A Maternal Serum Metabolite Ratio Predicts Large for Gestational Age Infants at Term: A Prospective Cohort Study

Context: Excessive birth weight is associated with maternal and neonatal complications. However, ultrasonically estimated large for gestational age (LGA; >90th percentile) predicts these complications poorly.
Objective: To determine whether a maternal serum metabolite ratio developed for fetal growth restriction (FGR) is predictive of birth weight across the whole range, including LGA at birth.
Methods: Metabolites were measured using ultrahigh performance liquid chromatography-tandem mass spectroscopy. The 4-metabolite ratio was previously derived from an analysis of FGR cases and a random subcohort from the Pregnancy Outcome Prediction study. Here, we evaluated its relationship at 36 weeks of gestational age (wkGA) with birth weight in the subcohort (n = 281). External validation in the Born in Bradford (BiB) study (n = 2366) used the metabolite ratio at 24 to 28 wkGA.
Results: The inverse of the metabolite ratio at 36 wkGA predicted LGA at term [the area under the receiver operating characteristic curve (AUROCC) = 0.82, 95% CI 0.73 to 0.91, P = 6.7 × 10−5]. The ratio was also inversely associated with birth weight z score (linear regression, beta = −0.29 SD, P = 2.1 × 10−8). Analysis in the BiB cohort confirmed that the ratio at 24 to 28 wkGA predicted LGA (AUROCC = 0.60, 95% CI 0.54 to 0.67, P = 8.6 × 10−5) and was inversely associated with birth weight z score (beta = −0.12 SD, P = 1.3 × 10−9). Conclusions: A metabolite ratio which is strongly predictive of FGR is equally predictive of LGA birth weight and is inversely associated with birth weight across the whole range.