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].
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]).
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.