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Fetus

Poster Session 3

(826) Integrating maternal genotypes to improve birth weight prediction in low-risk pregnancies

Wednesday, February 14, 2024
8:30 AM – 10:00 AM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level
Objective: Fetal growth potential is thought to be genetically driven, yet growth assessment tools do not utilize genetic data. Our aim was to determine whether integration of a maternal genetic risk score for birth weight (GRS-BW) would improve BW prediction in low-risk pregnancies.

Study Design: This was a secondary analysis of a prospective observational cohort of 10,038 nulliparas who underwent detailed clinical characterization. To predict “ideal” BW, we included births without risk factors for abnormal fetal growth: preterm birth, pre-gestational diabetes, chronic hypertension, chromosomal abnormalities, and stillbirth. We randomly selected 60% of participants as a training set and utilized log linear regression to derive a new model for ideal BW prediction using established variables (gestational age (GA), sex) and assessing new variables with evidence for effects on growth beyond transmitted alleles: GRS-BW, pre-pregnancy nutrition (Healthy Eating Index-2010), exercise during pregnancy (weekly metabolic equivalents), maternal weight, and gestational weight gain. Maternal SNP arrays were used to compute GRS-BW from 84 published BW-associated loci. We compared the performance of models with and without GRS-BW in the validation set.

Results: We analyzed N=7,816 births. In the training set, the “base model” (GA and sex only) had modest prediction of BW (R2=0.598). GRS-BW, early pregnancy weight, and final pregnancy weight were independently associated with BW (p< 0.001 for all), and their addition to the model increased the R2 to 0.644. Pre-pregnancy nutrition and pregnancy exercise were not independently associated with BW. In the validation set, the model with GA, sex, GRS-BW, and early pregnancy weight decreased the mean absolute error from 10.2% to 9.9% over the base model, while the model with all significant variables did not yield further improvement.

Conclusion: Integrating a maternal genetic risk score for BW marginally improved BW prediction in low-risk pregnancies. Further work is needed to determine whether genetic personalization of fetal growth potential can offer any clinical benefit.