Maternal serum uric acid levels in pregnancy and fetal growth

Objective: Studies of maternal serum uric acid (UA) in pregnancy focus primarily on high levels of UA, however, both low and high UA levels can be markers of oxidative stress, a biological state potentially linked to fetal growth. We therefore aimed to test whether low and high maternal serum UA levels during pregnancy are associated with atypical fetal growth (unusually small or large) measured as birthweight (BW) for gestational age.Methods: The Pregnancy Outcomes and Community Health Study enrolled 3019 pregnant women between their 16th-27th week of pregnancy from 52 clinics in five Michigan communities (1998-2004). Maternal UA levels were measured in blood collected at enrollment among a subcohort of 1291 participants. Infant BW and gestational age were used to calculate gestational age-specific BW Z-score. Infants were grouped as small (SGA = BW < 10th percentile), appropriate (AGA = BW 10th-90th percentile), or large (LGA) = BW > 90th percentile) for their gestational age. Analyses considered multiple potential confounders. Linear spline or multiple linear regression models were applied to evaluate the relationship between maternal UA levels and BW Z-score overall and within SGA, AGA, and LGA groups. Model robustness was tested through bootstrap, sensitivity analysis, and cross-validation techniques.Results: The relation between maternal UA levels and BW Z-score varied by infant group. Among SGA infants, the relation was nonlinear (J-shape): both extremes of UA had lower BW Z-score with a breakpoint of 0.267 mmol/L UA (adjusted regression coefficient β = 2.32, p = .01 for lower UA; adjusted β = -37.38, p < .01 for higher UA). Among AGA infants, there was no significant association, and among LGA infants, the relation was linear (adjusted β = 2.86, p = .03).Conclusions: Future research on maternal UA levels in pregnancy may benefit from considering both very low and high levels, and identifying in utero conditions associated with the two extremes.