Introduction: Serum platelet-activating factor (PAF) was proven to be associated with gestational hypertension. However, the predictive value of serum PAF at early pregnancy for the occurrence and outcomes of hypertensive disorders complicating pregnancy (HDCP) remained unclear. Methods: The demographic and clinical characteristics of patients were compared among the different subgroups. The serum PAF level was determined using an enzyme-linked immunosorbent assay. The predictive value of serum PAF for the occurrence and outcomes of HDCP was evaluated using receiver operating characteristic curve analysis. The correlation of serum PAF with blood pressure was assessed using Spearman analysis. Results: Both systolic blood pressure and diastolic blood pressure were significantly higher in HDCP patients, as well as the serum levels of TNF-α and IL-1β at diagnosis/enrollment, while serum levels of IL-10 showed the opposite trend. Serum PAF levels were significantly higher in patients with HDCP compared to normal pregnant women. Furthermore, serum PAF levels were higher in HDCP patients with mild preeclampsia compared to those with gestational hypertension and even more elevated in HDCP patients with severe preeclampsia at the early pregnancy stage and at diagnosis. In HDCP patients, increased serum PAF levels at early pregnancy and at diagnosis were associated with poor outcomes. Additionally, serum PAF levels could predict the occurrence of HDCP and poor outcomes. Conclusion: Serum PAF from HDCP patients at both the early pregnancy and diagnosis stages could effectively predict the occurrence and outcome of HDCP.

Hypertensive disorder complicating pregnancy (HDCP) is an exclusive condition in pregnant women. According to statistics, about 10% of pregnant women suffer from gestational hypertension (GH) worldwide [1], with 6–17% of primiparous women and 2–4% of twin pregnant women potentially suffering from GH during pregnancy [2‒4]. HDCP rapidly progresses to complex complications, serving as the primary contributor to maternal and perinatal morbidity and mortality [5]. It comprises a variety of conditions, including GH, preeclampsia (PE), eclampsia, and chronic hypertension during pregnancy [5, 6]. Currently, the cause of HDCP is not fully understood; simultaneously, effective prevention and treatment methods are still unavailable. Therefore, the early detection of HDCP is clinically important.

Platelet-activating factor (PAF) is a pro-inflammatory phospholipid involved in many different pathological and physiological processes, originating from a subset of phosphatidylcholines characterized by an ether bond at the sn-1 position on the glycerol backbone [7]. PAF functions by activating G proteins, activating phosphatidylinositol-specific phospholipase C [8, 9]. It plays a crucial role in modulating blood pressure by significantly impacting renal vascular circulation and is a minor precursor for low-density lipoprotein [9]. In pathological conditions, PAF is implicated in cardiac dysfunction, including cardiac anaphylaxis, hemorrhage, and septic shock. PAF also could promote the recruitment of leukocytes to inflamed tissue by enhancing their adhesion to the endothelium and facilitating their migration from the bloodstream into the surrounding tissue, consequently resulting in hypotension under normal levels [8, 9]. Additionally, PAF is a potent inflammatory mediator implicated in various pathological inflammatory conditions, including bronchial asthma, atherosclerosis, and kidney diseases [10]. PAF also regulates smooth muscle (SM) contractile activity by modulating endothelium-dependent relaxation of vascular SM [11]. Furthermore, PAF is involved in other pathological conditions, such as menstrual pain, premature birth, and prostate cancer progression [12‒14]. Notably, PAF induces stronger contractions in uterine SM tissue from pregnant females compared to nonpregnant females, suggesting an important role for PAF in pregnancy [15].

PE is a late pregnancy complication that influences an estimated 3% of women [16]. This condition is defined by high blood pressure, abnormal protein levels in the urine, and other systemic disturbances. If not addressed promptly, it can advance to eclampsia, with the characteristics of seizures and a significant risk of fatality to both the mother and fetus. PE poses diagnostic challenges due to its various clinical manifestations and the absence of a standardized diagnostic test [17]. Reduced inhibition of serum PAF has been observed to be associated with an increased incidence of PE [18]. An increased PAF is believed to elevate blood pressure by triggering vasoconstriction through heightened thromboxane production [19]. In specific instances, it has been reported that patients administered a PAF inhibitor, such as theophylline, show a reduced occurrence of PE [20, 21].

Therefore, this study employed a retrospective analysis of pregnant women with established medical records and retained blood samples at our hospital. The primary aim was to evaluate the predictive value of serum PAF in early pregnancy (11–13+6 weeks) for the occurrence of HDCP. Furthermore, the study aimed to compare the variations of serum PAF levels among patients with different HDCP severities in early pregnancy and at diagnosis, along with their correlation with blood pressure. Additionally, the research sought to determine the predictive value of serum PAF in early pregnancy and at diagnosis for outcomes in HDCP patients.

Participants

This is a retrospective study to analyze pregnant women with established records and retained blood samples in our hospital. It was approved by the Fourth Hospital of Shijiazhuang, and written informed consent was obtained from all participants. A total of 164 eligible pregnant women with HDCP and 90 normal women in the control group were successfully included in the study.

Diagnostic Criteria for HDCP

The diagnosis of HDCP was according to the American College of Obstetricians and Gynecologists (ACOG) 2013 guidelines. The diagnosis standards for PE follow these criteria.

  • 1.

    Blood pressure: prior blood pressure was normal, systolic blood pressure (SBP) was over 140 mm Hg, or diastolic blood pressure (DBP) was over 90 mm Hg after 20 weeks of pregnancy, which was measured at 4-h intervals.

  • 2.

    Proteinuria: the amount of urine protein within 24 h is more than 300 mg (or calculated based on limited-time urine collection) or the ratio of urine protein/creatinine is greater than 0.3 when proteinuria is present; the patient is accompanied by thrombocytopenia, liver dysfunction, kidney dysfunction, pulmonary edema, and brain or visual impairment when proteinuria is absent.

The diagnostic criteria for severe PE are established through the presence of PE symptoms, in conjunction with any of the following additional symptoms.

  • 1.

    SBP was greater than 160 mm Hg or DBP greater than 110 mm Hg at a 4-h interval after the patient had been bedridden, excluding prior use of antihypertensive drugs.

  • 2.

    The patient exhibits thrombocytopenia, characterized by a platelet count of less than 100,000/μL.

  • 3.

    The patient exhibits abnormal liver function, characterized by transaminase levels exceedingly twice the standard value or with persistent and intense pain in the upper right abdomen or diaphragm.

  • 4.

    The patient had progressive renal dysfunction, indicated by an elevated blood creatinine level exceeding 1.1 mg/dL or a twofold increase in blood creatinine in the absence of concurrent kidney diseases.

  • 5.

    The patient has pulmonary edema.

  • 6.

    The patient has presented with acquired brain injury or visual impairment.

Inclusion Criteria for the HDCP Group

Patients meeting the specified criteria will be included in the HDCP group.

  • 1.

    Pregnant women diagnosed with PE based on the above diagnostic criteria.

  • 2.

    The individual’s age exceeds 18 years.

  • 3.

    The patient is undergoing a pregnancy with a single fetus.

  • 4.

    The patient has completed prenatal registration within our hospital, retained blood samples, and underwent delivery at our hospital.

  • 5.

    The patient signed an informed consent form.

One hundred sixty-four pregnant women with HDCP were legally enrolled in the HDCP group.

Inclusion Criteria for the Normal Pregnancy Group

Pregnant women meeting the aforementioned criteria for the HDCP group, except for the HDCP diagnosis, are to be included in the normal pregnancy group. Our study included 90 normal pregnant women in the control group.

The Exclusion Criteria for the HDCP Group and Normal Pregnancy Group

Pregnant women who meet any of the following criteria will be excluded from the analysis.

  • 1.

    Preexisting hypertension before pregnancy.

  • 2.

    Managing multiple pregnancies.

  • 3.

    The patient presents with pregnancy diabetes, cerebrovascular disease, severe liver and kidney dysfunction, acute and chronic injuries, infections, rheumatism, rheumatoid, and other immune system-related diseases.

Enzyme-Linked Immunoassay for Serum PAF Detection

HDCP pregnant women at the early pregnancy stage (11–13+6 weeks) and at the diagnosis stage are required to fast for 12 h. Following fasting, 5 mL of blood was collected and subsequently subjected to centrifugation at 3,000 r/min for 10 min to isolate the serum, which was then frozen for subsequent testing. The serum PAF (ab287801, Abcam, MA, USA) is determined utilizing an enzyme-linked immunoassay kit procured from a commercial supplier.

Outcomes of Pregnant Women with HDCP

A poor outcome is defined for a pregnant woman who experiences one or more of the following events: prematurity, low birth weight, neonatal asphyxia, fetal distress, admission to a neonatal intensive care unit (ICU), neonatal mortality, premature rupture of membranes, or postpartum hemorrhage.

Follow-Up of Pregnancy Outcomes in HDCP Patients

The patient with HDCP underwent follow-up assessments and was subsequently categorized into two distinct groups based on their respective outcomes: the good outcome group and the poor outcome group.

Statistical Analysis

The statistical data were presented as mean ± SD. The significance of the comparison between the two groups was analyzed using the Mann-Whitney test, the unpaired t test with Welch’s correction, and Fisher’s exact test. Moreover, the significance of the comparisons among the three groups was tested using the Brown-Forsythe ANOVA test, followed by a Games-Howell multiple comparisons test.

The Clinical Characteristics of Pregnant Women with HDCP

One hundred sixty-four eligible HDCP pregnant women and 90 normal pregnant women were successfully included in our study. Through demographic and clinical comparison, it was found that there was no significant difference in age, gestational age at enrollment, and parity between the two groups (Table 1). However, there was a significant difference in SBP and DBP between the two groups (Table 1). Additionally, serum levels of TNF-α, IL-1β at diagnosis/enrollment were significantly higher in HDCP patients when compared to control, while IL-10 level showed the opposite trend.

Table 1.

Demographic and clinical characteristics of pregnant women with hypertensive disorders complicating pregnancy (HDCP) or control

CharacteristicsControl (n = 90)HDCP (n = 164)p value
Maternal age, years 27.64±5.28 28.11±5.56 0.204 
Gestational weeks at diagnosis/enrollment 34.73±4.15 35.12±3.97 0.196 
SBP at diagnosis/enrollment, mm Hg 113.89±10.49 151.62±16.83 <0.001 
DBP at diagnosis/enrollment, mm Hg 78.91±8.05 99.78±11.99 <0.001 
Parity, n (%) 
 Nulliparous 58 (64.4%) 96 (58.5%) 0.421 
 Multiparous 32 (35.6%) 68 (41.5%) 
Serum TNF-α at diagnosis/enrollment, pg/mL 25.32±5.28 67.14±10.55 <0.001 
Serum IL-1β at diagnosis/enrollment, pg/mL 19.46±4.73 55.42±10.06 <0.001 
Serum IL-10 at diagnosis/enrollment, pg/mL 36.84±5.97 26.67±5.39 <0.001 
CharacteristicsControl (n = 90)HDCP (n = 164)p value
Maternal age, years 27.64±5.28 28.11±5.56 0.204 
Gestational weeks at diagnosis/enrollment 34.73±4.15 35.12±3.97 0.196 
SBP at diagnosis/enrollment, mm Hg 113.89±10.49 151.62±16.83 <0.001 
DBP at diagnosis/enrollment, mm Hg 78.91±8.05 99.78±11.99 <0.001 
Parity, n (%) 
 Nulliparous 58 (64.4%) 96 (58.5%) 0.421 
 Multiparous 32 (35.6%) 68 (41.5%) 
Serum TNF-α at diagnosis/enrollment, pg/mL 25.32±5.28 67.14±10.55 <0.001 
Serum IL-1β at diagnosis/enrollment, pg/mL 19.46±4.73 55.42±10.06 <0.001 
Serum IL-10 at diagnosis/enrollment, pg/mL 36.84±5.97 26.67±5.39 <0.001 

The data are presented as mean ± SD or n (percentage). The comparisons of data between the two groups were done by Mann-Whitney test, unpaired t test with Welch’s correction or Fisher’s exact test.

SBP, systolic blood pressure; DBP, diastolic blood pressure.

Comparison of Serum PAF at the First Trimester among Different Groups

The level of serum PAF between two groups of pregnant women at the early pregnancy stage was analyzed. The results showed that the levels of serum PAF in HDCP patients during early pregnancy were significantly higher than those of normal pregnant women (Fig. 1a). Subsequently, the predictive value of serum PAF levels in HDCP patients at the early pregnancy stage was analyzed using a receiver operating characteristic curve (ROC) analysis. The analysis showed an area under the curve (AUC) value of 0.768, a sensitivity of 68.29%, and a specificity of 75.56%, suggesting that serum PAF may serve as a predictive indicator for the occurrence of HDCP (Fig. 1b). Finally, we compared the serum PAF levels among three subgroups at the early pregnancy stage. It can be observed that the serum PAF level at the early pregnancy stage gradually increases with the increase in severity of the condition (Fig. 1c).

Fig. 1.

a Comparison of serum PAF at the first trimester between pregnant women with HDCP (n = 164) and control normal pregnancy (n = 90). The data were presented as a box plot. ***p < 0.001 from unpaired t test with Welch’s correction. b ROC analysis of predictive values of serum PAF at first trimester for HDCP. c Comparison of serum PAF at the first trimester among GH (n = 67), mild PE (n = 60) and severe PE (n = 37) groups. *p < 0.05, **p < 0.01 from Brown-Forsythe ANOVA test followed by a Games-Howell’s multiple comparisons test.

Fig. 1.

a Comparison of serum PAF at the first trimester between pregnant women with HDCP (n = 164) and control normal pregnancy (n = 90). The data were presented as a box plot. ***p < 0.001 from unpaired t test with Welch’s correction. b ROC analysis of predictive values of serum PAF at first trimester for HDCP. c Comparison of serum PAF at the first trimester among GH (n = 67), mild PE (n = 60) and severe PE (n = 37) groups. *p < 0.05, **p < 0.01 from Brown-Forsythe ANOVA test followed by a Games-Howell’s multiple comparisons test.

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Comparison of Serum PAF at Different Time Points in HDCP Patients

Subsequently, we analyzed the changes in serum PAF in HDCP patients with different severity of HDCP. It was found that the concentration of serum PAF gradually increased with the increase in the severity of HDCP (Fig. 2a). Subsequently, we analyzed the changes in serum PAF concentration in HDCP patients at the early pregnancy stage and diagnosis stage of HDCP. It was found that the serum PAF in HDCP patients at diagnosis was higher than that the early pregnancy stage (Fig. 2b, c), indicating serum PAF level gradually increased with the progression of HDCP.

Fig. 2.

a Comparison of serum PAF at diagnosis among GH (n = 67), mild PE (n = 60) and severe PE (n = 37) groups. **p < 0.01 from Brown-Forsythe ANOVA test followed by a Games-Howell’s multiple comparisons test. b, c Comparison of serum PAF between the time of first trimester and diagnosis in pregnant women with HDCP, (n = 164). ***p < 0.001 from paired t test.

Fig. 2.

a Comparison of serum PAF at diagnosis among GH (n = 67), mild PE (n = 60) and severe PE (n = 37) groups. **p < 0.01 from Brown-Forsythe ANOVA test followed by a Games-Howell’s multiple comparisons test. b, c Comparison of serum PAF between the time of first trimester and diagnosis in pregnant women with HDCP, (n = 164). ***p < 0.001 from paired t test.

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Additionally, the serum levels of HDCP patients at the end of pregnancy were analyzed. The results indicated that serum PAF levels in 89 patients with favorable outcomes were significantly lower at the end of pregnancy compared to their levels at diagnosis (p = 0.002; online suppl. Fig. S1; for all online suppl. material, see https://doi.org/10.1159/000543242). In contrast, serum PAF levels in 75 patients with poor outcomes increased further at the end of pregnancy compared to diagnosis (p < 0.001; online suppl. Fig. S1). Among all HDCP patients, there was no significant difference in serum PAF levels between the end of pregnancy and diagnosis (p = 0.72; online suppl. Fig. S1).

Spearman Correlation Analysis of Serum PAF at Different Time Points with SBP and DBP at Diagnosis

To further analyze the correlation between blood pressure at diagnosis and serum PAF levels in HDCP patients during early pregnancy or diagnosis stage, the correlation between DBP, SBP, and PAF was analyzed. The analysis revealed the correlation coefficient (r value) between SBP and serum PAF at the first trimester to be 0.348 (Fig. 3a). Similarly, the correlation between DBP and serum PAF at the first trimester was 0.262 (Fig. 3b). Furthermore, the correlation between SBP and serum PAF at diagnosis was 0.419 (Fig. 3c), and between DBP and serum PAF at diagnosis was 0.483 (Fig. 3d). Simultaneously, the p value for all correlations was less than 0.001. These results indicated that serum PAF in HDCP patients during early pregnancy and at diagnosis is correlated with blood pressure.

Fig. 3.

Spearman correlation analysis of serum PAF at first trimester with SBP (a) and DBP (b) at the time of diagnosis in pregnant women with hypertensive disorders complicating pregnancy (HDCP, n = 164). Spearman correlation analysis of serum PAF at diagnosis with SBP (c) and DBP (d) at the time of diagnosis in pregnant women with HDCP (n = 164).

Fig. 3.

Spearman correlation analysis of serum PAF at first trimester with SBP (a) and DBP (b) at the time of diagnosis in pregnant women with hypertensive disorders complicating pregnancy (HDCP, n = 164). Spearman correlation analysis of serum PAF at diagnosis with SBP (c) and DBP (d) at the time of diagnosis in pregnant women with HDCP (n = 164).

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Clinical Classification of Pregnant Outcomes in Patients with HDCP

Among the 164 patients with HDCP, there were 67 cases of simple GH, 60 cases of PE, and 37 cases of severe PE. Afterwards, the outcomes of the pregnancy were also analyzed and recorded. It showed that 51 cases in the HDCP group while 6 cases in the control group were with prematurity, 43 cases in the HDCP group while 4 cases in the control group were with low birth weight, 12 cases in the HDCP group while no case in the control group were with neonatal asphyxia, 19 cases in the HDCP group while 1 case in the control group were with fetal distress, 23 cases in the HDCP group while no case in the control group were with fetal ICU, 3 cases in the HDCP group while 0 case in the control group were with neonatal mortality, 14 cases in the HDCP group while 1 case in the control group was with premature rupture of membranes, and 9 cases in the HDCP group while no case in the control group was with post-partum hemorrhage (Table 2). This result demonstrated that the percentage of pregnant with poor outcomes in the HDCP group was significantly higher than that in the control group.

Table 2.

Clinical classification and pregnant outcomes of pregnant women with hypertensive disorders complicating pregnancy (HDCP) or control

HDCP (n = 164)Control (n = 90)
Clinical classification, n (%) 
 GH 67 (40.8) 
 mPE 60 (36.6) 
 sPE 37 (22.6) 
Pregnant outcomes, n (%) 
 Prematurity 51 (31.1) 6 (6.7) 
 Low birth weight 43 (26.2) 4 (4.4) 
 Neonatal asphyxia 12 (7.3) 0 (0) 
 Fetal distress 19 (11.6) 1 (1.1) 
 Fetal ICU 23 (14.0) 0 (0) 
 Neonatal mortality 3 (1.8) 0 (0) 
 Premature rupture of membranes 14 (8.5) 1 (1.1) 
 Post-partum hemorrhage 9 (5.5) 0 (0) 
 Total poor outcomes 75 (45.7) 6 (6.7) 
HDCP (n = 164)Control (n = 90)
Clinical classification, n (%) 
 GH 67 (40.8) 
 mPE 60 (36.6) 
 sPE 37 (22.6) 
Pregnant outcomes, n (%) 
 Prematurity 51 (31.1) 6 (6.7) 
 Low birth weight 43 (26.2) 4 (4.4) 
 Neonatal asphyxia 12 (7.3) 0 (0) 
 Fetal distress 19 (11.6) 1 (1.1) 
 Fetal ICU 23 (14.0) 0 (0) 
 Neonatal mortality 3 (1.8) 0 (0) 
 Premature rupture of membranes 14 (8.5) 1 (1.1) 
 Post-partum hemorrhage 9 (5.5) 0 (0) 
 Total poor outcomes 75 (45.7) 6 (6.7) 

The data are presented as n (percentage).

GH, gestational hypertension; mPE, mild preeclampsia; sPE, severe preeclampsia.

Demographic and Clinical Characteristics of HDCP Patients with Good Outcomes or Poor Outcomes

The patients with HDCP were categorized into two groups based on their outcomes: a good outcomes group of 89 cases and a poor outcomes group of 75 cases. Afterwards, the demographic and clinical characteristics of the two groups were compared. There was no significant difference in maternal age and parity (Table 3). However, the SBP, DBP, and clinical classification had significant differences (Table 3).

Table 3.

Demographic and clinical characteristics between good pregnant outcomes and poor pregnant outcomes in pregnant women with hypertensive disorders complicating pregnancy (HDCP)

CharacteristicsGood (n = 89)Poor (n = 75)p value
Maternal age, years 27.74±4.98 28.48±5.73 0.182 
SBP at diagnosis, mm Hg 147.08±14.92 156.87±17.52 <0.001 
DBP at diagnosis, mm Hg 95.69±9.68 104.71±12.67 <0.001 
Parity, n (%) 
 Nulliparous 55 (61.8) 41 (54.7) 0.427 
 Multiparous 34 (38.2) 34 (45.3) 
Clinical classification, n (%) 
 GH 49 (55.1) 18 (24) <0.001 
 mPE 31 (34.8) 29 (38.7) 
 sPE 9 (10.1) 28 (37.3) 
CharacteristicsGood (n = 89)Poor (n = 75)p value
Maternal age, years 27.74±4.98 28.48±5.73 0.182 
SBP at diagnosis, mm Hg 147.08±14.92 156.87±17.52 <0.001 
DBP at diagnosis, mm Hg 95.69±9.68 104.71±12.67 <0.001 
Parity, n (%) 
 Nulliparous 55 (61.8) 41 (54.7) 0.427 
 Multiparous 34 (38.2) 34 (45.3) 
Clinical classification, n (%) 
 GH 49 (55.1) 18 (24) <0.001 
 mPE 31 (34.8) 29 (38.7) 
 sPE 9 (10.1) 28 (37.3) 

The data are presented as mean ± SD or n (percentage). The comparisons of data between the two groups were done by Mann-Whitney test, unpaired t test with Welch’s correction or Fisher’s exact test.

SBP, systolic blood pressure; DBP, diastolic blood pressure; GH, gestational hypertension; mPE, mild preeclampsia; sPE, severe preeclampsia.

The Predictive Value of Serum PAF for Pregnancy Outcomes

We analyzed the predictive value of serum PAF levels for outcomes in HDCP patients at two-time points: early pregnancy and diagnosis. The results showed that the serum PAF in HDCP patients with poor outcomes was significantly higher than that of patients with good outcomes at early pregnancy and diagnosis stages (Fig. 4a, c). Consequently, the predictive value of serum PAF for outcomes of HDCP was analyzed using ROC. The result showed that the AUC for serum PAF was 0.746 at the first trimester (Fig. 4b), 0.819 at diagnosis (Fig. 4d), with high sensitivity and specificity. The cutoff value for the AUC of serum PAF at the first trimester was 12.38 ng/mL, while at diagnosis was 15.51 ng/mL. In the ROC analysis of serum PAF levels between the first trimester of pregnancy and the time of HDCP diagnosis, the cutoff value was 15.03 ng/mL. These results demonstrated the serum PAF level at diagnosis had a more effective prediction for outcomes.

Fig. 4.

Comparisons of serum PAF at the time of first trimester (a) and diagnosis (c) between good pregnant outcomes (n = 89) and poor pregnant outcomes (n = 75) in pregnant women with HDCP. ROC analysis of the predictive values of serum PAF at the time of first trimester (b) and diagnosis (d) for poor outcomes in pregnant women with HDCP.

Fig. 4.

Comparisons of serum PAF at the time of first trimester (a) and diagnosis (c) between good pregnant outcomes (n = 89) and poor pregnant outcomes (n = 75) in pregnant women with HDCP. ROC analysis of the predictive values of serum PAF at the time of first trimester (b) and diagnosis (d) for poor outcomes in pregnant women with HDCP.

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HDCP has attracted significant attention globally due to its unclear pathogenesis, high incidence rate, and numerous adverse pregnancy outcomes [22]. However, effective preventive and therapeutic approaches have remained elusive. HDCP continues to exert a significant impact on maternal and infant health globally, often resulting in multiple organ failure and maternal mortality during the antenatal and postpartum periods. Moreover, HDCP majorly contributed to poor perinatal outcomes. Therefore, the pathogenesis of HDCP has long been a prominent focus of obstetrics research. Placental dysgenesis is widely acknowledged as a prominent pathological mechanism in HDCP [23]. However, with the progression of further study, abnormal changes in the maternal systemic system, including immune dysfunction, endothelial dysfunction and repair damage, abnormal coagulation and hemostasis mechanisms, and platelet activation, have also attracted more attention [24].

When GH progresses to severe PE, it frequently involves a decrease in platelet count [25]. Currently, clinical diagnosis and treatment focus on changes in platelet count as a diagnostic criterion for severe PE but ignore changes in platelet function and morphology. Research showed a decrease in platelet count accompanied by increased platelet volume in HDCP patients with mild or severe PE [26]. Meanwhile, this phenomenon had already appeared a week before the disease progression. Therefore, platelet volume can serve as a predictive indicator for disease progression [27]. One study analyzed coagulation parameters and platelet index as predictors of PE, showing that the AUC of mean platelet volume and prothrombin time were 0.605 and 0.624, respectively. This study proved that mean platelet volume can be used as a predictive indicator, but the effectiveness is not high [28]. Therefore, an effective prediction factor was crucial in clinical treatment.

PAF is a phospholipid mediator with a wide range of biological characteristics produced by various cells, including platelets, endothelial cells, and macrophages. In the vascular system, it increases the permeability of monolayer endothelial cells, activates monocytes/macrophages and neutrophils, and stimulates the contraction of SM cells [8]. Multiple studies have shown that PAF may be associated with vascular dysfunction in PE [19]. Zou et al. [29] have also confirmed that serum PAF is highly expressed in patients with HDCP. Our study showed that the serum PAF was significantly elevated in patients with HDCP, which is consistent with previous studies.

PAF promotes thrombosis and hypercoagulable blood pressure by strongly inducing platelet aggregation and inflammatory factor release and is considered a risk factor for cardiovascular and cerebrovascular diseases. Vascular endothelial injury in patients with GH can induce arachidonic acid metabolism in endothelial cells, promote the synthesis and release of PAF, and cause an increase in plasma PAF levels [30]. On the other hand, PAF, together with other platelet-activating substances (β – thrombomodulin, platelet factor 4) induced by endothelial injury, activates platelets and promotes local inflammatory response and neutrophil aggregation, ultimately leading to further elevation of blood pressure. In pregnant women with mild and severe PE, there is a progressive worsening of endothelial damage. Concurrently, there is an elevation in the synthesis and secretion of PAF, which contributes to the development of intravascular thrombosis, resulting in increased platelet consumption and a declining trend in PLT levels [31, 32]. Zou et al [29] have also confirmed that patients with severe PE have significantly higher levels of PAF than those with GH and PE, which can increase blood pressure and worsen disease progression. Our study has revealed a progressive increase in the serum PAF level as the severity of GH advanced, demonstrating a clear association between the worsening condition of HDCP and increased serum PAF level. Although the level of serum PAF increased in HDCP patients, the alteration pattern of serum PAF at different stages of pregnancy was unknown. Our analysis showed that serum PAF in HDCP patients at both the early pregnancy stage and diagnosis stage gradually increased with the increase in severity of HDCP.

If HDCP is not actively intervened, patients may experience respiratory depression and heart failure due to increased abdominal pressure, decreased visceral blood flow, and increased cardiac blood flow. Therefore, timely prediction of poor pregnancy outcomes can provide guidance for timely intervention. Our analysis revealed that the serum PAF level significantly increased in HDCP patients with poor outcomes. Furthermore, it was observed that the serum PAF level at the first trimester and diagnosis could effectively predict the outcome of HDCP patients with high AUC values. These findings strongly suggest that elevated PAF levels are closely associated with poor pregnancy outcomes. Therefore, we can recruit clinical HDCP patients and then treat them with PAF inhibitors to observe whether the incidence of HDCP decreases, as well as whether the probability of poor prognosis is reduced, thereby clarifying the causal role of PAF in HDCP.

It has been shown that the level of serum PAF can predict the occurrence and outcomes of HDCP, but there are still some issues that need to be addressed in the future. Elevated serum PAF levels are associated with HDCP, and further evidence is needed to establish the role of PAF as an independent factor for the risk of HDCP and its outcomes. In addition, both SBP and DBP are correlated with the serum level of PAF. It would be beneficial to investigate the predictive effect of combining PAF and blood pressure, as this could potentially enhance the effectiveness of the prediction model.

The serum levels of PAF were significantly higher in pregnant women with HDCP compared to normal pregnant women. With the progression of HDCP to PE, the levels of PLGF gradually increased. Importantly, it was observed that serum PAF in GH, mPE, and sPE patients at both the early pregnancy stage and diagnosis stage increased dramatically. Moreover, serum PAF also increased in HDCP patients with poor outcomes. ROC analysis demonstrated serum PAF could predict the occurrence and poor outcomes of HDCP patients.

This study protocol was reviewed and approved by the Fourth Hospital of Shijiazhuang. The study was performed in strict accordance with the Declaration of Helsinki, Ethical Principles for Medical Research Involving Human Subjects. Written informed consent was derived from the participants.

The authors declare they have no conflict of interest regarding this research study.

This work was supported by Medical Science Research Project of Hebei (20231659).

Data curation and analysis: Shasha Liu, Qianyu Lan, Weiling Li, Jiefang Zhang, Liman Fu, Yanlei Xu, and Yuan Li; drafting of the manuscript: Shasha Liu and Yuan Li; concept and design of the study: Yuan Li. All authors approved the publication the manuscript.

Additional Information

Shasha Liu and Qianyu Lan contributed equally to this work.

The data that support the findings of this study are not publicly available due to contain information that could compromise the privacy of research participants but are available from YLX upon reasonable request.

1.
Antza
C
,
Cifkova
R
,
Kotsis
V
.
Hypertensive complications of pregnancy: a clinical overview
.
Metabolism
.
2018
;
86
:
102
11
.
2.
Folk
DM
.
Hypertensive disorders of pregnancy: overview and current recommendations
.
J Midwifery Wom Health
.
2018
;
63
(
3
):
289
300
.
3.
Barton
JR
,
O’Brien
JM
,
Bergauer
NK
,
Jacques
DL
,
Sibai
BM
.
Mild gestational hypertension remote from term: progression and outcome
.
Am J Obstet Gynecol
.
2001
;
184
(
5
):
979
83
.
4.
Lei
F
,
Liu
D
,
Shen
Y
,
Zhang
L
,
Li
S
,
Liu
X
, et al
.
Study on the influence of pregnancy-induced hypertension on neonatal birth weight
.
J Investig Med
.
2018
;
66
(
6
):
1008
14
.
5.
Bernstein
PS
,
Martin
JN
Jr
,
Barton
JR
,
Shields
LE
,
Druzin
ML
,
Scavone
BM
, et al
.
National partnership for maternal safety: consensus bundle on severe hypertension during pregnancy and the postpartum period
.
Obstet Gynecol
.
2017
;
130
(
2
):
347
57
.
6.
Bernstein
PS
,
Martin
JN
Jr
,
Barton
JR
,
Shields
LE
,
Druzin
ML
,
Scavone
BM
, et al
.
Consensus bundle on severe hypertension during pregnancy and the postpartum period
.
J Obstet Gynecol Neonatal Nurs
.
2017
;
46
(
5
):
776
87
.
7.
Lindsberg
PJ
,
Hallenbeck
JM
,
Feuerstein
G
.
Platelet-activating factor in stroke and brain injury
.
Ann Neurol
.
1991
;
30
(
2
):
117
29
.
8.
Montrucchio
G
,
Alloatti
G
,
Camussi
G
.
Role of platelet-activating factor in cardiovascular pathophysiology
.
Physiol Rev
.
2000
;
80
(
4
):
1669
99
.
9.
Snyder
F
.
Platelet-activating factor and its analogs: metabolic pathways and related intracellular processes
.
Biochim Biophys Acta
.
1995
;
1254
(
3
):
231
49
.
10.
Kasperska-Zajac
A
,
Brzoza
Z
,
Rogala
B
.
Platelet-activating factor (paf): a review of its role in asthma and clinical efficacy of paf antagonists in the disease therapy
.
Recent Pat Inflamm Allergy Drug Discov
.
2008
;
2
(
1
):
72
6
.
11.
Montrucchio
G
,
Alloatti
G
,
Tetta
C
,
Roffinello
C
,
Emanuelli
G
,
Camussi
G
.
In vitro contractile effect of platelet-activating factor on Guinea-pig myometrium
.
Prostaglandins
.
1986
;
32
(
4
):
539
54
.
12.
Wang
R
,
Liu
J
,
Qiao
Y
,
Wang
X
,
Chen
J
,
Ma
Y
.
Efficacy of atosiban combined with ritodrine on spontaneous threatened preterm birth and its effect on paf and ffn levels
.
Am J Transl Res
.
2022
;
14
(
11
):
7942
50
.
13.
Xu
B
,
Gao
L
,
Wang
L
,
Tang
G
,
He
M
,
Yu
Y
, et al
.
Effects of platelet-activating factor and its differential regulation by androgens and steroid hormones in prostate cancers
.
Br J Cancer
.
2013
;
109
(
5
):
1279
86
.
14.
Ji
W
,
Chen
J
,
Mi
Y
,
Wang
G
,
Xu
X
,
Wang
W
.
Platelet-activating factor receptor activation promotes prostate cancer cell growth, invasion and metastasis via erk1/2 pathway
.
Int J Oncol
.
2016
;
49
(
1
):
181
8
.
15.
Kim
BK
,
Ozaki
H
,
Lee
SM
,
Karaki
H
.
Increased sensitivity of rat myometrium to the contractile effect of platelet activating factor before delivery
.
Br J Pharmacol
.
1995
;
115
(
7
):
1211
4
.
16.
Redman
CW
,
Sargent
IL
.
Latest advances in understanding preeclampsia
.
Science
.
2005
;
308
(
5728
):
1592
4
.
17.
Young
BC
,
Levine
RJ
,
Karumanchi
SA
.
Pathogenesis of preeclampsia
.
Annu Rev Pathol
.
2010
;
5
:
173
92
.
18.
Benedetto
C
,
Massobrio
M
,
Bertini
E
,
Abbondanza
M
,
Enrieu
N
,
Tetta
C
.
Reduced serum inhibition of platelet-activating factor activity in preeclampsia
.
Am J Obstet Gynecol
.
1989
;
160
(
1
):
100
4
.
19.
Rowland
BL
,
Vermillion
ST
,
Roudebush
WE
.
Elevated circulating concentrations of platelet activating factor in preeclampsia
.
Am J Obstet Gynecol
.
2000
;
183
(
4
):
930
2
.
20.
Sukonpan
K
,
Phupong
V
.
Serum calcium and serum magnesium in normal and preeclamptic pregnancy
.
Arch Gynecol Obstet
.
2005
;
273
(
1
):
12
6
.
21.
Longo
SA
,
Dola
CP
,
Pridjian
G
.
Preeclampsia and eclampsia revisited
.
South Med J
.
2003
;
96
(
9
):
891
9
.
22.
TePoel
MR
,
Saftlas
AF
,
Wallis
AB
.
Association of seasonality with hypertension in pregnancy: a systematic review
.
J Reprod Immunol
.
2011
;
89
(
2
):
140
52
.
23.
Chen
CC
,
Nien
CJ
,
Chen
LG
,
Huang
KY
,
Chang
WJ
,
Huang
,
H-M
.
Effects of sapindus mukorossi seed oil on skin wound healing: in vivo and in vitro testing
.
Int J Mol Sci
.
2019
,
20
(
10
):
2579
.
24.
Karthikeyan
VJ
,
Lip
GY
.
Endothelial damage/dysfunction and hypertension in pregnancy
.
Front Biosci
.
2011
;
3
:
1100
8
.
25.
Ma’ayeh
M
,
Costantine
MM
.
Prevention of preeclampsia
.
Semin Fetal Neonatal Med
.
2020
;
25
(
5
):
101123
.
26.
Nadar
S
,
Lip
GY
.
Platelet activation in the hypertensive disorders of pregnancy
.
Expert Opin Investig Drugs
.
2004
;
13
(
5
):
523
9
.
27.
Howarth
S
,
Marshall
LR
,
Barr
AL
,
Evans
S
,
Pontre
M
,
Ryan
N
.
Platelet indices during normal pregnancy and pre-eclampsia
.
Br J Biomed Sci
.
1999
;
56
(
1
):
20
2
.
28.
Han
L
,
Liu
X
,
Li
H
,
Zou
J
,
Yang
Z
,
Han
J
, et al
.
Blood coagulation parameters and platelet indices: changes in normal and preeclamptic pregnancies and predictive values for preeclampsia
.
PLoS One
.
2014
;
9
(
12
):
e114488
.
29.
Zou
YX
,
Hong
L
.
Expression and correlation analysis of serum lrrfip and paf in patients with gestational hypertension
.
Chin J Clin Obstet Gynecol
.
2020
;
21
:
2
.
30.
Meiling
ZJ
.
The effect of painless delivery on perinatal blood flow changes and platelet activation status in pregnant women with gestational hypertension
.
Matern Child Health Care China
.
2021
;
36
:
2253
.
31.
Gupta
P
,
Agarwal
R
,
Bhaskaran
S
,
Garg
S
,
Mehndiratta
M
,
Radhakrishnan
G
, et al
.
Evaluation of maternal plasma platelet activating factor acetylhydrolase activity and mrna expression in pre-eclampsia: a case control study
.
J Obstet Gynaecol
.
2021
;
41
(
5
):
726
32
.
32.
Mullers
SM
,
Burke
N
,
Flood
K
,
Cowman
J
,
O’Connor
H
,
Cotter
B
, et al
.
Altered platelet function in intrauterine growth restriction: a cause or a consequence of uteroplacental disease
.
Am J Perinatol
.
2016
;
33
(
8
):
791
9
.