Maternal Diabetes During Pregnancy Shapes Fetal Heart Fat

A meta-analysis

Understanding the Impact of Diabetes During Pregnancy

Diabetes mellitus (DM) has become one of the most common metabolic disorders worldwide, especially among women of childbearing age. Two major types are seen during pregnancy: Gestational Diabetes Mellitus (GDM)—glucose intolerance diagnosed during pregnancy—and Pregestational Diabetes Mellitus (PDM)—pre-existing type 1 or type 2 diabetes diagnosed before pregnancy.

Together, GDM and PDM affect a substantial number of pregnancies globally. GDM alone is estimated to complicate around 14% of all pregnancies. The prevalence of PDM varies by region, largely reflecting broader patterns in diabetes incidence.

Both GDM and PDM are associated with a range of adverse outcomes for both mother and child. These include increased risks of preeclampsia, preterm birth, fetal macrosomia, and perinatal complications. These conditions also pose longer-term health risks to the offspring, including a higher chance of obesity, insulin resistance, and type 2 diabetes later in life.

Researchers believe these effects may stem from disrupted fetal metabolic programming triggered by maternal hyperglycemia. In response, the scientific community has been seeking early, non-invasive indicators of fetal metabolic alterations that may appear in utero. One such candidate is fetal epicardial fat thickness (fEFT)—a measurable fat layer around the fetal heart that has shown potential as a marker of future cardiometabolic risk.

What Is Fetal Epicardial Fat and Why Does It Matter?

Epicardial fat is a visceral fat depot that surrounds the myocardium and coronary arteries. In adults, increased epicardial fat is closely linked to cardiometabolic disorders. fEFT, measurable through ultrasound, offers a way to evaluate fetal fat accumulation in real-time and may reflect early changes in fetal metabolism.

Previous studies have linked elevated fEFT to higher birth weight, increased adiposity, and early signs of metabolic dysfunction like hyperinsulinemia. However, findings have not always been consistent due to differences in study design, measurement methods, and populations.

New Meta-Analysis: Measuring the Link Between Maternal Diabetes and fEFT

A new meta-analysis published in Biomolecules and Biomedicine in 2025 pooled data from 10 observational studies (12 datasets) including 1,303 participants. Researchers aimed to determine whether maternal diabetes (GDM or PDM) is associated with changes in fEFT.

Key Findings

• Higher fEFT in diabetic pregnancies: Pregnant women with diabetes had significantly greater fetal epicardial fat thickness than those without (mean difference: 0.37 mm, 95% CI: 0.26–0.49, P < 0.001).

• Effect increases with gestational age: The difference in fEFT was more pronounced in pregnancies measured after 26 weeks, suggesting late gestation may be a critical window for fat accumulation.

• Consistent across diabetes types and demographics: Whether the mother had GDM or PDM, the association with increased fEFT held. The effect was also stable across study design, maternal age, and BMI categories.

• Robustness of results: Sensitivity analyses showed consistent outcomes, and publication bias was not evident based on funnel plot symmetry and Egger’s test.

What Drives the Increase in fEFT?

The authors explored several biological explanations grounded in current knowledge:

• Fetal hyperinsulinemia: Maternal hyperglycemia may lead to increased insulin levels in the fetus. Insulin promotes fat storage and cell growth, particularly in metabolically active areas like epicardial fat.

• Inflammation and oxidative stress: Diabetes in pregnancy often leads to higher levels of systemic inflammation and oxidative stress. These factors can further promote fat accumulation and alter normal fetal fat distribution.

• Placental changes: Diabetic pregnancies are linked to placental dysfunction—such as altered nutrient transport and increased vascular resistance—which may enhance glucose and lipid flow to the fetus.

• Epigenetic effects: Chronic hyperglycemia may lead to changes in fetal DNA methylation and gene expression, influencing fat metabolism and storage patterns long after birth.

Practical Implications for the Field

1. Early Identification of At-Risk Fetuses

Given that fEFT can be measured non-invasively via standard ultrasound, it holds potential as a screening tool in prenatal care for identifying fetuses at risk of future metabolic disorders.

2. Need for Standardization

One limitation identified in the study was the variation in ultrasound measurement techniques across studies. There is a clear need for standardized protocols for assessing fEFT in clinical and research settings.

3. Importance of Glycemic Control

The findings reinforce the value of tight glycemic control throughout pregnancy, especially in later gestation, to reduce the risk of excessive fetal fat accumulation.

4. Potential for Long-Term Monitoring

Future research should track fEFT from fetal life into infancy and beyond, to explore its potential as a long-term marker of metabolic health.

Limitations and Areas for Future Research

While the meta-analysis was rigorous, it was based exclusively on observational studies. This means that causal relationships cannot be definitively established. Additionally, factors such as maternal diet, exercise, and genetic background were not consistently accounted for.

Differences in the diagnostic criteria for GDM (e.g., IADPSG vs. DIPSI) also pose challenges in comparing data across regions. A larger number of studies using consistent criteria would allow for better subgroup comparisons in the future.

Final Thoughts

This meta-analysis offers compelling evidence that maternal diabetes during pregnancy is associated with increased fetal epicardial fat thickness, particularly in the later stages of gestation. These findings underscore the need for early identification, monitoring, and management of pregnancies complicated by diabetes.

While more work is needed to establish fEFT as a routine clinical marker, this study lays important groundwork for future research and clinical practice aimed at improving maternal and fetal health outcomes.

 

The translation of the preceding English text in Chinese:

 

一项荟萃分析

理解妊娠期糖尿病的影响

糖尿病（DM）已成为全球最常见的代谢性疾病之一，尤其在育龄女性中尤为普遍。在妊娠期，主要有两种类型的糖尿病：妊娠糖尿病（GDM）——即妊娠期间被诊断出的葡萄糖耐受异常，以及孕前糖尿病（PDM）——指妊娠前即已确诊的1型或2型糖尿病。

GDM和PDM在全球范围内共同影响着大量妊娠。仅GDM一项，估计就影响了大约14%的妊娠。而PDM的患病率因地区而异，这在很大程度上反映了各地糖尿病总体发病趋势的不同。

无论是GDM还是PDM，均与母婴双方的多种不良结局相关，包括子痫前期、早产、胎儿巨大儿和围产期并发症等。这些问题还可能对孩子的长期健康产生影响，例如肥胖、胰岛素抵抗以及成年后发展为2型糖尿病的风险增加。

研究人员认为，这些影响可能源于母体高血糖所引发的胎儿代谢编程紊乱。基于此，科学界正在寻找早期、无创的指标，以评估子宫内胎儿代谢的潜在变化。其中一个候选指标便是胎儿心外脂肪厚度（fEFT）——这是胎儿心脏周围可测量的一层脂肪组织，被认为可能预示未来心代谢疾病的风险。

什么是胎儿心外脂肪？它为何重要？

心外脂肪是一种包围心肌和冠状动脉的内脏脂肪组织。在成人中，心外脂肪增加已与多种心代谢疾病密切相关。而fEFT可通过超声实时测量，为评估胎儿脂肪积聚提供了一种方式，也可能反映胎儿代谢的早期变化。

已有研究将fEFT升高与出生体重增加、脂肪积聚增多以及如高胰岛素血症等代谢功能障碍的早期迹象联系起来。然而，由于研究设计、测量方法和人群的差异，研究结果并不完全一致。

最新荟萃分析：妊娠期糖尿病与fEFT的关系

2025年发表在《Biomolecules and Biomedicine》的一项新荟萃分析纳入了10项观察性研究（12个数据集），共1,303名参与者。研究目标是明确妊娠期糖尿病（无论GDM或PDM）是否与fEFT变化有关。

主要发现

• 糖尿病妊娠者fEFT更高：患糖尿病的孕妇其胎儿fEFT显著高于对照组（平均差值：0.37 mm，95%置信区间：0.26–0.49，P < 0.001）。

• 妊娠晚期影响更明显：26周之后测量的fEFT差异更大，提示妊娠晚期可能是脂肪积聚的关键时期。

• 结果一致性强：无论孕妇患有GDM或PDM，该相关性都存在，且在研究设计、孕妇年龄和BMI分类中均保持稳定。

• 结果稳健：敏感性分析结果一致，漏报偏倚通过漏斗图和Egger检验均未见明显。

fEFT升高的潜在机制

作者探讨了几种基于当前知识的生物学机制：

• 胎儿高胰岛素血症：母体高血糖可能导致胎儿胰岛素升高，胰岛素促进脂肪存储及细胞生长，特别是在心外脂肪等代谢活跃部位。

• 炎症与氧化应激：糖尿病妊娠常伴有全身炎症及氧化应激水平升高，进一步促进脂肪沉积并改变胎儿脂肪分布。

• 胎盘功能障碍：糖尿病妊娠与胎盘功能异常有关，如营养物质转运改变及血管阻力升高，可能加剧葡萄糖与脂质向胎儿转运。

• 表观遗传改变：长期高血糖可能改变胎儿DNA甲基化和基因表达，进而影响出生后脂肪代谢与储存模式。

对实践的启示

1. 早期识别高风险胎儿
   由于fEFT可通过常规超声无创测量，具备作为产前筛查工具的潜力，可用于识别未来代谢障碍风险较高的胎儿。

2. 测量标准化的必要性
   研究指出各研究中fEFT的超声测量方法存在差异，临床与研究中有必要建立统一的测量标准。

3. 强化血糖控制的重要性
   研究结果再次强调，在整个孕期，尤其是妊娠晚期保持良好血糖控制，可降低胎儿过度脂肪积聚的风险。

4. 长期随访潜力
   未来研究应追踪fEFT从胎儿期到婴儿期乃至更长时间，以探讨其作为代谢健康长期标志物的潜能。

研究局限与未来方向

尽管此次荟萃分析较为严谨，但其仅基于观察性研究，因此不能明确建立因果关系。此外，诸如孕妇饮食、运动和遗传背景等因素并未在所有研究中得到统一控制。

不同的GDM诊断标准（如IADPSG与DIPSI）也给跨地区数据比较带来困难。未来更多使用一致标准的研究将有助于更好地进行亚组分析。

总结

本荟萃分析提供了有力证据，显示妊娠期糖尿病与胎儿心外脂肪厚度增加有关，尤其在妊娠后期更为显著。这些发现强调了及早识别、监测和管理糖尿病妊娠的必要性。

尽管fEFT尚未成为常规临床标志物，但本研究为未来的科研和临床实践奠定了重要基础，有望推动母婴健康管理的进步。

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Reference:

Apizi Anwaier, Jian Li, Wei Liu, Liangjie Dong, Yunfei Ding, Zhaoxia Yu

Influence of maternal diabetes during pregnancy on ultrasound-measured fetal epicardial fat thickness: A meta-analysis.

Biomol Biomed [Internet]. 2025 Mar. 5 [cited 2025 Apr. 24];

Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/11909

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