https://orcid.org/0009-0004-9478-3356
Figures
Abstract
Background
Hyperuricemia is a recognized biochemical finding in preeclampsia (PE), but the reported frequency varies across low- and middle-income countries (LMICs). A pooled estimate from LMIC settings may help clarify the extent of this finding in hospital-based populations.
Objective
To estimate the pooled prevalence of hyperuricemia among women with preeclampsia in hospital-based studies from LMICs.
Methods
A systematic review and meta-analysis was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251107624). PubMed, Scopus, Web of Science, and Lens.org were searched for observational studies published from 2010 to 2025 reporting hyperuricemia among women with preeclampsia in LMIC hospital settings. Prevalence estimates were pooled using a random-effects model with logit transformation. Heterogeneity was assessed using Cochran’s Q, Tau², and I². Sensitivity analyses included subgrouping by hyperuricemia threshold and leave-one-out analysis.
Results
Eleven studies involving 1,099 women with preeclampsia from seven LMICs were included. The pooled prevalence of hyperuricemia was 53.47% (95% CI: 45.17% to 61.58%), with low-to-moderate heterogeneity (I² = 27.47%, p = 0.204). Included studies used different diagnostic thresholds for hyperuricemia, ranging from 5.0 to 7.0 mg/dL. All studies were hospital-based, and reporting of gestational age at the time of uric acid measurement was inconsistent.
Conclusions
Hyperuricemia was common among women with preeclampsia in hospital-based LMIC studies. These findings describe prevalence only and should not be interpreted as evidence of diagnostic accuracy, prognostic performance, or clinical utility. Future studies should standardize diagnostic thresholds and report gestational timing of uric acid measurement more consistently.
Citation: Muse FA, Hakizimana T, Abdikarim S, Abdulsalam D, Warsame FD, Noor FA, et al. (2026) Prevalence of hyperuricemia in preeclampsia: A systematic review and meta-analysis of studies from low - and middle - income countries. PLoS One 21(6): e0345152. https://doi.org/10.1371/journal.pone.0345152
Editor: María Teresa Llinás, Universidad de Murcia, SPAIN
Received: September 13, 2025; Accepted: June 7, 2026; Published: June 26, 2026
Copyright: © 2026 Muse et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Preeclampsia (PE) is a multisystem hypertensive disorder of pregnancy characterized by new-onset hypertension (blood pressure ≥140/90 mmHg) after 20 weeks of gestation, often with proteinuria or end-organ damage, such as impaired liver or kidney function, thrombocytopenia, or neurological symptoms [1,2]. Severe PE (blood pressure ≥160/110 mmHg) and eclampsia, characterized by new onset seizures or coma, are critical complications [1,3]. Globally, PE affects 2%–8% of pregnancies, contributing to 76,000 maternal and 500,000 fetal or newborn deaths annually [4]. In low- and middle-income countries (LMICs), the incidence is sevenfold higher (2.8% vs. 0.4% in developed countries), accounting for significant maternal mortality (e.g., 18% in Ghana, 30.7% in Rwanda) [2,5].
Hyperuricemia, defined as serum uric acid levels ≥375 µmol/L (≥6.3 mg/dL), is a hallmark of PE, often preceding hypertension and proteinuria [2,6]. Unlike normal pregnancies, where uric acid decreases due to enhanced renal clearance, preeclamptic pregnancies show elevated levels due to reduced tubular excretion and endothelial dysfunction [7]. Uric acid may contribute to PE pathogenesis by impairing placental remodeling, inducing oxidative stress, and promoting inflammation [4,8]. Despite its potential as a cost-effective biomarker, evidence on its prevalence and clinical significance in LMICs is inconsistent, with some studies linking it to adverse outcomes (e.g., preterm birth, low birth weight) and others questioning its predictive value [9]. Given the high burden of preeclampsia in LMICs and the fragmented nature of available evidence, this study aimed to estimate the pooled prevalence of hyperuricemia among women with preeclampsia in hospital-based LMIC studies.
Although hyperuricemia in preeclampsia has been described in individual studies, especially from hospital settings, a pooled estimate focused on LMIC populations remains limited. The contribution of this review is not to establish diagnostic or prognostic utility, but to quantify how commonly hyperuricemia is reported in women with preeclampsia across LMIC hospital-based studies and to identify methodological features, including threshold variability and incomplete reporting of gestational timing, that affect interpretation of this evidence base.
Methods
Protocol and registration
This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [10] and was registered with PROSPERO (CRD420251107624). Ethical approval was not required as only published data were analyzed.
Database and search strategy
The PICO framework was used to develop the study question: Population (P): pregnant women with PE in LMIC hospitals; Intervention (I): not applicable; Comparison (C): women with or without hyperuricemia; Outcome (O): pooled prevalence of hyperuricemia in PE. A comprehensive literature search was performed using PubMed, SCOPUS, Web of Science, Lens.org, and Google Scholar of relevant studies from January 2010 to May 2025, using terms for hyperuricemia (e.g., “hyperuricemia,” “serum uric acid”), preeclampsia (e.g., “preeclampsia,” “gestational hypertension”), LMIC settings (e.g., “low-income,” “Sub-Saharan Africa”), and pregnancy (e.g., “pregnant women”). Search strings are provided in S1 File. No language restrictions were applied during the search. However, only studies published in English or available in English translation were included in the final review.
Study selection
Eligible studies were observational, peer-reviewed, conducted in LMIC hospitals, and reported primary data on hyperuricemia prevalence in PE. Exclusions included randomized clinical trials, case reports, systematic and narrative reviews, non-LMIC or community-based studies, and non-English texts without translations. Two reviewers independently screened titles and abstracts using Rayyan, with full-text assessments by a third reviewer to resolve disputes.
Data extraction and quality assessment
Data were extracted using a standardized Excel form, capturing study characteristics, sample size, hyperuricemia definition, number of hyperuricemia cases, and prevalence estimates. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist, with scores ≥6 indicating high quality (S1 Table).
Statistical analysis
Prevalence proportions were logit-transformed and pooled using a random-effects model with restricted maximum likelihood estimation in Jamovi v2.6.44 using the MAJOR module. The pooled estimate was back-transformed and presented as a percentage with 95% confidence intervals. Statistical heterogeneity was assessed using Cochran’s Q, Tau², and I² statistics. Prespecified subgroup analysis was performed according to the diagnostic threshold used to define hyperuricemia. Leave-one-out sensitivity analysis was also conducted to evaluate the influence of individual studies on the pooled prevalence estimate and heterogeneity. Because this review synthesized single-group prevalence estimates rather than comparative intervention effects, formal assessment of publication bias and small-study effects was interpreted cautiously and treated as exploratory.
Results
Study selection
A total of 386 articles were initially obtained from the selected databases (PubMed: 36, Scopus: 75, Web of Science: 77, Lens.org: 198). A total of 82 duplicates were removed. This resulted in 304 titles and abstracts that were screened. Twenty-one articles were sought and underwent eligibility screening. Eleven studies were included in the final systematic review (Fig 1). The final studies included a total population of 1,099 women with PE from China, Nigeria, Ghana, Vietnam, Uganda, Ethiopia, and Pakistan. The prevalence of hyperuricemia in PE ranged from 36.1 to 75% (Table 1).
Meta-analysis results
The random-effects meta-analysis yielded a pooled prevalence of hyperuricemia in preeclampsia of 53.47% (95% CI: 45.17% to 61.58%) (Table 2). Between-study heterogeneity was low to moderate (Tau² = 0.0854; I² = 27.47%; Q = 13.367, df = 10, p = 0.204) (Table 3). The corresponding forest plot is shown in Fig 2.
The forest plot displays prevalence estimates and 95% confidence intervals for each study, with the pooled prevalence of 53.47%. Study weights reflect sample size and precision, with low-to-moderate heterogeneity (I² = 27.47%) evident from the alignment of confidence intervals.
Publication bias assessment
Publication bias assessments showed no significant bias. The fail-safe N was 0 (p = not reported), indicating limited protection against bias indicating that 5 additional studies with null findings would be needed to alter the significance of our pooled prevalence estimate. However, Kendall’s Tau (0.330, p = 0.160) and Egger’s regression (1.139, p = 0.255) suggested no significant bias (Fig 3, Table 4).
The funnel plot demonstrates the study effect sizes (logit-transformed prevalence) plotted against standard errors. The symmetric distribution around the pooled estimate suggests minimal publication bias, corroborated by non-significant Egger’s (p = 0.255) and Kendall’s Tau (p = 0.160) tests.
Exploratory small-study effect assessments were examined cautiously because the analysis pooled prevalence estimates rather than comparative effect sizes. These analyses were not considered central to interpretation of the main findings and were therefore not used to support firm conclusions regarding publication bias.
Equivalence testing
Two one-sided tests (TOST) for equivalence with bounds of ±0.5 logit units were significant (Z = −2.643, p = 0.004), indicating the pooled effect is statistically equivalent to zero within these bounds. The null hypothesis test was non-significant (Z = 0.817, p = 0.414; Table 5).
Regional variation
Prevalence varied by region, with West Africa (50.0–75.0%) and East Africa (38.7–70.6%) showing higher rates of hyperuricemia than South Asia (50.0%) and Southeast Asia (36.1%; Table 6). These descriptive differences should be interpreted cautiously because the number of studies per region was small and some regions were represented by only one study
Study quality assessment
Four studies were rated high quality (JBI score ≥6), with robust methodology and clear definitions. Six studies were moderate due to smaller sample sizes or methodological limitations. High-quality studies had larger sample sizes (>100) and robust methodology, while moderate-quality studies had smaller samples or less rigorous designs, potentially affecting precision (Table 7).
Discussion
This systematic review and meta-analysis found that hyperuricemia was reported in approximately half of women with preeclampsia in hospital-based LMIC studies, with a pooled prevalence of 53.47% (95% CI: 45.17% to 61.58%). This finding indicates that elevated serum uric acid is a common biochemical feature among women with preeclampsia in these settings. However, because this review synthesized prevalence data only, the findings should be interpreted descriptively and should not be taken as evidence of diagnostic accuracy, prognostic value, or clinical effectiveness.
Despite differences in sample sizes, designs, and diagnostic thresholds for hyperuricemia (ranging from >5.0 to ≥7.0 mg/dL), the meta-analysis exhibited low-to-moderate heterogeneity (I² = 26.46%, p = 0.215), suggesting relative consistency across included studies. This statistical homogeneity enhances the reliability of the pooled estimate and affirms the robustness of the prevalence findings across diverse LMIC populations.
The methodological quality of included studies was generally moderate to high, with four studies scoring ≥6 on the JBI scale. Most studies applied standard clinical definitions of PE and measured serum uric acid through laboratory assays. However, all studies were conducted in inpatient hospital settings, which may skew prevalence estimates toward more severe or referred cases, possibly underrepresenting the true population-level burden.
Prevalence varied geographically, with West Africa (50.0–75.0%) and East Africa (38.7–70.6%) showing higher rates than South Asia (50.0%) and Southeast Asia (36.1%). The highest prevalence was reported in Nigeria (75.0%) [6], while the lowest was in Vietnam (36.1%) [3]. These regional differences may reflect variations in clinical criteria and diagnostic protocols, or genetic susceptibility [15]. These regional discrepancies are consistent with earlier findings that suggest differences in the burden and severity of PE across global regions, particularly in women of African ancestry and specifically in Nigeria where PE is the leading cause of maternal mortality [5,16].
The findings from individual studies further align with the pooled result. For instance, Ugwuanyi et al. reported elevated uric acid levels in preeclamptic women compared to normotensive controls, supporting the association between hyperuricemia and PE [12]. Similarly, Hassen et al. found significantly higher mean uric acid concentrations in preeclamptic women (6.17 ± 1.04 mg/dL) versus controls (3.65 ± 1.19 mg/dL, p < 0.001), with a prevalence rate of 70.6% [1]. These consistent findings across studies affirm that hyperuricemia is a common biochemical abnormality in preeclamptic pregnancies in LMICs.
The highest recorded prevalence was observed in Nigeria (75.0%) [6], and the lowest in Vietnam (36.1%) [3], highlighting possible differences in disease severity, healthcare access, or baseline maternal health [4]. While focused more globally, this data also highlights the relevance of hyperuricemia as a marker of PE severity, particularly in early-onset disease. The current LMIC-specific findings address a critical evidence gap by providing focused data from settings where the burden is high and diagnostic resources are limited.
Taken together, the pooled prevalence of 53.47% from this meta-analysis confirms that hyperuricemia is a common finding in preeclamptic pregnancies across LMICs. This finding is in line with the pathophysiological understanding that hyperuricemia in PE results from reduced renal clearance and increased oxidative stress [1,12]. Moreover, Khurshid et al. [17] and Corominas et al. [4] have reported the diagnostic utility of serum uric acid, though such aspects extend beyond the primary scope of prevalence-focused analysis.
The main contribution of this review is to synthesize hospital-based evidence from LMIC settings, where the burden of preeclampsia is high and published data are often fragmented across individual studies. Rather than establishing a new biological or clinical role for uric acid, this review quantifies how commonly hyperuricemia is reported in women with preeclampsia in these settings and highlights key methodological limitations in the available literature.
The low-to-moderate heterogeneity suggests that reported prevalence was not highly inconsistent across included studies. Nevertheless, study-level differences in design, sample size, and diagnostic thresholds may still have influenced individual prevalence estimates. In particular, the threshold used to define hyperuricemia ranged from 5.0 to 7.0 mg/dL [9], which limits direct comparability across studies and highlights the need for more standardized reporting.
Regional variation was notable, with higher rates in West and East Africa [1,6] compared to Southeast Asia [3]. Study designs also influenced precision, with prospective cohorts such as Wehlie et al. yielding more consistent estimates than retrospective studies [8]. Inconsistent gestational timing may have further contributed to variations in prevalence reporting, as levels of hyperuricemia have been shown to increase with gestational weeks [4], while others have demonstrated a negative correlation [2,11].
An important issue in interpreting the pooled prevalence is the timing of serum uric acid measurement during pregnancy. Uric acid levels vary physiologically across gestation and may rise further with increasing disease severity. Because most included studies did not report gestational age or trimester at the time of measurement, it was not possible to determine whether timing contributed to the observed prevalence or to between-study variability. This limitation is particularly relevant because all included studies were hospital-based and may overrepresent women presenting later in pregnancy, after referral, or with more severe disease.
This meta-analysis is the first to synthesize the prevalence of hyperuricemia in PE within hospitals across LMICs, addressing a critical evidence gap. It includes studies from geographically diverse LMICs, enhancing the generalizability of findings within these settings. The analysis employed random-effects modeling and the TOST approach for rigorous statistical evaluation. A comprehensive assessment of publication bias using multiple tests and a funnel plot (Fig 3) confirmed minimal bias, strengthening confidence in the results.
Generalizability is also limited by the geographic distribution of included studies. Most studies were from Africa and Asia, and no eligible studies from Latin America were identified. Accordingly, the findings should not be interpreted as representative of all LMIC settings globally.
This review has several limitations. First, all included studies were hospital-based, which may overrepresent referred, later-presenting, or more severe cases and may therefore limit generalizability beyond inpatient settings. Second, diagnostic thresholds for hyperuricemia varied across studies, reducing comparability of prevalence estimates. Third, gestational age at the time of serum uric acid measurement was inconsistently reported, preventing trimester-specific analysis and limiting interpretation because uric acid levels vary across pregnancy. Fourth, most studies did not report severity-specific or outcome-specific data, so this review could not assess associations with maternal outcomes, disease severity, diagnostic performance, or prognostic value. Finally, the geographic representation of studies was limited, with evidence drawn mainly from Africa and Asia.
Implications for research and reporting
This review shows that hyperuricemia is commonly reported among women with preeclampsia in hospital-based LMIC studies. However, these findings do not establish whether serum uric acid has diagnostic accuracy, prognostic value, or usefulness for clinical decision-making. The main implications are methodological: future studies should adopt standardized thresholds for hyperuricemia, report gestational age at the time of testing, distinguish disease severity where possible, and evaluate clinical outcomes using prospective designs.The 52.00% prevalence is high and supports routine uric acid testing in LMICs antenatal care protocols. Hyperuricemia’s high sensitivity (65%) [17] and negative predictive value (99.5%) [4] make it a valuable tool for identifying high-risk preeclamptic patients, enabling timely interventions [8]. Policymakers should prioritize affordable uric acid assays and strengthen antenatal care infrastructure to reduce preeclampsia-related morbidity and mortality in LMICs. Training healthcare providers to interpret uric acid levels in the context of regional thresholds (e.g., > 6.0 mg/dL) could enhance risk stratification and resource allocation.
Future research directions
This review highlights key research priorities to advance understanding of hyperuricemia in PE within LMICs. Standardizing hyperuricemia thresholds would enhance comparability and clinical relevance. Longitudinal studies are needed to explore how changes in uric acid levels relate to adverse outcomes such as preterm birth and fetal growth restriction. Future meta-analyses should focus on specific clinical outcomes to strengthen the evidence base for guidelines. Broader inclusion of underrepresented LMIC regions would improve generalizability, while therapeutic trials targeting uric acid reduction could uncover new interventions for improving maternal and perinatal outcomes.
Conclusions
This systematic review and meta-analysis found that hyperuricemia is common among women with preeclampsia in hospital-based LMIC studies. The review provides a pooled estimate of prevalence, but it does not establish diagnostic accuracy, prognostic performance, or clinical utility. Interpretation should remain cautious because of variation in diagnostic thresholds, limited regional representation, and inconsistent reporting of gestational timing. Future research should standardize measurement and reporting and evaluate clinical and outcome-based associations prospectively.
Supporting information
S1 Table. Joanna Briggs Institute (JBI) Quality Scores.
https://doi.org/10.1371/journal.pone.0345152.s002
(DOCX)
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