Preeclampsia remains one of the most serious complications of pregnancy, contributing significantly to maternal and perinatal morbidity and mortality, particularly in low- and middle-income countries. It is characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, and in severe cases, can lead to eclampsia, HELLP syndrome, or intrauterine fetal demise. The global burden of preeclampsia is profound, with an estimated 2–8% of pregnancies affected worldwide. Despite extensive research, the pathogenesis of preeclampsia is incompletely understood and is believed to involve abnormal placentation, immune dysregulation, and widespread endothelial dysfunction [1].

Over the past two decades, attention has shifted toward identifying early biomarkers that could predict preeclampsia before clinical manifestations emerge. The first trimester of pregnancy presents a critical window during which the foundation for placental development and maternal vascular adaptation is laid. Disruption of these processes has been implicated in the pathophysiology of preeclampsia. In this context, cardiometabolic markers have gained interest for their potential to reflect systemic inflammation, insulin resistance, and lipid abnormalities that may precede overt disease [2].

High-sensitivity C-reactive protein (hs-CRP), a systemic inflammatory marker, has been found elevated in women who later develop preeclampsia. It reflects endothelial activation and inflammation, both hallmarks of preeclampsia [3]. Likewise, adiponectin, an adipokine with anti-inflammatory and insulin-sensitizing properties, is often reduced in metabolic disorders and may be decreased in pregnancies complicated by hypertensive disorders [4]. Dyslipidemia in early pregnancy, characterized by elevated triglycerides and low HDL-cholesterol levels, has also been associated with later preeclampsia, suggesting that early metabolic imbalance may influence placental function and vascular health [5].

Cardiometabolic syndrome—a constellation of insulin resistance, central obesity, dyslipidemia, and low-grade inflammation—has been implicated in adverse obstetric outcomes. Although it is well-recognized in non-pregnant populations, its role in pregnancy-related hypertensive disorders is an evolving area of study. Several early investigations hinted that components of the cardiometabolic profile may have predictive value, particularly when assessed in the first trimester [6].

Current obstetric practice lacks reliable, low-cost early screening tools for predicting preeclampsia, particularly in resource-constrained settings. Most strategies rely on mid-trimester Doppler studies or maternal risk scoring, which have limited sensitivity. There is a critical need to explore simple biochemical markers measurable in the first trimester that could identify women at high risk for developing preeclampsia and allow for timely preventive interventions, such as low-dose aspirin or enhanced surveillance [7, 8].

This study was conducted to evaluate the predictive value of select first-trimester cardiometabolic biomarkers—specifically hs-CRP, adiponectin, fasting insulin, and lipid profile—for the subsequent development of preeclampsia.

Study Design and Setting

This was a prospective observational study conducted in the Department of Obstetrics, Tripura Medical College and B.R. Ambedkar Teaching Hospital, Agartala, over a 12-month period from September 2009 to August 2010. The objective was to evaluate the association between early trimester cardiometabolic biomarkers and the subsequent development of preeclampsia.

Study Population

Pregnant women attending the antenatal outpatient department for routine first-trimester screening were assessed for eligibility. Inclusion criteria were:

• Singleton pregnancy
• Gestational age between 11 and 14 weeks confirmed by crown–rump length
• Age 18–40 years
• Willingness to participate and provide written informed consent

Exclusion criteria included:

• Pre-existing chronic hypertension, diabetes mellitus, renal or autoimmune disease
• Multiple gestation
• History of cardiovascular disease or thyroid dysfunction
• Any acute infection at the time of sample collection

Sample Size and Sampling Technique

A total of 200 participants were enrolled using consecutive sampling. Sample size was calculated assuming a 15% incidence of preeclampsia in the population, 80% power, and 5% alpha error to detect an odds ratio of 2.5 for predictive biomarkers.

Data Collection Procedures

At enrolment (11–14 weeks gestation), a fasting venous blood sample (10 mL) was collected to assess:

• hs-CRP (via immunoturbidimetry)
• Adiponectin (via ELISA)
• Fasting insulin (via chemiluminescence)
• Lipid profile including total cholesterol, triglycerides, HDL, LDL (via enzymatic colorimetric assays)

Demographic and clinical data, including age, BMI, parity, and socioeconomic status, were recorded using a structured questionnaire.

Participants were followed through the second and third trimesters until delivery. Preeclampsia was diagnosed based on ACOG 2002 criteria: blood pressure ≥140/90 mmHg on two occasions four hours apart after 20 weeks of gestation with proteinuria ≥300 mg in 24-hour urine collection or ≥1+ on dipstick testing.

Outcome Measures

The primary outcome was the development of preeclampsia. Secondary outcomes included gestational age at delivery, birth weight, and mode of delivery.

Statistical Analysis

Data were analyzed using SPSS version 17.0. Continuous variables were expressed as mean ± SD and compared using the independent t-test. Categorical variables were analyzed using the chi-square test. Logistic regression was used to identify independent predictors of preeclampsia. Predictive ability was assessed using receiver operating characteristic (ROC) curves and the area under the curve (AUC). A p-value <0.05 was considered statistically significant.

Ethical Considerations

The study was approved by the Institutional Ethics Committee Written informed consent was obtained from all participants

Table 1: Demographic Characteristics

Table 2: Primary Outcome Measures

Table 3: Secondary Outcomes

Table 4: Logistic Regression Results

Table 5: ROC Curve Data

Fig 1: AUC values for predictive cardio-metabolic markers

In this prospective study involving 200 pregnant women, key first-trimester cardiometabolic biomarkers demonstrated significant predictive value for the subsequent development of preeclampsia.

Demographically, women who developed preeclampsia (n=36) were slightly older (27.6 vs 26.3 years; p=0.042) and had a higher BMI (26.8 vs 24.7 kg/m²; p=0.018). A significantly greater proportion were primigravida (58.3% vs 42.1%; p=0.047) and from lower socioeconomic backgrounds (66.7% vs 39.6%; p=0.005), suggesting that these may be additional risk-modifying factors.

Primary biomarker comparisons revealed that hs-CRP levels were markedly higher in the preeclampsia group (4.8 mg/L) than in normotensive controls (2.6 mg/L), with high statistical significance (p<0.001). Conversely, adiponectin levels were lower in those who developed preeclampsia (5.2 μg/mL vs 8.1 μg/mL; p<0.001). Fasting insulin and triglycerides were also elevated in the preeclamptic group (17.6 μIU/mL vs 12.3 μIU/mL; p=0.003 and 192 mg/dL vs 151 mg/dL; p=0.008, respectively).

Secondary outcomes showed adverse consequences of preeclampsia, including earlier delivery (36.2 vs 38.7 weeks; p<0.001), lower birth weight (2390 g vs 2905 g; p<0.001), and a higher rate of cesarean section (63.9% vs 38.4%; p=0.014).

Logistic regression identified hs-CRP >3.5 mg/L (OR 4.2, 95% CI: 2.1–8.3; p<0.001) and adiponectin <6 μg/mL (OR 0.38, 95% CI: 0.18–0.79; p=0.009) as independent predictors of preeclampsia. ROC curve analysis supported their diagnostic performance, with hs-CRP yielding an AUC of 0.81 and adiponectin 0.76, indicating good discriminative ability.

Overall, elevated hs-CRP and reduced adiponectin in early pregnancy significantly correlated with preeclampsia risk, underscoring their potential utility as predictive screening tools in clinical settings.

Preeclampsia is a multifactorial disorder with origins rooted in early gestation, yet its clinical manifestations often appear much later in pregnancy. This delay in detectability underscores the critical need for early predictive markers that are both accessible and clinically meaningful. The present study sought to evaluate first-trimester cardiometabolic biomarkers—namely hs-CRP, adiponectin, fasting insulin, and triglycerides—as potential predictors of preeclampsia in a North-East Indian population.

The elevated hs-CRP levels observed among women who later developed preeclampsia are consistent with findings by Qiu et al. [9], who reported that early pregnancy systemic inflammation significantly increased the risk of preeclampsia. As a marker of vascular endothelial activation, hs-CRP serves not only as an indicator of systemic inflammation but may also reflect underlying subclinical atherogenesis, a process hypothesized to parallel preeclampsia pathogenesis [10 – Casas et al.].

Low adiponectin levels were another significant finding in our study, echoing the results of Mazaki-Tovi et al. [11], who demonstrated that hypoadiponectinemia was independently associated with subsequent preeclampsia. Adiponectin has anti-inflammatory and insulin-sensitizing effects, and its deficiency may contribute to the endothelial dysfunction and oxidative stress seen in preeclamptic pregnancies. This aligns with the growing hypothesis that metabolic dysregulation is not merely a comorbidity but a mechanistic contributor to preeclampsia [12 – Ramsay et al.].

Elevated fasting insulin and triglyceride levels were also predictive in our cohort, reinforcing the link between early gestational insulin resistance and adverse outcomes. Bartha et al. [13] previously noted that insulin resistance in early pregnancy, independent of maternal BMI, could herald a higher risk for preeclampsia. The interplay of hyperinsulinemia and lipid abnormalities may create a milieu conducive to endothelial damage, placental ischemia, and impaired spiral artery remodeling.

The clinical implications of these findings are considerable. In resource-limited settings, where sophisticated Doppler studies or genomic screening may not be feasible, the use of simple, serum-based assays for hs-CRP and adiponectin could allow for targeted surveillance and preventive interventions such as low-dose aspirin. This is particularly relevant in areas like North-East India, where preeclampsia remains underdiagnosed and under-monitored until advanced stages.

Nonetheless, several limitations must be acknowledged. The sample size, while adequate for primary analysis, limits subgroup stratification. We did not control for dietary or environmental factors that may influence biomarker levels. Moreover, while the study was prospective, biomarker thresholds were based on tertile distributions rather than absolute clinical cut-offs.

Future studies should aim to validate these findings in larger, ethnically diverse populations and explore combinatorial models integrating biochemical markers with uterine artery Doppler indices or maternal risk scores. Investigating the mechanistic pathways linking these biomarkers to placental development may also yield insights into early therapeutic targets.

This prospective study demonstrates that elevated levels of high-sensitivity C-reactive protein (hs-CRP) and decreased levels of adiponectin in the first trimester are significantly associated with the subsequent development of preeclampsia. These findings support the role of early cardiometabolic imbalance in the pathogenesis of preeclampsia and suggest that these biomarkers may serve as valuable predictive tools in clinical settings. Incorporating hs-CRP and adiponectin testing into routine antenatal care—especially in resource-limited environments—could facilitate early identification of high-risk pregnancies and enable timely preventive interventions. The use of accessible, cost-effective serum-based assays aligns with public health goals for reducing maternal morbidity. Further large-scale, multicentric studies are warranted to validate these results and to standardize biomarker thresholds for broader clinical use.

Acknowledgment: We acknowledge the support of the department faculty for their unwavering support while conducting this study.

Conflict of Interest:

The authors declare no conflicts of interest.

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