We found that the probability of twin pregnancy being complicated with preeclampsia was 13.16%, slightly higher than in previous reports. We performed a more comprehensive screening of high-risk factors for preeclampsia in twin pregnancies through the acquisition of clinical medical records of patients. The results of logistic multivariate analysis showed that primiparity, regular obstetric visits, pre-pregnancy BMI, CREm, URIC, MPV, HDL, LDH, Fib, Primipara, Pre-pregnancy BMI and Regular prenatal were independently associated with preeclampsia in twin pregnancies. The nomogram prediction model (concordance index 0.821) was further constructed with good accuracy and conformity, and was able to make individualized predictions for pregnant women with twin pregnancies complicated by preeclampsia, so as to allow for timeous clinical interventions and thus reduce the number of adverse outcomes in mothers and children.
The expert consensus published by the American College of Obstetricians and Gynecologists showed that primiparity, obesity, advanced age, and assisted reproductive technology were high-risk factors for pregnancies complicated by preeclampsia in singletons. Taguchi et al. found that pre-pregnancy BMI and primiparity were independent risk factors for preeclampsia in twin pregnancies.Similarly, in another prospective cohort study, Chen et al. reported that pre-pregnancy BMI was significantly associated with the risk of preeclampsia in twin pregnancies, which is consistent with our findings. In addition, regular antenatal check-ups, strengthening the monitoring for risk factors, and timely intervention can reduce the incidence of preeclampsia in twin pregnancies.
Various biochemical factors in maternal serum play an important role in the pathophysiological development of preeclampsia, and the composition, source and mechanism is different for each of these factors. At present, the serum markers used to screen for preeclampsia in twin pregnancies mainly include pregnancy-associated plasma protein A, placental protein 13, placental growth factor, inhibin A, and unconjugated estriol; however, widespread roll-out of these indicators is difficult to develop and promote in underdeveloped areas. Therefore, this study measures peripheral blood parameters, screens out predictive indicators with high sensitivity and specificity, and provides a basis for the development of economical and efficient screening programs for twin pregnancies with preeclampsia.
Previous studies on the relation between MPV and preeclampsia were based on pregnant women with singleton pregnancies, while there were fewer studies involving those with twin pregnancies. In a cohort study by they found that the peripheral blood MPV value of pregnant women with preeclampsia was significantly higher than that of normal pregnant women. A cross-sectional comparative study by Tesfay et al. showed that MPV had a good predictive value for the development of preeclampsia. However, these studies were based on singleton pregnancies; we found that an increase in peripheral blood MPV was associated with an increased risk of preeclampsia in twin pregnancies as well. The increase in MPV reflects the enhancement of platelet activation. In patients with preeclampsia, due to the increase in platelet consumption and destruction, the bone marrow produces and releases a large quantity of platelets, which leads to an increase in MPV. Conversely, preeclampsia may cause complex diseases in the endogenous blood coagulation pathway and consumes Fib, resulting in a decrease in Fib. We found an increase in the risk of preeclampsia in twin pregnancies with decreasing Fib, which is similar to the results reported in related studies.
Some studies have shown that, as pregnancy progresses, serum total cholesterol, TG, and LDL-C concentrations increase, and this abnormal dyslipidemia during pregnancy is related to preeclampsia and other adverse pregnancy outcomes. The pathophysiological basis may be that the increase in circulating lipid levels leads to an accumulation of lipids in endothelial cells, which reduces the release of prostacyclin and leads to oxidative stress. A meta-analysis by Spracklen et al. showed that low levels of HDL-C are significantly associated with the risk of preeclampsia and our study found that women with twin pregnancies who have low HDL-C also have this risk.
The main energy supply pathway to the placenta occurs through glycolysis. LDH is an intracellular enzyme required for glycolysis. Under hypoxic conditions, LDH is activated to promote glycolysis and produce large amounts of lactic acid. Therefore, elevated LDH levels often indicate cell damage and dysfunction. Studies have shown that peripheral blood LDH levels in patients with preeclampsia are significantly increased. Our study found this feature in twin pregnancies with preeclampsia. In addition, some scholars have found that high levels of LDH are significantly related to the occurrence of adverse perinatal outcomes in patients with preeclampsia. It is necessary to explore in future studies whether there is a dose-response relationship between high levels of LDH and the occurrence of adverse preeclampsia outcomes.
The kidney is an important organ involved in preeclampsia. Damage to glomerular endothelial cells and destruction of the relation between endothelial cells and podocytes are the main underlying pathogenetic mechanisms of preeclampsia.Patients with preeclampsia are prone to renal dysfunction caused by extensive renal arteriolar spasm. This causes glomerular swelling, decreased glomerular filtration rate, and decreased renal blood flow, which leads to obstruction of the excretion and clearance of renal metabolites such as URIC and CREm; this results in an increase in serum URIC and CREm. In a prospective case-control study, Enaruna et al. found that the URIC level of patients with preeclampsia was significantly increased, and that higher levels reflected disease severity. Jhee et al. developed models using machine learning to predict late-onset preeclampsia and found that CREm levels were one of the most influential variables included in the prediction models. Our study was in agreement with this, demonstrating that URIC and CREm levels were independent risk factors for preeclampsia in twin pregnancies.
We are aware of the limitations of our study. Our study is a single-center retrospective cohort study which may result in a risk of overestimating model performance. However, as a tertiary hospital in Southeast China, our number of cases is still representative and we believe the model would be useful in pregnancy supervision. Further prospective cohort and multi-center joint research will help to further expand the research results, improve the prediction accuracy of the model, and confirm the conclusions.
In summary, the prediction model of preeclampsia in twin pregnancies constructed in this study has good accuracy and high clinical application value, and can be used as a reference for obstetricians. We should pay attention to twin pregnancies with high-risk factors in clinical practice and perform careful screening, early intervention and active treatment, so as to reduce the occurrence of adverse pregnancy outcomes.