Predicting severe maternal outcomes in a network of sentinel sites in Latin-American countries.

OBJECTIVE: This study aimed to determine incidences of potentially life-threatening conditions (PLTC), maternal near misses (MNM), and maternal deaths (MD) in women who gave birth in participating facilities, and to determine the probability that a pregnancy involving a PLTC would evolve into an MNM and/or an MD. METHODS: This was a multicentric observational study implemented on a maternal network from August 2018 to May 2019 in five Latin-American countries. We summarized categorical variables as frequencies and continuous variables with median, interquartile range, and standard deviations. Positive and negative likelihood ratios were calculated and multivariate predictive models were built. RESULTS: There were 33 901 deliveries and miscarriages, of which 8.0% had at least one PLTC and 0.6% had an MNM. Hypertensive disorder was the most frequent condition to evolve into a severe maternal outcome. CONCLUSION: Identifying PLTC can help to prevent MNM and MD. The inclusion of these predictors in a real-time data registration system like the Perinatal Informatic System could work as a surveillance tool for early detection, leading to a reduction in the rate of worsening conditions.

Cáncer colorrectal. Variantes génicas en la vía de señalización BMP y ancestría en población mexicana / Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population

Resumen Introducción: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. Objetivo: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. Métodos: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. Resultados: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. Conclusiones: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Abstract Introduction: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. Objective: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. Methods: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. Results: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. Conclusions: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

Periodontitis prevalence and associated factors: a comparison of two examination protocols / Prevalencia y factores asociados a periodontitis: comparación de dos protocolos de examen WHO

ABSTRACT The fact that there are different epidemiological definitions of periodontitis and different evaluation protocols affects the estimate of periodontitis prevalence and of the influence of associated factors. The gold standard for periodontal examination is full-mouth record assessing CAL and PD. However, there are not always sufficient human and financial resources available to apply such assessment for epidemiological surveillance systems. Aim: This study was conducted to compare different protocols and definitions of periodontitis for assessing prevalence and the impact of related factors in adult patients who requested care at the School of Dentistry, UdelaR. Materials and Method: This was a cross-sectional study of 410 subjects with a high burden of disease in terms of NCDs and periodontitis. Clinical examination evaluated PD in all teeth and CAL in the CPI sextants (WHO 2013). Four periodontitis criteria were defined based on two examination protocols (WHO 2013 and WHO 1997) and two definitions of epidemiological case. Comparisons were made taking the 2013 WHO protocol as a reference. Results: Comparison of the two examination protocols showed that prevalence was underestimated when the WHO 1997 protocol was used to define moderate-severe and severe periodontitis, by 20% and 60%, respectively. Conclusions: When the severity of periodontitis was not considered, the WHO 2013 protocol did not provide more information on what factors increase the chance of periodontitis. However, when severity was considered, the associated factors were different. Consequently, in a small population, it would be worth using the WHO 2013 protocol, which is the closest to the full-mouth gold standard criterion.

RESUMEN La variabilidad en la definición epidemiológica de la periodontitis y los protocolos de evaluación afectan la medición de la prevalencia y su asociación con ciertos factores. Si bien, el patrón oro para el examen periodontal es el registro de boca completa, que evalúa la pérdida de inserción (CAL, por sus siglas en inglés) y profundidad de sondaje (PS, por sus siglas en inglés), los recursos no siempre están disponibles para los sistemas de vigilancia epidemiológica. Objetivo: En este estudio se compararon diferentes protocolos y definiciones de periodontitis evaluando la prevalencia y la asociación de factores relacionados en pacientes adultos que solicitaron atención en la Facultad de Odontología de la UdelaR. Materiales y Método: Los datos provienen de un estudio transversal de 410 sujetos con una elevada carga de enfermedad en términos de ENT y periodontitis. Se utilizó un examen clínico registrando PD en todos los dientes y CAL en los sextantes CPI (WHO 2013). Se definieron cuatro criterios de periodontitis basados en dos protocolos de examen y dos definiciones epidemiológicas de caso. Las comparaciones se realizaron tomando como referencia el protocolo de la OMS de 2013. Resultados: Al comparar los dos protocolos de examen, se verificó la subestimación de la prevalencia cuando se utilizó el protocolo de la OMS de 1997 para la definición de caso moderado-grave y para la periodontitis grave, siendo en el primer caso del 20% y en el segundo caso tres veces mayor que. Conclusiones: Si no se considera la gravedad de la periodontitis, el uso del protocolo de la OMS 2013 no proporciona más información sobre qué factores aumentan la probabilidad de periodontitis. Sin embargo, al analizar la gravedad, los factores asociados fueron diferentes. En consecuencia, en una población pequeña estaría justificado el esfuerzo de utilizar el protocolo de la OMS de 2013, ya que el criterio de referencia es la boca completa.

Cesarean section in Uruguay from 2008 to 2018: country analysis based on the Robson classification. An observational study.

BACKGROUND: The use of caesarean section has steadily increased, with Latin America being the region with the highest rates. Multiple factors account for that increase and the Robson classification is appropriate to compare determinants at the clinical level for caesarean section rates over time. The purpose of this study is to describe the evolution of caesarean section rates by Robson groups in Uruguay from 2008 to 2018 using a country level database. METHODS: We included the records of all women giving birth in Uruguay (pregnancies ≥22 weeks and weights ≥500 g) with valid data in the mode of childbirth recorded in the Perinatal Information System database between 2008 and 2018. Caesarean section rates were calculated by Robson groups for each of the years included, disaggregated by care sector (public/private) and by geographical area (Capital City/Non-Capital), with time trends and their significance analyzed using linear regression models. RESULTS: Of the total 485,263 births included in this research, the overall caesarean section rate was 43,1%. In 2018, among the groups at lower risk of caesarean section (1 to 4), the highest rates were seen in women in group 2B (98,8%), followed by those in group 4B (97,9%). A significant increase in the number of caesarean sections was seen in groups 2B (97,9 to 98,8%), 3 (8,36 to 11,1%) and 4 (A (22,7 to 26,9%) and B (95,4 to 97,9%) Significant growth was also observed in groups 5 (74,3 to 78,1%), 8 (90,6 to 95,5%), and 10 (39,1 to 46,7%). The private sector had higher rates of caesarean section for all groups throughout the period, except for women in group 9. The private sector in Montevideo presented the highest rates in the groups with the lowest risk of caesarean section (1, 2A, 3 and 4A), followed by the private sector outside of the capital. CONCLUSION: Uruguay is no exception to the increasing caesarean section trend, even in groups of women who have lower risk of requiring caesarean section. The implementation of interventions aimed at reducing caesarean section in the groups with lower obstetric risk in Uruguay is warranted.

Periodontitis prevalence and associated factors: a comparison of two examination protocols.

The fact that there are different epidemiological definitions of periodontitis and different evaluation protocols affects the estimate of periodontitis prevalence and of the influence of associated factors. The gold standard for periodontal examination is full-mouth record assessing CAL and PD. However, there are not always sufficient human and financial resources available to apply such assessment for epidemiological surveillance systems. AIM: This study was conducted to compare different protocols and definitions of periodontitis for assessing prevalence and the impact of related factors in adult patients who requested care at the School of Dentistry, UdelaR. MATERIALS AND METHOD: This was a cross-sectional study of 410 subjects with a high burden of disease in terms of NCDs and periodontitis. Clinical examination evaluated PD in all teeth and CAL in the CPI sextants (WHO 2013). Four periodontitis criteria were defined based on two examination protocols (WHO 2013 and WHO 1997) and two definitions of epidemiological case. Comparisons were made taking the 2013 WHO protocol as a reference. RESULTS: Comparison of the two examination protocols showed that prevalence was underestimated when the WHO 1997 protocol was used to define moderate-severe and severe periodontitis, by 20% and 60%, respectively. CONCLUSIONS: When the severity of periodontitis was not considered, the WHO 2013 protocol did not provide more information on what factors increase the chance of periodontitis. However, when severity was considered, the associated factors were different. Consequently, in a small population, it would be worth using the WHO 2013 protocol, which is the closest to the full-mouth gold standard criterion.

La variabilidad en la definición epidemiológica de la periodontitis y los protocolos de evaluación afectan la medición de la prevalencia y su asociación con ciertos factores. Si bien, el patrón oro para el examen periodontal es el registro de boca completa, que evalúa la pérdida de inserción (CAL, por sus siglas en inglés) y profundidad de sondaje (PS, por sus siglas en inglés), los recursos no siempre están disponibles para los sistemas de vigilancia epidemiológica. OBJETIVO: En este estudio se compararon diferentes protocolos y definiciones de periodontitis evaluando la prevalencia y la asociación de factores relacionados en pacientes adultos que solicitaron atención en la Facultad de Odontología de la UdelaR. Materiales y Método: Los datos provienen de un estudio transversal de 410 sujetos con una elevada carga de enfermedad en términos de ENT y periodontitis. Se utilizó un examen clínico registrando PD en todos los dientes y CAL en los sextantes CPI (WHO 2013). Se definieron cuatro criterios de periodontitis basados en dos protocolos de examen y dos definiciones epidemiológicas de caso. Las comparaciones se realizaron tomando como referencia el protocolo de la OMS de 2013. RESULTADOS: Al comparar los dos protocolos de examen, se verificó la subestimación de la prevalencia cuando se utilizó el protocolo de la OMS de 1997 para la definición de caso moderado-grave y para la periodontitis grave, siendo en el primer caso del 20% y en el segundo caso tres veces mayor que. CONCLUSIONES: Si no se considera la gravedad de la periodontitis, el uso del protocolo de la OMS 2013 no proporciona más información sobre qué factores aumentan la probabilidad de periodontitis. Sin embargo, al analizar la gravedad, los factores asociados fueron diferentes. En consecuencia, en una población pequeña estaría justificado el esfuerzo de utilizar el protocolo de la OMS de 2013, ya que el criterio de referencia es la boca completa.

Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population.

INTRODUCTION: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. OBJECTIVE: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. METHODS: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. RESULTS: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. CONCLUSIONS: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

INTRODUCCIÓN: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. OBJETIVO: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. MÉTODOS: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. RESULTADOS: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. CONCLUSIONES: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Dyslipidemia, Obesity, and Ethnicity in Mexican Children.

The aim of this study was to assess lipid disorders in children from five ethnic groups, both urban and indigenous, from northern and central Mexico. We measured the lipid profile to determine the ability of the body mass index (BMI) to discriminate an abnormally high lipid level using receiving operating characteristics (ROC). We analyzed the association and interaction of obesity and ethnicity with lipid disorders using generalized linear models in 977 children. The highest prevalence of lipid disorders (high TG, high TC, high LDL, high APOB, and dyslipidemia) was found in central Mexico-Mexico City and urban northern Mexico. The BMI performed better at predicting low HDL in Seris, a northern indigenous group (0.95, CI: 0.69-0.85), and Mexico City (0.75, CI: 0.69-0.82), and high LDL in Puebla (central Mexico, 0.80, CI: 0.69-0.85). Obesity significantly (p < 0.05) increases lipid disorders by around two times (OR~2) for almost all lipid markers. Obesity and ethnic interaction increase the lipid disorders by more than five times for different lipid markers and ethnic groups (high total cholesterol OR = 5.31; low HDL OR = 5.11, and dyslipidemia OR = 5.68). Lipid disorders are not restricted to children with high BMIs, but obesity exacerbates these. The emerging lipid disorder risk depends on the ethnic group.

Relación entre el consumo materno de carne vacuna durante el embarazo y los niveles de ferritina en el cordón umbilical / Relationship between maternal beef consumption during pregnancy and umbilical cord ferritin concentration / Relação entre o consumo materno de carne bovina durante a gravidez e os níveis de ferritina no cordão umbilical

Antecedentes: la nutrición durante el embarazo impacta en la salud del recién nacido, con efectos a nivel epigenético determinando consecuencias neurológicas a largo plazo. Las necesidades de hierro durante el embarazo se estiman en 27 mg/día. El hierro hemo que se absorbe mejor se encuentra en la carne. La determinación de ferritina en sangre de cordón umbilical permite evaluar los depósitos de hierro alcanzados durante la etapa fetal. Sus niveles se asociaron con efectos a largo plazo sobre el desarrollo infantil. Objetivos: el objetivo de este estudio de carácter exploratorio es determinar la relación entre el consumo de carnes rojas durante el tercer trimestre de gestación y el nivel de ferritina en el cordón umbilical. Métodos: se realizó un estudio observacional descriptivo con datos recolectados prospectivamente durante un año en el Departamento de Neonatología del Centro Hospitalario Pereira Rossell (CHPR) en Montevideo, Uruguay. Un total de 188 pacientes cumplieron los criterios de inclusión. Se extrajo sangre del cordón umbilical después de un pinzamiento estricto del cordón pasado un minuto de vida. La ferritina se midió utilizando el método de quimioinmunofluorescencia. Se aplicó una encuesta nutricional materna (cualitativo-cuantitativa) que midió la frecuencia de consumo de alimentos con fuente de hierro y las cantidades aproximadas consumidas durante el último trimestre del embarazo. Esta encuesta se centró en el consumo materno de carne vacuna como principal fuente de hierro hemínico en Uruguay. Se analizó la relación entre estas variables. Resultados: el déficit latente de hierro (ferritina en el cordón umbilical <100 ng/ml) se asoció con un menor consumo de carne vacuna durante el embarazo. Valor p de Fisher: 0,0133, OR: 3,71, IC del 95% (1,25-11,05). Conclusiones: este estudio considera adecuada la evidencia que relaciona que los niveles bajos de consumo total de hierro y de carne vacuna durante el tercer trimestre de gestación determinarán un mayor riesgo de déficit latente de hierro y de ferritina medido en el cordón umbilical. Los niveles descendidos de ferritina en cordón umbilical se asocian con un mayor riesgo de efectos adversos a largo plazo sobre la mielinización y el desarrollo neurocognitivo.

Background: nutrition during pregnancy impacts the foetus and the newborn health, it has consequences at the epigenetic level and determines long-term neurological consequences. Iron requirements during pregnancy are estimated at 27 mg/day. Iron is blood absorption from is most efficient from beef. Umbilical cord blood ferritin levels can be used to assess iron deposits reached during the foetal stage. Ferritin levels are linked to the child's long-term development. Objective: this exploratory study's objective is to determine the relationship between beef consumption during the first quarter of pregnancy and ferritin levels in the umbilical cord. Methods: we carried out a descriptive, observational study with prospectively collected data for one-year at the Neonatology Department of the Pereira Rossell Hospital Center (CHPR) in Montevideo, Uruguay. A total of 188 patients met the inclusion criteria. We extracted umbilical cord blood after a strict cord clamping after one minute of life. Ferritin was measured using the chemoimmunofluorescence method. We carried out a maternal nutritional survey using a qualitative-quantitative method and measured the frequency and approximate quantity of iron source food consumption during the last quarter of pregnancy. This survey was focused on maternal beef consumption as the major heme iron source in Uruguay. We analyzed the relationship between these variables. Results: latent iron deficiency (ferritin in the umbilical cord <100 ng / ml) was associated with lower beef consumption during pregnancy. Fisher p-value: 0.0133, OR: 3.71, 95% CI (1.25 - 11.05). Conclusions: this study agrees with the evidence that shows that low levels of total iron and beef consumption during pregnancy determine an increased risk of latent iron deficiency and lower levels of ferritin in newborns, and therefore, greater risk of long-term adverse effects on myelination and neurocognitive development.

Contexto: a nutrição durante a gravidez tem impacto sobre a saúde do recém-nascido, com efeitos no nível epigenético, determinando consequências neurológicas a longo prazo. As necessidades de ferro durante a gravidez são estimadas em 27 mg / dia. O ferro heme de melhor absorção e aquele encontrado na carne vacuna. A determinação da ferritina no sangue do cordão umbilical permite avaliar os depósitos de ferro atingidos na fase fetal. Seus níveis foram associados a efeitos de longo prazo no desenvolvimento das crianças. Objetivos: o objetivo deste estudo exploratório é determinar a relação entre o consumo de carne vermelha durante o terceiro trimestre de gestação e o nível de ferritina no cordão umbilical. Métodos: foi realizado um estudo observacional descritivo com dados coletados prospectivamente durante um ano no Departamento de Neonatologia do Centro Hospitalar Pereira Rossell (CHPR) em Montevidéu, Uruguai. Um total de 188 pacientes cumpriram os critérios de inclusão. O sangue do cordão umbilical foi coletado após clampeamento estrito do cordão após um minuto de vida da criança. A ferritina foi medida pelo método de quimioimunofluorescência. Aplicamos um inquérito nutricional materno (qualitativo-quantitativo) que mediu a frequência de consumo de alimentos com fonte de ferro e as quantidades aproximadas consumidas durante o último trimestre da gravidez. Esta pesquisa enfocou o consumo materno de carne bovina como principal fonte de ferro heme no Uruguai. A relação entre essas variáveis foi analisada. Resultados: a deficiência latente de ferro (ferritina no cordão umbilical <100 mg / ml) foi associada ao menor consumo de carne bovina durante a gestação. Valor de p de Fisher: 0,0133, OR: 3,71, IC 95% (1,25-11,05). Conclusões: este estudo concorda com as evidências que relacionam que os baixos níveis de ferro total e consumo de carne bovina durante o terceiro trimestre de gestação determinam um maior risco de déficit de ferro latente e ferritina mensurado no cordão umbilical. A redução dos níveis de ferritina no cordão umbilical está associada a um risco aumentado de efeitos adversos de longo prazo na mielinização e no desenvolvimento neurocognitivo.

Immune profiling of breast milk from mothers with treated celiac disease.

BACKGROUND: The protective effect of breastfeeding on celiac disease (CD) onset is controversial. We studied a wide range of milk components in milk produced by celiac mothers following long-term gluten-free diet (GFD) in comparison to milk produced by healthy mothers. METHODS: Breast-milk samples from celiac (n = 33) and healthy (n = 41) mothers were obtained during the first year of lactation. A panel of bioactive components was analyzed by enzyme-linked immunosorbent assay in the aqueous fraction. We studied molecules involved in defenses, immunoregulation, and strengthening of the gut-epithelial barrier. RESULTS: During late lactation (from 6 to 12 months after delivery), the content of total immunoglobulin A (IgA) and IgM was significantly lower in the milk produced by celiac patients. Nevertheless, gliadin (GFD)-specific IgA relative contribution was higher in this group, in contrast to tetanus toxoid-specific antibodies. The balance between pro-inflammatory and anti-inflammatory molecules was different. While interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 were most frequently found in samples from celiac mothers, soluble Toll-like receptor-2 prevalence was lower. CONCLUSIONS: We describe differences between the innate and adaptive immune profile of milk produced by celiac and healthy mothers. These results might explain previous controversial reports about breastfeeding and CD protection. IMPACT: In spite of a long-term adherence to GFD, the milk produced by mothers with CD exhibit a different immune profile, in relation with some immunoregulatory factors and antibody content. This work shows a more comprehensive characterization of milk from celiac mothers, including macronutrients, lysozymes, growth factors, and immunoregulatory components that had not been studied before. The present study widens the available data regarding the characteristics of human milk of celiac mothers following GFD. Further follow-up studies of the health of children who were breastfed by celiac mothers will be necessary in order to also estimate the impact of the present results therein.

Differential admixture in Latin American populations and its impact on the study of colorectal cancer.

Genome-wide association studies focused on searching genes responsible for several diseases. Admixture mapping studies proposed a more efficient alternative capable of detecting polymorphisms contributing with a small effect on the disease risk. This method focuses on the higher values of linkage disequilibrium in admixed populations. To test this, we analyzed 10 genomic regions previously defined as related with colorectal cancer among nine populations and studied the variation pattern of haplotypic structures and heterozygosity values on seven categories of SNPs. Both analyses showed differences among chromosomal regions and studied populations. Admixed Latin-American samples generally show intermediate values. Heterozygosity of the SNPs grouped in categories varies more in each gene than in each population. African related populations have more blocks per chromosomal region, coherently with their antiquity. In sum, some similarities were found among Latin American populations, but each chromosomal region showed a particular behavior, despite the fact that the study refers to genes and regions related with one particular complex disease. This study strongly suggests the necessity of developing statistical methods to deal with di- or tri-hybrid populations, as well as to carefully analyze the different historic and demographic scenarios, and the different characteristics of particular chromosomal regions and evolutionary forces.

Genomic Diversity in Sporadic Breast Cancer in a Latin American Population.

Among Latin American women, breast cancer incidences vary across populations. Uruguay and Argentina have the highest rates in South America, which are mainly attributed to strong, genetic European contributions. Most genetic variants associated with breast cancer were described in European populations. However, the vast majority of genetic contributors to breast cancer risk remain unknown. Here, we report the results of a candidate gene association study of sporadic breast cancer in 176 cases and 183 controls in the Uruguayan population. We analyzed 141 variants from 98 loci that have been associated with overall breast cancer risk in European populations. We found weak evidence for the association of risk variants rs294174 (ESR1), rs16886165 (MAP3K1), rs2214681 (CNTNAP2), rs4237855 (VDR), rs9594579 (RANKL), rs8183919 (PTGIS), rs2981582 (FGFR2), and rs1799950 (BRCA1) with sporadic breast cancer. These results provide useful insight into the genetic susceptibility to sporadic breast cancer in the Uruguayan population and support the use of genetic risk scores for individualized screening and prevention.

Predictive value of blood measurement of Complement System proteins and metabolic components for early detection of obstetric complications linked to poor placental function.

Preeclampsia-eclampsia syndrome (PES) is associated with severe obstetric complications and there are no efficient methods available for an early detection. We studied blood concentration of some immunological and metabolic markers in association with obstetric outcome in healthy pregnant women and patients with obstetric risk factors, by ELISA and biochemical tests. Patients with complications showed higher levels of CRP and C4 positively correlated with Triglycerides and Cholesterol concentrations. Our results provide evidence that Immunological and metabolic alterations contribute to obstetric complications and that biomarkers linked to these alterations could be useful for an early detection of these problems.

Effect of 15 BMI-Associated Polymorphisms, Reported for Europeans, across Ethnicities and Degrees of Amerindian Ancestry in Mexican Children.

In Mexico, the genetic mechanisms underlying childhood obesity are poorly known. We evaluated the effect of loci, known to be associated with childhood body mass index (BMI) in Europeans, in Mexican children from different ethnic groups. We performed linear and logistic analyses of BMI and obesity, respectively, in Mestizos and Amerindians (Seris, Yaquis and Nahuatl speakers) from Northern (n = 369) and Central Mexico (n = 8545). We used linear models to understand the effect of degree of Amerindian ancestry (AMA) and genetic risk score (GRS) on BMI z-score. Northern Mexican Mestizos showed the highest overweight-obesity prevalence (47.4%), followed by Seri (36.2%) and Central Mexican (31.5%) children. Eleven loci (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2/rs13130484, FAIM2/rs7132908, FAM120AOS/rs944990, LMX1B/rs3829849, ADAM23/rs13387838, HOXB5/rs9299) were associated with BMI and seven (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2 rs13130484, LMX1B/rs3829849) were associated with obesity in Central Mexican children. One SNP was associated with obesity in Northern Mexicans and Yaquis (SEC16B/rs543874). We found higher BMI z-score at higher GRS (ß = 0.11, p = 0.2 × 10-16) and at lower AMA (ß = -0.05, p = 6.8 × 10-7). The GRS interacts with AMA to increase BMI (ß = 0.03, p = 6.08 × 10-3). High genetic BMI susceptibility increase the risk of higher BMI, including in Amerindian children.

Effect of multi-component school-based program on body mass index, cardiovascular and diabetes risks in a multi-ethnic study.

BACKGROUND: Mexico occupies one of the first places worldwide in childhood obesity. Its Mestizo and Indigenous communities present different levels of westernization which have triggered different epidemiological diseases. We assessed the effects of a multi-component school-based intervention program on obesity, cardiovascular and diabetes risk factors. METHODS: A physical activity, health education and parent involvement (PAHEPI) program was developed and applied in six urban (Mestizo ethnic group) and indigenous (Seri and Yaqui ethnic groups) primary schools for 12 weeks. A total of 320 children aged 4-12 years participated in intervention program; 203 under Treatment 1 (PAHEPI program) and 117, only from Mestizo groups, under Treatment 2 (PAHEPI+ school meals). For Body Mass Index (BMI), cardiovascular and diabetes factors, pairwise comparisons of values at baseline and after treatments were done using Wilcoxon signed rank test. Generalized linear models were applied to assess the intervention effect by age, sex and nutritional status in relation to ethnicity and treatment. RESULTS: We observed improvements on BMI in children with overweight-obesity and in triglycerides in the three ethnic groups. The Mestizo ethnic group showed the largest improvements under Treatment 2. While Seris showed improvements only in cardiovascular risk factors, Yaquis also showed improvements in diabetes risk factors, though not in BMI. CONCLUSIONS: This study showed that the same intervention may have positive but different effects in different ethnic groups depending on their lifestyle and their emerging epidemiological disease. Including this type of intervention as part of the school curriculum would allow to adapt to ethnic group in order to contribute more efficiently to child welfare. TRIAL REGISTRATION: This study was retrospectively registered under the identifier NCT03768245 .

Genome-Wide Association Study of Body Mass Index and Body Fat in Mexican-Mestizo Children.

BACKGROUND: Childhood obesity is a major health problem in Mexico. Obesity prevalence estimated by body mass index (BMI) is almost half than that estimated by percent body fat (%BF) in the Childhood Obesity pediatric cohort (COIPIS). OBJECTIVE: We performed a genome-wide association study (GWAS) of BMI and %BF in 828 children from the COIPIS to identify markers of predisposition to high values for both phenotypes used for obesity classification. METHODS: For the GWAS we used the LAT Axiom 1, Affymetrix and 2.5 million single loci from the 1000 Genomes Phase 3 imputation panel. We used a linear model, adjusted by age, sex, and Amerindian ancestry assuming an additive inheritance model. RESULTS: Genome-wide significance (p ≤ 5.0 × 10-8) and 80% of statistical power was reached for associations of two loci in two genes (CERS3 and CYP2E1) to BMI. Also, 11 loci in six genes (ANKS1B, ARNTL2, KCNS3, LMNB1, SRGAP3, TRPC7) reached genome-wide significance for associations to %BF, though not 80% of statistical power. DISCUSSION: None of the SNPs were previously reported as being associated to BMI or %BF. In addition, different loci were found for BMI and %BF. These results highlight the importance of gaining deeper understanding of genetic markers of predisposition to high values for the phenotypes used for obesity diagnosis.

Análisis de la vía del parto en los diferentes escenarios asistenciales en Uruguay / Analysis of ways of delivery in the different health scenarios in Uruguay / Análise da via de parto nos diferentes setores assistenciais no Uruguai

Antecedentes: en Uruguay, el Ministerio de Salud ha seleccionado la disminución de las cesáreas innecesarias como uno de los objetivos sanitarios nacionales por considerarlo un problema de salud pública. Objetivos: analizar las tasas de cesáreas por sector asistencial: público versus privado y Montevideo versus interior, usando la clasificación de Robson como insumo para su disminución. Material y método: estudio descriptivo de corte transversal que categoriza cada nacimiento ocurrido en Uruguay en 2017 en uno de los diez grupos de Robson, según el sector de asistencia y el lugar geográfico donde ocurrió, informando el tamaño relativo, la tasa de cesáreas y las contribuciones absolutas y relativas hechas por cada grupo a la tasa global de cesáreas. Resultados: la tasa de cesáreas en 2017 fue de 44%. Los grupos que más contribuyeron a la tasa global de cesáreas (70% de las cesáreas practicadas en el país) fueron: mujeres con una o más cesáreas previas, cesáreas electivas o inducciones fallidas en nulíparas y el grupo de nulíparas de término con inicio espontáneo. Luego de ajustar por las variables pronósticas, la probabilidad de terminar en cesáreas en el sector privado fue 18% mayor que en el sector público, sin mostrar diferencias en los resultados perinatales. Las tasas de cesáreas por grupos de Robson en Montevideo y en el interior se muestran muy similares. Conclusiones: fomentar el parto vaginal después de una cesáreas, evitar cesáreas electivas e inducciones innecesarias y disminuir la primera cesáreas son las medidas propuestas para bajar las tasas de cesáreas innecesarias. Guías clínicas basadas en la mejor evidencia científica que sistematicen estas intervenciones ayudarán a implementar los cambios.

Background: in Uruguay, the Ministry of Public Health has set the reduction of unnecessary C-sections as one of the "National Health Goals", as it considers this a public health issue. Objectives: to analyse the C-section rates by health sector: the private sector versus the public sector and Montevideo versus the rest of the country, using the Robson classification and an input to be used to reduce the rate. Method: transversal descriptive study that categorizes every birth in Uruguay during 2017 according to the Robson criterion in one of the 10 groups, depending on the healthcare center and the geographical place of birth, reporting the relative size, the C-section rate and the absolute and relative contributions of each group to the global CS rate. Results: in 2017 the CS rare was 44%. The groups that contributed the most to the global CS rate (70% of the CS in the country) were the following: women with previous CS, elective CS or failed induced labor in nulliparous women and the term nulliparous women with spontaneous initiation of labor group. After adjusting the prognostic variables, the possibility of ending up in CS in the private sector was 18% higher than in the public sector, without there being any differences in terms of the perinatal results. CS rates by Robson group in Montevideo and the rest of the country are very similar. Conclusions: vaginal birth must be encouraged after a CS, elective CS and unnecessary induction of labor must be avoided, and the number of first CS needs to be reduced. These are the measures proposed to reduce the unnecessary CS rates. Clinical guidelines based on the best scientific evidence that systematize these interventions will contribute to the implementation of changes.

Antecedentes: o Ministério da Saúde do Uruguai (MS) definiu como um dos "Objetivos sanitários nacionais" a redução do número de cesáreas (CS) necessárias por considerar que este é um problema de saúde pública. Objetivos: analisar as taxas de CS por setor assistencial: público vs privado e geográfico: Montevideo vs Interior usando a classificação de Robson, como insumo para sua redução. Material e métodos: estudo descritivo transversal que classifica cada nascimento ocorrido no Uruguai em 2017, em um dos 10 grupos de Robson de acordo com o setor de assistência e o lugar onde aconteceu, informando tamanho relativo, taxa de CS e as contribuições absolutas e relativas de cada grupo à taxa global de CS. Resultados: a taxa de CS em 2017, foi de 44%. Os grupos que mais contribuíram para a taxa global de CS (70% das CSs realizadas no país) foram: as cesareadas previas, as cesáreas eletivas ou induções falidas em nulíparas e o grupo de nulíparas a termo com início espontâneo. Depois de ajustar pelas variáveis prognósticas, a probabilidade de terminar em CS no setor privado foi 18% maior que no setor público, sem diferenças nos resultados perinatais. As taxas de CS por grupos de Robson em Montevideo e no Interior foram similares. Conclusões: fomentar o parto vaginal depois de uma CS, evitar CS eletivas e induções desnecessárias e diminuir a quantidade de primeira CS, são las medidas propostas para reduzir as taxas de cesáreas desnecessárias. Pautas clínicas baseadas na melhor evidência científica que sistematizem estas intervenções ajudarão a implementar as mudanças propostas.

Global burden of disease among teenagers in Uruguay and its comparison with Latin America and the Caribbean. / Carga de enfermedad de los adolescentes en Uruguay y su comparación con la de América Latina y el Caribe.

INTRODUCTION: Adolescence is considered a healthy stage of life and therefore little studied. This study described mortality over time in teenagers in Uruguay and analysed the burden of disease at this stage of life by the measure of Years of Life Lost by Premature Death in Uruguay and by comparison with rates in Latin America and the Caribbean by sex, cause and sub-region. METHODOLOGY: Secondary data sources used were the national registry of deaths in Uruguay, the first Global Burden of Disease study in Uruguay and the information on the data visualisation page of the Institute of Metrics and Health Evaluation. Data were extracted by the authors and displayed in tables and graphs. RESULTS: Teenager mortality held roughly stable between 1997 and 2015. More years were lost to premature death among Uruguayan men, the main causes being traffic accidents, self-inflicted injuries and violence. The same behaviour occurs throughout the region. CONCLUSIONS: The social determinants of health connected with poverty and inequality play a role in the development of depression, risky and violent behaviour, which possibly explain the loss of years due to premature death in adolescence.

Introducción. La adolescencia es considerada una etapa de buena salud y por tanto poco estudiada. El objetivo de este estudio es describir la evolución de la mortalidad en adolescentes en Uruguay y analizar la carga de enfermedad en esta etapa de la vida, a través de la medida de los Años de Vida Perdidos por Muerte Prematura en Uruguay y su comparación con los de América Latina y el Caribe según sexo, causa y subregión. Metodología. Se utilizaron fuentes de datos secundarias: el registro nacional de defunciones del Uruguay, el primer estudio de Carga Global de Enfermedad en Uruguay y la información presentada por la página de visualización de datos del Instituto de Métricas y Evaluación en Salud. Resultados. La mortalidad en los adolescentes se ha mantenidos aproximadamente estable entre 1997 y 2015. Loa años perdidos por muerte prematura para el Uruguay son más en los hombres y sus principales causas son los accidentes de tránsito, heridas auto infringidas y violencia. El mismo comportamiento se presenta en la región. Conclusiones. Los determinantes sociales de la salud vinculados a la pobreza e inequidad tienen un rol en el desarrollo de depresión, conductas riesgosas y violentas que posiblemente expliquen la perdida de años por muerte prematura en esta etapa de la vida.

Carga de enfermedad de los adolescentes en Uruguay y su comparación con la de América Latina y el Caribe / Global burden of disease among teenagers in Uruguay and its comparison with Latin America and the Caribbean

Resumen Introducción. La adolescencia es considerada una etapa de buena salud y por tanto poco estudiada. El objetivo de este estudio es describir la evolución de la mortalidad en adolescentes en Uruguay y analizar la carga de enfermedad en esta etapa de la vida, a través de la medida de los Años de Vida Perdidos por Muerte Prematura en Uruguay y su comparación con los de América Latina y el Caribe según sexo, causa y subregión. Metodología. Se utilizaron fuentes de datos secundarias: el registro nacional de defunciones del Uruguay, el primer estudio de Carga Global de Enfermedad en Uruguay y la información presentada por la página de visualización de datos del Instituto de Métricas y Evaluación en Salud. Resultados. La mortalidad en los adolescentes se ha mantenidos aproximadamente estable entre 1997 y 2015. Loa años perdidos por muerte prematura para el Uruguay son más en los hombres y sus principales causas son los accidentes de tránsito, heridas auto infringidas y violencia. El mismo comportamiento se presenta en la región. Conclusiones. Los determinantes sociales de la salud vinculados a la pobreza e inequidad tienen un rol en el desarrollo de depresión, conductas riesgosas y violentas que posiblemente expliquen la perdida de años por muerte prematura en esta etapa de la vida.

Abstract Introduction. Adolescence is considered a healthy stage of life and therefore little studied. This study described mortality over time in teenagers in Uruguay and analysed the burden of disease at this stage of life by the measure of Years of Life Lost by Premature Death in Uruguay and by comparison with rates in Latin America and the Caribbean by sex, cause and sub-region. Methodology. Secondary data sources used were the national registry of deaths in Uruguay, the first Global Burden of Disease study in Uruguay and the information on the data visualisation page of the Institute of Metrics and Health Evaluation. Data were extracted by the authors and displayed in tables and graphs. Results. Teenager mortality held roughly stable between 1997 and 2015. More years were lost to premature death among Uruguayan men, the main causes being traffic accidents, self-inflicted injuries and violence. The same behaviour occurs throughout the region. Conclusions. The social determinants of health connected with poverty and inequality play a role in the development of depression, risky and violent behaviour, which possibly explain the loss of years due to premature death in adolescence.

Genetic susceptibility to pre diabetes mellitus and related association with obesity and physical fitness components in Mexican-Mestizos.

Pre diabetes mellitus (pre-DM) is considered an early-reversible condition that can progress to Type 2 diabetes mellitus (T2DM) which is the main cause of death for adult Mexican population. Gene variants influencing fasting glucose levels may constitute helpful tool for prevention purposes in pre-DM condition. Physically active Mexican-Mestizo adults (n=565) were genotyped for 6 single nucleotide polymorphisms (SNPs) (ADIPOQ rs2241766, ACSL1 rs9997745, LIPC rs1800588, PPARA rs1800206, PPARG rs1801282 and PPARGC1A rs8192678) related to lipid and carbohydrate metabolism. Fasting glucose was measured and values classified as pre-DM (≥100mg/dL) or normal fasting glucose. Logistic models were used to test associations between pre-DM condition and SNPs, and interaction with Body Mass Index (BMI) and physical fitness components. The A allele of ASCL1 rs9997745 conferred increased risk (OR=3.39, p=0.001) of pre-DM which is modulated by BMI. The A allele of the PPARGC1A rs8192678 showed significant SNP*BMI (OR=1.10, p=0.008) interaction effect for pre-DM risk, meaning that obese subjects showed higher pre-DM risk but normal weight subjects showed lower risk. The effect increased with age and was attenuated by higher cardiorespiratory values. We found that both ACSL1 rs9997745 and PPARGC1A rs8192678 are associated with pre-DM, and that BMI significantly modified their association.

IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in Uruguayan patients.

BACKGROUND: Host single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection. METHODS: DNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR. RESULTS: The distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7%, 42.4% and 11.9%, respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9%, 33.7% and 5.4%, respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant. CONCLUSION: Patients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence of chronic HCV infection in the cohort of Uruguayan population studied. Considering that a trend towards a higher frequency of "good" response genotypes was observed in responder patients, we believe that IL28B rs12979860 genotyping could be a useful tool for predicting different therapies outcome, including in the DAA era.