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A polygenic growth score and risk for large for gestational age birth weight

Maha Aamir1, Maisa Feghali2, Lynn Yee3

  • 1Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27607, USA.

Journal of the Endocrine Society
|March 2, 2026
PubMed

Insights

A polygenic growth score (PGS) can help identify fetuses at higher risk for large for gestational age (LGA) birth weight. This genetic risk assessment is particularly useful for mothers with a high body mass index (BMI).

Area of Science:

  • Reproductive biology
  • Genetics
  • Perinatal medicine

Background:

  • Large for gestational age (LGA) birth weight poses significant short- and long-term health risks to offspring.
  • Fetal genetics is a potential contributing factor to LGA birth weight.
  • Identifying at-risk fetuses is crucial for timely intervention and improved neonatal outcomes.

Purpose of the Study:

  • To evaluate the association between a polygenic growth score (PGS) and LGA birth weight.
  • To assess the interplay between PGS, maternal body mass index (BMI), and maternal glycemia in predicting LGA birth weight risk.
  • To determine the utility of PGS in identifying fetuses at increased risk for LGA birth weight.

Main Methods:

  • A previously developed PGS for LGA birth weight was calculated using offspring DNA from 3286 nulliparous individuals.
  • Statistical analyses included one-way ANOVA, chi-squared tests, and a regularized linear model.
  • The study examined the relationship between PGS tertiles, maternal BMI, and glucose challenge test results with LGA birth weight risk.

Main Results:

  • A PGS in the first tertile was associated with a reduced risk of LGA birth weight (aOR 0.71, 95% CI 0.53-0.94).
  • Conversely, the third PGS tertile was linked to an increased risk of LGA birth weight (aOR 1.29, 95% CI 1.02-1.63).
  • The highest odds of LGA birth weight were observed in individuals with a maternal BMI ≥35 kg/m² and either the second or third PGS tertile.

Conclusions:

  • A polygenic growth score (PGS) shows potential for identifying fetuses at elevated risk for large for gestational age (LGA) birth weight.
  • The predictive value of PGS is particularly pronounced in pregnancies complicated by maternal obesity (BMI ≥35 kg/m²).
  • Integrating genetic risk scores into prenatal care may enhance the management of pregnancies at risk for LGA birth weight.
Abstract

Keywords:
gestational diabeteslarge for gestational age birth weightobesitypolygenic scorepregnancy

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