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Cited by 24Birth, Development, and HealthPregnancy and preeclampsia studiesGestational Diabetes Research and Management

Fetal growth trajectories of babies born large-for-gestational age in the LIFECODES fetal growth study

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Bommarito, Paige A., Cantonwine, David E., Stevens, Danielle R., Welch, Barrett M., Davalos, Angel D., Zhao, Shanshan, McElrath, Thomas F., Ferguson, Kelly K.·2023·American Journal of Obstetrics and Gynecology
DOI 10.1016/j.ajog.2022.10.006PMC PMC9974610
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Abstract

Background Babies born large-for-gestational age have an increased risk of adverse health outcomes, including birth injuries, childhood obesity, and cardiometabolic disorders. However, little work has been done to characterize patterns of fetal growth among large-for-gestational age births, which may further elucidate high- and low-risk subgroups.Objective This study aimed to identify subgroups of large-for-gestational age births based on trajectories of fetal growth derived from prenatal ultrasound measurements and explore differences in sociodemographic, pregnancy, and birth outcome characteristics across subgroups.Study design This study identified and described trajectories of fetal growth among large-for-gestational age births (n=235) in the LIFECODES Fetal Growth Study. Ultrasound measurements of fetal growth in middle to late pregnancy were abstracted from health records. Group-based multi-trajectory modeling was applied to measurements of head circumference, abdominal circumference, and femur length z-scores to identify multivariate trajectories of fetal growth. Moreover, sociodemographic variables, pregnancy characteristics, and birth outcomes based on trajectory membership were summarized.Results This study identified 4 multivariate trajectories of fetal growth among large-for-gestational age births: catch-up growth (n=28), proportional abdominal circumference-to-femur length growth (n=67), disproportional abdominal circumference-to-femur length growth (n=96), and consistently large (n=44). Fetuses in the "catch-up growth" group exhibited small relative sizes in midpregnancy (ie, below average head circumference, abdominal circumference, and femur length z-scores) and large relative sizes in late pregnancy. Growth among these births was driven by increases in relative abdominal circumference and head circumference sizes. Participants who delivered births assigned to this group were less likely to have normal glucose control (40% vs 65%-75%) and more likely to have pregestational diabetes mellitus (36% vs 10%-17%) than other large-for-gestational age subgroups. In addition, the babies in this trajectory group were more likely to have macrosomia (86% vs 67%-73%) and to be admitted to the neonatal intensive care unit (32% vs 14%-21%) than other large-for-gestational age subgroups. In contrast, babies in the "consistently large" group had the largest relative size for all growth parameters throughout gestation and experienced a lower risk of adverse birth outcomes than other large-for-gestational age subgroups.Conclusion This study characterized several trajectories of fetal growth among large-for-gestational age births, which were related to different pregnancy characteristics and the distribution of adverse birth outcomes. Although the number of individuals within some trajectories was small, a subgroup that exhibited a catch-up growth phenotype during gestation was identified, which may be uniquely associated with exposure to pregestational diabetes mellitus and a higher risk of admission to the neonatal intensive care unit. These results have highlighted that the risk of adverse outcomes may not be evenly distributed across all large-for-gestational age births.

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  • Outcome misclassification from harmonization would likely be non-differential across subgroup analyses and would bias effect estimates toward the null if PFAS exposure was etiologically related to late-onset PE specifically.

    “This would have resulted in outcome misclassification, likely non-differential in nature across all subgroup analyses, which would be expected to bias the effect estimates toward the null, if PFAS exposure was etiologically related to late-onset PE specifically (Bommarito et al., 2023).”

    From Association between gestational PFAS exposure biomarkers and risk of preeclampsia in the ECHO Cohort (2026) · cites this paper as Bommarito et al., 2023

    The Strengths and limitations section discusses possible misclassification of fetal growth measurements when gestational age is rounded to completed weeks, not misclassification of preeclampsia outcomes. Searches for PFAS, late-onset preeclampsia, harmonization, and bias toward the null found no passage addressing the attributed claim. Page numbers were not available in our copy. (LLM, conf=0.77)

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  1. [17]Cantonwine DE, Ferguson KK, Mukherjee B, Utilizing Longitudinal Measures of Fetal Growth to Create a Standard Method to Assess the Impacts of Maternal Disease and Environmental Exposure. Supporting Information. Means and standard deviations (SD) or ultrasound parameters outside the clinically proscribed window of gestation.. PLOS ONE 2016; 11: e0146532. 26731406 PMC4701464

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Authors
Bommarito, P. A., Cantonwine, D. E., Stevens, D. R., Welch, B. M., Davalos, A. D., Zhao, S., McElrath, T. F., & Ferguson, K. K.
Affiliations
  • National Institute of Environmental Health Sciences (US)
  • Brigham and Women's Hospital (US)
  • University of Nevada, Reno (US)
  • National Institutes of Health (US)
Corresponding author
Ferguson, Kelly K.
ORCID
Venue
American Journal of Obstetrics and Gynecology
Publisher
Elsevier BV
Published
2023-03
Volume
228
Issue
3
Pages
340.e1-340.e20
ISSN
0002-9378 (ISSN-L)
DOI
10.1016/j.ajog.2022.10.006
PMC
PMC9974610
OpenAlex
W4304693505
Cited by
24
References
37
Citations by year
2026: 8 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 2
FWCI
4.39
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Obstetrics and Gynecology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (ZIA E103321)
  • National Institute of Environmental Health Sciences
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Keywords
large for gestational age, fetal growth trajectories, catch-up growth, macrosomia, head circumference, prenatal ultrasound, pregestational diabetes, neonatal intensive care admission, birth outcomes
MeSH terms
Birth Weight, Child, Female, Fetal Macrosomia, Gestational Age, Humans, Pregnancy, Pregnancy Complications, Ultrasonography, Prenatal, Fetal Development, Pediatric Obesity

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