Relationships among maternal serum uric acid in mid-pregnancy, maternal blood pressure, fetal growth, and placental pathology

摘要

Gestational hypertension in mother and atypical fetal growth (very small or very large infant) contribute to substantial adverse health and cost burden in society. In pregnant women, high maternal serum uric acid has been related to increased risk of gestational hypertension and poor fetal growth, but the association between low maternal serum uric acid and these health outcomes has been ignored. In addition, there are no studies on the relationship between maternal serum uric acid and placental pathology, a problem known to affect both maternal blood pressure and fetal growth. In this study, we investigated whether there is a J-shaped association between maternal serum uric acid in mid-pregnancy and three outcomes, mothers' blood pressure, birth weight for gestational age (Z-score), and placental pathology.;Our study data came from the Pregnancy Outcomes and Community Health (POUCH) Study cohort, which consisted of 3,019 pregnant women enrolled in the 16th-27th week of pregnancy from 52 clinics in Michigan during the period from August 1998 through June 2004. We considered maternal serum uric acid level measured in blood collected at enrollment as a continuous exposure variable and applied a linear spline with a multiple linear regression model or a restricted cubic spline with a multinomial logistic regression model. The robustness of our results was evaluated and assured by using bootstrap estimation of variance, sensitivity analysis, and 10- or 5-fold cross-validation.;Our results demonstrated that there was a J-shaped relationship between maternal serum uric acid in mid-pregnancy and gestational diastolic blood pressure (DBP) or mean arterial pressure (MAP) in pregnant women. The breakpoints were 2.6 mg/dL (for DBP) and 2.7 mg/dL (for MAP) of uric acid, respectively. By contrast, maternal systolic blood pressure (SBP) followed a positive linear trend with uric acid level increase. We also found a J-shaped relationship between birth weight Z-score and maternal serum uric acid in mid-pregnancy among small-for-gestational age (SGA) infants (birth weight less than 10 th percentile for gestational age); the breakpoint was 4.10 mg/dL. By contrast, in large-for-gestational age (LGA) infants (birth weight more than 90th percentile for gestational age) we observed a positive linear relationship between maternal serum uric acid and birth weight Z-score. Birth weight Z-score was not associated with maternal serum uric acid in the appropriate-for-gestational age (AGA) group (birth weight between 10th and 90th percentile for gestational age). Finally, we found that maternal serum uric acid concentration was associated with maternal vascular lesions in the placenta; the relationship was non-linear. Uric acid levels were not associated with fetal vascular lesions in the placenta.;We proposed that a common mechanism underlying our findings may be related to oxidative stress that follows exceptionally low or high serum uric acid concentration. Our findings may provide clues: 1) to guide the study of biological mechanisms underlying the non-linear relationship between maternal serum uric acid and maternal blood pressure, atypical fetal growth, and placental pathology; and 2) to allow researchers to consider maternal serum uric acid in pregnancy as a marker along with other indicators to predict the progression and/or severity of pregnancy-related health conditions or as a target for early intervention.