Fetal Body Composition in Twins and Singletons
Authors: Jessica L. Gleason, Wesley Lee, Zhen Chen, Kathryn A. Wagner, Dian He, William A. Grobman, Roger B. Newman, Seth Sherman, Robert Gore-Langton, Edward Chien, Luis Goncalves, Katherine L. Grantz
Journal: JAMA Pediatrics (2025)

Importance An emerging paradigm attributes third-trimester fetal growth deceleration in uncomplicated twin pregnancies to an evolutionary adaptive process. Evaluating longitudinal fetal soft-tissue development may provide important insights into differential fetal growth trajectories between twins and singletons. Objective To compare twin vs singleton lean and fat tissue growth across pregnancy. Design, Setting, and Participants Prospective cohort study of dichorionic twins and singletons with serial ultrasound scans to chart fetal growth (2009-2013) and collect fetal volume data to measure fat and lean tissue (2015-2019) in 12 US clinical centers. Participants were individuals with singleton (n = 2802 enrolled) and twin (n = 171 pairs enrolled) pregnancies who generally had no chronic disease. Data analysis was performed from September 2023 to June 2024. Exposure Twin status. Main Outcomes and Measures Abdominal area, maximum abdominal subcutaneous tissue thickness, fractional thigh volume, fractional lean thigh volume, fractional fat thigh volume, midthigh area (including lean and fat components), ratio of fractional fat thigh volume to fractional thigh volume, and ratio of midthigh fat area to midthigh area, measured up to 6 times between 15 and 37 weeks’ gestation. Results Analyses included 315 twin and 2604 singleton fetuses. The mean (SD) maternal age at delivery was 31.3 (6.1) years for twins and 28.2 (5.5) years for singletons, with a mean (SD) gestational age at delivery of 35.2 (4.2) weeks for twins and 39.2 (1.7) weeks for singletons. Mean twin abdominal measurements were significantly smaller than those of singletons between 25 and 37 weeks’ gestation for area (difference at 25 weeks, −48.6 [95% CI, −102.2 to −5.1] mm 2 ; difference at 37 weeks, −480.5 [95% CI, −677.2 to −283.5] mm 2 ) and between 27 and 37 weeks for maximum abdominal subcutaneous tissue thickness (difference at 27 weeks, −0.13 [95% CI, −0.24 to −0.02] mm; difference at 37 weeks, −0.40 [95% CI, −0.68 to −0.13] mm). Beginning at 15 weeks, fractional thigh volumes were significantly smaller for twins (mean fractional thigh volume difference, −0.11 [95% CI, −0.16 to −0.07] cm 3 ; mean fractional fat thigh volume difference, −0.08 [95% CI,−0.12 to −0.05] cm 3 ) relative to singletons, persisting through 37 weeks (mean fractional thigh volume difference, −7.55 [95% CI, −11.76 to −3.34] cm 3 ; mean fractional fat thigh volume difference, −5.60 [95% CI, −8.37 to −2.82] cm 3 ). Mean fractional lean thigh volume was significantly smaller for twins at 15 to 16 and 23 to 36 weeks. For the ratio of fractional fat thigh volume to fractional thigh volume, twins had a 2.7% to 4.2% smaller fat percentage between 15 and 37 weeks compared with singletons. Conclusions and Relevance Twins had proportionally less fat tissue accumulation in utero compared with singletons as early as 15 weeks’ gestation, when competition for nutritional resources was low. Persistent findings of smaller twin sizes and less fat accumulation across pregnancy support the concept of an early evolutionary adaptive process in otherwise uncomplicated dichorionic twin growth.