Early-onset neonatal sepsis as a risk factor for peri-intraventricular hemorrhage in premature infants / Sepse precoce como fator de risco para hemorragia peri-intraventricular em prematuros

ABSTRACT Objective: To assess early-onset sepsis as a risk factor of peri-intraventricular hemorrhage in premature infants born at less than or equal to 34 weeks' gestation and admitted to a neonatal intensive care unit (NICU). Methods: This retrospective cohort study included premature patients born at less than or equal to 34 weeks' gestation who were admitted to the NICU of a tertiary hospital in southern Brazil, and born from January 2017 to July 2021. Data were collected from patients' medical records. Early-onset sepsis was measured according to the presence or absence of diagnosis within the first 72 hours of life, whereas the outcome, peri-intraventricular hemorrhage, was described as the presence or absence of hemorrhage, regardless of its grade. Results: Hazard ratios were calculated using Cox regression models. A total of 487 patients were included in the study, of which 169 (34.7%) had some degree of peri-intraventricular hemorrhage. Early-onset sepsis was present in 41.6% of the cases of peri-intraventricular hemorrhage, which revealed a significant association between these variables, with increased risk of the outcome in the presence of sepsis. In the final multivariate model, the hazard ratio for early-onset sepsis was 1.52 (95% confidence interval 1.01-2.27). Conclusion: Early-onset sepsis and the use of surfactants showed to increase the occurrence of the outcome in premature children born at less than or equal to 34 weeks' gestation. Meanwhile, factors such as antenatal corticosteroids and gestational age closer to 34 weeks' gestations were found to reduce the risk of peri-intraventricular hemorrhage.

RESUMO Objetivo: O objetivo do presente trabalho foi avaliar a sepse precoce como fator de risco para hemorragia peri-intraventricular (HPIV) em prematuros com 34 semanas ou menos, admitidos em Unidade de Terapia Intensiva (UTI) Neonatal. Métodos: Este estudo de coorte retrospectivo incluiu pacientes prematuros com 34 semanas ou menos, que receberam alta da UTI Neonatal de hospital terciário, no sul do Brasil, nascidos no período de janeiro de 2017 a julho de 2021. Os dados foram coletados por meio dos prontuários desses pacientes. A sepse precoce foi mensurada conforme a presença ou a ausência do diagnóstico nas primeiras 72 horas de vida. Já o desfecho, hemorragia peri-intraventricular, foi descrito conforme a presença ou ausência da hemorragia, independentemente do grau. Resultados: Hazard ratios (HR) foram calculados por meio de modelos de regressão de Cox. Foram incluídos no estudo 487 pacientes. Destes, 169 (34,7%) apresentaram algum grau de hemorragia peri-intraventricular. A sepse precoce esteve presente em 41,6% dos casos de hemorragia peri-intraventricular e apresentou associação significativa, elevando o risco do desfecho quando presente. No modelo multivariável final, o HR para a sepse precoce foi de 1,52 (intervalo de confiança de 95% — IC95% 1,01-2,27). Conclusão: Sepse precoce e uso de surfactante demonstraram aumentar a ocorrência do desfecho em crianças prematuras até 34 semanas, enquanto fatores como corticoide antenatal e idades gestacionais mais próximas a 34 semanas mostraram reduzir o risco de ocorrência hemorragia peri-intraventricular.

Hipernatremia en pacientes con estado crítico por afecciones neurológicas

Fundamento: los trastornos del sodio son los más comunes y menos entendidos en pacientes con lesión cerebral aguda debido al papel principal que desempeña el sistema nervioso central en la regulación de la homeostasis del sodio y agua lo que puede llevar a complicaciones graves y resultados adversos, incluyendo la muerte. Objetivo: determinar la contribución a la mortalidad de la hipernatremia en pacientes con estado crítico por afecciones neurológicas. Métodos: estudio observacional analítico sobre 55 pacientes que ingresaron en las unidades de atención al grave del Hospital Universitario Arnaldo Milián Castro, entre octubre del 2020 y mayo del 2022, con independencia del valor del sodio plasmático a su admisión en el servicio, así como durante su estadía en las unidades de atención al grave. Se emplearon métodos estadísticos univariados y bivariados en el análisis de los datos. Resultados: el promedio de edad fue de 60±16 años. Los diagnósticos más relevantes fueron la hemorragia intraparenquimatosa (56,37 %), el trauma craneoencefálico y el accidente cerebrovascular isquémico (ambos 30 %). Las concentraciones plasmáticas de sodio mostraron diferencias significativas (pX2= 0,000), siendo la media mayor a las 24 horas de ingreso (174,2±133,6) y la menor al 5to día (102,9±72,9). Existió correlación significativa entre las concentraciones plasmáticas de sodio al ingreso ( 24 h y 72 h) y el estado al egreso. En el análisis bivariado individual por período, solo a las 24 horas hubo relación significativa, en este periodo la hipernatremia contribuyó a la mortalidad en 1,78 veces más que en aquellos que no tenían el sodio elevado (OR=1,78 con IC: 1,39-3,4). Conclusiones: la hipernatremia en el paciente con estado crítico por afecciones neurológicas se asocia con incremento de la mortalidad.

Background: sodium disorders are the most common and least understood in patients with acute brain injury due to the major role played by the central nervous system in regulating sodium and water homeostasis, which can lead to serious complications and adverse outcomes, including death. Objective: to determine the hypernatremia contribution to mortality in patients with neurological conditions in critical state. Methods: longitudinal analytical observational study on 55 patients who were admitted to the acute care units at the Arnaldo Milián Castro University Hospital, between October 2020 and May 2022, regardless of the plasma sodium value upon admission to the service, as well as during their stay in the critical care units. Univariate and bivariate statistical methods were used in data analysis. Results: the average age was 60 ± 16 years. The most relevant diagnoses were intraparenchymal hemorrhage (56.37%), head trauma, and ischemic stroke (both 30%). Plasma sodium concentrations showed significant differences (pX2= 0.000), with the highest average at 24 hours of admission (174.2 ± 133.6) and the lowest at the 5th day (102.9 ± 72.9). There was a significant correlation between plasma sodium concentrations at admission, 24h and 72h with the state at discharge. In the individual bivariate analysis by period, there was only a significant relationship after 24 hours. In this period, hypernatremia contributed 1.78 times more to mortality than in those who did not have elevated sodium (OR=1.78 with CI: 1,39-3,4). Conclusions: hypernatremia in critically ill patients with neurological conditions is associated with increased mortality.

Tamaño del léxico en niños(as) muy prematuros y prematuros extremos de 24 meses: un estudio transversal / Vocabulary size in very preterm and extremely preterm infants: a cross-sectional study

Las investigaciones muestran que un número importante de niños nacidos prematuros (antes de las 37 semanas de gestación) presentan dificultades en su desarrollo, entre ellas el desarrollo lingüístico. Las investigaciones previas indican que algunas complicaciones biomédicas, como la hemorragia intraventricular (los grados III y IV), la leucomalacia periventricular y la displasia broncopulmonar, incrementan la probabilidad de presentar alteraciones en el desarrollo de la cognición y/o del lenguaje, por lo que se hace necesario realizar investigaciones que proporcionen más información y con ello poder anticiparse a posibles consecuencias en los aprendizajes futuros de estos niños nacidos bajo la condición de prematuridad. Es así, que los objetivos de este estudio fueron medir el tamaño del léxico temprano en niños muy prematuros y prematuros extremos (con y sin complicaciones biomédicas) a los 24 meses de edad corregida, así como también determinar la asociación entre número de complicaciones biomédicas presentes y el tamaño del léxico. Para ello, se trabajó con 108 niños divididos en tres grupos: 39 niños prematuros de alto riesgo (con complicaciones biomédicas), 36 niños prematuros de bajo riesgo (sin complicaciones biomédicas asociadas a alteraciones del lenguaje y /o cognición) y 33 niños nacidos de término. Todos fueron evaluados con el Inventario II de Desarrollo de Habilidades Comunicativas MacArthur-Bates. Los resultados muestran que los niños nacidos de término tienen significativamente mayor tamaño del léxico que los prematuros, no existiendo diferencias en los resultados entre prematuros de bajo riesgo y los prematuros de alto riesgo. Por otra parte, el tamaño del léxico no presenta correlación con las complicaciones biomédicas.

Research shows that a significant number of children born preterm (before 37 weeks of gestation) have developmental difficulties, among them disturbances in language development. Studies indicate that some biomedical complications such as intraventricular hemorrhage (grades III and IV), periventricular leukomalacia, and bronchopulmonary dysplasia increase the probability of cognitive and/or language development disorders. Therefore, there is a need to conduct more studies that provide information that allows anticipating possible consequences in the learning process of children born prematurely. The aims of this study were to measure the early vocabulary size in very preterm and extremely preterm children (with and without biomedical complications) at 24 months of corrected age and to determine the association between the number of biomedical complications and vocabulary size. To that effect, we worked with 108 children divided into three groups: 39 high-risk preterm children (with biomedical complications), 36 low-risk preterm children (without biomedical complications associated with language and/or cognitive disturbances), and 33 full-term children. All children were evaluated using the MacArthur-Bates Communicative Development Inventory II. The results show that the vocabulary size of full-term children is significantly larger than that of preterm children and that no differences exist between the group of high-risk versus low-risk preterm children. On the other hand, vocabulary size does not correlate withbiomedical complications.

Dilated optic nerve sheath by ultrasound predicts mortality among patients with acute intracerebral hemorrhage / A bainha do nervo óptico dilatada na ultrassonografia prediz mortalidade na hemorragia intraparenquimatosa aguda

Abstract Background Intracerebral hemorrhage (ICH) is a deadly disease and increased intracranial pressure (ICP) is associated with worse outcomes in this context. Objective We evaluated whether dilated optic nerve sheath diameter (ONSD) depicted by optic nerve ultrasound (ONUS) at hospital admission has prognostic value as a predictor of mortality at 90 days. Methods Prospective multicenter study of acute supratentorial primary ICH patients consecutively recruited from two tertiary stroke centers. Optic nerve ultrasound and cranial computed tomography (CT) scans were performed at hospital admission and blindly reviewed. The primary outcome was mortality at 90-days. Multivariate logistic regression, ROC curve, and C-statistics were used to identify independent predictors of mortality. Results Between July 2014 and July 2016, 57 patients were evaluated. Among those, 13 were excluded and 44 were recruited into the trial. Their mean age was 62.3 ± 13.1 years and 12 (27.3%) were female. On univariate analysis, ICH volume on cranial CT scan, ICH ipsilateral ONSD, Glasgow coma scale, National Institute of Health Stroke Scale (NIHSS) and glucose on admission, and also diabetes mellitus and current nonsmoking were predictors of mortality. After multivariate analysis, ipsilateral ONSD (odds ratio [OR]: 6.24; 95% confidence interval [CI]: 1.18-33.01; p = 0.03) was an independent predictor of mortality, even after adjustment for other relevant prognostic factors. The best ipsilateral ONSD cutoff was 5.6mm (sensitivity 72% and specificity 83%) with an AUC of 0.71 (p = 0.02) for predicting mortality at 90 days. Conclusion Optic nerve ultrasound is a noninvasive, bedside, low-cost technique that can be used to identify increased ICP in acute supratentorial primary ICH patients. Among these patients, dilated ONSD is an independent predictor of mortality at 90 days.

Resumo Antecedentes A hemorragia intraparenquimatosa (HIP) aguda apresenta elevada morbimortalidade e a presença de hipertensão intracraniana (HIC) confere um pior prognóstico. Objetivo Avaliamos se a dilatação do diâmetro da bainha do nervo óptico (DBNO) através do ultrassom do nervo óptico (USNO) na admissão hospitalar seria preditora de mortalidade. Métodos Estudo multicêntrico e prospectivo de pacientes consecutivos com HIP supratentorial primária aguda admitidos em dois centros terciários. Ultrassom do nervo óptico e tomografia computadorizada (TC) de crânio foram realizados na admissão e revisados de forma cega. O desfecho primário do estudo foi a mortalidade em 3 meses. Análises de regressão logística, curva de característica de operação do receptor (ROC, na sigla em inglês) e estatística-C foram utilizadas para identificação dos preditores independentes de mortalidade. Resultados Entre julho de 2014 e julho de 2016, 44 pacientes foram incluídos. A idade média foi 62,3 (±13,1) anos e 12 (27,3%) eram mulheres. Na análise univariada, o volume da HIP na TC de crânio, DBNO ipsilateral à HIP, glicemia, escala de coma de Glasgow (ECG) e NIHSS na admissão hospitalar, e também diabetes mellitus e não-tabagista foram preditores de mortalidade. Após análise multivariada, o DBNO ipsilateral à HIP permaneceu como preditor independente de mortalidade (odds ratio [OR]: 6,24; intervalo de confiança [IC] de 95%: 1,18-33,01; p = 0,03). O melhor ponto de corte do DBNO ipsilateral como preditor de mortalidade em 3 meses foi 5,6mm (sensibilidade 72% e especificidade 83%) e área sob a curva (AUC, na sigla em inglês) 0,71 (p = 0,02). Conclusão O USNO é um método não-invasivo, beira-leito, de baixo custo, que pode ser empregado para estimar a presença de HIC em pacientes com HIP supratentorial primária aguda. A presença de DBNO dilatada é um preditor independente de mortalidade em 3 meses nesses pacientes.

Reference values for cerebral ventricular size in neonates with gestational age of 33 +0-41 +6 weeks / 中华围产医学杂志

Objective:To establish the reference values and neurological intervention cutoffs for cerebral ventricular size in neonates born at 33 +0-41 +6 weeks of gestation and to investigate the influential factors and reliability of the related indices. Methods:This study prospectively recruited 1 370 1-to 7-day neonates born or hospitalized at the Hunan Provincial Maternal and Child Health Care Hospital from February to August 2021. All the neonates, who were born between 33 +0 and 41 +6 weeks of gestation, were subjected to ultrasound scanning to obtain the indices, including ventricular index (VI), anterior horn width (AHW), thalamo-occipital distance (TOD), and ventricular height (VH). The reference value and neurological intervention cutoff for each index were set. Quantile regression was used to estimate the correlation between each index and continuous covariates [gestational age at birth (GA) and birth weight (BW)]. Mann-Whitney U test was used to analyze the differences in the medians of indices in different categorical covariates groups (males/females, left/right lateral ventricles, vaginal delivery/cesarean section, and singleton/multiple births). Intraclass correlation coefficient (ICC) calculated by a two-way mixed effect model and absolute agreement was used to access intra-rater reliability; ICC via a two-way random effect model and absolute agreement was utilized to rate inter-rater reliability (pool reliability: ICC below 0.50; moderate reliability: ICC between 0.50 and 0.75; good reliability: ICC between 0.75 and 0.90; excellent reliability: ICC exceeding 0.90). Results:The upper limits of reference values for AHW, TOD, VI, and VH in 555 (40.5%) preterm neonates were 2.7-3.5 mm, 20.9-22.5 mm, 12.6-13.7 mm, and 3.8-4.9 mm, and in 815 (59.5%) term newborns were 3.4-4.3 mm, 18.6-21.3 mm, 14.2-14.7 mm, and 3.4-3.8 mm, respectively. The cutoff of neurosurgical intervention for each index was the upper limit of reference value plus 4 mm. AHW median was positively correlated with GA [partial regression coefficient (PRC): 0.12, P<0.05], while TOD and VH medians were negatively correlated with GA (PRC:－0.31 and－0.06, both P<0.05). VI, AHW, and TOD medians were positively associated with BW (PRC: 0.46, 0.23, and 0.97, all P<0.05). The medians of VH, AHW, and TOD in the left cerebral ventricular exceeded those in the right cerebral ventricular, respectively (VH: 2.0 vs 1.8 mm, U=836 071.50; AHW: 1.8 vs 1.7 mm, U=874 141.50; TOD: 13.6 vs 12.5 mm, U=738 409.00, all P<0.05). The medians of AHW and VI in male neonates were greater than those in female newborns, respectively (AHW: 1.8 vs 1.7 mm, U=834 124.00; VI: 11.1 vs 10.8 mm, U=884 156.50, both P<0.05). The neonates delivered vaginally had greater AHW median, but smaller TOD median than those delivered by cesarean section (AHW: 2.0 vs 1.6 mm, U=685 546.00, P<0.001; TOD: 13.1 vs 12.9 mm, U=850 797.00, P=0.010). The AHW median in singleton newborns exceeded that in multiple births (1.9 vs 1.4 mm, U=356 999.00, P<0.001). The lower limits of 95% confidence intervals for intra-rater and inter-rater ICCs exceeded 0.75 and 0.50, respectively. Conclusion:Reference values and surgical intervention thresholds for VI, AHW, TOD, VH of newborns with a gestational age of 33 +0-41 +6 weeks were preliminarily established, and the reliability of these indicators were verified.

Risk factors of hydrocephalus secondary to severe intraventricular hemorrhage in preterm infants / 中国新生儿科杂志

Objective:To study the risk factors of secondary hydrocephalus after severe intraventricular hemorrhage (IVH) in preterm infants for prevention and early identification of post-hemorrhagic hydrocephalus (PHH).Methods:From June 2013 to June 2021, preterm infants with severe IVH admitted to our hospital were retrospectively analyzed. They were assigned into PHH group and non-PHH group. Rank sum test or chi-square test was used for comparison between the two groups and multivariate logistic regression analysis was used to analyze the risk factors of PHH in preterm infants.Results:A total of 246 preterm infants with severe IVH were enrolled, including 68 cases (27.6%) in the PHH group and 178 cases (72.4%) in the non-PHH group. Multivariate logistic stepwise regression analysis showed that male gender ( OR=2.014, 95% CI 1.063-3.817), gestational age ≤30 week ( OR=2.240, 95% CI 1.210-4.146), 5-min Apgar score ≤5 ( OR=3.980, 95% CI 1.483-10.685), placental abruption ( OR=2.940, 95% CI 1.324-6.531) were independent risk factors for PHH in preterm infants and thrombocytopenia was the protective factor for PHH in preterm infants ( OR=0.305, 95% CI 0.147-0.632). The incidence of moderate thrombocytopenia in non-PHH group was significantly higher than PHH group ( P<0.05). No significant differences existed in the incidences of mild and severe thrombocytopenia between the two groups ( P>0.05). Conclusions:Male gender, gestational age ≤30 week, 5-min Apgar score ≤5, placental abruption are risk factors for PHH in premature infants with severe IVH and moderate thrombocytopenia has protective effects.

Ventricular hemorrhage secondary to spontaneous intracerebral hemorrhage: pathophysiological, imaging evaluation and treatment / 国际脑血管病杂志

Intraventricular hemorrhage (IVH) accounts for about 3%-5% of all intracerebral hemorrhage, which can be divided into primary and secondary IVH. Primary IVH is mostly caused by choroid plexus vascular or subependymal artery rupture, and secondary IVH refers to spontaneous intracerebral hemorrhage that breaks into the ventricle and the prognosis was poor. This article reviews the pathophysiological mechanism, severity assessment, and treatment progress of secondary IVH.

Circular RNA hsa_circ_0087893 participates in intraventricular hemorrhage occurrence and progression possibly as a competitive endogenous RNA in preterm infants / 南方医科大学学报

OBJECTIVE@#To screen for differentially expressed circular RNAs (circRNAs) in the serum of preterm infants with intraventricular hemorrhage (IVH) and explore the competitive endogenous RNA (ceRNA) mechanism of circRNAs in IVH in these infants.@*METHODS@#Fifty preterm infants (gestational age of 28 to 34 weeks) admitted in our department between January, 2019 and January, 2020 were enrolled in this study, including 25 with a MRI diagnosis of IVH and 25 without IVH. Serum samples were collected from 3 randomly selected infants from each group for profiling differentially expressed circRNAs using circRNA array technique. Gene ontology (GO) and pathway analyses were performed to reveal the function of the identified circRNAs. The circRNA-miRNA-mRNA network was constructed to identify the co-expression network of hsa_circ_ 0087893.@*RESULTS@#A total of 121 differentially expressed circRNAs were identified in the infants with IVH, including 62 up-regulated and 59 down-regulated circRNAs. GO and pathway analyses showed that these circRNAs were involved in multiple biological processes and pathways, including cell proliferation, activation and death, DNA damage and repair, retinol metabolism, sphingolipid metabolism, cell adhesion molecules. Among these circRNAs, hsa_circ_0087893 was found to have significant down-regulation in IVH group and co-express with 41 miRNAs and 15 mRNAs (such as miR-214-3p, miR-761, miR-183-5p, AKR1B1, KRT34, PPP2CB, and HPRT1).@*CONCLUSION@#The circRNA hsa_circ_0087893 may function as a ceRNA and play an important role in the occurrence and progression of IVH in preterm infants.

Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks.@*METHODS@#PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis.@*RESULTS@#A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05).@*CONCLUSIONS@#Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

Cerebral hemodynamic monitoring and risk factors of severe intraventricular hemorrhage in extremely and very preterm infants: a case control study / 中国新生儿科杂志

Objective:To study the risk factors, cerebral hemodynamics and clinical outcomes of extremely and very preterm infants with severe intraventricular hemorrhage (IVH).Methods:From January 2019 to December 2019, premature infants with gestational age (GA) <32 w admitted to our hospital were assigned into severe IVH group and non-severe IVH group. Risk factors for severe IVH were analyzed. According to clinical outcomes, severe IVH group was further assigned into improvement subgroup and no-improvement subgroup. Cerebral hemodynamic parameters were compared between the two groups.Results:A total of 346 eligible neonates were enrolled in this study. The incidence of severe IVH was 11.0% (38 cases). The incidences of Grade Ⅲ and Ⅳ IVH were 8.7% (30/346) and 2.3% (8/346), respectively. Multivariate logistic regression analysis showed that CA < 28 w ( OR=4.365, 95% CI 1.055~18.054), 5 min Apgar score ≤7 ( OR=8.749, 95% CI 2.214~36.042), chorioamnionitis ( OR=3.245, 95% CI 1.127～9.344), PaCO 2 fluctuation within 1 h >25 mmHg ( OR=7.728, 95% CI 1.738~80.907) and vasoactive drugs usage ( OR=10.883, 95% CI 3.746~31.621) were the risk factors of severe IVH. 20 cases in severe IVH group were improved at discharge and 12 cases showed no improvement at discharge. Improvement subgroup showed quicker reduction of the middle cerebral artery flow resistance and faster recovery of the mean flow velocity than the no-improvement subgroup. Conclusions:GA <28 w, 5 min Apgar score ≤7, chorioamnionitis, PaCO 2 fluctuation within 1 h >25 mmHg and vasoactive drugs usage are risk factors of severe IVH in extremely and very preterm infants. Cerebral hemodynamic monitoring may provide initial assessment for the clinical outcomes for severe IVH.

Risk factors of periventricular-intraventricular hemorrhage in premature infants / 中国小儿急救医学

Objective:To analyze the potential risk factors of periventricular-intraventricular hemorrhage(PIVH)in premature infants.Methods:A retrospective study was conducted on clinical data of 279 premature infants admitted to the Affiliated Hospital of Guizhou Medical University From January 1, 2019 to December 31, 2019, who completed cranial ultrasound during hospitalization.According to the cranial ultrasound with or without PIVH, the cases were divided into PIVH group and non-PIVH group.The premature infants with PIVH were divided into severe PIVH(grade Ⅲ and Ⅳ)group and mild PIVH(grade Ⅰand Ⅱ)group according to the PIVH grades.A total of 25 factors, which may influnce PIVH, were analyzed by univariate analysis, and then multivariate Logistic stepwise regression analysis(stepwise backwards method)was performed to determine the major risk factors.Results:(1)A total of 279 premature infants were included in the study, 133 of them in PIVH group, and 146 of them in non-PIVH group.Univariate analysis showed that there were statistically significant differences in 14 factors between two groups, including full treatment of antenatal steroid, gestation age, birth weight, neonatal asphyxia, hypothermia, early onset sepsis, metabolic acidosis, hypernatremia, anemia, respiratory distress syndrome, noninvasive ventilation, invasive ventilation, invasive ventilation within 72 hours after birth, and lumbar puncture within 72 hours after birth( P<0.05). Multivariate analysis showed that gestational age( OR=0.709, 95% CI 0.602-0.835), and full treatment of antenatal steroid( OR=0.354, 95% CI 0.189-0.664) were protective factors for PIVH in premature infants, while neonatal asphyxia( OR=2.425, 95% CI 1.171-5.023), hypothermia( OR=2.097, 95% CI 1.088~4.041), early onset sepsis( OR=12.898, 95% CI 1.433-115.264), metabolic acidosis( OR=2.493, 95% CI 1.398-4.442), invasive ventilation within 72 hours after birth( OR=5.408, 95% CI 1.156-25.297), lumbar puncture within 72 hours after birth ( OR=5.035, 95% CI 1.269-19.993) were independent risk factors for PIVH in premature infants( P<0.05). (2) Among 133 cases of premature PIVH, 20 cases were severe PIVH and 13 cases were mild PIVH.Univariate analysis showed that there were statistically significant differences in 5 factors between two groups, including antenatal magnesium sulfate, gestation age, early onset sepsis, abnormal coagulation, and lumbar puncture within 72 hours after birth.Multivariate analysis showed that early onset sepsis( OR=4.392, 95% CI 1.343-14.367) and abnormal coagulation( OR=3.502, 95% CI 1.234-9.867) were independent risk factors for severe PIVH in premature infants( P<0.05). Conclusion:Gestational age is negatively correlated with the occurrence of PIVH in premature infants, and completion of more than a course of treatment for antenatal dexamethasone is an independent protective factor of PIVH in premature infants.Neonatal asphyxia, metabolic acidosis, hypothermia(<35 ℃), early onset sepsis, invasive ventilation within 72 hours after birth, and lumbar puncture within 72 hours after birth are independent risk factors for PIVH in premature infants.Abnormal coagulation and early onset sepsis are independent risk factors for severe PIVH in premature infants.

Risk factors of periventricular-intraventricular hemorrhage in premature infants / 中国小儿急救医学

Objective:To analyze the potential risk factors of periventricular-intraventricular hemorrhage(PIVH)in premature infants.Methods:A retrospective study was conducted on clinical data of 279 premature infants admitted to the Affiliated Hospital of Guizhou Medical University From January 1, 2019 to December 31, 2019, who completed cranial ultrasound during hospitalization.According to the cranial ultrasound with or without PIVH, the cases were divided into PIVH group and non-PIVH group.The premature infants with PIVH were divided into severe PIVH(grade Ⅲ and Ⅳ)group and mild PIVH(grade Ⅰand Ⅱ)group according to the PIVH grades.A total of 25 factors, which may influnce PIVH, were analyzed by univariate analysis, and then multivariate Logistic stepwise regression analysis(stepwise backwards method)was performed to determine the major risk factors.Results:(1)A total of 279 premature infants were included in the study, 133 of them in PIVH group, and 146 of them in non-PIVH group.Univariate analysis showed that there were statistically significant differences in 14 factors between two groups, including full treatment of antenatal steroid, gestation age, birth weight, neonatal asphyxia, hypothermia, early onset sepsis, metabolic acidosis, hypernatremia, anemia, respiratory distress syndrome, noninvasive ventilation, invasive ventilation, invasive ventilation within 72 hours after birth, and lumbar puncture within 72 hours after birth( P<0.05). Multivariate analysis showed that gestational age( OR=0.709, 95% CI 0.602-0.835), and full treatment of antenatal steroid( OR=0.354, 95% CI 0.189-0.664) were protective factors for PIVH in premature infants, while neonatal asphyxia( OR=2.425, 95% CI 1.171-5.023), hypothermia( OR=2.097, 95% CI 1.088~4.041), early onset sepsis( OR=12.898, 95% CI 1.433-115.264), metabolic acidosis( OR=2.493, 95% CI 1.398-4.442), invasive ventilation within 72 hours after birth( OR=5.408, 95% CI 1.156-25.297), lumbar puncture within 72 hours after birth ( OR=5.035, 95% CI 1.269-19.993) were independent risk factors for PIVH in premature infants( P<0.05). (2) Among 133 cases of premature PIVH, 20 cases were severe PIVH and 13 cases were mild PIVH.Univariate analysis showed that there were statistically significant differences in 5 factors between two groups, including antenatal magnesium sulfate, gestation age, early onset sepsis, abnormal coagulation, and lumbar puncture within 72 hours after birth.Multivariate analysis showed that early onset sepsis( OR=4.392, 95% CI 1.343-14.367) and abnormal coagulation( OR=3.502, 95% CI 1.234-9.867) were independent risk factors for severe PIVH in premature infants( P<0.05). Conclusion:Gestational age is negatively correlated with the occurrence of PIVH in premature infants, and completion of more than a course of treatment for antenatal dexamethasone is an independent protective factor of PIVH in premature infants.Neonatal asphyxia, metabolic acidosis, hypothermia(<35 ℃), early onset sepsis, invasive ventilation within 72 hours after birth, and lumbar puncture within 72 hours after birth are independent risk factors for PIVH in premature infants.Abnormal coagulation and early onset sepsis are independent risk factors for severe PIVH in premature infants.

Impact of bundle implementation on the incidence of peri/intraventricular hemorrhage among preterm infants: a pre-post interventional study

ABSTRACT BACKGROUND: Peri/intraventricular hemorrhage (PIVH) is a frequent cause of death and morbidity among preterm infants. Few studies have addressed the use of bundles for preventing PIVH. OBJECTIVE: To evaluate the efficacy of a bundle of interventions designed to decrease the incidence of intraventricular hemorrhage at hospital discharge among preterm infants. DESIGN AND SETTING: Pre-post interventional study with retrospective and prospective data collection performed before and after bundle implementation in the neonatal intensive care unit of a university hospital. METHODS: Infants with gestational age < 32 weeks without malformations, who survived > 6 days were included. The bundle consisted of the following actions during the first 72 hours of life: maintenance of head in neutral position with the body in supine position, minimal handling, including delay of lumbar puncture until after 72 hours and absence of respiratory therapy maneuvers. Cranial ultrasound was performed on days 3, 7 and 28, or later if needed. The effect of the bundle was analyzed through logistic regression and results were adjusted for confounding variables. RESULTS: 167 infants met the inclusion criteria; 146 (87%) were analyzed. Bundle implementation was associated with decreased chances of PIVH at hospital discharge (odds ratio 0.29; 95% confidence interval 0.13-0.65). Cerebrospinal fluid collection within the first 72 hours increased the odds of PIVH of any grade during the hospital stay fourfold, after adjustment for all variables included in the model. CONCLUSION: Implementation of a bundle of interventions to avoid intraventricular hemorrhage was effective for decreasing the incidence of all grades of PIVH in preterm infants.

Hemorragia intraventricular en prematuros menores de 28 semanas en un hospital general de Lima, 2013 - 2017 / Intraventricular hemorrhage in premature infants under 28 weeks in general hospital of Lima, 2013 - 2017

RESUMEN: Objetivo : Determinar la incidencia y características clínicas de la hemorragia intraventricular (HIV) en los prematuros menores de 28 semanas, nacidos en un hospital general. Material y Métodos : Estudio observacional, descriptivo, longitudinal, de cohorte retrospectiva, que incluyó a los prematuros menores de 28 semanas gestacionales (PT28), que sobrevivieron al primer día de vida, examinados con ecografía cerebral y atendidos en la unidad neonatal del Hospital Cayetano Heredia del 2013 al 2017. Se excluyeron los neonatos con malformaciones cerebrales, y aquellos con datos perinatales incompletos. Resultados : Se identificaron 84 PT28, de los cuales se incluyeron 72, doce fueron excluidos por malformaciones y falta de datos. La relación varón/ mujer fue 1.6. La frecuencia de HIV fue de 58.3% (42/72). En la forma temprana se encontraron 52.4% (22/42) y en la tardía 47.6% (20/42). Los grados severos se presentaron en el 64% (27/42). La hidrocefalia posthemorrágica ocurrió en 26% (11/42) y el infarto hemorrágico venoso en 21.4% (9/42). Fallecieron 51 pacientes, con una tasa de letalidad del 76.1% (32/42). Conclusiones : La HIV fue muy frecuente, severa y letal en los PT28, la mitad de los casos ocurrieron en los primeros tres días y el resto durante las dos primeras semanas de vida. Los factores asociados fueron el menor peso de nacimiento, el trabajo de parto y el neumotórax.

ABSTRACT: Objective : To determine the incidence and clinical characteristics of intraventricular hemorrhage (IVH) in premature infants younger than 28 weeks, born in a general hospital. Material and Methods : Observational, descriptive, longitudinal, retrospective cohort study, which included premature infants less than 28 weeks gestational (PT28), who survived the first day of life, examined with brain ultrasound and cared for in the neonatal unit of Hospital Cayetano Heredia del 2013 to 2017. Neonates with brain malformations and those with incomplete perinatal data were excluded. Results : 84 PT28 were identified, of which 72 were included, twelve were excluded due to malformations and lack of data. The male / female ratio was 1.6. The frequency of HIV was 58.3% (42/72). 52.4% (22/42) were found in the early form and 47.6% (20/42) in the late form. Severe grades were present in 64% (27/42). Posthemorrhagic hydrocephalus occurred in 26% (11/42) and venous hemorrhagic infarction in 21.4% (9/42). 51 patients died, with a fatality rate of 76.1% (32/42). Conclusions : HIV was very frequent, severe and lethal in the TST28, half of the cases occurred in the first three days and the rest during the first two weeks of life. Associated factors were lower birth weight, labor, and pneumothorax.

Riesgo de daño cerebral en prematuros menores de 34 semanas expuestos a corioamnionitis histológica, Lima, Perú / Risk of brain damage in premature infants under 34 weeks of gestational age exposed to histological chorioamnionitis Lima, Peru

RESUMEN Objetivos: Evaluar el riesgo de daño cerebral en prematuros menores de 34 semanas expuestos a corioamnionitis histológica (CAH). Materiales y métodos: Se realizó un estudio de cohortes en el Hospital Cayetano Heredia, durante el 2015. Fueron incluidos prematuros menores de 34 semanas que tuvieran examen histopatológico de la placenta. Los tipos de CAH evaluados fueron subcorionitis, corionitis, corioamnionitis, con o sin funisitis. El daño cerebral se evaluó en tres periodos de edad, entre 0 y 7 días, entre 7 y 30 días y a las 40 semanas gestacionales corregidas. Se realizó un seguimiento neurológico y controles con ecografía cerebral. Resultados: Se estudiaron 85 prematuros, 47,1% eran mujeres y la media de la edad gestacional fue de 30,9 semanas. El 42% (36/85) nacieron expuestos a CAH. La ruptura prematura de membrana fue la principal generatriz de sepsis, y la sepsis se relacionó con daño neurológico. La CAH estuvo asociada con hemorragia intraventricular (HIV) durante la primera semana y con lesiones de la sustancia blanca entre los 7 y 30 días de edad (p = 0,035). El tipo corioamnionitis de CAH se asoció al daño neurológico durante la primera semana (RR = 2,11; IC 95%: 1,09-4,11) y entre los 7 y 30 días de vida (RR = 2,72; IC 95%: 1,07-6,88). Conclusiones: La corioamnionitis fue un factor de riesgo para desarrollar lesiones cerebrales en prematuros menores de 34 semanas, para HIV durante los primeros 7 días y lesiones de sustancia blanca entre los 7 y los 30 días de edad. A las 40 semanas de edad corregida, los prematuros extremos con CAH tuvieron lesiones cerebrales más extensas.

ABSTRACT Objectives: To assess the risk of brain damage in premature infants under 34 weeks of gestational age exposed to histological chorioamnionitis (HCA). Materials and methods: A cohort study was conducted at the Hospital Cayetano Heredia, during 2015. Premature infants under 34 weeks of gestational age, who had histopathological examination of the placenta, were included. The types of HCA evaluated were sub-chorionitis, chorionitis, chorioamnionitis, with or without funisitis. Brain damage was evaluated in three age periods, between 0 and 7 days, between 7 and 30 days and at 40 weeks of corrected gestational age. A neurological follow-up and regular controls were performed with brain ultrasound. Results: A total of 85 premature infants were included, 47.1% were women and the mean gestational age was 30.9 weeks. From the total, 42% (36/85) were born exposed to HCA. Premature rupture of membranes was the main cause of sepsis, which was related to neurological damage. HCA was associated with intraventricular hemorrhage (IVH) during the first week and with white matter lesions between 7 and 30 days of age (p = 0.035). The chorioamnionitis type of HCA was associated with neurological damage during the first week (RR = 2.11, 95% CI: 1.09-4.11) and between 7 and 30 days of age (RR = 2.72, 95% CI: 1.07-6.88). Conclusions: Chorioamnionitis was a risk factor for developing brain injuries in premature infants under 34 weeks of gestational age. It was also a risk factor for HIV during the first 7 days and for white matter injuries between 7 and 30 days of age. At 40 weeks of corrected gestational age, extreme premature infants with HCA had more extensive brain damage.

Aspectos desconocidos de la relación entre el sistema de grupo sanguíneo ABO y las morbilidades en prematuros / Unknown aspects of the relationship between ABO blood group system and preterm morbidities

Objetivos. Se ha demostrado, en diversos estudios llevados a cabo en adultos, que los grupos sanguíneos desempeñan un papel importante en muchas enfermedades. El objetivo fue investigar si hay una relación entre las morbilidades y el sistema de grupos sanguíneos ABO en lactantes prematuros.Metodología. En este estudio de cohorte retrospectivo, se incluyó a recién nacidos prematuros que habían nacido con menos de 32 semanas de gestación y con un peso al nacer inferior a 1500 g. Se los agrupó por grupo sanguíneo (0, A, B, AB) y por morbilidades de la prematurez y se los comparó.Resultados. Se analizaron los datos de 1785 recién nacidos prematuros de muy bajo peso al nacer. La comparación entre los grupos sanguíneos A y no A reveló que los lactantes de grupo sanguíneo A tenían una incidencia más alta de conducto arterial persistente (CAP) (48,7 % frente a 39,7 %, p = 0,005) y displasia broncopulmonar (DBP) (27 % frente a 20,8 %, p = 0,04), mientras que la incidencia de la hemorragia intraventricular de grado ≥3 era más baja (5,1 % frente a 10,1 %, p = 0,006).Conclusión. Este estudio es la primera y más grande investigación sobre la relación entre los grupos sanguíneos y las morbilidades en los prematuros. Con estos resultados se demuestra que el grupo sanguíneo A podría ser un factor de riesgo de CAP y DBP

Objectives. Blood groups have been shown to play an important role in a lot of diseases in various studies conducted in adults. The objective was to investigate whether there is a relationship between morbidities and ABO blood groups system in preterm infants.Methodology. This retrospective cohort study included preterm neonates born at < 32 weeks of gestation with a birth weight < 1500 g. Neonates were grouped by blood type (O, A, B, AB) and morbidities of prematurity were compared among these groups. Results. Data pertaining to 1785 very low birth weight preterm neonates were analyzed. Comparison of the A and non-A blood groups revealed that infants with blood group A had significantly higher incidence of patent ductus arteriosus (PDA) (48.7 % vs. 39.7 %, p = 0.005) and bronchopulmonary dysplasia (BPD) (27 % vs. 20.8 %, p = 0.04), while the incidence of grade ≥ 3 intraventricular hemorrhage was lower (5.1 % vs. 10.1 %, p = 0.006).Conclusion. This study represents the first and biggest series examination of the relationship between blood groups and preterm morbidities. Our results show that blood group A may be a risk factor for PDA and BPD.

Anterior Communicating Artery Aneurysm Uncommon Hemorrhagic Presentation: Case Report

Intracranial aneurysm rupture causes subarachnoid hemorrhage in 80% of the cases, and it may be associated with intracerebral hemorrhage and/or intraventricular hemorrhage (IVH) in 34% and 17% of the patients, respectively. However, on rare occasions, aneurysm rupturemay be present causing isolate intracerebral hemorrhage or IVH without subarachnoid hemorrhage. We describe an unusual case of an anterior communicating aneurysm rupture presented with IVH, without subarachnoid hemorrhage. Although isolated IVH is rare, aneurysm rupture is a possible condition. Patients presenting with head computed tomography revealing IVH without subarachnoid hemorrhage should be promptly investigated with contrasted image exam to identify and treat possible causes, even in the absence of subarachnoid hemorrhage.

Preterm infants with peri/intraventricular hemorrhage have poorer habituation responses to external stimuli / Neonatos prematuros com hemorragia peri-intraventricular apresentam respostas de habituação piores a estímulos externos

ABSTRACT Objective: To evaluate the association between intra-ventricular hemorrhage and habituation responses to external stimuli in preterm infants at 36-38 weeks post-conceptual age. Methods: Cross-sectional study of infants with gestational age <32 weeks. Intra-ventricular hemorrhage was identified by cranial ultrasonography and classified according to Papile et al. (1978). The luminous (flashlight), sound (rattle, bell), and tactile stimuli were presented, and the responses were scored according to Lester and Tronik (2004). Habituation response scores were compared between groups by Student's t-test. The association between IVH and habituation scores was evaluated by linear regression adjusted for GA, clinical severity score, post-conceptual age at habituation assessment, sepsis, and bronchopulmonary dysplasia. Results: Sixty-five infants were studied, 20 with intra-ventricular hemorrhage (16 grades I/II; four grades III/IV) and 45 without intra-ventricular hemorrhage. Infants with intra-ventricular hemorrhage had lower gestational age (28.2 ± 2.2 vs. 29.7 ± 1.7 weeks) and birth weight (990 ± 305 vs. 1275 ± 360 g). Infants with intra-ventricular hemorrhage at 36-38 weeks post-conceptual age had lower habituation scores to light (4.21 ± 2.23 vs. 6.09 ± 2.44), rattle (3.84 ± 2.12 vs. 6.18 ± 2.27), and bell (3.58 ± 1.74 vs. 5.20 ± 2.47) after controlling for confounders. No differences were found for tactile stimulus. Conclusion: Infants with gestational age <32 weeks and intra-ventricular hemorrhage had poorer habituation responses to external stimuli than those without intra-ventricular hemorrhage at 36-38 weeks post-conceptual age.

RESUMO Objetivo: Avaliar a associação entre hemorragia intraventricular e as respostas de habituação a estímulos externos em neonatos prematuros com idade pós-conceptual de 36-38 semanas. Métodos: Estudo transversal com neonatos com idade gestacional < 32 semanas. A hemorragia intraventricular foi identificada por ultrassonografia craniana e classificada de acordo com Papile et al. (1978). Os estímulos luminosos (lanterna), sonoros (chocalho, sino) e táteis foram apresentados e as respostas foram pontuadas de acordo com Lester & Tronik (2004). Os escores das respostas de habituação foram comparadas entre os grupos pelo teste t de Student. A associação entre a hemorragia intraventricular e os escores de habituação foi avaliada por regressão linear ajustada para a idade gestacional, escore de gravidade clínica, idade pós-conceptual na avaliação da habituação, sepse e displasia broncopulmonar. Resultados: 65 neonatos foram estudados, 20 com hemorragia intraventricular (16 graus I/II;4 graus III/IV) e 45 sem hemorragia intraventricular. Os neonatos com hemorragia intraventricular apresentaram menor idade gestacional (28,2 ± 2,2 vs. 29,7 ± 1,7 semanas) e peso ao nascer (990 ± 305 vs. 1275 ± 360 g). Os neonatos com hemorragia intraventricular na idade pós-conceptual de 36-38 semanas apresentaram escores de habituação menores a luz (4,21 ± 2,23 vs. 6,09 ± 2,44), chocalho (3,84 ± 2,12 vs. 6,18 ± 2,27) e campainha (3,58 ± 1,74 vs. 5,20 ± 2,47) após controle para variáveis de confusão. Nenhuma diferença foi encontrada para os estímulos táteis. Conclusão: Neonatos com idade gestacional < 32 semanas e hemorragia intraventricular apresentaram respostas de habituação piores a estímulos externos que os sem hemorragia intraventricular, na idade pós-conceptual de 36-38 semanas.

Hemorragia intraventricular y leucomalacia periventricular en neonatos de bajo peso al nacer en tres hospitales de Lima, Perú / Intraventricular hemorrhage and periventricular leukomalacia in low birth-weight neonates in three hospitals in Lima, Peru

RESUMEN Con el objetivo de describir la frecuencia y severidad de la hemorragia intraventricular y leucomalacia periventricular en neonatos de bajo peso en tres hospitales de Lima, Perú se evaluaron 385 neonatos menores de 2000 g de peso al nacer durante mayo del 2012 a julio del 2014. Se obtuvo ultrasonidos cerebrales a las 40 semanas de gestación, 3-5 días de vida y 3-4 semanas de vida. Hemorragia intraventricular se presentó en 19,2% neonatos con menos de 1500 g y fue severa (grado III o con infarto hemorrágico periventricular) en 9,6% neonatos menores de 1500 g. La mortalidad en neonatos con hemorragia intraventricular fue de 47,1%, se encontró leucomalacia periventricular en 5,4% de los neonatos menores de 1500 g. Ambos diagnósticos fueron más frecuentes en neonatos con menor peso. La frecuencia de hemorragia intraventricular es similar a lo reportado en otros países; sin embargo, la severidad y mortalidad es mayor.

ABSTRACT To describe the frequency and severity of intraventricular hemorrhage and periventricular leukomalacia in low birth-weight neonates in three hospitals in Lima, Peru, 385 newborn babies weighing under 2,000 g at birth were evaluated between May 2012 and July 2014. Brain ultrasounds were obtained at 40 weeks' gestation, 3-5 days of life, and 3-4 weeks of life. Intraventricular hemorrhage occurred in 19.2% of neonates weighing under 1,500 g and was severe (grade III or with periventricular hemorrhagic infarction) in 9.6% of neonates under 1,500 g. Mortality in infants with intraventricular hemorrhage was 47.1%, while periventricular leukomalacia was found in 5.4% of neonates 1,500 g and under; both diagnoses were more frequent in lower-weight babies. The frequency of intraventricular hemorrhage is similar to that reported in other countries; however, severity and mortality are greater.

Mecanismos de lesión cerebral en niños prematuros / Mechanisms of brain injury of the premature baby

Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.