Placenta location, a prognostic determinant for the incidence of preeclampsia

doi:10.21203/rs.3.rs-5095663/v1

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Placenta location, a prognostic determinant for the incidence of preeclampsia

https://doi.org/10.21203/rs.3.rs-5095663/v1

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Background: Preeclampsia is one of the complications of pregnancy with uncertain etiology. Nevertheless, it is believed that the condition may arise due to abnormal trophoblastic invasion, resulting in vascular remodeling and increased resistance in the spiral arteries. It is assumed that the location of the placenta might have contributed to the formation of trophoblastic invasion and further placental supply. The current study aims to investigate the association of placental location with the incidence of preeclampsia

Methods: The current case-control study was conducted on 206 primigravid pregnant patients undergone routine screening ultrasonography study between 14 and 26 gestational weeks to determine the location of the placenta (anterior, posterior, or lateral). The patients were categorized as cases that met the criteria of high-risk for preeclampsia (n=106) or the controls (n=100).

Results: Logistic regression assessment revealed that increased age (OR: 1.047, 95%CI: 0.89-1.12; P-value=0.033), BMI> 25 kg/m2 (OR: 4.61, 95%CI: 1.02- 10.02; P-value=0.038), and anterior (OR: 2.79, 95%CI: 1.08-9.43; P-value=0.038) and posterior (OR: 1.056, 95%CI: 0.89-1.12; P-value=0.033) location of placenta were the predicting factors for the incidence of preeclampsia.

Conclusion: Based on the findings of the current study, anterior and posterior location of the placenta, increased age and BMI above 25 kg/m² were the predicting factors for preeclampsia development. Given that, it is recommended to closely monitor the individuals with anteriorly located placenta aiming at early diagnosis of persistent hypertension and applying approaches to minimize the adverse effects of preeclampsia.

Pregnancy

Preeclampsia

Placenta

Pregnancy complications

Hypertensive disorders account for 5–10% of all pregnancy-associated complications among which preeclampsia is the most critical one accounting for 3–7% of all pregnancies worldwide (1). This syndrome is defined as new hypertension with the systolic blood pressure of more than 140 and diastolic pressure of 90 mmHg after 20 weeks of gestational age together with proteinuria (more than 0.3 g/24 hours) and is contributed as one of the leading causes of morbidity and mortality; if remained untreated (2).

Despite the uncertain etiology of preeclampsia, it is believed that the condition may arise due to abnormal trophoblastic invasion, resulting in vascular remodeling and increased resistance in the spiral arteries. The uteroplacental vessel development occurs in two phases, primarily before the end of the first trimester and then, within 12–16 weeks of pregnancy. Therefore, the diastolic notch as indicative of resistance in Doppler of the uterine arteries can be justified (3). It is assumed that inappropriate uteroplacental vessel development can lead to hypoxia-reperfusion injury in the placenta, causing an accumulation of free radicals and reactive oxygen species within the maternal systemic circulation. Consequently, there is a disturbance in the balance between angiogenic and antiangiogenic factors, as well as vasodilators and vasoconstrictors (4).

The uterine and ovarian arteries play a critical role in supplying blood flow to the uterus. Each uterine artery is responsible for providing perfusion to the corresponding side of the uterus, and it contains numerous branches as well as anastomoses with the contralateral uterine artery (5). Ultrasonography studies have shown that the centrally located placenta has similar resistance in uterine arteries and the uteroplacental flow of blood and both uterine arteries participate to meet the needs, while this resistance differs in the uterine arteries with the laterally located placenta (6).

Previous studies have indicated that there are differences in blood supply distribution within the uterus based on the site of implantation and the location of the placenta. These differences are believed to have a significant impact on the outcome of the pregnancy (7, 8). Furthermore, evidence has shown variations in uteroplacental Doppler flow between the central and lateral sites in pregnancies with unilateral placentas. Additionally, there is also a known relationship between abnormal Doppler measurements and the occurrence of pre-eclampsia (9). However, it is important to note that there is limited research specifically focusing on the direct association between placental location and the development of pre-eclampsia, without considering other influencing factors. Given that, the current study aims to investigate whether the location of the placenta could serve as a straightforward predictor for the development of pre-eclampsia in the third trimester.

Study population

The current case-control study was conducted on 206 primigravid pregnant patients undergone routine screening ultrasonography study for preeclampsia at Shahid Beheshti Hospital, a tertiary referral center of obstetrics and gynecology, affiliated with Isfahan University of Medical Sciences, from April 2021 to May 2022.

The study proposal that met the tenets of the Helsinki Declaration was primarily proposed to the Ethics Committee of Isfahan University of Medical Sciences and approved via code number “IR.MUI.MED.REC.1398.498”. The study protocol was entirely explained to the patients and their spouses, they were reassured regarding the confidentiality of their personal information and the safety of the applied modes for both the mother and the fetus, and signed written consent.

Primigravid individuals with singleton pregnancies who had at least one-second trimester ultrasound examination (between 14 and 26 weeks) were included as cases and controls. High-risk preeclampsia patients were categorized as cases if they had characteristics including persistent high blood pressure after 20 weeks of pregnancy, elevated protein levels in the urine, low platelet count, and other indications of organ dysfunction such as lung fluid accumulation, and kidney or liver problems.

Those individuals with persistently elevated blood pressure between 14–24 weeks of pregnancy, a history of diabetes or hyperlipidemia, smoking history, no knowledge about the family history of preeclampsia, more than 20% flaw in the medical data, and who withdrew from the study were excluded.

The study population entered into the investigation through convenience sampling until reaching the desired number of participants. Medically qualified evaluators handled the participant enrollment, assignment, and assessment.

Then, the patients were categorized as cases or controls. Cases were selected among the individuals who were hospitalized due to the presence of parameters compatible with a high risk for preeclampsia in the third trimester. The counterparts were selected from those primigravid women who showed no signs of preeclampsia during the same period.

Data collection

Primarily, the baseline data of the patients including age, height, weight, and body mass index were gathered in a checklist.

All the included individuals had undergone at least one sonographic examination in the second trimester (between 14 to 26 weeks). Therefore, gestational age, as well as placenta location (lateral, anterior, posterior, and fundal), were recruited and entered into the checklist.

Statistical analysis:

The obtained data were entered into the Statistical Package for Social Sciences (Released 2009 PASW statistics for Windows; SPSS Inc., Chicago, IL, USA) version 26. The categorical variables were presented as absolute numbers and percentages, while the continuous variables were presented as mean ± standard deviation. The Chi-square test was applied to compare the categorical variables. Continuous variables were compared using One-way analysis of variance (ANOVA). Logistic regression was employed to investigate the factors associated with the occurrence of preeclampsia, and the odds ratio (OR) was reported as an index. A significance level of less than 0.05 was considered in all the analyses.

In the current study, data from 206 primigravid women in two groups of cases (n = 106) who were diagnosed with preeclampsia and controls (n = 100) were evaluated. The mean age and gestational age of the studied population were 30.02 ± 7.01 years and 34.15 ± 4.36 weeks, respectively.

The majority of the individuals had anterior placenta location (44.7%) followed by posterior (38.8%), fundal (10.2%), and lateral (6.3%) positions. Considering the location of the placenta, the studied individuals were similar in terms of age (P-value = 0.297), BMI (P-value = 0.512), and gestational age (P-value = 0.511).

Based on the logistic regression assessment, age, BMI, and anterior and posterior location of the placenta were the predicting factors for the incidence of preeclampsia. Accordingly, every single older age was accompanied by about 4% (95%CI: 0.89–1.12; P-value = 0.033) in the risk of preeclampsia development. Similarly, those with BMI > 25 kg/m2 had up to 4.613 folds (95%CI: 1.02–10.02; P-value = 0.038) increased risk for preeclampsia. The anterior location of the placenta increased the risk of preeclampsia incidence by 2.79 times (95%CI: 1.08–9.43; P-value = 0.038), while this risk was limited to 5% in posteriorly located ones. The lateral or fundal placenta represents no risk for the incidence of preeclampsia.

We sought the predisposing factors for the development of preeclampsia, particularly placenta location, in primigravid women. Given that, 206 individuals in two groups of cases with preeclampsia diagnosis and normal controls were evaluated. We found that increased age, elevated BMI, and anterior and posterior location of the placenta were independent predictors for preeclampsia development.

The main scope of the current study was to evaluate the role of placenta location assessed in the second trimester of pregnancy to predict the probability of preeclampsia development in the third trimester. We found that the majority of the placentas were located anteriorly, posteriorly, fundally, and laterally, respectively. Nevertheless, the most surprising outcome of our study was the predicted role of the anterior placenta for the incidence of preeclampsia accounting for more than 2.7 folds. Besides, the posterior location of the placenta was associated with a 5% increase in the risk of preeclampsia development.

A confirmatory study was conducted by Kaur et al. who similarly evaluated primigravid women in terms of whether placental location and Doppler assessment of the uterine artery at 18 to 24 weeks gestation could serve as predictors of preeclampsia. Although they divided their patients into centrally versus laterally located placentas, their outcomes were similar to ours as preeclampsia occurred in 87% and 13% of those with central and lateral placentas, respectively (10). Besides, Magann et al. presented that placenta location has no predicting role in prognosticating the incidence of preeclampsia (11). Nevertheless, most of the studies in the literature have stated the opposite data.

Keshavarz et al. conducted another study in which they investigated whether the placental position observed during a standard ultrasound examination in the second trimester could serve as a reliable predictor of preeclampsia development in the third trimester. They compared complex deliveries with preeclampsia versus normal deliveries and found that the lateral placenta had a significant effect, with an odds ratio of 2.1. Therefore, they recommended that pregnancies with lateral placentas should be closely monitored for early detection of elevated blood pressure and consequently, prevent from probable organ damage (2). Kaku and colleagues published another study in agreement with the predictive role of laterally located placenta for the development of preeclampsia. However, most of their patients had lateral placenta (66%) compared with the other 36% with central ones. It is worth noting that the majority of those with preeclampsia were primigravid in their study (12). In the study by Rai et al. involving singleton pregnant women, 65.1% had central placentas and 34.9% had lateral placentas. Sixteen percent of the patients developed preeclampsia, among whom 75% had laterally located placentas. This study indicated that those with laterally located placenta have 6.1 times higher chances of developing of preeclampsia than centrally located placenta (3). Other investigations also reported different odds ratios ranging from 2.7–5.6(1, 13–16).

The mainstay for which the location of the placenta has been considered a predictor for preeclampsia incidence stands on the differences in the resistance of the arteries supplying the placenta. It has been shown that both uterine arteries have a significant number of branches and that each supplies the corresponding side of the uterus. Although anastomosis between the arteries exists, it is not well-elucidated that they are functionally appropriate enough to compensate for each other. It is assumed that the centrally located placenta is equally nourished by the arteries leading to relatively more reasonable resistance in spiral arteries with minimal disturbances in blood supply which in turn leads to a decreased risk of hypoxia-reperfusion in the placenta. While in the laterally located placenta, the majority of the uteroplacental blood flow is primarily provided by one of the uterine arteries with some contribution from the collaterals derived from the other artery. As the degree of collateral circulation might variably differ in all the women, insufficient contribution might have a predisposing role in the development of preeclampsia (3). Normal placentation is integral for cytotrophoblastic invasion, a condition that seems to be impaired in preeclampsia. Additionally, despite the vague pathophysiology of preeclampsia, it is assumed that a proinflammatory process including a combination of syncytiotrophoblast stress, systemic endothelial dysfunction, oxidative stress, and systemic inflammation plays a significant role in this phenomenon (17). Thus, an inappropriate cytotrophoblastic invasion might lead to blood supply disturbances in the placenta leading to the accumulation of free radicals and reactive oxygen species responsible for oxidative stress and endothelial dysfunction (4).

Based on the findings of the current study, every single year increase in maternal age was accompanied by 4% increase in the probability of preeclampsia development in our patients. Surfing the literature shows that advanced maternal age has been considered a significant predictor of preeclampsia occurrence. Accordingly, several systematic reviews and meta-analyses have focused on adverse outcomes of pregnancy in older ages (18–20); however, it should be noted that ages older than 35 years old are factored in the definition of advanced maternal age(21). Probably, the reason for a slight increase of about 4% only in the risk of preeclampsia development has occurred as the majority of our patients had younger ages.

We also observed that the individuals with BMI above 25 kg/m2 were for up to 5% at increased risk of experiencing preeclampsia in their pregnancy. He and colleagues conducted a study in which they found that overweight and obesity were associated with 1.71 and 2.48 times rise in the probability of preeclampsia incidence (22). Other investigations also presented an increased rate of preeclampsia incidence among overweight/ obese individuals ranging from 18% to more than 4.2 folds (23–25). In this regard, Jancsura and colleagues presented that overweight/ obese individuals have a heightened pro-inflammatory state, which increases risk for preeclampsia (26). This claim relies on the theory regarding the pro-inflammatory pathophysiology of preeclampsia (17, 27).

In summary, we found no association between the laterally location of the placenta and preeclampsia development, while the major body of evidence presented that individuals with lateral placenta are at increased risk for preeclampsia. Probably this has occurred due to the design of our study as we have included primigravid women only or evaluated anterior and fundal placentas, as well. Accordingly, further studies in this regard are strongly recommended.

Based on the findings of the current study, anterior and posterior location of the placenta, increased age and BMI above 25 kg/m² were the predicting factors for preeclampsia development. Given that, it is recommended to closely monitor the individuals with anteriorly located placenta aiming at early diagnosis of persistent hypertension and applying approaches to minimize the adverse effects of preeclampsia.

Ethical approval

The study protocol was approved by the Research Committee of Isfahan University of Medical Sciences and the Ethics committee has confirmed it (Ethics code: IR.MUI.MED.REC.1398.498)

Consent for publication

The patient provided written informed consent for the publication of this manuscript. Patients understand that their names will not be published and due efforts will be made to conceal their identity but anonymity cannot be guaranteed.

Availability of data and materials

All data and materials are available upon request.

Competing interests

The authors declare that they have no competing interests.

Funding

This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions

Study concept or design (F.A., M.A., and M.B.) involves the initial idea and concept for the study and the overall design of the research project.
Data collection: M.G. gathers the necessary data or information for the study.
Data analysis or interpretation: Asieh Maghami is involved in analyzing the collected data using statistical methods or other analytical techniques.
Writing the paper: M.G. drafts the manuscript.
Reviewing and editing: A., M.A., and M.B. contribute to reviewing and editing and are involved in critically reviewing the manuscript for clarity, accuracy, and scientific rigor.

Acknowledgement

"Not applicable"

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No competing interests reported.

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You are reading this latest preprint version

Placenta location, a prognostic determinant for the incidence of preeclampsia

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Version 1

Abstract

Background

Methods and material

Study population

Data collection

Statistical analysis:

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1