Principles of studying low-level neurotoxic exposures in children: using the Seychelles Child Development Study of methyl mercury as a prototype

Epidemiological studies to determine the impact of low level toxic exposure on child development are important in guiding clinical and public health action. However, carrying out such studies and interpreting their findings presents a number of significant challenges to the investigators. First, they must find a cohort with suitable exposure, select a biomarker that will accurately determine the level of exposure and determine the endpoints that are most likely to detect subtle differences in neurodevelopment. Following that, the logistics of the study must be organised and collaboration established with the local population and health authorities. To accurately interpret the data, they must also accurately determine covariates that impact child development. After the data are collected, interpreting the findings presents a further challenge. Throughout this process, the study must adhere to fundamental epidemiological principles and clearly defined statistical approaches. This paper discusses those principles and uses the Seychelles Child Development Study to show how one epidemiological study addressed them.     

In utero DDT exposure and breast density before age 50

Prior studies in the Child Health and Development Studies (CHDS) found in utero exposure to the pesticide, dichlorodiphenyltrichloroethane (DDT), increased breast cancer risk by age 52. Mammographic density is considered a primary risk factor for breast cancer. We conducted a study of 309 daughters from the CHDS to examine in utero DDT exposure and mammographic density in midlife. Among daughters with high (>75th percentile) exposure to p,p’-Dichlorodiphenyldichloroethylene (DDE), p,p’-DDT was significantly correlated with increased dense area and percent density regardless of her body mass in midlife. In the subset of women with lower (<75th percentile) p,p-DDE, p,p’-DDT was associated with increased non-dense breast area. This was explained by adjustment for midlife BMI suggesting that p,p’-DDT may be obesogenic. In aggregate our findings indicate that early life p,p’-DDT exposure impacts breast density in a complex way that depends on the hosts biological ability to sequester and process DDT and levels of exposure.     

四川省首例COVID-19婴儿病例分析及文献复习

目的探讨1例输入性、家庭聚集性严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的2^＋个月龄新型冠状病毒疾病(COVID-19)婴儿的临床流行病学资料及影像学资料特点，并进行文献复习。 方法选择2020年2月7日，四川省金堂县第一人民医院收治的2^＋个月龄COVID-19婴儿为研究对象。采用回顾性分析方法，收集该例婴儿的临床病例资料，对其临床流行病学特点、影像学资料、诊断、治疗方案及预后进行分析。本研究对报道COVID-19婴儿的相关文献进行复习，设定检索策略为：以"婴儿""新型冠状病毒肺炎""新型冠状病毒疾病""2019-nCoV""NCP""SARS-CoV-2""COVID-19""infant"等为关键词，在PubMed、Medline、中国知网、维普中文科技期刊数据库、万方数据知识服务平台，以及"医学界儿科频道"等公众平台及新闻网站中，检索相关文献，检索时间设定为2019年12月1日至2020年2月21日。总结符合本研究纳入、排除标准的文献中报道的COVID-19婴儿临床特点及其诊断、治疗方案与预后。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。 结果①病史采集、诊断、治疗结果：患儿，男性，生后2个月＋29 d；2020年1月18日，患儿姨妈自武汉返蓉，密切接触后，患儿出现气促、轻微咳嗽、腹泻等症状。入院后，患儿检查结果显示，肺炎支原体及衣原体、甲型及乙型流感病毒抗原均呈阴性。胸部CT检查结果显示，患儿双肺胸膜下多发性浅淡磨玻璃病灶。2次鼻咽拭子SARS-CoV-2核酸检测均呈阳性。根据流行病学史、临床与影像学表现及核酸检测结果，确诊为普通型COVID-19患儿。经过对症治疗后，患儿气促、咳嗽临床症状消失，胸部影像学检查结果显示，肺部炎症病灶吸收，SARS-CoV-2核酸检测呈阴性。目前，患儿继续观察中，等候出院。②文献复习结果：按照本研究设定的文献检索策略，共计检索出5篇国内有关婴儿COVID-19文献及2篇婴儿COVID-19新闻报道，涉及18例COVID-19婴儿的临床特点、诊断、治疗方案及预后等研究。这18例COVID-19婴儿，均具有家庭聚集性、输入性感染特点(武汉COVID-19患者接触史)。其中，3例新生儿及其母亲均为SARS-CoV-2感染者。出生后，对2例新生儿进行有效隔离，无感染者接触史。这18例COVID-19婴儿的首发症状为：发热5例(27.8%)、咳嗽及下呼吸道症状3例(16.7%)、打喷嚏及吐奶1例(5.6%)、无症状3例(16.7%)、病史不详6例(33.3%)。其中，7例婴儿文献报道胸部CT检查结果，并且均存在异常，表现为双肺或单侧肺纹理增粗、磨玻璃影和(或)实变影。除2例婴儿未报道预后情况外，其余16例婴儿均预后良好，无死亡病例报道。 结论文献报道的COVID-19婴儿及纳入本研究的1例婴儿，均具有输入性、家庭聚集性感染特点，而且对新生儿患者，目前尚不能排除母婴垂直传播可能性。对于临床症状相对较轻，肺部病变范围相对较小且局限的COVID-19婴儿，一般预后较好。在COVID-19暴发流行期，应尽可能加强儿童，特别是婴儿的防护，避免输入性、家庭聚集性SARS-CoV-2感染。