Objective
The purpose of this study was to evaluate national trends in the rate of pregnancy-related hospitalizations for venous thromboembolism (VTE) from 1994-2009 and to estimate the prevalence of comorbid conditions among these hospitalizations.
Study Design
An estimated 64,413,973 pregnancy-related hospitalizations among women 15-44 years old were identified in the 1994-2009 Nationwide Inpatient Sample. Trends in VTE-associated pregnancy hospitalizations were evaluated with the use of variance-weighted least squares regression. Chi-square tests were used to assess changes in prevalence of demographics and comorbid conditions, and multivariable logistic regression was used to evaluate the likelihood of VTE during the study period after adjustment for comorbid conditions. Antepartum, delivery, and postpartum hospitalizations were evaluated separately and reported in 4-year increments.
Results
From 1994-2009, there was a 14% increase in the rate of overall VTE-associated pregnancy hospitalizations; antepartum and postpartum hospitalizations with VTE increased by 17% and 47%, respectively. Between 1994-1997 and 2006-2009, the prevalence of hypertension and obesity doubled among all VTE-associated pregnancy hospitalizations; significant increases in diabetes mellitus and heart disease were also noted. A temporal increase in the likelihood of a VTE diagnosis in pregnancy was observed for antepartum hospitalizations from 2006-2009 when compared with 1994-1997 (adjusted odds ratio, 1.62; 95% confidence interval, 1.48–1.78).
Conclusion
There has been an upward trend in VTE-associated pregnancy hospitalizations from 1994-2009 with concomitant increases in comorbid conditions. Clinicians should have a heightened awareness of the risk of VTE among pregnant women, particularly among those with comorbid conditions, and should have a low threshold for evaluation in women with symptoms or signs of VTE.
Venous thromboembolism (VTE), a disease characterized by deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important cause of maternal morbidity and death in the United States and other developed countries. Although the rate of maternal mortality in developed countries has declined over the past few decades, PE remains one of the leading causes of maternal deaths in the United States. The overall prevalence of thromboembolic events during pregnancy is estimated to be 2 per 1000 deliveries, which represents a 4-fold increase in risk when compared with the nonpregnant population. In the postpartum period, rates of 25-99 per 10,000 women-years have been reported with up to 21.5-fold to 84-fold increase in risk in the first 6 weeks after birth when compared with nonpregnant nonpostpartum women. This increased risk may be due to physiologic changes such as hormonally induced decreased venous outflow, mechanical obstruction by the uterus, decreased mobility, and vascular injury ; however, hypercoagulability that is associated with pregnancy may be the most important contributing factor. Other factors that are associated with increased risk for pregnancy-related VTE include history of thrombosis, black race, heart disease, sickle cell disease, diabetes mellitus, lupus, advanced maternal age, obesity, hemorrhage, and cesarean delivery.
Few studies have examined trends in the incidence of pregnancy-related VTE in the United States, and these studies have shown variable results. For example, using data from a population-based cohort study in Olmsted County, MN, Heit et al reported no change in the incidence of clinically validated VTE among pregnant and postpartum women from 1966-1995. In contrast, James and Stein et al analyzed data from the National Hospital Discharge Survey and documented a significantly increased trend in the rate of DVT diagnosis among pregnancy-associated hospitalizations in the United States between 1982 and 1999.
The main objective of this analysis was to describe recent national trends in pregnancy-related hospitalizations that were complicated by VTE. Furthermore, in light of recent data that suggest an increasing prevalence of factors that are associated with VTE (such as heart disease, diabetes mellitus, obesity, and postpartum hemorrhage ), we also evaluated the relationship between pregnancy-related VTE and concurrent medical conditions and pregnancy complications over the study period.
Materials and Methods
The data that were used for this study were obtained from the 1994-2009 Nationwide Inpatient Sample (NIS) Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. The NIS is the largest nationwide all-payer inpatient database in the United States and contains information on hospital use, diagnoses, procedures, and charges for a 20% stratified sample of US community hospitals from participating states. Each year of the NIS includes approximately 5-8 million inpatient stays from approximately 1000 hospitals. The number of hospitals that contributes data has increased over time; during 2009, the NIS was drawn from 44 states and encompassed approximately 96% of all US hospital discharges. Because discharge sample weights were calculated within each sampling stratum, estimates for a nationwide representative population can be computed. The data have no personal identifiers and therefore was exempt from review by the institutional review board of the Centers for Disease Control and Prevention.
Hospitalizations for women who were 15-44 years old with a pregnancy-related discharge diagnosis were included for each year. Pregnancy hospitalizations were identified with the use of the International Classification of Diseases, Ninth Revision , Clinical Modification (ICD-9-CM) diagnostic codes 630-677, V22, V23, V24, V28, and 792.3; ICD-9-CM procedure codes 72-75; and diagnosis-related group codes (DRG) 370-384 for DRG version 24 and earlier or 765-782 for DRG version 25 and later. These hospitalizations were classified further hierarchically into delivery, postpartum, and antepartum hospitalizations. Delivery hospitalizations were identified with a previously validated method ; postpartum hospitalizations were identified by the fifth digit of “4” in ICD-9-CM codes for primary or secondary diagnosis, ICD-9-CM code V24 for any diagnosis, and postpartum DRG codes (376-377 for DRG version 24 and earlier or 769 or 776 for DRG version 25 and later). Antepartum hospitalizations were identified by the fifth digit of “3” in ICD-9-CM codes for primary or secondary diagnosis; ICD-9-CM codes V22, V23, V28, and 792.3 for any diagnosis; and antepartum DRG codes (378-384 for DRG version 24 and earlier or 770, 777-782 for DRG version 25 and later).
VTE diagnoses were identified by the presence of ICD-9-CM codes for DVT (671.3x, 671.4x, 671.5x, 671.9x, 451.11, 453.9, 451.19, 451.2, 451.81, 453.2, 453.40-453.42, 453.8, and 453.9) or PE (673.2x, 673.8x, 415.11, and 415.19) in any of the 15 available discharge diagnostic fields. Medical conditions and pregnancy complications that were reported during the hospitalization were identified similarly by ICD-9-CM codes and included anemia (280-281, 285.9, and 648.2), chronic and gestational diabetes mellitus (250.0-250.9, 648.0, and 648.8), essential and secondary hypertension (401-405, 642.0-642.2, and 642.9), obesity (278.0 and 649.1), blood transfusion (99.00-99.09), cesarean delivery (74.0-74.2, 74.4, 74.99, and 669.7), antepartum or postpartum hemorrhage (641.1-641.3, 641.8-641.9, and 666.0-666.3), multiple gestation (651 and V27.2-V27.7), preeclampsia (642.4-642.5 and 642.7), and postpartum infection (670 and 672). The specific conditions and ICD-9-CM codes that were used to define chronic heart disease have been described in detail elsewhere.
All statistical analyses were conducted with SUDAAN software (version 10; RTI International, Research Triangle Park, NC) to account for the complex sampling design of the NIS. The study period was divided into 4-year intervals (1994-1997, 1998-2001, 2002-2005, and 2006-2009), and the rate of DVT only, PE with or without DVT (PE with or without DVT), and VTE per 1000 deliveries was calculated during each 4-year interval for each hospitalization type (antepartum, delivery, and postpartum). Differences in the distribution of patient and hospital characteristics and concurrent conditions in 1994-1997, compared with 2006-2009, among VTE-associated pregnancy hospitalizations were assessed with the use of Rao-Scott χ 2 . A probability value of < .05 was considered significant; estimates with relative standard errors of ≥50% were considered unstable and were omitted; estimates with relative standard errors of 30-50% are statistically unreliable and were flagged, and the remaining estimates have a relative standard error of <30%.
Temporal trends were assessed by variance weighted regression. Because this method does not assume homogeneity of variance across the sample years, the computed probability values take into account differing sample variances for each year. Stata software (version 11; StataCorp, College Station, TX) was used for this component of the analysis.
Multivariable logistic-regression analysis was used to assess the likelihood of VTE diagnosis in the years 1998-2001, 2002-2005, and 2006-2009 compared with 1994-1997 after adjustment for maternal age, primary payer (public, private, self, or other), hospital region (northeast, midwest, south, west), hospital location (rural vs urban), and the aforementioned medical and pregnancy-related conditions.
Results
In the period of 1994-2009, there were an estimated 64,413,973 pregnancy-related hospitalizations; of those, 118,982 hospitalizations (0.18%) had a VTE diagnosis reported. For all types of VTE-associated pregnancy hospitalizations between 1994-1997 and 2006-2009, approximately one-half occurred in women 25-34 years old ( Table 1 ). Regardless of hospitalization type, the proportion of VTE hospitalizations among women 15-24 years old decreased between 1994-1997 and 2006-2009 ( Table 1 ). VTE-associated pregnancy hospitalizations were more prevalent in hospitals that were located in urban areas, and this proportion increased over the study period among antepartum and postpartum hospitalizations (85.5-91.8% and 83.2-89.3%, respectively).
| Variable | Hospitalization, % | |||||
|---|---|---|---|---|---|---|
| Antenatal | Delivery | Postnatal | ||||
| 1994-1997 (n =8597) | 2006-2009 (n = 11,476) | 1994-1997 (n = 11,607) | 2006-2009 (n = 12,419) | 1994-1997 (n = 6052) | 2006-2009 (n = 10,047) | |
| Age categories, y | ||||||
| 15-24 | 33.0 | 30.7 a | 34.8 | 26.9 a | 35.4 | 29.9 a |
| 25-34 | 52.1 | 49.7 | 48.9 | 50.3 | 46.1 | 51.2 |
| 35-44 | 15.0 | 19.6 | 16.3 | 22.8 | 18.4 | 18.9 |
| Primary payer | ||||||
| Public | 52.6 | 45.0 a | 52.4 | 50.7 | 51.3 | 45.7 |
| Private | 38.8 | 45.4 | 40.4 | 42.5 | 41.1 | 46.6 |
| Self-pay | 5.1 | 5.6 | 3.2 | 3.0 | 3.2 | 3.9 |
| Other | 3.6 | 4.1 | 3.9 | 3.8 | 4.4 | 3.8 |
| Region of hospital | ||||||
| Northeast | 20.9 | 18.6 | 23.1 | 20.2 | 19.3 | 15.3 |
| Midwest | 27.1 | 24.0 | 26.1 | 23.0 | 26.9 | 27.9 |
| South | 29.2 | 36.0 | 31.3 | 35.5 | 33.7 | 37.8 |
| West | 22.8 | 21.5 | 19.5 | 21.2 | 20.0 | 19.0 |
| Hospital location | ||||||
| Rural | 14.5 | 8.3 a | 11.5 | 10.1 | 16.8 | 10.7 a |
| Urban | 85.5 | 91.8 | 88.5 | 89.9 | 83.2 | 89.3 |
| Disposition of patient | ||||||
| Routine discharge | 79.6 | 85.2 a | 91.4 | 90.7 | 87.8 | 80.5 a |
| Transfer to short term hospital | 5.0 | 5.2 | 0.6 | 1.1 | 1.6 | 2.7 |
| Other transfers b | 1.3 | 0.5 | 0.7 | 0.7 | 1.6 | 1.9 |
| Home health care | 12.5 | 7.1 | 5.4 | 6.3 | 7.1 | 13.3 |
| Death in hospital | — | 0.5 d | 0.9 | 0.8 | 0.7 d | 0.7 |
| Other c | 1.6 | 1.4 | 1.0 | 0.4 d | 1.2 | 0.8 |
a Rao-Scott χ 2 probability value < .05: distribution of variable from 1994-1997 vs distribution from 2006-2009
b Included skilled nursing facility, intermediate care, and another type of facility
c Included left against medical advice and discharged alive, destination unknown
For all types of pregnancy hospitalizations, the rate of VTE-associated hospitalization increased 14% between 1994-1997 and 2006-2009 (1.74-1.99 per 1000 deliveries), and the rate of hospitalization associated with PE (with or without DVT) increased by 128% (0.32-0.73 per 1000 deliveries; Table 2 ). In contrast, the rate of DVT-associated hospitalization decreased from 1.42-1.26 per 1000 deliveries between 1994-1997 and 2006-2009. When stratified by hospitalization type, VTE-associated antepartum and postpartum hospitalizations increased by 17% and 47%, respectively; however, there was no significant change in the rate of VTE-associated delivery hospitalization. The rate of DVT remained constant or declined slightly for antepartum, delivery, and postpartum hospitalizations; the rate of PE (with or without DVT) increased regardless of hospitalization type.
| Variable | Years of study | P value a | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 1994-1997 | 1998-2001 | 2002-2005 | 2006-2009 | ||||||
| Weighted, n | Rate per 1000 deliveries, % | Weighted, n | Rate per 1000 deliveries, % | Weighted, n | Rate per 1000 deliveries, % | Weighted, n | Rate per 1000 deliveries, % | ||
| All hospitalizations | |||||||||
| DVT only | 21,459 | 1.42 | 19,990 | 1.28 | 22,953 | 1.39 | 21,571 | 1.26 | .02 |
| PE with/without DVT | 4797 | 0.32 | 5778 | 0.37 | 10,058 | 0.61 | 12,371 | 0.73 | < .001 |
| All VTE | 26,256 | 1.74 | 25,768 | 1.65 | 33,011 | 1.99 | 33,942 | 1.99 | < .001 |
| Antenatal hospitalizations | |||||||||
| DVT only | 6932 | 0.46 | 6659 | 0.43 | 7925 | 0.48 | 7425 | 0.44 | .22 |
| PE with/without DVT | 1665 | 0.11 | 2103 | 0.13 | 3477 | 0.21 | 4051 | 0.24 | < .001 |
| All VTE | 8597 | 0.57 | 8762 | 0.56 | 11,402 | 0.69 | 11,476 | 0.67 | < .001 |
| Delivery hospitalizations | |||||||||
| DVT only | 10,175 | 0.67 | 8550 | 0.55 | 9944 | 0.60 | 9437 | 0.55 | .03 |
| PE with/without DVT | 1432 | 0.09 | 1659 | 0.10 | 2577 | 0.16 | 2982 | 0.17 | < .001 |
| All VTE | 11,607 | 0.77 | 10,209 | 0.65 | 12,521 | 0.76 | 12,419 | 0.73 | .55 |
| Postnatal hospitalizations | |||||||||
| DVT only | 4352 | 0.29 | 4781 | 0.31 | 5084 | 0.31 | 4709 | 0.28 | .66 |
| PE with/without DVT | 1700 | 0.11 | 2016 | 0.13 | 4004 | 0.24 | 5338 | 0.31 | < .001 |
| All VTE | 6052 | 0.40 | 6797 | 0.44 | 9088 | 0.55 | 10,047 | 0.59 | < .001 |
a P value for trend estimated using variance weighted regression.
Between 1994-1997 and 2006-2009, the proportion of VTE-associated antepartum and postpartum hospitalizations with a report of anemia increased (12.5-18.9% and 21.8-31.4%, respectively); no change was noted for delivery hospitalizations ( Table 3 ). For all 3 types of VTE-associated pregnancy hospitalizations, the prevalence of comorbid heart disease, hypertension, and obesity increased significantly between 1994-1997 and 2006-2009. The prevalence of blood transfusions reports more than doubled among delivery and postpartum hospitalizations that were complicated by VTE between 1994-1997 and 2006-2009 (3.2-9.1% and 3.6-8.0%, respectively). Among VTE-associated delivery hospitalizations, the frequency of cesarean delivery increased (47.1-54.3%); the frequency of postpartum infections declined (17.7-7.1%) over the study period. The proportion of VTE-associated delivery and postpartum hospitalizations with hemorrhage and preeclampsia also increased significantly between 1994-1997 and 2006-2009.
| Variable | Years of study, % | |||||
|---|---|---|---|---|---|---|
| 1994-1997 (n = 8597) | 2006-2009 (n = 11,476) | 1994-1997 (n = 11,607) | 2006-2009 (n = 12,419) | 1994-1997 (n = 6052) | 2006-2009 (n = 10,047) | |
| Medical condition | ||||||
| Anemia | 12.5 | 18.9 a | 24.0 | 23.1 | 21.8 | 31.4 a |
| Diabetes mellitus | 4.0 | 4.4 | 6.6 | 9.0 a | 1.5 b | 4.0 a |
| Heart disease | 5.4 | 9.0 a | 5.9 | 9.3 a | 7.7 | 16.6 a |
| Hypertension | 1.6 | 5.4 a | 2.6 | 4.2 a | 3.5 | 10.5 a |
| Obesity | 3.1 | 7.5 a | 1.4 | 5.0 a | 3.9 | 8.2 a |
| Pregnancy-related conditions | ||||||
| Blood transfusion | 1.2 | 2.4 | 3.2 | 9.1 a | 3.6 | 8.0 a |
| Cesarean delivery | N/A | N/A | 47.1 | 54.3 a | N/A | N/A |
| Hemorrhage | 1.5 | 1.7 | 10.2 | 12.8 a | 4.7 | 6.1 a |
| Multiple gestation | 2.6 | 3.5 | 3.5 | 4.4 | N/A | N/A |
| Preeclampsia | 1.0 | 0.8 | 7.8 | 9.7 a | 1.8 | 3.8 a |
| Postnatal infection | N/A | N/A | 17.7 | 7.1 a | 12.2 | 11.5 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
