重庆市孕前生殖健康与出生结局队列：设计简介与建设概况

出生队列是研究生命早期暴露对健康结局影响的重要工具, 但目前缺乏有力支撑孕前暴露特别是父系暴露对生殖健康和妊娠结局影响研究的大型队列平台。重庆市孕前生殖健康与出生结局队列研究是起始于孕前阶段, 同等关注男女双方的环境、心理、行为等暴露因素对生殖健康和不良妊娠结局影响的前瞻性队列研究。项目于2019年正式启动, 计划招募有生育意愿的育龄夫妇20 800人。通过随访, 调查志愿者2年内是否自然受孕。对进入妊娠期的女性志愿者, 在孕早、中、晚期进一步随访, 并对分娩的子代随访至2岁, 监测早产、低出生体重、出生缺陷、神经功能发育障碍等结局发生情况。各阶段分别采集相应的数据信息和生物样本, 包括精液、外周血、尿液、胎盘、脐带、脐带血、口腔拭子等。截至2022年1月, 已纳入志愿者8 698人, 分布于重庆市所有38个区/县。本队列建设目标是成为涵盖父母双方的前瞻性大样本孕前出生队列, 将以独特的设计和更加全面的视角阐明全生育周期特别是孕前期暴露因素对生殖健康和不良出生结局的影响及机制。     

Parent-reported birth information: birth weight,birth length and gestational age. Validation study in the SENDO project

ObjectiveTo test the validity of parent-reported birth information obtained through an online, self-administered questionnaire.MethodThe SENDO project is a prospective and dynamic paediatric cohort of Spanish children aged 4 to 6 years old at recruitment. Objective data from medical birth records were compared to parent-reported data getting intra-class correlation coefficients (ICC) for quantitative variables and weighted Kappa Index for qualitative ones. Percentage of responders and of total agreement was also evaluated.ResultsParental response rate was over 99% for birth weight and gestational age and 76% for birth length. ICC for birth weight was 0.95 (95% confidence interval [95%CI]: 0.94-0.96) and 0.78 (95%CI: 0.73-0.83) for birth length, both showing very high correlations. The total agreement percentage for gestational age was 97%, and Kappa weighted index was 0.90 (95%CI: 0.89-0.90), showing a very high agreement as well.ConclusionsWe found high correlations and excellent agreement in parent-reported birth data 4 to 6 years after delivery. Our results show parent-reported birth data, especially birth weight, are valid for use in epidemiological research.     

中国国家出生队列研究质量控制策略与措施

出生队列是研究孕前和孕期各种环境暴露因素与胎儿、婴幼儿、青少年健康之间关系的有效方法。出生队列建设周期长、环节众多,研究质量可能受到多种因素的影响。本文对中国国家出生队列建设过程中的各项质量保证和质量控制措施进行梳理,归纳总结建设经验。以期为相关队列研究提供经验,减少相关因素对队列研究的影响,提升队列研究质量。中国国家出生队列在质量保证的顶层设计方面采取一系列措施保障研究质量,包括研究中心筛选、成员管理系统开发、标准化操作流程制定及工作人员规范化培训;在质量控制方面,包括针对队列数据产生过程的实时、及时、定时质控,针对生物样本采集、处理及保存的全周期质控,以及针对参与工作人员的培训、督查和量化考核的全面立体质控。     

中国国家出生队列建设背景和设计简介

随着生活行为方式、自然和社会环境的急剧变化,育龄人口生殖健康状况持续下降,快速增加的由辅助生殖技术（ART）孕育的子代的远期健康状况亟待评估。因此,妇幼保健和生殖健康相关研究关注的重点亟需从妊娠期、围产期的死亡和严重疾病表型逐渐向全生命周期和全疾病谱拓展。为了满足这样的研究需求,在我国12个省（自治区、直辖市）启动了中国国家出生队列（China National Birth Cohort）建设,计划以家庭为单位,招募3万个自然妊娠家庭和3万个ART家庭的人群,并对夫妻双方以及孕育的子代开展长期随访,收集夫妻和子代的环境暴露、生殖生育、精神心理、行为习惯等多方面暴露数据。同时采集外周血、尿液、脐血、卵泡液和精浆、精子等多种类型的生物样本。该出生队列对于我国妇幼健康和生殖医学研究具有极其重要支撑作用和深远影响。本文即是对国家出生队列的建设概况和基本设计做简要介绍。     

中国国家出生队列研究调查对象的基线特征分析

目的 探讨生命早期环境因素、遗传因素和遗传与环境交互作用对子代近期和远期健康的影响以及系统评价和比较辅助生殖受孕和自然受孕人群的妊娠结局和子代健康相关结局。方法 中国国家出生队列（CNBC）研究是一项覆盖辅助生殖受孕家庭和自然受孕家庭的多中心前瞻性出生队列研究。2016年,CNBC项目陆续在我国12个省（自治区、直辖市）的24所医院启动,以家庭为单位纳入研究对象,并在辅助生殖治疗前、胚胎移植、孕早期、孕中期、孕晚期及分娩时以及出生后第42天、6个月、12个月、36个月多个时点采集数据信息和生物样本。结果 截至2020年6月,CNBC共纳入27 044个辅助生殖受孕家庭,29 589个自然受孕家庭,CNBC的研究人群中绝大部分为城市居民。在辅助生殖受孕家庭中,男女双方分别有65.5%和63.7%为大学及以上文化程度,年龄为（33.83±5.52）和（32.38±4.67）岁;女方83.2%为初产妇,吸烟率为0.8%,饮酒率为2.1%。在自然受孕家庭中,男女双方分别有81.5%和86.5%为大学及以上文化程度,年龄为（32.06±5.09）和（30.40±4.27）岁,女方67.2%为初产妇,吸烟率为0.1%,饮酒率为2.2%。不同地区的辅助生殖受孕家庭和自然受孕家庭的基线特征均有差异。结论 CNBC的建立将为研究生命早期遗传、环境因素、遗传-环境交互作用以及辅助生殖技术治疗相关因素对出生后子代健康的影响提供了重要资源。     

History of pandemic H1N1-containing influenza vaccination and risk for spontaneous abortion and birth defects

BackgroundOne recent study suggested an association between receipt of pandemic H1N1 (pH1N1)-containing vaccines in consecutive influenza seasons and spontaneous abortion, but corroborating scientific evidence is limited. In the present study, we leveraged a population of vaccine-compliant pregnant military women to examine history of pH1N1-containing influenza vaccination and adverse pregnancy outcomes. Because seasonal influenza vaccination is compulsory for military service, safety concerns regarding repeat vaccination are particularly relevant in this population.MethodsPregnancies and live births from Department of Defense Birth and Infant Health Research program data were linked with military personnel immunization records to identify women vaccinated with a pH1N1-containing vaccine in pregnancy prior to 21 6/7 weeks’ gestation, October 2009–April 2015. Cox and modified Poisson regression models estimated associations between vaccination with pH1N1- versus non–pH1N1-containing influenza vaccine in the season prior to the index pregnancy, and spontaneous abortion and birth defects, respectively. Cox models were calculated for two periods of follow-up: through (1) 21 6/7 weeks’ gestation and (2) 28 days postvaccination.ResultsOf 26,264 pregnancies, 21,736 (82.8%) were among women who received a dose of pH1N1-containing vaccine in the prior influenza season and 4,528 (17.2%) were among women who received non–pH1N1-containing vaccine in the prior influenza season. Among 23,121 infants, 19,365 (83.8%) and 3,756 (16.2%) had mothers exposed and unexposed to pH1N1-containing vaccine in the prior influenza season, respectively. The adjusted hazard ratio (aHR) for spontaneous abortion approximated 1.0 across the complete follow-up period (95% confidence interval [CI]: 0.89–1.13) and was slightly elevated when censored at 28 days postvaccination, though the CI was imprecise (aHR: 1.19; 95% CI: 0.97–1.46). No associations with birth defects were observed.ConclusionThis work lends additional safety evidence and support for vaccination against pH1N1 in pregnancy, regardless of the vaccine received in the prior influenza season.