Hypertensive disorders of pregnancy, particularly preeclampsia, along with intrauterine growth restriction (IUGR), represent two of the most critical complications that contribute to maternal and perinatal morbidity and mortality worldwide. Preeclampsia, a multisystem disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, is believed to originate from abnormal placentation and endothelial dysfunction. IUGR, on the other hand, often coexists with or follows a similar pathophysiological trajectory, primarily due to impaired uteroplacental perfusion and placental insufficiency [1].

The ability to accurately predict these conditions early in pregnancy is of paramount importance for obstetric management and timely intervention. Among the various biomarkers studied for this purpose, second trimester serum β-human chorionic gonadotropin (β-HCG) has been extensively evaluated. β-HCG, a glycoprotein hormone produced by trophoblastic tissue, plays a crucial role in modulating maternal physiological responses to pregnancy and in promoting angiogenesis and trophoblastic invasion [2]. Abnormally elevated levels of β-HCG in the second trimester have been associated with an increased risk of preeclampsia and IUGR, potentially serving as an early biochemical indicator of defective placentation [3,4].

In addition to biochemical markers, Doppler velocimetry of the uterine arteries provides a non-invasive means to assess uteroplacental blood flow dynamics. Colour Doppler ultrasound, particularly when performed in the second trimester, can reveal increased resistance or notching in the uterine artery waveform, both of which are predictive of impaired trophoblastic invasion and reduced uterine perfusion [5]. Several studies have indicated that increased uterine artery pulsatility index (PI) and resistance index (RI), as well as the presence of bilateral diastolic notches, are significantly associated with the subsequent development of preeclampsia and IUGR [6].

Combining maternal serum biomarkers with uterine artery Doppler velocimetry has shown promise in improving predictive accuracy. The dual approach integrates functional and structural insights into placental development, thereby increasing the sensitivity and specificity of screening protocols [7]. Particularly in primigravidas, who inherently lack a prior pregnancy history that could aid in risk stratification, such combined assessments could enhance early detection and optimize antenatal surveillance [8].

Despite ongoing research, there remains no universally accepted single screening test for preeclampsia or IUGR. Variability in screening protocols and population-specific differences further complicate the establishment of standardized guidelines. However, the identification of reliable second trimester predictors is especially valuable in low-resource settings, where universal first trimester screening might not be feasible [9]. Hence, mid-trimester assessment using accessible, cost-effective tools like β-HCG measurement and uterine artery Doppler ultrasound offers a practical solution for risk assessment in routine obstetric care [10].

The present study aims to investigate the role of second trimester serum β-HCG levels and uterine artery colour Doppler velocimetry parameters in predicting the development of preeclampsia and intrauterine growth restriction among primigravid women. By evaluating the correlation between these parameters and pregnancy outcomes, the study seeks to contribute to the growing body of evidence on effective screening tools for placental insufficiency-related complications.

Study Design and Setting

This was a prospective observational study conducted in the Department of Obstetrics and Gynaecology at a tertiary care teaching hospital over a period of 18 months. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants.

Study Population

A total of 120 primigravida women attending routine antenatal check-ups between 13 and 20 weeks of gestation were enrolled using purposive sampling. Inclusion criteria included singleton pregnancy, confirmed gestational age by first trimester ultrasound, and absence of pre-existing hypertension, diabetes mellitus, renal disease, or other chronic illnesses. Exclusion criteria were multifetal gestation, congenital anomalies detected on anomaly scan, history of recurrent pregnancy loss, and use of assisted reproductive techniques.

Data Collection and Procedure

Demographic and clinical data including age, BMI, gestational age at recruitment, and obstetric history were collected using a predesigned proforma. All enrolled women underwent:

1. Serum β-HCG estimation:

A venous blood sample (3 mL) was drawn between 14–20 weeks of gestation. Serum β-HCG levels were measured using a chemiluminescence immunoassay technique. The values were interpreted in multiples of median (MoM) for gestational age. A β-HCG value >2.5 MoM was considered elevated.

2. Uterine artery colour Doppler velocimetry:

Transabdominal colour Doppler ultrasound was performed using a 3.5–5 MHz curvilinear probe. Both right and left uterine arteries were assessed at the apparent crossover of the external iliac artery and uterine artery. Pulsatility index (PI), resistance index (RI), and presence or absence of early diastolic notching were recorded. Mean PI >1.45 and presence of bilateral notching were considered abnormal.

Participants were followed until delivery. Primary outcomes assessed were development of:

• Preeclampsia, defined as BP ≥140/90 mmHg after 20 weeks gestation with proteinuria ≥300 mg/24 hr.
• Intrauterine Growth Restriction (IUGR), defined as estimated fetal weight <10th percentile for gestational age on serial ultrasonography.

Statistical Analysis

Data were entered in Microsoft Excel and analyzed using SPSS version 25. Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as frequencies and percentages. Associations between elevated β-HCG, abnormal Doppler indices, and adverse outcomes (preeclampsia/IUGR) were assessed using Chi-square test and unpaired t-test. A p-value <0.05 was considered statistically significant. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for both β-HCG and Doppler findings.

A total of 120 primigravida women were included and followed until delivery. The mean age of participants was 25.4 ± 3.2 years, and the mean gestational age at recruitment was 17.3 ± 1.9 weeks.

Table 1: Serum β-HCG Levels and Pregnancy Outcome

Women with elevated second trimester serum β-HCG levels (≥2.5 MoM) had significantly higher rates of preeclampsia (72%) and IUGR (71%). In contrast, only 28% and 29% of those with normal β-HCG (<2.5 MoM) developed preeclampsia and IUGR, respectively. This suggests a strong association between elevated β-HCG and adverse pregnancy outcomes. The association was statistically significant (p<0.001).

Table 2: Uterine Artery Doppler Findings and Outcomes

Abnormal uterine artery Doppler findings (either elevated PI >1.45 or bilateral notching) were significantly more prevalent among those who developed preeclampsia (89%) and IUGR (85%). In contrast, 80% of women with normal pregnancies had normal Doppler findings. The presence of bilateral notching and elevated PI was strongly correlated with poor placental perfusion. These differences were statistically significant (p<0.01).

Table 3: Combined Predictive Accuracy of β-HCG and Doppler

When β-HCG and uterine artery Doppler were used individually, their sensitivities for predicting adverse outcomes were 72.2% and 77.7%, respectively. However, when combined, the sensitivity increased to 88.9% and specificity to 91.3%, with a high negative predictive value (96.5%). This indicates that the dual-marker strategy enhances screening performance significantly over either marker alone.

Table 4: Gestational Age and Birth Weight Based on Predictors

Participants with both elevated β-HCG and abnormal Doppler delivered significantly earlier (mean 35.1 weeks) and had lower mean birth weights (2100g) compared to those with no abnormal findings. Those with only one predictor positive had intermediate outcomes. The differences in gestational age and birth weight across groups were statistically significant (p<0.001). These findings suggest that the combination of predictors can help identify pregnancies at risk of preterm birth and fetal growth restriction.

Table 1: Distribution Based on Serum β-HCG Levels (MoM) and Pregnancy Outcome

Table 2: Uterine Artery Doppler Abnormalities and Pregnancy Outcomes

Table 3: Combined Predictive Accuracy of β-HCG and Doppler in Predicting Adverse Outcomes

Table 4: Gestational Age and Birth Weight Based on Predictor Positivity

Preeclampsia and intrauterine growth restriction (IUGR) remain two of the most significant complications of pregnancy, particularly in primigravidas, and are closely associated with poor placental development. The current study aimed to evaluate the predictive value of two accessible screening tools—second trimester serum β-HCG and uterine artery colour Doppler velocimetry—in identifying pregnancies at risk for these complications. The results of this prospective observational study demonstrate that both elevated β-HCG levels and abnormal Doppler findings are significantly associated with the later development of preeclampsia and IUGR, especially when used in combination.

The findings of the present study indicate that women with β-HCG levels ≥2.5 MoM had a substantially higher incidence of preeclampsia and IUGR. This supports previous research suggesting that elevated β-HCG in the second trimester may reflect trophoblastic stress and early placental dysfunction [6]. Trophoblast invasion and remodeling of the uterine spiral arteries are crucial processes during early gestation, and disruptions in these processes can result in poor placental perfusion. Elevated β-HCG levels may be a compensatory response to suboptimal placental implantation or ischemia. Moreover, β-HCG also plays a role in promoting angiogenesis; dysregulated levels could therefore signal inadequate placental vascular development [7].

Similarly, uterine artery Doppler velocimetry findings revealed that increased pulsatility index (PI >1.45) and the presence of bilateral diastolic notches were significantly more frequent among those who later developed preeclampsia or IUGR. These findings are consistent with studies that have demonstrated uterine artery Doppler abnormalities as early indicators of impaired trophoblastic invasion and high-resistance uteroplacental circulation [8]. The presence of notching and high PI reflects increased vascular resistance, which is incompatible with the low-resistance flow needed for optimal fetal development. In particular, bilateral notching has been associated with more severe forms of uteroplacental insufficiency [9].

The diagnostic accuracy of these markers was further enhanced when used in combination. Our study showed that the combined sensitivity and specificity of elevated β-HCG and abnormal uterine artery Doppler for predicting preeclampsia or IUGR reached 88.9% and 91.3%, respectively. This highlights the potential utility of integrated biochemical and biophysical markers for second trimester screening. Similar dual-parameter approaches have been proposed in prior studies and are being explored in various international screening models [10].

Interestingly, the dual-positive group in our cohort also experienced significantly earlier deliveries and lower neonatal birth weights, reinforcing the clinical relevance of these predictors. Pregnancies with both elevated β-HCG and abnormal Doppler findings were more likely to end in preterm birth and deliver growth-restricted infants. These outcomes underscore the utility of such screening not only for risk stratification but also for guiding the intensity of prenatal surveillance and interventions [11].

While first trimester markers such as pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF), and mean arterial pressure (MAP) have shown good predictive accuracy, their availability in many low- and middle-income countries is limited. In contrast, serum β-HCG and uterine artery Doppler studies are more readily available and cost-effective, making them suitable for routine second trimester screening in resource-constrained settings [12].

This study focused specifically on primigravidas, a population with inherently limited obstetric history that makes early risk stratification more challenging. The identification of simple, reliable, and non-invasive screening tools is particularly important in this group, as first-time pregnancies are often at higher risk for preeclampsia due to immunological maladaptation and inadequate maternal-fetal interface remodeling [13]. The ability to identify high-risk individuals in the second trimester opens opportunities for timely prophylactic measures, such as the administration of low-dose aspirin, closer monitoring, and planned delivery strategies to improve outcomes [14].

Despite the promising findings, certain limitations of the study must be acknowledged. The sample size, although adequate for preliminary evaluation, limits the generalizability of the results. Larger multicentric studies are needed to confirm these findings across diverse populations. Additionally, the Doppler measurements were obtained only once during the second trimester. Serial Doppler evaluations may provide better insight into evolving uteroplacental resistance patterns [15].

This study demonstrates that elevated second trimester serum β-HCG levels (≥2.5 MoM) and abnormal uterine artery Doppler findings (high PI and/or bilateral notching) are significant predictors of preeclampsia and intrauterine growth restriction in primigravidas. When used together, these markers offer high sensitivity and specificity, improving early detection of at-risk pregnancies. Incorporating these cost-effective and accessible screening tools into routine antenatal care, especially in low-resource settings, can facilitate timely interventions, closer monitoring, and improved maternal-fetal outcomes. Given the increased predictive accuracy when used in combination, this dual-parameter approach should be considered as a practical alternative to more complex first trimester models where advanced testing is not available.

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