In a groundbreaking study poised to redefine prenatal care practices, researchers have meticulously compared various first-trimester combined screening methods to predict preeclampsia within the Indonesian population. The study, led by Al Fattah, A.N., Mahindra, M.P., and Yusrika, M.U. and published in the Journal of Perinatology in 2025, offers striking insights into the efficacy of different screening algorithms, potentially altering how clinicians approach early detection and intervention for this life-threatening pregnancy complication. Preeclampsia, a hypertensive disorder affecting pregnant women globally, remains a leading cause of maternal and neonatal morbidity and mortality, particularly in low- and middle-income countries such as Indonesia.
Early screening for preeclampsia during the first trimester is a clinical priority, aiming to identify at-risk pregnancies to implement preventive treatments like low-dose aspirin. However, established screening protocols developed primarily in Western populations have shown mixed performance when applied in different ethnic and geographic contexts. This study distinctly addresses that gap by evaluating multiple combined screening strategies—including maternal history, biophysical markers, and biochemical parameters—within the Indonesian demographic framework. The researchers’ integrated methodology encompassed maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and serum biomarkers such as placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A).
Methodological rigor was evident through their prospective cohort design, enrolling a significant sample size representative of various Indonesian ethnic groups and geographic regions. By longitudinally collating clinical, hemodynamic, and serological data in the first trimester, the research cohort enabled robust statistical analyses of each screening approach’s sensitivity, specificity, positive predictive value, and overall predictive accuracy. The multi-modal screening frameworks were subjected to rigorous comparative analysis, highlighting nuances in biomarker performance linked with underlying genetic and environmental variability endemic to Indonesia.
One of the study’s pivotal findings demonstrated that the inclusion of Doppler ultrasound measurement of the uterine artery pulsatility index significantly enhances the accuracy of preeclampsia risk prediction beyond maternal history and biochemical markers alone. This hemodynamic parameter reflects impaired placental perfusion, a pathophysiological hallmark of early-onset preeclampsia, and may manifest differently across populations due to variances in vascular physiology. When coupled with serum PlGF levels—a marker of angiogenesis—screening efficacy was markedly elevated, enabling clinicians to stratify maternal risk profiles with unprecedented precision.
Interestingly, the research underscores how pregnancy-associated plasma protein-A (PAPP-A), despite its established role in aneuploidy screening, exhibited variable predictive power for preeclampsia within the Indonesian cohort. This differential performance suggests that universal biomarker thresholds may not be applicable globally, necessitating locally calibrated reference ranges and risk algorithms. Such a discovery calls for regional customization in prenatal screening protocols to mitigate false-negative and false-positive rates, thereby optimizing resource allocation in healthcare settings.
Moreover, the findings emphasize the synergistic effect of combining maternal clinical data with biophysical and biochemical markers to create an integrative risk prediction model. This multifactorial approach counters the limitations of relying on isolated parameters and addresses the complex etiology of preeclampsia, which involves immunological maladaptation, endothelial dysfunction, and genetic predisposition. The study cogently argues for an adaptive screening framework that incorporates population-specific variables and dynamically adjusts thresholds based on real-world epidemiological data.
In the context of Indonesian public health, where maternal mortality rates remain relatively high, these insights are particularly vital. The implementation of improved first-trimester screening algorithms can inform timely prophylactic interventions, reducing the incidence of severe preeclampsia and related obstetric complications such as eclampsia, preterm birth, and fetal growth restriction. Furthermore, the research highlights the logistical feasibility of integrating advanced ultrasound and biomarker assays into routine antenatal visits within Indonesia’s healthcare infrastructure, including regional hospitals and community clinics.
The research team also recognized socioeconomic and geographic disparities across Indonesia that may influence screening accessibility and outcomes. Their analysis factored in urban versus rural healthcare delivery disparities, variations in nutritional status, and environmental factors such as altitude and endemic diseases. These layers of complexity reinforce the need for comprehensive prenatal screening strategies that are not only clinically effective but also equitable and culturally sensitive.
The paper’s discussion extends to the technological and operational challenges inherent in scaling up combined screening protocols. While Doppler ultrasound and serum biomarker assays enhance predictive accuracy, their deployment requires trained personnel, advanced equipment, and consistent quality control measures. Investing in healthcare workforce training and infrastructure modernization emerges as a critical prerequisite for successful widescale implementation, ensuring that early prediction translates into meaningful clinical intervention.
From a scientific standpoint, this study fills an important void by contextualizing preeclampsia screening within the unique genetic admixture of the Indonesian population—a diverse archipelago with more than 300 distinct ethnic groups. The genetic heterogeneity potentially influences biomarker expression and vascular responses, underscoring the importance of population-tailored research. These findings contribute valuable data to the global effort aimed at refining predictive models to accommodate ethnic and geographical diversity, thereby enhancing the global applicability of screening tools.
At the molecular level, the research sheds light on the angiogenic imbalance implicated in preeclampsia pathogenesis. The pivotal role of PlGF, its interaction with anti-angiogenic factors like soluble fms-like tyrosine kinase-1 (sFlt-1), and the resulting endothelial dysfunction represent a fertile ground for novel diagnostic and therapeutic avenues. By validating PlGF-based assays in an Indonesian cohort, the study expands the evidence base, reinforcing the biomarker’s utility in diverse populations.
The study also suggests potential for integrating genetic and epigenetic markers into future screening paradigms. While such advanced molecular diagnostics were beyond the scope of the current research, the authors advocate for continued exploration of how genetic predisposition and environmental epigenetic modifications interact to influence preeclampsia susceptibility. Such integrative research may ultimately refine risk stratification algorithms and facilitate personalized prenatal care.
Importantly, this research may prompt policymakers and healthcare stakeholders in Indonesia and similar settings to reevaluate national prenatal screening guidelines. By demonstrating the superiority of combined screening approaches, especially those incorporating UtA-PI and PlGF, the study makes a compelling case for guideline updates. This could catalyze improved population health outcomes by mitigating the burden of hypertensive disorders in pregnancy.
The implications extend further, as early identification of at-risk pregnancies enables resource optimization, aligning frontline healthcare interventions with the needs of vulnerable mothers. Early preventive strategies, including low-dose aspirin prophylaxis initiated before 16 weeks gestation, are most effective when predicated on accurate risk prediction—a threshold that this study moves closer to achieving within the Indonesian context.
Finally, the publication of this comparative analysis in a high-impact perinatology journal reflects its significance in advancing obstetric medicine. The detailed insights into multicentric data, combined with rigorous statistical validation, provide a model framework for similar investigations in other ethnically diverse and resource-constrained regions globally, contributing to a broader agenda of equitable maternal health.
As the global medical community continues to grapple with the challenge of preeclampsia detection and prevention, such population-specific, integrative screening studies herald a new era of precision prenatal medicine. These insights not only promise to transform clinical pathways in Indonesia but also offer a blueprint for optimizing maternal-fetal health outcomes worldwide by tailoring screening technologies to the unique physiological and sociodemographic landscapes of diverse populations.
Subject of Research: First trimester combined screening methods for preeclampsia prediction in the Indonesian population
Article Title: Comparison of first trimester preeclampsia combined screening performances with various approaches in the Indonesian population
Article References:
Al Fattah, A.N., Mahindra, M.P., Yusrika, M.U. et al. Comparison of first trimester preeclampsia combined screening performances with various approaches in the Indonesian population. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02316-y
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41372-025-02316-y
Tags: biochemical parameters in pregnancybiophysical markers for preeclampsia screeningearly detection of pregnancy complicationsfirst trimester preeclampsia screeninghypertensive disorders in pregnancyIndonesian prenatal care practiceslow-dose aspirin for preeclampsia preventionmaternal characteristics and preeclampsia riskmaternal health in Indonesiaplacental growth factor in preeclampsiaresearch on maternal and neonatal morbidityscreening algorithms for preeclampsia