European Journal of Cardiovascular Medicine

Hypertensive disorders of pregnancy (HDP) represent one of the most significant causes of maternal and perinatal morbidity and mortality worldwide, forming a major component of the obstetric “deadly triad” alongside hemorrhage and infection. Globally, preeclampsia complicates approximately 7–10% of pregnancies, while in India, its incidence is estimated between 8–10%. Despite decades of research, the precise etiology of preeclampsia remains elusive, though several hypotheses such as placental ischemia, genetic predisposition, immune maladaptation, and oxidative stress have been proposed. Among these, the oxidative stress hypothesis has gained the most support in recent years.^[1]

Emerging evidence suggests that altered lipid metabolism and the resultant dyslipidemia may play a key role in the pathophysiology of preeclampsia. Abnormal lipid profiles are believed to contribute to oxidative stress and vascular endothelial dysfunction, both hallmark features of preeclampsia. In particular, elevated levels of small dense low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), along with reduced high-density lipoproteins (HDL), have been associated with endothelial injury and exaggerated vasoconstriction. These lipid abnormalities may initiate or exacerbate the cascade of oxidative stress, promoting lipid peroxidation and endothelial dysfunction that underlie the clinical manifestations of hypertensive disorders in pregnancy.^[2]

Pregnancy itself is a state of physiological hyperlipidemia, intended to meet the energy requirements of the developing fetus. However, in preeclampsia, these lipid elevations often exceed normal gestational limits, leading to pathologic consequences. The imbalance between vasodilators such as prostacyclin (PGI₂) and vasoconstrictors such as thromboxane A₂ (TXA₂) is thought to be influenced by lipid-derived oxidative stress. This imbalance causes generalized vasospasm, increased vascular permeability, and ischemic damage to maternal organs and the placenta, contributing to adverse maternal and fetal outcomes including eclampsia, placental abruption, intrauterine growth restriction (IUGR), and perinatal death.^[3]

Several studies have demonstrated a strong correlation between dyslipidemia and the severity of preeclampsia, indicating that lipid profile assessment may serve as a useful tool in predicting the development and progression of hypertensive disorders of pregnancy. Elevated total cholesterol, triglycerides, and LDL levels, along with decreased HDL concentrations, have been consistently reported in women with preeclampsia compared to normotensive pregnant women. The early identification of such lipid alterations may therefore aid in risk stratification and timely intervention.^[4][5]

Aim:

To compare serum lipid profiles in hypertensive and normotensive pregnant women and correlate them with maternal and fetal outcomes.

Objectives:

1. To evaluate the serum lipid profile in hypertensive and normotensive pregnant women.
2. To compare the differences in lipid parameters between the two groups.
3. To correlate abnormal lipid levels with adverse maternal and fetal outcomes.

Source of Data: The study was conducted on pregnant women attending or admitted to the Department of Obstetrics and Gynaecology at Basaveshwar Teaching and General Hospital and Sangameshwar Teaching and General Hospital, M.R. Medical College, Kalaburagi.

Study Design: A hospital-based comparative prospective study.

Study Duration: Conducted over a period of one year.

Sample Size: 100 pregnant women (50 hypertensive cases and 50 normotensive controls).

Inclusion Criteria:

• Pregnant women aged 18–35 years.
• Gestational age >28 weeks.
• Group A (controls): Normotensive antenatal women.
• Group B (cases): Women with gestational hypertension, mild preeclampsia (BP ≥140/90 mmHg), severe preeclampsia or eclampsia (BP ≥160/110 mmHg with proteinuria).

Exclusion Criteria:

• Pre-existing diabetes mellitus or chronic hypertension.
• Renal, hepatic, or thyroid disorders.
• Severe anemia (Hb <8 g%).
• Polycystic ovarian syndrome, tuberculosis, or surgical illness.
• Known fetal anomalies.

Procedure and Methodology: Venous blood samples (5 mL) were collected from all participants under aseptic conditions after an overnight fast (8–12 hours). Samples were allowed to clot and centrifuged at 2500 rpm for 20 minutes to separate serum. Each serum sample was analyzed for:

1. Total Cholesterol. 2. Triglycerides. 3. HDL Cholesterol. 4. LDL Cholesterol.

Biochemical Estimation Methods:

Total Cholesterol: Enzymatic method using cholesterol esterase, cholesterol oxidase, and peroxidase.

Triglycerides: Enzymatic method employing lipoprotein lipase, glycerol kinase, and glycerol-3-phosphate oxidase.

HDL Cholesterol: Accelerator selective detergent method.

LDL Cholesterol: Two-reagent detergent-based enzymatic method. All analyses were performed at 37°C using automated biochemistry analyzers with endpoint readings at appropriate wavelengths (e.g., 540–700 nm).

Sample Processing: Serum was processed immediately after collection to prevent lipid degradation. All reagents were prepared as per manufacturer protocols, and instruments were calibrated regularly to ensure accuracy.

Statistical Methods: Descriptive and inferential statistical analyses were performed. Continuous variables were expressed as mean ± standard deviation (SD). Z-tests were applied to compare means and proportions. Scatter plots and regression analyses were used to evaluate correlations between lipid parameters and clinical outcomes. A p-value <0.05 was considered statistically significant.

Data Collection: All demographic, clinical, and biochemical data were recorded in a predesigned proforma, including maternal age, blood pressure, gestational age, mode of delivery, and neonatal outcomes such as birth weight and Apgar score.

Table 1: Overall comparison of clinical profile and maternal–fetal outcomes (N = 100)

*Composite: any of preterm, IUGR, LBW, Apgar<7, or NICU admission.

Table 1 presents the overall comparison of the clinical profile and maternal–fetal outcomes between hypertensive and normotensive pregnant women (N = 100). A statistically significant elevation of both systolic and diastolic blood pressure was observed among hypertensive participants (mean 151.8 ± 9.7 mmHg and 96.4 ± 7.8 mmHg, respectively) compared with normotensive controls (mean 118.3 ± 8.9 mmHg and 76.9 ± 6.7 mmHg, p < 0.001). The mean birth weight of neonates was significantly lower in the hypertensive group (2713 ± 357 g) than in the normotensive group (2937 ± 319 g, p = 0.0013). Hypertensive women had longer hospital stays (4.3 ± 1.2 days) versus normotensive women (3.5 ± 1.0 days, p < 0.001). Cesarean deliveries were more frequent in the hypertensive cohort (42.0 % vs 22.0 %; RR 1.91; p = 0.032). Similarly, the incidences of preterm birth, intrauterine growth restriction (IUGR), and low-birth-weight infants were significantly higher among hypertensive women (p < 0.05 for each). Composite adverse neonatal outcomes occurred in 36 % of hypertensive pregnancies versus 18 % in normotensive ones (RR 2.0; p = 0.043). Although Apgar < 7 and NICU admissions were more common in hypertensive women, these differences did not reach statistical significance.

Table 2: Serum lipid profile in hypertensive vs normotensive pregnant women (N = 100)

Table 2 compares the serum lipid profiles between the two groups. All lipid fractions, except HDL-C, were significantly elevated in hypertensive pregnancies. Mean total cholesterol (224.7 ± 32.9 mg/dL vs 198.6 ± 28.4 mg/dL), triglycerides (204.3 ± 41.8 mg/dL vs 165.7 ± 37.5 mg/dL), LDL-C (139.8 ± 27.6 mg/dL vs 118.4 ± 24.9 mg/dL), VLDL-C (40.9 ± 8.7 mg/dL vs 33.1 ± 7.5 mg/dL), and non-HDL-C (183.0 ± 31.8 mg/dL vs 149.4 ± 29.3 mg/dL) were all significantly higher among hypertensive women (p < 0.001 for each). In contrast, HDL-C was markedly reduced (41.7 ± 6.9 mg/dL vs 49.2 ± 7.4 mg/dL, p < 0.001). The TC/HDL ratio, an indicator of atherogenic risk, was significantly higher in hypertensive women (5.45 ± 1.02) compared to controls (4.12 ± 0.89, p < 0.001).

Table 3: Between-group differences in lipid parameters (effect sizes and tests)

Table 3 further quantifies the between-group differences in lipid parameters using effect sizes. The largest standardized effect (Cohen’s d = 1.39) was observed for the TC/HDL ratio, followed by non-HDL-C (d = 1.10) and HDL-C (d = -1.05). Triglycerides also showed a strong effect (d = 0.97), emphasizing their substantial elevation in hypertensive women. All lipid differences were statistically significant (p < 0.001).

Table 4: Correlation of abnormal lipid levels with adverse neonatal outcome** (N = 100)

Table 4 explores the association between abnormal lipid levels and adverse neonatal outcomes. The risk of unfavorable neonatal outcomes was approximately two- to three-fold higher among mothers with elevated lipid fractions or low HDL-C. Women with triglycerides ≥ 175 mg/dL had nearly double the risk (RR 1.93; p = 0.032), while those with LDL-C ≥ 130 mg/dL had a two-fold increase (RR 2.05; p = 0.015). Low HDL-C (<45 mg/dL) and elevated non-HDL-C (≥160 mg/dL) were both significantly associated with higher neonatal complications (p = 0.004 and 0.0025, respectively). The strongest association was found for TC/HDL ratio ≥ 4.5, which tripled the risk of adverse outcomes (RR 3.02; p = 0.0007).

Table 1, women with HDP had markedly higher systolic/diastolic pressures and significantly worse perinatal indicators lower birthweight (mean difference -224 g), higher risks of cesarean section (RR 1.91), preterm birth (RR 2.33), IUGR (RR 3.00), LBW (RR 2.29), and a doubled composite adverse neonatal outcome (RR 2.00). These magnitudes align with large cohort and review data showing HDP is consistently associated with growth restriction, prematurity, and higher intervention rates Mohammed GK et al.(2020)^[6]. The non-significant trends for Apgar <7 and NICU admission echo reports where risk elevations attenuate after adjustment for gestational age and birthweight Jaiswal A et al.(2021)^[7].

Table 2 demonstrates a clear atherogenic lipid pattern in the hypertensive group: higher TC, TG, LDL-C, VLDL-C, non-HDL-C and lower HDL-C, with a pronounced rise in TC/HDL ratio. The direction and scale of these differences parallel classic case–control and prospective reports.  Ambad R et al.(2020)^[8] first highlighted elevated TG and reduced HDL-C in preeclampsia compared with normotensive pregnancies, while Chen W et al.(2022)^[9] reported higher small dense LDL and oxidative modification in HDP. Shiferaw M et al.(2021)^[10] likewise found significantly higher TG/VLDL and lower HDL-C among preeclamptic women. More recently, meta-analytic syntheses corroborate increased TC, TG, LDL-C and decreased HDL-C across gestation in women who develop preeclampsia, supporting the external validity of estimates. The strong separation we observed for non-HDL-C and the TC/HDL ratio is clinically meaningful because these composite measures integrate multiple atherogenic fractions and often outperform single lipoproteins for risk stratification Kumari P et al.(2023)^[11].

Effect sizes in Table 3 reinforce that dyslipidemia in HDP is not marginal but large: the TC/HDL ratio (d=1.39) and non-HDL-C (d=1.10) showed the largest standardized differences, followed by substantial effects for HDL-C (negative direction) and TG. These rankings mirror prior work where TG elevation and HDL-C depression consistently emerge as the most discriminating lipid changes in preeclampsia Murmu S et al.(2020)^[12]. Mechanistically, hypertriglyceridemia enhances hepatic VLDL output and fuels lipid peroxidation, while low HDL-C diminishes reverse cholesterol transport and antioxidant capacity together promoting endothelial dysfunction central to HDP pathophysiology Zaman I et al.(2022)^[13].

Table 4 links these abnormalities to neonatal risk. Elevated TG (≥175 mg/dL), LDL-C (≥130 mg/dL), non-HDL-C (≥160 mg/dL), low HDL-C (<45 mg/dL), and a high TC/HDL ratio (≥4.5) each correlated with ~2–3-fold higher adverse neonatal outcomes. This gradient is consistent with reports that maternal hypertriglyceridemia and low HDL-C are independently associated with IUGR, preterm birth, and composite morbidity after accounting for blood pressure and proteinuria Haymanot T et al.(2020)^[14]. The strongest signal for the TC/HDL ratio (RR=3.0) dovetails with cardiometabolic literature identifying this index as a robust proxy of atherogenic risk and oxidative stress in pregnancy Mahajan S et al.(2023)^[15] & Guo J et al.(2025)^[16].

The present study demonstrates that hypertensive pregnant women exhibit significantly altered serum lipid profiles characterized by elevated total cholesterol, triglycerides, LDL-C, VLDL-C, and non-HDL-C, along with reduced HDL-C levels and a higher TC/HDL ratio compared to normotensive pregnant women. These dyslipidemic changes were strongly associated with adverse maternal and fetal outcomes such as preterm birth, intrauterine growth restriction, and low birth weight. The findings reinforce that lipid abnormalities contribute to endothelial dysfunction and oxidative stress, key mechanisms in the pathogenesis of hypertensive disorders of pregnancy. Routine assessment of lipid profiles during antenatal care could therefore serve as an early marker for identifying women at higher risk and guide timely preventive strategies to improve perinatal outcomes.

LIMITATIONS OF THE STUDY

This study was limited by its single-center design and relatively small sample size, which may restrict the generalizability of findings to broader populations. The cross-sectional nature precludes establishing a causal relationship between dyslipidemia and hypertensive disorders. Dietary habits, genetic predisposition, and pre-pregnancy lipid levels were not controlled, which could have influenced lipid profile variations. Serial measurements across gestation were not performed, preventing evaluation of temporal lipid changes. Additionally, neonatal outcomes were short-term; long-term follow-up for metabolic effects in offspring was beyond the study’s scope.

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