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Journal of Peking University(Health Sciences) >

2025 , Vol. 57 >Issue 3: 487 - 495

DOI: https://doi.org/10.19723/j.issn.1671-167X.2025.03.012

Associations of metabolic dysfunction-associated steatotic liver disease and cardiometabolic risk factor abnormalities with adverse pregnancy outcomes

  • Shuhan YANG 1 ,
  • Yixin LI 2 ,
  • Haoliang CUI 3 ,
  • Youxin WANG 1 ,
  • Yuying WU 1 ,
  • Mingyue WANG 1 ,
  • Yifan YANG 1 ,
  • Nur Enkar 1 ,
  • Lei YANG , 4, * ,
  • Hui WANG , 1, *
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  • 1. Department of Maternal and Child Health, School of Public Health, Peking University, Beijing 100191, China
  • 2. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
  • 3. Department of Global Health, School of Public Health, Peking University, Beijing 100191, China
  • 4. Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 100050, China
YANG Lei, e-mail,
WANG Hui, e-mail,

Received date: 2025-02-07

  Online published: 2025-06-13

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Abstract

Objective: To investigate the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of adverse pregnancy outcomes, and to analyze the impact of the type and severity of cardiometabolic risk factor (CMRF) abnormalities on this association. Methods: A retrospective cohort study was conducted among primiparous women with singleton pregnancies who had registered at Beijing Friendship Hospital from March 10, 2020, to December 31, 2022. A total of 2 623 women were included. Basic characteristics and delivery outcomes were documented, liver ultrasound and relevant prenatal examinations were performed, and adverse pregnancy outcomes were diagnosed. Modified Poisson regression models were used to analyze the association between MASLD and adverse pregnancy outcomes. The relationship between the type or severity of CMRF abnormalities in MASLD and the risk of adverse pregnancy outcomes was also explored. Results: After adjusting for confounding factors including age, gestational weight gain, and education level, MASLD was associated with an increased risk of cesarean section (RR=1.531, 95%CI: 1.304-1.799, P < 0.001), gestational diabetes mellitus (GDM; RR=2.409, 95%CI: 1.948-2.979, P < 0.001), pregnancy-associated hypertension (PAH; RR=3.062, 95%CI: 2.069-4.533, P < 0.001), preterm birth (RR=2.145, 95%CI: 1.342-3.429, P=0.001), and large for gestational age (LGA; 2.224, 95%CI: 1.599-3.095, P < 0.001). However, no significant associations were found for small for gestational age or postpartum hemorrhage. After adjusting for other CMRF abnormalities, the risk of adverse pregnancy outcomes varied among MASLD pregnant women with different CMRF abnormalities: the body mass index abnormal group had higher risks of cesarean section, GDM, PAH, preterm birth, and LGA; the glucose abnormal group had an increased risk of GDM; the blood pressure abnormal group had a higher risk of PAH; the high density lipoprotein cholesterol abnormal group had higher risks of cesarean section, GDM, and PAH; and the triglyceride abnormal group was associated with higher risks of GDM and preterm birth. Additional, as the severity of CMRF abnormalities increased, the risks of cesarean section (RR=1.199, 95%CI: 1.112-1.292, P < 0.001), GDM (RR=1.478, 95%CI: 1.345-1.624, P < 0.001), PAH (RR=1.626, 95%CI: 1.367-1.934, P < 0.001), preterm birth (RR=1.384, 95%CI: 1.120-1.710, P=0.003), and LGA (RR=1.422, 95%CI: 1.224-1.650, P < 0.001) continued to rise. Conclusion: MASLD during pregnancy is associated with an increased risk of multiple adverse pregnancy outcomes, and the type and severity of CMRF abnormalities significantly influence this association. These results suggest that attention should be paid to the specific CMRF abnormalities when diagnosed MASLD, as this may help to facilitate targeted interventions and reduce the risk of adverse pregnancy outcomes.

Key words： Cardiometabolic risk factor; Pregnancy outcome; Liver disease; Metabolic dysfunction-associated steatotic liver disease; Adverse pregnancy outcome

Cite this article

Shuhan YANG , Yixin LI , Haoliang CUI , Youxin WANG , Yuying WU , Mingyue WANG , Yifan YANG , Nur Enkar , Lei YANG , Hui WANG . Associations of metabolic dysfunction-associated steatotic liver disease and cardiometabolic risk factor abnormalities with adverse pregnancy outcomes[J]. Journal of Peking University(Health Sciences), 2025 , 57(3) : 487 -495 . DOI: 10.19723/j.issn.1671-167X.2025.03.012

非酒精性脂肪性肝病(nonalcoholic fatty liver disease，NAFLD)已成为目前成人中最常见的慢性肝病之一[1]，美国流行病学数据显示，妊娠期NAFLD的患病率持续上升，从2007年至2015年增长超过3倍[2]。北京市的一项研究显示，18~49岁的育龄女性NAFLD患病率为13.5%[3]。妊娠过程中，孕妇的正常代谢水平发生变化，出现生理性胰岛素抵抗增强[4]，且心血管负荷较大[5]。NAFLD与胰岛素抵抗状态相关，且可能增加患者心血管负荷[4]，此时存在NAFLD可能会危害孕妇和胎儿健康。
随着研究的深入，NAFLD被证实与心脏的代谢风险紧密相关[6]，2023年，代谢相关脂肪性肝病(metabolic dysfunction-associated steatotic liver disease，MASLD)这一新命名被提出[7-8]，约95%的NAFLD患者可以诊断为MASLD[1]。目前关于MASLD与不良妊娠结局相关性的研究较为少见，有研究提示妊娠期MASLD与妊娠期高血压相关[9]。同时，MASLD的诊断标准中包含了五种心脏代谢风险指标(cardiometabolic risk factor，CMRF)异常，这些指标虽均与心脏代谢疾病风险相关，但其与机体状态改变间的关联存在差异。例如，体重指数(body mass index，BMI)升高可导致胰岛素抵抗[10]，高密度脂蛋白胆固醇(high density lipoprotein cholesterol，HDL-C)水平降低与炎症反应增强和胆固醇转运异常相关[11]，血压升高则与心脏压力增大相关[12]。包含不同CMRF异常的MASLD患者与不良妊娠结局风险之间的相关性是否具有差异仍需进一步研究。
本研究旨在探讨妊娠期MASLD及其CMRF异常种类和严重程度与不良妊娠结局风险的关联，为论证孕早期筛查MASLD并区分CMRF异常种类及严重程度的必要性提供依据，并为优化孕期保健策略提供理论支撑，以降低不良妊娠结局的发生风险，保障孕妇与胎儿健康。

1 资料与方法

1.1 研究对象

本研究采用回顾性队列研究，研究对象来自2020年3月10日至2022年12月31日在首都医科大学附属北京友谊医院产科建立个人孕期档案、妊娠年龄为20~49周岁的单胎初产孕妇。该时间段共纳入4 542名孕妇，排除存在以下情况的孕妇：(1)多胎妊娠或非首次分娩者(n=11)；(2)过量饮酒者(每日饮酒量>20 g，n=3)；(3)曾被诊断为其他慢性肝病者，包括酒精性肝病、病毒性肝炎、胆管炎和自身免疫性肝炎(n=173)；(4)基本信息、既往病史、肝脏超声检查结果、产前检查结果及分娩结局数据缺失者(n=237)。最终符合条件的孕妇共4 118人纳入本研究。在此基础上，本研究纳入CMRF异常及脂肪性肝病同时存在或两种疾病均不存在的孕妇，共计2 623人。其中，符合MASLD诊断标准(同时存在CMRF异常及脂肪性肝病)的孕妇为MASLD组，共302人；既无CMRF异常也无脂肪性肝病的孕妇为对照组，共2 321人。本研究开始前获得首都医科大学附属北京友谊医院医学伦理委员会批准(批件号：2023-P2-175-02)，由于数据进行了匿名化处理，伦理委员会批准豁免知情同意。

1.2 研究方法

1.2.1 基本信息及体格检查

孕产妇基本信息(年龄、末次月经、学历、吸烟饮酒史等)和既往病史在建档时由工作人员询问并记录。身高、体重、血压等体格检查项目在建档及产前检查时由统一培训的工作人员测量。

1.2.2 孕前BMI计算及分级

鉴于妊娠早期体重变化不显著，以建档时体重作为孕前体重的参考，结合孕妇身高及孕前体重计算孕前BMI。根据中国卫生行业标准《成人体重判定》(WS/T 428—2013)[13]对孕前BMI进行分级，定义BMI < 18.5 kg/m2为消瘦，18.5 kg/m2≤BMI < 24 kg/m2为正常，24 kg/m2≤BMI < 28 kg/m2为超重，BMI≥28 kg/m2为肥胖。

1.2.3 孕期增重计算及分级

孕期增重为分娩前末次体重测量值与孕前体重测量值的差值。参照中国卫生行业标准《妊娠期妇女体重增长推荐值标准》(WS/T 801—2022)[14]，将孕期增重水平分为不足、正常、过多三组。

1.2.4 血液样本采集及检测

所有血液样本均由首都医科大学附属北京友谊医院按照标准流程采集，血液生化检查等需要空腹采集或其他提前准备操作的检查均在孕产妇空腹8 h后或按照准备流程操作后进行血液样本采集。使用美国Beckman Coulter AU5821型自动生化分析仪及原装配套试剂进行血液生化检查和75 g葡萄糖口服糖耐量试验，使用美国伯乐BIO-RAD AminexHPX-87C 125-0095液相色谱分析柱及原装配套试剂进行血清糖化血红蛋白水平检测。

1.2.5 肝脏超声检查和脂肪性肝病诊断

所有孕妇在妊娠14周前进行肝脏超声检查，检查前一天晚上要求孕妇清淡饮食，当天测定前空腹禁水禁食。肝脏超声检查由专业技术人员使用飞利浦iU Elite版四维彩色超声机(美国)进行，并根据检查结果诊断是否存在脂肪性肝病[15]。

1.2.6 CMRF异常的定义及诊断

CMRF异常包括五种指标异常，满足以下至少一项的孕妇被诊断为存在CMRF异常[8]：(1)BMI异常：孕前BMI≥24 kg/m2；(2)血糖异常：空腹血糖≥5.6 mmol/L(100 mg/dL)或糖化血红蛋白≥5.7%(39 mmol/L)或确诊2型糖尿病或正在接受2型糖尿病治疗；(3)血压异常：血压≥130/85 mmHg或在接受特异性抗高血压药物治疗；(4)HDL-C异常：血浆HDL-C≤1.3 mmol/L(50 mg/dL)或在接受降脂治疗；(5)甘油三酯(triglyceride，TG)异常：血浆TG≥1.70 mmol/L(150 mg/dL)或在接受降脂治疗。其中，第2~5项指标的诊断依据为在妊娠14周前进行肝脏超声检查时同步完成的体格检查和血液检测结果，以及建档时采集的既往病史资料。

1.2.7 MASLD的诊断与分组

满足以下条件的研究对象被诊断为MASLD[8]：(1)存在脂肪性肝病；(2)存在CMRF异常；(3)无过量饮酒及其他慢性肝病病史。根据MASLD孕妇的CMRF异常种类，建立BMI异常组包含全部存在BMI异常的MASLD孕妇，同理，分别建立血糖异常组、血压异常组、HDL-C异常组和TG异常组，各组间研究对象存在重复。根据MASLD孕妇符合CMRF异常的数量，对其严重程度进行分组：仅有1种CMRF异常的MASLD孕妇划入轻度CMRF异常组，有2种CMRF异常的MASLD孕妇划入中度CMRF异常组，有3种及以上CMRF异常的MASLD孕妇划入重度CMRF异常组。

1.2.8 不良妊娠结局的诊断

本研究的不良妊娠结局包括剖宫产、妊娠期糖尿病、妊娠相关高血压、早产、小于胎龄儿、大于胎龄儿和产后出血。由专业医师在产前检查过程中对两种不良妊娠结局(妊娠期糖尿病、妊娠相关高血压)及其他相关疾病进行诊断和记录，在分娩后记录孕妇的分娩结局及另外五种不良妊娠结局的诊断结果。妊娠期糖尿病定义为妊娠前未被诊断为2型糖尿病，在妊娠24~28周孕妇空腹血糖水平≥5.1 mmol/L，或餐后1小时血糖水平≥10 mmol/L，或餐后2小时血糖水平≥8.5 mmol/L[16]。妊娠相关高血压包括妊娠期高血压、子痫前期和子痫，存在至少一种可诊断[17]。早产定义为妊娠20+0周至36+6周分娩[18]。大于胎龄儿定义为出生体重高于同胎龄儿体重的第90百分位数的新生儿；小于胎龄儿为出生体重低于同胎龄儿体重的第10百分位数的新生儿[19-20]。产后出血定义为产妇在阴道分娩后24 h内出血量超过500 mL，或剖宫产后24 h内出血量超过1 000 mL[21]。

1.3 统计学分析

采用R 4.3.3软件，连续变量以均数±标准差表示，组间比较采用t检验；分类变量以n(%)表示，组间比较采用卡方检验。运用修正Poisson回归方法建立模型，以对照组为参照，分析MASLD组及不同CMRF异常组的不良妊娠结局相对危险度(relative risk，RR)。将MASLD孕妇的CMRF异常程度作为有序变量(0级：对照组；1级：轻度CMRF异常组；2级：中度CMRF异常组；3级：重度CMRF异常组)，采用修正Poisson回归分析方法建立模型，以对照组(0级)为基线，探究CMRF异常程度变化与不良妊娠结局风险的相关性。其中，模型1未调整协变量；模型2调整年龄(岁)、孕期增重水平(不足/正常/过多)和受教育水平(大学本科以下/大学本科及以上)；在对不同CMRF异常组进行分析时，建立模型3进一步调整BMI异常(是/否)、血糖异常(是/否)、血压异常(是/否)、HDL-C异常(是/否)和TG异常(是/否)，但当其中任意变量作为因变量时，不将其作为协变量进行调整。双侧检验，P < 0.05认为差异有统计学意义。

2 结果

研究对象的基本资料及不良妊娠结局的发生：研究共纳入研究对象2 623人，其中MASLD组302人，对照组2 321人。与对照组相比，MASLD组的年龄、孕前体重、孕前BMI、分娩前体重和血压更高，而孕期增重和受教育水平更低(P均 < 0.001，表 1)。在MASLD组中，各有8.9%和8.3%的孕妇存在慢性高血压及2型糖尿病病史。七种不良妊娠结局中，剖宫产的发生率在两组中均为最高，妊娠期糖尿病次之。MASLD组的剖宫产(62.9% vs. 37.1%)、妊娠期糖尿病(40.1% vs. 15.6%)、妊娠相关高血压(12.6% vs. 3.8%)、早产(7.9% vs. 3.5%)和大于胎龄儿(16.2% vs. 6.8%)的发生率均高于对照组(P均 < 0.001)。小于胎龄儿和产后出血的发生率差异无统计学意义。
表1 研究对象的基本资料及不良妊娠结局发生情况

Table 1 Baseline characteristics and incidence of adverse pregnancy outcomes in participants

Variables Control group(n=2 321) MASLD group(n=302) χ2/t P
Maternal age/years 31.20 ± 3.12 32.57 ± 3.64 6.23 < 0.001
   < 35 2 075 (89.4) 226 (74.8) 51.31 < 0.001
  ≥35 246 (10.6) 76 (25.2)
Height/cm 162.86±5.10 162.79±5.42 0.22 0.824
Pre-pregnancy weight/kg 53.98±5.61 74.54±11.88 29.64 < 0.001
Pre-pregnancy BMI/(kg/m2) 20.34±1.75 28.07±3.85 34.46 < 0.001
  Underweight 329 (14.2) 0 (0.0) 2 294.87 < 0.001
  Normal weight 1 992 (85.8) 34 (11.3)
  Overweight 0 (0.0) 131 (43.4)
  Obese 0 (0.0) 137 (45.4)
Weight before delivery/kg 67.78±7.58 84.46±12.88 22.01 < 0.001
Gestational weight gain/kg 13.81±4.92 9.92±6.41 10.16 < 0.001
  Insufficient 263 (11.3) 79 (26.2) 61.10 < 0.001
  Adequate 1 096 (47.3) 93 (30.8)
  Excessive 959 (41.4) 130 (43.0)
Systolic blood pressure/mmHg 111.61±9.95 122.41±11.65 15.39 < 0.001
Diastolic blood pressure/mmHg 66.02±7.91 73.97±9.26 14.27 < 0.001
Education level
  Below bachelor’s degree 439 (18.9) 86 (28.5) 14.67 < 0.001
  Bachelor’s degree or higher 1 882 (81.1) 216 (71.5)
Primiparous 2 263 (97.5) 295 (97.7) < 0.001 1.000
Chronic hypertension history 0 (0.0) 27 (8.9) 200.98 < 0.001
Type 2 diabetes mellitus history 0 (0.0) 25 (8.3) 185.32 < 0.001
Adverse pregnancy outcome
  Cesarean section 861 (37.1) 190 (62.9) 73.11 < 0.001
  Gestational diabetes mellitus 362 (15.6) 121 (40.1) 104.88 < 0.001
  Pregnancy-associated hypertension 88 (3.8) 38 (12.6) 43.26 < 0.001
  Preterm birth 82 (3.5) 24 (7.9) 12.31 < 0.001
  Large for gestational age 158 (6.8) 49 (16.2) 31.26 < 0.001
  Small for gestational age 336 (14.5) 39 (12.9) 0.42 0.517
  Postpartum hemorrhage 149 (6.4) 15 (5.0) 0.73 0.393

Categorical variables were presented as n (%), and compared using the Chi-square test; Continuous variables were presented as ${\bar x}$±s, and compared using the student’s t test. BMI, body mass index; MASLD, metabolic dysfunction-associated steatotic liver disease.

MASLD与不良妊娠结局的相关性：与对照组相比，MASLD组的剖宫产(调整后RR=1.531，95%CI：1.304~1.799，P < 0.001)、妊娠期糖尿病(RR= 2.409，95%CI: 1.948~2.979，P < 0.001)、妊娠相关高血压(RR=3.062，95%CI: 2.069~ 4.533，P < 0.001)、早产(RR=2.145，95%CI: 1.342~ 3.429，P=0.001)和大于胎龄儿(RR=2.224，95%CI: 1.599~ 3.095，P < 0.001)发生风险升高(图 1)。
图1 MASLD与不良妊娠结局的相关性分析

Figure 1 Associations between MASLD and the risk of adverse pregnancy outcomes

Model 1 was unadjusted; Model 2 was adjusted for age, education level, and gestational weight gain. MASLD, metabolic dysfunction-associated steatotic liver disease.

不同CMRF异常组的不良妊娠结局: 不同CMRF异常组中剖宫产和妊娠期糖尿病的发生率均较高，其中，血糖异常组的妊娠期糖尿病(71.74%)发生率在五组中最高，差异存在统计学意义(P=0.001)，其他各不良妊娠结局的发生率在四组间存在差异，但差异均无统计学意义(表 2)。
表2 不同CMRF异常组的不良妊娠结局发生情况

Table 2 Incidence of adverse pregnancy outcomes in different CMRF abnormalities groups

Adverse pregnancy outcome BMI abnormal group (n=268) Glucose abnormal group (n=46) Blood pressure abnormal group (n=40) HDL-C abnormal group (n=164) TG abnormal group (n=83) χ2 P
Cesarean section 166 (61.94) 34 (73.91) 26 (65.00) 102 (62.20) 48 (57.83) 3.48 0.481
Gestational diabetes mellitus 107 (39.93) 33 (71.74) 19 (47.50) 64 (39.02) 37 (44.58) 17.96 0.001
Pregnancy associated hypertension 35 (13.06) 5 (10.87) 4 (10.00) 21 (12.80) 10 (12.05) 0.45 0.978
Preterm birth 21 (7.84) 4 (8.70) 5 (12.50) 10 (6.10) 8 (9.64) 2.25 0.689
Large for gestational age 44 (16.42) 11 (23.91) 8 (20.00) 22 (13.41) 18 (21.69) 4.63 0.328
Small for gestational age 34 (12.69) 5 (10.87) 7 (17.50) 21 (12.80) 11 (13.25) 0.94 0.919
Postpartum hemorrhage 12 (4.48) 4 (8.70) 1 (2.50) 9 (5.49) 6 (7.23) 2.66 0.617

The incidence was presented as n (%) and compared using the Chi-square test. BMI, body mass index; CMRF, cardiometabolic risk factor; HDL-C, high density lipoprotein cholesterol；TG, triglyceride.

不同CMRF异常MASLD与不良妊娠结局的相关性: 与对照组相比，不同CMRF异常组的不良妊娠结局风险存在差异(表 3)。模型2中，仅调整部分协变量时，不同CMRF异常组均与多种不良妊娠结局风险升高相关。在模型3中，进一步调整其他种类CMRF异常后，BMI异常组的剖宫产(RR=1.572，95%CI：1.224~2.018，P < 0.001)、妊娠期糖尿病(RR=2.308，95%CI: 1.665~3.198，P < 0.001)、妊娠相关高血压(RR=3.288，95%CI: 1.859~5.814，P < 0.001)、早产(RR=2.459，95%CI: 1.231~4.913，P=0.011) 和大于胎龄儿(RR=2.266，95%CI: 1.388~ 3.697，P=0.001)风险升高。血糖异常组仅妊娠期糖尿病风险升高(RR=6.734，95%CI: 1.934~23.444，P=0.003)，血压异常组仅妊娠相关高血压风险升高(RR=15.649，95%CI: 1.194~205.006，P=0.036)。HDL-C异常组的剖宫产(RR=1.971，95%CI: 1.226~ 3.170，P=0.005)、妊娠期糖尿病(RR=2.098，95%CI: 1.067~4.126，P=0.032)和妊娠相关高血压(RR= 3.764，95%CI: 1.172~12.091，P=0.026)风险升高，TG异常组的妊娠期糖尿病(RR=2.862，95%CI: 1.314~6.235，P=0.008)和早产(RR=4.285，95%CI: 1.031~17.810，P=0.045) 风险升高。
表3 不同CMRF异常MASLD与不良妊娠结局的相关性分析

Table 3 Associations between different types of CMRF abnormalities in MASLD and the risk of adverse pregnancy outcomes

Adverse pregnancy outcome Control group BMI abnormal group Glucose abnormal group Blood pressure abnormal group HDL-C abnormal group TG abnormal group
RR (95% CI) P RR (95% CI) P RR (95% CI) P RR (95% CI) P RR (95% CI) P
Cesarean section
Model 1 1.000 1.670(1.414, 1.972) < 0.001 1.992 (1.414, 2.807) < 0.001 1.752 (1.186, 2.588) 0.005 1.677(1.366, 2.059) < 0.001 1.559 (1.166, 2.085) 0.003
Model 2 1.000 1.498(1.264, 1.776) < 0.001 1.617 (1.139, 2.298) 0.007 1.509 (1.017, 2.240) 0.041 1.518(1.232, 1.869) < 0.001 1.363 (1.015, 1.830) 0.040
Model 3 1.000 1.572(1.224, 2.018) < 0.001 2.779 (0.796, 9.705) 0.109 3.206 (0.714, 14.395) 0.128 1.971(1.226, 3.170) 0.005 1.371 (0.641, 2.934) 0.416
Gestational diabetes mellitus
Model 1 1.000 2.560(2.063, 3.176) < 0.001 4.600 (3.221, 6.569) < 0.001 3.046 (1.920, 4.831) < 0.001 2.502(1.918, 3.264) < 0.001 2.85 8 (2.03 8, 4.009) < 0.001
Model 2 1.000 2.411(1.930, 3.012) < 0.001 3.825 (2.628, 5.567) < 0.001 2.548 (1.591, 4.081) < 0.001 2.284(1.741, 2.997) < 0.001 2.506 (1.773, 3.544) < 0.001
Model 3 1.000 2.308 (1.665, 3.198) < 0.001 6.734 (1.934, 23.444) 0.003 2.174 (0.267, 17.688) 0.468 2.098(1.067, 4.126) 0.032 2.862 (1.314, 6.235) 0.008
Pregnancy-associated hypertension
Model 1 1.000 3.444(2.328, 5.096) < 0.001 2.867 (1.164, 7.059) 0.022 2.638 (0.968, 7.184) 0.058 3.377(2.098, 5.436) < 0.001 3.178 (1.652, 6.112) < 0.001
Model 2 1.000 3.161(2.113, 4.728) < 0.001 2.3 89 (0.944, 6.049) 0.066 2.526 (0.913, 6.987) 0.074 3.221(1.981, 5.239) < 0.001 2.793 (1.427, 5.467) 0.003
Model 3 1.000 3.288(1.859, 5.814) < 0.001 6.097 (0.372, 100.030) 0.205 15.649 (1.194, 205.006) 0.036 3.764(1.172, 12.091) 0.026 2.372 (0.319, 17.662) 0.399
Preterm birth
Model 1 1.000 2.218(1.373, 3.582) 0.001 2.461 (0.902, 6.715) 0.079 3.538 (1.434, 8.727) 0.006 1.726(0.895, 3.328) 0.103 2.728 (1.320, 5.638) 0.007
Model 2 1.000 2.185(1.333, 3.582) 0.002 2.055 (0.728, 5.800) 0.174 2.932 (1.161, 7.407) 0.023 1.650(0.846, 3.217) 0.142 2.408 (1.146, 5.062) 0.020
Model 3 1.000 2.459(1.231, 4.913) 0.011 1.239 (0.191, 8.030) 0.823 - - 1.333(0.182, 9.738) 0.777 4.285 (1.031, 17.810) 0.045
Large for gestational age
Model 1 1.000 2.410(1.725, 3.366) < 0.001 3.510 (1.905, 6.467) < 0.001 2.935 (1.443, 5.972) 0.003 1.969(1.260, 3.076) 0.003 3.183 (1.955, 5.183) < 0.001
Model 2 1.000 2.249(1.595, 3.171) < 0.001 3.270 (1.732, 6.174) < 0.001 2.844 (1.382, 5.852) 0.005 1.832(1.164, 2.884) 0.009 3.019 (1.832, 4.976) < 0.001
Model 3 1.000 2.266(1.388, 3.697) 0.001 4.962 (0.485, 50.773) 0.177 - - 1.376(0.416, 4.549) 0.601 3.223 (0.980, 10.593) 0.054
Small for gestational age
Model 1 1.000 0.876(0.615, 1.246) 0.460 0.750 (0.310, 1.814) 0.523 1.208 (0.571, 2.553) 0.621 0.884(0.569, 1.373) 0.583 0.915 (0.502, 1.668) 0.771
Model 2 1.000 0.916(0.641, 1.310) 0.631 0.785 (0.322, 1.916) 0.596 1.227 (0.577, 2.606) 0.595 0.909(0.583, 1.419) 0.676 0.949 (0.519, 1.738) 0.867
Model 3 1.000 0.925(0.536, 1.594) 0.778 4.515 (0.564, 36.128) 0.155 - - 1.265(0.467, 3.432) 0.644 1.132 (0.275, 4.656) 0.863
Postpartum hemorrhage
Model 1 1.000 0.697(0.387, 1.256) 0.230 1.355 (0.502, 3.657) 0.549 0.389 (0.054, 2.783) 0.347 0.855(0.436, 1.675) 0.648 1.126 (0.498, 2.547) 0.776
Model 2 1.000 0.668(0.369, 1.212) 0.185 1.205 (0.439, 3.313) 0.717 0.349 (0.049, 2.508) 0.296 0.806(0.409, 1.589) 0.533 1.014 (0.445, 2.313) 0.974
Model 3 1.000 0.487(0.167, 1.420) 0.188 2.519 (0.134, 47.306) 0.537 - - 0.503(0.065, 3.890) 0.510 2.517 (0.628, 10.086) 0. 192

Model 1 was unadjusted; Model 2 was adjusted for age, education level, and gestational weight gain; Model 3 was adjusted for age, education level, gestational weight gain, BMI abnormality, glucose abnormality, blood pressure abnormality, HDL-C abnormality, and TG abnormality. However, when any of these variables was the dependent variable, it was not adjusted as a covariate. BMI, body mass index; CMRF, cardiometabolic risk factor; HDL-C, high density lipoprotein cholesterol; MASLD, metabolic dysfunction-associated steatotic liver disease; TG, triglyceride. -, indicates unstable risk estimation results.

不同CMRF异常程度组的不良妊娠结局: 轻度CMRF异常组、中度CMRF异常组和重度CMRF异常组分别包括104人、125人和73人(表 4)。四组研究对象的剖宫产、妊娠期糖尿病、妊娠相关高血压、早产和大于胎龄儿发生率差异均有统计学意义(P均 < 0.05)，其中，中度和重度CMRF异常组的剖宫产、妊娠期糖尿病、妊娠相关高血压和早产发生率较高。小于胎龄儿和产后出血发生率在四组间的差异无统计学意义。
表4 不同CMRF异常程度组的不良妊娠结局

Table 4 Incidence of adverse pregnancy outcomes in groups with different degrees of CMRF abnormalities

Adverse pregnancy outcome Control group (n=2 321) Mild CMRF abnormality group (n=104) Moderate CMRF abnormality group (n=125) Severe CMRF abnormality group (n=73) χ2 P
Cesarean section 861 (37.1) 65 (62.50) 78 (62.40) 47 (64.38) 74.26 < 0.001
Gestational diabetes mellitus 362 (15.6) 36 (34.62) 48 (38.40) 37 (50.68) 114.27 < 0.001
Pregnancy-associated hypertension 88 (3.8) 10 (9.62) 19 (15.20) 9 (12.33) 49.05 < 0.001
Preterm birth 82 (3.5) 7 (6.73) 11 (8.80) 6 (8.22) 14.07 0.003
Large for gestational age 158 (6.8) 19 (18.27) 13 (10.40) 17 (23.29) 43.97 < 0.001
Small for gestational age 336 (14.5) 11 (10.58) 19 (15.20) 9 (12.33) 1.56 0.669
Postpartum hemorrhage 149 (6.4) 3 (2.88) 8 (6.40) 4 (5.48) 2.20 0.532

The incidence was presented as n (%) and compared using the Chi-square test. CMRF, cardiometabolic risk factor.

MASLD的CMRF异常程度与不良妊娠结局的相关性: 以对照组(0级)为基线，调整年龄、孕期增重水平和受教育水平后，CMRF异常程度从轻度到重度每升高一个等级，MASLD孕妇发生剖宫产的风险升高19.9%(RR=1.199，95%CI：1.112~1.292，P < 0.001)，妊娠期糖尿病的风险升高47.8%(RR= 1.478，95%CI: 1.345~1.624，P < 0.001)，妊娠相关高血压的风险升高62.6%(RR=1.626，95%CI: 1.367~1.934，P < 0.001)，早产的风险升高38.4%(RR=1.384，95%CI: 1.120~1.710，P=0.003)，大于胎龄儿的风险升高42.2%(RR=1.422，95%CI: 1.224~1.650，P < 0.001)；未见MASLD孕妇的小于胎龄儿和产后出血风险随CMRF异常程度变化(表 5)。
表5 CMRF异常程度变化与不良妊娠结局的相关性分析

Table 5 Associations between change in degree of CMRF abnormality and the risk of adverse pregnancy outcomes

Adverse pregnancy outcome RR (95%CI) P
Cesarean section
  Model 1 1.258 (1.169, 1.354) < 0.001
  Model 2 1.199 (1.112, 1.292) < 0.001
Gestational diabetes mellitus
  Model 1 1.529 (1.396, 1.675) < 0.001
  Model 2 1.478 (1.345, 1.624) < 0.001
Pregnancy-associated hypertension
  Model 1 1.672 (1.416, 1.974) < 0.001
  Model 2 1.626 (1.367, 1.934) < 0.001
Preterm birth
  Model 1 1.432 (1.166, 1.758) < 0.001
  Model 2 1.384 (1.120, 1.710) 0.003
Large for gestational age
  Model 1 1.465 (1.268, 1.692) < 0.001
  Model 2 1.422 (1.224, 1.650) < 0.001
Small for gestational age
  Model 1 0.962 (0.820, 1.129) 0.639
  Model 2 0.981 (0.834, 1.153) 0.812
Postpartum hemorrhage
  Model 1 0.929 (0.723, 1.194) 0.567
  Model 2 0.905 (0.702, 1.167) 0.443

Model 1 was unadjusted; Model 2 was adjusted for age, education level, and gestational weight gain. CMRF, cardiometabolic risk factor.

3 讨论

本研究发现，妊娠期MASLD与多种不良妊娠结局风险升高相关，包括剖宫产、妊娠期糖尿病、妊娠相关高血压、早产和大于胎龄儿。在控制其他种类CMRF异常的影响后，不同CMRF异常的MASLD与不良妊娠结局间的相关性存在差异，BMI异常MASLD与剖宫产、妊娠期糖尿病、妊娠相关高血压、早产和大于胎龄儿发生风险升高相关；血糖异常MASLD仅与妊娠期糖尿病风险升高相关；血压异常MASLD仅与妊娠相关高血压风险升高相关；HDL-C异常MASLD与剖宫产、妊娠期糖尿病和妊娠相关高血压风险升高相关；TG异常MASLD与妊娠期糖尿病和早产风险升高相关。值得注意的是，随着MASLD的CMRF异常严重程度增高，多种不良妊娠结局的发生风险呈持续上升趋势。
本研究中MASLD对不良妊娠结局的影响与妊娠期NAFLD的作用相似[22]，这与大多数NAFLD患者可被诊断为MASLD的观点一致[1]。然而，本研究发现，不同CMRF异常MASLD与不同的不良妊娠结局风险升高相关。BMI异常MASLD与多种不良妊娠结局风险升高相关，其风险变化趋势与全部MASLD孕妇的不良妊娠结局风险变化趋势相似，这可能是由于超重和肥胖会影响机体总体的代谢状态，导致胰岛素抵抗和代谢紊乱[23]，并在妊娠期持续影响孕妇健康状态，增加多种不良妊娠结局的风险[10]。血糖异常和血压异常的MASLD对不良妊娠结局风险的影响与疾病发病机制相符，HDL-C水平降低易导致机体胆固醇运输障碍、炎症水平升高以及血管内皮功能障碍，可能导致HDL-C异常的MASLD孕妇剖宫产、妊娠期糖尿病和妊娠相关高血压风险升高[11, 24-25]。此外，妊娠期间的高脂血症可能会增加娠期糖尿病及早产的发病风险[26]，这与TG异常组内观察到的风险变化相符。
随着MASLD孕妇CMRF异常程度的升高，其发生不良妊娠结局的风险持续升高。尽管不同MASLD孕妇的CMRF异常有所不同，但CMRF包含的五种指标均能在一定程度上反映机体的代谢功能紊乱水平[27-28]。现有的研究已提示，随着异常指标数量的增加，孕妇的整体代谢紊乱程度趋于严重[29]。有学者发现，机体代谢紊乱严重程度与其血糖和血压水平的异常程度密切相关[30-31]。代谢紊乱不仅会导致孕妇体重增长，还可能通过影响胎盘功能、胎儿营养供应及内分泌环境，引发胎儿生长异常[32]，并导致剖宫产、大于胎龄儿和早产等不良妊娠结局的发生[25, 33]。
本研究系统分析了MASLD与多种不良妊娠结局的相关性，对存在不同CMRF异常种类及严重程度的MASLD孕妇进行分析，结果提示不同种类CMRF异常的MASLD与不良妊娠结局风险之间的相关性存在差异，且MASLD孕妇的多种不良妊娠结局风险随CMRF异常严重程度的加重而升高，这一发现提示，MASLD孕妇内部存在不同的不良妊娠结局风险，强调了在诊断MASLD时关注具体CMRF异常种类及严重程度的必要性，这不仅有助于筛选出高危人群，还可为精准实施针对性预防干预措施提供依据，有助于降低不良妊娠结局的发生风险，为保障孕妇及胎儿健康提供了科学支持，具有重要的临床指导意义。
本研究存在一定的局限性：首先，肝脏超声检查与诊断由多位超声科医师分别完成，尽管有明确的诊断指南作为参考，但不同孕妇的诊断结果可能存在一定误差，但医师均经过严格培训且具有丰富的诊断经验，能够将误差控制在可接受范围内；其次，尽管本研究纳入了302名MASLD患者，但在对不同种类CMRF异常进行分组分析时，部分分组研究对象数量相对较少，如血压异常组，未观察到早产、大于胎龄儿、小于胎龄儿和产后出血的风险，未来需要通过更大样本量的研究进一步验证本研究的结论。
综上所述，本研究发现妊娠期MASLD与多种不良妊娠结局风险升高相关，且不同种类CMRF异常的MASLD与不良妊娠结局间的相关性存在差异。随着MASLD孕妇CMRF异常程度的加重，多种不良妊娠结局的发生风险持续升高。这一研究结果提示，在诊断MASLD时需进一步关注CMRF异常的种类及严重程度，为未来筛选高危人群、实施针对性孕期干预及健康教育工作提供理论依据，进而优化孕期保健资源的合理配置。

利益冲突  所有作者均声明不存在利益冲突。

作者贡献声明  杨树涵：设计研究方案，收集、整理与分析数据，撰写论文；李奕昕：设计研究方案, 分析数据；崔浩亮：收集、整理与分析数据；王佑新：收集与整理数据，撰写论文；吴玉莹、王明月、杨依凡、恩卡尔·努尔：收集与整理数据；杨磊：收集与整理数据，审定论文；王辉：设计研究方案，审定论文。

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