Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, 3052, Australia.
Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Reprod Health. 2017 Sep 20;14(1):117. doi: 10.1186/s12978-017-0377-3.
Children conceived by assisted reproductive technologies (ART) currently comprise 4% of Australian births. The manipulation of biological parameters related to fertilization and implantation are integral to successful ART but potentially pose a risk to the longer-term health of the offspring. There is consensus that many common adult health problems (particularly cardiovascular, metabolic and respiratory conditions) have their origins in early life, possibly before birth, and that risk trajectories track through childhood until clinical disease manifests in adulthood. Early life epigenetic variation may play a role in this process. However little is known about the long-term health of individuals conceived by ART. In a previous study, based on telephone-interviews, we found that young adults conceived by in vitro fertilization (IVF) had significantly more maternal reported atopic respiratory, endocrine, nutritional, and metabolic conditions than non-IVF conceived matched controls. Here we outline the protocol for a follow-up biomedical assessment of this cohort and a questionnaire to obtain information on potential confounders.
We are conducting a clinical review of an existing, well characterised cohort comprising 547 IVF-conceived adults and 549 matched controls. We are measuring cardiovascular intermediate phenotypes, metabolic parameters and respiratory function, complemented by epigenome-wide DNA methylation analysis. A pilot study demonstrated the feasibility of our proposed protocol and its acceptability to participants. Participants attend a 2-3 h clinical assessment and complete a study-specific online questionnaire. Measurements include: 1) cardiovascular phenotypes: carotid artery intima-media thickness and distensibility, retinal vascular calibre, resting blood pressure, pulse wave velocity and pulse wave analysis; 2) respiratory function: spirometry, plethysmography, multiple breath washout; 3) auxology: height, weight, waist circumference, bio-impedance. Blood is collected for 4) biomarkers of cardiometabolic profile including inflammatory markers and 5) epigenetic analysis.
Recruitment for this clinical review is challenging as many of the participants have moved to regional, interstate or international locations. Additionally, many female participants are pregnant or breastfeeding, and are therefore ineligible. Nevertheless, comprehensive strategies have been developed to optimize recruitment. Given the increasing use of IVF and related technologies, the potential long-term consequences for risk of common adult diseases is an important clinical and public health issue.
通过辅助生殖技术（ART）受孕的儿童目前占澳大利亚出生人口的 4%。受精和着床相关生物参数的操作是 ART 成功的关键，但可能对后代的长期健康构成风险。人们普遍认为，许多常见的成年健康问题（特别是心血管、代谢和呼吸系统疾病）起源于生命早期，甚至可能在出生前就已经存在，并且风险轨迹会贯穿整个儿童期，直到成年后出现临床疾病。早期生活中的表观遗传变化可能在此过程中发挥作用。然而，人们对通过 ART 受孕的个体的长期健康状况知之甚少。在之前的一项基于电话访谈的研究中，我们发现通过体外受精（IVF）受孕的年轻成年人，其母亲报告的过敏性呼吸道、内分泌、营养和代谢疾病明显多于非 IVF 受孕的匹配对照组。在这里，我们概述了对该队列进行后续生物医学评估的方案以及获取潜在混杂因素信息的问卷。
我们正在对现有的、特征良好的队列进行临床回顾，该队列包括 547 名 IVF 受孕的成年人和 549 名匹配对照。我们正在测量心血管中间表型、代谢参数和呼吸功能，并辅以全基因组 DNA 甲基化分析。一项试点研究表明，我们提出的方案是可行的，且参与者能够接受。参与者参加 2-3 小时的临床评估，并完成一份特定于研究的在线问卷。测量包括：1）心血管表型：颈动脉内膜中层厚度和顺应性、视网膜血管口径、静息血压、脉搏波速度和脉搏波分析；2）呼吸功能：肺活量测定、体积描记法、多次呼吸冲洗；3）人体测量学：身高、体重、腰围、生物阻抗。采集血液用于 4）心血管代谢特征的生物标志物，包括炎症标志物和 5）表观遗传分析。
由于许多参与者已经搬到了地区、州际或国际地点，因此对这项临床回顾的招募具有挑战性。此外，许多女性参与者正在怀孕或哺乳期，因此不符合条件。尽管如此，已经制定了全面的策略来优化招募。鉴于 IVF 和相关技术的使用日益增加，ART 对常见成人疾病风险的潜在长期后果是一个重要的临床和公共卫生问题。
