On the issue of preeclampsia screening efficiency

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Introduction

Hypertensive disorders during pregnancy remain one of the leading causes of maternal and perinatal morbidity and mortality, which makes the prediction and prevention of subsequent complications an urgent and persistent challenge in modern obstetrics [1]. According to WHO data, hypertensive syndrome affects 4–8 % of pregnant women, with severe preeclampsia (PE) diagnosed in approximately 5 per 1,000 pregnancies and eclampsia in 5 per 10,000 pregnancies1. In the Russian Federation, PE prevalence ranges from 7 % to 16 %, showing no downward trend due to increasing rates of severe and atypical PE forms [2; 3]. PE and eclampsia rank among the top causes of mortality in pregnant, laboring, and postpartum women [4; 5].

Despite numerous studies on the etiology, pathogenesis, and development of new methods for prediction, prevention, and treatment, the incidence of hypertensive pregnancy complications remains high [6]. Issues of prediction, early diagnosis of preeclampsia (PE), and forecasting subsequent complications remain extremely relevant to this day.

Traditional screening for preeclampsia risk is mandated by most international clinical guidelines. It involves assessing clinical risk factors in early pregnancy [7]. Risk factors are evaluated independently and summed either without specifying risk levels or by classifying them as high-risk when any major factor is present or moderate-risk with one or more moderate factors2. While simple, this approach fails to comprehensively integrate factors or provide systematic risk stratification for this complication [8].

According to current Russian clinical guidelines, PE risk group stratification is recommended during preconception counseling or at the first prenatal visit. Optimal PE screening incorporates risk calculation based on clinical risk factors, mean arterial pressure (MAP) measurement, uterine artery pulsatility index assessment, and placental growth factor (PlGF) testing. However, PlGF remains a minimally accessible biochemical marker in practice3.

The management strategy for pregnant women who either did not undergo screening or were classified as moderate-risk after screening remains unresolved. This creates a need to develop and implement unified prediction algorithms to enable timely preventive measures for this severe pregnancy complication.

The objective of the study was to analyze risk factors for preeclampsia development and evaluate their role in predicting this complication through retrospective analysis of medical records data.

Materials and Methods

The study was conducted at the M.A. Tverie Perm Regional Clinical Hospital (GBUZ PK GKB). A retrospective analysis of medical records (delivery records, pregnancy exchange cards) was performed for 55 patients with completed pregnancies. Two groups were formed: Group I comprised 33 postpartum women with diagnosed preeclampsia (PE) – the main study group, while Group II included 22 patients without hypertensive complications – the comparison group.

A comprehensive assessment of clinical and anamnestic risk factors for PE was performed, such as: PE, fetal growth restriction, premature detachment of a normally situated placenta, antenatal fetal death in a previous pregnancy; family history of PE, hydatidiform mole, thromboses, polycystic ovary syndrome in the medical history; advanced maternal age, primigravidity, multiple pregnancy, interpregnancy interval of less than 2 years or more than 10 years, pregnancy conceived with a new sexual partner, pregnancy resulting from assisted reproductive technologies, first-trimester chorionic detachment, obesity, excessive gestational weight gain, as well as the presence of extragenital pathologies: chronic kidney disease, diffuse connective tissue disorders, chronic arterial hypertension, diabetes mellitus, antiphospholipid syndrome, migraine, and uncontrolled hypothyroidism.

The study also included an analysis of first-trimester comprehensive screening data from 11 weeks to 13 weeks 6 days: mean arterial pressure (MAP), uterine artery pulsatility index (PI), pregnancy-associated plasma protein A (PAPP-A) levels. Uterine artery PI and PAPP-A were assessed in multiples of the median (MoM), while MAP was evaluated in mmHg and MoM. Risk calculation was performed using software developed by the Fetal Medicine Foundation (FMF).

In Group 1 patients, 8 women lacked proper first screening data in their medical records due to either not being registered for prenatal care or late registration, as well as non-compliance with first screening protocols; therefore, they were excluded from the study.

Statistical analysis of the obtained results was performed using StatTech v. 3.1.6 software (developer: StatTech LLC, Russia).

The Shapiro-Wilk test was used to assess whether quantitative variables followed a normal distribution.

Quantitative variables with normal distribution were described using arithmetic means (M) and standard deviations (SD), with 95 % confidence interval (95 % CI) boundaries. For quantitative data without normal distribution, median (Me) and lower and upper quartiles (Q₁–Q₃) were used.

Categorical data were described using absolute values and percentages. Comparison of proportions in multinomial contingency tables was performed using Pearson’s chi-square test.

Comparison between two groups for quantitative variables with non-normal distribution was performed using the Mann–Whitney U-test.

Results and Discussion

The mean age of subjects in Group I was 28.4 ± 7.0 years, while in Group II it was 29.4 ± 5.3 years.

Among Group I patients, moderate PE was diagnosed in one case (4 %), while severe PE was diagnosed in 24 women (96 %). Early-onset PE (before 34 weeks of gestation) developed in 9 cases (36 %), and late-onset PE – in 16 cases (64 %). All patients had singleton pregnancies. The mean gestational age at delivery was 35.3 ± 3.6 weeks in Group I and 39.9 ± 1.1 weeks in Group II.

Analysis of reproductive age parameters in the compared groups revealed no statistically significant differences (p>0.05).

The mean body weight at delivery was 81.2 ± 15.7 kg in Group I and 79.1 ± 1.5 kg in Group II (p>0.05). Prior to pregnancy, obesity was diagnosed in 4 (16 %) patients in Group I and in 1 (4.5 %) patient in Group II (p>0.05).

No patients in either study group had a history of placental abruption in previous pregnancies, hydatidiform mole, antiphospholipid syndrome, diabetes mellitus, uncontrolled hypothyroidism, or were over 40 years of age. There were no cases of pregnancy with a new sexual partner among patients in either group.

Analysis of clinical and anamnestic risk factors such as history of PE, fetal growth restriction in previous pregnancy, family history of PE, history of thromboses, history of polycystic ovary syndrome, interpregnancy interval of less than 2 years or more than 10 years, pregnancy resulting from assisted reproductive technologies, first-trimester chorionic detachment, obesity, excessive gestational weight gain, chronic kidney disease, diffuse connective tissue disorders, chronic arterial hypertension, migraine, and uncontrolled hypothyroidism revealed no statistically significant differences between the groups (p>0.05).

In Group I, primigravidity was observed in 16 cases (64 %), compared to 5 cases (21.7 %) in Group II. The differences were statistically significant (p< 0.01). The odds of developing preeclampsia were 6.0 times higher in primigravid women than in multigravid women (95 % CI: 1.7–21.9).

A history of antenatal fetal demise was present in 4 cases (16 %) in Group I and absent in Group II, which also proved to be a significant risk factor (p< 0.01).

Analysis of cumulative preeclampsia risk factors revealed: in Group I, no patients lacked risk factors (0 %), while in Group II, 5 women (22.8 %) had none; 3 patients (12 %) in Group I had one risk factor versus 9 (40.9 %) in Group II; 8 (32 %) in Group I had two risk factors compared to 6 (27.3%) in Group II; 9 (36 %) in Group I had three risk factors versus 1 (4.5 %) in Group II; and finally, 5 women (20 %) in Group I had four or more risk factors compared to 1 (4.5 %) in Group II.

Comparative analysis of first-trimester screening parameters revealed no statistically significant differences in uterine artery PI or PAPP-A levels between the study groups (p > 0.05). However, significant differences were observed in mean arterial pressure (MAP) between the compared groups (p < 0.05).

Elevated mean arterial pressure (MAP) in the first trimester proved to be a significant risk factor for hypertensive disorders in the second half of pregnancy (Tables 1, 2). The mean gestational age at first-trimester screening was 12.5 ± 0.5 weeks in Group I and 12.2 ± 0.6 weeks in Group II.

 

Table 1 Analysis of mean arterial pressure by pregnancy outcomes, mmHg

Group	Mean arterial pressure, mmHg			p
	Me	Q₁ – Q₃	n
I	91,5	84,8–93,5	25	0,000154
II	83,1	78,0–85,4	22

 

Table 2 Analysis of mean arterial pressure by pregnancy outcomes, MoM

Group	Mean arterial pressure, МоМ			p
	Me	Q₁ – Q₃	n
I	1,1	1,0–1,10	25	0,0002037
II	1,0	0,9–1,0	22

 

According to risk calculation results using FMF software, only 4 cases (16 %) in Group I were identified as high risk for early-onset preeclampsia, while no such cases were observed in Group II.

It should be noted that in Group I, prophylactic acetylsalicylic acid therapy was recommended in 13 cases (52 %). The mean gestational age at initiation of preventive measures was 17.5 ± 5.9 weeks, i.e., by the completion of the second wave of cytotrophoblast invasion, after which preventive measures become ineffective [9; 10].

Conclusions

The study revealed that the principal clinical and anamnestic risk factors for preeclampsia development were: primigravidity, antenatal fetal demise in previous pregnancy, and higher baseline mean arterial pressure. The standardized preeclampsia screening method based on first-trimester risk calculation identified high-risk cases in only 16 % of instances.

Thus, despite the widespread implementation of comprehensive preeclampsia screening programs, the prediction problem remains unsolved. Given the limited availability of expensive laboratory markers for predicting obstetric complications across different healthcare levels, the search for reliable anamnestic and clinical predictors remains relevant. Particular attention should be given to a multifactorial approach based on assessing factor combinations, as no single isolated marker can provide high screening sensitivity. This necessitates further development of unified algorithms for early prediction of hypertensive pregnancy complications, which would enable timely prevention of this severe condition.

 

1 WHO recommendations: policy of interventionist versus expectant management of severe pre-eclampsia before term. Geneva: World Health Organization 2018.

2 Galinova I.V., Sadykova G.K., Olina A.A. Method for forming a high-risk group for pregnancy and childbirth complications. Database Registration Certificate RU 2021621285, 17.06.2021. Application No. 2021621182 dated 10.06.2021; Clinical Guidelines of the Ministry of Health of the Russian Federation “Normal Pregnancy”. Moscow, 2023.

3 Clinical Guidelines of the Ministry of Health of the Russian Federation “Preeclampsia. Eclampsia. Edema, Proteinuria and Hypertensive Disorders During Pregnancy, Childbirth and the Postpartum Period”. Moscow, 2021.

About the authors

M. M. Padrul

Ye.A. Vagner Perm State Medical University

Email: elena_turova06@mail.ru
ORCID iD: 0000-0002-6111-5093

DSc (Medicine), Professor, Head of the Department of Obstetrics and Gynecology №1

Russian Federation, Perm

Е. V. Turova

Ye.A. Vagner Perm State Medical University

Author for correspondence.
Email: elena_turova06@mail.ru
ORCID iD: 0009-0006-8019-5048

Assistant of the Department of Obstetrics and Gynecology №1

Russian Federation, Perm

A. G. Trushkov

Ye.A. Vagner Perm State Medical University

Email: elena_turova06@mail.ru
ORCID iD: 0009-0002-6068-8436

Associate Professor of the Department of Obstetrics and Gynecology №2

Russian Federation, Perm

References

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