Flanagan Emily W, Drews Kimberly L, Cade W Todd, Franks Paul W, Gallagher Dympna, Phelan Suzanne, Van Horn Linda, Redman Leanne M
Pennington Biomedical Research Center, Baton Rouge, Louisiana.
Doctor of Physical Therapy Division, Duke University School of Medicine, Durham, North Carolina.
JAMA Netw Open. 2025 Aug 1;8(8):e2528264. doi: 10.1001/jamanetworkopen.2025.28264.
Prenatal intensive behavioral therapy (IBT) interventions that promote adequate gestational weight gain (GWG) have had variable and mostly modest effects on clinically relevant maternal and infant outcomes. It is unknown whether different maternal obesity metabolic phenotypes underlie the heterogeneity in response.
To examine GWG, adverse perinatal outcomes, substrate changes, and differential changes in each in a prenatal IBT intervention conducted among pregnant individuals with 2 identified obesity phenotypes.
DESIGN, SETTING, AND PARTICIPANTS: The Lifestyle Interventions for Expectant Moms (LIFE-Moms) trial was a consortium of 7 independent but collaborative multicenter randomized clinical trials that took place between November 1, 2012, and December 31, 2017, and evaluated a prenatal IBT intervention on GWG and perinatal outcomes among women with overweight and obesity. Statistical analysis for the present preplanned secondary analysis was conducted from March 29, 2023, to June 4, 2025. Participants (n = 1150) had a confirmed viable singleton pregnancy and no previous diagnosis of cardiometabolic diseases. This analysis was limited to those with obesity. Participants were classified into 2 groups: obesity with no additional qualifying cardiometabolic disease risk factors (metabolically healthy obesity [MHO]) or obesity with 2 qualifying risk factors (metabolically unhealthy obesity [MUO]) in early pregnancy.
A behavioral lifestyle intervention incorporating diet and physical activity was delivered to increase adherence to the National Academy of Medicine GWG guidelines.
GWG (total and adherence to guidelines), adverse perinatal outcomes, substrate changes, and infant body composition. Analysis was conducted on an intent-to-treat basis.
The mean (SD) age of the 640 participants was 30.2 (5.6) years, and the participants presented in early pregnancy with a mean (SD) body mass index of 35.2 (4.1). Participants in the MUO (n = 172) and MHO (n = 228) groups did not differ in response to treatment in weight outcomes, adverse perinatal outcomes, or substrate changes, with the exception that patients in the intervention group experienced smaller mean (SE) triglyceride increases more in the MUO group than in the MHO group (90.3% [7.4%] vs 81.8% [8.3%]; P = .02). After adjustment for maternal baseline demographics and treatment group, individuals with MUO had lower GWG (0.30 [0.23] kg/wk) compared with individuals with MHO (0.41 [0.27] kg/wk; P < .001), a 36.7% difference, and had a lower proportion exceed weight gain guidelines (57.0% [98 of 172] vs 68.0% [155 of 228]; P = .03). Participants with MUO had a higher incidence of gestational diabetes (23.8% [41 of 172] vs 9.8% [22 of 228]; P = .001) and had infants with a higher proportion of adiposity (mean [SD], 12.5% [3.9%] vs 11.7% [3.7%] fat; P = .05) compared with participants with MHO.
In this preplanned secondary analysis of a randomized clinical trial of an IBT on GWG among pregnant individuals, those with MUO experienced less GWG, had a higher incidence of gestational diabetes, and had infants with a higher proportion of adiposity compared with those who MHO. Data supported that the maternal obesity metabolic phenotype has a greater clinical effect on adverse maternal and infant clinical outcomes compared with GWG alone and did not contribute to a differential response to a lifestyle intervention. Future interventions should identify methods to better optimize the maternal metabolic milieu as early in pregnancy as possible to reduce the intergenerational transmission of metabolic disease.
ClinicalTrials.gov Identifiers: NCT01545934, NCT01616147, NCT01771133, NCT01631747, NCT01768793, NCT01610752, NCT01812694.
促进孕期体重适度增加（GWG）的产前强化行为疗法（IBT）干预措施，对临床相关的母婴结局产生的影响不一，且大多较为有限。尚不清楚不同的母体肥胖代谢表型是否是导致反应异质性的原因。
在一项针对具有两种已确定肥胖表型的孕妇进行的产前IBT干预中，研究GWG、不良围产期结局、底物变化以及各项指标的差异变化。
设计、地点和参与者：“准妈妈生活方式干预”（LIFE-Moms）试验是由7项独立但协作的多中心随机临床试验组成的联合体，于2012年11月1日至2017年12月31日进行，评估了一项产前IBT干预对超重和肥胖女性的GWG及围产期结局的影响。本次预先计划的二次分析的统计分析于2023年3月29日至2025年6月4日进行。参与者（n = 1150）确诊为单胎存活妊娠，且既往无心血管代谢疾病诊断。该分析仅限于肥胖者。参与者被分为两组：妊娠早期无其他合格心血管代谢疾病风险因素的肥胖者（代谢健康肥胖 [MHO]）或有2项合格风险因素的肥胖者（代谢不健康肥胖 [MUO]）。
实施一项结合饮食和体育活动的行为生活方式干预，以提高对美国医学科学院GWG指南的依从性。
GWG（总量及对指南的依从性）、不良围产期结局、底物变化和婴儿身体成分。分析采用意向性分析。
640名参与者的平均（标准差）年龄为30.2（5.6）岁，妊娠早期的平均（标准差）体重指数为35.2（4.1）。MUO组（n = 172）和MHO组（n = 228）的参与者在体重结局、不良围产期结局或底物变化方面对治疗的反应无差异，但干预组患者中，MUO组的平均（标准误）甘油三酯升高幅度（90.3% [7.4%]）大于MHO组（81.8% [8.3%]）（P = 0.02）。在对母体基线人口统计学和治疗组进行调整后，与MHO组个体（0.41 [0.27] kg/周）相比，MUO组个体的GWG较低（0.30 [0.23] kg/周）（P < 0.001），差异为36.7%，且超过体重增加指南的比例较低（57.0% [172例中的98例] 对68.0% [228例中的155例]；P = 0.03）。与MHO组参与者相比，MUO组参与者患妊娠期糖尿病的发生率更高（23.8% [172例中的41例] 对9.8% [228例中的22例]；P = 0.001），其婴儿的肥胖比例更高（平均 [标准差]，12.5% [3.9%] 对11.7% [3.7%] 脂肪；P = 0.05）。
在这项针对孕妇GWG的IBT随机临床试验的预先计划的二次分析中，与MHO组相比，MUO组个体的GWG较少，妊娠期糖尿病发生率较高，且其婴儿的肥胖比例更高。数据支持母体肥胖代谢表型对母婴不良临床结局的临床影响大于单独的GWG，且对生活方式干预的反应无差异。未来的干预措施应确定方法，尽早在孕期优化母体代谢环境，以减少代谢疾病的代际传播。
ClinicalTrials.gov标识符：NCT01545934、NCT01616147、NCT01771133、NCT01631747、NCT01768793、NCT01610752、NCT01812694。
