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Pregnancy and the puerperium are well-established risk factors for venous thromboembolism (VTE). During pregnancy, it is estimated that the incidence of VTE is between10–20 events per 10 000 [1–7]. Although the actual incidence of pregnancy-associated VTE is very low, VTE accounts for 1.1 deaths per 100 000 deliveries, which is 5–10% of all maternal deaths [5]. Thus, pregnancy-associated VTE represents a major maternal health problem worldwide.

Most previous studies regarding pregnancy-associated VTE were conducted in Caucasian populations. In spite of the clinical significance of pregnancy-associated VTE, a nationwide epidemiologic study has never been conducted in an Asian population. This is probably because VTE occurs infrequently during pregnancy and the incidence of VTE in Asian populations has generally been lower than that in Caucasian populations [8]. Therefore, a nationwide epidemiologic study was performed that used the Korean Health Insurance Review and Assessment Service (HIRA) database to provide basic information regarding the incidence of pregnancy-associated VTE.

Recently, we reported that the incidence of VTE in the Korean population is approximately one-tenth to one-fifth of that reported in the Caucasian population [8]. As an extension of the epidemiologic study that investigated the difference between ethnicities, we carried out the pregnancy-associated VTE study in the Korean population using the Korean Health Insurance Review and Assessment Service (HIRA) database to provide basic information regarding the incidence of pregnancy-associated VTE. HIRA is a government-affiliated organization that builds an accurate claims review and quality assessment system for the National Health Insurance [9]. All pregnancy-associated VTE cases were included when both diagnostic codes according to the Korean Classification of Disease, fifth edition and medication codes, for example I80.2 [deep vein thrombosis (DVT), not otherwise specified (NOS)], I80.3 (embolism or thrombosis of the lower extremity, NOS), I26 [pulmonary thromboembolism (PE)], I26.0 (PE with a mention of acute cor pulmonale), I26.9 (PE, NOS), O87.1 (DVT, postpartum) and O88 (obstetric embolism) were simultaneously identified.

A total of 147 cases of pregnancy-associated VTE were identified in the Korean population during the 5-year period (2006–2010) examined. The distribution by age group (in descending frequency) was as follows: 30–34 years, 39.4%; 25–29 years, 32.6%; 35–39 years, 20.4%; 15–24 years, 4.1%; ≥ 40 years, 3.4%. Eighty patients (54.5%) were nulliparous, whereas 67 patients (45.6%) were multiparous. With regard to the type of delivery, 69 patients (46.9%) had a vaginal delivery and 78 patients (53.1%) had a cesarean section. Four patients (2.7%) had multiple pregnancies, two patients (1.4%) had premature rupture of the membranes and two patients (1.4%) had preeclampsia/eclampsia. Forty-four (29.9%) and 103 (70.1%) patients were diagnosed with antenatal and postnatal VTE, respectively.

During the 5-year study period, there were 1 795 064 deliveries in Korean. Thus, the total incidence of pregnancy-associated VTE was 0.82 (per 10 000 deliveries) [95% confidence interval (CI), 0.69–0.96]. The annual incidence of pregnancy-associated VTE was 0.70 in 2006, 0.58 in 2007, 0.72 in 2008, 1.04 in 2009 and 1.06 in 2010 (Fig. 1A). These data indicate that the incidence of pregnancy-associated VTE increased steadily from 2007 to 2010. The incidence of pregnancy-associated VTE (per 10 000 deliveries) was 0.47 (95% CI, 0.17–1.03) at 15–24 years of age, 0.71 (95% CI, 0.52–0.94) at 25–29 years of age, 0.76 (95% CI, 0.57–0.98) at 30–34 years of age, 1.47 (95% CI, 0.99–2.10) at 35–40 years of age and 2.33 (95% CI, 0.76–5.43) at over 40 years of age. The odds ratio (OR) for VTE was 1.07 (95% CI, 0.73–1.57; = 0.73) at 30–34 years of age, 2.08 (95% CI, 1.32–3.28; = 0.002) at 35–40 years of age and 3.29 (95% CI, 1.31–8.26; = 0.01) at over 40 years of age.

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Figure 1.  The incidence of pregnancy-associated venous thromboembolism (VTE) (per 10 000 deliveries) in Korean women. (A) The annual incidence of pregnancy-associated VTE. (A) The incidence of pregnancy-associated VTE by age.

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This study is the largest national population-based epidemiologic study ever done in Asia. In this present study, the incidence rate of pregnancy-associated VTE in the Korean population was found to be approximately 10% of that reported in the Caucasian population. Based on our previous study [8], pregnancy-associated VTE cases account for only 0.3% of the total number of VTE cases (in 2008). The reported annual incidence (per 10 000 deliveries) of VTE was 16.7–19.98 in North America [1,4,5], 8.5 in the United Kingdom [6], 8.87 in Denmark [7], 10 in Norway [2] and 13 in Sweden [3]. Genetic mutations have been suggested as the most plausible cause for this significant difference between Asians and Caucasians. During pregnancy, the thrombogenic potential of these genetic mutations is enhanced by the hypercoagulable state induced by the normal pregnancy-associated changes to several coagulation factors [10–12]. Approximately 50% of pregnant women with VTE have thrombophilia, whereas only 10% of the overall Caucasian population is affected [13].

Advanced maternal age has been reported as a risk factor for pregnancy-associated VTE [14], and our results support such an association. In the present study, the incidence of pregnancy-associated VTE increased steadily with age. Compared with the standard age group of pregnant women (25–29 years of age), older age (35–40-years old) pregnant women were approximately twice as likely to have a VTE, and pregnant women over the age of 40 were three times as likely. Based on the HIRA database, the number of deliveries involving women over the age of 35 years in Korea rapidly increased during the 5-year period of this study. The percentage of deliveries in the older age group (over 35 years old) accounted for was 10.2% in 2006, 11.2% in 2007, 12.5% in 2008, 13.5% in 2009 and 15.2% in 2010. Based on these data, the recent increase in pregnancy-associated VTE in Korea may be explained by the steady increase in deliveries by women over the age of 35 years. In contrast to our results, the Rochester Epidemiology Project reported that younger women were the most likely to develop a VTE during pregnancy [4]. Moreover, they did not find that increasing age increased the risk of developing a VTE in the postpartum period. However, they could not find any significant risk factors for this phenomenon. This discrepancy should be investigated in a large, prospective, cohort study in the future.

In conclusion, the present study demonstrates a lower incidence of pregnancy-associated VTE in Asian compared with Caucasian women; however, it also demonstrates a yearly increasing incidence of pregnancy-associated VTE in the Korean population.

Acknowledgements

  1. Top of page
  2. Acknowledgements
  3. Disclosure of Conflict of Interests
  4. References

We would especially like to thank Eun Sug Hwang, Assistant Manager from Healthcare Statistics & Information Disclosure Division, Healthcare Policy Research Department, Korean Health Insurance Review & Assessment Services for data retrieval.

Disclosure of Conflict of Interests

  1. Top of page
  2. Acknowledgements
  3. Disclosure of Conflict of Interests
  4. References

The authors state that they have no conflict of interest.

References

  1. Top of page
  2. Acknowledgements
  3. Disclosure of Conflict of Interests
  4. References