Fetal Polygenic Growth Score and Risk for Large for Gestational Age Birth Weight in Nulliparas: Secondary Analysis of...

Large for gestational age birth weight is associated with both short- and long-term health consequences for offspring, and fetal genetics may contribute to risk for large for gestational age birth weight.

We evaluated the relationship between a polygenic growth score and the risk for large gestational age birth weight. We also delineated the between the polygenic growth score and risk for large for gestational age birth weight in relation to maternal glycemia and body mass index, both of which are established risk factors for large for gestational age birth weight.

This is a secondary analysis of a prospective multicenter cohort study in which nulliparous individuals were recruited from eight clinical sites in the United States. A subset of infants (n=3865) with DNA available were genotyped, and a previously developed polygenic growth score for large for gestational age birth weight was calculated. We evaluated the relationship between tertiles of the polygenic growth score, maternal body mass index, and glycemia assessed by the 50-gram glucose challenge test on the risk for large for gestational age birth weight using one-way ANOVA and Chi-squared tests as well as a regularized linear model.

Of the 3,865 individuals with infant genotype available, 3,286 (84.9%) were included in this analysis. A polygenic growth score in the first tertile was associated with a lower risk for large for gestational age (OR 0.71, 95% CI 0.53- 0.94), while a polygenic growth score in the third tertile was associated with a higher risk for large for gestational age birth weight (OR 1.29, 95% CI 1.02- 1.63). Maternal body mass index was more strongly associated with the risk for large for gestational birth weight than maternal glycemia. The odds of large for gestational age birth weight were significantly higher with a maternal body mass index ≥35 kg/m² and a PGS of either the second tertile (OR 3.54, 95% CI 1.96- 6.38) or third tertile (OR 2.69, 95% CI 1.54 - 4.71).

The polygenic growth score has a modest ability to identify fetuses at higher or lower risk for Large for gestational age birth weight in a multiracial cohort from the United States. Polygenic growth score could assist with identification of those fetuses at increased risk for LGA birth weight among individuals with a BMI ≥35 kg/m², which may allow for targeted interventions such as dietary and lifestyle modifications to optimize the in-utero environment.