Ethical guidelines for birth defect prevention recommended by experts. / 出生缺陷预防的伦理指导原则专家建议.

China's maternal and child health work is still facing many challenges, such as unbalanced development and inadequate services. Since the adjustment of the family planning policy, the proportion of older and more productive sub-parturient women have increased, the risk for birth defects has increased, the demand for newborn safety has further increased, and the work of maternal and child health is facing new challenges. The experts from the medicine, medical ethics, sociology, and other fields put forward the principle of ethical guidance for birth defect prevention after full discussion and continuous revision based on expert proposals, which include the principle of life dignity, love, scientific principle, fair principle, respect for autonomy principle, the principle of beneficence and the principle of good privacy protection. The guideline can serve the birth defect prevention clinical practice, be better to respect and safeguard the legitimate rights and interests of people at childbearing age, eliminate ethics cognition pitfalls of birth defect prevention, and regulate the behavior of birth defect prevention-related ethics.

Cardiopatia congênita afeta cerca de 30 mil crianças por ano no Brasil

As cardiopatias congênitas são um conjunto de malformações na estrutura ou na função do coração que surgem durante o desenvolvimento fetal.

Surco perineal: un viejo poco conocido / Perineal groove: a little-known old man

Introducción: El surco perineal es una malformación infrecuente dela línea media. Se trata de un surco húmedo, mucoso y no queratinizado localizado en la línea media del periné desde la horquilla vulvar hastael borde anal anterior. Es una malformación infrecuente, usualmente asintomática y de resolución espontánea en la mayoría de los casos. Esta anomalía es frecuentemente confundida con otras malformaciones por lo que su reconocimiento es fundamental para evitar yatrogenia. Caso clínico: Se presenta el caso de una recién nacida con una lesión asintomática en la línea media del periné sospechosa de malformación anorrectal. Tras valoración por el Servicio de Cirugía Pediátrica se diagnosticó de surco perineal. Comentarios: Debido a la infrecuencia y escasa documentación bibliográfica del surco perineal, esta malformación es desconocida paramuchos sanitarios. Este caso expone la importancia de tener presente estaanomalía para evitar diagnósticos erróneos, tratamientos innecesarios y estrés familiar.(AU)

Introduction: Perineal groove is an infrequent midline malformation. It is a humid, mucosal, non keratinized groove located at theperineal midline, extending from the vulvar fourchette to the anterioranal border. It is rare and usually asymptomatic, and it heals spontane-ously in most cases. It is frequently mistaken for other malformations,which means correctly identifying it is essential to avoid iatrogenesis. Clinical case: We present the case of a female newborn with anasymptomatic lesion at the perineal midline consistent with anorectal malformation. Following assessment by the Pediatric Surgery Department, she was diagnosed with perineal groove. Discussion: Perineal groove is a little known malformation amonghealthcare professionals as it is infrequent and there are not many publications in the literature about it. This case demonstrates how importantit is to keep this abnormality in mind to avoid erroneous diagnoses, unnecessary treatments, and family stress.(AU)

Efficacy of 4.0 mg versus 0.4 mg Folic Acid Supplementation on the Reproductive Outcomes: A Randomized Controlled Trial.

Folic acid (FA) supplementation prevents neural tube defects (NTDs), but the effects on other reproductive outcomes are unclear. While common recommendation is 0.4 mg/day in addition to regular nutrition, the most appropriate dose of FA is still under debate. We investigated the effects of a higher dose of periconception FA on reducing adverse reproductive outcomes. In this multicenter double-blind randomized controlled trial (RCT), 1060 women (aged 18-44 years and planning a pregnancy) were randomly assigned to receive 4.0 mg or 0.4 mg of FA daily. The primary outcome was the occurrence of congenital malformations (CMs). A composite outcome including one or more adverse pregnancy outcomes was also evaluated. A total of 431 women had a natural conception within 1 year. The primary outcome occurred in 8/227 (3.5%) women receiving 4.0 mg FA and 9/204 (4.4%) women receiving 0.4 mg FA (RR 0.80; 95%CI 0.31 to 2.03). The composite outcome occurred in 43/227 (18.9%) women receiving 4.0 mg FA and 75/204 (36.8%) women receiving 0.4 mg FA (RR 0.51; 95%CI 0.40 to 0.68). FA 4.0 mg supplementation was not associated with different occurrence of CMs, compared to FA 0.4 mg supplementation. However, FA 4.0 mg supplementation was associated with lower occurrence of other adverse pregnancy outcomes.

An Evaluation of Human Induced Pluripotent Stem Cells to Test for Cardiac Developmental Toxicity.

To prevent congenital defects arising from maternal exposure, safety regulations require pre-market developmental toxicity screens for industrial chemicals and pharmaceuticals. Traditional embryotoxicity approaches depend heavily on the use of low-throughput animal models which may not adequately predict human risk. The validated embryonic stem cell test (EST) developed in murine embryonic stem cells addressed the former problem over 15 years ago. Here, we present a proof-of-concept study to address the latter challenge by updating all three endpoints of the classic mouse EST with endpoints derived from human induced pluripotent stem cells (hiPSCs) and human fibroblasts. Exposure of hiPSCs to selected test chemicals inhibited differentiation at lower concentrations than observed in the mouse EST. The hiPSC-EST also discerned adverse developmental outcomes driven by novel environmental toxicants. Evaluation of the early cardiac gene TBX5 yielded similar toxicity patterns as the full-length hiPSC-EST. Together, these findings support the further development of hiPSCs and early molecular endpoints as a biologically relevant embryotoxicity screening approach for individual chemicals and mixtures.

Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus.

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1-2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal­neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.

Reducing the Burden of Anemia and Neural Tube Defects in Low- and Middle-Income Countries: An Analysis to Identify Countries with an Immediate Potential to Benefit from Large-Scale Mandatory Fortification of Wheat Flour and Rice.

Using a predetermined set of criteria, including burden of anemia and neural tube defects (NTDs) and an enabling environment for large-scale fortification, this paper identifies 18 low- and middle-income countries with the highest and most immediate potential for large-scale wheat flour and/or rice fortification in terms of health impact and economic benefit. Adequately fortified staples, delivered at estimated coverage rates in these countries, have the potential to avert 72.1 million cases of anemia among non-pregnant women of reproductive age; 51,636 live births associated with folic acid-preventable NTDs (i.e., spina bifida, anencephaly); and 46,378 child deaths associated with NTDs annually. This equates to a 34% reduction in the number of cases of anemia and 38% reduction in the number of NTDs in the 18 countries identified. An estimated 5.4 million disability-adjusted life years (DALYs) could be averted annually, and an economic value of 31.8 billion United States dollars (USD) generated from 1 year of fortification at scale in women and children beneficiaries. This paper presents a missed opportunity and warrants an urgent call to action for the countries identified to potentially avert a significant number of preventable birth defects, anemia, and under-five child mortality and move closer to achieving health equity by 2030 for the Sustainable Development Goals.

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.

Association of Improved Periconception Hemoglobin A1c With Pregnancy Outcomes in Women With Diabetes.

Importance: Prepregnancy diabetes is associated with higher perinatal and maternal morbidity, especially if periconception glycemic control is suboptimal. It is not known whether improved glycemic control from preconception to early pregnancy and midpregnancy periods can reduce the risk of adverse perinatal and maternal outcomes. Objective: To determine whether a net decline in glycated hemoglobin A1c (HbA1c) from preconception to the first half of pregnancy is associated with a lower risk of adverse outcomes for mother and child. Design, Setting, and Participants: This population-based cohort study was completed in all of Ontario, Canada, from 2007 to 2018. Included were births among women with prepregnancy diabetes whose HbA1c was measured within 90 days preconception and again from conception through 21 weeks completed gestation (early pregnancy to midpregnancy). Statistical analysis was performed from July to September 2020. Exposures: Net decrease in HbA1c from preconception to early pregnancy and midpregnancy. Main Outcomes and Measures: The main outcome was a congenital anomaly from birth to age 1 year. Other outcomes included preterm birth or perinatal mortality among offspring as well as severe maternal morbidity (SMM) or death among mothers. Adjusted relative risks (aRRs) were calculated per 0.5% absolute net decline in HbA1c from preconception up to early pregnancy and midpregnancy, adjusting for maternal age at conception, preconception HbA1c and hemoglobin concentration, and gestational age at HbA1c measurement. Results: A total of 3459 births were included, with a mean (SD) maternal age of 32.6 (5.0) years at conception. Overall, the mean (SD) HbA1c decreased from 7.2% (1.6%) preconception to 6.4% (1.1%) in early pregnancy to midpregnancy. There were 497 pregnancies (14.4%) with a congenital anomaly, with an aRR of 0.94 (95% CI, 0.89-0.98) per 0.5% net decrease in HbA1c, including for cardiac anomalies (237 infants; aRR, 0.89; 95% CI, 0.84-0.95). The risk was also reduced for preterm birth (847 events; aRR, 0.89; 95% CI, 0.86-0.91). SMM or death occurred among 191 women (5.5%), with an aRR of 0.90 (95% CI, 0.84-0.96) per 0.5% net decrease in HbA1c. Conclusions and Relevance: These findings suggest that women with prepregnancy diabetes who achieve a reduction in HbA1c may have improved perinatal and maternal outcomes. Further study is recommended to determine the best combination of factors, such as lifestyle changes and/or glucose-lowering medications, that can influence periconception HbA1c reduction.

The Reproductive Journey in the Genomic Era: From Preconception to Childhood.

It is estimated that around 10-15% of the population have problems achieving a pregnancy. Assisted reproduction techniques implemented and enforced by personalized genomic medicine have paved the way for millions of infertile patients to become parents. Nevertheless, having a baby is just the first challenge to overcome in the reproductive journey, the most important is to obtain a healthy baby free of any genetic condition that can be prevented. Prevention of congenital anomalies throughout the lifespan of the patient must be a global health priority. Congenital disorders can be defined as structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth, or sometimes may only be detected later during childhood. It is considered a frequent group of disorders, affecting 3-6% of the population, and one of the leading causes of morbidity and mortality. Congenital anomalies can represent up to 30-50% of infant mortality in developed countries. Genetics plays a substantial role in the pathogenesis of congenital anomalies. This becomes especially important in some ethnic communities or populations where the incidence and levels of consanguinity are higher. The impact of genetic disorders during childhood is high, representing 20-30% of all infant deaths and 11.1% of pediatric hospital admissions. With these data, obtaining a precise genetic diagnosis is one of the main aspects of a preventive medicine approach in developed countries. The field of reproductive health has changed dramatically from traditional non-molecular visual microscope-based techniques (i.e., fluorescence in situ hybridization (FISH) or G-banding karyotype), to the latest molecular high-throughput techniques such as next-generation sequencing (NGS). Genome-wide technologies are applied along the different stages of the reproductive health lifecycle from preconception carrier screening and pre-implantation genetic testing, to prenatal and postnatal testing. The aim of this paper is to assess the new horizon opened by technologies such as next-generation sequencing (NGS), in new strategies, as a genomic precision diagnostic tool to understand the mechanisms underlying genetic conditions during the "reproductive journey".

Effectiveness of community-based folate-oriented tertiary interventions on incidence of fetus and birth defects: a protocol for a single-blind cluster randomized controlled trial.

BACKGROUND: Birth defects are the main cause of fetal death, infant mortality and morbidity worldwide. However, the etiology of birth defects remains largely unknown. Maternal folate status during periconception plays an important role in organogenesis and folic acid supplement reduces the risk of neural tube defects, congenital heart diseases, and several other birth defects. This trial seeks to evaluate the effectiveness of folate-oriented tertiary interventions during periconception on the incidence of fetus and birth defects. METHODS: This is a single-blind, two-arm cluster randomized controlled trial in Shanghai, China. Eligible women from 22 clusters are recruited at pre-pregnancy physical examinations clinical settings. Compared to the routine perinatal care group (control arm), folate-oriented tertiary interventions will be provided to the intervention arm. The core interventions consist of assessments of folate status and metabolism, folate intake guidance, and re-evaluation of folate status to ensure red blood cell folate level above 400 ng/ml (906 nmol/L) before pregnancy. Screening and consulting of fetus and birth defects, and treatments of birth defects during pregnancy and afterward will be provided to both arms. The primary outcome is a composite incidence of fetus defects, stillbirth, and neonatal birth defects identified from the confirmation of pregnancy to 28 days after birth. Secondary outcomes include maternal and offspring adverse complications and cost-effectiveness of folate-oriented tertiary interventions. This protocol adheres to the SPIRIT Checklist. DISCUSSION: To achieve the recommended folate status before or during pregnancy is still a challenge worldwide. This community-based cluster-randomized controlled intervention trial will evaluate the effectiveness of a package of interventions aiming at achieving recommended maternal folate status covering pre- and during pregnancy in reducing fetus and birth defects. Our study has the potential to improve the community-based practice of reducing modifiable risk factors of disease and improving primary prevention of the defects in China. The procedures would formulate the policy on folic acid supplementation during periconception against birth defects in primary care settings. TRIAL REGISTRATION: Clinical Trial Registry, NCT03725878 . Prospectively registered on 31 October 2018.

Mechanisms of oocyte aneuploidy associated with advanced maternal age.

It is well established that maternal age is associated with a rapid decline in the production of healthy and high-quality oocytes resulting in reduced fertility in women older than 35 years of age. In particular, chromosome segregation errors during meiotic divisions are increasingly common and lead to the production of oocytes with an incorrect number of chromosomes, a condition known as aneuploidy. When an aneuploid oocyte is fertilized by a sperm it gives rise to an aneuploid embryo that, except in rare situations, will result in a spontaneous abortion. As females advance in age, they are at higher risk of infertility, miscarriage, or having a pregnancy affected by congenital birth defects such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Turner syndrome (monosomy X). Here, we review the potential molecular mechanisms associated with increased chromosome segregation errors during meiosis as a function of maternal age. Our review shows that multiple exogenous and endogenous factors contribute to the age-related increase in oocyte aneuploidy. Specifically, the weight of evidence indicates that recombination failure, cohesin deterioration, spindle assembly checkpoint (SAC) disregulation, abnormalities in post-translational modification of histones and tubulin, and mitochondrial dysfunction are the leading causes of oocyte aneuploidy associated with maternal aging. There is also growing evidence that dietary and other bioactive interventions may mitigate the effect of maternal aging on oocyte quality and oocyte aneuploidy, thereby improving fertility outcomes. Maternal age is a major concern for aneuploidy and genetic disorders in the offspring in the context of an increasing proportion of mothers having children at increasingly older ages. A better understanding of the mechanisms associated with maternal aging leading to aneuploidy and of intervention strategies that may mitigate these detrimental effects and reduce its occurrence are essential for preventing abnormal reproductive outcomes in the human population.

The effect of the National Birth Defects Intervention Project on the prevention of congenital disabilities among children in China: a natural experiment.

Most childhood disabilities are caused by congenital factors such as birth defects. The present study aims to evaluate the effect of periconceptional nutrition intervention on the prevention of congenital disability among Chinese children using the National Birth Defects Intervention Project as a natural experiment. We obtained individual-level data from the Second National Sample Survey on Disability, a nationally representative survey, and 110 365 children born between September 1999 and August 2003 were included for analysis. Difference-in-differences estimates of the project effects on congenital disability were captured by exploiting temporal variation in the timing of project exposure across four birth cohorts along with geographical variation in project category at the province level. The findings contribute to an emerging body of evidence showing that prenatal micronutrient intervention before and during early pregnancy could substantially reduce the risk of congenital disability in childhood (OR 0·73; 95 % CI 0·57, 0·94). The National Birth Defects Intervention Project improved the awareness of reproductive health and disability prevention in the population. It highlights the need for a potential policy change focusing on early-life health investment in China.

Maternal use of folic acid and multivitamin supplements and infant risk of birth defects in Norway, 1999-2013.

The association between folic acid supplementation and birth defects other than neural tube defects (NTD) remains unclear. We used a log-binomial regression model to investigate if periconceptional folic acid and/or multivitamin use was associated with birth defects in Norway with prospectively collected data from the Medical Birth Registry of Norway (MBRN) during 1999-2013. We used the European Surveillance of Congenital Anomalies (EUROCAT) classification system to define eleven organ-specific major birth defect groups (nervous system, eye, ear-face-neck, cardiovascular system, respiratory system, oral clefts, digestive system, abdominal wall, urinary system, genital organs and limb), with additional subgroups. Fetuses or infants whose mothers used folic acid and/or multivitamin supplements before and during pregnancy were classified as exposed. During the years 1999-2013, 888 294 (99·0 %) live-born infants, 6633 (0·7 %) stillborn infants and 2135 (0·2 %) fetuses from terminated pregnancies due to fetal anomalies were registered in the MBRN. Among the live- and stillborn infants of women who used vitamin supplements compared with infants of non-users, the adjusted relative risk (aRR) was 0·94 (95 % CI 0·91, 0·98) for total birth defects (n 18 382). Supplement use was associated with reduced risk of abdominal wall defects (aRR 0·58; 95 % CI 0·42, 0·80, n 377), genital organ defects (aRR 0·81; 95 % CI 0·72, 0·91, n 2299) and limb defects (aRR 0·81; 95 % CI 0·74, 0·90, n 3409). Protective associations were also suggested for NTD, respiratory system defects and digestive system defects although CI included the null value of 1. During the full study period, statistically significant associations between supplement use and defects in the eye, ear-face-neck, heart or oral clefts were not observed.

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)

The effects of preconception examinations on birth defects: a population-based cohort study in Dongguan City, China.

Objective: To evaluate the effect of preconception examinations programs on the prevention of birth defects in Dongguan City during 2013-2017.Methods: The data were from preconception examinations system and the birth defects surveillance system during 2013-2017. The study population included 63,175 infants born to mothers accepted preconception examinations during pregnancy (the screening group) and 649,862 infants whose mother did not check (the control group). The infants included for stillbirth, dead fetus, live birth between 28 weeks of gestation and 7 days after birth and legal pregnancy termination. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to examine for the association between birth defects and preconception examinations. We also conducted a stratified analysis based on infant gender and disease classification, and maternal age and region.Results: The incidence of birth defects in the screening group was 134.55/10,000, while that in the control group was 241.53/10,000. Preconception examinations can effectively reduce the incidence of birth defects (BDs) (RR: 0.557, 95%CI: 0.520-0.597). Bifid spine (RR: 0.076, 95%CI: 0.011-0.545), anencephalia (RR: 0.134, 95%CI: 0.033-0.543) and anorectal atresia or stenosis (RR: 0.151, 95%CI: 0.048-0.471) were controlled best, and Down syndrome (RR: 0.684, 95%CI: 0.435-1.075) was no effect. Young maternal age (14-19 years) and old maternal age will increase the risk of birth defects. Preconception examinations had the best effect for pregnant women under 25 years of age (RR: 0.465, 95%CI: 0.387-0.559), and were relatively poor for women aged 30-34 years (RR: 0.678, 95%CI: 0.593-0.776). The incidence of the urban was significantly higher than that of the rural. The effect of preconception examinations to prevent birth defects was more effective in urban areas (RR: 0.453, 95%CI: 0.391-0.525) than in rural areas (RR: 0.577, 95%CI: 0.533-0.625). The incidence of BDs in males was higher than that in females.Conclusions: By implementing preconception examinations project, birth defects in Dongguan have been well controlled. This can provide reference for other developing countries to prevent birth defects.

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.