Complicaciones neurológicas de la prematuridad / Neurological consequences of prematurity

Resumen Los nacimientos prematuros representan un in dicador importante de salud de un país. Estos niños tienen un mayor riesgo de mortalidad y morbilidad. Las principales lesiones encefálicas en los prematuros incluyen lesiones de la sustancia blanca, hemorragias intracraneanas y lesiones cerebelosas, que pueden ser detectadas mediante ecografía encefálica y resonancia magnética, siendo esta última la técnica más sensible. Estas lesiones pueden tener repercusión a largo plazo en el neurodesarrollo de los prematuros, con un mayor riesgo de parálisis cerebral, trastornos cognitivos, con ductuales, sensoriales y del aprendizaje, entre otros. Es fundamental aplicar estrategias de prevención y aten ción temprana para reducir las consecuencias negativas de las lesiones encefálicas asociadas a la prematuridad.

Abstract Premature births are an important health indicator for a country. These children have a higher risk of mor tality and morbidity. The main brain injuries in preterm infants include white matter injuries, intracranial hem orrhages, and cerebellar injuries. These injuries can be detected through brain ultrasound and magnetic reso nance imaging (MRI), with MRI being the most sensitive technique. Perinatal brain injuries may have long-term consequences on the neurodevelopment of preterm infants, with an increased risk of cerebral palsy, cogni tive, behavioral, sensory, and learning disorders, among others. It is key to implement prevention strategies and early intervention to reduce the negative consequences of brain injuries associated with prematurity.

Corioamnionitis histológica y neurodesarrollo en niños prematuros menores de 34 semanas, Lima-Perú

Para determinar los efectos de la corioamnionitis histológica en el neurodesarrollo de los prematuros menores de 34 semanas evaluados a los 2 años de edad corregida se realizó un estudio secundario de casos y controles. Fueron analizados los datos clínicos, hallazgos histológicos de la placenta e índices del desarrollo medidos por la Escala Bayley III de 38 niños expuestos y 53 niños no expuestos. Las infecciones genitourinarias de la madre y la sepsis precoz fueron más frecuentes en el grupo expuesto (p<0,005). Las dimensiones del desarrollo cognitivo, motor y lenguaje fueron normales en ambos grupos. Los expuestos al subtipo subcorionitis obtuvieron menor desempeño en las tres dimensiones. La corioamnionitis histológica no mostró influencia sobre el neurodesarrollo en prematuros menores de 34 semanas a los 2 años de edad. Se recomienda estudios longitudinales y multicéntricos para definir los efectos a largo plazo.

SUMMARY The objective of this study was to determine the effects of histologically diagnosed chorioamnionitis on neurodevelopment of premature babies born with less than 34-week gestational age who were assessed at two-year corrected age. A secondary case-control study was carried out. Clinical data, placental histological findings, and development indexes assessed using the Bayley III scale were analyzed in 38 exposed children and 53 non-exposed children. Genitourinary infections in mothers and early sepsis were more frequent in the exposed group (p<0.005). Cognitive development, motor development and language were normal in both groups. Those children exposed to the chorionitis subtype had lower scores in the aforementioned variables. Histologically diagnosed chorioamnionitis did not show any influence on neurodevelopment in premature babies born with less than 34-week gestational age when they were assessed at two years. Longitudinal and multicenter studies are advised in order to define the long-term effects.

A neonate with filamin A gene-associated periventricular nodular heterotopia / 中华围产医学杂志

This paper reported a neonate with periventricular nodular heterotopia associated to filamin A ( FLNA) gene mutation. The female patient was born at 29 +6 weeks of gestation to a mother who had intractable seizures and a history of two adverse pregnancy outcomes. Postnatal cranial ultrasound showed multiple hypoechoic masses on the walls of bilateral ventricles, which presented as "sawtooth pattern". MRI revealed gray matter displacement, unclear edge of gray and white matter, wavy bilateral ventricles and multiple nodular signals. Whole exon sequencing showed that the patient carried a maternally-inherited and likely pathogenic heterozygous mutation of chrX:153579307 in the FLNA gene (NM_00111 0556; p.Glu2376fsTer9), which caused the periventricular nodular heterotopia in the neonate. The patient was followed up until eight months of age and no convulsion or obvious abnormality in her growth or development was reported.

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.

Glaucoma-simulating cupping in a patient with periventricular leukomalacia: a clinical case report / Escavação simulando glaucoma em paciente com leucomalácia periventricular: relato de caso clínico

ABSTRACT Non-glaucomatous papillary cupping constitutes an important differential diagnosis in daily medical practice. There are patients diagnosed and treated as glaucoma, who do not present the disease and are part of the large group of non-glaucomatous optic neuropathies. This case emphasizes directing the diagnostic gaze to these "apparently glaucomatous" optic nerves through a case of periventricular leukomalacia. Patients with a history of prematurity, alterations in the cerebral white matter and presence of optic nerve excavations with normal intraocular pressures.

RESUMO A escavação papilar não glaucomatosa constitui um importante diagnóstico diferencial na prática médica diária. Há pacientes que recebem o diagnóstico de e tratamento para glaucoma, que não apresentam a doença e fazem parte do grande grupo de neuropatias ópticas não glaucomatosas. Este caso enfatiza o direcionamento do olhar diagnóstico para nervos ópticos "aparentemente glaucomatosos" através de um episódio de leucomalácia periventricular. Pacientes com histórico de prematuridade, alterações na substância branca do cérebro e presença de escavações do nervo óptico com pressões intraoculares normais.

Ocular signs, visual and general developmental outcome in Indian children with radiologically proven periventricular leukomalacia

Purpose: Owing to the paucity of literature on Indian children with periventricular leukomalacia (PVL), this retrospective study aimed to describe the visual and associated developmental abnormalities in a series of affected children attending a tertiary level eye care facility. Methods: Children with radiologically confirmed PVL who attended the Pediatric Department of a tertiary eye hospital were included and underwent a detailed ocular and general developmental assessment. Results: Of the 75 children, the mean age was 2.3 years, the mean follow?up was 3.1 years, 68% were males and 43% were born preterm. Grade I PVL was identified in 13 children (17%), Grade 2 PVL in 39 (52%), and Grade 3 PVL in 23 (31%). Premies with ?2 kg (72.5%) and term babies with >2 kg (75%) had a greater association of PVL occurrence with a preponderance to severe PVL; 46% of the children were visually impaired which was significantly higher in the children with Grade 3 PVL (74%) than those with Grade 2 PVL (15%). Strabismus was common (80%) with a change in deviation over time. Seventy?one percent of the children had a refractive error, frequently myopic astigmatism. All the children except two had a delay in one or more general developmental milestones. Conclusion: PVL occurrence is observed both in the babies born at term and premies, resulting in significant ocular and systemic morbidities. We recommend a system in place for early identification and referral to initiate an early intervention program which goes a long way toward improving the quality of life in these children

The incidence and risk factors of periventricular-intraventricular hemorrhage in extremely preterm infants / 中国新生儿科杂志

Objective:To study the incidence and risk factors of periventricular- intraventricular hemorrhage (PIVH) in extremely preterm infants (EPI) with gestational age (GA)<28 weeks.Methods:A retrospective study was performed in 304 cases of EPI hospitalized between January 2016 and December 2018. The infants were assigned into two groups according to whether PIVH occurred. Univariate analysis and Logistic regression analysis were used to determine the risk factors of PIVH.Results:Among the 304 cases,101 (33.2%) developed PIVH and 44 (14.5%) developed severe PIVH.The incidences of PIVH and severe PIVH in EPI with birth weight (BW) <750 g were 50.6% and 31.0%. The incidences of PIVH and severe PIVH in EPI with GA<26 weeks were 51.4% and 27.5%. Logistic regression analysis revealed that advanced GA ( OR=0.697, 95% CI 0.543~0.895, P=0.005) decreased the risk of PIVH. Prolonged invasive mechanical ventilation ( OR=1.121, 95% CI 1.007~1.249, P=0.037) and use of vasoactive drugs ( OR=1.373, 95% CI 1.040~1.812, P=0.025) within the first week of life increased the risk of PIVH. Conclusions:The incidences of PIVH and severe PIVH in EPI are quite high. Smaller GA, longer use of invasive mechanical ventilation and vasoactive drugs within the first week will increase the risk of PIVH in EPI.

The correlation between γδ-T lymphocyte subset in early postnatal peripheral blood and brain injury of preterm infants / 中华实用儿科临床杂志

Objective:To investigate the correlation between preterm infants with brain injury and the proportion of lymphocyte subsets, especially γδ-T cells in the postnatal peripheral blood, and to determine the predictive potential of γδ-T cells in the early peripheral blood in brain injury.Methods:It was a prospective study involving 106 preterm infants with gestational age less than 34 weeks who were delivered in the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University from January 1, to June 1, 2021.Relative levels of γδ-T , CD4 + T, CD8 + T, CD3 + T and total lymphocyte subsets in peripheral blood collected within the first 24 hours after birth were measured by flow cytometry.Recruited infants were divided into brain injury group (36 cases) and non-brain injury group (70 cases) according to serial cranial ultrasound and magnetic resonance imaging(MRI) at the corrected gestational age of 36-37 weeks.Differences in general conditions and the proportion of lymphocyte subsets between groups were compared by the t-test or Chi- square test.Patients in brain injury group were further divided into intracranial hemorrhage(ICH) group(8 cases), periventricular leukomalacia (PVL) group (6 cases)and diffuse white matter damage (WMD) group(22 cases). The proportion of lymphocyte subsets among the different groups was compared by One- Way ANOVA, followed by the LSD- t test. Results:The proportion of γδ-T cells in postnatal peripheral blood of preterm infants at 24 hours after birth in brain injury group was significantly lower than that of non-brain injury group [(0.09±0.12)% vs.0.15±0.13)%, t=-2.445, P=0.016]. No significant differences in the proportion of the CD4 + and CD8 + T cell subsets were found between them.Both preterm infants in PVL group and WMD group had a significantly lower proportion of γδ-T cells at 24 hours after birth compared to that of the non-brain injury group [(0.03±0.05)%, (0.07±0.09)% and (0.15±0.13)%], respectively, ( t=-2.190, -2.659, all P<0.05). Conclusions:γδ-T cells in early postnatal peripheral blood may be involved in the development of brain injury in preterm infants and they had early predictive value for preterm infants at high risk of brain injury, especially the leukomalacia and diffuse white matter injury.

Postnatally confirmed COL4A1 mutation in a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia / 中华围产医学杂志

We report a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia during pregnancy who was postnatally detected with a de novo mutation in the COL4A1 gene by genetic testing of umbilical cord blood. Multiple fresh hemorrhagic foci were detected in the fetal brain parenchyma and cerebellar hemisphere by ultrasound at 25 gestational weeks. Regular re-examination of the nervous system's ultrasound and magnetic resonance imaging (MRI) indicated recurrent multiple intraparenchymal hemorrhages followed by cystic leukomalacia. However, karyotyping and chromosomal microarray analysis of amniotic fluid showed no abnormality. The newborn was born by cesarean section at 37 +3 gestational weeks with an Apgar score of 10 at 1 and 5 min. Repeated apnea occurred after birth. MRI detected new intraparenchymal hemorrhage and cystic leukomalacia on the six-day of life. The infant's limb muscle tone remained low on the 90-day follow-up. The patient was lost to follow up. Whole-exome sequencing of the cord blood identified a de novo heterozygous mutation- c.4738G>A in the COL4A1 gene (NM_001845.4; p.G1580S) neither parent carried. It suggests that the genetic test of the COL4A1 mutation should be considered for fetuses with intracranial hemorrhage in the prenatal diagnosis, especially those with recurrent fetal intraparenchymal hemorrhage followed by cystic leukomalacia. Genetic tests could help analyze the fetal prognosis, and guide the delivery mode.

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.

Repercusión de la corioamnionitis como factor de riesgo en la sepsis materna y neonatal temprana / Impact of Chorioamnionitis as a risk factor in early neonatal and maternal sepsis / Impacto da coioamnionite como fator de risco nasepse materna e neonatal precoce

RESUMEN Introducción: se realiza una revisión bibliográfica sobre la repercusión de la corioamnionitis como factor de riesgo en la sepsis neonatal temprana para la madre y el neonato en el Hospital provincial Universitario Docente "Carlos M. de Céspedes" en Bayamo, Granma en los cinco primeros meses del año 2019. Objetivo: profundizar el conocimiento de este factor de riesgo, suetiopatogenia, factores predisponentes, diagnóstico clínico y de laboratorio, riesgos para la madre y repercusión en el recién nacido, su prevención y tratamiento. Métodos: se utilizaron libros de texto específicos de Medicina y se realizó la recopilación de artículos de Internet a través de buscadores como el Servicio de la Editorial Elsevier, Secretaría de Ciencia y Técnica de la Nación, LILACS, MEDLINE con la asistencia del buscador específico PUBMED, IMBIOMED, La Biblioteca Cochrane, SciELO. Resultados: su incidencia en los partos pretérmino es mayor que en las gestaciones a término. Representa una de las tres principales causas de infección antes de término del embarazo con membranas íntegras y en caso de rotura prematura de membranas. Conclusiones: la repercusión en la madre incluye el parto pretérmino, si cesárea (atonía uterina o hemorragia postparto, absceso pélvico, tromboembolismo y endometritis, sepsis puerperal y la infección del torrente sanguíneo, mientras que en el neonato la leucomalacia periventricular con la consiguiente hemorragia periventricular, la broncodisplasia pulmonar, enterocolitis necrotizante, parálisis cerebral y el retraso mental.

ABSTRACT Introduction: a bibliographical review on the impact of Chorioamnionitis as a risk factor in early neonatal sepsis for the mother and the newborn in the provincial University Hospital "Carlos M. de Céspedes" is carried out in Bayamo, Granma in the first five months of the year 2019. Objective: to deepen the knowledge of this risk factor, its pathogenesis, predisposing factors, clinical and laboratory diagnosis, risks to the mother and repercussion in the newborn, its prevention and treatment. Methods: medicine-specific textbooks were used and the collection of Internet articles was made through search engines such as the service of the Editorial Elsevier, Secretariat of Science and Technology of the nation, LILACS, MEDLINE with the assistance of Specific search engine PUBMED, imbiomed, the Cochrane Library, SciELO. Results: its incidence in preterm births is greater than in term gestations. It represents one of the three main causes of infection before the end of pregnancy with intact membranes and in case of premature rupture of membranes. Conclusion: the impact on the mother includes preterm delivery, if caesarean section (uterine sluggishness or postpartum hemorrhage, pelvic abscess, thromboembolism and endometritis, puerperal sepsis and bloodstream infection, while in the neonate the Periventricular periventricular with consequent periventricular hemorrhage, pulmonary broncodisplasia, necrotizing enterocolitis, cerebral palsy and mental retardation.

RESUMO Introdução: uma revisão bibliográfica é realizada sobre o impacto da coioamnionite como fator de risco na sepse neonatal precoce para mãe e recém-nascidos no Hospital Escolar Provincial "Carlos M. de Céspedes" em Bayamo, Granma nos primeiros cinco meses de 2019. Objetivo: aprofundar o conhecimento desse fator de risco, sua etiopatogeneia, fatores predisponderantes, diagnóstico clínico e laboratorial, riscos para a mãe e impacto sobre o recém-nascido, sua prevenção e tratamento. Métodos: foram utilizados livros didáticos específicos de Medicina e o recolhimento de artigosna Internet foi realizado por meio de mecanismos de busca como o Serviço de Publicação Elsevier, Secretaria de Ciência e Técnica da Nação, LILACS, MEDLINE com o auxílio do mecanismo de busca específico PUBMED, IMBIOMED, The Cochrane Library, SciELO. Resultados: sua incidência em partos prematuros é maior do que nas gestações a termo. Representa uma das três principais causas de infecção antes do fim da gravidez com membranas completas e em caso de ruptura prematura de membranas. Conclusões: o impacto sobre a mãe inclui nascimento prematuro, se cesariana (atonia uterina ou hemorragia pós-parto, abscesso pélvico, tromboembolismo e endometrite, sepse pós-parto e infecção por corrente sanguínea, enquanto na leucomalacia periventricular neonate com hemorrhagem periventricular consequente, broncododisplasia pulmonar, enterocolite necrosante, paralisia cerebral e retardo mental.

Ecografía transfontanelar en la enfermedad hipóxico isquémica del recién nacido. Presentación de un caso / Transfontanellar ultrasound in hypoxic diseasenewborn ischemic. Presentation of a case

RESUMEN La enfermedad hipóxico-isquémica constituye una de las principales causas de morbi-mortalidad neurológica en el recién nacido. Las diferentes adaptacio-nes vasculares a la hipoxia tanto en el neonato pretérmino como en niño a término hacen que su presentación en neuroimagen, sobre todo en el ultrasonido (US) sea caracterizable según el territorio afectado y el momento de la enfermedad. El ultrasonido se ha convertido en una poderosa herramienta para la evaluación del recién nacido con sospecha de EHI, y el patrón de las lesiones tiene importantes implicaciones en el tratamiento y en el pronóstico neurológico a largo plazo. A continuación, presentamos el caso de un recién nacido masculino, prematuro extremo, que requirió reanimación cardiopulmonar avanzada en el nacimiento y que además presento dos episodios de parada cardiorrespiratoria en el segundo y tercer día de vida, en el cual se llegó al diagnóstico con patrones ecográficos característicos de lesión isquémica y además se detalla la evolución de los hallazgos en el tiempo.Palabras claves: Enfermedad hipóxico-isquémica, ultrasonido transfontanelar, matriz germinal, leucomalacia periventricular.

ABSTRACT Hypoxic-ischemic disease is one of the main causes of neurological morbidity and mortality in the newborn. The different vascular adaptations to hypoxia in both the preterm and term infants make their presentation on neuroimaging, especially on ultrasound (US), characterizable according to the affected terri-tory and the time of the disease. Ultrasound has become a powerful tool for evaluating the newborn with suspected IBD, and the pattern of the lesions has important implications for treatment and long-term neurological prognosis. Next, we present the case of a male newborn, extremely premature, who required advanced cardiopulmonary resuscitation at birth and who also presented two episodes of cardiorespiratory arrest on the second and third day of life, in which the diagnosis was reached with patterns sonographic characteristics of ischemic injury and also the evolution of the findings over time.Keywords: Hypoxic-ischemic disease, transfontanelar ultrasound, germ matrix, periventricular leukomalacia

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.

Demyelination in experimental intraventricular neurocysticercosis / Desmielinização na neurocisticercose intraventricular experimental

Abstract Neurocysticercosis (NCC) is classified as a neglected tropical disease, which affects mainly Latin America and Africa in spite of some reports in North America and Europe. NCC represents the cause of up to 30% of the reported cases of epilepsy in endemic countries. The NCC injuries present direct relation to the development stage, location, and number of parasites as well as to the host immune response. This study aimed the characterization of the inflammatory response and tissue injuries by means of the analyses of the periventricular and parenchymatous demyelination through the experimental intraventricular NCC infection. Therefore, BALB/c mice were submitted to experimental NCC inoculation with Taenia crassiceps cysticerci. Their brains were removed at 7, 30, 60, and 90 days after the inoculation (DAI), and analyzed after staining with hematoxylin and eosin (HE), Luxol Fast Blue, and Nissl. It was possible to observe ventriculomegaly, inflammatory infiltration composed by polymorphonuclear and mononuclear cells, and foamy macrophages. The presence of inflammatory cells was associated with neurodegeneration detected by the areas with demyelination observed initially in the periventricular area and lately in the parenchyma. In conclusion, the presence of cysticerci and the consequent inflammation were able to promote initial periventricular demyelination followed by parenchymatous demyelination as the infection progressed.

Resumo A neurocisticercose (NCC) é classificada como uma doença tropical negligenciada que afeta principalmente a América Latina e a África, apesar de alguns relatos na América do Norte e na Europa. A NCC é responsável por cerca de 30% dos casos de epilepsia em países endêmicos. Estas lesões parecem ter estreita relação com o estádio de desenvolvimento, com a localização e o número de parasitas, bem como a resposta imune do hospedeiro. O presente estudo objetivou caracterizar a resposta de células inflamatórias e as lesões teciduais pela análise da desmielinização periventricular e parenquimatosa ao longo da infecção experimental de NCC intraventricular. Para tanto, camundongos BALB/c foram submetidos a NCC experimental através da inoculação de cisticercos de Taenia crassiceps. O encéfalo foi retirado aos 7, 30, 60 e 90 dias após inoculação (DAI) e analisado após coloração por Hematoxilina e Eosina (HE), Luxol Fast Blue e Nissl. Observou-se ventriculomegalia, processo de infiltração inflamatório composto por células polimorfonucleares, mononucleares e macrófagos espumosos. A presença de células inflamatórias foi associada com neurodegeneração, observada pelas áreas de desmielinização que foram inicialmente periventricular e mais tardiamente no parênquima. Em conclusão, observa-se que a presença dos cisticercos e a inflamação foram capazes de promover desmielinização periventricular inicial e parenquimatosa conforme houve progressão tardia da infecção.

Clinical and genetic analysis of a patient with periventricular nodular heterotopia 7 caused by NEDD4L gene variant / 中华医学遗传学杂志

Objective@#To explore the genetic basis of a patient featuring global developmental delay, intellectual disability, cleft palate, seizures and hypotonia.@*Methods@#Clinical examination and laboratory tests were carried out. Peripheral blood samples were obtained from the patient and his parents. Whole genomic DNA was extracted and subjected to next generation sequencing. Candidate variation was analyzed by using bioinformatic software and validated by Sanger sequencing.@*Results@#The proband was found to carry a heterozygous c. 2117T>C (p.Leu706Pro) variant of the NEDD4L gene, which was a de novo variant validated by Sanger sequencing and predicted to be likely pathogenic according to the American College of Medical Genetics Guidelines.@*Conclusion@#The heterozygous variant of c. 2117T>C (p.Leu706Pro) of the NEDD4L gene probably underlies the disorders in the patient.

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.

Fibrodisplasia osificante progresiva plus por una variante patogénica del gen ACVR1: caso clínico / Fibrodysplasia ossificans progressiva: report of one case

Fibrodysplasia ossificans progressiva (FOP) or myositis ossificans, is a genetic disease, with a prevalence of 1 in 2.000.000. It is caused by pathogenic variants in ACVR1 gene and characterized by soft tissue heterotopic ossification, starting in the second decade of life. It is associated to early mortality caused by respiratory complications. It evolves in flare-ups, triggered by soft tissue injuries; therapy is symptomatic, using analgesia, steroids and diphosphonates. We report a 12-year-old female with left renal agenesis, hallux valgus and intellectual disability, presenting with a six months history of thoracic kyphosis, tender nodules in the thorax, and rigidity of right elbow and left knee. Clinical examination revealed dysmorphic facial features. A magnetic resonance showed heterotopic ossification nodules, which was confirmed with spinal radiography. These findings prompted the diagnosis of FOP. Pain treatment was started, and prednisone was used during flare-ups. The ACVR1 gene was analyzed and a pathogenic variant, p. Arg206His, was found, confirming the diagnosis of FOP.

A case of FLNA gene mutation with respiratory insufficiency and periventricular heterotopia

Filamin A is an actin-binding protein and, in humans, is encoded by FLNA gene in the long arm of X chromosome. Filamin A plays a role in the formation of cytoskeleton by crosslinking actin filaments in cytoplasm. FLNA mutations affect cytoskeletal regulatory processes and cellular migrating abnormalities that result in periventricular heterotopia. A 5-month-old girl was hospitalized because of breathing difficulty and was diagnosed as having periventricular heterotopia with laryngomalacia, cricopharyngeal incoordination, pulmonary hypertension, and chronic lung disease. A genetic test was performed to find the cause of periventricular heterotopia, and FLNA gene mutation (c.5998+1G>A) was confirmed for the first time in Korea. After discharge, she developed respiratory failure due to a viral infection at 8 months of her age. In spite of management with mechanical ventilation, she died of pneumothorax and pulmonary hemorrhage. Herein, we report a case of FLNA gene mutation who presented with periventricular nodular heterotopia with respiratory insufficiency.