Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a condition that occurs when a blood clot forms in a vein. During pregnancy, pregnant women have an approximately 4-fold increased risk of VTE than non-pregnant women due to venous stasis, pelvic vein compression by the uterine, and hypercoagulability. The incidences of VTE in pregnant women ranged from 0.82 to 19.97 per 10,000 deliveries in various countries and regions worldwide (1, 2). A meta-analysis of 20 studies reported that the pooled overall incidence of pregnancy-related VTE was 12 per 10,000 deliveries (3). VTE is a leading cause of maternal mortality and morbidity, posing a great threat to the health of mothers worldwide. Therefore, identifying more potential high-risk factors and strengthening VTE risk assessment and thromboprophylaxis among high-risk populations is of vital importance in the early prevention of VTE among pregnant women (4).

The known risk factors for pregnancy-related VTE included a personal past medical history of VTE, cesarean section delivery, preeclampsia, assisted reproduction methods, and other risk factors such as maternal age, parity, multiple pregnancies, gestational diabetes mellitus (GDM), and smoking (5–7). Meteorological conditions such as seasonal changes were found to have an important influence on the development of cardiovascular diseases (CVDs), leading to disorders of fibrinolysis, coagulation, and arterial blood pressure. Using data from 19 countries with seasonal variation, mortality from overall CVD and non-CVD/non-cancer was found to show a seasonal pattern (peak to nadir difference), being higher in winter than in summer (8).

Some previous studies have found that the occurrences of VTE/DVT/PE in hospitalized patients may be related to the seasons. Most studies found a high incidence of VTE/DVT/PE in winter, (9–17). some in autumn, (17–19) and a few in summer (20) and spring (21, 22). There was also one study reporting non-seasonal occurrences of VTE among hospitalized patients (23). The studies mentioned above have relatively small sample sizes (n < 2,800) and are mostly from a single center. Only three prior studies were performed in the Chinese population, and the conclusions were not consistent [with two being highest in winter (13, 14) and one being non-seasonal (23)]. At present, there is no prior report on the seasonal occurrences of VTE in pregnant women. Therefore, there is an urgent need for a large multi-center cohort of pregnant women to investigate the seasonality of VTE in pregnant women. Our hypothesis was that the season of delivery might be associated with VTE among pregnant women.

Based on a retrospective cohort of pregnant women in seven designated sites in Hubei Province, China, this study aimed to explore the relationships between the season of delivery and new-onset VTE during hospitalization.

To the best of our knowledge, this is the first study to report the seasonal variations of VTE in pregnant women. This study demonstrated that pregnant women who delivered in the summer, autumn, and winter had a significantly increased risk of VTE during hospitalization compared with those who delivered in spring. IVF, GDM, and preterm birth were risk factors for VTE. We adjusted for these covariates in the logistic regression models and restricted the analyses among pregnant women without IVF, GDM, and preterm, and the results still remained robust. Compared with pregnant women who delivered in March, April, and May, those who delivered in June, July, September, November, December, and February had a higher risk of VTE during hospitalization.

The occurrences of CVD have been found to be seasonal. The relationships between the seasons and the occurrences of VTE in hospitalized patients had been reported by some studies, although the conclusions were not completely consistent. Most studies found that hospitalized patients had the highest incidence of VTE in winter, (9–17) and few studies found the highest incidence of VTE in spring/summer (20–22) or no seasonality (23). Our results are similar to those conducted in Italy, Turkey, Israel, and the United States. The MASTER Registry in 25 Italian hospitals observed that VTE was most frequent in autumn (32.9%) and less frequent in spring (19%) (18). A cross-sectional study in Turkey found that the highest number of PE cases were seen in autumn (29.8%) (19). Results from the Italian Ministry of Health showed that PE hospital admissions increased by 1.07 and 0.96% in autumn and winter, respectively (17). A study from Northern Israel demonstrated that DVT and/or PE cases were most frequent in November and least frequent in May (28) which was consistent with our results. Results from East Birmingham Hospital showed that the incidence of PE in autumn was significantly higher than in the rest of the year (29).

Of the studies mentioned above, three were conducted in China. Li et al. found a winter peak in DVT patients in Shenyang (13). The lower the ambient temperature, the higher the incidence of DVT. Tan et al. suggested that hospitalized patients in Beijing were more likely to have PE in winter than in other seasons (14). A study by Lee et al. found that the percentages of VTE peaked in summer and troughed in spring (23). However, it represented non-significant seasonal differences in VTE risk in hospitalized patients in Taiwan (23). Of the three studies, the climates in the first two (Shenyang: temperate and semihumid continental climate; Beijing: temperate monsoon climate) were significantly different from that in the present study (subtropical monsoon climate), while the climate in the third study (subtropical monsoon climate/tropical monsoon climate) was similar to that in the present study. The sample size was smaller than ours (theirs: 2774; ours: 37778), which may make it difficult to observe significant differences. The current study is the only one performed on a pregnant population. It found that pregnant women who delivered in autumn had the highest incidences of VTE during hospitalization. Pregnant women who delivered in summer and winter also had an increased risk of VTE during hospitalization.

We hypothesized that our discordance with other studies may be related to the variance of the study population (pregnant women and hospitalized patients), meteorological factors (e.g., altitude, temperature, air pressure, and humidity), definitions of seasons, outcomes (VTE/DVT/PE), ethnic (genetic factors), sample size (previous studies had sample sizes of <2,800), and number of designated centers (single center and multi-center). The participants in this study are all from Hubei Province, China; therefore, we should be cautious when extrapolating the current findings to populations in other countries and regions.

The mechanisms underlying the increased risk of VTE during hospitalization among pregnant women who delivered in summer, autumn, and winter remain unclear. Pollution, climatological variables, and biological programming during pregnancy may explain the results. Participants may be more susceptible to VTE after air pollution exposure (e.g., PM_2.5) (30). Thermoregulatory arteriovenous shunt vasoconstriction was found to promote DVT by generating venous stasis and hypoxia (31). The increased risk of VTE in summer may be related to increased temperature (32) and dehydration. Dehydration was found to be a major risk factor for VTE in human (33) and animal studies (34). The increased risk of VTE in winter may be explained by the cold temperature, the increase in blood viscosity (21), a hypercoagulable state that was ascribed to elevated fibrinogen levels (35), peripheral vasoconstriction, and the limited physical activity due to the colder temperature (36). A study among mice found that cold exposure (4°C air temperature) could reduce serum adiponectin, which may help in protection against arteriosclerosis (37). In this study, participants who delivered in autumn yielded the highest VTE risk compared to winter or summer. Given that the temperatures in autumn and spring were similar, we hypothesize that the increased risk of VTE in autumn may be associated with the rapid change in temperature and air pressure in autumn (38). The exact mechanisms are still unclear, and more research should be carried out in the future.

Pregnant women with IVF pregnancy have an increased risk of VTE due to increased estrogen levels that lead to hypercoagulability (7). GDM increases the risk of VTE, which may be related to the vascular inflammation promoted by high blood glucose (39). Preterm delivery was observed to be a conventional pregnancy-associated VTE risk factor (40). In this study, potential confounders of IVF pregnancy, GDM, and preterm were adjusted and considered in sensitivity analyses. The main results were still stable, indicating that the associations between the season of delivery and VTE during hospitalization were independent of the covariates mentioned above.

Our study has several strengths that are worth mentioning. First, this is the first study to report an increased risk of VTE occurring in pregnant women who delivered in other seasons compared with those who delivered in spring. Second, the sample sizes of previous studies on the seasonal occurrences of VTE were less than 2,800, and the sample size of this study was the largest. Most of the previous studies were single-center studies, whereas this study is a multi-center study, thus the reliability of the study results increased. Third, this study has the ability to exclude those who had VTE or medication thromboprophylaxis within 2 weeks of admission, which clarified the results. Fourth, all the data in this study were diagnosed and analyzed by two researchers independently. If there was any inconsistency, a third researcher would participate to make the data more reliable. This study had comprehensive covariates including demographic, lifestyle, history of reproduction, and disease, allowing for adjustment.

This study has several limitations. First, certain women may possess a genetic inclination toward the development of VTE, which is referred to as hereditary thrombophilia. Hereditary factors were not considered in this study, though participants with a history of prenatal VTE were excluded. Second, retrospective data collection may be prone to missing data, measurement errors, and inaccuracy. Pregnant women who were overweight or obese before pregnancy had an increased risk of VTE. Although this study included as many covariates as possible, pre-pregnancy body mass index was not considered. Subsequent studies should include the covariate of pre-pregnancy body mass index. Third, this study only discussed the relationships between season and VTE. The relationships between meteorological factors (e.g., temperature and humidity) and VTE remain to be investigated in the future. Finally, the rates of VTE vary greatly between Chinese and foreign populations. The participants of this study were all from Hubei Province, China, a tropical monsoon climate region. Therefore, caution is required when extrapolating the conclusions of this study to populations in other countries and regions.

In conclusion, this is the first study demonstrating that pregnant women who delivered in summer, autumn, and winter had a significantly increased risk of VTE during hospitalization compared with those who delivered in spring. This study suggests that VTE risk assessment and thromboprophylaxis should be strengthened in pregnant women, especially for those who delivered in summer, autumn, and winter, which might have important public health implications in the prevention of VTE. More multi-center and mechanistic studies are warranted in the future.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding authors.

The studies involving humans were approved by Tongji Medical College affiliated with Huazhong University of Science and Technology. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants' legal guardians/next of kin because the information was retrieved from the medical records retrospectively.

QL: Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Validation, Visualization, Writing – original draft, Writing – review & editing. HoW: Conceptualization, Data curation, Formal analysis, Validation, Writing – review & editing. HuW: Formal analysis, Validation, Writing – review & editing. JD: Formal analysis, Validation, Writing – review & editing. ZC: Formal analysis, Validation, Writing – review & editing. WL: Formal analysis, Validation, Writing – review & editing. RZ: Formal analysis, Validation, Writing – review & editing. SC: Formal analysis, Validation, Writing – review & editing. JG: Formal analysis, Validation, Writing – review & editing. HL: Formal analysis, Validation, Writing – review & editing. YC: Formal analysis, Validation, Writing – review & editing. XY: Formal analysis, Validation, Writing – review & editing. SD: Formal analysis, Validation, Writing – review & editing. YT: Formal analysis, Validation, Writing – review & editing. YX: Formal analysis, Validation, Writing – review & editing. PW: Formal analysis, Validation, Writing – review & editing. FZ: Formal analysis, Validation, Writing – review & editing. XW: Formal analysis, Validation, Writing – review & editing. LT: Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Validation, Writing – original draft, Writing – review & editing. YH: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Validation, Visualization, Writing – original draft, Writing – review & editing.