European Journal of Cardiovascular Medicine

The complex range of conditions known as pregnancy-related hypertension disorders has a significant negative impact on people's health in both developed and developing countries worldwide.  They play a significant role in maternal and newborn mortality and morbidity.  Around the world, hypertension disorders impact five to ten percent of pregnancies.  A high-risk pregnancy condition that can endanger both the mother and the unborn child is pre-eclampsia.  Pre-eclampsia is responsible for 16–18% of maternal deaths and up to 40% of fetal deaths. [1] Eclampsia or severe pre-eclampsia kills around 200 pregnant women every day, or 72,000 women annually.  According to data from the National Eclampsia Registry (NER) over the last three years, 2,554 people in India presented with eclampsia, and the incidence of hypertensive diseases is 10.08 percent (11,266 out of 1,11,725 births). [2] The prevalence of pre-eclampsia is higher in first-time mothers, at 13–20%.  The only condition that kills more pregnant women than pre-eclampsia/eclampsia is hemorrhage.  A woman in a developing country has a roughly 300-fold greater risk of developing pre-eclampsia or eclampsia than a woman in a wealthy country.  The startlingly early age at which many couples decide to get married is reflected in the fact that 17% of pre-eclampsia patients are teenagers, despite numerous education efforts and laws.  Young adults (those between the ages of 21 and 30) made up about 76% of the patients, making them an especially susceptible and ill demographic.  Since 81% of patients with pre-eclampsia are also pregnant for the first time, the ailment is primarily a primi gravida condition.

Hypertension (blood pressure 140 mmHg systolic or 90 mmHg diastolic) is regarded as new-onset at or after 20 weeks of pregnancy and may be a sign of gestational hypertension, pre-eclampsia, or transient gestational hypertension. [3]. By recording normal blood pressure before or throughout the first few months of pregnancy, a pregnancy-related decline in blood pressure can be prevented.  A normal blood pressure reading, when measured for the first time after 12 weeks of pregnancy, may merely reflect the normal drop in blood pressure from baseline that occurs by the end of the first trimester; however, this drop may have hidden underlying chronic hypertension. It has been connected to fetal developmental delays and is a leading cause of disease and death in both mothers and their babies.  Additionally, pre-eclampsia increases the risk of cardiovascular disease in the future for both the mother and the child.  Although pre-eclampsia is widely acknowledged to be a severe health problem, unresolved questions regarding its origin have caused progress in the condition's prevention and treatment to stall.

Study Area: The DARBHANGA MEDICAL COLLEGE AND HOSPITAL. This hospital is a tertiary care referral centre in eastern India.

Study Design: Prospective observational study

Study Population: One hundred first-time mothers who met the study's requirements were enrolled between weeks 11 and 14 of their pregnancies. Six weeks after giving birth, they continued to be monitored to see how they were doing.

Study Duration: The time frame for this 18-month research was from March 2021 to December 2022.

Sample Size: 100

Inclusion Criteria:

·         Primigravida in first trimester with singleton pregnancy

·         Willing to participate in study

Exclusion Criteria:

·         Women with history of chronic hypertension.

·         Women with diabetes.

·         Women with chronic renal, liver or autoimmune disorders

·         Multiple pregnancy

Follow Up: Till 6 weeks postpartum

Ethical Issue:

Ethical clearance The DARBHANGA MEDICAL COLLEGE AND HOSPITAL institutional ethics committee gave its permission to the study before it began.

Informed Consent

All pregnant women who met the selection criteria and their partners were briefed on the nature of the study (Appendix I) and gave their consent in writing (Appendix II). They may leave the study whenever they wanted. All patients had a thorough history obtained, and then they were examined from head to toe and inside the stomach to rule out any underlying medical conditions.

Statistical Analysis:

For statistical analysis, data were initially entered into a Microsoft Excel spreadsheet and then analyzed using SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism (version 5). Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests, which compare the means of independent or unpaired samples, were used to assess differences between groups. Paired t-tests, which account for the correlation between paired observations, offer greater power than unpaired tests. Chi-square tests (χ² tests) were employed to evaluate hypotheses where the sampling distribution of the test statistic follows a chi-squared distribution under the null hypothesis; Pearson's chi-squared test is often referred to simply as the chi-squared test. For comparisons of unpaired proportions, either the chi-square test or Fisher’s exact test was used, depending on the context. To perform t-tests, the relevant formulae for test statistics, which either exactly follow or closely approximate a t-distribution under the null hypothesis, were applied, with specific degrees of freedom indicated for each test. P-values were determined from Student's t-distribution tables. A p-value ≤ 0.05 was considered statistically significant, leading to the rejection of the null hypothesis in favour of the alternative hypothesis.

Table1. Distribution of the patients in Assisted (A) and Spontaneous (S) conception

Table 2. Distribution of Incidence of preeclampsia among women with normal and low PIGF levels

Table 3: Distribution of mean SBP at 1" visit (before 14 weeks of gestation)

Table 4: Distribution of mean BMI of the subjects

In our study, pre-eclampsia was observed in 11 patients (37.93%) in the assisted group and 21 patients (29.58%) in the spontaneous group. Although the incidence appeared higher in the assisted group, the difference was not statistically significant (p = 0.41).In our study, among patients with pre-eclampsia, 6 patients (17.14%) had normal values (>1.16), while 26 patients (40%) had abnormal values (<1.16). This difference was statistically significant (p = 0.01), indicating a potential association between abnormal values and pre-eclampsia.In our study, the mean systolic blood pressure (SBP) at the first visit was 112.86 ± 5.42 mmHg in the non-pre-eclampsia group and 114.06 ± 5.7 mmHg in the pre-eclampsia group. The difference was not statistically significant (p = 0.17).In our study, the mean BMI was 25.97 ± 8.53 kg/m² in the non-pre-eclampsia group and 26.49 ± 8.48 kg/m² in the pre-eclampsia group. This difference was statistically significant (p = 0.001), suggesting a possible association between higher BMI and pre-eclampsia.

Pre-eclampsia is linked to a high rate of morbidity and mortality in both the mother and the fetus.  Predicting pre-eclampsia in the first trimester of pregnancy is a relatively new concept.  Only a small number of screening methods have achieved adequate sensitivities and specificities for predicting pre-eclampsia, including biochemical screening indicators used for Down syndrome.  The varied nature of pre-eclampsia makes it impossible to predict with a single test.

We studied 100 first-time moms getting prenatal treatment at DMCH's outpatient clinic during a one-year period.  Between weeks 11 and 14 of pregnancy, transabdominal ultrasonography was utilized to assess the maternal serum PIGF levels in these women.  After 20 weeks of pregnancy, pre-eclampsia was noted at every appointment, and patients were observed for a total of six weeks following delivery.

The age range of the patients in this study was 26 to 35 years old.  Most of the patients in CN Sheela's (2012) investigations [4]

The BMI test for patients with normotension and pre-eclampsia.  The BMI measurements in the two groups were found to be significantly correlated.  Normotensive individuals had an average BMI of 25.97 kg/m2, while pre-eclamptic patients had an average BMI of 26.49 kg/m².

Motedayen et al. (2019)[5] also found that the average BMI of normal and pre-eclamptic individuals was 25.13 and 26.33 kg/m², which is consistent with the current study.  According to the study, one of the significant predictors in determining a pregnant woman's chance of developing pre-eclampsia is her body mass index.  An rise in BMI may raise the risk of pre-eclampsia.

The current investigation discovered no correlation between conception methods and pre-eclampsia.  37.93% of the 29 patients who had assisted conception went on to develop pre-eclampsia.  However, 29.58% of the 71 patients who conceived naturally went on to develop pre-eclampsia.  According to the findings, using an assisted conception method increases the chance of pre-eclampsia.

Conversely, Almasi-Hashiani (2019)[6] discovered a statistically significant correlation between the incidence of pre-eclampsia and the assisted method of conception, but also demonstrated an elevated risk of pre-eclampsia in patients with helped conception.  Different sample sizes, regional variances, study periods, and illness progression stages could all contribute to this statistical discrepancy.  According to Higgins and Green56, a number of possible factors, such as sample size, time period, regional trends, developmental stage, and type of research, may influence contentious statistical analysis.  The SBP and DBP at various gestational and postpartum phases. According to the current research, blood pressure is a key indicator of pre-eclampsia risk, particularly after 20 weeks of pregnancy.

Bullarbo and Rylander (2015) [7] also identified blood pressure measurement as a relevant parametric criterion for assessing pre-eclampsia, which is consistent with the current findings.  In the current investigation, we discovered that the PIGF MoM values in the pre-eclamptic and normotensie groups were 0.79 ± 0.40 and 1.16 ± 0.50, respectively.  Compared to the control group, it was lower in the pre-eclamptic group (Table 8.1).  With a sensitivity of 87.46%, a specificity of 75.62%, a positive predictive value of 53.21%, a negative predictive value of 94.17%, and an accuracy of 78%, the study's ROC curve indicated that the ideal cutoff PIGF value was ≤0.763 MoM.

A review by Chau et al. (2017) [8] also confirmed that PIGF concentration detection is an essential metric for pre-eclampsia diagnosis, prognosis, and treatment, which is consistent with current findings.  This could lower the rate of fetal death.

Our research also supports the findings of Salem et al. (2017)[9], who found that pre-eclamptic women's serum PIGF concentration was significantly lower (0.85 ± 0.2) than that of healthy women (1.02 ± 0.3).  50  Using the ROC curve, the study's ideal cutoff PIGF value was ≤0.91 MoM, yielding 90% sensitivity, 82.6% specificity, 36.5% positive predictive value, 98.7% negative predictive value, and 83% accuracy.

Similarly, Myatt et al. (2012)[10] discovered that PIGF was considerably lower in pre-eclamptic women than in controls (0.83 vs. 1.04, P<0.001).  With a specificity of 80% and a sensitivity of 32%, PIGF exhibited the largest area under the curve (0.61).

The median PIGF MoM values in a different study by Sung et al. (2017) [11] were 0.92 (95% CI 0.22 to 2.85).  It was 0.75± 0.29 in the preeclamptic group, compared to 1.00± 0.42 in the normotensive group.

According to Keikkala E (2014) [12], women who developed pre-eclampsia had substantially lower PIGF concentrations (median MoM, 95% CI: 0.62, 0.53 -0.79; P<0.001) than controls (1.00, 0.93-1.06).  Comparing women with early-onset (0.46, 0.21 0.67; P < 0.001) or severe pre-eclampsia (0.46, 0.40-0.60; P < 0.001) to controls revealed an even larger difference.  Salem et al. (2017) [13] observed similar results, showing higher specificity (99.3%) and PPV (89.5%) when the mean PI of uterine arteries at 11–13 weeks of pregnancy was compared to the first trimester PIGF serum level using a cut-off value <0.91MoM and a cut-off value ≥1.69.

The sensitivity of maternal serum biochemical indicators (PIGF) in our study was lower than anticipated, which may be explained by the difficulties of differentiating between high-risk and low-risk individuals as well as the difficulty of finding an enriched group for preeclampsia research.

A single maternal blood biomarker has a low clinically significant predictive value for preeclampsia.  These biomarkers, however, are more beneficial when combined with other metrics.

We concluded that placental growth factor, or PLGF, has become a promising biomarker for pre-eclampsia assessment and early identification.  Reduced PLGF levels were found to be substantially linked to pre-eclampsia in our investigation, confirming its use in detecting placental malfunction.  PLGF is a quantifiable, non-invasive marker that can help with risk assessment, prompt diagnosis, and better handling of impacted pregnancies.  Clinical decision-making may be improved and maternal and fetal outcomes may be improved by integrating PLGF testing into regular prenatal screening.  To confirm its usefulness and establish defined cut-off values for clinical practice, more extensive research is required.

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2.       Asha MB. Clinical Study of Maternal and Perinatal Outcome in Eclampsia (Master's thesis, Rajiv Gandhi University of Health Sciences (India)).

3.       Vindhyashree S. Study of Lipid Profile Parameters in Gestational Hypertension, Pre Eclampsia, Eclampsia in Comparison with Normal Pregnancy (Master's thesis, Rajiv Gandhi University of Health Sciences (India)).

4.       Sheela CN, Karanth S, Venkatachala RP, Sebastian R, Chandrakala BS, Crasta J. Twin pregnancy with a complete hydatidiform mole and coexisting foetus. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2016 Aug 1;5(8):2882.

5.       Motedayen M, Rafiei M, Tavirani MR, Sayehmiri K, Dousti M. The relationship between body mass index and preeclampsia: A systematic review and meta-analysis. International journal of reproductive biomedicine. 2019 Jul 31;17(7):463.

6.       Almasi-Hashiani A, Omani-Samani R, Mohammadi M, Amini P, Navid B, Alizadeh A, Khedmati Morasae E, Maroufizadeh S. Assisted reproductive technology and the risk of preeclampsia: an updated systematic review and meta-analysis. BMC pregnancy and childbirth. 2019 Dec;19:1-3.

7.       Bullarbo M, Rylander R. Diastolic blood pressure increase is a risk indicator for pre-eclampsia. Archives of Gynecology and Obstetrics. 2015 Apr;291:819-23.

8.       Chau K, Hennessy A, Makris A. Placental growth factor and pre-eclampsia. Journal of human hypertension. 2017 Dec;31(12):782-6.

9.       Salem H, Bauer E, Kirsch R, Berasategui A, Cripps M, Weiss B, Koga R, Fukumori K, Vogel H, Fukatsu T, Kaltenpoth M. Drastic genome reduction in an herbivore’s pectinolytic symbiont. Cell. 2017 Dec 14;171(7):1520-31.

10.    Myatt L, Clifton RG, Roberts JM, Spong CY, Hauth JC, Varner MW, Wapner RJ, Thorp Jr JM, Mercer BM, Grobman WA, Ramin SM. The utility of uterine artery Doppler velocimetry in prediction of preeclampsia in a low-risk population. Obstetrics & Gynecology. 2012 Oct 1;120(4):815-22.

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12.    Keikkala E, Ranta JK, Vuorela P, Leinonen R, Laivuori H, Väisänen S, Marttala J, Romppanen J, Pulkki K, Stenman UH, Heinonen S. Serum hyperglycosylated human chorionic gonadotrophin at 14–17 weeks of gestation does not predict preeclampsia. Prenatal diagnosis. 2014 Jul;34(7):699-705.

13.    Salem H, Bauer E, Kirsch R, Berasategui A, Cripps M, Weiss B, Koga R, Fukumori K, Vogel H, Fukatsu T, Kaltenpoth M. Drastic genome reduction in an herbivore’s pectinolytic symbiont. Cell. 2017 Dec 14;171(7):1520-31.