Nested case-control study of maternal herpes viruses in relation to gastroschisis

母体疱疹病毒与腹裂相关的巢式病例对照研究

• 批准号: 8511889
• 负责人: MARTHA M. WERLER
• 金额: $ 9.26万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-10 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8511889
• 关键词: Accounting; Address; Affect; Age; Alcohol consumption; Animal Model; Biological; Birth; Body mass index; Breast Cancer Risk Factor; Cardiovascular Diseases; Characteristics; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Congenital Abnormality; Cytomegalovirus; Data Sources; Defect; Development; Diet; Drug usage; Epidemiology; Etiology; Family; Fetal Development; Finland; First Pregnancy Trimester; Gastroschisis; Genitourinary system; Geographic Locations; Goals; Gravidity; Herpesviridae; Human Herpesvirus 2; Human Herpesvirus 4; Illicit Drugs; Infection; Infectious Agent; Inherited; Intestines; Investigation; Knowledge; Lead; Life Style; Link; Maternal Age; Measures; Mechanics; Medical; Mothers; Multiple Sclerosis; Names; Nested Case-Control Study; Operative Surgical Procedures; Organ; Pathogenesis; Pathway interactions; Pattern; Phenotype; Pregnancy; Pregnant Women; Prevalence; Prevention; Prevention Measures; Public Health; Recurrence; Reporting; Research; Research Personnel; Risk; Risk Factors; Sampling; Serological; Serum; Simplexvirus; Smoking; Stomach; Time; Upper Respiratory Infections; Vitamin D; abdominal wall; base; case control; cigarette smoking; cohort; congenital infection; maternal serum; offspring; parity; prevent; public health relevance; residence; teenage mother; young mother

DESCRIPTION (provided by applicant): Gastroschisis, a congenital abdominal wall defect where the bowel and other organs are outside of the body at birth, has substantial surgical and medical consequences. Gastroschisis stands out from other birth defects in that it has a low recurrence risk, occurs most often in the offspring of younger mothers, has been increasing in prevalence over the past several decades, and sometimes occurs in clusters. Although cigarette smoking, high alcohol intake, and illicit drug use are more common in young mothers and have been linked to gastroschisis risk, they do not account for the strong inverse relation with maternal age. The epidemiologic characteristics of gastroschisis suggest an infectious agent may be in the developmental pathway. Certain infectious agents are known to cause birth defects, but gastroschisis has not been identified as part of a congenital infection phenotype. We have identified four infectious agents with patterns of occurrence that match the epidemiologic profile of gastroschisis: Epstein-Barr virus, herpes simplex virus 2, cytomegalovirus, and Chlamydia trachomatis. However, a clear biological mechanism through which these infectious agents could disrupt fetal development to produce the isolated gastroschisis defect is lacking at present. Thus, we propose this exploratory project, to quickly and efficiently identify whether these infectious agents are associated with gastroschisis and whether a large-scale, clinically-oriented study is warranted to explore biologic mechanisms. The aims of this exploratory study will be achieved simply and efficiently by a nested case-control study within the Finnish Maternity Cohort. First trimester maternal serum samples have been banked on over 1.7 million pregnancies, including approximately 401 gastroschisis-affected pregnancies. Two controls will be matched to each case by maternal age. Serologic evidence of primary or recurrent infection during early gestation (when gastroschisis develops) will be compared between cases and controls, taking the matching factors, birth year, geographic region, parity, body mass index, smoking, and vitamin D into account. The use of first trimester serum samples to measure infection status overcomes the challenge of retrospective maternal report that has been used in the majority of previous studies of risk factors for gastroschisis. This exploratory project has enormous potential to develop a new trajectory of gastroschisis research, which could lead to knowledge of its pathogenesis, to an explanation of the strong inverse maternal age association and increasing prevalence over time, and to prevention. Because first trimester serum samples capture the etiologically relevant time frame for most birth defects, this developmental project could spur new research agendas for many birth defects.

描述（由申请人提供）：胃静脉，是一种先天性腹壁缺陷，肠子和其他器官在出生时就在体内，具有实质性的外科手术和医疗后果。胃切西斯（Gastroschisis）脱离了其他出生缺陷，因为它具有低复发风险，最常发生在年轻母亲的后代，在过去几十年中的患病率一直在增加，有时会发生在集群中。尽管吸烟，高酒精摄入量和非法吸毒在年轻母亲中更为常见，并且与胃癌风险有关，但它们与产妇年龄的牢固相反。胃肠道的流行病学特征表明，传染剂可能处于发育途径中。已知某些感染剂会导致先天缺陷，但胃静脉曲子尚未被确定为先天性感染表型的一部分。我们已经确定了四种具有与胃肠道的流行病学特征相匹配的传染剂：爱泼斯坦 - 巴尔病毒，单纯疱疹病毒2，巨细胞病毒和沙眼衣原体。然而，目前缺乏一种清晰的生物学机制，通过这些机制这些传染性剂可能破坏胎儿发育以产生孤立的胃肠道缺陷。因此，我们提出了这个探索性项目，以快速有效地确定这些传染性药物是否与胃静脉曲相关，以及是否有必要进行大规模的，临床上的研究以探索生物学机制。这项探索性研究的目的将通过芬兰孕妇队列中的嵌套病例对照研究简单有效地实现。头三年的血清样本已被押注超过170万例，其中包括大约401例受胃胃造成的妊娠。到产妇年龄，将将两个控件与每种情况匹配。在病例和对照组之间将比较早期妊娠期间原发或复发感染的血清学证据，将匹配因子，出生年份，地理区域，奇偶校验，体重指数，吸烟和维生素D进行比较。使用头三个月的血清样品测量感染状况克服了回顾性母亲报告的挑战，这些报告已用于大多数先前关于胃危风险因素的研究。这个探索性项目具有开发胃肠道研究的新轨迹的巨大潜力，这可能会导致对其发病机理的了解，从而解释了强大的孕产妇年龄关联，并且随着时间的推移和预防的越来越多。由于头三个月的血清样品捕获了大多数先天缺陷与病因相关的时间范围，因此该发展项目可能会刺激许多先天缺陷的新研究议程。