Perinatal factors associated with early deaths of preterm infants born in Brazilian Network on Neonatal Research centers

Objective: To evaluate perinatal factors associated with early neonatal death in preterm infants with birth weights (BW) of 400-1,500 g.Methods: A multicenter prospective cohort study of all infants with BW of 400-1,500 g and 23-33 weeks of gestational age (GA), without malformations, who were born alive at eight public university tertiary hospitals in Brazil between June of 2004 and May of 2005. Infants who died within their first 6 days of life were compared with those who did not regarding maternal and neonatal characteristics and morbidity during the first 72 hours of life. Variables associated with the early deaths were identified by stepwise logistic regression.Results: A total of 579 live births met the inclusion criteria. Early deaths occurred in 92 (16%) cases, varying between centers from 5 to 31%, and these differences persisted after controlling for newborn illness severity and mortality risk score (SNAPPE-II). According to the multivariate analysis, the following factors were associated with early intrahospital neonatal deaths: gestational age of 23-27 weeks (odds ratio - OR = 5.0; 95%CI 2.7-9.4), absence of maternal hypertension (OR = 1.9; 95%CI 1.0-3.7), 5th minute Apgar 0-6 (OR = 2.8; 95%CI 1.4-5.4), presence of respiratory distress syndrome (OR = 3.1; 95%CI 1.4-6.6), and network center of birth.Conclusion: Important perinatal factors that are associated with early neonatal deaths in very low birth weight preterm infants can be modified by interventions such as improving fetal vitality at birth and reducing the incidence and severity of respiratory distress syndrome. The heterogeneity of early neonatal rates across the different centers studied indicates that best clinical practices should be identified and disseminated throughout the country.

Children and adolescents in full-time special education : an epidemiological and magnetic resonance imaging study

The need for special education (SE) is increasing. The majority of those whose problems are due to neurodevelopmental disorders have no specific aetiology. The aim of this study was to evaluate the contribution of prenatal and perinatal factors and factors associated with growth and development to later need for full-time SE and to assess joint structural and volumetric brain alterations among subjects with unexplained, familial need for SE. A random sample of 900 subjects in full-time SE allocated into three levels of neurodevelopmental problems and 301 controls in mainstream education (ME) provided data on socioeconomic factors, pregnancy, delivery, growth, and development. Of those, 119 subjects belonging to a sibling-pair in full-time SE with unexplained aetiology and 43 controls in ME underwent brain magnetic resonance imaging (MRI). Analyses of structural brain alterations and midsagittal area and diameter measurements were made. Voxel-based morphometry (VBM) analysis provided detailed information on regional grey matter, white matter, and cerebrospinal fluid (CSF) volume differences. Father’s age ≥ 40 years, low birth weight, male sex, and lower socio-economic status all increased the probability of SE placement. At age 1 year, one standard deviation score decrease in height raised the probability of SE placement by 40% and in head circumference by 28%. At infancy, the gross motor milestones differentiated the children. From age 18 months, the fine motor milestones and those related to speech and social skills became more important. Brain MRI revealed no specific aetiology for subjects in SE. However, they had more often ≥ 3 abnormal findings in MRIs (thin corpus callosum and enlarged cerebral and cerebellar CSF spaces). In VBM, subjects in full-time SE had smaller global white matter, CSF, and total brain volumes than controls. Compared with controls, subjects with intellectual disabilities had regional volume alterations (greater grey matter volumes in the anterior cingulate cortex bilaterally, smaller grey matter volume in left thalamus and left cerebellar hemisphere, greater white matter volume in the left fronto-parietal region, and smaller white matter volumes bilaterally in the posterior limbs of the internal capsules). In conclusion, the epidemiological studies emphasized several factors that increased the probability of SE placement, useful as a framework for interventional studies. The global and regional brain MRI findings provide an interesting basis for future investigations of learning-related brain structures in young subjects with cognitive impairments or intellectual disabilities of unexplained, familial aetiology.

New approaches to improve the cord blood unit hematopoietic progenitor cell content

Cord blood is a well-established alternative to bone marrow and peripheral blood stem cell transplantation. To this day, over 400 000 unrelated donor cord blood units have been stored in cord blood banks worldwide. To enable successful cord blood transplantation, recent efforts have been focused on finding ways to increase the hematopoietic progenitor cell content of cord blood units. In this study, factors that may improve the selection and quality of cord blood collections for banking were identified. In 167 consecutive cord blood units collected from healthy full-term neonates and processed at a national cord blood bank, mean platelet volume (MPV) correlated with the numbers of cord blood unit hematopoietic progenitors (CD34+ cells and colony-forming units); this is a novel finding. Mean platelet volume can be thought to represent general hematopoietic activity, as newly formed platelets have been reported to be large. Stress during delivery is hypothesized to lead to the mobilization of hematopoietic progenitor cells through cytokine stimulation. Accordingly, low-normal umbilical arterial pH, thought to be associated with perinatal stress, correlated with high cord blood unit CD34+ cell and colony-forming unit numbers. The associations were closer in vaginal deliveries than in Cesarean sections. Vaginal delivery entails specific physiological changes, which may also affect the hematopoietic system. Thus, different factors may predict cord blood hematopoietic progenitor cell numbers in the two modes of delivery. Theoretical models were created to enable the use of platelet characteristics (mean platelet volume) and perinatal factors (umbilical arterial pH and placental weight) in the selection of cord blood collections with high hematopoietic progenitor cell counts. These observations could thus be implemented as a part of the evaluation of cord blood collections for banking. The quality of cord blood units has been the focus of several recent studies. However, hemostasis activation during cord blood collection is scarcely evaluated in cord blood banks. In this study, hemostasis activation was assessed with prothrombin activation fragment 1+2 (F1+2), a direct indicator of thrombin generation, and platelet factor 4 (PF4), indicating platelet activation. Altogether three sample series were collected during the set-up of the cord blood bank as well as after changes in personnel and collection equipment. The activation decreased from the first to the subsequent series, which were collected with the bank fully in operation and following international standards, and was at a level similar to that previously reported for healthy neonates. As hemostasis activation may have unwanted effects on cord blood cell contents, it should be minimized. The assessment of hemostasis activation could be implemented as a part of process control in cord blood banks. Culture assays provide information about the hematopoietic potential of the cord blood unit. In processed cord blood units prior to freezing, megakaryocytic colony growth was evaluated in semisolid cultures with a novel scoring system. Three investigators analyzed the colony assays, and the scores were highly concordant. With such scoring systems, the growth potential of various cord blood cell lineages can be assessed. In addition, erythroid cells were observed in liquid cultures of cryostored and thawed, unseparated cord blood units without exogenous erythropoietin. This was hypothesized to be due to the erythropoietic effect of thrombopoietin, endogenous erythropoietin production, and diverse cell-cell interactions in the culture. This observation underscores the complex interactions of cytokines and supporting cells in the heterogeneous cell population of the thawed cord blood unit.

Nutrition, growth and body composition in infancy

This thesis is presented in two parts. Data for this research is from the Cork BASELINE (Babies after SCOPE, Evaluating Longitudinal Impact using Neurological and Nutritional Endpoints) Birth Cohort Study (n = 2137). In this prospective birth cohort study, pediatric follow-up with in-person appointments were repeated from the time of birth through to 2, 6 and 12 months, and at 2 years. Body composition was measured by air displacement plethysmography at birth and at 2 months using the PEA POD Infant Body Composition Tracking System. This thesis provides the first extensive report on the study’s 2 year assessment. In part one, the aims were to investigate potential early-life risk factors for childhood overweight and obesity, including rapid growth and body composition in infancy and umbilical cord concentrations of leptin and high molecular weight (HMW) adiponectin. This research is the first to describe rapid growth in early infancy in terms of changes in direct measures of body composition. These are also the first data to examine associations between umbilical cord leptin and HMW adiponectin concentrations and changes in fat and lean mass in early infancy. These data provide additional insight into characterising the growth trajectory in infancy and into the role of perinatal factors in determining infant growth and subsequent overweight/obesity risk. In part two of this thesis, the aims were to quantify vitamin D intake and status at 2 years and to investigate whether 25-hydroxyvitamin D [25(OH)D] concentrations in early pregnancy and in umbilical cord blood are associated with infant growth and body composition. There was a low prevalence of vitamin D deficiency among Irish 2 year olds (n = 742) despite a high prevalence of inadequate intakes and high latitude (51°N). Maternal 25(OH)D concentrations at 15 weeks gestation and cord 25(OH)D concentrations at delivery were not associated with infant growth or adiposity.

Factores de riesgo perinatales para sobrepeso y obesidad en escolares en una población bogotana

Objetivo: Evaluar el impacto de los factores maternos y perinatales: peso previo al embarazo, presencia de hipertensión, diabetes y tabaquismo, peso al nacer y tiempo de lactancia con el desarrollo de sobrepeso y obesidad en los niños de 5 a 10 años en una población bogotana. Materiales y métodos: se realizó un diseño de casos y controles no pareado, incluyendo 528 niños con sus respectivas madres con una relación 1:2, en quienes se identificaron los descritos, y también factores postnatales relevantes: dieta, ejercicio y tiempo de pantalla. Se analizó con un modelo de regresión logística binomial la importancia de cada uno para la patología Resultados:Se encontró una mayor prevalencia de casos en los estratos 1 y 2 comparados con los demás estratos (p= 0,034). También se encontraron diferencias en la prevalencia de sobrepeso y obesidad en las madres de los casos (27%; p =0,01), mayor ingesta calórica en el grupo de los controles (42,9% vs 30,9%; p= 0,04). En el modelo de regresión logística se encontró que los factores que en conjunto mostraron significancia estadística fueron, un peso al nacer mayor de 2500 gr OR 2,31(IC 95%:1,13-4,78 p=0,021), un IMC materno antes de la gestación > de 25 OR 3,42(IC 95%:1,42-8,29 p=0,06), peso al año mayor de 7,5 kg OR 2,77 (IC 95%:1,11-2,78 p=0,028) y una ingesta calórica entre 600 a 1900 calorías/día OR 1.58 (IC 95%:1,06-2,35 p=0,02).Conclusiones: son factores de riesgo para el desarrollo de la obesidad infantil, la progresión hacia un percentil superior en peso, antes el embarazo, nacimiento y primer año de vida.

Prevalencia de TSH neonatal elevada y factores perinatales relacionados con asfixia Bogotá 2012

Introducción: la asfixia perinatal es la tercera causa de muerte en menores de 5 años. Las secuelas neurológicas suponen una carga importante para las familias y los sistemas de salud (1). Los estudios que relacionan el efecto de la asfixia perinatal sobre las hormonas tiroideas son escasos. El estudio sobre predictores de asfixia es un tema de investigación permanente. El objetivo principal fue determinar la prevalencia de TSH de cordón elevada y su relación con factores perinatales asociados a asfixia. Métodos: estudio descriptivo retrospectivo. La muestra estuvo conformada por todos los recién nacidos con TSH de cordón elevada y un segundo grupo seleccionado de forma aleatoria con TSH de cordón normal. Tomada de una población de neonatos atendidos en una clínica de Bogotá durante el 2012. Resultados: la prevalencia de TSH de cordón elevada fue de 14,7%. Los resultados sugieren una posible asociación entre alteraciones en las pruebas de bienestar fetal, presencia de infección materna, parto distócico, dificultad respiratoria y APGAR bajo y la presencia de TSH elevada p<0,05. Discusión: La alta prevalencia de TSH de cordón elevada podría relacionarse con las características de alto riesgo que presenta esta población. La elevación transitoria de la TSH neonatal de cordón en neonatos con alteraciones del bienestar fetal asociada a eventos hipóxicos agudos, sugiere que esta hormona podría ser un marcador de asfixia perinatal.

Factores perinatales para riesgo de sobrepeso y obesidad en niños de 4 a 5 años en Colombia 2010.

Introducción: La OMS revela que en 2010 alrededor de 43 millones de niños menores de 5 años presentan sobrepeso. En Colombia según la Encuesta Nacional de Situación Nutricional en Colombia en su versión 2005, mostraba una prevalencia general de sobrepeso de 3.1% niños de 0 a 4 años. Es una condición de salud de origen multifactorial en la que interviene factores genéticos, ambientales, maternos y perinatales. Objetivo: Establecer la asociación de riesgo entre el bajo peso al nacer y el desarrollo de sobrepeso y obesidad en niños de 4 a 5 años. Metodología: Se realizó un estudio observacional descriptivo retrospectivo de corte transversal con los datos nutricionales, maternos y perinatales de la Encuesta Nacional de Demografía en Salud del año 2010 en Colombia. Se analizó la asociación entre la variable independiente bajo peso al nacer con el desenlace sobrepeso y obesidad en menores de 4 a 5 años, usando como medida el IMC según la edad. Se realizaron análisis univariados, bivariados y de regresión logística con un modelo de riesgo según las variables que inciden en el desenlace y la variable independiente. Resultados: La muestra obtenida para el estudio fue de 2166 niños de 4 a 5 años de edad quienes cumplían los criterios de inclusión. La prevalencia de sobrepeso u obesidad en la primera infancia fue de 21.8% (472) y el bajo peso al nacer. Los resultados sugieren la asociación de bajo peso y sobrepeso u obesidad es de ORajustado= 0.560 (0.356 – 0.881). Conclusiones: Los resultados sugieren que existe una asociación como factor protector entre el bajo peso y el sobrepeso u obesidad en la primera infancia. Sin embargo, debido al comportamiento de las variables consideradas en la muestra no hay suficiente información para rechazar completamente la hipótesis nula.

Prevalencia de anemia con sus factores asociados en niños/as de 12 a 59 meses de edad y capacitación a los padres de familia en el Centro de Desarrollo Infantil de la Universidad de Cuenca. Cuenca, diciembre 2015 - mayo 2016

OBJETIVO: Determinar la prevalencia de anemia en niños y niñas de 12 a 59 meses de edad con sus factores asociados, y capacitación a padres de familia en el Centro de Desarrollo Infantil de la Universidad de Cuenca (CEDIUC), METODOLOGÍA: Esta investigación se basó en un estudio descriptivo – transversal de prevalencia, se efectuó mediante la obtención de pruebas de hemoglobina a 90 niños/as de 12 a 59 meses de edad y cuestionarios a los padres sobre factores de riesgo; a los mismos se les aplicó encuestas validadas para visualizar el grado de conocimientos, actitudes y prácticas sobre la alimentación y nutrición respecto a la deficiencia de hierro. Se manejó frecuencias y porcentajes, y para las variables numéricas media, mediana y moda en programas estadísticos. RESULTADOS: La prevalencia de anemia fue en total del 43,3%, el 30% de los niños/as presentó anemia leve y un 13,3% padeció de anemia moderada. La afección tuvo un asocio importante con respecto a la edad, género, lugar de residencia, condición socioeconómica, factores perinatales y estado nutricional actual. Sobre los conocimientos y prácticas en relación a la alimentación, se pudo señalar que gracias a las capacitaciones se mejoró del 31,4% a un 89,9% al finalizar el estudio. CONCLUSIÓN: Se logró evidenciar ciertas relaciones importantes entre anemia e indicadores de riesgo a pesar del número reducido de participantes. Brindar charlas y talleres de manera periódica a los padres y personal del CEDIUC para mejorar sus conocimientos y prevenir complicaciones a futuro se considera oportuno, necesario y preventivo.

Elevación transitoria de TSH neonatal asociada a factores de riesgo de parto pretérmino

Introducción: La hipotiroxinemia es una alteración transitoria frecuente en el prematuro que resuelve sin medicación, es importante conocer los factores que se asocian con esta alteración para disminuir el tratamiento inoportuno y el aumento de costos en atención en salud que puede implicar un diagnóstico errado de hipotiroidismo congénito. Por medio de este estudio se evaluó la asociación entre elevación transitoria de la TSH neonatal y algunas variables asociadas a parto pretérmino en pacientes atendidos en la Clínica Materno Infantil Colsubsidio nacidos entre Enero 2014 a Abril de 2015. Metodología: Se realizó un estudio de casos y controles, analítico, retrospectivo. Los casos fueron prematuros con elevación de TSH sin hipotiroidismo congénito, los controles fueron prematuros con TSH normal, seleccionados de manera aleatoria 70 casos, 140 controles con una relación 1:2. Se realizaron asociaciones mediante prueba de chi cuadrado y análisis multivariado para controlar factores de confusión. Resultados: La edad gestacional promedio para casos fue 34.6±1.8, para controles 34.2±2.4. Ambas poblaciones fueron comparables. Los factores con resultados estadísticamente significativos fueron: Pielonefritis (p 0.04), hipertensión inducida por el embarazo (p 0.00), presencia de anemia (p 0.02) y embarazo múltiple (p0.03). Los resultados de regresión logística establecieron que la pielonefritis, hipertensión y anemia son factores de riesgo con resultados estadísticamente significativos. Discusión: Los resultados permitieron documentar que existen factores de riesgo para prematurez, como la pielonefritis, anemia materna e hipertensión inducida por el embarazo, que influyen en los valores de TSH de cordón umbilical que no necesariamente conllevan al desarrollo de hipotiroidismo congénito

Balance of growth factors in the human perinatal lung : Implications for physiological lung development and link to bronchopulmonary dysplasia

The aims of this Thesis was to evaluate the role of proangiogenic placental growth factor (PlGF), antiangiogenic endostatin and lymphangiogenic vascular endothelial growth factor (VEGF) -C as well as the receptors vascular endothelial growth factor receptor (VEGFR) -2 and VEGFR-3 during lung development and in development of lung injury in preterm infants. The studied growth factors were selected due to a close relationship with VEGF-A; a proangiogenic growth factor important in normal lung angiogenesis and lung injury in preterm infants. The thesis study consists of three analyses. I: Lung samples from fetuses, preterm and term infants without lung injury, as well as preterm infants with acute and chronic lung injury were stained by immunohistochemistry for PlGF, endostatin, VEGF-C, VEGFR-2 and VEGFR-3. II: Tracheal aspirate fluid (TAF) was collected in the early postnatal period from a patient population consisting of 59 preterm infants, half developing bronchopulmonary dysplasia (BPD) and half without BPD. PlGF, endostatin and VEGF-C concentrations were measured by commercial enzyme-linked immunosorbent assay (ELISA). III: Cord plasma was collected from very low birth weight (VLBW) (n=92) and term (n=48) infants in conjuncture with birth and endostatin concentrations were measured by ELISA. I: All growth factors and receptors studied were consistently stained in immunohistochemistry throughout development. For endostatin in early respiratory distress syndrome (RDS), no alveolar epithelial or macrophage staining was seen, whereas in late RDS and BPD groups, both alveolar epithelium and macrophages stained positively in approximately half of the samples. VEGFR-2 staining was fairly consistent, except for the fact that capillary endothelial staining in the BPD group was significantly decreased. II: During the first postnatal week in TAF mean PlGF concentrations were stable whereas mean endostatin and VEGF-C concentrations decreased. Higher concentrations of endostatin and VEGF-C correlated with lower birth weight (BW) and associated with administration of antenatal betamethasone. Parameters reflecting prenatal lung inflammation associated with lower PlGF, endostatin and VEGF-C concentrations. A higher mean supplemental fraction of inspired oxygen during the first 2 postnatal weeks (FiO2) correlated with higher endostatin concentrations. III: Endostatin concentrations in term infants were significantly higher than in VLBW infants. In VLBW infants higher endostatin concentrations associated with the development of BPD, this association remained significant after logistic regression analysis. We conclude that PlGF, endostatin and VEGF-C all have a physiological role in the developing lung. Also, the VEGFR-2 expression profile seems to reflect the ongoing differentiation of endothelia during development. Both endostatin and VEGFR-2 seem to be important in the development of BPD. During the latter part of the first postnatal week, preterm infants developing BPD have lower concentrations of VEGF-A in TAF. Our findings of disrupted VEGFR-2 staining in capillary and septal endothelium seen in the BPD group, as well as the increase in endostatin concentrations both in TAF and cord plasma associated with BPD, seem to strengthen the notion that there is a shift in the angiogenic balance towards a more antiangiogenic environment in BPD. These findings support the vascular hypothesis of BPD.

Risk factors for perinatal death in two different levels of care: a case-control study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Perinatal and early adulthood factors associated with adiposity

We used body mass index (BMI) and waist circumference (WC) as fat indicators to assess whether perinatal and early adulthood factors are associated with adiposity in early adulthood. We hypothesized that risk factors differ between men and women and are also different when WC is used for measuring adiposity as opposed to BMI. We conducted a longitudinal study based on a sample of 2,063 adults from the 1978/1979 Ribeirao Preto birth cohort. Adjustment was performed using four sequential multiple linear regression models stratified by sex. Both perinatal and early adulthood variables influenced adulthood BMI and WC. The associations differed between men and women and depending on the measure of abdominal adiposity (BMI or WC). Living with a partner, for both men and women, and high fat and alcohol intake in men were factors that were consistently associated with higher adulthood BMI and WC levels. The differences observed between sexes may point to different lifestyles of men and women, suggesting that prevention policies should consider gender specific strategies.

Perinatal and early life factors associated with symptoms of depression in Brazilian children

Background: Few studies have been conducted on the association between perinatal and early life factors with childhood depression and results are conflicting. Our aim was to estimate the prevalence and perinatal and early life factors associated with symptoms of depression in children aged 7 to 11 years from two Brazilian birth cohorts. Methods: The study was conducted on 1444 children whose data were collected at birth and at school age, in 1994 and 2004/2005 in Ribeirao Preto, where they were aged 10-11 years and in 1997/98 and 2005/06 in Sao Luis, where children were aged 7-9 years. Depressive symptoms were investigated with the Child Depression Inventory (CDI), categorized as yes (score >= 20) and no (score < 20). Adjusted and non-adjusted prevalence ratios (PR) were estimated by Poisson regression with robust estimation of the standard errors. Results: The prevalence of depressive symptoms was 3.9% (95% CI = 2.5-5.4) in Ribeirao Preto and 13.7% (95% CI = 11.0-16.4) in Sao Luis. In the adjusted analysis, in Ribeirao Preto, low birth weight (PR = 3.98; 95% CI = 1.72-9.23), skilled and semi-skilled manual occupation (PR = 5.30; 95% CI = 1.14-24.76) and unskilled manual occupation and unemployment (PR = 6.65; 95% CI = 1.16-38.03) of the household head were risk factors for depressive symptoms. In Sao Luis, maternal schooling of 0-4 years (PR = 2.39; 95% CI = 1.31-4.34) and of 5 to 8 years (PR = 1.80; 95% CI = 1.08-3.01), and paternal age < 20 years (PR = 1.92; 95% CI = 1.02-3.61), were independent risk factors for depressive symptoms. Conclusions: The prevalence of depressive symptoms was much higher in the less developed city, Sao Luis, than in the more developed city, Ribeirao Preto, and than those reported in several international studies. Low socioeconomic level was associated with depressive symptoms in both cohorts. Low paternal age was a risk factor for depressive symptoms in the less developed city, Sao Luis, whereas low birth weight was a risk factor for depressive symptoms in the more developed city, Ribeirao Preto.