Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

BACKGROUND: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population. METHODS: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age. RESULTS: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic. CONCLUSIONS: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.

A case-control study characterizing polydactyly risk factors in Bogotá and Cali, Colombia between 2002 and 2020.

BACKGROUND: Polydactyly is a congenital abnormality characterized by the presence of additional fingers on one or more extremities. In Colombia, polydactyly accounted for 17% of musculoskeletal congenital abnormalities in 2021, with a prevalence of 6.03 per 10,000 live births. The purpose of this study was to determine the prevalence of polydactyly and identify associated risk factors in Bogotá and Cali, Colombia, from 2002 to 2020. METHODS: A retrospective case-control study design was employed, analyzing data from birth defect reports provided by the Program for the Prevention and Follow-up of Congenital Defects and Orphan Diseases surveillance system. Cases included live births or stillbirths with polydactyly, while controls consisted of infants without congenital abnormality, matched in terms of birth date and hospital. Prevalence of polydactyly was calculated and risk factors were assessed through odds ratios obtained by logistic regression models, considering a 95% confidence interval. RESULTS: Among the 558,255 births included in the study, 848 cases of polydactyly were identified, resulting in a prevalence rate of 15.19 per 10,000 live births. Risk factors associated with polydactyly included male newborn sex, pregestational diabetes, and a family history of malformation among first-degree relatives. CONCLUSION: These findings highlight the importance a surveillance system aimed to characterize populations with congenital abnormalities, providing a better option for analyzing risk factors, help improving prevention, diagnosis, notification, and optimal treatment in patients.

Risk factors characterisation for CHD: a case-control study in Bogota and Cali, Colombia, 2002-2020.

OBJECTIVE: CHDs correspond to 28% of all congenital anomalies, being the leading cause of infant mortality in the first year of life. Thus, it is essential to explore risk factors for CHDs presentation, allowing the detection of probable cases within a population. METHODS: We identified newborns with CHDs within a cohort from the Program for the Prevention and Monitoring of Congenital Defects in Bogota and Cali, 2002-2020. Cases were classified as isolated, complex isolated, polymalformed, and syndromic. Variables were analysed by comparing case and control averages with Student's t test using a 95% confidence level. RESULTS: Prevalence obtained was 19.36 per 10 000 live births; non-specified CHD, ventricular septal defect, and atrial septal defect were the most prevalent. As risk factors were found: paternal and maternal age above 45 years, pregestational diabetes, mother's body mass index above 25, low educational level, and socio-economic status. As protective factors: folic acid consumption within the first trimester and pregestational period. CONCLUSION: Different risk and protective factors associated with the presentation of CHDs have been described. We consider that public health strategies should be aimed to reduce risk factors exposure. Also, improving diagnosis and prognosis by having a close monitoring on high-risk patients.

Congenital hypothyroidism in Bogotá, Colombia: a current description (2015-2021).

OBJECTIVES: Congenital hypothyroidism (CH) is a decrease in thyroid hormone function in newborns, being one of the leading causes of neurological deficits and long-term metabolic complications. This study aims to determine the prevalence and characteristics of CH cases in Bogotá, Colombia, between 2015 and 2021, as notified through the mandatory report to the Public Health Surveillance System (PHSS). METHODS: A retrospective cross-sectional study was conducted. All live births (LB) with a weight ≥500 g, diagnosed with CH with or without goiter (ICD-10 codes E030 and E031, respectively) in Bogotá during 2015-2021 were analyzed. RESULTS: For a total of 201 cases, the prevalence rate was 3.29 cases per 10,000 LB. 92.54 % were classified as isolated cases of CH, 4.48 % syndromic, and 2.98 % polymalformated. A total of 16.92 % was small for gestational age. The mean gestational age was 37.38 weeks (SD 2.76), 26.87 % were preterm births. Among the mothers, 8.96 % suffered from pregnancy-related or chronic diseases, the most common being hypertensive disorders of pregnancy and pre-existant hypothyroidism (without clarity concerning etiology). A total of 66.67 % of cases did not receive treatment after diagnosis. Treatment was established by an average age of 27 days after birth (SD 36.02) and 17 days after case notification to the PHSS (SD 36.13). CONCLUSIONS: Observed prevalence is similar to the rate reported by health authorities in Colombia but inferior to reports from high-income countries, highlighting the importance of improvements in the Colombian LB's screening program. Time to diagnosis and treatment was observed to be prolonged, suggesting that new pathways are required for timely CH treatment.

Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2.

BACKGROUND: The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). METHODS: To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups-a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). RESULTS: The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. CONCLUSION: In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.

Prevalence and mortality among children with anorectal malformation: A multi-country analysis.

PURPOSE: We examined the total prevalence, trends in prevalence, and age-specific mortality among individuals with anorectal malformation (ARM) METHODS: We conducted a retrospective cohort study using data from 24 population- and hospital-based birth defects surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) from 18 countries and for births from 1974 to 2014. We estimated pooled and program-specific total prevalence per 10,000 total births. Poisson regression was used to assess time trends in prevalence from 2001 to 2012 when most programs contributed data. We calculated selected age-specific proportions of deaths, stratified by case status RESULTS: The pooled total prevalence of ARM was 3.26 per 10,000 total births (95% Confidence Interval = 3.19, 3.32) for birth years 1974-2014. About 60% of cases were multiple or syndromic. Prevalence of multiple, syndromic, and stillborn cases decreased from 2001 to 2012. The first week mortality proportion was 12.5%, 3.2%, 28.3%, and 18.2% among all, isolated, multiple, and syndromic cases, respectively CONCLUSIONS: ARM is relatively rare, with multiple and syndromic cases showing decreasing prevalence during the study period. Mortality is a concern during the first week of life, and especially among multiple and syndromic cases. Our descriptive epidemiological findings increase our understanding of geographic variation in the prevalence of ARM and can be used to plan needed clinical services. Exploring factors influencing prevalence and mortality among individuals with ARM could inform future studies.

Damaging variants in FOXI3 cause microtia and craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. METHODS: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. RESULTS: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. CONCLUSION: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.

Opportunities and challenges for newborn screening and early diagnosis of rare diseases in Latin America.

Rare diseases (RDs) cause considerable death and disability in Latin America. Still, there is no consensus on their definition across the region. Patients with RDs face a diagnostic odyssey to find a correct diagnosis, which may last many years and creates a burden for caregivers, healthcare systems, and society. These diagnostic delays have repercussions on the health and economic burden created by RDs and continue to represent an unmet medical need. This review analyzes barriers to the widespread adoption of newborn screening (NBS) programs and early diagnostic methods for RDs in Latin America and provides recommendations to achieve this critical objective. Increasing the adoption of NBS programs and promoting early diagnosis of RDs are the first steps to improving health outcomes for patients living with RDs. A coordinated, multistakeholder effort from leaders of patient organizations, government, industry, medical societies, academia, and healthcare services is required to increase the adoption of NBS programs. Patients' best interests should remain the guiding principle for decisions regarding NBS implementation and early diagnosis for RDs.

Association between risk polymorphisms for neurodegenerative diseases and cognition in colombian patients with frontotemporal dementia.

Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disease of presenile onset. A better characterization of neurodegenerative disorders has been sought by using tools such as genome-wide association studies (GWAS), where associations between single nucleotide polymorphisms (SNPs) and cognitive profiles could constitute predictive biomarkers for these diseases. However, in FTD, associations between genotypes and cognitive phenotypes are yet to be explored. Here, we evaluate a possible relationship between genetic variants and some cognitive functions in an FTD population. Methodology: A total of 47 SNPs in genes associated with neurodegenerative diseases were evaluated using the Sequenom MassARRAY platform along with their possible relationship with performance in neuropsychological tests in 105 Colombian patients diagnosed with FTD. Results and discussion: The SNPs rs429358 (APOE), rs1768208 (MOBP), and rs1411478 (STX6), were identified as risk factors for having a low cognitive performance in inhibitory control and phonological verbal fluency. Although the significance level was not enough to reach the corrected alpha for multiple comparison correction, our exploratory data may constitute a starting point for future studies of these SNPs and their relationship with cognitive performance in patients with a probable diagnosis of FTD. Further studies with an expansion of the sample size and a long-term design could help to explore the predictive nature of the potential associations we identified.

A Multicountry Analysis of Prevalence and Mortality among Neonates and Children with Bladder Exstrophy.

OBJECTIVE: Bladder exstrophy (BE) is a rare but severe birth defect affecting the lower abdominal wall and genitourinary system. The objective of the study is to examine the total prevalence, trends in prevalence, and age-specific mortality among individuals with BE. STUDY DESIGN: We conducted a retrospective cohort study. Data were analyzed from 20 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research in 16 countries. Live births, stillbirths, and elective terminations of pregnancy for fetal anomaly (ETOPFA) diagnosed with BE from 1974 to 2014. Pooled and program-specific prevalence of BE per 100,000 total births was calculated. The 95% confidence intervals (CI) for prevalence were estimated using Poisson approximation of binomial distribution. Time trends in prevalence of BE from 2000 to 2014 were examined using Poisson regression. Proportion of deaths among BE cases was calculated on the day of birth, day 2 to 6, day 7 to 27, day 28 to 364, 1 to 4 years, and ≥5 years. Mortality analysis was stratified by isolated, multiple, and syndromic case status. RESULTS: The pooled total prevalence of BE was 2.58 per 100,000 total births (95% CI = 2.40, 2.78) for study years 1974 to 2014. Prevalence varied over time with a decreasing trend from 2000 to 2014. The first-week mortality proportion was 3.5, 17.3, and 14.6% among isolated, multiple, and syndromic BE cases, respectively. The majority of first-week mortality occurred on the first day of life among isolated, multiple, and syndromic BE cases. The proportion of first-week deaths was higher among cases reported from programs in Latin America where ETOPFA services were not available. CONCLUSIONS: Prevalence of BE varied by program and showed a decreasing trend from 2000 to -2014. Mortality is a concern among multiple and syndromic cases, and a high proportion of deaths among cases occurred during the first week of life. KEY POINTS: · Total prevalence of BE was 2.58 per 100,000 births.. · Prevalence decreased from 2000 to 2014.. · The first-week mortality was 9.3%..

Analysis of early neonatal case fatality rate among newborns with congenital hydrocephalus, a 2000-2014 multi-country registry-based study.

BACKGROUND: Congenital hydrocephalus (CH) comprises a heterogeneous group of birth anomalies with a wide-ranging prevalence across geographic regions and registry type. The aim of the present study was to analyze the early neonatal case fatality rate (CFR) and total birth prevalence of newborns diagnosed with CH. METHODS: Data were provided by 25 registries from four continents participating in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) on births ascertained between 2000 and 2014. Two CH rates were calculated using a Poisson distribution: early neonatal CFR (death within 7 days) per 100 liveborn CH cases (CFR) and total birth prevalence rate (BPR) per 10,000 births (including live births and stillbirths) (BPR). Heterogeneity between registries was calculated using a meta-analysis approach with random effects. Temporal trends in CFR and BPR within registries were evaluated through Poisson regression modeling. RESULTS: A total of 13,112 CH cases among 19,293,280 total births were analyzed. The early neonatal CFR was 5.9 per 100 liveborn cases, 95% confidence interval (CI): 5.4-6.8. The CFR among syndromic cases was 2.7 times (95% CI: 2.2-3.3) higher than among non-syndromic cases (10.4% [95% CI: 9.3-11.7] and 4.4% [95% CI: 3.7-5.2], respectively). The total BPR was 6.8 per 10,000 births (95% CI: 6.7-6.9). Stratified by elective termination of pregnancy for fetal anomalies (ETOPFA), region and system, higher CFR were observed alongside higher BPR rates. The early neonatal CFR and total BPR did not show temporal variation, with the exception of a CFR decrease in one registry. CONCLUSIONS: Findings of early neonatal CFR and total BPR were highly heterogeneous among registries participating in ICBDSR. Most registries with higher CFR also had higher BPR. Differences were attributable to type of registry (hospital-based vs. population-based), ETOPFA (allowed yes or no) and geographical regions. These findings contribute to the understanding of regional differences of CH occurrence and early neonatal deaths.

MicroRNAs as Potential Liquid Biopsy Biomarker for Patients with Castration-Resistant Prostate Cancer.

Purpose: To identify micro-RNAs (miRNAs) expression profiles in peripheral blood plasma that could play a role as potential biomarkers in patients who progressed to castration-resistant prostate cancer (CRPC). Liquid biopsy analysis of miRNAs is a fast-developing field with a considerable likelihood to predict tumor progression and metastasis by targeting genes involved in oncogenesis. Patients and Methods: Differential expression analysis of miRNAs profile in CRPC patients was performed by creating small RNA libraries of circulating miRNAs using HiSeq2500 Illumina platform. A secondary analysis of aligned reads with miRNA identification and quantification was performed using miARmaSeq. Using the Bowtie algorithm, the selected variants were compared to reference nucleotide sequence GRCh38 and miRbase. Novel miRNA sequences were structurally analyzed using mirDeep2®. Results: A total of 16 patients with CRPC were included for analysis. Identified circulating miRNAs were hsa-miR-885-3p, hsa-miR-4467, hsa-miR-4686, hsa-miR-146a-3p, hsa-miR-6514-5p. Genes identified as regulated by these miRNAs were GPR56, BDNF, CTNND1, C17orf62, and DTNA. Conclusion: We explored the miRNA expression profile in patients with CRPC, identifying five miRNAs implicated in the regulation of genes involved in prostate cancer (PCa) oncogenesis and progression. We also found miRNA 855-3p in peripheral blood for the first time, which has a critical role in tumor growth mechanisms and higher expression profile than in healthy individuals.

Association between maternal infections during pregnancy and congenital defects in their offspring: a population-based case-control study in Bogota and Cali, Colombia 2001-2018.

Infections are frequent during pregnancy and their teratogenic role is well documented in Toxoplasmosis, other infections, Rubella, Cytomegalovirus, and Herpes simplex (TORCH). However, the in-utero development effects of the rest of the infections that affect pregnant women are unknown. We described a cohort of patients with major Birth Defects (BD) and the exposure to infections during pregnancy from the information of Congenital Defects Surveillance Programs of two Colombian cities (Bogota and Cali) between 2001 and 2018. We evaluated associations between groups of maternal infections and BD among 3096 cases and 7446 controls that were registered. BD presentation was more frequent as isolated (64.3%), polymalformed (23.2%), and syndromic (12.4%). Infections during pregnancy were present in 52.5% of cases and 44.6% of controls. The most common single infection between cases and controls was vaginal infection. The most common polyinfection was vaginal and urinary tract infection. We found an association between BD and vaginal infections with an odds ratio (OR) 1.18 (CI 1.08-1.30), urinary tract infections OR 1.16 (CI 1.05-1.28), gastrointestinal infections OR 2.06 (IC 1.18-3.59), respiratory infections OR 1.56 (IC 1.28-1.9) and viral infections OR 1.88 (IC 1.18-3.0). Knowing the teratogenic effect of infections is important to extend prevention, screening, timely diagnosis, and appropriate treatment to pregnant women.

Prevalence of aortic coarctation in Bogotá-Colombia from 2001 to 2018. The diagnostic needs to improve. / Prevalencia de coartación aórtica en Bogotá-Colombia de 2001 a 2018. El diagnóstico debe mejorar

OBJECTIVES: Aortic coarctation is the most frequent structural anomaly out of congenital heart diseases. This congenital defect is an important cause of death worldwide. We sought to determine the prevalence of aortic coarctation in Colombia and whether new policies have had an impact on its diagnosis. METHODS: In this study information from the Bogotá birth defect surveillance program during the years 2001-2018 from 63 hospitals was used. 537,026 live births of any weight and stillbirths of any weight were analyzed. The information was stored in a database on the servers of the Health Secretariat and the Pontificia Universidad Javeriana. We analyzed the presence of aortic coarctation according to the newborn's sex, weight, size, mother's age, and gestational age at the time of birth and when coarctation is accompanied by other types of congenital malformations. RESULTS: The prevalence of aortic coarctation in Bogotá during the years 2001-2018 found in this study was 1.25 in 10,000 live births. We also found that prevalence of aortic coarctation in Bogotá changes throughout the years having a significant increase in the year 2018 with 6.57 cases in 10,000 live births. CONCLUSIONS: This prevalence is higher than the one found in a study with data from 2001 to 2014, which suggests an improvement in the country's epidemiological surveillance and medical training. However, the prevalence found in Bogotá is still lower compared to the prevalence worldwide and from other continents, the prevalence for Latinamerica was significantly lower as compared to those in Asia, Europe, and United States so we emphasize the importance of continuing with improvements, such as standardizing screening methods and sensitivity of said methods in a local scale as well as a continental scale.

OBJETIVOS: La coartación aórtica es la anomalía estructural más frecuente de las cardiopatías congénitas. Este defecto congénito es una causa importante de muerte en todo el mundo. Buscamos determinar la prevalencia de la coartación aórtica en Colombia y si las nuevas políticas han tenido un impacto en su diagnóstico. MÉTODOS: En este estudio se utilizó información del programa de vigilancia de defectos de nacimiento de Bogotá durante los años 2001-2018 en 63 hospitales. Se analizaron 537,026 nacidos vivos de cualquier peso y nacidos muertos de cualquier peso. La información fue almacenada en una base de datos de los servidores de la Secretaría de Salud y de la Pontificia Universidad Javeriana. Se analizó la presencia de coartación aórtica de acuerdo al sexo del recién nacido, peso, tamaño, edad de la madre y edad gestacional en el momento del nacimiento y cuando la coartación se acompañó de otros tipos de malformaciones congénitas. RESULTADOS: La prevalencia de la coartación aórtica en Bogotá durante los años 2001-2018 encontrados en este estudio fue de 1.25 en 10,000 nacidos vivos. También encontramos que la prevalencia de coartación aórtica en Bogotá ha cambiado a lo largo de los años, teniendo un aumento significativo en el año 2018 con 6.57 casos en 10,000 nacidos vivos. CONCLUSIONES: Esta prevalencia es mayor que la encontrada en un estudio con datos de 2001 a 2014, lo que sugiere una mejora en la vigilancia epidemiológica y la formación médica del país. Si bien, la prevalencia encontrada en Bogotá es menor en comparación con la prevalencia a nivel mundial y de otros continentes, la prevalencia para el continente de Latinoamérica también es significativamente menor con respecto a Asia, Europa y Estados Unidos, por lo que enfatizamos la importancia de continuar con las mejoras, como la estandarización de los métodos de detección y la sensibilidad de dichos métodos tanto a nivel local como a nivel del continente.

Creation of a Pilot Surgical Program for the Comprehensive Management of Patients with Congenital Urological Malformations / Creación de un programa quirúrgico piloto para el manejo integral de pacientes con malformaciones urológicas congénitas

Objectives Congenital malformations constitute the first cause of morbidity and mortality in childhood in Latin America. That is why, since 2001, a surveillance system for congenital malformations has been implemented in Bogota - Colombia. However, despite the increase in detection, an impact on treatment has not been achieved. The present study describes our experience with a novel social program focused on congenital urologic disorders. Methods The present manuscript is a retrospective observational study. We reviewed two national databases containing patients with congenital malformations. Patients were actively contacted to verify the status of the malformations. Children in whom the malformation was confirmed were offered a free consultation with a multidisciplinary group. After screening for surgical indications, patients were scheduled for surgery. Results Between November 2018 and December 2019, 60 patients were identified. In total 44, attended the consultation; the remaining did not attend due to financial or travel limitations. The most common condition assessed was hypospadias. In total, 29 patients underwent surgery. The total cost of care was of US$ 5,800. Conclusions Active search improves attention times and reduces the burden of disease. The limitations to be resolved include optimizing the transportation of patients and their families, which is a frequent limitation to access health care.

Objetivos Las malformaciones congénitas corresponden a la principal causa de morbimortalidad en la infancia en América Latina, motivo por el cual desde el 2001 se viene implementando un sistema de vigilancia epidemiológica de malformaciones congénitas en Bogotá, Colombia. Sin embargo, a pesar del aumento en la cobertura del reporte obligatorio, no se ha logrado un impacto sobre su tratamiento. Este estudio busca mostrar nuestra experiencia con un programa integral de pacientes con malformaciones urológicas congénitas. Métodos El presente es un estudio observacional retrospectivo. Los menores con malformaciones congénitas fueron identificados en dos bases de datos nacionales que incluyen pacientes con malformaciones congénitas. Los pacientes reportados fueron contactados telefónicamente para verificar el estado actual de la malformación. A aquellos niños en quienes se les confirmó la malformación, se les ofreció de manera gratuita una consulta con un grupo multidisciplinario. Una vez confirmadas las indicaciones quirúrgicas, fueron llevados a cirugía. Resultados Se identificaron 60 pacientes entre noviembre del 2018 y diciembre de 2019. De los pacientes identificados, 44 acudieron a consulta. Los demás no asistieron por limitaciones económicas. La principal condición valorada fue hipospadias. En total, 29 pacientes fueron llevados a cirugía. El costo total de la atención de estos pacientes fue de 22 millones de pesos colombianos. Conclusiones La búsqueda activa mejora los tiempos de atención y reduce la carga de la enfermedad. Una de las limitaciones aun por resolver es optimizar el transporte de los pacientes y sus familias, que resulta una limitación frecuente para el acceso a la salud.

Association between Genitourinary and Congenital Heart Defects: A 52-year Case-Control Study of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) / Asociación entre cardiopatías congénitas y malformaciones congénitas urinarias: Un estudio de casos y controles de 52 años del Estudio Colaborativo Latino Americano de Malformaciones Congénit

Background Congenital urological anomalies are present in 4.3/10 thousand newborns, and their association with other anomalies may increase the overall mortality and disability. The present study establishes the risk of having congenital urological anomalies presenting associated cardiopathies. Methods We conducted a retrospective case-control study using the Latin American Collaborative Study of Congenital Malformations (Estudio Colaborativo Latino Americano de Malformaciones Congénitas, ECLAMC, in Spanish). The analysis included all registered cases of congenital urological malformation from 1967 to 2019. Patients with or without associated heart defects were included for the statistical analysis. Odds ratios (ORs) were calculated using a 95% confidence interval (95% CI). We compared the variables with the Chi-squared test and analysis of variance (ANOVA). The statistical analysis was performed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Armonk, NY, United States) software, version 27.0. Values of p < 0.05 were considered statistically significant. Results A total of 7,767,161 newborns were evaluated, and 17,834 genital and upper urinary tract malformations were identified. Of these, 64.2% were genital anomalies, and 35.8% were abnormalities of the upper urinary tract. Genitourinary malformations and concomitant congenital heart defects (GU + C) were observed in 3.5% of the cases. Subjects with GU + C had a higher number of malformations (4.59 ± 2.3) than patients without heart defects (1.53 ± 1.58) (p < 0.000). The OR was of 3.61 (range: 1.86­7.00) for cloacal exstrophy, of 4.01 (range: 3.14­5.12) for imperforate anus, of 5.52 (range: 3.92­7.78) for horseshoe kidney, and of 13.7 (range: 6.65­28.22) for trisomy 21 (Down syndrome) with malformations of the upper urinary tract. Conclusion The association of congenital heart defects with urological anomalies is higher for complex congenital anomalies such as imperforate anus, cloacal exstrophy, and ho

Introducción Las malformaciones congénitas urológicas están presentes en 4,3/10 mil, y su asociación con otros defectos puede aumentar la mortalidad global y la discapacidad. Este estudio analiza la presentación de las malformaciones congénitas urológicas asociadas a las cardiopatías congénitas. Métodos Este es un estudio retrospectivo de casos y controles que usa el Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). Se incluyeron todos los casos registrados de malformaciones congénitas urológicas de 1967 a 2019, y todos los casos con y sin defectos cardiacos. Se calculó la razón de disparidad (RD) usando un intervalo de confianza del 95% (IC 95%). Se probó la hipótesis con el Chi-cuadrado y análisis de la varianza (analysis of variance, ANOVA, en inglés). Se realizó el análisis estadístico por medio del programa Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Armonk, NY, Estados Unidos), versión 27.0. Se consideró la significancia estadística con valores de p < 0,05. Resultados Se evaluaron 7.767.161 recién nacidos, y se identificaron 17.834 malformaciones genitales y del tracto urinario superior. De estas, 64,2% fueron genitales, y 35,8%, de vías urinarias superiores. El 3,5% de los casos tenían malformaciones genitourinarias y defectos cardiacos congénitos concomitantes (GU + C). Aquellos con GU + C tenían mayor número de malformaciones (4,59 ± 2,3) que los pacientes sin defectos cardiacos (1,53 ± 1,58) (p < 0,000). La RD fue de 3.61 (rango: 1,86­700) para la extrofia cloacal, de 4,01 (3,14­5,12) para el ano imperforado, de 5,52 (3,92­7,78) para el riñón en herradura, y de 13,7 (6,65­28,22) para la trisomía 21 (síndrome de Down) con malformaciones del tracto urinario superior. Conclusión La asociación entre defectos cardiacos congénitos y anomalías urológicas es significativa en malformaciones congénitas complejas como el ano imperforado, la extrofia cloacal, y el riñón en herradura. Los pacientes con síndrome de Down y malformaciones urológicas tienen la mayor probabilidad.

Prevalence of microcephaly: the Latin American Network of Congenital Malformations 2010-2017.

Objective: The Latin American Network of Congenital Malformations: ReLAMC was established in 2017 to provide accurate congenital anomaly surveillance. This study used data from ReLAMC registries to quantify the prevalence of microcephaly from 2010 to 2017 (before, during and after the Zika virus epidemic). Design: Nine ReLAMC congenital anomaly registries provided case-level data or aggregate data for any live births, still births or terminations of pregnancy with microcephaly. Births to pregnant women infected with Zika virus first occurred in Brazil in 2015, and in the remaining registry areas in 2016 with the exception of Chile that did not experience Zika virus. Therefore the prevalence of microcephaly for 2010-2014 and individual years 2015, 2016 and 2017 was estimated using multilevel random effect Poisson models. Clinical classification and characteristics of the cases were compared pre and post Zika for all centres providing individual case-level data. Results: The prevalence of microcephaly for all registries excluding Brazil was 2.3 per 10 000 (95% CI 2.0 to 2.6) for 2010-2014 rising to 5.4 (95% CI 4.8 to 6.0) in 2016 and 5.9 (95% CI 5.3 to 6.6) in 2017. Brazil had a prevalence of 0.6 per 10 000 (95% CI 0.5 to 0.6) in 2010-2014, rising to 5.8 (95% CI 5.6 to 6.1) in 2015, 8.0 (95% CI 7.6 to 8.3) in 2016 and then falling in 2017. Only 29 out of 687 cases of microcephaly were reported as congenital Zika syndrome in countries excluding Brazil. Conclusions: The prevalence of microcephaly was influenced both by Zika causing congenital Zika syndrome and by increased reporting awareness.

Geographical Distribution of Access to Healthcare in Patients Diagnosed with Hypospadias / Distribución geográfica del acceso a la asistencia sanitaria en pacientes con diagnóstico de hipospadias

Objective Hypospadias is a congenital disease of unknown etiology involving multiple epigenetic, genetic, and endocrinological factors. It is a highly incapacitating condition. Its surgical management is one of the most frequent surgical procedures done by pediatric urologists. Furthermore, the geographical distribution and healthcare access is limited in Colombia. The Colombian Ministry of Health has consolidated a nationwide registry called Integrated Social Protection Information System (SISPRO, in the Spanish acronym) to collect comprehensive information on the use and frequency of resources associated with health care in Colombia. The aim of the present study was to analyze the number of cases reported between 2014 and 2018 and the geographical distribution of access to healthcare of patients with hypospadias in Colombia. Methods An observational, retrospective study of hypospadias in Colombia, 2014­ 2018, was performed using data extracted from the Individual Health Records System (RIPS) in SISPRO. Satscan, version 9.6 was used to perform a distribution analysis of the georeferenced population using a Poisson model. To visualize the results, the software projected the result onto a Google Earth map. Results Between January 2014 and December 2018, a total of 8,990 cases of hypospadias were evaluated in Colombia. The geographical distribution in the national territory has areas with high evaluation rates. On average, the departments in which the majority of cases were evaluated during the study period were Bogotá, D.C., Antioquia, and Valle del Cauca (2,196, 1,818 and 1,151 cases, respectively). The statistical analysis of the space exploration (►Fig. 1) identified the area with the highest concentration of cases (red) and the areas in which the lowest number of patients was evaluated (blue). The geographical distribution showed increasing trends in areas near the center of the country, especially in the cities of Bogotá, Cali, Ibagué, and Pereira. Conclusion There is a greater concentration of cases evaluated in the center of the country, where the cities with better access to subspecialized medical care are located. This highlights inequalities in health services and the opportunity for surgical care among regions of the country. If we consider that the prevalence rates of hypospadias remain stable, 87% of the patients with hypospadias will not be evaluated by a subspecialist.

Objetivo Hipospadias es una enfermedad congénita de etiología desconocida que involucra múltiples factores epigenéticos, genéticos y endocrinológicos. Es una condición sumamente incapacitante. Su manejo quirúrgico es uno de los procedimientos quirúrgicos más frecuentes realizados por urólogos pediátricos. Además, la distribución geográfica y el acceso a la atención médica son limitados en Colombia. El Ministerio de Salud de Colombia ha consolidado un registro a nivel nacional denominado Sistema Integrado de Información de Protección Social (SISPRO) para recopilar información integral sobre el uso y frecuencia de los recursos asociados a la atención de la salud en Colombia. El objetivo del presente estudio fue analizar el número de casos notificados entre 2014 y 2018 y la distribución geográfica del acceso a la atención médica por los pacientes con hipospadias en Colombia. Métodos Se realizó un estudio observacional y retrospectivo de hipospadias en Colombia, 2014-2018, utilizando datos extraídos del Sistema de Registros Sanitarios Individuales (RIPS) en SISPRO. Se usó Satscan, versión 9.6 para realizar un análisis de distribución de la población georreferenciada usando un modelo de Poisson. Para visualizar los resultados, el software proyectó el resultado en un mapa de Google Earth. Resultados Entre enero de 2014 y diciembre de 2018, se evaluaron un total de 8.990 casos de hipospadias en Colombia. La distribución geográfica en el territorio nacional tiene áreas con mayor concentración de la atención de pacientes con hipospadias, al igual que áreas sin atención de esta condicion. En promedio, los departamentos donde se evaluaron la mayoría de los casos durante el período de estudio fueron Bogotá, D.C., Antioquia, y Valle del Cauca (439.2, 363.6, y 230.2, respectivamente). El análisis estadístico de la exploración espacial ([Figura 1]) identificó el área con la mayor concentración de casos (rojo) y las áreas donde se evaluó el menor número de pacientes (azul). La distribución geográfica mostró tendencias crecientes en áreas cercanas al centro del país, especialmente en las ciudades de Bogotá, Cali, Ibagué y Pereira. Conclusiones Existe una mayor concentración de casos evaluados en el centro del país, donde se encuentran las ciudades con un mejor acceso a atención médica subespecializada. Esto pone de relieve las desigualdades en el acceso a los servicios de salud y la oportunidad de atención quirúrgica entre las regiones del país. Si consideramos que las tasas de prevalencia de hipospadias permanecen estables, aproximadamente el 87% de los pacientes con hipospadias no serán evaluados por un subespecialista.

Parental Reports of Intervention Services and Prevalence of Teasing in a Multinational Craniofacial Microsomia Pediatric Study.

ABSTRACT: Children with craniofacial microsomia (CFM) are at increased risk for educational and social concerns. This study describes intervention services and frequency of teasing in a multinational population of children with CFM. Caregivers of children with CFM ages 3 to 18 years in the US and South America were administered a questionnaire. Additional information was gathered from medical charts and photographs. Participants (N = 169) had an average age of 10.1 ±â€Š6.2 years, were primarily male (60%), and from the US (46%) or Colombia (32%). Most participants had microtia and mandibular hypoplasia (70%). They often had unilateral (71%) or bilateral (19%) hearing loss and 53% used a hearing aid. In the US, special education services were provided for 48% of participants enrolled in school; however, similar services were rare (4%) in South America and reflect differences in education systems. Access to any intervention service was higher in the US (80%) than in South America (48%). Caregivers reported children showed diagnosis awareness by an average age of 4.4 ±â€Š1.9 years. Current or past teasing was reported in 41% of the children, starting at a mean age of 6.0 ±â€Š2.4 years, and most often took place at school (86%). As half of the US participants received developmental and academic interventions, providers should screen for needs and facilitate access to services. Given diagnosis awareness at age 4 and teasing at age 6, providers are encouraged to assess for psychosocial concerns and link to resources early in treatment.

Analysis of Heritability Across the Clinical Phenotypes of Frontotemporal Dementia and the Frequency of the C9ORF72 in a Colombian Population.

Frontotemporal dementia (FTD) is a highly heritable condition. Up to 40% of FTD is familial and an estimated 15% to 40% is due to single-gene mutations. It has been estimated that the G4C2 hexanucleotide repeat expansions in the C9ORF72 gene can explain up to 37.5% of the familial cases of FTD, especially in populations of Caucasian origin. The purpose of this paper is to evaluate hereditary risk across the clinical phenotypes of FTD and the frequency of the G4C2 expansion in a Colombian cohort diagnosed with FTD. Methods: A total of 132 FTD patients were diagnosed according to established criteria in the behavioral variant FTD, logopenic variant PPA, non-fluent agrammatic PPA, and semantic variant PPA. Hereditary risk across the clinical phenotypes was established in four categories that indicate the pathogenic relationship of the mutation: high, medium, low, and apparently sporadic, based on those proposed by Wood and collaborators. All subjects were also examined for C9ORF72 hexanucleotide expansion (defined as >30 repetitions). Results: There were no significant differences in the demographic characteristics of the patients between the clinical phenotypes of FTD. The higher rate phenotype was bvFTD (62.12%). In accordance with the risk classification, we found that 72 (54.4%) complied with the criteria for the sporadic cases; for the familial cases, 23 (17.4%) fulfilled the high-risk criteria, 23 (17.4%) fulfilled the low risk criteria, and 14 (10.6%) fulfilled the criteria to be classified as subject to medium risk. C9ORF72 expansion frequency was 0.76% (1/132). Conclusion: The FTD heritability presented in this research was very similar to the results reported in the literature. The C9ORF72 expansion frequency was low. Colombia is a triethnic country, with a high frequency of genetic Amerindian markers; this shows consistency with the present results of a low repetition frequency. This study provides an initial report of the frequency for the hexanucleotide repeat expansions in C9ORF72 in patients with FTD in a Colombian population and paves the way for further study of the possible genetic causes of FTD in Colombia.