BACKGROUND Studies have inconsistently observed that children conceived by IVF or ICSI have higher blood pressure compared to children not conceived by these ARTs. OBJECTIVE AND RATIONALE The aim was to perform a systematic review and meta-analysis of blood pressure measures of offspring conceived by ART and those conceived naturally. Resolving the suspicion of ART as a risk factor of higher blood pressure, and therefore of heart disease, has public health and clinical implications. SEARCH METHODS A biomedical librarian searched the Embase, PubMed, and Web of Science databases. Searches were limited to records published in English since 1978. Grey literature was searched. Inclusion criteria were humans born via infertility treatment (vs no treatment) who underwent a blood pressure assessment. Exclusion criteria were non-human participants, non-quantitative studies, absence of a control group, and specialty populations (e.g. cancer patients only). Two reviewers independently screened each record’s title and abstract and full text using Covidence, extracted data using Excel, and assessed bias using the National Heart, Lung, and Blood Institute’s Quality Assessment Tool for cohort studies. OUTCOMES Of 5082 records identified, 79 were included in the systematic review and 36 were included in the meta-analysis of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in ART and non-ART groups. Overall, 34 reports including 40 effect sizes from 25 unique cohorts, compared blood pressure between ART (N = 5229) and non-ART (N = 8509, reference) groups with no covariate adjustment. No standardized mean differences (SMD) in SBP (0.06 per SD of mmHg, 95% CI = −0.05, 0.18) or DBP (0.11, 95% CI = −0.04, 0.25) by treatment were found, but the heterogeneity was considerable (I2=76% for SBP and 87% for DBP). Adjusted analyses were presented in 12 reports, representing 28 effect sizes from 21 unique cohorts (N = 2242 treatment vs N = 37 590 non-treatment). Studies adjusted for varied covariates including maternal (e.g. age, education, body mass index, smoking, pregnancy complications), child (e.g. sex, age, physical activity, BMI, height), and birth characteristics (e.g. birth weight and gestational age). Adjusted results similarly showed no SMD for SBP (−0.03, 95% CI = −0.13, 0.08) or DBP (0.02, 95% CI = −0.12, 0.16), though heterogeneity remained high (I2 = 64% and 86%). Funnel plots indicated a slight publication bias, but the trim and fill approach suggested no missing studies. Removal of five studies which adjusted for birth outcomes (potentially over-adjusting for mediators) made no material difference. Type of treatment (e.g. IVF vs ICSI), period effects by birth year (≤2000 vs >2000), offspring age group (<8, 8–14, 15+), or study location (e.g. Europe) did not modify the results. WIDER IMPLICATIONS In conclusion, conception by ART was not associated with offspring blood pressure in a meta-analysis, although considerable heterogeneity was observed. Given the increasing number of children born using ART, perpetuating a difference in blood pressure would mean unnecessary risk screening for many children/adults on a population level. At a clinical level, couples considering these reproductive technologies have some reassurance that there is no evidence of strong vascular ‘programming’ due to the techniques used. REGISTRATION NUMBER PROSPERO No. CRD42022374232.

中文翻译：

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不孕症治疗和后代血压——系统评价和荟萃分析


背景 研究不一致地观察到，与非这些 ART 受孕的儿童相比，通过 IVF 或 ICSI 受孕的儿童血压更高。客观和基本原理 目的是对通过 ART 受孕的后代和自然受孕的后代的血压测量值进行系统评价和荟萃分析。消除 ART 是高血压的危险因素，从而消除心脏病的怀疑，具有公共卫生和临床意义。检索方法 生物医学图书馆员检索了 Embase、PubMed 和 Web of Science 数据库。检索仅限于 1978 年以来以英文出版的记录。检索了灰色文献。纳入标准是通过不孕症治疗（与未治疗相比）出生并接受血压评估的人。排除标准是非人类参与者、非定量研究、没有对照组和特殊人群（例如 仅癌症患者）。两名评价员使用 Covidence 独立筛选每条记录的标题、摘要和全文，使用 Excel 提取数据，并使用美国国家心肺血液研究所的队列研究质量评估工具评估偏倚。结果 在确定的 5082 条记录中，79 条被纳入系统评价，36 条被纳入 ART 和非 ART 组收缩压 （SBP） 和舒张压 （DBP） 的荟萃分析。总体而言，34 份报告包括来自 25 个独特队列的 40 个效应量，比较了 ART （N = 5229） 和非 ART （N = 8509，参考）组之间的血压，没有协变量调整。SBP （0.06/mmHg 标准差，95% CI = -0.05， 0.18） 或 DBP （0.11， 95% CI = -0.04， 0.25） 通过治疗，但异质性相当大 （I2=76% SBP 和 87%） DBP。调整后的分析在 12 份报告中呈现，代表来自 21 个独特队列的 28 个效应量 （N = 2242 次治疗 vs N = 37 590 次非治疗）。研究调整了不同的协变量，包括母亲（例如年龄、教育程度、体重指数、吸烟、妊娠并发症）、儿童（例如性别、年龄、身体活动、BMI、身高）和出生特征（例如出生体重和胎龄）。调整后的结果同样显示 SBP （-0.03， 95% CI = -0.13， 0.08） 或 DBP （0.02， 95% CI = -0.12， 0.16） 没有 SMD，尽管异质性仍然很高 （I2 = 64% 和 86%）。漏斗图显示轻微的发表偏倚，但修剪和填充方法表明没有遗漏的研究。删除 5 项根据出生结局进行调整的研究（可能对介质进行过度调整）没有实质性差异。治疗类型（例如 IVF 与 ICSI）、按出生年份划分的时期效应（≤2000 与 >2000）、后代年龄组（<8、8-14、15+）或研究地点（例如欧洲）没有改变结果。更广泛的影响 总之，在一项荟萃分析中，ART 受孕与后代血压无关，尽管观察到相当大的异质性。鉴于使用 ART 出生的儿童数量不断增加，血压差异持续存在将意味着在人群水平上对许多儿童/成人进行不必要的风险筛查。在临床层面上，考虑这些生殖技术的夫妇可以放心，由于所使用的技术，没有证据表明存在强烈的血管“编程”。注册号 PROSPERO 编号CRD42022374232。