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Am J Perinatol
DOI: 10.1055/a-2682-5886
Original Article

Fetal Body Composition and Organ Growth in Pregnancies Complicated by First-Trimester Vaginal Bleeding Status: NICHD Fetal 3D Study

Alexandra Jean-Louis 
1   Division of Population Health Research, Division of Intramural Research, Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States
,
Jessica L. Gleason 
1   Division of Population Health Research, Division of Intramural Research, Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States
,
Zhen Chen
2   Division of Population Health Research, Division of Intramural Research, Biostatistics and Bioinformatics Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States
,
Kathryn A. Wagner
1   Division of Population Health Research, Division of Intramural Research, Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States
,
Dian He
3   The Prospective Group, Inc., Fairfax, Virginia, United States
,
Roger Newman
4   Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Medical University of South Carolina, Charleston, South Carolina, United States
,
William A. Grobman
5   Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States
,
Robert Gore-Langton
6   The Emmes Company, Rockville, Maryland, United States
,
Seth Sherman
6   The Emmes Company, Rockville, Maryland, United States
,
Magdalena Sanz Cortes
7   Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, United States
,
Edward K. Chien
8   Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, Ohio, United States
,
Luis F. Goncalves 
9   Department of Radiology, Phoenix Children's Hospital, Phoenix, Arizona, United States
,
Jagteshwar Grewal
10   Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States
,
Katherine L. Grantz 
1   Division of Population Health Research, Division of Intramural Research, Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States
› Author Affiliations
Funding Information This research was supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH); and, in part, with Federal funds for the Fetal 3D Study (Contract Numbers: HHSN275201300026I; HHSN275201500002C) and, in part, the NICHD Fetal Growth Studies—Singletons (Contract Numbers: HHSN275200800013C; HHSN275200800002I; HHSN27500006; HHSN275200800003IC; HHSN275200800014C; HHSN275200800012C; HHSN275200800028C; HHSN275201000009C). The contributions of the NIH authors were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services. Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health. Clinical Trial Registration This study is registered with Clinicaltrials.gov, identifiers: NCT00912132 and NCT03266198.
› Further Information
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Abstract

Objective

This study aimed to explore associations between self-reported first-trimester vaginal bleeding status and fetal body composition and organ volumes measured by three-dimensional (3D) ultrasound across pregnancy.

Study Design

The NICHD Fetal 3D Study (2015–2019) included individuals with singleton pregnancies at low risk for fetal growth abnormalities (n = 2,634). Fetal body composition measures of arm, abdomen, and thigh, and organ volumes including cerebellum, lung, kidney, and liver, were measured up to five times between 15 and 40 weeks using 3D ultrasound. Women were grouped by cumulative days of self-reported first-trimester vaginal bleeding: 0 (no bleeding, reference), 1, or >1 day. Linear mixed models, with quadratic and cubic terms for gestational age, including global tests for overall differences in trajectories and weekly pairwise comparisons, were fit to compare groups by fetal anthropometric measures, adjusted for maternal age, race/ethnicity, prepregnancy body mass index, parity, and infant sex.

Results

Most women had no bleeding (n = 2,144, 81.4%), whereas 211 (8.0%) reported 1 day and 279 (10.6%) reported >1 day. Compared with no bleeding, fetuses of women with >1 day of bleeding had 75.1 to 264.0 mm2 smaller abdominal area between 30 and 40 weeks, 1.1 to 4.0 cm3 smaller fractional thigh volume between 33 and 40 weeks, 0.4 to 2.4 cm3 smaller fractional fat thigh volumes between 30 and 40 weeks, and 0.8 to 1.6 cm3 larger cerebellar volumes between 35 and 40 weeks. Fetuses of women with 1 day of bleeding had 2.6 to 4.8 cm3 smaller liver volume between 26 and 35 weeks compared with no bleeding.

Conclusion

First-trimester bleeding was associated with smaller fetal abdominal area and decreased adiposity compared with no bleeding, whereas organ growth trajectories were increased for the cerebellum and decreased for the liver. Fetal 3D measures may provide insight into how first-trimester gestational bleeding potentially influences fetal growth and development with implications for possible postnatal health outcomes.

Key Points

  • First trimester bleeding group had smaller abdomen and liver and larger cerebellum.

  • Thigh fat was smaller in women with moderate/severe and consistent bleeding across pregnancy.

  • Fetal volume differences may improve understanding of bleeding and fetal growth.

Keywords

first-trimester bleeding - fetal growth - body composition - organ growth - fetal development

Note

This work was presented, in part, as a poster presentation at the Annual Society for Pediatric and Perinatal Epidemiologic Research Meeting and Society for Epidemiologic Research Meeting in June 2024.


Supplementary Material



Publication History

Received: 20 May 2025

Accepted: 13 August 2025

Accepted Manuscript online:
14 August 2025

Article published online:
09 September 2025

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