Performance of the FMF First-Trimester Preeclampsia Screening Model and Aspirin Prophylaxis Outcomes in Vietnam: A Prospective Cohort Study

Performance of the FMF First-Trimester Preeclampsia Screening Model and Aspirin Prophylaxis Outcomes in Vietnam: A Prospective Cohort Study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 20 March 2026 V1 Latest version Share on Performance of the FMF First-Trimester Preeclampsia Screening Model and Aspirin Prophylaxis Outcomes in Vietnam: A Prospective Cohort Study Authors : Bui Minh Cuong , Truong Huu Cuong 0009-0007-8304-6096 [email protected] , Nguyen Thanh Mai , Nguyen Thu Huong , Vu Thi Huyen , and Do Duy Long Authors Info & Affiliations https://doi.org/10.22541/au.177399395.57227360/v1 168 views 51 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Early identification of women at high risk of preeclampsia allows timely preventive interventions, particularly aspirin prophylaxis. The first-trimester screening model developed by the Fetal Medicine Foundation (FMF) combines maternal characteristics with biophysical and biochemical markers to improve prediction accuracy. Objective: To evaluate the performance of the FMF first-trimester screening model for preeclampsia and to assess pregnancy outcomes following aspirin prophylaxis in high-risk women. Methods: This prospective cohort study included 1,187 singleton pregnancies at 11 weeks 3 days to 13 weeks 6 days of gestation who underwent first-trimester preeclampsia screening at Quang Ninh Obstetrics and Pediatrics Hospital, Vietnam, between November 2023 and November 2025. Screening was performed using the FMF algorithm incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF). Women identified as high risk received aspirin prophylaxis. Pregnancy and neonatal outcomes were subsequently analyzed. Results: Among 1,187 screened pregnancies, 84 women (7.1%) were classified as high risk for preeclampsia. Each 1-mmHg increase in MAP was associated with an approximately 12.5% increase in the risk of preeclampsia, while each 0.1-unit increase in UtA-PI increased the risk by approximately 27.8%. Conversely, each 1 pg/mL decrease in PlGF was associated with a 7.0% increase in risk. The overall incidence of preeclampsia was 0.8% (9/1,187), with 66.7% of cases occurring in the high-risk group. No cases of early-onset preeclampsia (<34 weeks) were observed, and most cases occurred at ≥37 weeks and were non-severe. Women who developed preeclampsia had lower gestational age at delivery and lower neonatal birth weight. Intrauterine growth restriction and neonatal intensive care unit admission were more frequent among pregnancies complicated by preeclampsia and among those classified as high risk. Conclusion: First-trimester screening using the FMF model combined with early aspirin prophylaxis in high-risk women was associated with favorable maternal and neonatal outcomes. This strategy appears feasible and may be suitable for broader implementation in routine obstetric care in Vietnam. 1. INTRODUCTION Preeclampsia is a multisystem disorder of pregnancy characterized by new-onset hypertension and organ dysfunction after 20 weeks of gestation. It affects approximately 2–8% of pregnancies worldwide and remains a major cause of maternal and perinatal morbidity and mortality, particularly in low- and middle-income countries [1]. Hypertensive disorders of pregnancy are responsible for a substantial proportion of maternal deaths globally and are also associated with adverse perinatal outcomes, including preterm birth, fetal growth restriction, and stillbirth [2]. The pathophysiology of preeclampsia is complex and is believed to involve abnormal placentation, impaired trophoblastic invasion of the spiral arteries, and endothelial dysfunction. These abnormalities result in reduced uteroplacental perfusion and an imbalance between angiogenic and anti-angiogenic factors, including decreased placental growth factor (PlGF) [3]. Because clinical manifestations usually appear in the second half of pregnancy, early identification of women at high risk has become an important strategy for prevention and management. In recent years, several screening models have been developed to predict preeclampsia in early pregnancy. Among these, the screening algorithm proposed by the Fetal Medicine Foundation (FMF) has gained widespread attention. This model combines maternal demographic characteristics with biophysical and biochemical markers, including mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and maternal serum placental growth factor (PlGF) [4]. Previous studies have demonstrated that this combined screening approach can achieve high detection rates for early-onset preeclampsia with relatively low false-positive rates [5]. Early identification of high-risk pregnancies allows the implementation of preventive strategies such as low-dose aspirin. Evidence from the Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial demonstrated that administration of low-dose aspirin initiated before 16 weeks of gestation significantly reduced the incidence of preterm preeclampsia among women identified as high risk through first-trimester screening [6]. Despite the growing evidence supporting first-trimester screening for preeclampsia, most validation studies have been conducted in European populations. Data regarding the performance and feasibility of the FMF screening model in Southeast Asian populations, including Vietnam, remain limited. Differences in maternal characteristics and healthcare systems may influence the predictive performance of screening models. Therefore, this study aimed to evaluate the performance of first-trimester preeclampsia screening using the FMF model and to assess the outcomes of aspirin prophylaxis among high-risk pregnant women at Quang Ninh Obstetrics and Pediatrics Hospital. 2. MATERIALS AND METHODS 2.1 Study design and setting This study was designed as a prospective observational study with longitudinal follow-up. It was conducted at Quang Ninh Obstetrics and Pediatrics Hospital, a tertiary maternity care center in Quang Ninh Province, Vietnam. The study was carried out from November 2023 to November 2025. All eligible pregnant women attending routine antenatal care during the study period were invited to participate. 2.2 Study population Inclusion criteria Pregnant women were eligible for inclusion if they met the following criteria: • Singleton pregnancy • Gestational age between 11 weeks 3 days and 13 weeks 6 days • Live fetus confirmed by ultrasound • No detectable fetal structural abnormalities at the time of screening • Willingness to participate and provide written informed consent • Availability for follow-up until delivery • No contraindications to the use of low-dose aspirin Exclusion criteria Participants were excluded from the study if they had: • Miscarriage, preterm birth, or stillbirth unrelated to preeclampsia or its complications • Eclampsia or complications of preeclampsia not relevant to the screening outcome • Non-compliance with low-dose aspirin prophylaxis after being identified as high risk for preeclampsia • Incomplete clinical data or loss to follow-up 2.3 Sample size and sampling method The required sample size was calculated using the formula for estimating a single population proportion. The significance level was set at α = 0.05. The expected prevalence of preeclampsia was assumed to be p = 0.038, based on the study by Tran Manh Linh (2020)[7], and the desired absolute precision was d = 0.011. Based on these parameters, the minimum required sample size was 1,160 pregnant women. At the end of the study period, 1,187 pregnant women met all inclusion criteria and none of the exclusion criteria and were therefore included in the final analysis. 2.4 Study procedure Eligible pregnant women underwent first-trimester screening for preeclampsia during routine antenatal visits. Maternal demographic and clinical information was collected using a standardized data collection form. Maternal height and weight were measured to calculate body mass index (BMI). Blood pressure measurements were obtained from both arms using a validated automated blood pressure device according to a standardized protocol after the participant had rested for at least 5 minutes in a seated position. Mean arterial pressure (MAP) was calculated based on systolic and diastolic blood pressure values. Ultrasound examination was performed to determine crown–rump length (CRL) for gestational age assessment. Bilateral uterine artery Doppler measurements were obtained to determine the uterine artery pulsatility index (UtA-PI). Venous blood samples were collected for the measurement of placental growth factor (PlGF) concentrations. The individual risk of developing preeclampsia was calculated using the algorithm provided by the Fetal Medicine Foundation (FMF), which integrates maternal characteristics, mean arterial pressure, uterine artery Doppler indices, and PlGF levels. All participants received counseling regarding the screening results and were followed prospectively until delivery to evaluate pregnancy outcomes. 2.5 Study variables Maternal characteristics Maternal variables collected included: • Maternal age • Body mass index (BMI) • Gravidity and parity • Method of conception (spontaneous or in vitro fertilization) • Obstetric history • Pre-existing medical conditions Screening parameters The screening parameters included: • Mean arterial pressure (MAP) • Uterine artery pulsatility index (UtA-PI) • Placental growth factor (PlGF) concentration Outcomes Primary outcomes Estimated risk of preeclampsia according to the FMF screening model Occurrence of preeclampsia during pregnancy Secondary outcomes • Gestational age at delivery • Neonatal birth weight • Other pregnancy and neonatal outcomes 2.6 Outcome definition Preeclampsia was diagnosed according to current international obstetric guidelines. The diagnosis was based on the development of new-onset hypertension after 20 weeks of gestation accompanied by proteinuria or evidence of maternal organ dysfunction. The risk of preeclampsia in early pregnancy was estimated using the combined screening model developed by the Fetal Medicine Foundation, which integrates maternal characteristics, mean arterial pressure, uterine artery Doppler measurements, and first-trimester PlGF levels. 2.7 Statistical analysis All data were entered into Microsoft Excel and subsequently analyzed using SPSS statistical software. Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR), depending on the distribution of the data. Categorical variables were presented as frequencies and percentages. Comparisons between groups were performed using appropriate statistical tests, including the chi-square test or Fisher’s exact test for categorical variables and the independent t-test or Mann–Whitney U test for continuous variables. Logistic regression analysis was used to identify potential predictors of preeclampsia. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the screening parameters. The area under the ROC curve (AUC), sensitivity, and specificity were calculated. A p-value < 0.05 was considered statistically significant. 2.8 Ethical considerations The study protocol was reviewed and approved by the Biomedical Research Ethics Committee of Quang Ninh Obstetrics and Pediatrics Hospital. All participants were informed about the objectives, procedures, potential benefits, and risks of the study prior to enrollment. Written informed consent was obtained from each participant. All personal information was kept strictly confidential and used solely for research purposes. 3. RESULTS From November 2023 to November 2025, a total of 2283 pregnant women underwent preeclampsia (PE) screening at 11 – 13+6 weeks of gestation at Quang Ninh Obstetrics and Pediatrics Hospital. Among them, 1335 pregnant women agreed to participate in the study. After excluding 41 cases due to stillbirth, pregnancy termination, miscarriage, or preterm birth not related to preeclampsia, and 107 cases lost to follow-up, a total of 1187 pregnant women met the eligibility criteria and were included in the analysis. Study procedure flowchar: Eligible pregnant women n = 2283 ↓ Pregnancy women agree n = 1335 ↓ Exclude( stillbirth, termination, miscarriage, or preterm birth not related to PE+ lost to follow- up) n = 148 ↓ Included in the analysis n = 1187 ↓ ↓ High rick Low rick n = 84 n = 1103 ↓ Implementary Aspirin) 3.1. Prevalance of hight- rick preeclampsia according to the FMF model The mean maternal age in the study population was 29.76 ± 5.74 years, ranging from 16 to 49 years. Among the 1,187 pregnant women, 258 (21.7%) were aged ≥ 35 years, while 929 (78.3%) were aged < 35 years. The proportion of women classified as high risk for preeclampsia was 22/258 (8.5%) in the ≥ 35 years group, compared with 62/929 (6.7%) in the < 35 years group. This difference was not statistically significant, with an odds ratio (OR) of 1.30 (95% CI: 0.78–2.16), p = 0.30. The mean body mass index (BMI) of the participants was 21.62 ± 3.11 kg/m², ranging from 13.49 to 44.06 kg/m². A total of 147 women (12.4%) had BMI ≥ 25 kg/m², while 1,040 women (87.6%) had BMI < 25 kg/m². Women with BMI ≥ 25 kg/m² had a higher likelihood of being classified as high risk for preeclampsia compared with those with BMI < 25 kg/m², with an OR of 1.90 (95% CI: 1.08–3.33), p = 0.02, indicating a statistically significant difference. Table 3.1.1. Age, BMI distribution of pregnant women participating in the study Age Mean ± SD: 29.76 ± 5.74 Min – Max: 16 – 49 ≥ 35 258 22 236 1.30 (0.78 – 2.16) 1.9 (1.08 – 3.33) 0.30 0.02 < 35 929 62 867 Total 1187 84 1103 BMI (kg/m²) Mean ± SD: 21.62 ± 3.11 Min – Max: 13.49 – 44.06 ≥ 25 147 17 130 < 25 1040 67 973 Total 1187 84 1103 A history of preeclampsia was reported in 4 women (0.34%), of whom 2 were classified as high risk and 2 as low risk according to the screening model. Among these cases, 3 developed preeclampsia, while 1 did not. Chronic hypertension was identified in 1 participant (0.08%), who was classified as high risk and subsequently developed preeclampsia. Similarly, diabetes mellitus was present in 1 woman (0.08%), who was also categorized as high risk and developed preeclampsia during pregnancy. Systemic lupus erythematosus was recorded in 1 case (0.08%), which was classified as high risk; however, this pregnancy did not develop preeclampsia. No participants reported antiphospholipid syndrome, chronic kidney disease, smoking, or alcohol abuse in the study population. Overall, these maternal medical conditions were rare in the cohort, limiting further statistical analysis of their association with preeclampsia. Table 3.1.2. Medical history of pregnant women participating in the study History of preeclampsia 4 0.34 2 2 3 1 Chronic hypertension 1 0.08 1 0 1 0 Diabetes mellitus 1 0.08 1 0 1 0 Systemic lupus erythematosus 1 0.08 1 0 0 1 Antiphospholipid syndrome; chronic kidney disease; smoking; alcohol abuse 0 0 0 0 0 0 In the study, 487 (41.03%) were nulliparous and 700 (58.97%) were multiparous. In the nulliparous group, 51 women were classified as high risk and 436 as low risk for preeclampsia. Only 2 cases of preeclampsia occurred among nulliparous women, while 485 pregnancies did not develop preeclampsia. In contrast, among multiparous women, 33 were classified as high risk and 667 as low risk, with 7 cases of preeclampsia and 693 pregnancies without preeclampsia. Regarding the interpregnancy interval, 579 women (48.78%) had an interval of < 10 years, of whom 24 were classified as high risk and 555 as low risk. In this group, 6 pregnancies developed preeclampsia, while 573 did not. An interpregnancy interval ≥ 10 years was observed in 121 women (10.19%), including 9 high-risk and 112 low-risk cases, with 1 case of preeclampsia and 120 pregnancies without the condition. In terms of the mode of conception, the majority of pregnancies resulted from natural conception (1,125 cases; 94.78%), including 77 high-risk and 1,048 low-risk pregnancies, with 8 cases of preeclampsia. Meanwhile, 62 pregnancies (5.22%) were conceived through in vitro fertilization (IVF), among which 7 were classified as high risk and 55 as low risk, with 1 case of preeclampsia and 61 pregnancies without preeclampsia. Table 3.1.3. Characteristics of pregnancies participating in the study Nulliparous 487 41.03 51 436 2 485 Multiparous 700 58.97 33 667 7 693 Interpregnancy interval < 10 years 579 48.78 24 555 6 573 Interpregnancy interval ≥ 10 years 121 10.19 9 112 1 120 Natural conception 1125 94.78 77 1048 8 1117 IVF 62 5.22 7 55 1 61 The mean mean arterial pressure (MAP) in the study population was 80.45 ± 7.60 mmHg, with an optimal threshold of 81.40 mmHg for predicting preeclampsia. MAP demonstrated a moderate predictive performance with an AUC of 0.70, sensitivity of 69%, and specificity of 62%. Pregnant women with MAP above the threshold had a 3.70-fold higher risk of preeclampsia (OR = 3.70; 95% CI: 2.29–5.97; p < 0.001). Similar results were observed when MAP was expressed as MoM, with an AUC of 0.70, sensitivity of 68%, specificity of 64%, and OR = 3.78 (95% CI: 2.36–6.08; p < 0.001). The mean uterine artery pulsatility index (UtA-PI) was 1.75 ± 0.47, with a threshold of 1.81. UtA-PI showed good predictive performance, with an AUC of 0.78, sensitivity of 84%, and specificity of 60%. Women with UtA-PI above the threshold had an 8.08-fold increased risk of preeclampsia (OR = 8.08; 95% CI: 4.42–14.76; p < 0.001). Similarly, UtA-PI expressed as MoM yielded an AUC of 0.78, sensitivity of 81%, specificity of 62%, and OR = 6.81 (95% CI: 3.90–11.89; p < 0.001). The mean placental growth factor (PlGF) level was 67.63 ± 30.32 pg/mL, with a threshold of 44.55 pg/mL. PlGF showed good predictive ability, with an AUC of 0.75, sensitivity of 57%, and specificity of 84%. Lower PlGF levels were associated with a 7.12-fold higher risk of preeclampsia (OR = 7.12; 95% CI: 4.49–11.29; p < 0.001). When expressed as MoM, PlGF demonstrated an AUC of 0.77, sensitivity of 60%, specificity of 82%, and OR = 7.10 (95% CI: 4.46–11.29; p < 0.001). Overall, UtA-PI showed the highest predictive value, followed by PlGF, while MAP demonstrated moderate predictive performance for identifying pregnancies at risk of preeclampsia. Table 3.1.4. MAP, UtA-PI, and PlGF of pregnant women participating in the study MAP (mmHg) 80.45 ± 7.60 81.40 0.70 0.69 0.62 3.70 (2.29–5.97) <0.001 MAP (MoM) 0.98 ± 0.09 1.00 0.70 0.68 0.64 3.78 (2.36–6.08) <0.001 UtA-PI 1.75 ± 0.47 1.81 0.78 0.84 0.6 8.08 (4.42–14.76) <0.001 UtA-PI (MoM) 1.04 ± 0.28 1.10 0.78 0.81 0.62 6.81 (3.90–11.89) <0.001 PlGF (p/mL) 67.63 ± 30.32 44.55 0.75 0.57 0.84 7.12 (4.49–11.29) <0.001 PlGF (MoM) 1.05 ± 0.42 0.733 0.77 0.60 0.82 7.10 (4.46–11.29) <0.001 3.2. Aspirin prophylaxis in pregnant women at high risk of preeclampsia Among the 84 women classified as high risk by the screening model, 6 cases of preeclampsia (7.14%) were identified, compared with 3 cases (0.27%) in the low-risk group. The risk of developing preeclampsia was significantly higher in the high-risk group, with an odds ratio (OR) of 28.21 (p < 0.001). Regarding the timing of disease onset, no cases of early-onset preeclampsia (<34 weeks) were observed in either group. Preeclampsia occurring between 34 and <37 weeks was identified in 3 women (3.57%) in the high-risk group, while no cases were recorded in the low-risk group. Preeclampsia at ≥37 weeks of gestation occurred in 3 women (3.57%) in the high-risk group and 3 women (0.27%) in the low-risk group, corresponding to an OR of 13.58 (p = 0.006). All preeclampsia cases in the study presented with clinical symptoms. The proportion of symptomatic preeclampsia was 6 cases (7.14%) in the high-risk group and 3 cases (0.27%) in the low-risk group, with a significantly increased risk in the high-risk group (OR = 28.21, p < 0.001). Most cases were preeclampsia without severe features, accounting for 5 cases (5.95%) in the high-risk group and 3 cases (0.27%) in the low-risk group, with an OR of 23.21 (p < 0.001). Only one case (1.19%) of preeclampsia with severe features was observed, and it occurred in the high-risk group. Table 3.2.1. Characteristics of preeclampsia cases by risk group Preeclampsia cases 6 (7.14) 3 (0.27) 28.21 <0.001 PE <34 weeks 0 (0.00) 0 (0.00) PE 34–<37 weeks 3 (3.57) 0 (0.00) PE ≥37 weeks 3 (3.57) 3 (0.27) 13.58 0.006 PE with symptoms 6 (7.14) 3 (0.27) 28.21 <0.001 Without severe features 5 (5.95) 3 (0.27) 23.21 <0.001 With severe features 1 (1.19) 0 (0.00) The mean gestational age at delivery in the study population was 38.84 ± 0.88 weeks. Women who developed preeclampsia (PE) had a lower gestational age at delivery compared with those without PE (36.86 ± 1.35 vs. 38.85 ± 0.85 weeks). The mean neonatal birth weight was 3176 ± 366 g overall. Infants born to mothers with PE had a substantially lower birth weight than those born to mothers without PE (2244 ± 623 g vs. 3183 ± 355 g). Fetal growth restriction (FGR) was observed in 35 cases (2.9%) in the total cohort. However, the proportion was markedly higher among pregnancies complicated by PE, occurring in 7 of 9 cases (77.8%), compared with 28 of 1,178 cases (2.4%) in pregnancies without PE. Similarly, NICU admission occurred more frequently in neonates born to mothers with PE (2/9; 22.2%) compared with those without PE (11/1,178; 0.9%). No cases of eclampsia, HELLP syndrome, placental abruption, stillbirth, or perinatal death were recorded in the study population. Table 3.2.2. Pregnancy outcomes with PE Gestational age at delivery (weeks) Mean ± SD 38.84 ± 0.88 36.86 ± 1.35 38.85 ± 0.85 Birth weight (g), Mean ± SD 3176 ± 366 2244 ± 623 3183 ± 355 Fetal growth restriction 35 (2.9%) 7 (77.8%) 28 (2.4%) NICU admission 13 (1.1%) 2 (22.2%) 11 (0.9%) Eclampsia / HELLP / placental abruption / stillbirth / perinatal death 0 0 0 The mean gestational age at delivery in the overall study population was 38.84 ± 0.88 weeks. Women in the high-risk group who received aspirin prophylaxis had a slightly lower mean gestational age at delivery compared with the low-risk group (38.53 ± 1.06 vs. 38.86 ± 0.86 weeks). The mean birth weight of newborns was 3175 ± 367 g overall. Infants born to mothers in the high-risk group treated with aspirin had a lower mean birth weight than those in the low-risk group (2944 ± 398 g vs. 3193 ± 358 g). Fetal growth restriction (FGR) was observed in 35 cases (3.0%) in the total cohort. The proportion of FGR was higher in the high-risk group receiving aspirin (7/84; 8.3%) compared with the low-risk group (28/1103; 2.5%). Similarly, NICU admission occurred more frequently among neonates in the high-risk group treated with aspirin (5/84; 6.0%) than in the low-risk group (8/1103; 0.7%). No cases of eclampsia, HELLP syndrome, placental abruption, stillbirth, or perinatal death were reported in either group. Table 3.2.2. Pregnancy outcomes with hight- rick PE Gestational age at delivery (weeks) 38.84 ± 0.88 38.86 ± 0.86 38.53 ± 1.06 Birth weight (g) 3175 ± 367 3193 ± 358 2944 ± 398 Fetal growth restriction 35 (3.0%) 28 (2.5%) 7 (8.3%) NICU admission 13 (1.1%) 8 (0.7%) 5 (6.0%) Eclampsia, HELLP syndrome, placental abruption, stillbirth, perinatal death 0 0 0 4. DISCUSSION 4.1. Maternal age, BMI, and clinical factors associated with the risk of preeclampsia 4. DISCUSSION 4.1. Maternal age, BMI, and clinical factors associated with the risk of preeclampsia In the present study, the mean maternal age was 29.76 ± 5.74 years, and 21.7% of participants were aged ≥35 years. Although the proportion of women classified as high risk for preeclampsia was slightly higher among those aged ≥35 years, the difference was not statistically significant. Advanced maternal age has been widely recognized as a potential risk factor for hypertensive disorders in pregnancy due to age-related vascular changes and a higher prevalence of metabolic conditions. Several studies have suggested that women aged ≥35 years have an increased risk of preeclampsia compared with younger women [8,9]. However, when maternal characteristics are incorporated into multifactorial first-trimester screening models, the independent contribution of maternal age may become less pronounced [10]. In contrast, maternal body mass index (BMI) showed a significant association with the risk of preeclampsia in this study. Women with BMI ≥25 kg/m² had a 1.9-fold higher likelihood of being classified as high risk compared with those with lower BMI. This finding is consistent with previous studies reporting that overweight and obesity are important risk factors for preeclampsia [11,12]. Elevated BMI has been associated with chronic low-grade inflammation, endothelial dysfunction, insulin resistance, and impaired placental development, all of which may contribute to abnormal placentation and the subsequent development of hypertensive disorders during pregnancy [13]. Regarding maternal medical history, conditions such as previous preeclampsia, chronic hypertension, and diabetes mellitus were relatively rare in our study population but were more frequently observed among women classified as high risk. Previous research has consistently identified a history of preeclampsia as one of the strongest predictors of recurrence, with recurrence rates varying depending on disease severity and gestational age at onset in prior pregnancies [14]. Similarly, chronic hypertension and pre-existing metabolic disorders have been recognized as major contributors to the development of preeclampsia due to their effects on maternal cardiovascular function and placental perfusion [15]. Overall, our findings suggest that maternal BMI and pre-existing medical conditions play an important role in identifying women at increased risk of preeclampsia, whereas maternal age alone may have a limited predictive value when integrated into comprehensive screening algorithms. 4.2. MAP, UtA-PI, and PlGF in relation to the risk of preeclampsia In the present study, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) measured in the first trimester showed significant associations with the risk of preeclampsia. These findings support the concept that preeclampsia originates from abnormal placentation and impaired maternal cardiovascular adaptation early in pregnancy, which can be detected through a combination of biophysical and biochemical markers. MAP demonstrated moderate predictive performance, with an AUC of 0.70 and a threshold of 81.40 mmHg, corresponding to a 3.7-fold increased risk of preeclampsia. Similar results were observed when MAP was expressed as multiples of the median (MoM). Previous studies have reported that elevated MAP in early pregnancy reflects increased systemic vascular resistance and early endothelial dysfunction, both of which are key features in the pathophysiology of preeclampsia [16,17]. Consequently, MAP has been incorporated as a core component in several first-trimester screening models for hypertensive disorders in pregnancy. Among the parameters evaluated in this study, UtA-PI showed the highest predictive value, with an AUC of 0.78 and an odds ratio of 8.08 when the threshold of 1.81 was applied. Increased UtA-PI reflects impaired trophoblastic invasion of the spiral arteries and increased uteroplacental vascular resistance, which are characteristic features of abnormal placentation [18]. These findings are consistent with previous studies demonstrating that abnormal uterine artery Doppler indices in early pregnancy are strongly associated with the subsequent development of preeclampsia, particularly early-onset disease [19]. PlGF also showed good predictive performance, with an AUC of 0.75 and high specificity (84%) at a threshold of 44.55 pg/mL. Lower PlGF levels were associated with a more than seven-fold increased risk of preeclampsia in our study. PlGF is a pro-angiogenic factor produced by the placenta, and reduced levels are thought to reflect placental dysfunction and impaired angiogenesis, which are central mechanisms in the development of preeclampsia [20]. Numerous studies have demonstrated that reduced PlGF levels in early pregnancy are associated with an increased risk of placental-mediated complications, including preeclampsia and fetal growth restriction [21]. Overall, our findings highlight the importance of combining biophysical markers (MAP and UtA-PI) with biochemical markers (PlGF) to improve the identification of women at increased risk of preeclampsia in early pregnancy. This multifactorial approach has been widely adopted in contemporary screening strategies and has shown superior predictive performance compared with individual markers alone [22]. 4.3. First-trimester FMF preeclampsia screening results and the effectiveness of aspirin prophylaxis In our study, first-trimester preeclampsia screening using the FMF model at 11 – 13⁺⁶ weeks classified 7.1% of pregnant women as high risk. This proportion falls within the optimal screening-positive rate of 5 – 10% recommended by FMF and FIGO, suggesting appropriate real-world application identifying truly high-risk women while limiting unnecessary aspirin prophylaxis in the low-risk population [23]. This finding is comparable to studies by Poon et al. applying the FMF model in general populations, where the proportion classified as high risk is commonly around 8 – 10% [23]. The FMF model demonstrated clear risk stratification in our population. Although the high-risk group accounted for only 7.1% of the cohort, it included most preeclampsia cases, whereas the low-risk group comprised > 90% of pregnant women with very few preeclampsia cases. This pattern is consistent with studies using the FMF competing risks approach, in which the primary value of first-trimester screening is accurate identification of truly high-risk women, outperforming screening based solely on maternal clinical risk factors [24]. The mean gestational age at aspirin initiation in our study was 12,83 ± 0.59 weeks (earliest 11+6 and latest 14+1 weeks), and no participant initiated aspirin after 14 weeks. This timing lies within the “golden window” associated with optimal prophylactic benefit, particularly for early-onset disease. Aspirin discontinuation timing in our study also aligns with international practice: the mean gestational age at discontinuation was 35,95 ± 0,26 weeks, consistent with FIGO recommendations and the ASPRE trial, in which aspirin is generally stopped at 36 weeks to maintain preventive benefit without increasing intrapartum bleeding risk. Adherence was high: 1 case (1.2%) discontinued early due to gastric pain; 3 cases (3.6%) temporarily interrupted due to vaginal bleeding and later resumed; and 2 cases (2.4%) discontinued before 36 weeks due to the development of preeclampsia. Evidence from Roberge et al. and meta-analyses by Henderson et al. indicates that adherence < 80% substantially reduces, or may abolish, aspirin’s preventive effect; therefore, high adherence likely contributed to the favorable outcomes observed. The effectiveness of aspirin prophylaxis is reflected by the low overall preeclampsia rate (0.8%) and the absence of cases with onset before 34 weeks. Most high-risk women received 150 mg aspirin initiated within the first-trimester “golden window,” similar to the ASPRE protocol. In ASPRE, Rolnik et al. demonstrated that early aspirin prophylaxis significantly reduced preterm preeclampsia compared with placebo [25]. The absence of early-onset preeclampsia in our study supports the effectiveness of early screening combined with targeted aspirin prophylaxis. Notably, most preeclampsia cases in our study were late-onset and without severe features, and no severe complications such as eclampsia, HELLP syndrome, or placental abruption were observed. This pattern is consistent with the “shift in disease spectrum” described in recent reviews, whereby aspirin reduces severe, placenta-related early-onset forms, while any remaining cases tend to occur later and have a more favorable maternal–fetal prognosis [25]. Chaemsaithong et al. emphasized that the greatest benefit of first-trimester screening combined with aspirin lies in reducing preterm and severe preeclampsia rather than eliminating all cases [26]. 4.4. Pregnancy outcomes Pregnancy outcomes in our study reflect the predictive value and practical impact of the FMF first-trimester screening model and aspirin prophylaxis in the high-risk group. Although the overall preeclampsia rate was low (0,8%), adverse outcomes were concentrated mainly in the preeclampsia group and the high-risk group, consistent with placental perfusion-related pathophysiology. Gestational age at delivery was lower in the preeclampsia group than in the non-preeclampsia group (36.86 ± 1,35 vs 38.85 ± 0,86 weeks; p < 0.01), likely reflecting medically indicated earlier delivery to reduce maternal and fetal risk. Birth weight was also significantly lower in the preeclampsia group (2244 ± 623 g vs 3183 ± 355 g; p < 0.01), consistent with the consequences of chronic uteroplacental hypoperfusion. These findings are in line with studies by Nicolaides, Poon, and Akolekar, which link preeclampsia with preterm birth and low birth weight [26]. Notably, no births occurred before 34 weeks; three deliveries occurred at 34 – 37 weeks and all were in the high-risk group. This distribution resembles findings from ASPRE, in which early screening and aspirin prophylaxis reduced early-onset disease and shifted adverse events to later gestation with improved prognosis [25]. Fetal growth restriction was observed in 2.9% of the cohort, and 77.8% of preeclampsia cases were accompanied by fetal growth restriction. The high-risk group receiving aspirin prophylaxis had a higher fetal growth restriction rate than the low-risk group (8.3% vs 2.5%), suggesting that the FMF model may also identify other placenta-related adverse outcomes beyond preeclampsia [26]. The NICU admission rate was low (1.1%) but higher in the preeclampsia and high-risk groups. No severe events such as eclampsia, HELLP syndrome, placental abruption, stillbirth, or perinatal death were recorded, which may be attributable to early screening, accurate risk stratification, and close follow-up. In summary, our pregnancy outcome data suggest that the FMF first-trimester preeclampsia screening model has clear practical value, enabling accurate risk stratification, reducing early-onset and severe disease, and improving obstetric and neonatal outcomes, consistent with recommendations from FMF, FIGO, and WHO [27]. 5. Conclusion First-trimester screening for preeclampsia using the Fetal Medicine Foundation (FMF) algorithm, which integrates maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF), demonstrated good ability to identify pregnant women at increased risk of preeclampsia. In this study, women classified as high risk had a significantly higher incidence of preeclampsia compared with those in the low-risk group. Among the screening parameters, UtA-PI and PlGF showed stronger predictive performance, while MAP provided moderate predictive value. The implementation of aspirin prophylaxis in high-risk pregnancies may contribute to reducing the occurrence of severe early-onset preeclampsia, as no cases of preeclampsia before 34 weeks of gestation were observed in our cohort. 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Keywords diagnostic studies early pregnancy general obstetrics Authors Affiliations Bui Minh Cuong Quang Ninh University of Industry View all articles by this author Truong Huu Cuong 0009-0007-8304-6096 [email protected] Quang Ninh University of Industry View all articles by this author Nguyen Thanh Mai Quang Ninh University of Industry View all articles by this author Nguyen Thu Huong Quang Ninh University of Industry View all articles by this author Vu Thi Huyen Quang Ninh University of Industry View all articles by this author Do Duy Long Quang Ninh University of Industry View all articles by this author Metrics & Citations Metrics Article Usage 168 views 51 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Bui Minh Cuong, Truong Huu Cuong, Nguyen Thanh Mai, et al. Performance of the FMF First-Trimester Preeclampsia Screening Model and Aspirin Prophylaxis Outcomes in Vietnam: A Prospective Cohort Study. Authorea . 20 March 2026. 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