Neonatal screening of ABO/RhD blood group and direct antiglobulin Coombs test. Experience of a single institution.

BACKGROUND: Evaluating the ABO/RhD blood group and the direct antiglobulin Coombs test (DAT) at birth is recommended good practice, but there is variability in its universal implementation. This study aims to show the comparative results in various variables of clinical impact during the hospital stay of neonates with positive DAT compared with those with negative DAT, based on the systematic detection of the ABO/RhD group and DAT at birth. METHODS: Newborns between 2017 and 2020 in a high-risk pregnancy care hospital were included. The ABO/RhD and DAT group was determined in umbilical cord samples or the first 24 hours of life. Demographic, maternal, and neonatal variables were recorded. The association between the variables was estimated using the odds ratio (OR). RESULTS: 8721 pairs were included. The DAT was positive in 239 newborns (2.7%), with the variables associated with positive PDC being maternal age > 40 years (OR: 1.5; 95% CI: 1.0 to 2.3), birth by cesarean section (1.4; 1.1-2.0), mother group O (6.4; 3.8-11.8), prematurity (3.6; 2.6-5.0), birth weight < 2500 g (2.1; 1.6-2.8), newborn group A (15.7; 10.7-23.1) and group B (17.6; 11.4-27.2), hemoglobin at birth < 13.5 g/dl (4.5; 2.8-7.1) and reticulocytosis > 9% (1.9; 1.2 to 3.1). DISCUSSION: The frequency of neonatal positive PDC was 2.7%, with a significant association with maternal/neonatal incompatibility to the ABO and RhD group, with a substantial impact on various neonatal variables. These results support the policy of universal implementation at the birth of the ABO/RhD and DAT determination.

INTRODUCCIÓN: La determinación del grupo sanguíneo ABO/RhD y la prueba directa de Coombs (PDC) al nacimiento son una práctica recomendada, pero existe variabilidad en su implementación universal. Se presentan los resultados de la determinación al nacimiento del grupo ABO/RhD y la PDC en una cohorte institucional. MÉTODOS: Se incluyeron los recién nacidos entre 2017 y 2020 en un hospital de atención a embarazos de alto riesgo. Se determinó el grupo ABO/RhD y se realizó la PDC en muestras de cordón umbilical o en las primeras 24 horas de vida. Se registraron las variables demográficas, maternas y neonatales. Se estimó la asociación entre las variables mediante la razón de probabilidad (OR). RESULTADOS: Se incluyeron 8721 binomios. La PDC fue positiva en 239 recién nacidos (2.7%), siendo las variables asociadas a la PDC positiva la edad materna > 40 años (OR: 1.5;IC95%: 1.0-2.3), el nacimiento por vía cesárea (1.4; 1.1-2.0), la madre del grupo O (6.4; 3.8-11.8), la prematuridad (3.6; 2.6-5.0); el peso al nacer < 2500 g (2.1; 1.6-2.8); el neonato del grupo A (15.7; 10.7-23.1) o del grupo B (17.6; 11.4-27.2), la hemoglobina al nacer < 13.5 g/dl (4.5; 2.8-7.1) y la reticulocitosis > 9% (1.9; 1.2 a 3.1). DISCUSIÓN: La frecuencia de PDC positiva neonatal es del 2.7%, con asociación significativa la incompatibilidad materna/neonatal al grupo ABO y RhD, con impacto significativo en diversas variables neonatales. Estos resultados apoyan la política de implementación universal al nacimiento de la determinación de ABO/RhD y PDC.

Use of computational biology to compare the theoretical tertiary structures of the most common forms of RhCE and RhD.

BACKGROUND AND OBJECTIVES: Computational biology analyses the theoretical tertiary structure of proteins and identifies the 'topological' differences between RhD and RhCE. Our aim was to identify the theoretical structural differences between the four isoforms of RhCE and RhD using computational biological tools. MATERIALS AND METHODS: Physicochemical profile was determined by hydrophobicity and electrostatic potential analysis. Secondary and tertiary structures were generated using computational biology tools. The structures were evaluated and validated using Ramachandran algorithm, which calculates the single score, p-value and root mean square deviation (RMSD). Structures were overlaid on local refinement of 'RhAG-RhCE-ANK' (PBDID 7uzq) and RhAG to compare their spatial distribution within the membrane. RESULTS: All proteins differed in surface area and electrostatic distance due to variations in hydrophobicity and electrostatic potential. The RMSD between RhD and RhCE was 0.46 ± 0.04 Å, and the comparison within RhCE was 0.57 ± 0.08 Å. The percentage of amino acids in the hydrophobic thickness was 50.24% for RhD while for RhCE it ranged between 73.08% and 76.68%. The RHAG hydrophobic thickness was 34.2 Å, and RhCE's hydrophobic thickness was 33.83 Å. We suggest that the C/c antigens differ exofacially at loops L1 and L2. For the E/e antigens, the difference lies in L6. By contrast, L4 is the same for all proteins except Rhce. CONCLUSION: The physicochemical properties of Rh proteins made them different, although their genes are homologous. Using computational biology, we model structures with sufficient precision, similar to those obtained experimentally. An amino acid variation alters the folding of the tertiary structure and the interactions with other proteins, modifying the electrostatic environment, the spatial conformations and therefore the antigenic recognition.

Analysis of a Novel Mexican Variant of the HBB Gene Associated with ß-Thalassemia Using Bioinformatic Tools.

We present a study performed on 54 unrelated subjects, with and without thalassemic features. Two primer pairs were proposed to perform Sanger sequencing of the complete HBB gene. The bioinformatic analysis was performed taking advantage of the availability of free online tools. In the sample, we found 11 variants, 10 reported, and one novel. Among the variants found, six are clinically important: three encode a premature stop codon [codon 39 (C>T) (HBB: c.118C>T); IVS-II-1 (G>A) (HBB: c.315+1G>A), and one not reported], a double substitution within the same allele [Hb Borås (HBB: c.266T>G) and Hb Santa Giusta Sardegna (HBB: c.282T>C)], and one whose pathogenicity is not yet defined [Hb Fannin-Lubbock I (HBB: c.359G>A)]. Even though the variants Hb Borås and Hb Santa Giusta Sardegna have been described, there is no report of their combined occurrence on the same allele, which could cause hemolytic anemia. Although the p.Leu88Arg and p.Cys93Trp variants do not alter the final length of the protein, the bioinformatic results suggest that there are differences in the tertiary structure of ß-globin genes, mainly affecting helices E and F, being the motifs of interaction with the heme group. The novel variant is a 4 bp insertion that modifies the open reading frame, changing the last amino acid residue and causing a premature stop codon (HBB: c.291-294insGCAC). The variant was associated with ß-thalassemia (ß-thal). Bioinformatic analysis made it possible to predict the consequences that the new variant of the HBB gene caused on the ß-globin tertiary structure.

Embarazo y COVID-19. Consideraciones en la práctica de la hematología / Pregnancy and COVID-19. Considerations in the practice of Hematology

Resumen La enfermedad por coronavirus 2019 (COVID-19) en una población vulnerable, como es el caso de la mujer embarazada, feto y recién nacido, obliga a establecer estrategias efectivas y seguras centradas en la seguridad del binomio madre-hijo. El objetivo del presente reporte es presentar los resultados de la revisión de las fuentes de información secundaria (metaanálisis y revisión sistemática) del estado del arte en el avance del conocimiento de la COVID-19 durante el embarazo. En diferentes reportes se ha insistido en que la mortalidad materna por COVID-19 es baja. Sin embargo, la razón de mortalidad materna (RMM) aumentó de 30.9 a 45.5 defunciones por cada 100,000 nacimientos, es decir, mostró un incremento del 36.32% respecto a la misma semana del 2019. Pero el tema no se limita a la COVID-19, el aumento en la RMM es del 24.% para hemorragia materna, del 20% para la enfermedad hipertensiva y del 28.5% para sepsis puerperal. Sin embargo, por su naturaleza de condición inédita y el comportamiento particular de la COVID-19 durante el periodo perinatal, la generación de nuevos datos, su integración a información accesible y su análisis clínico epidemiológico inevitablemente proporcionarán nuevas evidencias que deberán integrarse a la gestión y práctica clínica. No existe un comportamiento hematológico característico o de las complicaciones trombóticas o hemorrágicas de la paciente con COVID-19, son características clínicas similares a las que se presenta en sus pares sin embarazo. El aumento global en todas las causas de mortalidad materna no son exclusivas de la COVID-19, lo que expone las deficiencias del sistema de salud en términos de atención primaria de la salud, vigilancia prenatal y planificación familiar, entre otros programas más; adicional al impacto de la COVID-19. Es una necesidad imperiosa el rediseño de las políticas públicas en términos de atención primaria para la salud a toda la población, en particular para las mujeres embarazadas.

Abstract Coronavirus disease 2019 (COVID-19) in a vulnerable population, such as the pregnant woman, fetus, and newborn, requires an establishment of effective and safe strategies focused on the safety of the mother-child binomial. The objective of this report is to present the results of the review of secondary information sources (meta-analysis and systematic review), of the state of the art in the advancement of knowledge of the disease due to COVID-19 during pregnancy. Different reports have insisted that maternal mortality from COVID-19 is low. However, the maternal mortality ratio (MMR) increased from 30.9 to 45.5 deaths per 100,000 births, that is, it showed an increase of 36.32% compared to the same week of 2019. Due to its unprecedented condition and the particular behavior of the COVID-19 disease during the perinatal period, the generation of new data, its integration into accessible information and its epidemiological clinical analysis will inevitably provide new evidence that must be integrated into clinical management and practice. But the issue is not limited to COVID-19, the increase in MMR is 24% for maternal obstetric hemorrhage, 20% for hypertensive disease, and 28.5% for puerperal sepsis. There is no characteristic hematological behavior and the appearance of thrombotic or hemorrhagic complications in the patient with COVID-19, without clinical characteristics similar to those seen in her non-pregnant peers. The global increase in all causes of maternal mortality are not exclusive to COVID-19, which exposes the deficiencies of the health system in terms of primary health care, prenatal surveillance, family planning, among other programs; additional to the impact of COVID-19. The redesign of public policies in terms of primary health care for the entire population is an urgent need, particularly for pregnant women.

Low prevalence of IgG antibodies against antigens of HEV genotypes 1 and 3 in women with a high-risk pregnancy.

The aim of the study was to assess whether high-risk pregnant women have a higher prevalence of HEV during the perinatal period. This was a cross-sectional study of 428 patients: Group 1, 127 women with a high-risk pregnancy; Group 2, 97 asymptomatic people with reactivity to HCV or HBV; Group 3, 94 patients with clinical symptoms suggestive of HEV infection; and Group 4, 110 healthy blood donors from an urban area of Mexico City. ELISA was used to measure antibody to HEV genotypes 1 and 3. The prevalence rates of anti-HEV IgG antibodies were 0.79% in Group 1, 2.1% in Group 2, 7.4% in Group 3, and 0% in Group 4. Women with a high-risk pregnancy did not have a higher prevalence of HEV infection in this clinical setting.

Clara Cell Protein Expression in Mechanically Ventilated Term and Preterm Infants with Respiratory Distress Syndrome and at Risk of Bronchopulmonary Dysplasia: A Pilot Study.

The aim of this pilot study was to determine Clara cell protein (CC16) concentration in bronchoalveolar lavages (BAL) fluid from full-term and preterm (<37 weeks' gestational age) neonates requiring respiratory support, having symptoms of neonatal respiratory distress syndrome, and at risk of bronchopulmonary dysplasia (BPD). We hypothesized that CC16 may be predictive of BPD diagnosis regardless of gestational age. BAL fluid CC16 was measured by ELISA at birth and at day 7 of life. Both groups that developed BPD showed significantly decreased BAL fluid CC16 levels compared to those infants that did not develop the disease. CC16 positively correlated with diagnosis of BPD and negatively with the severity of the disease. These results suggest that BAL fluid CC16 levels may have a diagnostic value at day 7 for BPD in both term and preterm infants. This study demonstrates the potential utility of BAL fluid CC16 levels as a biomarker for BPD in term infants.

[Molecular identification of Hemoglobin D Punjab in cases detected in two families]. / Identificación molecular de la hemoglobina D Punjab en dos familias.

BACKGROUND: Hemoglobin D Punjab is the world most common variant hemoglobin D; in Mexico there are reports of isolated cases. Our goal is to present the clinical and molecular study in two families with HbD Punjab. The objective was to submit molecular diagnosis of two families with Hb D Punjab and clinical features. CLINICAL CASE: Family 1: neonate with maternal history of HbS carrier. Father and sister with natural variants for the evaluated mutations, mother, brother and index case were heterozygous for HbD Punjab. Family 2: neonate with positive neonatal screening for detection of abnormal hemoglobins. Mother and index case were heterozygous for HbD Punjab, homozygous for HFE H63D, and Gilbert's syndrome UGT1A1*28 heterozygous. Father heterozygous for HFE H63D and sister homozygous for such mutation. The study of two families for HbD Punjab, HbS, ß-thalassemia, HFE and Gilbert syndrome was performed by real time PCR. CONCLUSION: The molecular identification of HbD Punjab is an accessible methodological proposal that can adequately distinguish carriers subjects; through this method two additional cases, one initially identified as HbS.

Introducción: la hemoglobina D Punjab (HbD Punjab) es la variante mundial más frecuente de hemoglobina D. En México se tienen reportes de casos aislados. El objetivo es presentar el diagnóstico molecular de dos familias con HbD Punjab y sus características clínicas. Casos clínicos: familia 1: neonato cuya madre era portadora de HbS. El padre y la hermana tenían variante natural para las mutaciones evaluadas, madre, hermano y caso índice heterocigotos para HbD Punjab. Familia 2: neonato con tamiz neonatal positivo para la detección de hemoglobinas anormales. Madre y caso índice fueron heterocigotos para HbD Punjab, homocigotos para HFE H63, y heterocigotos para síndrome de Gilbert UGT1A1*28. Padre, heterocigoto para HFE H63D, y hermana homocigoto para dicha mutación. El estudio de las dos familias para HbD Punjab, HbS, beta-talasemia, HFE y síndrome de Gilbert se hizo mediante PCR en tiempo real. Conclusión: la identificación molecular de la HbD Punjab es una propuesta metodológica accesible y permite diferenciar adecuadamente a los portadores. A través de esta metodología se identificaron dos casos adicionales en nuestro país, uno de ellos identificado inicialmente como HbS.

Frequency of hepatitis C virus infection in a single institution in Mexico with a focus on birth-cohort population.

 Background and rationale for the study. The generation of people born before 1965 is a high-risk group for developing chronic hepatitis C virus (HCV) infection. AIM: To report the experience on single institution of HCV infection under birth-cohort or baby boomers effect. MATERIAL AND METHODS: We used a cross-sectional design of consecutive subjects older than 18 years referred for serological evaluation for anti-HCV and detection of HCV RNA. RESULTS: A total of 7,658 people were included. The global prevalence of HCV antibody was 4.5% (344/7658). The frequency with anti-HCV antibodies were 74 (10.9%), 158 (7.3%), and 112 (2.3%) for people born before 1945, 1945-1965, and 1966-1992, respectively (p < 0.01). The subjects HCV RNA-positive were 88.9%, 68.7%, and 44.4%, respectively (p < 0.001). The viral load was > 100,000 IU/mL in 74.4% of those positive for HCV RNA. Groups of older patients and anti-VHC, with year of birth before 1965, are more likely to show reactivity to HCV RNA and significant viral load (OR 10.0, CI 95% 4.8 to 20.1). CONCLUSION: We observed a high prevalence of unrecognized chronic HCV infection. The prevalence of HCV infection in people born before 1945 was twice the value of those born after 1965. Further studies are needed to determine the impact on health care services. Future work should focus on determining the appropriate model for the care of people at risk of chronic HCV.

Estimation of umbilical cord blood leptin and insulin based on anthropometric data by means of artificial neural network approach: identifying key maternal and neonatal factors.

BACKGROUND: Leptin and insulin levels are key factors regulating fetal and neonatal energy homeostasis, development and growth. Both biomarkers are used as predictors of weight gain and obesity during infancy. There are currently no prediction algorithms for cord blood (UCB) hormone levels using Artificial Neural Networks (ANN) that have been directly trained with anthropometric maternal and neonatal data, from neonates exposed to distinct metabolic environments during pregnancy (obese with or without gestational diabetes mellitus or lean women). The aims were: 1) to develop ANN models that simulate leptin and insulin concentrations in UCB based on maternal and neonatal data (ANN perinatal model) or from only maternal data during early gestation (ANN prenatal model); 2) To evaluate the biological relevance of each parameter (maternal and neonatal anthropometric variables). METHODS: We collected maternal and neonatal anthropometric data (n = 49) in normoglycemic healthy lean, obese or obese with gestational diabetes mellitus women, as well as determined UCB leptin and insulin concentrations by ELISA. The ANN perinatal model consisted of an input layer of 12 variables (maternal and neonatal anthropometric and biochemical data from early gestation and at term) while the ANN prenatal model used only 6 variables (maternal anthropometric from early gestation) in the input layer. For both networks, the output layer contained 1 variable to UCB leptin or to UCB insulin concentration. RESULTS: The best architectures for the ANN perinatal models estimating leptin and insulin were 12-5-1 while for the ANN prenatal models, 6-5-1 and 6-4-1 were found for leptin and insulin, respectively. ANN models presented an excellent agreement between experimental and simulated values. Interestingly, the use of only prenatal maternal anthropometric data was sufficient to estimate UCB leptin and insulin values. Maternal BMI, weight and age as well as neonatal birth were the most influential parameters for leptin while maternal morbidity was the most significant factor for insulin prediction. CONCLUSIONS: Low error percentage and short computing time makes these ANN models interesting in a translational research setting, to be applied for the prediction of neonatal leptin and insulin values from maternal anthropometric data, and possibly the on-line estimation during pregnancy.

Design of a protocol for obtaining genomic DNA from saliva using mouthwash: Samples taken from patients with periodontal disease.

BACKGROUND: Obtaining high quality genomic DNA safely and economically is vital for diverse studies of large populations aimed at evaluating the role of genetic factors in susceptibility to disease. AIM: This study was to test a protocol for the extraction of high quality genomic DNA from saliva samples obtained with mouthwash and taken from patients with periodontal disease. METHODS: Saliva samples were taken from 60 patients and then stored at room temperature. DNA extraction was carried out at distinct post-sampling times (10, 20 and 30 days). Evaluation of genomic DNA was performed with spectrophotometry, electrophoresis, and PCR genotyping and sequencing. RESULTS: The greatest concentration of DNA obtained was 352 µg at 10 days post-sampling, followed by 121.025 µg and 19.59 µg at 20 and 30 days, respectively. When determining the purity of DNA with the spectrophotometric ratio of 260/230, the relations of 1.20, 1.40 and 0.781 were obtained for 10, 20 and 30 days, respectively. In all samples, it was possible to amplify the product of 485 bp and the sequence of the amplicons showed 95% similarity to the reference sequence. CONCLUSION: The present protocol represents an easy, safe and economical technique for obtaining high quality genomic DNA.

[Molecular identification of glucose-6-phosphate dehydrogenase (G6PD) detected in neonatal screening]. / Identificación molecular de la glucosa-6-fosfato deshidrogenasa (G6PD) detectada en el tamiz neonatal.

AIMS: To present the strategy of identifying the molecular variants of G6PD detected in neonatal screening (NS). MATERIAL AND METHODS: We present a series of incident cases of newborns positive for G6PD deficiency detected in NS. From nuclear DNA with the methodology of real-time PCR we sought molecular G6PD variants: G202A, A376G, T968C and C563T. RESULTS: Of a total of 21,619 neonates, 41 cases were reactive in NS for G6PD (189.6/100,000 RN screened rate), 34 cases confirmed the molecular variant of G6PD (157.3/100,000 RN screened rate). The most frequent allele combination G202A/A376G (G6PD ratio and median activity, 0.460 and 1.72 ± 0.35 U/g Hb, respectively), followed by G202A (0.170 and 1.74 ± 0.27 U/g Hb) and A376G/T968C (ratio 0.150 and 1.10 ± 0.44 U/g Hb). The T968C allelic variant showed lower enzyme activity than the rest (1.1 ± 0.4; p = 0.02). Two women were detected with G6PD deficiency with G202A/A376G and G202A variant. CONCLUSIONS: African alleles were prevalently detected in neonatal screening. This strategy allows the identification of molecular variants involved in 80% of cases.

Variaciones en el recuento diferencial leucocitario desde el nacimiento hasta los primeros dos meses de edad en nacidos a término con bajo riesgo perinatal / Variations in the differential leukocyte count from birth through the first two months of age in term infants with low perinatal risk

Introducción: La presencia de neutropenia o neutrofilia se observa en la evaluación del neonato con sospecha de sepsis; sin embargo, en ausencia de infección sistémica, su incidencia no ha sido estimada en nuestra población. Material y métodos: En una cohorte de recién nacidos a término de bajo riesgo perinatal, seguidos desde el nacimiento hasta los dos meses de edad; se evaluaron la cuenta de leucocitos, neutrófilos (NT), linfocitos totales (LT) y la frecuencia de neutropenia a estas edades. Resultados: Se incluyeron 110 recién nacidos de bajo riesgo perinatal, evaluados al nacer, al mes y a los dos meses de edad. Los leucocitos totales promedio fueron de 18,950/µL (IC 95% 10,255 a 29,170), 11,250/µL (6,030-17,045) y 9,750/µL (6,055-17,900); los linfocitos totales de 7,442/µL (4,736-11,326), 8,198/µL (2,625-12,559) y 7,478/µL (4,276-12,782); los neutrófilos totales de 7,818/µL (2,853-13,809), 2,112 (927-7,021) y 1,944 (737-3,618), respectivamente. La incidencia de neutropenia significativa (< 750/L) fue del 0.9 al nacimiento, 2.7 al mes y 5.5% a los dos meses de edad. La neutrofilia (> 9,500/L) se presentó en el 35.5% de los neonatos al nacimiento, pero en ningún caso hacia el resto de las edades de estudio. Conclusiones: La presencia de neutropenia o neutrofilia es un cambio fisiológico en el neonato o lactante menor de bajo riesgo. Este hecho debe ser considerando en su interpretación particular en la evaluación de la sepsis a estas edades.

Introduction: The presence of neutropenia or neutrophilia is observed in the evaluation of the neonate with suspected sepsis; however, its incidence has not been estimated in our population in the absence of systemic infection. Material and methods: A cohort of newborns at term, with low perinatal risk, were followed from birth to two months of age, leukocyte count, neutrophils (NT), and total lymphocyte (TL) were evaluated; the frequency of neutropenia at these ages was determined. Results: We included 110 infants; the mean values of the total leukocyte count were 18,950/µL (CI 95% 10,255-29,170); 11,250/µL (6,030-17,045) and 9,750/µL (6,055-17,900); total lymphocytes, 7,442/µL (4,736 to 11,326), 8,198/µL (2,625-12,559) and 7,478/µL (4,276-12,782); total neutrophil count, 7,818/µL (2,853 to 13,809), 2,112 (927-7,021) and 1,944 (737-3,618) at birth, one and two months, respectively. Significant neutropenia (< 750/L) was 0.9 at birth, 2.7 at one month and 5.5% at two months of age. Neutrophilia (> 9,500/L) was present in 35.5% of infants at birth, but in none in the first and second months of age. Conclusions: The presence of neutropenia or neutrophilia is a physiological change in low-risk infants. This fact must be considered when evaluating sepsis at this age.

Evaluación del estado en la reserva neonatal de hierro y las mutaciones del gen HFE / Assessment of neonatal iron store and HFE gene mutations

Introducción: Se presenta la evaluación de la asociación entre la reserva de hierro (Fe) y los polimorfismos del gen de la hemocromatosis (HFE) en neonatos de alto riesgo perinatal. Métodos: Se incluyó una serie de neonatos de alto riesgo perinatal en los que se evaluó la reserva de Fe con la medición de la ferritina sérica (FS). Se dividieron en tres grupos: sobrecarga de Fe (SoFe), con FS >1,000 µg/l; reserva normal de Fe, con FS de 154-1,000 µg/l; y reserva baja de Fe, con FS <154 µg/l. Mediante PCR en tiempo real se buscaron las mutaciones C282Y, H63D y S65C del gen HFE. Resultados: Se estudiaron 97 neonatos. De ellos, 24 casos presentaron SoFe (proporción 0.247) y FS de 1,789 µg/l (IC 95% 1,376-2,201); 36 casos, reserva normal de FS (0.371), FS de 461 µg/l (389-533); y 37 casos, reserva baja de FS (0.381) y FS 82 µg/l (69-96). No hubo casos detectados para las mutaciones C282Y o S65C. Se identificó la variante H63D HFE en 18 neonatos (frecuencia génica de 0.185): la condición de heterocigoto (H63D/WT) en doce casos (frecuencia génica 0.124) y de homocigoto (H63D/H63D) en seis casos (frecuencia génica 0.062). La frecuencia alélica de H63D fue de 0.092. Los variante H63D HFE no mostró asociación con los neonatos de reserva normal de Fe contra reserva baja (OR 1.2; IC 95% 0.3-4.3) ni los de reserva normal contra neonatos con SoFe (OR 2.5; 0.7-9.2). Conclusiones: Cerca del 25% de neonatos de alto riesgo tendrá sobrecarga de Fe. Aún con el posible sesgo de selección, las variantes del gen HFE no influyen sobre el estado de la reserva de Fe.

Background: The association between iron stores (Fe) and HFE gene polymorphisms on high-risk neonates is shown. Methods: We included newborns with high perinatal risk. Newborns were divided into three groups for measurements of serum ferritin (SF): iron overload (IO) with SF 1000 µg/L, normal iron stores (NIS) with SF 154-1000 µg/L and low iron stores (LIS) with SF <154 µg/L. We used real-time PCR for identification of polymorphisms C282Y, H63DE, and S65C of the HFE gene. Results: We studied 97 newborns with IO in 24 cases (ratio 0.247) and SF 1789 µg/L (95% CI 1376-2201), NIS in 36 cases (0.371), and SF of 461 µg/L (389-533) and LIS in 37 cases (0.381) and SF 82 µg/L (69-96). There were no cases detected for C282Y or S65C mutations. We identified 18 neonates with H63D HFE variant (gene frequency 0.185) with heterozygous condition (H63D/ WT) in 12 cases (gene frequency 0.124) and homozygote (H63D/H63D) in six cases (gene frequency 0.062). H63D allele frequency was 0.092. The HFE H63D variant showed no association for comparing infants with NIS vs. LIS (OR 1.2, 95% CI 0.3-4.3) and NIS vs. IO newborn infant (OR 2.5, 0.7-9.2). Conclusions: In high-risk neonates ∼25% show IO even with the possible selection bias. HFE gene variants do not influence on the neonatal iron stores.

Bioética en tiempo real: El Límite de la viabilidad en los recién nacidos / Bioethics in real time: The limit of viability in newborn infants

Introducción: los avances en la medicina perinatal en sociedades con mayor desarrollo industrial, han generado reducción en las tasas de mortalidad neonatal con una gradual disminución en la edad gestacional con posibilidades de supervivencia. Objetivo: analizar los elementos bioéticos considerados en la toma de decisiones para establecer los límites de viabilidad en el recién nacido. Metodología: se realizó una búsqueda bibliográfica en distintas fuentes y bases de datos electrónicas sobre los aspectos éticos, legal y humanista en relación con el límite de la viabilidad en los recién nacidos. Resultados y conclusiones: se describen dos escenarios clínicos, que son la plataforma para ejemplificar e iniciar el análisis del dilema ético que condiciona el límite de la viabilidad; se discute la zona gris de la neonatología de acuerdo a tasas de sobrevivencia y tasas de mortalidad en distintos países con diferentes características, dividiéndolos en países desarrollados o subdesarrollados. Se realiza el análisis bioético del dilema, en base a las teorías éticas y modelos de discernimiento: teorías utilitarista, deontológica y aretológica...

Advances in perinatal medicine over the past decades have led to reduced rates in neonatal mortality with a gradual decrease in gestational age with chances of survival. The aim of this review is to analyze the elements considered in bioethical decision making to establish the limits of viability in the newborn infant. A literature search was conducted in different sources and electronic databases on different ethics, legal and humanitarian aspects in relation to the limit of neonatal viability. We describe two clinical scenarios, which are the platform to start the analysis of the ethical dilemma that determines the limit of viability. We discuss the “gray zone” of neonatology according to survival and mortality rates in different countries with distinctive characteristics, dividing them into developed and developing countries. Bioethical analysis is performed of the dilemma, based on ethical theories and models of judgment: utilitarian, deontological and aretological theories...

[Acute adverse effects in transfusion. Proposals for the hemosurveillance system]. / Efectos nocivos agudos de las transfusiones. Propuestas para el Sistema de Hemovigilancia en México.

The management model based on risk prevention has become a major influence in shaping policies for transfusion safety. There are approximately sixty interactions between the health worker and the patient during the transfusion process,representing the number of times where you have the opportunity to make a mistake.We present an analysis of the weaknesses of the National Blood System, with particular attention to the haemovigilance donor and patient. The proposals include the implementation of the National Blood containing the need to establish from the National Blood Safety, significant changes in the regulatory framework and the internal regulations of the Ministry of Health, the CNTS and COFEPRIS. Is required to promote and coordinate the collection of accurate information from the committees of transfusion medicine, which will be accompanied by an initial diagnosis from the National Survey of Blood. Requires notice to other forms of funding to ensure the viability of the projects operating blood bank. Finally, as a strategic resource, the blood is of public, so access should not be restricted.

Pérdida de peso corporal y velocidad de crecimiento postnatal en recién nacidos menores de 1,500 gramos durante su estancia en un hospital de tercer nivel de atención / Body weight and postnatal growth velocity in premature ≤ 1,500 g during their hospital stay in a teartiary level of care

Introducción: La pérdida de peso en los primeros cinco a siete días de vida y el crecimiento en los prematuros depende de muchos factores. Existe una asociación inversa entre la edad gestacional y la pérdida de peso corporal en la primera semana de vida: a menor edad gestacional y menor peso al nacimiento es más difícil lograr una velocidad de crecimiento adecuada. Los objetivos de este estudio fueron determinar la pérdida de peso corporal en recién nacidos ≤ 1,500 g, calcular la velocidad de crecimiento absoluta (g/día) y relativa (g/kg/día), y correlacionar la pérdida ponderal porcentual con la edad gestacional. Material y métodos: Estudio observacional, longitudinal y retrospectivo de recién nacidos ≤ de 1,500 g. Las variables de estudio fueron edad gestacional, peso, talla y perímetro cefálico al nacer, con seguimiento de peso diario, talla y perímetro cefálico semanal. Se calculó la pérdida ponderal máxima, la velocidad de crecimiento y se correlacionó la pérdida ponderal máxima con la edad gestacional. Resultados: Se analizaron 101 casos, con edad gestacional promedio de 30.2 ± 2.3, peso al nacer de 1,190.7 g ± 204.5, 42 neonatos (41.6%) fueron con peso bajo para la edad gestacional y 59 (58.4%) con peso adecuado para la edad gestacional. El porcentaje máximo de pérdida de peso fue de 8.6 ± 4.5%, la recuperación del peso se presentó en el día 10.9 ± 5.2; la velocidad de crecimiento fue de 19.3 ± 5.4 g/día y 16.9 ± 5.4 g/kg/día; a menor edad gestacional hay mayor pérdida ponderal máxima con una correlación negativa baja y significativa (r = -0.422, p < 0.0001). Conclusiones: La velocidad de crecimiento absoluta (g/d) y relativa (g/kg/d) son útiles en la valoración nutricia diaria de todo recién nacido prematuro, permite detectar patrones de crecimiento subóptimos y realizar de manera oportuna intervenciones nutricionales para mejorar la velocidad de crecimiento. La pérdida ponderal en recién nacidos prematuros tiene una asociación significativa negativa, inversa con la edad gestacional.

Introduction: Weight loss in the first five to seven days of life and growth in preterm infants depends on many factors. In the first week of life, there is an inverse association between gestational age and loss of body weight; with very low birth weight and low gestational age is more difficult to achieve adequate growth velocity. The objectives were to determine the loss of body weight in infants less than 1,500 g calculate, the absolute growth velocity (g/day) and relative (g/kg/day), and correlate the percentage weight loss and gestational age. Methods: Observational, longitudinal and retrospective study of preterm neonates ≤ 1,500 g. The variables analyzed were at birth: weight, gestational age, length, and cephalic circumference, then monitoring the weight per day, and length and cephalic circumference, per week. It was calculated maximum weight loss and growth velocity. For maximum weight loss and gestational age, Pearson correlation was used. Results: Cases of 101 infants, with birth weight 1,190.7 ± 204.5 g and gestational age of 30.2 ± 2.3 were analyzed, 42 neonates (41.6%) had low birth weight for gestational age and 59 (58.4%) adequate weight for gestational age; the maximum average of weight loss was 8.6% ± 4.5; loss was presented in day 4.2 ± 1.7 and weight regain was presented on day 10.9 ± 5.2. Growth velocity was 19.3 ± 5.4 g/day and 16.9 ± 5.4 g/kg/day, an inverse negative correlation was observed between weight loss and gestational age (r = -0.422, p < 0.0001). Conclusions: The absolute growth velocity (g/day) and relative (g/kg/day) are useful in assess the nutritional condition in premature infants, and gives the opportunity to clinicians detect suboptimal growth velocity patterns and make adequate interventions. An inverse negative correlation was observed between weight loss and gestational age.

Control térmico en el recién nacido pretérmino / Thermal control in preterm newborn

La historia del control térmico neonatal data de finales del siglo XIX con la observación de Pierre Budin en el Hospital de Maternidad de París; Budin reportó una disminución en la mortalidad del 66 al 38% en recién nacidos con peso ≤ 2,000 gramos, posterior a la introducción de medidas de control térmico. Con el número creciente de prematuros de muy bajo peso que se atienden hoy en día en las Unidades de Cuidado Intensivo Neonatal es esencial que pediatras, neonatólogos y todo el personal involucrado en la atención entiendan la transición y la adaptación fisiológica que estos niños deben hacer, con la finalidad de proporcionarles un ambiente térmico óptimo con la tecnología que está disponible en la actualidad. La revisión concluye con la evaluación de la información disponible en estudios clínicos, mediante niveles de evidencia y grados de recomendación de acuerdo al sistema GRADE.

The history of neonatal thermal control dates from the late XIX century, with the observation of Pierre Budin in Paris Maternity Hospital, reporting a decrease in mortality from 66 to 38% in infants weighing ≤ 2,000 grams, after the introduction of thermal control measures. With the growing number of very low birth weight infants who are seen today in the Neonatal Intensive Care Units, it is essential that pediatricians, neonatologists and all staff involved in the care, understand the transition and physiological adaptation children should do, with the aim of providing a optimal thermal environment thermal environment with currently available technology. The review concludes with an evaluation of available information on clinical studies, using levels of evidence and grades of recommendation, according to the GRADE system.

Association between genotype and plasma levels of thrombin-activated fibrinolysis inhibitor (TAFI) in the development of preeclampsia.

INTRODUCTION: The objective was to evaluate if thrombin-activated fibrinolysis inhibitor (TAFI) polymorphisms (G505A, C1040T, and G-438A), and TAFIa plasma levels are associated with preeclampsia. MATERIALS AND METHODS: In a case-control study design, we evaluated preeclampsia patients and women with uncomplicated pregnancies. The TAFI polymorphisms were determined by real-time PCR method, and TAFIa plasma levels were established with a chromogenic assay. RESULTS: We included 87 women in each group. The TAFIa levels in the preeclampsia group were 20.4 µg/mL (CI 95% 17.3-23.5), while in the control group, they were significantly lower: 13.3 µg/mL (12.0-14.5, p 0.003). There were no differences in the genotype distribution or allelic frequency of TAFI polymorphisms between the two groups. In preeclampsia patients and controls heterozygous for the G505A polymorphism, the TAFIa values were 22.8 (16.7-28.9 µg/mL) and 13.2 (11.3-15.0 µg/mL, p 0.019), respectively. In G505A homozygous polymorphism the TAFIa values were 25.7 (18.7-32.6 µg/mL) and 13.5 (1.6-21.9 µg/mL, p 0.041), respectively. In the C1040T and G-438A TAFI wild type polymorphisms, the TAFIa values were 18.3 (12.5-23.9 µg/mL) and 11.5 (9.9-35.0, p 0.033), and 19.4 (10.9-27.9 µg/mL) and 12.5 (10.8-14.2 µg/mL, p 0.006), respectively, without differences in other genotypes. CONCLUSIONS: Preeclampsia by itself may be responsible for the increase in TAFIa values rather than the presence of polymorphisms.

[RH hybrid box identification in subjects with Rh negative phenotype from Mexico's Valley]. / Identificación de la caja RH híbrida en el fenotipo Rh negativo de sujetos del valle de México.

BACKGROUND: The prevalence of the RhD and RhCE gene alleles is related to the ethnic mixture. The aim of this report is to describe the predominant molecular mechanisms in RhD negative subjects residents from Mexico's valley according to the phenotype of RhCE. METHODS: Blood samples from RhD negative women and men were studied. The RhD/RhCE phenotype was identified by hemagglutination and Rh hybrid box by PCR-FRLP with PstI. RESULTS: 216 subjects were included. The RhD phenotypes were ccdee in 179 cases (82.8%), Ccdee in 15 cases (11.6%), ccdEe in seven (3.2%), CcdEe in four (1.9%), and CcdEE in a single subject (0.5%). In five cases, RhD hybrid box was not amplified (2.3%), 21 cases were hemizygotes (9.7%), and 188 cases homozygotes (87%), for RhD hybrid box. The homozygote condition was more frequent in those individuals with phenotype ccdee (87%). The allelic frequency of RhD hybrid box was 0.928. The frequency of Rhcc haplotype was higher in those subjects homozygotes for RhD hybrid box (chi2 = 4.658, p < 0.05). CONCLUSIONS: In this population, RhD gene deletion is the main molecular mechanism to generate to RhD negative condition and this depends on the European mixture.