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CC BY-NC-ND 4.0 · Journal of Fetal Medicine 2024; 11(04): 204-211
DOI: 10.1055/s-0045-1809044
Original Article

Clinical Utility of sFlt/PlGF Ratio in the Management of Hypertensive Disorders of Pregnancy: A Retrospective Cohort Study in a Tertiary Care Center

Tanisha Gupta
1   Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
,
K. Aparna Sharma 
1   Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
,
Anubhuti Rana
1   Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
,
Garima Wadhwa
1   Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
,
Vatsla Dadhwal
1   Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India
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Abstract

Objectives

Hypertensive disorders of pregnancy (HDP) remain significant contributors to maternal and neonatal morbidity and mortality. These conditions arise from an imbalance between pro- and antiangiogenic factors from the placenta. The soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio has emerged as a promising biomarker for predicting preeclampsia and its complications. This study evaluates the clinical utility of the sFlt-1/PlGF ratio in predicting adverse outcomes and guiding management.

Methods

In this observational cohort study, pregnant women, either diagnosed with or at high risk for HDP, were recruited. Serum levels of sFlt-1 and PlGF were measured, and patients were classified into two groups based on a cutoff ratio of 38. Strict fetomaternal surveillance was done until delivery. Statistical analyses included comparisons of outcomes between groups and the predictive performance of the sFlt-1/PlGF ratio using receiver operating characteristic (ROC) curves.

Results

The study found that a high sFlt-1/PlGF ratio (> 38) was significantly associated with an increased likelihood of adverse fetomaternal outcomes. The high ratio group had a higher incidence of preeclampsia (75% vs. 20%, p = 0.0012), fetal growth restriction (65% vs. 5%, p = 0.0001), and a shorter enrolment and delivery period (median 13.5 vs. 23 days, p = 0.04884). ROC analysis demonstrated strong predictive performance with an area under the curve of 0.892, indicating high accuracy in identifying patients at risk for adverse outcomes.

Conclusion

The sFlt-1/PlGF ratio effectively stratified patients into high risk and low risk categories for adverse fetomaternal outcomes. This study supports the integration of the sFlt-1/PlGF ratio into clinical practice to enhance risk assessment and decision making in managing HDP.

Implications in Clinical Practice

This study highlights the clinical utility of the sFlt-1/PlGF ratio in the management of HDP. By effectively stratifying patients into high risk and low risk categories, this biomarker enables targeted surveillance and intervention, reducing unnecessary hospital admissions and improving maternal and fetal outcomes. Its integration into routine prenatal care can enhance risk assessment and optimize resource allocation, particularly in low resource settings.


 

Keywords

preeclampsia - hypertensive disorders of pregnancy - sFlt-1/PlGF ratio - preterm delivery - fetal growth restriction

Introduction

Preeclampsia (PE) affects 5 to 8% of pregnancies globally and continues to be a leading cause of maternal and neonatal morbidity and mortality, particularly in developing countries.[1] A recent report indicated that Southeast Asian populations, particularly during the preterm period, face a 1.5-fold increased risk of developing PE.[2] Additionally, a large-scale meta-analysis revealed that approximately 1 in every 11 pregnant women in India is diagnosed with hypertensive disorders.[3] While the exact cause of hypertensive disorders in pregnancy (HDP) is still unclear, growing evidence indicates that these conditions may stem from an imbalance between placental proangiogenic and antiangiogenic factors.[4] This imbalance is thought to damage the maternal vascular endothelium, resulting in the clinical symptoms associated with these disorders.[5] [6] Early identification and effective management are crucial for improving outcomes. The soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio has emerged as a promising tool for assessing the risk of PE and related complications. While this ratio is yet to be incorporated into clinical practice or included in clinical guidelines for predicting adverse maternal and neonatal outcomes, recent research has extensively discussed its potential applications.[7] [8] The sFlt-1/PlGF ratio has emerged as a promising tool for assessing the risk of PE and related complications. Landmark studies such as the PRrediction of short term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) and Real life Outpatient Biomarker Use in Hypertensive Pregnancies in Low Resource Environments (ROBUST) have demonstrated their role in predicting the short term risk of PE in high income settings.[8] [9] However, data on its predictive accuracy in low resource environments remains scarce. This study aims to bridge this gap by evaluating the utility of the sFlt-1/PlGF ratio in an Indian tertiary care setting. A cutoff ratio of ≤ 38 has been validated for ruling out PE within 1 week, while higher values correlate with increasing disease severity.[7] [8] Despite this, its real world applicability in guiding clinical decision making, particularly in resource limited settings, remains underexplored. By assessing its predictive value for adverse fetomaternal outcomes, this study aims to establish its potential role in improving risk stratification and optimizing management strategies in such settings.


 

Methods

This retrospective observational cohort study was conducted over 1 year at a single tertiary care hospital in Delhi, India, after obtaining ethical clearance. The study included pregnant women aged 18 years or older with a singleton pregnancy who were either diagnosed with a HDP or identified as high risk for developing HDP based on criteria defined by the American College of Obstetricians and Gynecologists (ACOG).[10] The diagnosis of gestational hypertension, PE (with or without severe features), and chronic hypertension was made following the 2020 ACOG guidelines.[10]

PE was characterized by a systolic blood pressure (SBP) of at least 140 mm Hg or a diastolic blood pressure (DBP) of at least 90 mm Hg, measured on two occasions at least 4 hours apart after 20 weeks of gestation, accompanied by proteinuria. In cases without proteinuria, severe PE was identified based on criteria such as an SBP of 160 mm Hg or above, or a DBP of 110 mm Hg or above on two occasions at least 4 hours apart (or requiring immediate intravenous antihypertensive treatment). Additional criteria included thrombocytopenia (platelet count below 100,000/µL), serum creatinine levels exceeding 1.1 mg/dL or doubling without other renal disease, liver transaminase levels elevated to at least twice the normal level, pulmonary edema, persistent headaches unresponsive to treatment, or visual disturbances.[10]

The exclusion criteria consisted of fetal chromosomal or structural abnormalities, severe features of PE, maternal cardiac conditions, hematologic disorders, and multiple pregnancies. Following informed consent, baseline maternal demographic details were recorded, along with medical and obstetric histories. Information on symptoms, clinical signs, and laboratory parameters associated with PE was also gathered. Participants underwent serum biochemical marker testing, including sFlt and PlGF levels, following the standard operating procedures of the laboratory. A 3-mL fasting venous blood sample was collected in a gel separator Vacutainer tube from the study population by following the standard protocol. After collection, the blood was allowed to clot at room temperature for 30 minutes. It was then centrifuged at 2,000 × g for 10 minutes under refrigerated conditions to separate the serum from whole blood. PlGF and sFlt-1 concentrations were quantified by electrochemiluminescence immunoassay in maternal serum. The quantification process used the Sandwich immunoassay method, facilitated by the Cobas e801 module, Roche Diagnostics, Basel, Switzerland. This method used a closed system utilizing Roche Diagnostic reagent kits. Standard validation protocols were performed before the execution of these tests. The quality of these immunoassays was rigorously monitored by participation in internal quality control programs, provided by Roche Diagnostics. Based on previous studies, these women were classified into high and low ratio groups with a sFlt-1/PlGF cutoff ratio of 38.[7]

The primary outcomes assessed included adverse maternal outcomes, adverse fetal outcomes, the interval from sample collection to delivery, and gestational age at delivery. Adverse maternal outcomes considered were the development of severe PE features, elevated liver enzymes, low platelet count (HELLP) syndrome, development of eclampsia, intensive care unit (ICU) admission, placental abruption, and maternal death. Adverse neonatal outcomes included fetal growth restriction (FGR),[11] medically indicated preterm birth at ≤ 34 weeks' gestation, neonatal ICU (NICU) admission, intrauterine demise, and perinatal death. The Strengthening the Reporting of Observational Studies in Epidemiology diagram of the study is shown in [Fig. 1].

Zoom
Fig. 1 Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) diagram of the study.

Statistical Analysis

Baseline characteristics and outcomes were compared between the low ratio and high ratio groups. Continuous variables such as age, gestational age at enrolment, interval from enrolment to delivery, and laboratory values are reported as median with interquartile range (IQR) due to their nonnormal distribution. The normality of the data was assessed using the Shapiro–Wilk test. Comparisons of continuous variables were performed using the Wilcoxon rank sum test. Categorical variables are presented as frequencies and proportions, with comparisons made using the chi-square test or Fisher's exact test when cell counts were small. A two sided p-value of less than 0.05 was considered statistically significant.

The predictive performance of the sFlt/PlGF ratio was evaluated by estimating the likelihood ratio, sensitivity, specificity, and area under the curve (AUC) using receiver operating characteristic (ROC) curves, with corresponding 95% confidence intervals (CIs). Cutoff points were determined using the Youden index, which is calculated as Sensitivity + Specificity – 1. The cutoff value was selected to maximize the tradeoff between sensitivity and specificity, ensuring optimal discrimination between adverse and nonadverse outcomes, reflecting the best balance between detecting true positives while minimizing false positives.


 

 

Results

The study included a total of 40 pregnant women, with 20 (50%) having a low sFlt/PlGF ratio (< 38) and 20 (50%) having a high sFlt/PlGF ratio (≥ 38). At the time of enrolment, 11 patients (27.5%) had chronic hypertension, another 11 (27.5%) had gestational hypertension, and 19 patients (47.5%) had PE without severe features. The baseline characteristics between the two groups showed no significant differences in age, nulliparity, mode of conception, chronic hypertension, history of PE or eclampsia, gestational hypertension, renal disorders, or diabetes mellitus, as shown in [Table 1]. The median gestational age at enrolment was slightly higher in the low ratio group compared with the high ratio group, but the difference was not statistically significant (324/7 vs. 302/7 weeks; p = 0.130). The sFlt/PlGF ratio was significantly higher in the high ratio group compared with the low ratio group (median 177.5 vs. 10.9; p < 0.00001). Out of the 19 patients who had PE at enrolment, 15 patients (75%) belonged to the high ratio group compared with only 4 patients (20%) in the low ratio group. This difference was statistically significant (p = 0.0012).

Table 1

Baseline characteristics of pregnant women in low and high ratio groups

Characteristic

Total (n = 40)

Low ratio (< 38) (n = 20)

High ratio (> 38)

(n = 20)

p-Value

Age (y) (median, IQR)

27.5 (23, 32)

28 (24.75, 32)

24.5 (21.75, 32)

0.392

Nulliparity (%)

19 (47.5)

8 (40)

11 (55)

0.902

IVF conception (%)

5 (12.5)

3 (15)

2 (10)

0.632

Chronic HTN (%)

11 (27.5)

4 (20)

7 (35)

0.478

Previous h/o PE or eclampsia (%)

5 (12.5)

4 (20)

1 (5)

0.914

Gestational HTN (%)

11 (27.5)

8 (40)

3 (15)

0.155

Preeclampsia (%)

19 (47.5)

4 (20)

15 (75)

0.0012

Renal disorder

2 (5)

Zero

2 (10)

0.4872

Diabetes mellitus

1 (2.5)

1 (5)

Zero

1.00

Smoker

Zero

Zero

Zero

–

Gestational age at enrolment (median, IQR)

313/7 (31, 356/7)

324/7 (315/7, 352/7)

302/7 (30, 336/7)

0.130

sFlt/PlGF ratio (median, IQR)

37.25 (11.5, 170.5)

10.9 (3.38, 15.25)

177.5 (61.25, 336.8)

< 0.00001

Abbreviations: HTN, hypertension; IQR, interquartile range; IVF, in vitro fertilization; PE, preeclampsia; sFlt/PlGF, soluble fms-like tyrosine kinase-1/placental growth factor.


Note: Data are presented as median (quartile 1, quartile 3) or n (%) depending on variable type. The p-Values which are significant are bold faced.


Adverse fetomaternal outcomes occurred in 19 patients (47.5%), with 4 patients (20%) in the low ratio group and 15 patients (75%) in the high ratio group, which was statistically significant (p = 0.0012), as shown in [Table 2]. Features of severe PE were more frequent in the high ratio group, with 5 patients (25%) compared with 1 patient (5%) in the low ratio group, although this difference was not statistically significant (p = 0.1818). HELLP syndrome occurred in 1 patient (5%) in each group (p = 1.000). No cases of eclampsia, ICU admissions, pulmonary edema, or maternal deaths were reported in either group, as shown in [Table 2]. Fetal outcomes ([Table 2]) showed more pronounced differences between the two groups. FGR was significantly more common in the high ratio group, affecting 13 patients (65%) compared with 1 patient (5%) in the low ratio group (p = 0.0001). The median latency between enrolment and delivery was significantly shorter in the high ratio group (13.5 days, IQR 7.75–17.25) compared with the low ratio group (23 days, IQR 10.75–53.25), with a p-value of 0.04884. Preterm delivery occurred in 22 patients (55%), with 16 patients (80%) in the high ratio group and 6 patients (30%) in the low ratio group (p = 0.0036). Notably, 3 out of the 6 preterm deliveries in the low ratio group and 1 out of the 18 in the high ratio group were attributable to factors other than PE, including scar tenderness, preterm labor, and fetal anemia. NICU admission was required for 18 newborns (45%), with 14 admissions (70%) from the high ratio group and 4 admissions (20%) from the low ratio group (p = 0.0036). There were 2 cases of intrauterine demise in the high ratio group (10%), but this difference was not statistically significant compared with the low ratio group (p = 0.4872).

Table 2

Comparison of maternal and fetal outcomes between the high and low ratio groups

Outcome

Total (n = 40) (%)

Low ratio (< 38) (n = 20) (%)

High ratio (> 38) (n = 20)

p-Value

Adverse maternal or fetal outcome[a] (%)

19 (47.5)

4 (20)

15 (75)

0.0012

PE with severe features (%)

6 (15)

1 (5)

5 (25)

0.1818

Impending features of eclampsia (%)

1 (2.5)

1 (5)

0

1.000

HELLP (%)

2 (5)

1 (5)

1 (5)

1.000

Abruption (%)

1 (2.5)

1 (5)

0

1.000

Eclampsia (%)

0

0

0

–

ICU admission (%)

0

0

0

–

Pulmonary edema (%)

0

0

0

–

Maternal deaths (%)

0

0

0

–

Indication for delivery (%)

 Gestational HTN

 Chronic HTN

 PE without severe features

 PE with severe features severe/impending/HELLP

 Other

 Fetal indication[b]

9 (22.5)

3 (7.5)

3 (7.5)

8 (20)

6 (15)

11 (27.5)

6 (30)

3 (15)

2 (10)

3 (15)

5 (25)

1 (5)

3 (15)

0

1 (5)

5 (25)

1 (5)

10 (50)

0.4506

0.2308

1.000

0.6948

0.1818

0.0033

Caesarean delivery (%)

28 (70)

14 (70)

15 (75)

1.000

Preterm delivery (%)

22 (55)

6 (30)

16 (80)

0.0036

Latency between enrolment and delivery (d) (median, IQR)

14(7.75, 25)

23 (10.75, 53.25)

13.5 (7.75, 17.25)

0.04884

Fetal growth restriction (%)

14 (35)

1 (5)

13 (65)

0.0001

Intrauterine demise (%)

0

0

2 (10)

0.4872

NICU stay (%)

18 (45)

4 (20)

14 (70)

0.0036

Perinatal deaths (%)

0

0

2 (10)

0.4872

Abbreviations: HELLP, hemolysis, elevated liver enzymes and low platelet; HTN, hypertension; ICU, intensive care unit; IQR, interquartile range; NICU, neonatal ICU; PE, preeclampsia.


Note: The p-Values which are significant are bold faced.


a The preterm deliveries that were due to other reasons (three in low ratio and one in high ratio were excluded from the adverse fetal or maternal outcome).


b Fetal indications included fetal distress, poor Manning score, spontaneous decelerations in nonstress test, absent or reversal of end diastolic flow.


The ROC analysis demonstrated strong predictive performance for adverse outcomes for the sFlt/PlGF ratio. The AUC was 0.892 (95% CI 0.792–0.992), with a p-value of < 0.001, indicating a high degree of accuracy in predicting adverse outcomes ([Fig. 2]). At this cutoff, the sensitivity was 73.68% (95% CI 48.8–90.9) and the specificity was 95.24% (95% CI 76.2–99.9), with a positive likelihood ratio of 15.47 and a negative likelihood ratio of 0.28. The Youden index, which maximizes the balance between sensitivity and specificity, was calculated to be 0.6892. The corresponding optimal cutoff value of > 60.2 was selected as it provided the highest combined sensitivity (73.68%) and specificity (95.24%), minimizing false positives and false negatives, highlighting the ratio's robustness as a predictive tool for adverse maternal and fetal outcomes ([Table 3]).

Zoom
Fig. 2 The receiver operating characteristic (ROC) curve for soluble fms-like tyrosine kinase-1/placental growth factor (sFlt/PlGF) ratio for predicting adverse maternal and fetal outcome.
Table 3

Predictive performance of sFlt/PlGF for severe fetomaternal outcomes

sFlt/PlGF ratio

Sensitivity

95% CI

Specificity

95% CI

+LR

–LR

≥ 1.96

100.00

82.4–100.0

0.00

0.0–16.1

1.00

> 5.4

100.00

82.4–100.0

33.33

14.6–57.0

1.50

0.00

> 7.74

94.74

74.0–99.9

33.33

14.6–57.0

1.42

0.16

> 12.98

94.74

74.0–99.9

61.90

38.4–81.9

2.49

0.085

> 18

84.21

60.4–96.6

61.90

38.4–81.9

2.21

0.26

> 20

84.21

60.4–96.6

66.67

43.0–85.4

2.53

0.24

> 31

78.95

54.4–93.9

66.67

43.0–85.4

2.37

0.32

> 42.3

78.95

54.4–93.9

85.71

63.7–97.0

5.53

0.25

> 54.6

73.68

48.8–90.9

85.71

63.7–97.0

5.16

0.31

> 60.2

73.68

48.8–90.9

95.24

76.2–99.9

15.47

0.28

> 109.2

57.89

33.5–79.7

95.24

76.2–99.9

12.16

0.44

> 162.5

57.89

33.5–79.7

100.00

83.9–100.0

0.42

> 891

0.00

0.0–17.6

100.00

83.9–100.0

1.00

Abbreviations: CI, confidence interval; LR, likelihood ratio; sFlt/PlGF, soluble fms-like tyrosine kinase-1/placental growth factor.


Note: The cut off value with best combined sensitivity and specificity with least false positives and negatives are bold faced.



 

Discussion

Our study demonstrated that a high sFlt/PlGF ratio is strongly linked to an increased likelihood of adverse fetomaternal outcomes and a higher probability of preterm delivery, although the overall incidence of adverse events was low, limiting generalizability. This suggests that the sFlt/PlGF ratio could be a valuable tool for categorizing patients into high risk and low risk groups, allowing for more targeted monitoring and triage. High risk patients could receive more intensive surveillance, while low risk patients could benefit from routine home monitoring, which is particularly advantageous in low resource settings. This better risk stratification can potentially prevent unnecessary preterm deliveries, reduce unnecessary hospital admissions, and avoid inappropriate discharges.

The Preeclampsia Open Study demonstrated that the sFlt-1/PlGF ratio impacted clinical decision making regarding hospital admissions, resulting in changes to hospitalization plans for 16.9% of cases (20 out of 118) after clinicians became aware of the ratio values.[12] While earlier research has indicated that sFlt1 and/or PlGF levels can be useful in diagnosing PE, there is limited data on the relationship between these levels and subsequent adverse maternal and perinatal outcomes.[9] [13] [14] [15] [16] [17] In the PROGNOSIS study, an sFlt-1/PlGF ratio cutoff of ≤ 38 ruled out PE within 1 week (negative predictive value [NPV] 99.3%) or 4 weeks (NPV 94.3%), while ratio values above 38 ruled in PE within 4 weeks (positive predictive value [PPV] > 36%).[9] In our study, 75% of the patients with a ratio > 38 had PE, thus providing similar results.

There is increasing evidence supporting the potential use of the sFlt1/PlGF ratio to identify women at higher risk for near term adverse maternal and perinatal outcomes. However, the exact predictive accuracy of this ratio has varied across studies, mainly due to differences in the patient populations studied. The PROGNOSIS Asia study indicated that a sFlt-1/PlGF ratio of ≤ 38 had a high NPV of 98.9% (95% CI 97.6–99.6%) for excluding fetal adverse events within 1 week. In contrast, a ratio exceeding 38 demonstrated a PPV of 53.5% (95% CI 45.0–61.8%) for predicting fetal complications within a 4 week period.[18] The Rule Out PreEclampsia (ROPE) study, which prospectively followed 616 pregnant women suspected of having PE, revealed that the median sFlt-1/PlGF ratio at the time of presentation was significantly higher in those who experienced adverse outcomes compared with those who did not (47.0 [IQR, 15.5–112.2] vs. 10.8 [IQR, 4.1–28.6]; p < 0.0001).[19]

Evidence on the use of the sFlt-1/PlGF ratio in low resource settings is currently limited. The ROBUST study, which assessed 50 patients, reported that those with a high risk ratio (> 85) had a significantly higher prevalence of severe PE (90.91% vs. 8.00%, p < 0.0001), increased maternal complications (18.18% vs. 0%, p = 0.04), and delivered at earlier gestational ages (32.57 vs. 37.43 weeks, p = 0.0001), consistent with findings from our research.[8]

Angiogenic profiles have also been shown to predict the timing of delivery in patients with suspected PE.[8] [20] [21] In fact, women with an sFlt-1/PlGF ratio of > 38 also had a shorter remaining time to delivery compared with women with an sFlt-1/PlGF ratio of ≤ 38, independent of whether they developed PE or not.[18] A retrospective study using sFlt-1/PlGF cutoff values for risk stratification categorized patients into high-risk (> 85), intermediate risk (38–85), and low risk (< 38) groups. The study found that those in the high- and intermediate risk categories had significantly shorter times to delivery compared with the low risk group (4 vs. 8 vs. 29 days).[7] We found that women with a low level had a longer time to delivery.

Sixty five percent of patients in our high ratio group had FGR, compared with only 5% in the low ratio group, highlighting the strong predictive accuracy of this ratio in identifying FGR. In a prospective, observational, single center cohort study including FGR pregnancies, 75% of cases had an sFlt-1/PlGF ratio of ≥ 85.[20] A multicenter retrospective cohort study showed that an sFlt-1/PlGF ratio of > 655 is almost always associated with FGR.[22] Another study demonstrated that sFlt-1/PlGF levels were significantly higher across all stages of FGR compared with small for gestational age cases and controls. Additionally, the median values varied significantly among the different FGR severity stages, with stage I at 9.76, stage II at 284.3, and stage III at 625.02 (p < 0.05).[23]

In our study, while the biomarker demonstrated potential predictive power for several pregnancy outcomes, certain variables did not show significant differences when analyzed. Notably, outcomes such as ICU admissions showed no significant variation in relation to the biomarker. One possible explanation for this lack of significant difference could be related to the nature of ICU admissions, which are influenced by a combination of severe comorbidities and acute medical events that may not be fully captured by a single biomarker. Additionally, confounding factors such as gestational age, maternal health status, and treatment interventions could have played a role in masking the biomarker's ability to predict ICU admission outcomes.

The AUC in our ROC analysis was 0.892, with a p-value of < 0.001, indicating a high degree of accuracy in predicting adverse outcomes at a cutoff value of sFlt/PlGF ratio of > 60.2 with a sensitivity of 73.68%, specificity of 95.24%, and positive and negative likelihood ratio of 15.47 and 0.28, respectively. In a previous study, ROC analysis suggested that an sFlt1/PlGF cut point of 85 (AUC 0.89) would allow the maximum number of participants to be correctly classified with regard to adverse outcomes (87%) with a sensitivity of 72.9%, specificity of 94.0%, positive likelihood ratio of 12.2, and negative likelihood ratio of 0.29.[19] In an Indian study on 91 patients with PE, sFlt/PlGF ratio at a cutoff of 71.92 was the best biomarkers when compared with other biochemical markers to predict adverse maternal (AUC 0.81; 95% CI, 0.72 − 0.90) and fetal (AUC, 0.88; 95% CI, 0.80 − 0.96) outcomes in PE.[24]

The clinical implications of this biomarker for low resource settings remain underexplored. In environments with limited access to advanced diagnostics and management facilities, it could offer a promising alternative for improving maternal and fetal outcomes. However, feasibility concerns must be addressed. Cost effectiveness is a key factor if the biomarker requires expensive equipment, its use may be restricted to urban centers, limiting accessibility. Additionally, proper training is essential for health care workers unfamiliar with its interpretation. Infrastructure challenges also need consideration. If the biomarker requires sophisticated laboratory facilities, implementation may be difficult. However, if adapted for point of care testing, it could be integrated into existing maternal health programs with minimal resources, enhancing accessibility in underserved areas.

The study stands out as one of the few studies specifically focusing on the Indian population with a thorough examination of both maternal and fetal outcomes on the basis of sFlt/PlGF ratio. However, the study also faces several limitations. The small sample size and the heterogeneity of the population may affect the generalizability of the findings. Being a single center study and a retrospective cohort based analysis further restricts its applicability. The retrospective design may introduce selection bias, as data collection was dependent on available records, which might not fully capture all relevant clinical details. Additionally, the study population was limited to a specific setting, which could affect the generalizability of the findings. Additionally, the lack of comparison with other biochemical or clinical markers limits the scope of the findings. This study highlights the clinical utility of the sFLT-1/PlGF ratio in the early identification and better triaging of HDP. By enabling more accurate risk stratification, this biomarker can significantly improve maternal and fetal outcomes, particularly in low resource settings where targeted monitoring is crucial.

This study demonstrates the potential of biomarkers as a valuable tool in clinical practice for improving diagnosis and patient outcomes. However, its integration into routine care requires careful consideration. To facilitate the adoption of this biomarker, we recommend conducting further validation studies across diverse populations to provide stronger evidence by minimizing selection bias and allowing for standardized data collection. Such studies would help validate the predictive performance of the sFlt/PlGF ratio and assess its utility across different clinical settings to establish its robustness and generalizability. A thorough cost effectiveness analysis will also be crucial in evaluating its affordability and accessibility in real world settings.


 

 

Conflict of Interest

None declared.

Authors' Contributions

T.G. and K.A.S. led the study design. T.G., K.A.S., A.R., and G.W. contributed to data collection and interpretation. T.G. performed the statistical analysis and drafted the manuscript. V.D., K.A.S., and A.R. critically reviewed and approved the final version.


Ethical Approval

This study was approved by the Institutional Ethics Committee of AIIMS, New Delhi (Approval No. AIIMSA2325/7.10.2024) and the study adhered to the principles of the Helsinki Declaration.



Address for correspondence

K. Aparna Sharma, MBBS, MD, DNB, FICOG
Department of Obstetrics and Gynecology, All India Institute of Medical Sciences
New Delhi 110029
India   

Publication History

Article published online:
15 May 2025

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Zoom
Fig. 1 Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) diagram of the study.
Zoom
Fig. 2 The receiver operating characteristic (ROC) curve for soluble fms-like tyrosine kinase-1/placental growth factor (sFlt/PlGF) ratio for predicting adverse maternal and fetal outcome.