Preeclampsia is a specific disease which is relatively common pregnancy complications and great harm to the mother and child [1], with an incidence of 2–8% [2]. The disease is characterized by hypertension (140/90 mmHg) after 20 weeks of gestation, with or without proteinuria ($>$0.3 g), and various complications of other systems (such as thrombocytopenia, liver impairment, renal impairment, pulmonary edema, emerging central nervous system abnormalities, or visual disturbances) [3]. Its risk factors include multiple pregnancies and maternal factors: race, age, obesity, gestational diabetes, chronic hypertension, assisted reproduction, kidney disease and autoimmune diseases [4, 5]. The only way to treat the disease is to give birth, so means for early prediction, early prevention, and targeted prenatal monitoring are crucial. At present, the research on early prediction of preeclampsia at home and abroad still focuses on clinical research and measurement of angiogenesis spectrum. These include placental growth factor (PlGF), vascular endothelial growth factor, soluble fms-like tyrosine kinase (sFlt-1), fetal hemoglobin, cell-free fetal DNA (cff DNA), soluble fetal DNA angiotensin Ⅱ type 1 receptor activating antibody (AT1-AA), proteomics, etc. In recent years, the proportion of older parturients in pregnant women has gradually increased. Blood hypercoagulability is a physiological phenomenon of pregnancy [6]. Vascular endothelial injury, one of the pathogenetic mechanisms of preeclampsia, activates platelets and coagulation factors to further aggravate blood hypercoagulation, thus facilitating thrombosis [7, 8]. D-dimer reflects the dynamic process of fibrin polymerization and decomposition. Imbalance between the anticoagulant and coagulant promoting functions damages the endothelial function of placental trophoblastic cells [9]. Further increase of inflammatory mediators induces oxidative stress, resulting in placental dysfunction and adverse fetal outcomes [10]. D-dimer levels are high in women with preeclampsia, but no studies have been conducted to determine whether D-dimer levels are different in women with preeclampsia at different ages. Therefore, the purpose of this study was to evaluate the relationship between D-dimer during pregnancy and preeclampsia at different ages, and help to better predict the maternal and infant outcomes of preeclampsia pregnant women of different ages.

Preeclampsia is a pregnancy-specific disease that causes adverse outcomes for mothers and infants [12]. In order to predict preeclampsia earlier, many studies are still trying to find ideal markers [13]. It is well known that D-dimer is a potential predictor of preeclampsia [14], and we further clarified the predictive value of D-dimer in different age groups of preeclampsia. No similar studies have been reported. The level of D-dimer is high during pregnancy, which is a normal physiological phenomenon. Our study also confirmed that the level of D-dimer in the preeclampsia group was significantly higher than that in normotensive pregnancy [8]. Further studies found that the D-dimer levels of preeclampsia women over 30 years of age were significantly higher than those of preeclampsia women below 30 years of age. D-dimer is the final degradation product of fibrin, reflecting the level of polymerization and decomposition of fibrin [15]. In order to increase placental blood perfusion, the body compensatively promotes vascular constriction, resulting in high blood pressure and further promoting the occurrence of preeclampsia [16]. Placental ischemia can increase the production of sFlt-1, angiotensin II (Ang II) type 1 autoantibodies and TNF-$\alpha$, leading to maternal vascular endothelial dysfunction [17]. Studies have shown that reducing the placental arterial perfusion pressure in rats can induce a rat model of preeclampsia, resulting in restricted fetal growth and development [18]. In addition, increased placental vascular resistance forces the muscular segment of the artery to maintain narrowing and contraction, increases maternal circulation and placental lipid peroxidation, and decreases antioxidant activity, which further increases lipid peroxidation and decreases antioxidant activity [19]. Studies have shown that the end products of fatty acid oxidation in maternal plasma, umbilical cord plasma and placental tissue of pregnant patients with fetal growth restriction are higher than those in healthy pregnant patients [20]. We also showed that the fetal birth weight of pregnant women with preeclampsia was significantly lower than that of the normotensive pregnancy group, which had a certain impact on the infant.

The damage of vascular endothelial cells is the basic pathological change of preeclampsia. D-dimer levels have been found to correlate with C-reactive protein (CRP) [21]. Elevated D-dimer is likely associated with vasculitic status. PTX3 is a novel inflammatory marker, which can lead to the prothrombotic state caused by endothelial dysfunction [22]. In studies of disease severity in COVID-19 patients, PTX3 is positively correlated with plasma D-dimer and is involved in coagulation dysfunction [23]. Silvia Galbiati et al. [24] found that serum PTX3 was significantly elevated in pregnant women with preeclampsia, which supports our conclusion.

In the acute phase caused by tissue and blood vessel injury, fibrinogen is a key component of thrombosis and hemostasis [25]. By detecting plasma fibrinogen $\gamma$ chain concentration, Zhu Yuli et al. [26] found that fibrinogen synthesis and degradation disorders may be one of the important mechanisms of preeclampsia. This was inconsistent with our experimental results, which showed that the mean fibrinogen in the preeclampsia group was higher than that in the normotensive pregnancy group, but the difference was not statistically significant. Meanwhile, the ROC curve showed that the predicted area was larger in the middle-aged pregnancy group. In the middle-aged pregnant women, the D-dimer cutoff value was 1.86 µg/mL, the sensitivity was 28%, and the specificity was 89%. The cutoff value of D-dimer was 1.67 µg/mL, the sensitivity was 56%, and the specificity was 84%. Hence, D-dimer has a higher predictive value for preeclampsia in older pregnant women. In order to exclude the interference of other variables, such as the time of delivery of primipara or menpara, age and so on, we used multiple regression method to verify the above conclusions.

Elevated D-dimer was an independent factor associated with increased incidence of venous thromboembolism, myocardial infarction, and cerebral infarction [27]. If the D-dimer of pregnancy body is high, it is easy to activate the coagulation system. The mother-to-fetus interface vascular endothelium is easy to be damaged. Next, amniotic fluid enters the maternal circulation through potential channels, leading to the occurrence of amniotic fluid embolism. Research shows that preeclampsia increases the risk of an ominous complication such as amniotic fluid embolism [28].

If D-dimer is high in an older pregnant woman during prenatal examination, the clinician should closely monitor the pregnancy blood pressure, urine routine, placental growth factor, etc. Notably, this was the first study to describe the D-dimer levels associated with blood pressure differences among pregnant women of different ages. However, the sample size of this study was so small that the results could be biased. Large prospective trials are needed to investigate the predictive value of D-dimer in preeclampsia at different ages.

Prenatal D-dimer level maybe associated with preeclampsia occurrence in pregnant women over 30 years of gestational age than in women before 30 years of age.

All data generated or analyzed during this study are included in this published article.

The experimental ideas are designed by TTL. HPZ and TTL interpretate the data for work and write the discussion of the manuscript. YJH designed and made critical revisions to the paper. SHC and JYZ collected and analyzed data. All authors contributed to editorial changes in the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. All authors read and approved the final manuscript.

All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Wenzhou People’s Hospital (approval number: 2021-346).

Not applicable.

This study was funded by the Wenzhou Science and Technology Bureau (Y20210027).

The authors declare no conflict of interest.