Department for Congenital Disorders, Danish National Biobank and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Slagelse Hospital, Slagelse, Denmark.
PLoS One. 2021 May 27;16(5):e0252343. doi: 10.1371/journal.pone.0252343. eCollection 2021.
Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors.
A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score.
Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes.
Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and-particularly-in combination, with CHDs are needed.
先天性心脏病（CHD）是最常见的先天性畸形。CHD 的病因复杂。基于大样本队列研究和系统评价及荟萃分析的结果报告显示，母亲患有肥胖症、糖尿病、高血压和子痫前期等代谢紊乱性疾病会增加后代患 CHD 的风险，所有这些疾病都与胰岛素抵抗或高血糖有关。然而，临床实际情况是这些情况往往同时发生。因此，本综述的目的既是评估现有关于母亲代谢紊乱与后代 CHD 之间关联的证据，这些代谢紊乱包括肥胖症、糖尿病、高血压、子痫前期、血脂异常，以及代谢综合征等组合作为危险因素的意义。
使用 PubMed 和 Embase 对 1990 年 1 月 1 日至 2021 年 1 月 14 日期间发表的论文进行了系统的文献检索。如果研究发表于英文期刊、为病例对照或队列研究，则符合纳入标准。感兴趣的暴露因素为母亲超重或肥胖、高血压、子痫前期、糖尿病、血脂异常和/或代谢综合征，感兴趣的结局为后代 CHD。此外，研究还根据质量评估评分进行了纳入。
在 2250 项确定的研究中，有 32 项符合纳入标准。除了一项研究外，所有研究均仅调查了单个代谢紊乱。一些疾病（肥胖症、妊娠期糖尿病和高血压）使 CHD 的发病风险略有增加，而孕前糖尿病和早发型子痫前期与 CHD 强烈相关，不同 CHD 亚型之间没有一致的差异。一项研究表明，母亲肥胖症和妊娠期糖尿病的联合作用可能具有相加效应。
需要进一步研究葡萄糖-胰岛素稳态的异常在妊娠期常见的代谢紊乱及其发病机制中的作用，以及这些异常作为单一疾病，尤其是作为单一疾病和/或与 CHD 共同存在时的联合作用。
