Uric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery

doi:10.1016/j.ajog.2005.06.066

American Journal of Obstetrics and Gynecology

Volume 194, Issue 1, January 2006, Pages 160.e1-160.e8

https://doi.org/10.1016/j.ajog.2005.06.066 Get rights and content

Objective

We investigated changes in serum uric acid across pregnancy in women with gestational hyperuricemia at delivery, with and without preeclampsia, compared with normal pregnant and women with preeclampsia without gestational hyperuricemia.

Study design

This was a nested case-control study of 116 controls, 27 women with preeclampsia with predelivery hyperuricemia, 37 women with preeclampsia without predelivery hyperuricemia, and 35 women with gestational hypertension with hyperuricemia at delivery but without proteinuria. Serum uric acid and creatinine was measured across pregnancy.

Results

Women with predelivery hyperuricemia, with and without preeclampsia, had increased uric acid concentrations across pregnancy compared with controls, after 25 weeks' gestation compared with women with preeclampsia without predelivery hyperuricemia. Adjusting for differences in glomerular filtration by serum creatinine accounted for part but not all of the increase in serum uric acid among women with preeclampsia and predelivery hyperuricemia.

Conclusions

Among women with hyperuricemia at delivery, elevations in uric acid occur early. Multiple mechanisms may contribute to increased uric acid including changes in renal function.

Section snippets

Study population

We conducted a nested case-control study of 215 women enrolled in an ongoing investigation of preeclampsia at Magee-Womens Hospital (Pittsburgh, PA). The study was approved by the institutional review board and informed consent was obtained from all subjects. Women were excluded from the study if they had multiple fetuses, chronic hypertension, renal disease, diabetes, other preexisting medical conditions, previous preeclampsia, or history of illicit drug use. Subjects were matched for maternal

Results

The demographic and clinical characteristics of the study subjects are presented in Table I. Women with preeclampsia (HP and HPU) had increased average blood pressures before 20 weeks of gestation, compared with control pregnant women and HU pregnant women. In addition, women with HPU preeclampsia delivered earlier and their infant's birth weight and birth weight centile were decreased, compared with control pregnant women, the HP preeclamptic women, and the HU pregnant women. Interestingly,

Comment

Uric acid is the end product of purine metabolism; it is synthesized by the enzyme xanthine oxidase, and in humans most circulating uric acid is produced in the liver. During uncomplicated pregnancies serum uric acid concentrations decrease by 25% to 35% in early pregnancy but then increase throughout pregnancy until toward the end of pregnancy when they approach nonpregnant values.¹² It is proposed that these pregnancy-mediated changes in serum uric acid are primarily the result of altered

References (27)

R.B. Ness et al.
Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications
Am J Obstet Gynecol
(1996)
J.M. Slemons et al.
The uric acid content of maternal and fetal blood
J Biol Chem
(1917)
K.H. Lim et al.
The clinical utility of serum uric acid measurements in hypertensive diseases of pregnancy
Am J Obstet Gynecol
(1998)
C.W. Redman et al.
Plasma-urate measurements in predicting fetal death in hypertensive pregnancy
Lancet
(1976)
L.C. Chappell et al.
A longitudinal study of biochemical variables in women at risk of preeclampsia
Am J Obstet Gynecol
(2002)
A. Many et al.
Hyperuricemia and xanthine oxidase in preeclampsia revisited
Am J Obstet Gynecol
(1996)
H.E. Fadel et al.
Hyperuricemia in pre-eclampsia. A reappraisal
Am J Obstet Gynecol
(1976)
R.J. Johnson et al.
Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease
Am J Kidney Dis
(1999)
C.W. Redman et al.
The pathogenesis of pre-eclampsia
Gynecol Obstet Fertil
(2001)
J.M. Roberts
Pregnancy related hypertension

L. Duley

Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean

Br J Obstet Gynaecol

(1992)

R.L. Goldenberg et al.

Prevention of premature birth

N Engl J Med

(1998)

Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy

Am J Obstet Gynecol

(2000)

Cited by (123)

Integrated metabolomics and machine learning approach to predict hypertensive disorders of pregnancy
2023, American Journal of Obstetrics and Gynecology MFM
Citation Excerpt :
Deoxyadenosine levels showed a negative correlation between uric acid and protein. Uric acid, the product of purine metabolism, is found to be elevated in women with HDP.39,40 Even though many studies show that uric acid is associated with HDP, its use as a marker for the diagnosis of hypertension disorders is not globally established.
Hypertensive disorders of pregnancy account for 3% to 10% of maternal-fetal morbidity and mortality worldwide. This condition has been considered one of the leading causes of maternal deaths in developing countries, such as India.
This study aimed to discover hypertensive disorders of pregnancy–specific candidate urine metabolites as markers for hypertensive disorders of pregnancy by applying integrated metabolomics and machine learning approaches.
The targeted urinary metabolomics study was conducted in 70 healthy pregnant controls and 133 pregnant patients having hypertension as cases. Hypertensive disorders of pregnancy–specific metabolites for disease prediction were further extracted using univariate and multivariate statistical analyses. For machine learning analysis, 80% of the data were used for training (79 for hypertensive disorders of pregnancy and 42 for healthy pregnancy) and validation (27 for hypertensive disorders of pregnancy and 14 for healthy pregnancy), and 20% of the data were used for test sets (27 for hypertensive disorders of pregnancy and 14 for healthy pregnancy).
The statistical analysis using an unpaired t test revealed 44 differential metabolites. Pathway analysis showed mainly that purine and thiamine metabolism were altered in the group with hypertensive disorders of pregnancy compared with the healthy pregnancy group. The area under the receiver operating characteristic curves of the 5 most predominant metabolites were 0.98 (adenosine), 0.92 (adenosine monophosphate), 0.89 (deoxyadenosine), 0.81 (thiamine), and 0.81 (thiamine monophosphate). The best prediction accuracies were obtained using 2 machine learning models (95% for the gradient boost model and 98% for the decision tree) among the 5 used models. The machine learning models showed higher predictive performance for 3 metabolites (ie, thiamine monophosphate, adenosine monophosphate, and thiamine) among 5 metabolites. The combined accuracies of adenosine from all models were 98.6 in the training set and 95.6 in the test set. Moreover, the predictive performance of adenosine was higher than other metabolites. The relative feature importance of adenosine was also observed in the decision tree and the gradient boost model.
Among other metabolites, adenosine and thiamine metabolites were found to differentiate participants with hypertensive disorders of pregnancy from participants with healthy pregnancies; hence, these metabolites can serve as a promising noninvasive marker for the detection of hypertensive disorders of pregnancy.
Maternal serum uric acid, creatinine and blood urea levels in the prediction of pre-eclampsia among pregnant women attending ANC and delivery services at Bahir Dar city public hospitals, northwest Ethiopia: A case-control study
2022, Heliyon
Citation Excerpt :
Some reports showed that elevated maternal serum uric acid concentration could be used for the prediction of adverse fetal outcomes such as; preterm labor, low birth weight, neonatal death [14, 15, 16] and intrauterine fetal death (IUFD) [17]. Higher serum uric acid concentration in preeclamptic women occurs primarily due to a reduction in glomerular filtration rate that leads to endothelial dysfunction or it may be due to an increase in xanthine oxidase activity which could be served as the biomarkers of PE [18]. Creatinine is the metabolic end product of creatine.
Pre-eclampsia (PE) is a metabolic disorder that adversely affects the lives of mother and their infants. Even though, several studies have been conducted on PE, no effective diagnostic and therapeutic agents were developed so far. Hence, this study was designed to evaluate serum uric acid, blood urea and creatinine levels in the prediction of PE.
A hospital-based case-control study was conducted among pregnant women. A simple random sampling technique was applied to select study participants. The socio-demographic and clinical data were collected using an interview-administered questionnaire. Serum samples were used to determine the maternal uric acid, urea and creatinine levels via an automated chemistry analyzer. Independent sample t-test, Pearson correlation test and receiver operating characteristic (ROC) curve analysis were performed to check the association and diagnostic accuracy of variables to PE.
The mean ages (in years) of the case and control groups were 27.98 ± 5.64 and 27.33 ± 4.45, respectively. The mean serum uric acid and blood urea levels were significantly higher in pre-eclamptic women than in normotensive pregnant women (6.27 ± 0.20 vs 4.43 ± 0.15, and 8.50 ± 3.99 vs 5.67 ± 2.19), respectively but the serum creatinine level is non-significantly increased in cases as compared to controls (0.70 ± 0.05 vs 0.50 ± 0.01). The areas under the ROC curve of serum uric acid, creatinine and blood urea levels were 0.785, 0.735 and 0.764 (sensitivity: 69%, 60.7%, 67.9%; specificity: 73.8%, 75%, 71.4%) with the cutoff points of ≥5.25 mg/dL, ≥0.565 mg/dL and ≥6.5 mg/dL, respectively.
In this study, we observed a significantly higher concentration of serum uric acid and blood urea values in pre-eclampsia as compared with normotensive pregnant women. Therefore, this suggested that serum uric acid; blood urea and creatinine values can be associated with PE. Moreover, serum uric acid, blood urea and creatinine levels could be carefully utilized as a diagnostic marker for PE, but their inclusion in routine diagnostic test to PE requires large-scale multi-center prospective studies that corroborate our findings.
Cardiometabolic Antecedents of Preeclampsia
2021, Chesley’s Hypertensive Disorders in Pregnancy
In this chapter, we advance the concept that maternal cardiometabolic factors interact with placental factors to promote inflammation, endothelial cell dysfunction, and the maternal preeclampsia syndrome. We also summarize evidence suggesting that the same underlying factors that contribute to preeclampsia also increase a woman's risk of developing cardiovascular disease (CVD) in later life. The majority of data on candidate factors contributing to preeclampsia have been retrospective in nature, relying on measurements conducted either in early pregnancy, prior to onset of clinical symptoms of preeclampsia, or months to years postpregnancy after clinical symptoms of preeclampsia have resolved (and in the absence of a placenta). Because of the logistical difficulties of recruiting preconception cohorts of women, few studies have investigated cardiovascular risk factors before pregnancy in relation to risk of preeclampsia. Nevertheless, a substantial body of literature on prepregnancy cardiometabolic antecedents of preeclampsia is now available. This updated chapter therefore surveys the available data on cardiometabolic risk factors before conception in relation to risk of preeclampsia. There is evidence for prepregnancy factors potentially related to, and unrelated to, the metabolic syndrome consistent with a heterogeneous etiology of preeclampsia. These data support the hypothesis that chronic, underlying factors present before pregnancy, including metabolic and cardiac antecedents, contribute to both risk of preeclampsia and risk of later-life CVD.
Epidemiology of Hypertensive Disorders in Pregnancy
2021, Chesley’s Hypertensive Disorders in Pregnancy
The epidemiologic literature relating to hypertension in pregnancy has grown exponentially since Chesley’s 20-page chapter in the first edition of his 1978 treatise. New data characterize the occurrence, risk factors, predictors, natural history, and molecular epidemiology of preeclampsia. Those epidemiologic findings and the methods used to conduct them are critically assessed in this updated revision of the chapter. New evidence indicating that preeclampsia is a syndrome secondary to multiple pathophysiological pathways is presented. We address the heterogeneity among risk factors and clinical predictors that serve as “markers” of the disorder, but also consider the possibility that preeclampsia is a potential cause of future cardiovascular disease.
Oral L-glutamine rescues fructose-induced poor fetal outcome by preventing placental triglyceride and uric acid accumulation in Wistar rats
2020, Heliyon
Metabolic adaptation of pregnant mothers is crucial for placental development and fetal growth/survival. However, evidence exists that indiscriminate consumption of fructose-enriched drink (FED) during pregnancy disrupts maternal-fetal metabolic tolerance with attendant adverse fetal outcomes. Glutamine supplementation (GLN) has been shown to exert a modulatory effect in metabolic disorders. Nevertheless, the effects of GLN on FED-induced poor fetal outcome, and in particular the impacts on placental uric acid/lipid accumulation are unknown. The present study was conducted to test the hypothesis that oral GLN improves fetal outcome by attenuating placental lipid accumulation and uric acid synthesis in pregnant rats exposed to FED.
Pregnant Wistar rats (160–180 g) were randomly allotted to control, GLN, FED and FED + GLN groups (6 rats/group). The groups received vehicle by oral gavage, glutamine (1 g/kg) by oral gavage, fructose (10%; w/v) and fructose + glutamine, respectively, through gestation.
Data showed that FED during pregnancy caused placental inefficiency, reduced fetal growth, and caused insulin resistance with correspondent increase in fasting blood glucose and plasma insulin. FED also resulted in an increased placental triglyceride, total cholesterol and de novo uric acid synthesis by activating adenosine deaminase and xanthine oxidase activities. Moreover, FED during pregnancy led to increased lipid peroxidation, lactate production with correspondent decreased adenosine and glucose-6-phosphate dehydrogenase-dependent antioxidant defense. These alterations were abrogated by GLN supplementation.
These findings implicate that high FED intake during pregnancy causes poor fetal outcome via defective placental uric acid/triglyceride-dependent mechanism. The findings also suggest that oral GLN improves fetal outcome by ameliorating placental defects through suppression of uric acid/triglyceride accumulation.
Predictive value of serum uric acid levels for adverse maternal and perinatal outcomes in pregnant women with high blood pressure. A systematic review and meta-analysis
2020, European Journal of Obstetrics and Gynecology and Reproductive Biology
High serum uric acid seems to be associated with pre-eclampsia. The expected utility of uric acid is related to the probability of occurrence of maternal and neonatal complications. We evaluated the accuracy of uric acid in predicting adverse maternal and perinatal outcomes in pregnant women with high blood pressure.
We performed an electronic search for studies evaluating the accuracy of high serum uric acid levels in pregnant women with high blood pressure. The assessment of risk of bias was performed using the QUIPS tool. For each included study, we collected data about study characteristics and diagnostic test accuracy to construct 2 × 2 tables. Pooled sensitivity (Se), specificity (Sp) and diagnostic odds ratio (DOR) were estimated using a bivariate model. Grading the quality of the evidence was assessed using the GRADE approach.
Twenty-one studies, testing more than 6,000 women, met the inclusion criteria. The majority of studies were at low risk of bias. Ten studies evaluated the role of serum uric acid to predict pre-eclampsia, the pooled Se was 0.74 (95%CI 0.71-0.77), Sp was 0.66 (95%CI 0.63-0.68), and DOR was 9.67 (95%CI 4.57-20.47). The overall quality of evidence was evaluated as low. The GRADE rating was downgraduate for risk of bias and inconsistency.
No robust evidence currently exists to suggest that uric acid measurement is useful in predicting maternal and perinatal adverse outcomes.

View all citing articles on Scopus

Supported by National Institutes of Health Grants 5 P01 HD30367 and 5 M01-RR00056.

Supplemental material available at: www.ajog.org.

View full text

General Obstetrics and Gynecology: ObstetricsUric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery

Objective

Study design

Results

Conclusions

Section snippets

Study population

Results

Comment

Am J Obstet Gynecol

J Biol Chem

Am J Obstet Gynecol

Lancet

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Kidney Dis

Gynecol Obstet Fertil

Pregnancy related hypertension

Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean

Br J Obstet Gynaecol

Prevention of premature birth

N Engl J Med

Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy

Am J Obstet Gynecol

General Obstetrics and Gynecology: Obstetrics
Uric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery