[Vitamin D level in umbilical cord blood of late preterm infants and the effect of vitamin D3 supplementation on the behavioral development of infants and young children: a prospective randomized controlled study]. / æ™šæœŸæ—©äº§å„¿è„è¡€ç»´ç”Ÿç´ Dæ°´å¹³åŠç»´ç”Ÿç´ D3è¡¥å å¯¹å©´å¹¼å„¿è¡Œä¸ºå‘è‚²çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the level of 25 hydroxyvitamin D [25(OH)D] in late preterm infants and the effect of vitamin D3 supplementation on the neurobehavioral development of infants and young children. METHODS: In this prospective study, 161 late preterm infants who were admitted from June 2017 to June 2020 were enrolled. According to the level of 25(OH)D in umbilical cord blood, they were divided into three groups: sufficiency group (n=52), insufficiency group (n=53), and deficiency group (n=56). Each group was further divided into subgroup A (vitamin D3 800 IU/d) and subgroup B (individualized vitamin D3 supplementation) using a random number table. The levels of 25(OH)D were measured at 3 months after birth and at the corrected ages of 10 months and 18 months. The neurobehavioral development levels were determined by the Gesell Developmental Scale at the corrected ages of 10 months and 18 months. RESULTS: Within 24 hours and 3 months after birth, the insufficiency group and the deficiency group had a significantly lower level of 25(OH)D than the sufficiency group (P<0.05), and the insufficiency group had a significantly higher level of 25(OH)D than the deficiency group (P<0.05). In the deficiency group, subgroup B had a significantly higher level of 25(OH)D than subgroup A (P<0.05) at 3 months after birth. At the corrected ages of 10 months and 18 months, the insufficiency and deficiency groups had significantly lower scores of five functional areas of the Gesell Development Scale than the sufficiency group (P<0.05). Compared with the insufficiency group, the deficiency group had a significantly lower score of language at the corrected age of 10 months and a significantly lower score of gross motor at the corrected age of 18 months (P<0.05). Compared with subgroup A of the deficiency group, subgroup B had a significantly higher score of adaptive ability at the corrected age of 10 months and significantly higher scores of adaptive ability and response ability at the corrected age of 18 months (P<0.05). CONCLUSIONS: There is a significant difference in the level of 25(OH)D in umbilical cord blood in late preterm infants. Individualized vitamin D supplementation appears to be more effective for the treatment of vitamin D deficiency. Vitamin D level at birth and in early infancy has certain influence on neurobehavioral development.

Lung Ultrasound, a Better Choice for Neonatal Pneumothorax: A Systematic Review and Meta-analysis.

Neonatal pneumothorax is a life-threatening condition. Chest X-ray is the main diagnostic method but has some defects. Lung ultrasound has emerged as a diagnostic method in recent years. The aim of this review was to compare the diagnostic accuracy of lung ultrasound against chest X-ray in neonates with pneumothorax. We searched the Chinese journal full-text database, Wanfang database, China biomedical document service system, Weipu Chinese science and technology periodical full-text database, EMBASE, PubMed, The Cochrane Library and Web of Science (up to January 2020) for prospective studies on the diagnostic accuracy of lung ultrasound in neonates with pneumothorax. Statistical analysis was undertaken using Meta-DiSc software, version 1.4 (Romany Cajal Hospital, Madrid, Spain). The search returned 528 studies, of which 8 full texts were assessed for eligibility against the inclusion/exclusion criteria. The overall specificity and sensitivity of lung ultrasound in the diagnosis of neonatal pneumothorax was 98% (95% confidence interval [CI]: 0.94-0.99) and 99% (95% CI: 0.98-1.00), respectively. The diagnostic odds ratio was 920.01 (95% CI: 265.81-3184.33), and the area under the curve was 0.996 7 (Q* = 0.978 5). However, the chest X-ray was always taken as the reference standard with a sensitivity of 82% (95% CI: 0.72-0.90), a specificity of 96% (95% CI: 0.90-0.99) and a diagnostic odds ratio of 44.54 (95% CI: 4.30-460.98). Study analysis studies indicated that the sensitivity of lung ultrasound in diagnosing pneumothorax excepted chest X-ray as the single diagnosis criteria was 98% (95% CI: 0.93-1.00), the specificity was 100% (95% CI: 0.96-1.00) and the diagnostic odds ratio was 965.39 (95% CI: 161.195781.93), showing a higher accuracy than chest X-ray. In conclusion, lung ultrasound had better sensitivity and specificity than chest X-ray in the diagnosis of pneumothorax. Some ultrasonic signs (absence of lung sliding or B-lines) had a high sensitivity in the diagnosis, which could be used to diagnose pneumothorax. Lung point could help judge the severity of pneumothorax. Its presence indicates that pneumothorax is mild to moderate; otherwise, pneumothorax is severe.

Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus.

Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.

[Effect of PR-957 on the formation of A1 reactive astrocytes].

OBJECTIVE: To study the effect of PR-957 on the formation of A1 reactive astrocytes. METHODS: The cerebral cortices of 1-day-old female rats were obtained and cultured for primary astrocytes. These cells were divided into 3 groups: control, lipopolysaccharide (LPS), and LPS+PR-957. The LPS group was treated with LPS (at a concentration of 5 µmol/L) for 48 hours; the LPS+PR-957 group was treated with PR-957 (at a final concentration of 200 nmol/L) for 1 hour and then LPS for 48 hours. Enzyme-linked immunosorbent assay was used to determine the expression of complement 3 (C3, a marker for A1 reactive astrocytes) and tumor necrosis factor alpha (TNF-α). Quantitative real-time PCR was used to determine the relative mRNA expression of glypican-6 (GPC6), SPARC-like 1 (SPARCL1), and lipocalin-2 (LCN2). All the above experiments were repeated three times independently. RESULTS: C3 expression was almost not observed in the control group, but was observed in both the LPS group and the LPS+PR-957 group, with significantly lower expression observed in the LPS+PR-957 group (P<0.05). The expression of TNF-α was consistent with that of C3. Compared with the control group, the LPS and the PS+PR-957 groups had significantly reduced mRNA expression levels of GPC6 and SPARCL1 but significantly increased mRNA expression level of LCN2 (P<0.001). Compared with the LPS group, the LPS+PR-957 group had significantly increased mRNA expression levels of GPC6 and SPARCL1 but significantly reduced mRNA expression level of LCN2 (P<0.001). CONCLUSIONS: LPS can induce the transformation from astrocytes to A1 reactive astrocytes, and PR-957 can inhibit the formation of LPS-induced A1 reactive astrocytes.

Brain Injury in Neonatal Hypoglycemia: A Hospital-Based Cohort Study.

BACKGROUND: Neonatal hypoglycemia is more prevalent and can cause severe neurological sequelae. The objective of this study was to assess the patterns of neuroradiologic changes in neonatal hypoglycemia. METHODS: A retrospective cohort study was conducted on 66 neonatal hypoglycemia patients, and the magnetic resonance imaging (MRI) and clinical records were reviewed. RESULTS: Magnetic resonance imaging showed evidences of abnormality in 54.54% (36 of 66) of hypoglycemic infants. The most common abnormal findings were located on the parietal and occipital lobes of the brains. The number of days with hypoglycemia was significantly higher for abnormal MRI infants (P < .001), and prolonged/recurrent hypoglycemia was remarkably distinguished for abnormal MRI infants (P < .001). Patients with abnormal MRI findings did not have a lower blood glucose than infants without abnormal MRI findings (P > .05), but the lowest blood glucose was significantly lower for the patients with seizures (P < .01). CONCLUSIONS: The pattern of bilateral occipital cortical injury is the most common abnormality for neonatal hypoglycemia. The number of days with hypoglycemia, not the lower blood glucose, was significantly related to abnormal MRI infants.

[A review on the prevention and treatment of congenital cytomegalovirus infection in mothers and infants].

Human cytomegalovirus (HCMV) has a high infection rate worldwide, and 85%-90% of congenital cytomegalovirus (CMV) infections are asymptomatic at birth, with the clinical manifestations of hearing loss, psychomotor retardation, and learning disabilities, while 10%-15% are symptomatic infections. Some preterm infants develop CMV infection after birth, which can cause sepsis-like syndrome, thrombocytopenia, neutropenia, liver injury, and lung injury. However at present, women of childbearing age have a lack of awareness of CMV. CMV education and hygiene precautions for pregnant women can prevent CMV infections in themselves and congenital CMV infections in their infants. No definite results have been obtained from the studies on the effect of CMV vaccine and high-titer immunoglobulin in preventing congenital CMV infection in fetuses. Recent studies have confirmed that the specificity and sensitivity of urinary or salivary CMV-DNA detection have reached more than 98%, which contributes to the early diagnosis of congenital CMV infection. In addition to short-term treatment with ganciclovir, long-term treatment with oral valganciclovir is safe for symptomatic congenital CMV infection and appears to have a better clinical effect than the short-term treatment. In the future, it is necessary to strengthen the health education for pregnant women, enhance the mother-to-child management of CMV infection, conduct the research on CMV vaccine, and further standardize treatment regimens.

Congenital Hyperinsulinism in China: A Review of Chinese Literature Over the Past 15 Years.

OBJECTIVE: Congenital hyperinsulinism (CHI) is a rare but severe cause of hypoglycemia. The present study investigates the clinical presentation, therapeutic outcomes and genetic mutations of CHI in Chinese individuals over the past 15 years. METHODS: The authors retrospectively reviewed one case in their department and 206 cases reported from January 2002 to October 2016 in China. PubMed, Ovid Medline, Springer and Wanfang Database, CBMD database, and CKNI database were the sources used to collect the data. RESULTS: In total, 207 cases were recruited. Of these, the ages of 100 (48.3%) were within the 4th week after birth. Seventy-seven cases (37.2%) were born large for gestational age (LGA). Seizures occurred in 140 cases (67.6%). Among 140 cases (67.6%) who were administered diazoxide treatment, 90 (64.3%) were responsive. Seven cases (3.4%) received octreotide treatment and 19 cases (9.2%) underwent surgery. 63/129 cases (48.8%) were detected to have gene mutations, including ABCC8 (69.8%), KCNJ11 (12.7%), GLUD1, GCK, HADH, and HNF4A. Among the diazoxide-unresponsive cases, gene mutations were detected in 20/36 (55.6%) cases with ABCC8 and in 2 (5.6%) cases with KCNJ11. Among the diazoxide-responsive cases, gene mutations were detected in 8 patients with ABCC8, 4 with KCNJ11, 5 with GLUD1, and 1 with GCK. CONCLUSION: The present study indicates that most CHI cases occurred in neonates and that 1/3 of the cases were born LGA. ABCC8 and KCNJ11 are the most common gene mutations. More than half of the diazoxide-unresponsive CHI detected mutations are in ABCC8 and KCNJ11 genes. The GLUD1 gene mutations cause diazoxide-responsive CHI. Identifying the gene mutations can assist in the diagnosis and treatment of CHI.

Enterovirus infection in febrile neonates: A hospital-based prospective cohort study.

AIM: This study aims to investigate clinical characteristics and microbiological results and to assess the predictors for enterovirus infection in febrile neonates. METHODS: A prospective cohort study was conducted on 334 febrile patients (age: 0.33-28 days) in 2011-2012 years. Enterovirus RNA was detected by reverse transcription polymerase chain reaction on faeces or cerebrospinal fluid (CSF). Clinical characteristics were compared, and non-conditional logistic regression analysis was performed to determine independent predictors for enterovirus infection. RESULTS: There were 131 episodes of neonatal enterovirus infection (39.22%). Forty-eight (36.64%) developed respiratory symptoms, 69 (52.67%) had diarrhoea, 22 (16.79%) had poor feeding and 34 (25.95%) had rash. Eighteen (13.74%) had lower platelet counts, and CSF specimens were positive for enterovirus RNA in 44.27% (58/131) whose CSF revealed a mean white blood cell counts of 100.38 ± 147.97 cells/mm(3) (range: 2-668 cells/mm(3) ). The positivity of stool 38.92% (130/334) was significantly higher than that of CSF specimens 26.24% (58/221) for enterovirus RNA (P < 0.01). By logistic regression analysis, the following independently predicted enterovirus infection: abnormal CSF test (odds ratio (OR): 12.426, 95% confidence interval (CI): 5.633-27.413), thrombocytopenia (OR: 3.647, 95% CI: 1.312-10.136), duration of fever >3.25 (d) (OR: 2.293, 95% CI: 1.279-4.113), highest temperature >38.35 (°C) (OR: 2.094, 95% CI: 1.342-4.123) and negative bacterial culture (OR: 5.073, 95% CI: 1.504-17.114). CONCLUSIONS: Our data indicated that enteroviruses should be routinely considered in the differential diagnosis of febrile neonates. The factors, which may predict the risk of neonatal enterovirus infection, were abnormal CSF test, thrombocytopenia, duration of fever >3.25 (d), highest temperature >38.35 (°C) and negative bacterial culture.

[Risk factors for hearing impairment induced by cytomegalovirus infection].

OBJECTIVE: To investigate the risk factors for hearing impairment induced by cytomegalovirus (CMV) infection in children. METHODS: One hundred and fifty-eight children diagnosed with CMV infection were enrolled as subjects. Based on the results of the brainstem auditory evoked potential (BAEP) test, patients were classified into normal hearing group (n=117; BAEP≤35) and abnormal hearing group (n=41; BAEP>35). A retrospective analysis was performed on the general information, routine blood indices, liver function, copy number of CMV-DNA in urine and breast milk. The receiver operating characteristic (ROC) curve was used to predict the copy number of CMV-DNA resulting in abnormal BAEP. The Spearman rank correlation analysis was used to test the correlations of the copy number of CMV-DNA in urine with the degree of hearing impairment and platelet count. RESULTS: The incidence rates of platelet abnormality and abnormal liver function and the copy number of CMV-DNA in urine were significantly higher in the abnormal hearing group than in the normal hearing group (P<0.01). According to the ROC curve, the copy number of CMV-DNA in urine had a sensitivity of 46.3% and a specificity of 93.2% in predicting hearing impairment when it reached 1.415×10(6) per mL. The results of correlation analysis showed that the degree of hearing impairment was positively correlated with the copy number of CMV-DNA (r=0.382, P<0.01); the platelet count was negatively correlated with the copy number of CMV-DNA in urine (r=-0.233, P=0.003). CONCLUSIONS: An increased copy number of CMV-DNA in urine might be a risk factor for hearing impairment induced by CMV infection. Children are likely to have hearing impairment when the copy number of CMV-DNA reaches 1.415×10(6) per mL. The monitoring of hearing should be strengthened in CMV-infected children with a decreased platelet count.

[Vitamin A level and diseases of premature infants].

Vitamin A is a fat-soluble vitamin, and it is not only necessary for the normal growth and development of epithelial cells, but also plays a very important role in the normal growth and development of the retina, lungs, gastrointestinal tract, brain, and immune system. Studies have confirmed that the low level of vitamin A in premature infants at birth can last through the entire infancy. Recently, there have been particular concerns about the level of vitamin A and development of diseases in premature infants, with major focuses on the related mechanisms of action of vitamin A in respiratory distress syndrome, chronic lung disease, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus, and infections in premature infants, which still awaits further investigation.This paper summarizes and analyzes the current status of research on vitamin A level and diseases of premature infants at home and abroad. In addition, although enough evidence suggests that vitamin A supplementation is beneficial to preterm infants, evidence is still lacking for recommended methods for supplementation and dose of vitamin A, and further studies are needed.

Enterovirus infections are associated with white matter damage in neonates.

AIM: To explore the imaging findings of neonatal infants infected with enteroviruses. METHODS: A retrospective study was conducted on 12 patients who were diagnosed with encephalitis caused by enterovirus. Clinical presentation, cranial ultrasonography (cUS), magnetic resonance imaging (MRI) findings and neurodevelopment outcome of 12 cases were analysed. RESULTS: Twelve infants, with a gestational age of 35 to 39 weeks, presented at 36 to 41 weeks postmenstrual age with clinical symptoms of enterovirus infections. Ten of 12 neonatal infants had a fever and 4 of 12 presented with a sepsis-like illness. cUS in one preterm infant showed periventricular echogenicity. Neonatal MRI confirmed white matter changes in 12 infants. Follow-up of infants were 18 months. Outcome was variable with cerebral palsy in 2 infants and normal neurodevelopment outcome in 10 infants. CONCLUSIONS: Enterovirus may cause severe central nervous system infection in the neonatal period. The neuroimaging studies are informative and should be a part of care for infants with enteroviruses.

Neonatal diabetes mellitus in China: a case report and review of the Chinese literature.

To recognize the clinical characteristics and outcomes of neonatal diabetes mellitus (NDM), the authors retrospectively reviewed 1 NDM baby in their department and compared their data with 39 NDM cases reported in the available Chinese literature between January 1986 and December 2010. Most of the cases were located near the eastern and southern coasts of China, and clinical manifestation of 72.5% of the cases occurred in 4-week-old infants. Hyperglycemia and glycosuria findings were seen in all the patients and in 47.5% with intrauterine growth retardation. Moreover, 30.0% of the cases had polyuria, 52.5% had dehydration, and 47.5% had ketoacidosis. Cases with hyperglycemia, dehydration, and ketoacidosis recovered mostly. Ten NDM cases had persisted after 1 to 11 years of follow-up, 3 cases maintained normal blood sugar, and 7 cases had poor sugar control. NDM is a rare condition and early management includes fluid and insulin and later management depends on the transient or permanent nature of the condition.

Risk factors and outcomes for retinopathy of prematurity in neonatal infants with a birth weight of 1,501-2,000 g in a Chinese Neonatal Unit.

OBJECTIVE: To determine the risk factors and outcomes of retinopathy of prematurity (ROP) in infants with a birth weight of 1,501-2,000 g. MATERIALS AND METHODS: Clinical characteristics and risk factors were compared and nonconditional logistic regression analysis was performed to determine independent predictors for ROP. RESULTS: There were 54 (9.8%) cases of ROP in 553 patients with a birth weight of 1,501-2,000 g. The most common classification of ROP was in stage 1 (50/54, 92.6%; stages 2 and 3 ROP: 2 infants each). By logistic regression analysis, the following factors independently predicted ROP: gestational age at birth ≤ 34 weeks [odds ratio (OR): 9.01; 95% confidence interval (CI): 1.18-68.70], septicemia (OR: 2.88; 95% CI: 1.30-6.36) and perinatal asphyxia (OR: 5.74; 95% CI: 2.35-14.01). CONCLUSION: ROP occurred commonly among infants with a birth weight of 1,501-2,000 g. The risk factors were gestational age at birth ≤ 34 weeks, septicemia and perinatal asphyxia.

Early gestational intrauterine infection induces postnatal lung inflammation and arrests lung development in a rat model.

OBJECTIVE: In order to investigate the early gestational inflammation effect on the prenatal and postnatal lung development, identification of the proinflammatory cytokines (IL-1ß and TNF-α), genes implicated in angiogenesis (Vascular endothelial growth factor [VEGF], fms-like tyrosine kinase-1 [Flt-1], fetal liver kinase-1 [Flk-1]), and surfactant proteins (SPs) were observed. METHODS: Escherichia coli (E. coli) was inoculated into uterine cervix of pregnant rats at embryonic day 15 (E15) during pseudoglandular period of lung development and the control group was inoculated with normal saline. IL-1ß, TNF-α, VEGF, Flt-1, Flk-1, SP-A, and SP-B mRNA in pup's lung at E17, 19, 21 and postnatal day (P) 1, 3, 7, 14 were quantified by real-time RT-PCR. Western blot or immunohistochemistry analysis was also performed for the evaluation of VEGF, Flk-1, Flt-1, and SP-A expression in pup's lung. RESULTS: Compared with the control group, the fetal lung of the E. coli-treated group was more immature, the postnatal lung development was impaired marked by less alveoli, fewer secondary septa, and thicker alveolar wall. The lung weight and lung/body weight ratio were lower in the E. coli-treated group pups. IL-1ß and TNF-α mRNA were increased significantly in E. coli-treated pup's lung after birth, but no significant difference of IL-1ß and TNF-α mRNA levels in fetal lung were found between the two groups. SP-A expression was depressed at E17, E19, and E21 after intrauterine E. coli treated, accompanied with lower SP-B mRNA level at E19 and E21. Furthermore, intrauterine E. coli treated reduced the VEGF mRNA and protein levels in the fetal lung at E17 and E19, while the expression of Flt-1 and Flk-1 were higher at P7, P14 and P1, P7, P14, respectively, compared to the controls. CONCLUSIONS: These results suggested early gestational intrauterine E. coli infection could induce a postnatal pulmonary inflammation and might arrest the alveolarization in developing lung which was involved with the VEGF signaling. However, intrauterine E. coli infection could not induce the increase of proinflammatory cytokines in fetal lung and might fail to accelerate the maturation of fetal lung.

Intrauterine infection/inflammation and perinatal brain damage: role of glial cells and Toll-like receptor signaling.

The mechanisms or pathophysiology that leads to preterm brain damage including white matter damage during development are complex and not fully understood. Intrauterine infection/inflammation can significantly affect perinatal brain development and result in significant alterations in brain structure and function. Glial cells and Toll-like receptors (TLRs) are vital players in central nervous system immune response; dysregulation of this response plays an important role in brain damage. Intrauterine infection/inflammation has immunomodulatory effects and induces specific alterations in the TLRs response in many tissues. Recent findings indicate that intrauterine infection/inflammation could promote inflammatory processes in brain and in glial cells by up-regulating cytokines and inflammatory mediators, and by activating signaling pathways and transcriptional factors (nuclear factor-kappaB) implicated in inflammatory injury. TLRs may be involved in intrauterine infection-mediated inflammatory signaling, and intrauterine infection/inflammation could interfere with the TLR4 recruitment into the lipid rafts, leading to an effect on the TLR signaling transduction. In summary, current results suggest that TLRs are key mediators of intrauterine infection/inflammation induced preterm brain damage.

Neonatal lupus erythematosus: three case reports and review of the Chinese literature.

To recognize the clinical characteristics and outcomes of neonatal lupus erythematosus (NLE), the authors retrospectively review 3 NLE babies in their department and compared their data with 51 NLE cases reported in the available Chinese literature between January 1991 and December 2008. Most of the cases were located near the eastern coast of China, and clinical manifestation of 72.22% of the cases occurred in 2-week-old babies. Skin findings occurred in 94.44% of the patients, 12.96% with complete heart block (CHB), 22.22% with thrombocytopenia, and 14.81% with transient elevated transaminase levels. Cutaneous lesions, thrombocytopenia, and transaminase level showed improvement; 3 CHB cases had persisted after 7 to 10 years follow-up, and 1 case died in 5 months. Twenty-four (44.44%) pregnant woman with anti-Ro/SSA and/or anti-La/SSB antibodies are asymptomatic, and antibody status is first indicated when their child shows symptoms of NLE. Thus, all pregnant women should be screened for anti-Ro/ SSA and anti-La/SSB antibodies.

Notch signaling: key role in intrauterine infection/inflammation, embryonic development, and white matter damage?

The mechanisms or pathophysiologies that lead to cerebral white matter damage during development are complex and not fully understood. It is postulated that exposure of the preterm brain to inflammatory cytokines during intrauterine infection/inflammation contributes to brain white matter damage, and this damage may affect the function and differentiation of progenitor oligodendrocyte cells under physiological conditions. The Notch pathway, an important signaling pathway controlling various cells' differentiation, functions in the timing of oligodendrocyte differentiation, and Notch signaling may contribute to white matter damage and may mediate neurogenesis in a pathophysiological phase. Recent studies have led to recognition of the role of the Notch pathway in neurogenesis in cerebral ischemic damage and in myelination and axonal damage of neurodegenerative diseases. Moreover, Notch plays a critical role in steering an immune response toward inflammation by regulating expression of various cytokines and proinflammatory cytokines resulting in the activation of Notch signaling. Thus, the Notch signaling pathway likely plays a key role in intrauterine infection/inflammation, brain development, and white matter damage, and future research directed toward understanding its role will be important. Insofar as Notch signaling could have an important effect on neurogenesis, mobilization of progenitor cells is one strategy for compensating for the neuronal losses seen in white matter damage after intrauterine infection/inflammation.

Erythropoietin attenuates white matter damage, proinflammatory cytokine and chemokine induction in developing rat brain after intra-uterine infection.

To investigate the possible ameliorating effect of recombinant human erythropoietin (rhEPO) on white matter damage, pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine Escherichia coli infection. E. coli was inoculated into uterine cervix of the time-pregnant rats and the control was injected with normal saline. Following maternal E. coli inoculation, the pups received a single intraperitoneal injection of rhEPO at a dose of 5000 IU/kg body weight immediately after birth. Immunohistochemical staining and Western blot analysis for 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), neurofilament (NF) and glial fibrillary acidic protein (GFAP) were performed to assess white matter damage in pup brains at post-natal day 1 (P1), P3 and P7. Pro-inflammatory cytokines and chemokines were detected by real-time quantitative RT-PCR at the mRNA levels to evaluate the inflammatory response in pup brains at P1, P3 and P7. A single dose of rhEPO treatment (5000 IU/kg body weight) attenuated white matter damage in developing rat brain after intra-uterine E. coli infection. The protein levels of CNPase and NF in pup brains at P7 significantly increased after post-natal rhEPO treatment as compared with the intra-uterine E. coli-treated group. Also, post-natal rhEPO injection markedly attenuated the intra-uterine E. coli infection-induced increases in GFAP protein expression and the mRNA levels of pro-inflammatory cytokines and chemokines. Post-natal EPO administration as a single dose may exert a neuroprotective effect on white matter damage by reducing pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine E. coli infection.