Hypertension-related complications, such as intravascular coagulation and histopathologic lesions (mostly massive perivillous fibrin deposition), may also affect blood flow to the fetus and therefore affect normal growth. Furthermore, elevated blood pressure may hamper the development of the placental villous tree. ^[1] This results in a general decline in placental function and a decrease in fetal growth. Therefore, gestational hypertension is a major risk factor for the birth of SGA neonates. ^[2]

In the context of screening for preeclampsia in the first trimester, the standard practice of administering aspirin is influenced by the data related to arterial pressure and blood flow in both uterine arteries, which is consistent with the findings from the ASPRE trial. Modern predictive models for PE according to the Fetal Medicine Foundation’s algorithm, including history with risk factors, uterine artery flows, and blood pressure measurements, determine the risk of PE and FGR, and the inclusion of biochemical markers such as PAPP-A or PlGF in this risk calculation further increases the sensitivity of the method. ^[3]

The human chorionic gonadotropin is a hormone composed of glycoprotein consisting 237 amino acids with a molecular weight of 36.7 kDa. It has two subunits; α-hCG having a molecular weight of 14.5 kDa and β-hCG having a molecular weight of 22.2 kDa. It is mostly produced by syncytiotrophoblastic cells of the placenta during pregnancy and small concentration of β-hCG is also secreted by the pituitary gland, liver and the colon. During pregnancy β-hCG has been observed to play a fundamental role, it stimulates the corpus luteum to produce progesterone to maintain the pregnancy. ^[4]

Since, β-hCG have a different role in pregnancy, thus one study suggested low levels of serum β-hCG as a predictor of poor pregnancy outcome in early pregnancy and the common complications related to altered β-hCG are ectopic pregnancies as well as spontaneous miscarriage. On the other hand, levels of β-hCG can vary extensively among women with normal pregnancies. ^[5]

Typically, serum and urine concentrations of β-hCG rise exponentially in the first trimester of pregnancy, doubling about every 24 hours during the first 8 weeks and the peak β-hCG level is usually around 10 weeks of gestation and then β-hCG levels decrease until about the 16^th week of gestation where they remain fairly constant until term. The patients which observe β-hCG levels plateau prior to 8 weeks or which fail to double commonly have a non-viable pregnancy, whether intrauterine or extrauterine. ^[6,7]

4.1 This is prospective, Non-Randomized and observational study was conducted in the Department of Biochemistry, Index Medical College from 2022 to 2023.

4.1.1 Inclusion criteria

First time pregnant women, who was aged 18- 40 years with singleton pregnancy, was included in the study.

4.1.2 Exclusion criteria

First time pregnant women who was aged less than 18 years and more than 40 years or had multiple pregnancies were excluded from the study.

Recruitment of study participants

A total of 200 pregnant women attending the antenatal clinic of the Department of Obstetrics and Gynaecology and Biochemistry was interviewed over a period of 13 months (from 1 July, 2022 to 31st July, 2024).

Out of these 130 singleton pregnant women was found eligible and recruited into the study. Detailed information was given about the study and informed consent obtained for participation in the study. Each subject was randomly and consecutively selected, representing a cross- sectional study of the Indore population.

Women at POG >22 weeks with Singleton pregnancy were included a one hundred thirty Hypertensive women as case group and control group include another one hundred thirty normotensive women after matching the parity and gestation age.

The gestational age at recruitment was 14-24 weeks (second trimester). Gestational age was estimated from the date of last menstrual period (LMP), if it was available, and confirmed from the abdomen/pelvic ultra sound scan. The abdomen/pelvic ultra sound scan also looked for fetal defects and multiple pregnancies. Gestational age was expressed in completed weeks (eg 12 weeks 6 days, is taken as 12 weeks).

At the time of recruitment, each subject completed a questionnaire with the help of the principal investigator. The questionnaire obtained information on maternal age, maternal weight, and height, smoking habits, alcohol intake, intake of drug supplements (such as iron, folic acid and vitamins), marital status, religion, tribe, educational background, occupation, blood group and Rhesus factor, family history of high BP and gestational hypertension.

The weight was measured to the nearest kilograms (kg) and height to the nearest centimeter (cm) to calculate the Body Mass Index (BMI). Blood pressure was taken after the subjects had rested for 15 minutes.

4.4 Demographics

The demographics that was recorded for each subject was maternal age, marital status, religion, ethnicity, educational background, occupation, gestational age (using the day of LMP and AUS), weight, height, blood pressure, smoking habits, intake of alcohol and supplements usage, blood group and Rhesus factor and sickling status.

4.5 Laboratory analysis

4.5.1 Hb and urine protein determination

Measurement of Hb was immediately performed after blood collection using ABx pentra 60 C+ automated hemocounter. Urine protein was also determined by the use of dip sticks.

4.6 Statistical analyses

Student’s t-test was used to test for differences between means of concentrations of Mg2+ and hCG at recruitment and between mean concentrations of Mg2+ and hCG in normal and adverse pregnancies. Means of Hb, SBP and DBP, UP, BMI, and age in the cases group was all compared with that of the controls. Statistical significance was determined at P< 0.05. The SPSS software version 29^th was used in all calculations to establish the significance

Graph 5.1: Distribution of Age of the patient’s

In our study the percentage of individuals under 20 years is the same for both groups (5.3%). P-value = 0.679: This indicates no statistically significant difference in the prevalence of individuals under 20 between the PIH and normotensive groups. In this age group, the PIH group has 39 individuals (30%), while the normotensive group has 55 individuals (42.3%). P-value = 0.029: This is less than 0.05, indicating a statistically significant difference. This means that individuals in this age group are more likely to be normotensive compared to having PIH.

Graph 5.2: Distribution of area wise patients

In this study, the distribution of individuals between rural and urban areas is slightly different for the PIH and normotensive groups. However, these differences are not statistically significant, as the p-value in both cases is greater than the typical threshold of 0.05. Rural Areas: A higher percentage of individuals with PIH (60.7%) live in rural areas compared to normotensive individuals (50.7%). However, this difference could be due to chance and is not significant. Urban Areas: A higher percentage of normotensive individuals (49.3%) live in urban areas compared to those with PIH (39.3%). Again, this difference is not statistically significant.

Graph 5.3: Distribution of Socioeconomic status

Graph 5.4: Distribution of BMI

Graph 5.5: Distribution of patient according to period of gestation

Graph 5.6: Systolic blood pressure of the patients are depicted below.

In this study, Normotensive Group: All normotensive individuals have systolic BP <140 mmHg. By definition, systolic BP <140 mmHg is classified as normal, so this result aligns with expectations. PIH Group: None of the individuals with PIH have systolic BP <140 mmHg, as hypertension is characterized by systolic BP ≥140 mmHg. A majority of PIH cases (52.3%) have systolic BP in the 140–150 mmHg range, indicative of mild hypertension. A significant proportion (37.6%) have systolic BP in the 150–160 mmHg range, while a smaller subset (10%) have readings >160 mmHg, suggesting severe hypertension. This indicates a statistically significant difference in systolic BP distribution between the PIH and normotensive groups. The absence of overlap between the groups highlights the distinction in BP levels.

Graph 5.7: Diastolic blood pressure of the patients are depicted below

The majority of individuals in both groups fall into this age range. The PIH group has a slightly higher percentage (43.07%) than the normotensive group (36.1%). P-value = 0.256: This is greater than 0.05, indicating no statistically significant difference in the proportion of individuals in this age range between the two groups. In this age group, the PIH group has 28 individuals (21.53%) compared to 21 individuals (16.1%) in the normotensive group. P-value = 0.435: Again, this is greater than 0.05, showing no significant difference between the two groups.

“Patients diagnosed with PIH saw a significant increase in their systolic BP levels in both the early and late stages of the disease. According to the findings of this research, beta-hCG levels in the blood and lipid profiles taken during the second trimester of pregnancy can assist in the identification of pregnant women who are at an increased risk of developing PIH, preeclampsia, or eclampsia. ^[8-12] Upadhyay et al demonstrated that the ratio of albumin to creatinine is an extremely accurate predictor of the presence of proteinuria and that it is suitable for use as a convenient alternative test. ^[13]

The beta-hCG blood levels were discovered to be a significant clinical diagnostic for predicting PE during the early stages of the second trimester. On the other hand, their predictive power was found to be restricted during the first trimester. ^[14] However, further study on the predictive ability of hCG in populations that are bigger and more diverse is required needed. ^[115] Similar to present study Kumari et al documented. When compared with normotensive women, hypertensive disorders of pregnancy are associated with greater levels of serum betahCG. The levels are also greater in patients who have severe preeclampsia as opposed to patients who have nonsevere preeclampsia, and they are higher in primigravida hypertension women as opposed to multigravida hypertensive women. ^[16]

In cases of early onset preeclampsia, it has also been noted that the levels of b-hCG in the serum are higher than normal. Therefore, determining the levels of b-hCG in the blood can potentially assist in the early identification of hypertensive disease of pregnancy, and it also has the potential to act as an indication of the degree to which the condition has progressed. ^[17] Because of its low sensitivity and the difficulty in determining where the cut off value should be, the serum b-hCG test has limited application as a diagnostic tool. ^[18] Serum beta-hCG estimate in primigravida patients at the middle of the first trimester (13-20 weeks) is an excellent predictor of PIH, and greater levels of beta-hCG are related with increased PIH severity. ^[19]

The current study revealed that maternal serum beta hCG estimate in the mid-trimester (13-20 weeks) is a good predictor of the development of hypertensive problems during pregnancy. ^[20] Raised ACR levels were shown to be associated with illness severity as well as a poor fetomaternal outcome in our investigation. ^[21] Amin et al demonstrated that the random urine protein: creatine ratio is a more accurate means of assessing proteinuria in hypertensive pregnant women than the dipstick approach. ^[22]

Clinical laboratories, on the other hand, should standardise the reference values for their setting. ^[23] Study showed that measuring second trimester beta-hCG levels is useful in clinical practice to identify women who will develop PIH in the same pregnancy. Also, higher levels of beta-hCG are associated with increase severity of PIH. The sample size for this study being small, necessitate the need of further large scale studies considering the importance of B-hCG in PIH prediction. ^[24]

This study showed that estimation of serum Beta HCG levels in early second trimester of pregnancy is a useful indicator to identify women who are likely to develop gestational hypertension in the same pregnancy. The level of beta HCG is strongly associated with development of GHT. This can be used as “POWERFUL PREDICTIVE TOOL” by the obstetricians for early identification and expert management of gestational hypertension. βHCG are low to be useful as a mass screening marker as a single tool and therefore it should be combined with other serum markers and ultrasound parameters like Doppler study of uterine vessels, which will help in improving its role as a screening tool.

1. Olsen RN, Woelkers D, Dunsmoor-Su R, LaCoursiere DY. Abnormal second-trimester serum analytes are more predictive of preterm preeclampsia. Am J Obstet Gynecol. 2014;207:228. doi: 10.1016/j.ajog.2012.06.006. e1-7. [DOI] [PubMed] [Google Scholar]
2. Ree PH, Hahn WB, Chang SW, Jung SH, Kang JH, Cha DH, Kang MS, Huh JY. Early detection of preeclampsia using inhibin a and other second-trimester serum markers. Fetal Diagn Ther. 2014;29:280. doi: 10.1159/000322742. –. [DOI] [PubMed] [Google Scholar]
3. Yefet E, Kuzmin O, Schwartz N, Basson F, Nachum Z. Predictive Value of Second-Trimester Biomarkers and Maternal Features for Adverse Pregnancy Outcomes. Fetal Diagn Ther. 2017. 
4. Fafula VR, Iefremova PU, Onufrovych KO, Maksymyuk VH, Besedina SA, Nakonechnyi AI, Vorobets ZD, Vorobets DZ. Alterations in Arginase-No-Synthase System of Spermatozoa in Human Subjects with Different Fertility Potential. J Med Biochem. 2018;37:134.
5. Jelliffe-Pawlowski LL, Baer RJ, Currier RJ, Lyell DJ, Blumenfeld YJ, El-Sayed YY, Shaw GM, Druzin ML. Early-onset severe preeclampsia by first trimester pregnancy- associated plasma protein A and total human chorionic gonadotropin. Am J Perinatol. 2015;32:703. doi: 10.1055/s-0034-1396697
6. Revankar VM, Narmada L. Assessment of serum β- hCG and lipid profile in early second trimester as predictors of hypertensive disorders of pregnancy. Int J Gynecol Obstet. 2017;138:331. doi: 10.1002/ijgo.12225. –. [DOI] [PubMed] [Google Scholar]
7. Oliveira N, Magder LS, Blitzer MG, Baschat AA. Firsttrimester prediction of pre-eclampsia: external validity of algorithms in a prospectively enrolled cohort. Ultra – sound Obstet Gynecol. 2014;44:279. doi: 10.1002/uog.13435. –. [DOI] [PubMed] [Google Scholar]
8. Scazzocchio E, Figueras F, Crispi F, Meler E, Masoller N, Mula R, Gratacos E. Performance of a first-trimester screening of preeclampsia in a routine care low-risk setting. Am J Obstet Gynecol. 2014;208:203e, 1. doi: 10.1016/j.ajog.2012.12.016. –. [DOI] [PubMed] [Google Scholar]
9. Parra Cordero M, Rodrigo R, Barja P, Bosco C, Rencoret G. Prediction of early and late pre–eclampsia from maternal characteristics, uterine artery Doppler and markers of vasculogenesis during first trimester of pregnancy. Ultrasound Obstet Gynecol. 2014;41:538. doi: 10.1002/uog.12264. –. 
10. Kuc S, Wortelboer EJ, van Rijn BB, Franx A, Visser GH, Schielen PC. Evaluation of 7 serum biomarkers and uterine artery Doppler ultrasound for first-trimester prediction of preeclampsia: a systematic review. Obstet Gynecol Surv. 2014;66:225. doi: 10.1097/OGX.0b013e3182227027. –. [DOI] [PubMed] [Google Scholar]
11. Kaijomaa M, Rahkonen L, Ulander VM, Hamalainen E, Alfthan H, Markkanen H, Heinonen S, Stefanovic V. Low maternal pregnancy–associated plasma protein A during the first trimester of pregnancy and pregnancy outcomes. Int J Gynecol Obstet. 2017;136:76. doi: 10.1002/ijgo.12002. –. [DOI] [PubMed] [Google Scholar]
12. Huang T, Hoffman B, Meschino W, Kingdom J, Okun N. Prediction of adverse pregnancy outcomes by combinations of first and second trimester biochemistry markers used in the routine prenatal screening of Down syndrome. Prenat Diagn. 2014;30:471. doi: 10.1002/pd.2505.  
13. Jobe SO, Tyler CT, Magness RR. Aberrant synthesis, metabolism and plasma accumulation of circulating estrogens and estrogen metabolites in preeclampsia: implications for vascular dysfunction. Hypertension. 2014;61:480. doi: 10.1161/HYPERTENSIONAHA.111.201624. –. 
14. Cohen JL, Smilen KE, Bianco AT, Moshier EM, Ferrara LA, Stone JL. Predictive value of combined serum biomarkers for adverse pregnancy outcomes. Euro J Obstet Gynecol Reprod Biol. 2014;181:89. doi: 10.1016/j.ejogrb.2014.07.018. –. [DOI] [PubMed] [Google Scholar]
15. Husslein, H., Lausegger, F., Leipold, H. & Worda, C. Association between pregnancy-associated plasma protein-A and gestational diabetes requiring insulin treatment at 11–14 weeks of gestation. J. Matern. Fetal Neonatal. Med. 25, 2230–2233 (2014).
16. Nguyen-Ngo, C., Jayabalan, N., Salomon, C. & Lappas, M. Molecular pathways disrupted by gestational diabetes mellitus. J. Mol. Endocrinol. 63, R51–R72. https://doi.org/10.1530/jme-18-0274 (2019).
17. Huber, A. V., Saleh, L., Prast, J., Haslinger, P. & Knöfer, M. Human chorionic gonadotrophin attenuates NF-kappaB activation and cytokine expression of endometriotic stromal cells. Mol. Hum. Reprod. 13, 595–604. https://doi.org/10.1093/molehr/gam032 (2017).
18. Zhang, Z., Yu, D., Yin, D. & Wang, Z. Activation of PI3K/mTOR signaling pathway contributes to induction of vascular endothelial growth factor by hCG in bovine developing luteal cells. Anim. Reprod. Sci. 125, 42–48. https://doi.org/10.1016/j.anireprosci.2011. 03.002 (2021).
19. Honarjoo, M., Kohan, S., Zarean, E. & Tarrahi, M. J. Assessment of β-human-derived chorionic gonadotrophic hormone (βhCG) and pregnancy-associated plasma protein A (PAPP-A) levels as predictive factors of preeclampsia in the frst trimester among Iranian women: A cohort study. BMC Pregnancy Childbirth 19, 1–5 (2019).
20. Quattrocchi, T. et al. Maternal serum PAPP-A as an early marker of obstetric complications?. Fetal Diagn. Ter. 37, 33–36. https:// doi.org/10.1159/000365147 (2015).
21. Gu W, Lin J, Hou Y. The value of maternal first and second trimester serum data of β-hCG, PAPP-A, AFP and uE3 in the prediction of preeclampsia. Zhonghua Fu Chan Ke Za Zhi. 2015;50:101.
22. . Kagan, K. O., Wright, D., Valencia, C., Maiz, N. & Nicolaides, K. H. Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free β-hCG and pregnancy-associated plasma protein-A. Hum. Reprod. 23, 1968–1975 (2018).
23. Nicolaides, K. H. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat. Diagn. 31, 7–15 (2014).
24. Said, M., Campbell, D., Azzam, M. & MacGillivray, I. Beta-human chorionic gonadotrophin levels before and afer the development of pre-eclampsia. BJOG Int. J. Obstetr. Gynaecol. 91, 772–775 (2014).