Prevalência e fatores associados às malformações congênitas em nascidos vivos / Prevalencia y factores asociados a las malformaciones congénitas en nacidos vivos / Prevalence and factors associated with congenital malformations in live births

Resumo Objetivo: Estimar a prevalência de malformações congênitas e identificar os fatores associados em nascidos vivos. Métodos: Estudo transversal, de base populacional, com dados do Sistema de Informações sobre nascidos vivos. Procedeu-se a uma análise estatística bivariada (teste Qui-quadrado) e multivariada (regressão logística múltipla) para avaliar a associação entre as variáveis e o desfecho (nascidos vivos que possuem ou não malformações congênitas). Resultados: Registraram-se 346.874 nascidos vivos, desses 3.473 apresentaram algum tipo de malformação congênita, com prevalência média de 1,0%. Na análise múltipla os fatores, positivamente associados à prevalência foram: duração da gestação menor que 37 semanas (OR= 1,17), idade materna entre 20 e 29 anos (OR= 0,893), tipo de gravidez única (OR= 1,775), tipo de parto (OR= 0,827) e consultas de pré-natal inferior a seis (OR= 1,214). Conclusão: As variáveis apontadas no estudo integraram um modelo preditivo que pode auxiliar no planejamento dos serviços de saúde, sugerir hipóteses sobre os fatores etiológicos, e subsidiar as ações do pré-natal com atenção para os fatores identificados.

Resumen Objetivo: Estimar la prevalencia de malformaciones congénitas e identificar los factores asociados en nacidos vivos. Métodos: Estudio transversal, de base poblacional, con datos del Sistema de Información sobre nacidos vivos. Se procedió a un análisis estadístico bivariado (prueba χ2 de Pearson) y multivariado (regresión logística múltiple) para evaluar la relación entre las variables y el resultado (nacidos vivos que tienen o no tienen malformaciones congénitas). Resultados: Se registraron 346.874 nacidos vivos, de los cuales 3.473 presentaron algún tipo de malformación congénita, con prevalencia promedio de 1,0 %. En el análisis múltiple, los factores asociados de forma positiva a la prevalencia fueron: duración de la gestación menor a 37 semanas (OR= 1,17), edad materna entre 20 y 29 años (OR= 0,893), tipo de gestación única (OR= 1,775), tipo de parto (OR= 0,827) y consultas de atención prenatal inferiores a seis (OR= 1,214). Conclusión: Las variables observadas en el estudio integran un modelo predictivo que puede ayudar a la planificación de los servicios de salud, sugerir hipótesis sobre los factores etiológicos y respaldar las acciones de la atención prenatal con énfasis en los factores identificados.

Abstract Objective: To estimate the prevalence of congenital malformations and to identify associated factors in live births. Methods: Cross-sectional study, population-based, with data from the Live Births Information System. A bivariate statistical analysis (Chi-square test) and a multivariate statistical analysis (multiple logistic regression) were performed to evaluate the association between the variables and the outcome (live-births with or without congenital malformations). Results: A total of 346,874 live births were registered, of which 3,473 presented some type of congenital malformation, with an average prevalence of 1.0%. In the multiple analysis, the factors positively associated with prevalence were: duration of pregnancy less than 37 weeks (OR = 1.17), maternal age between 20 and 29 years (OR = 0.893), singleton pregnancy (OR = 1.775), type of delivery (OR - 0.827), and number of prenatal consultations inferior to six (OR = 1.214). Conclusion: The variables pointed out in the study integrated a predictive model that can help in the planning of health services, suggest hypotheses regarding etiological factors, and finance prenatal care actions with attention to the identified factors.

A importância do metilfolato na prevenção dos defeitos abertos do tubo neural / The importance of methylfolate in the prevention of open neural tube defects

A suplementação periconcepcional com vitamina B9 ou folato é considerada medida efetiva para diminuir a ocorrência e a recorrência de defeitos do tubo neural (DTNs). É recomendada para todas as mulheres que planejam gravidez ou que possam engravidar. O ácido fólico necessita passar por processos enzimáticos necessários à metabolização para a sua forma ativa L-5-metiltetrahidrofolato (L-metilfolato, 5-MTHF) envolvida nos processos biológicos e que circula no plasma. A enzima metilenotetrahidrofolato redutase (MTHFR) é de fundamental importância para fornecer 5-MTHF, forma biologicamente ativa. A presença de polimorfismo do gene da MTHF-redutase promove menor atividade enzimática e menor produção de L-metilfolato.(AU)

ZikaPLAN: addressing the knowledge gaps and working towards a research preparedness network in the Americas.

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.

Asesoramiento genético a gestantes con defectos congénitos mayores / Genetic counseling to pregnant women with major congenital defects

Introducción: Los defectos congénitos mayores son resultado de un defecto de desarrollo intrínseco y desde su comienzo en un órgano o en una región anatómica. Su unión con otros formarán los síndromes caracterizados por un conjunto de defectos múltiples por malformación, disrupción o deformidad con afectación de varias áreas del desarrollo y con íntima relación histopatológica. Objetivo: Evaluar la efectividad del asesoramiento genético en gestantes basado en evidencias ultrasonográficas de defectos congénitos mayores. Métodos: Se realizó un estudio descriptivo transversal en el Policlínico José Martí Pérez del municipio de Santiago de Cuba. El universo estuvo conformado por la totalidad de las gestantes con evidencias ultrasonográficas de defectos congénitos mayores en los años 2016-2017. La información obtenida se procesó de forma computarizada y se aplicó el porcentaje como medida de resumen. Resultados: La aparición y detección de los defectos congénitos en las gestantes adolescentes afecta principalmente el sistema cardiaco, asociado a cromosomopatías, sistema renal, nervioso central, interrumpiéndose el mayor número de gestantes con defectos congénitos mayores. Conclusiones: Se evidenció que con el asesoramiento genético como herramienta de prevención de los defectos congénitos, se logró la terminación voluntaria del embarazo en la mayoría de los casos manteniendo la tasa de mortalidad infantil por debajo de los propósitos nacionales, mediante la detección precoz de los defectos congénitos en la Atención Primaria de Salud(AU)

Introduction: Major congenital defects result from any intrinsic development defect and from their beginning in an organ or in an anatomical region. Their union with others shall form the syndromes characterized by a set of multiple defects due to malformation, disruption or deformity with involvement of several development areas and with an intimate histopathological relationship. Objective: To evaluate the effectiveness of genetic counseling in pregnant women based on ultrasonographic evidence of major congenital defects. Methods: A cross-sectional descriptive study was carried out at José Martí Pérez Polyclinic in Santiago de Cuba Municipality. The study population was made up of all pregnant women with ultrasonographic evidence of major congenital defects in the years 2016 and 2017. The information obtained was processed in a computerized way and the percentage was applied as a summary measure. Results: The onset and detection of congenital defects in adolescent pregnant women mainly affects the cardiac system, associated to chromosomopathies, the renal system, the central nervous system, terminating the greater amount of pregnant women with major congenital defects. Conclusions: Genetic counseling was evidenced to be a tool for the prevention of congenital defects, by which voluntary termination of pregnancy can be achieved in most cases, keeping infant mortality rate below national purposes, through early detection of congenital defects in primary health care(AU)

47-Fold rise of diabetes in childbearing age Chilean women: Markov model and cost-effectiveness of prevention of birth defects.

AIM: Prevalence of type 2 diabetes mellitus (T2DM) during childbearing age in Chile had a 47-fold rise in 7 years, reaching 120 844 women, half of which are unaware of their condition. We aimed to project pregnancies and births among Chilean women of childbearing age (WCBA) with T2DM and report the incidence of birth defects and the associated years of life lost and lifetime costs. METHODS: Markov model of cohort of WCBA with T2DM (WCBA-DM) with a 20-year time horizon (2018-2037), using data from previous studies. Two scenarios were assessed: scenario A: no universal detection of T2DM and scenario B: universal screening of T2DM using glycosylated hemoglobin levels. Both lifetime costs and disability-adjusted life years (DALY) were calculated with a 5% discount rate (US$ of 2017). RESULTS: In scenario A, 12 163 infants with birth defects could be born among the analyzed cohort, resulting in 243 260 years of life lost, 296 652 DALY and in lifetime costs of US$ 1 957 657 966. In scenario B, the first three figures could be reduced by 70.4% to 3599 infants with birth defects, 71 980 years of life lost and 87 794 DALY. Due to the addition of diabetes screening and new patient costs to scenario B, there would be a lesser reduction (67.3%) in total lifetime costs, to US$ 640 669 296. CONCLUSION: Screening of diabetes in WCBA would yield a 20-year reduction of 70.4% in the number of infants with birth defects, years of life lost and DALY. Total lifetime costs could be reduced by 67.3%.

Epilepsia na gravidez / Epilepsy in pregnancy

As epilepsias constituem uma das mais frequentes condições neurológicas encontradas na gravidez, ocorrendo entre 0,5% e 1% das gestações. O risco de morte materna está aumentado em 10 vezes nas grávidas epilépticas. Na gestante, o diagnóstico adequado é fundamental, já que deve ser afastada a possibilidade de se tratar de crise de eclâmpsia, doença exclusiva do período gravídico-puerperal. A preocupação materna quanto aos efeitos adversos (malformações) das drogas antiepilépticas no bebê pode levar à descontinuação ou redução da dose do medicamento, aumentando o risco de convulsão ou de morte súbita e inesperada na epilepsia (SUDEP). Nesta revisão foi dada atenção única e exclusiva às recomendações do Royal College of Obstetricians and Gynaecologists.(AU)

Epilepsiy is one of the most frequent neurological conditions found in pregnancy, occurring in 0.5 to 1% of pregnancies. The maternal death risk is increased 10-fold in epileptic pregnancies. In pregnant women, its adequate diagnosis is essential, since eclampsia is a differential diagnosis, which is disease exclusive to the pregnancy-puerperal period. Maternal concerns about the adverse effects (malformations) of antiepileptic drugs in the infant may lead to the discontinuation or reduction of the drug dose, increasing the risk of seizure or sudden and unexpected death in epilepsy (SUDEP). In this review exclusive attention was given to the recommendations of the Royal College of Obstetricians and Gynecologists.(AU)

Knowledge, attitudes and practices of pregnant women in Martinique in the immediate aftermath of the Zika virus outbreak.

INTRODUCTION: The WHO and the HCSP recognize the Zika virus as a public health problem of international concern primarily because of the foetal risks. During the epidemic in Martinique, several modifications to the normal obstetrical follow-up were set up and information had to be delivered to pregnant women about these modifications, the attitudes to prevent infection and the signs motivating additional visits. The objective of our work was to evaluate the knowledge, attitudes and practices of pregnant women in Martinique about the risks associated with Zika infection during pregnancy in the immediate aftermath of the epidemic. MATERIALS AND METHODS: A descriptive cross-sectional survey was conducted from February to May 2017. It took place through an anonymous and standardized face-to-face questionnaire. The questions dealt with the pregnant women general knowledge about the virus, information disseminated by media on this subject, the potential risks, the protective measures taken and the monitoring throughout the pregnancy in case of infection. RESULTS: The total sample consisted of 297 pregnant women. Despite a weak adherence to individual and domestic protection recommendations, we found a good level of knowledge about Zika virus from pregnant women in Martinique. The fetal risk in case of maternal infection was known for 96.6% of those surveyed, individual protective measures were followed by 64.6% of women, 77.0% knew where to go in case of suspected infection, and 79.4% reported that the modifications in follow-up mainly concerned ultrasound monitoring. CONCLUSION: The awareness campaign on zika virus had a significant impact on population's knowledge and main practical information was correctly captured. The information did not spill excessive fear. Nevertheless, modification of individual behavior appeared harder to obtain.

Zika Virus Outbreak - Should assisted reproduction patients avoid pregnancy?

OBJECTIVE: To discuss the requirement from the National Health Surveillance Agency (ANVISA), for assisted reproduction treatment patients to undergo laboratory tests for ZIKV detection, and if the public health authorities and government leaders' recommendations to women simply avoid pregnancy is prudent. METHODS: This study was performed in a university-affiliated in vitro fertilization center in Brazil. We present a critical discussion on the risk of microcephaly due to ZIKV infection and the prevalence of other harmful pathogens to vulnerable pregnant women and infants. We assessed, 954 patients undergoing intracytoplasmic sperm injection cycles (ICSI), between April and November of 2016, concerning the results of ZIKV test, according to different regions in Brazil. RESULTS: Patients undergoing ICSI cycles were split into groups, according to their region of origin: 28 (3.0%) were from the North, 27 (2.8%) were from the Northeast, 40 (4.2%) were from the Midwest, 830 (87.2%) were from the Southeast, and 29 (3.0%) were from the South. Concerning the diagnosis, 112 samples had a positive or inconclusive result for ZIKV, by chromatography immunoassay. These samples were re-analyzed by ELISA and no result was positive. All positive results were from the Southeast region and none from the Northeast or Midwest regions, which are considered endemic regions. CONCLUSION: ZIKV test before the onset of assisted reproduction treatments does not rule out the risk of the infection during pregnancy. In addition, although ZIKV infection risk is extremely high, the microcephaly risk due to ZIKV is not higher than the risk of miscarriage and birth defects due to other recognized pathogens.

Biphasic effect of alpha-linolenic acid on glucose-induced dysmorphogenesis and lipoperoxidation in whole rat embryo in culture.

Type 1 diabetes mellitus complicated with pregnancy, know as diabetic embryopathy, is the cause of neonatal malformations and low for gestational age neonates. With the use of the whole-embryo culture system, it has been demonstrated that high glucose causes embryo dysmorphogenesis, and that oxidative stress appears to be the main mechanism. In recent years, beneficial effect of omega-3 fatty acids has been demonstrated in various diabetic models, and in diabetic complications. Since diabetic embryopathy is mediated probably through membrane lipoperoxidation, This study was designed to find if omega-3 fatty acids could ameliorate the effect of high glucose over the dysmorphogenesis of whole rat embryo in culture. Postimplantational rat embryos were cultured in hyperglycemic media, with addition of alpha-linolenic acid, and morphologic and morphometric parameters were registered. Also, lipoperoxidation and fatty acids composition were measured in cultured embryos. Growth of embryos cultured in presence of glucose was very affected, whereas lipoperoxidation was increased, and it was found that Triton X-100 causes similar results than glucose. Addition of low micromolar doses of alpha-linolenic acid overcome the effect of high glucose or Triton X-100, but higher doses does not ameliorates the effects of the carbohydrate or the detergent. Paradoxically, there are not significant changes in fatty acids composition, although the U/S fatty acids ratio shows an increasing tendency by high glucose and a normalizing tendency by omega-3 fatty acids. In conclusion, glucose and Triton X-100 induces in vitro dysmorphogenesis in post-implantational rat embryos associated with increased lipoperoxidation; and this nocive effect could be ameliorated by low micromolar doses of ALA.

Clinical recommendations for women exposed to Zika

Zika is an infectious disease that continues to pose an enduring threat worldwide. The disease is of particular concern to women of childbearing age, as the virus can cause devastating birth defects or fetal loss if acquired during pregnancy. Clinicians caring for women capable of becoming pregnant must inform women regarding the potential for Zika transmission via mosquito bites in affected regions as well as by sexual contact with exposed partners. Because of the global scope of the disease, clinicians caring for pregnant patients should evaluate for risk of Zika exposure to provide patients guidance in decision making related to virus prevention and testing.

Zika es una enfermedad infecciosa que aún representa una amenaza de largo plazo en todo el mundo. La enfermedad es especialmente peligrosa para las mujeres en edad fértil, ya que si se adquiere durante el embarazo, el virus puede causar defectos congénitos devastadores o pérdida del feto. Profesionales de la salud encargados del cuidado de las mujeres con planes de quedar embarazadas deberían informar a estas pacientes sobre el potencial de transmisión de Zika a través de picaduras de mosquitos en regiones afectadas, así como, por contacto sexual con parejas expuestas. Debido a los resultados de la extensión global de la enfermedad, los profesionales de salud que cuidan a las pacientes embarazadas también necesitan evaluar el riesgo de contacto con Zika para proporcionar orientación a los pacientes en la adopción de decisiones relacionadas con la prevención y las pruebas de este virus.

Mitigating Prenatal Zika Virus Infection in the Americas.

BACKGROUND: Because of the risk for Zika virus infection in the Americas and the links between infection and microcephaly, other serious neurologic conditions, and fetal death, health ministries across the region have advised women to delay pregnancy. However, the effectiveness of this policy in reducing prenatal Zika virus infection has yet to be quantified. OBJECTIVE: To evaluate the effectiveness of pregnancy-delay policies on the incidence and prevalence of prenatal Zika virus infection. DESIGN: Vector-borne Zika virus transmission model fitted to epidemiologic data from 2015 to 2016 on Zika virus infection in Colombia. SETTING: Colombia, August 2015 to July 2017. PATIENTS: Population of Colombia, stratified by sex, age, and pregnancy status. INTERVENTION: Recommendations to delay pregnancy by 3, 6, 9, 12, or 24 months, at different levels of adherence. MEASUREMENTS: Weekly and cumulative incidence of prenatal infections and microcephaly cases. RESULTS: With 50% adherence to recommendations to delay pregnancy by 9 to 24 months, the cumulative incidence of prenatal Zika virus infections is likely to decrease by 17% to 44%, whereas recommendations to delay pregnancy by 6 or fewer months are likely to increase prenatal infections by 2% to 7%. This paradoxical exacerbation of prenatal Zika virus exposure is due to an elevated risk for pregnancies to shift toward the peak of the outbreak. LIMITATION: Sexual transmission was not explicitly accounted for in the model because of limited data but was implicitly subsumed within the overall transmission rate, which was calibrated to observed incidence. CONCLUSION: Pregnancy delays can have a substantial effect on reducing cases of microcephaly but risks exacerbating the Zika virus outbreak if the duration is not sufficient. Duration of the delay, population adherence, and the timing of initiation of the intervention must be carefully considered. PRIMARY FUNDING SOURCE: National Institutes of Health.

Comportamiento clínico epidemiológico de los defectos congénitos en La Habana / Clinical and epidemiological situation of congenital defects in La Habana province

INTRODUCCIÓN: los defectos congénitos son causa importante de morbilidad y mortalidad infantil porque representan un problema de salud global. En Cuba estos defectos constituyen la segunda causa de muerte en niños menores de un año, lo que hace necesario la existencia de sistemas de vigilancia que permitan analizar el comportamiento de estas alteraciones. OBJETIVO: caracterizar clínica y epidemiológicamente a los recién nacidos con defectos congénitos, así como describir el comportamiento de los defectos congénitos diagnosticados prenatalmente por los diferentes programas. MÉTODOS: se realizó un estudio observacional y descriptivo basado en la información del Registro Cubano de Malformaciones Congénitas correspondiente a un periodo de 5 años. Se estudiaron un total de 1 816 recién nacidos con defectos congénitos y 1 238 interrupciones terapéuticas voluntarias, para un total de 3 054 productos de la gestación con defectos congénitos. RESULTADOs: el 81,2 % de estos defectos fueron aislados, con respecto a las malformaciones múltiples los más frecuentes fueron los síndromes. Según el área de residencia, la mayor frecuencia de los defectos en nacidos vivos se presentó en Boyeros, con 272, y predominaron las interrupciones terapéuticas en Arroyo Naranjo con un total de 116. El 14,2 % de la mortalidad en niños menores de un año estuvo asociada a defectos congénitos. CONCLUSIONES: los defectos congénitos más frecuentes son los aislados, dentro de ellos, predominan las cardiopatías congénitas. Con respecto a los defectos congénitos múltiples, los más frecuentes son los síndromes. El municipio de Boyeros presenta el mayor número de nacimientos con defectos congénitos, mientras que el municipio de Arroyo Naranjo presenta el mayor número de interrupciones terapéuticas.

INTRODUCTION: congenital defects are significant causes of infant mortality and morbidity because they represent a global health problem. These defects in Cuba are the second cause of death in children aged less than one year, which makes it necessary to have surveillance systems that allow analyzing the behavior of these disorders. OBJECTIVE: to clinically and epidemiologically characterize the newborns with congenital defects as well as to describe the behavior of such defects diagnosed before birth by the different programs. METHODS: observational and descriptive study based on the information provided by the Cuban Register of Congenital Malformations in a 5 year period. One thousand and eight hundred sixteen newborn with congenital defects and 1 238 voluntary therapeutic abortions were studied for a total number of 3 054 gestational products with congenital defects. RESULTS: in the study, 81.2 % of these defects were single; in the multiple malformations the most common were syndromes. According to the area of residence, the highest frequency of defects in newborns was found in Boyeros municipality with 272 and the voluntary therapeutic abortions predominated in Arroyo Naranjo municipality with 116. The mortality rate of 14.2% in children under one year of age was associated to congenital defects. CONCLUSIONS: the most frequent congenital defects were single, being congenital cardiopathies predominant. Regarding the multiple congenital defects, syndromes were the most common. Boyeros municipality presented the highest number of births with congenital defects whereas Arroyo Naranjo municipality has the highest number of therapeutic abortions.

Prenatal diagnosis: From policy to practice. Two distinct ways of managing prognostic uncertainty and anticipating disability in Brazil and in France.

Prenatal diagnosis (PND) has gradually established itself as part of the pregnancy monitoring process, with a view to reducing the number of births of children exposed to disability by combining the use of biomedical tools with laws that authorise abortion in cases of foetal pathology. This article looks at how laws which vary from one country to another modulate the way in which PND practices are organised on a daily basis, determine the discourse of practitioners and lead them to adopt specific stances during prenatal consultations with couples coping with a foetal anomaly. We present a comparative ethnographic study, which took place between 2009 and 2011 in France and Brazil, in reference units, based on observation of consultations, professional meetings, and interviews with health practitioners. The fact that access to abortion due to foetal pathology is possible in France, and criminalised in Brazil, conditions how doctors analyse the framework of their medical practice and approach the issue of disability with couples during consultations. In France, practitioners would appear to be satisfied with a professional framework that they themselves created. Faced with prognostic uncertainty, the legal obligation to inform encourages them to discuss all of the potential complications of the diagnosed anomalies and leads them to provide probabilistic information about the life of the child to be, supported by evidence-based medicine. In Brazil, in the public service, the lack of access to abortion has created a malaise among practitioners who criticise this impediment to the objective nature of their practice and to the quality of the information that they provide. Some use prognostic uncertainty to direct the thoughts of women and couples towards the dynamics proper to each individual human trajectory within a given family and a specific social environment.