Maternal serum uric acid concentration and pregnancy outcomes in women with pre‐eclampsia/eclampsia

Abstract Objectives To determine the relationship between maternal serum uric acid levels and fetal/neonatal complications in women with pre‐eclampsia/eclampsia, and to establish a predictive threshold value. Methods A diagnostic test and historical cohort study conducted by prospective cross‐sectional data collection on pregnant women with pre‐eclampsia/eclampsia at Hue University Hospital, Vietnam, between March 2015 and July 2017. Pre‐eclampsia was diagnosed based on ACOG criteria. Serum uric acid levels were measured by enzymatic colorimetric testing using a Cobas c 501 analyzer (Roche Diagnostics, Mannheim, Germany). Fetal complications included intrauterine growth restriction, preterm delivery, fetal death, and neonatal death. Results There were 205 women enrolled. Serum uric acid at a cutoff of 393 μmol/L is a good predictor of fetal/neonatal complications (AUC 0.752), with 64.4% sensitivity and 79.5% specificity. High uric acid level (≥393 μmol/L) resulted in increased risk of preterm birth (OR 6.367, 95% CI 3.009–13.084), low Apgar scores (OR 5.514, 95% CI 1.877–16.198), intrauterine growth restriction (OR 7.188, 95% CI 3.592–14.382), and neonatal death (OR 7.818, 95% CI 1.614–37.867). There was no relationship between uric acid level and fetal death (OR 1.803, 95% CI 0.355–9.168). Conclusions Maternal serum uric acid concentration is a good predictor of fetal/neonatal outcomes in women with pre‐eclampsia/eclampsia.


| INTRODUCTION
Uric acid is the final substance in the process of purine metabolism. 1,2 Elevated levels are considered to be an early biomarker of kidney damage in women with pre-eclampsia and also a factor in predicting fetal death. 1,3 The role of uric acid as the possible cause of maternal and fetal deaths in pre-eclamptic patients (10%-15% and 5.9%, respectively) is controversial and the subject of ongoing study. 3 In addition to complications for the mother, pre-eclampsia can also result in serious consequences for the fetus, including fetal distress, intrauterine growth restriction (IUGR), and preterm or perina- In Vietnam, although there have been many studies on preeclampsia in terms of prevention, early diagnosis, and pregnancy outcomes, there are limited studies that have investigated uric acid concentration and its role in predicting severe fetal complications in pre-eclamptic patients. The aim of the present study was to determine the relationship between maternal serum uric acid levels and fetal/ neonatal complications in women with pre-eclampsia/eclampsia, and to establish a predictive value for these complications.

| MATERIALS AND METHODS
A diagnostic test and historical cohort study conducted by prospective cross-sectional data collection on singleton pregnant women with pre-eclampsia/eclampsia admitted to the Department of Obstetrics  preterm birth, APGAR score less than 7 in the first minute, fetal death, IUGR, or neonatal death. Groups were compared using the t test for independent samples. Values are given as mean and standard deviation (SD) or absolute number and percentage. Results are expressed as odds ratio (OR) with 95% confidence interval (CI) or two-sided P value.
P<0.05 was considered statistically significant.

| RESULTS
During the study period, 205 pregnant women with pre-eclampsia/ eclampsia met the eligibility criteria and were recruited consecutively.
The general characteristics of the study population and the fetal/neonatal complications are shown in Table 1. The mean age of the study participants was 30.6 ± 6.7 years, and there was no significant difference in age between group 1 (pre-eclampsia) and group 2 (severe preeclampsia/eclampsia). Differences in parity and BMI were also not significant between the groups.
Uric acid concentration was significantly higher in group 2 com- There was no association between uric acid level and maternal factors such as age, parity, or delivery method ( Table 4). The only associated factor was severe pre-eclampsia/eclampsia (OR 5.188, 95% CI 2.790-9.649; P<0.001).

| DISCUSSION
This cross-sectional study of 205 pregnant women with preeclampsia/eclampsia aimed to assess the role of maternal serum uric acid levels in predicting pregnancy outcomes. The study was also designed to establish a predictive threshold value of maternal uric acid levels and occurrence of fetal complications. The association of biomarkers, including uric acid, with adverse outcomes in pre-eclamptic pregnant women is discussed in ACOG guidelines 10 ; however, its utility as a diagnostic marker is still debated.
T A B L E 1 General characteristics of the study population and fetal/neonatal outcomes. a   The present study had some limitations, such as missing maternal data for preconception and prenatal care, which made the assessment of maternal risks more difficult.

Characteristics Group 1: Pre-eclampsia (n=112)
In conclusion, maternal serum uric acid concentration was a good prognostic factor for monitoring and prognosis of fetal/neonatal outcomes in women with pre-eclampsia/eclampsia. There was a relationship between high uric acid level and the risk of preterm birth, low Apgar index, IUGR, and neonatal death, but not fetal death.

AUTHOR CONTRIBUTIONS
LMT contributed to study design, data analysis, manuscript drafting, and critical discussion. NHL, PLN, and NVQH contributed to data collection, analysis, manuscript drafting, and critical discussion. LDD contributed to data analysis, manuscript drafting, and critical discussion. TQV and CNT contributed to data interpretation, manuscript drafting, and critical discussion. All authors were involved in drafting the work or revising it critically.
T A B L E 5 Multivariable logistic regression for predicted fetal/ neonatal outcomes based on uric acid threshold of 393 μmol/L.