A Longitudinal 1H NMR-Based Metabolic Profile Analysis of Urine from Hospitalized Premature Newborns Receiving Enteral and Parenteral Nutrition.

Preterm newborns are extremely vulnerable to morbidities, complications, and death. Preterm birth is a global public health problem due to its socioeconomic burden. Nurturing preterm newborns is a critical medical issue because they have limited nutrient stores and it is difficult to establish enteral feeding, which leads to inadequate growth frequently associated with poor neurodevelopmental outcomes. Parenteral nutrition (PN) provides nutrients to preterm newborns, but its biochemical effects are not completely known. To study the effect of PN treatment on preterm newborns, an untargeted metabolomic 1H nuclear magnetic resonance (NMR) assay was performed on 107 urine samples from 34 hospitalized patients. Multivariate data (Principal Component Analysis, PCA, Orthogonal partial least squares discriminant analysis OPLS-DA, parallel factor analysis PARAFAC-2) and univariate analyses were used to identify the association of specific spectral data with different nutritional types (NTs) and gestational ages. Our results revealed changes in the metabolic profile related to the NT, with the tricarboxylic acid cycle and galactose metabolic pathways being the most impacted pathways. Low citrate and succinate levels, despite higher glucose relative urinary concentrations, seem to constitute the metabolic profile found in the studied critically ill preterm newborns who received PN, indicating an energetic dysfunction that must be taken into account for better nutritional management.

Genetic spectrum and clinical early natural history of glucose-6-phosphate dehydrogenase deficiency in Mexican children detected through newborn screening.

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) newborn screening is still a matter of debate due to its highly heterogeneous birth prevalence and clinical expression, as well as, the lack of enough knowledge on its natural history. Herein, we describe the early natural clinical course and the underlying GDPD genotypes in infants with G6PDd detected by newborn screening and later studied in a single follow-up center. G6PDd newborns were categorized into three groups: group 1: hospitalized with or without neonatal jaundice (NNJ); group 2: non-hospitalized with NNJ; and group 3: asymptomatic. Frequencies of homozygous UGT1A1*28 (rs34983651) genotypes among G6PDd patients with or without NNJ were also explored. RESULTS: A total of 81 newborns (80 males, one female) were included. Most individuals (46.9%) had NNJ without other symptoms, followed by asymptomatic (42.0%) and hospitalized (11.1%) patients, although the hospitalization of only 3 of these patients was related to G6PDd, including NNJ or acute hemolytic anemia (AHA). Nine different G6PDd genotypes were found; the G6PD A-202A/376G genotype was the most frequent (60.5%), followed by the G6PD A-376G/968C (22.2%) and the Union-Maewo (rs398123546, 7.4%) genotypes. These genotypes produce a wide range of clinical and biochemical phenotypes with significant overlapping residual enzymatic activity values among class I, II or III variants. Some G6PD A-202A/376G individuals had enzymatic values that were close to the cutoff value (5.3 U/g Hb, 4.6 and 4.8 U/g Hb in the groups with and without NNJ, respectively), while others showed extremely low enzymatic values (1.1 U/g Hb and 1.4 U/g Hb in the groups with and without NNJ, respectively). Homozygosity for UGT1A1*28 among G6PDd patients with (11.9%, N = 5/42) or without (10.3%, N = 4/39) NNJ did not shown significant statistical difference (p = 0.611). CONCLUSION: Wide variability in residual enzymatic activity was noted in G6PDd individuals with the same G6PD genotype. This feature, along with a documented heterogeneous mutational spectrum, makes it difficult to categorize G6PD variants according to current WHO classification and precludes the prediction of complications such as AHA, which can occur even with > 10% of residual enzymatic activity and/or be associated with the common and mild G6PD A-376G/968C and G6PD A-202A/376G haplotypes.

A Proinflammatory Immune Response Might Determine Toxoplasma gondii Vertical Transmission and Severity of Clinical Features in Congenitally Infected Newborns.

Toxoplasma gondii is the etiological agent of toxoplasmosis. Mother-to-child transmission of this parasite can occur during pregnancy. Newborns with congenital toxoplasmosis may develop central nervous system impairment, with severity ranging from subclinical manifestations to death. A proinflammatory/regulated specific immune profile is crucial in the defense against the parasite; nevertheless, its role in the infected pregnant women and the congenitally infected offspring has been poorly explored, and there is still no consensus about its relation to parasite vertical transmission or to severity and dissemination in the congenitally infected newborns. This work aimed to characterize these relations by means of principal component and principal factor analyses. For this purpose, we determined the specific production of the four immunoglobulin G antibody subclasses, cytokines, and lymphocyte proliferation in the T. gondii-infected pregnant women-10 who transmitted the infection to their offspring and seven who did not-as well as in 11 newborns congenitally infected and grouped according to disease severity (five mild and six moderate/severe) and dissemination (four local and seven disseminated). We found that the immune response of nontransmitter women differed from that of the transmitters, the latter having a stronger proinflammatory response, supporting a previous report. We also found that newborns who developed moderate/severe disease presented higher levels of lymphocyte proliferation, particularly of CD8+ and CD19+ cells, a high proportion of tumor necrosis factor α producers, and reduced expression of the immune modulator transforming growth factor ß, as opposed to children who developed mild clinical complications. Our results suggest that a distinctive, not regulated, proinflammatory immune response might favor T. gondii vertical transmission and the development of severe clinical manifestations in congenitally infected newborns.

Immunoglobulin Concentrations in Plasma and Saliva During the Neonatal Period.

BACKGROUND: Screening for infectious diseases in newborns using immunoglobulin (Ig)A-, IgM-, and IgE-specific antibodies is expensive and impractical. To determine if total levels of these Igs can be used for screening purposes, thus simplifying the process, their basic levels in the 1(st) month of extrauterine life need to be determined. Additionally, the ability to simplify screening by using saliva also needs to be determined. The aim of this study was to determine IgA, IgM, and IgE concentrations in plasma and saliva in newborns, correlation between the samples, and relationship between Ig levels and newborn age. METHODS: We enrolled 53 apparently healthy newborns, paired samples of plasma and saliva were collected, and total IgA, IgM, and IgE concentrations determined by capture enzyme-linked immunosorbent assay. The correlation between plasma and saliva values was calculated by Spearman's rank correlation coefficient and the IgA, IgM, and IgE distributions were analyzed by the Shapiro-Wilk test. We also determined the level of each Ig concentration according to age. RESULTS: IgA and IgM levels in plasma and IgA levels in saliva increased significantly during 1(st) month of life, especially in the 2(nd) week and 3(rd) week, with a good correlation of IgA between plasma and saliva. IgE levels in both plasma and saliva and IgM levels in saliva were very low or absent. CONCLUSION: These results suggest that Igs in saliva could be good biomarkers for newborn screening programs during the 1(st) week of life. This study established reference values for Igs according to age in the neonatal period.

Molecular diagnosis and genotyping of cases of perinatal toxoplasmosis in Mexico.

Toxoplasma gondii congenital transmission depends partially on parasite load and genotype. Both factors were examined in 4 mother/newborn pairs with perinatal infection acquired in central Mexico. Type I and type I-related strains were identified. These results add information regarding T. gondii strains prevailing in humans, although neither the genotype nor the load were related to vertical transmission or damage.

Dificultad respiratoria por deficiencia de surfactante en un hospital público de tercer nivel sin maternidad. Factores asociados a mortalidad / Respiratory distress due to surfactant deficiency in a third-level hospital with no in-patient deliveries. Factors related to mortality

Introducción. La deficiencia de surfactante causa frecuentemente dificultad respiratoria en prematuros; se realizó este trabajo para conocer los factores asociados a la mortalidad por esta causa. Métodos. Se analizaron 257 casos. Se obtuvieron datos demográficos, antecedentes, enfermedades asociadas, uso de surfactante y desenlace. Se compararon las variables independientes entre sobrevivientes y fallecidos usando χ², razón de momios con intervalo de confianza al 95% o prueba t de Student. Se subdividió la serie en 1500 g de peso buscando diferencias. Resultados. El 60% fueron varones. El peso promedio fue de 1666 g y el promedio de semanas de gestación fue de 31. En 9% hubo inducción de madurez pulmonar. Falleció el 30%. Se encontró diferencia estadística entre vivos y fallecidos en el promedio de peso (1812 g en vivos y 1321g en fallecidos; P<0.001) y en edad gestacional (32 vs 29 semanas, P<0.001). Los factores de riesgo asociados a defunción estadísticamente significativos fueron diabetes materna (RM:9.8; IC95: 1-89) y amenaza de aborto (RM: 13.2; IC95: 2.8-62). No hubo diferencia significativa entre los que se les aplicó surfactante y los que no, ni entre los que se aplicó antes o después de 3,6 o 12 horas. Conclusiones. La mortalidad por deficiencia de surfactante aún es alta, principalmente entre los más pequeños. En esta serie el surfactante no disminuyó la mortalidad.

Background: Surfactant deficiency is a frequent cause of respiratory distress in the preterm newborn. The aim of this study is to determine the factors associated with mortality. Methods: We studied 257 cases in a tertiary-care neonatal intensive care unit with no in-hospital deliveries. We compared survivors and deaths with the χ2 test and calculated odds ratio and confidence interval at 95%. We subdivided the cases at 1500 g looking for any differences. Results: Of the newborns, 60% were male. Mean birth weight was 1666 g and gestational age was 31 weeks. In only 9% was there pulmonary maturation induction with steroids. Overall mortality was 30%. Statistical differences were found between live newborns and deaths according to mean birth weight (1812 g vs 1321 g, p <0.001) and gestational age (32 vs 29 weeks, p <0.001). Associated risk factors were maternal diabetes (OR 9.8, 95% CI: 1-89) and abortion threat (OR 13.2; 95% CI: 2.8-62). There was no difference between those babies who received or did not receive surfactant or when it was received before or after 3, 6 or 12 h. Conclusions: Mortality due to surfactant deficiency was high, especially among lower birth weight infants. Surfactant did not lower mortality in this group.

[Fetal cardiac rhabdomyoma as a rare cause of hydrops fetalis. A report of a case]. / Rabdomioma cardiaco fetal como causa rara de hydrops fetalis. Reporte de un caso.

Cardiac tumors are rare entities at any age. The reported incidence in fetal echocardiograms is 0.17%. This case report presents the detection of a cardiac rhabdomyoma in a 27.5 weeks of gestational age (WGA) fetus during a routine sonogram. Treatment with terbutaline, as a cardiac inotropic and chronotropic agent, was started because of fetal bradichardia of 86 beats per minute, as well as fetal lung maturity inductors. At 30 WGA furosemide was added because of fetal hydrops. At 32 WGA a cesarean section was performed. The fetal development at the time of birth was in accordance to the gestational age, the newborn weight was 1,820 g and the Apgar score was 1-0, at one and five minutes after delivery. The newborn died immediately after the interruption of the umbilical circulation, because of a 90% obstruction of the left ventricular cavity caused by the tumor. The present case is an evidence of the utility of a medical treatment in a severely ill fetus, that allowed it to continue with its normal development for four weeks after the diagnosis and opens the possibility for fetal medical therapy in the future for similar cases.

[Neonatal sepsis morbidity and mortality in a tertiary care hospital]. / Morbilidad y mortalidad por sepsis neonatal en un hospital de tercer nivel de atención.

OBJECTIVE: To compare the epidemiological, clinical and microbiological profiles between patients with neonatal sepsis who lived or died. MATERIAL AND METHODS: The medical records of patients with neonatal sepsis were retrospectively reviewed at Instituto Nacional de Pediatría (National Pediatric Institute) of Secretaría de Salud (Ministry of Health) in Mexico City, between 1992 and 2000. Neonatal sepsis cases were classified as surviving or not after 90 days of postnatal follow-up. The survivor and decreased groups were compared using Mann-Whitney's U test for continuous variables, and the chi-squared test or the Fisher's exact test for categorical variables. Significantly associated variables were included in a Cox proportional hazards model. A p-value < 0.05 was considered statistically significant for all analyses. RESULTS: A total of 116 patients with neonatal sepsis were included (65 live and 51 dead). Multivariate analysis showed that fetal distress, respiratory distress, a delayed capillary fill up, a low platelet count, and a positive hemoculture for Klebsiella pneumoniae were significant risk factors for death. CONCLUSIONS: Epidemiological, clinical, laboratory, and microbiological variables are significant predictors of death in newborns with neonatal sepsis. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Morbilidad y mortalidad por sepsis neonatal en un hospital de tercer nivel de atención / Morbidity and mortality due to neonatal sepsis in a tertiary care hospital

OBJETIVO: Comparar el comportamiento de un grupo de recién nacidos sépticos que fallecieron contra un grupo de recién nacidos sépticos vivos. MATERIAL Y MÉTODOS: Revisión retrospectiva de expedientes de un grupo de recién nacidos con sepsis neonatal, atendidos en el Instituto Nacional de Pediatría, de la Secretaría de Salud de México, en la Ciudad de México, D.F., entre 1992 y 2000, los cuales se dividieron en recién nacidos sépticos vivos y fallecidos a los 90 días de seguimiento máximo. Se compararon las variables entre los grupos a través de U de Mann Whitney en el caso de variables numéricas, y ji cuadrada o prueba exacta de Fisher en el caso de variables categóricas. Las variables significativas en el análisis bivariado se incluyeron en uno de riesgos proporcionales de Cox. En todos los análisis se consideró como significativo un valor de p< 0.05. RESULTADOS: Se incluyeron 116 casos (65 vivos, 51 fallecidos). El antecedente de sufrimiento fetal, la presencia de dificultad respiratoria, el llenado capilar prolongado, la presencia de plaquetopenia y el hemocultivo positivo a Klebsiella pneumoniae estuvieron significativamente asociados con mayor riesgo de muerte en el modelo multivariado. CONCLUSIONES: Existen antecedentes epidemiológicos, clínicos, de laboratorio y microbiológicos capaces de predecir significativamente el riesgo de muerte a lo largo de la hospitalización de un recién nacido séptico

Eficacia de un analizador de bilirrubina no invasivo en neonatos / Utility of a non-invasive bilirubin transcutaneous analyzer in neonates

Introducción. La ictericia es una causa frecuente de consulta en el recién nacido. Se han intentado métodos para determinar su intensidad en forma no invasiva. Se realizó el presente estudio para evaluar la utilidad de un analizador no invasivo de bilirrubina. Material y métodos. Se estudiaron 22 neonatos con ictericia, a quienes se les determinó bilirrubina sérica total y bilirrubina transcutánea en la piel de la frente, tórax y abdomen con el método de espectrofotometría de reflectancia (Bilichek de Spectrx). Se realizó comparación de resultados en los diferentes sitios contra la bilirrubina sérica total. Para el análisis estadístico se realizó prueba de correlación de Pearson. Resultados. La mejor correlación fue en la piel de la frente con un coeficiente de pearson de 0.958 (P<0.001) con error estándar estimando de 1.87 mg/dL. Conclusión. La determinación predictiva transcutánea es eficaz cuando se usa dentro de los límites de funcionamiento del analizador no invasivo de bilirrubina

Hipocalcemia en prematuros / Hypocalcemia in premature infants

Se estudiaron prospectivamente 56 recién nacidos prematuros que ingresaron al Departamento de Cuidados Intensivos Neonatales del I.N.P. durante un año. Se encontró hipocalcemia en 24 casos (0.43 por ciento). La patología más frecuentemente asociada a hipocalcemia, al momento de la hospitalización, fue dificultad respiratoria, 20 de 24 paciantes (0.8 por ciento); asfixia, 14 a 24 (0.6 por ciento) septicemía, 10 de 24 (0.4 por ciento) y hemorragia intracraneana, 8 de 24 (0.3 por ciento). La asociación hipocalcemia/sexo femenino fue de 13 a 24 (0.5 por ciento) y ayuno/hipocalcemia 17 de 24 (0.7, cifras altamante significativas con p<0.05 y p<0.01, respectivamente. El temblor fino y la hipotensión fueron más frecuentes en hipocalcémicos que en normocalcémicos. Los niños que recibieron furosemide requirieron aporte terapéutico de calcio por más tiempo que los que no lo recibieron (p<0.001)

Recién nacidos con poliglobulia. Tratamiento comparativo con plasma y con solución salina / Polycythemia in the newborns. Comparative treatment with plasma and saline isotonic solution

Se realizó un estudio experimental, aleatorio y controlado en 32 recién nacidos con poliglobulia; se analizó comparativamente su manejo con plasma o solución salina isotonica en 16 niños de cada grupo respectivamente. No hubo diferencias estadísticamente significativas entre los dos grupos en sexo, edad gestacional y cronológica, peso corporal, estado nutricional y condiciones clínicas; tampoco en los valores plasmáticos de sodio, cloro, bicarbonato, glucosa ni complicaciones. Se concluye que el uso de solución salina es tan eficaz como el plasma para disminuir de manera significativa el hematócrito; no hay diferencias estadísticamente significativas entre ambos procedimientos. Es preferible la solución salina pues no tiene los riesgos inmunológicos ni infecciosos del plasma; es más accesible y menos costosa

Pericarditis: experiencia de 12 años en el Instituto Nacional de Pediatría / Pericarditis: twelve years experience at the Instituto Nacional de Pediatría

Se estudiaron 77 pacientes con pericarditis en el Instituto Nacional de Pediatría en un periodo de 12 años. La edad varió de 19 días a 20 años. Hubo 42 por ciento de varones y 58 por ciento de mujeres. Los síntomas más frecuentes fueron fiebre, disnea, tos, dolor torácico. Los signos más frecuentes fueron hepatomegalia, taquicardia, palidez e insuficiencia cardiaca. Las causas más importantes fueron artritis reumatoide juvenil, infecciones, lupus eritematoso sistémico y la forma crónica inespecífica. Once pacientes presentaron taponamiento cardiaco y siete cursaron con la forma constructiva. Se realizó pericardiocentesis en 17 pacientes y a 10 se les realizó pericardiectomía. Fallecieron 16 pacientes

Absorción intestinal deficiente de lactosa (AIDL) en niños con diarrea aguda sin deshidratación / Lactose deficient intestinal apsortion in children with acute diarrhea without dehydration

Se estudiaron 55 niños con diarrea aguda sin deshidratación para determinar si presentaban o no absorción intestinal deficiente de lactosa (AIDL) por medio de la prueba de iones hidrógeno en aire espirado. La AIDL se encontró en 24/55 niños. Al contrastar la prueba de iones hidrógeno en aire espirado contra pH y azúcares reductores en heces para el diagnóstico de AIDL, no hubo diferencias estadísticamente significativas. Rotavirus fue el agente patógeno más frecuentemente involucrado (12/55 casos); sin embargo, sólo en dos se demostró AIDL. Se formaron dos grupos de acuerdo al resultado de la prueba. Grupo I, sin AIDL y Grupo II con AIDL. Al primero se le administró leche entera, leche modificada o ambas en proteínas con lactosa y el grupo II se dividió en tres subgrupos alimentados con fórmulas con lactosa, sin lactosa y soya sin lactosa. No hubo diferencias estadísticamente significativas en la frecuencia de niños por la prueba de iones hidrógeno, en tanto que en 5/24 niños ocurrió entre la 2a y 4a semana y en 2/24 en la semana 9 y 10. por lo tanto, el empleo de fórmulas sin lactosa, o sin soya ni lactosa en niños con diarrea aguda sin deshidratación no parece justificarse

Enfermedad de membrana hialina / Hyaline membrane disease

La enfermedad de membrana hialina es una entidad grave originada por deficiencia de factor surfactante. La prematurez es el facator más importante en la etiología. El tratamiento es difícil y la morbimortalidad elevada. Se discuten los diversos elementos terapéuticos.