indicators for the early diagnosis of brain injury after HIE and prognosis are lacking. This study aimed to examine the predictive value of serum neuron-specific enolase (NSE), amplitude-integrated electroencephalography (aEEG), and magnetic resonance imaging (MRI), alone and in combination, for the neurological outcomes in neonates with HIE. METHODS: Newborns with HIE born and treated at the Third Affiliated Hospital of An-Hui Medical University were consecutively included in this prospective cohort study (June 2013 to December 2020). Encephalopathy was classified as mild, moderate or severe according to Samat and Sarnat. All patients were assessed serum 1-day NSE and 3-day NSE levels after birth. The children were classified by neurological examination and Bayley Scales of Infant Development II at 18 months of age. ROC analysis was used to evaluate the predictive accuracy of the neurodevelopment outcomes. RESULTS: A total of 50 HIE neonates were enrolled (normal group: 32 (64.0%), moderate delay: 5 (10.0%), severe delay: 30(26.0%)) according to Bayley II scores. Serum 3-day NSE levels increased with worsening neurodevelopment outcomes (normal: 20.52 ± 6.42 µg/L vs. moderate: 39.82 ± 5.92 µg/L vs. severe: 44.60 ± 9.01 µg/L, P < 0.001). The MRI findings at 4-7 days after birth were significantly different among the three groups (P < 0.001). Forty-two (84.0%) children had abnormal aEEG. The combination of the three abnormalities combined together had 100% sensitivity, 97.70% specificity, 98.25% PPV, and 99.98% NPV. CONCLUSIONS: MRI, aEEG, and 3-day NSE can predict the neurological prognosis of newborns with HIE without hypothermia treatment. Their combination can improve the predictive ability for long-term neurobehavioral prognosis.

Neonatal myofibrillar myopathy type II associated with biallelic UNC-45B gene novel mutation and perinatal myasthenia as the core phenotype: A case report.

Myofibrillar myopathy (MFM) is characterized by phenotypic heterogeneity; decreased function of the myosin-directed chaperone, UNC-45B protein, leads to MFM II, which is characterized by slow progressive proximal myasthenia. Currently, only two studies have reported 11 cases worldwide. This study aimed to conduct genetic research and etiological analysis of a neonatal case of perinatal myasthenia who eventually died due to autonomic dyspnea. The case involved a newborn female admitted for weak cries and groaning. Physical examination revealed shallow and irregular spontaneous breathing, difficulty feeding, hip flexion and knee flexion in both lower limbs, hypotonia (level 1), less translation action, and inability to resist gravity. The child died at 23 days after birth. Gene testing, mutation analysis, and crystal structure analysis were conducted. Cell culture and plasmid construction were conducted, followed by western blot analysis. Pathological changes, including Z-line breakage, were observed in the muscle biopsies of different tissues. Gene testing showed that UNC-45B had a novel compound heterozygous mutation (c.2357T>A/p.Met786Lys, c.2591A>C/p.His864Pro), and in vitro functional experiments showed that the variants could lead to a decrease in protein expression. This study expands the UNC-45B mutation and phenotype spectrum by reporting an MFM II case in a Chinese patient for the first time.

[Association between maternal pre-pregnancy body mass index and adverse outcomes of late preterm infants].

OBJECTIVE: To study the association between maternal pre-pregnancy body mass index (BMI) and adverse outcomes of late preterm infants (LPI). METHODS: A total of 367 LPI who were born from January 2011 to December 2015 and admitted to the neonatal ward were enrolled. The BMI criteria for Chinese population were used to analyze the factors for maternal pre-pregnancy BMI and its association with adverse outcomes of LPI (1 minute Apgar score ≤7, delivery room resuscitation, hospitalization days after birth >7 days, and ventilation duration ≥6 hours). RESULTS: Of all LPIs, there were 64 LPI (17.4%) in the low maternal pre-pregnancy BMI group, 243 LPI (66.2%) in the normal maternal pre-pregnancy BMI group, and 60 LPI (16.4%) in the high maternal pre-pregnancy BMI group. Low pre-pregnancy BMI was the risk factor for 1 minute Apgar score ≤7 (OR=3.243, 95% CI: 1.102-9.546) and need for delivery room resuscitation (OR=3.492, 95%CI: 1.090-11.190), and high pre-pregnancy BMI was the risk factor for hospitalization days after birth >7 days (OR=1.992, 95%CI: 1.024-3.874). CONCLUSIONS: Abnormal maternal pre-pregnancy BMI has adverse effects on the outcomes of LPI. In order to reduce these adverse outcomes BMI should be controlled within the normal range in pregnant women.

Sex differences in brain MRI abnormalities and neurodevelopmental outcomes in a rat model of neonatal hypoxia-ischemia.

PURPOSE/AIM OF THE STUDY: Hypoxic-ischemic brain injury (HIBI) is associated with high mortality and neurodevelopmental deficits. We explored gender influence in a HIBI rat model. MATERIALS AND METHODS: Sprague-Dawley rats underwent HIBI on postnatal day (P) 7. Nervous reflexes, footprints, Morris water maze performances and magnetic resonance imaging (MRI) were analyzed. RESULTS: Mortality rate was higher in HIBI males (20%) than in females (12.5%). Growth rate was slower in the HIBI group (p < 0.05), but was similar between HIBI males and females. HIBI rats showed impaired performances in the cliff aversion reflex, negative geotaxis reflex and gait tests at P14 (p < 0.05), but not at P9 or P11. There were no significant differences for the cliff aversion reflex and gait tests between genders. Negative geotaxis reflex impairment at P14 was more severe in HIBI males (p < 0.05). Step length and toe distance contralateral (but not ipsilateral) to the cerebral damage were shorter in HIBI rats, and were shorter in HIBI males than females (p < 0.05). Morris water maze latency time and swimming distance were longer in the HI group than in controls, and prolonged in HIBI males compared with females (p < 0.05). In the HIBI group, MRI showed more severe injury at P10 and P67 in males than in females (p < 0.05). CONCLUSIONS: Male rats are more vulnerable to the detrimental consequences of HIBI, with more severe nervous reflex deficits, brain injury, memory impairment and hemiplegic paralysis than female rats. Serial neurobehavioral follow-up is still executed on the HIBI infants who is absent of detectable abnormalities in early children.

[Human umbilical cord blood mononuclear cell transplantation promotes long-term neurobehavioral functional development of newborn SD rats with hypoxic ischemic brain injury].

OBJECTIVE: To explore the effect of human umbilical cord blood mononuclear cells (UCBMC) promoting nerve behavior function and brain tissue recovery of neonatal SD rat with hypoxic ischemic brain injury (HIBI). METHOD: A modified newborn rat model that had a combined hypoxic and ischemic brain injury as described by Rice-Vannucci was used, early nervous reflex, the Morris water maze and walking track analysis were used to evaluate nervous behavioral function, and brain MRI, HE staining to evaluate brain damage recovery. RESULT: Newborn rat Rice-Vannucci model showed significant brain atrophy, obvious hemiplegia of contralateral limbs,e.g right step length [(7.67 ± 0.46) cm vs. (8.22 ± 0.50) cm, F = 1.494] and toe distance [(0.93 ± 0.06) cm vs. (1.12 ± 0.55) cm, F = 0.186] were significantly reduced compared with left side, learning and memory ability was significantly impaired compared with normal control group (P < 0.01); Cliff aversion [(8.44 ± 2.38) s vs.(14.22 ± 5.07) s, t = 4.618] and negative geotaxis reflex time [(7.26 ± 2.00) s vs. (11.76 ± 3.73) s, t = 4.755] on postnatal 14 days of HIBI+ transplantation group were significantly reduced compared with HIBI+NaCl group (P < 0.01) ; the Morris water maze experiment showed escape latency [ (23.11 ± 6.64) s vs. (34.04 ± 12.95) s, t = 3.356] and swimming distance [ (9.12 ± 1.21) cm vs.(12.70 ± 1.53) cm, t = 17.095] of HIBI+transplantation group were significantly reduced compared with those of HIBI+NaCl group (P < 0.01) ; the residual brain volume on postnatal 10 d [ (75.37 ± 4.53)% vs. (67.17 ± 4.08)%, t = -6.017] and 67 d [ (69.05 ± 3.58)% vs.(60.83 ± 3.69)%, t = -7.148]of HIBI+ transplantation group were significantly larger than those of HIBI+NaCl group (P < 0.01); After human UCBMC transplantation, left cortical edema significantly reduced and nerve cell necrosis of HIBI+ transplantation group is not obvious compared with HIBI+NaCl group. CONCLUSION: Human UCBMC intraperitoneal transplantation significantly promoted recovery of injured brain cells and neurobehavioral function development.