J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 7, Number 6, June 2015, pages 400-416

Evolving Trends in the Epidemiology, Resource Utilization, and Outcomes of Pregnancy-Associated Severe Sepsis: A Population-Based Cohort Study

Figure 1. The age-adjusted annual incidence of PASS. PASS: pregnancy-associated severe sepsis; TEP: total estimated pregnancy.

**Table 1.** The Demographic and Chronic Illness Characteristics of Hospitalizations With Pregnancy-Associated Severe Sepsis
Characteristic	n = 1,007
^aDerived for hospitalizations with non-masked zip code (n = 939). ^bBased on conditions included in the Deyo-Charlson co-morbidity index. ^cHuman immunodeficiency virus. ^dCo-morbid conditions not included in the Deyo-Charlson index.
Age (years, n (%))
< 20	160 (15.9)
20 - 34	689 (68.4)
≥ 35	158 (15.7)
Race, n (%)
Hispanic	429 (42.6)
White	308 (30.6)
Black	205 (20.4)
Other	63 (6.3)
Missing	2 (0.2)
Health insurance, n (%)
Private	324 (32.2)
Medicaid	537 (53.3)
Uninsured	94 (9.3)
Other	50 (5.0)
Missing	2 (0.2)
Poverty level ≥ 20%, n (%)^a	241 (25.7)
Chronic co-morbidities, n (%)^b
Any	310 (30.8)
Myocardial infarction	21 (2.1)
Congestive heart failure	89 (8.8)
Peripheral vascular disease	9 (0.9)
Cerebrovascular disease	29 (2.9)
Chronic pulmonary disease	54 (5.4)
Connective tissue disease	16 (1.6)
Peptic ulcer disease	5 (0.5)
Chronic liver disease	89 (8.8)
Diabetes mellitus	39 (3.9)
Chronic kidney disease	34 (3.4)
Malignancy	6 (0.6)
HIV infection^c	4 (0.4)
Deyo-Charlson score
Mean (SD)	0.51 (0.96)
Median (IQR)	0 (0 - 1)
Other conditions, n (%)^d
Smoking	30 (3.0)
Drug abuse	52 (5.2)
Alcohol abuse	2 (0.2)
Obesity	46 (4.6)
Teaching hospitals
Number (%) of hospitals	35 (17.9)
Number (%) of hospitalizations	310 (30.8)

Table 1. The Demographic and Chronic Illness Characteristics of Hospitalizations With Pregnancy-Associated Severe Sepsis

Characteristic

n = 1,007

^aDerived for hospitalizations with non-masked zip code (n = 939). ^bBased on conditions included in the Deyo-Charlson co-morbidity index. ^cHuman immunodeficiency virus. ^dCo-morbid conditions not included in the Deyo-Charlson index.

Age (years, n (%))

< 20

160 (15.9)

20 - 34

689 (68.4)

≥ 35

158 (15.7)

Race, n (%)

Hispanic

429 (42.6)

White

308 (30.6)

Black

205 (20.4)

Other

63 (6.3)

Missing

2 (0.2)

Health insurance, n (%)

Private

324 (32.2)

Medicaid

537 (53.3)

Uninsured

94 (9.3)

Other

50 (5.0)

Missing

2 (0.2)

Poverty level ≥ 20%, n (%)^a

241 (25.7)

Chronic co-morbidities, n (%)^b

Any

310 (30.8)

Myocardial infarction

21 (2.1)

Congestive heart failure

89 (8.8)

Peripheral vascular disease

9 (0.9)

Cerebrovascular disease

29 (2.9)

Chronic pulmonary disease

54 (5.4)

Connective tissue disease

16 (1.6)

Peptic ulcer disease

5 (0.5)

Chronic liver disease

89 (8.8)

Diabetes mellitus

39 (3.9)

Chronic kidney disease

34 (3.4)

Malignancy

6 (0.6)

HIV infection^c

4 (0.4)

Deyo-Charlson score

Mean (SD)

0.51 (0.96)

Median (IQR)

0 (0 - 1)

Other conditions, n (%)^d

Smoking

30 (3.0)

Drug abuse

52 (5.2)

Alcohol abuse

2 (0.2)

Obesity

46 (4.6)

Teaching hospitals

Number (%) of hospitals

35 (17.9)

Number (%) of hospitalizations

310 (30.8)

**Table 2.** The Categories of Pregnancy-Related Hospitalizations, Obstetric Risk Factors, Sites of Infection, and Reported Microbiology of Hospitalizations With Pregnancy-Associated Severe Sepsis
Characteristic	n = 1,007
^aThere were 26 fetal loss/induced abortion-related hospitalizations whose only pregnancy-related diagnosis was ICD-9-CM code 639.XX, precluding assignment to either group; upper estimates of the number and percent of fetal loss and induced abortion hospitalizations were provided after the slash for each. ^bSelected conditions acquired or associated with pregnancy, but not included among other listed co-morbidities. ^cThe total reported percentage exceeds 100, as more than one infection site has been reported for some hospitalizations.
Type of pregnancy-related hospitalization, n (%)
Fetal loss^a	104 (10.3)/130 (12.9)
Abortion^a	9 (0.9)/35 (3.5)
Antepartum	247 (24.5)
Delivery	378 (37.5)
Postpartum	243 (24.1)
Obstetric risk factors, n (%)^b
Multiple gestation	9 (0.9)
Retained products of conception	31 (3.1)
Prolonged rupture of membranes	11 (1.1)
Preeclampsia/eclampsia	93 (9.2)
Anemia	350 (34.8)
Gestational diabetes	24 (2.4)
Site of infection, n (%)^c
Respiratory	250 (24.8)
Urinary	335 (33.3)
Genital	418 (41.5)
Abdominal	98 (9.7)
Device-related	36 (3.6)
Other	50 (5.0)
Microbiology, n (%)
Gram-positive	118 (11.7)
Gram-negative	184 (18.3)
Anerobes	9 (0.9)
Other bacteria	31 (3.1)
Fungal	13 (1.3)
Not reported	652 (64.7)

Table 2. The Categories of Pregnancy-Related Hospitalizations, Obstetric Risk Factors, Sites of Infection, and Reported Microbiology of Hospitalizations With Pregnancy-Associated Severe Sepsis

Characteristic

n = 1,007

^aThere were 26 fetal loss/induced abortion-related hospitalizations whose only pregnancy-related diagnosis was ICD-9-CM code 639.XX, precluding assignment to either group; upper estimates of the number and percent of fetal loss and induced abortion hospitalizations were provided after the slash for each. ^bSelected conditions acquired or associated with pregnancy, but not included among other listed co-morbidities. ^cThe total reported percentage exceeds 100, as more than one infection site has been reported for some hospitalizations.

Type of pregnancy-related hospitalization, n (%)

Fetal loss^a

104 (10.3)/130 (12.9)

Abortion^a

9 (0.9)/35 (3.5)

Antepartum

247 (24.5)

Delivery

378 (37.5)

Postpartum

243 (24.1)

Obstetric risk factors, n (%)^b

Multiple gestation

9 (0.9)

Retained products of conception

31 (3.1)

Prolonged rupture of membranes

11 (1.1)

Preeclampsia/eclampsia

93 (9.2)

Anemia

350 (34.8)

Gestational diabetes

24 (2.4)

Site of infection, n (%)^c

Respiratory

250 (24.8)

Urinary

335 (33.3)

Genital

418 (41.5)

Abdominal

98 (9.7)

Device-related

36 (3.6)

Other

50 (5.0)

Microbiology, n (%)

Gram-positive

118 (11.7)

Gram-negative

184 (18.3)

Anerobes

9 (0.9)

Other bacteria

31 (3.1)

Fungal

13 (1.3)

Not reported

652 (64.7)

**Table 3.** Changes in the Incidence, Patient Characteristics, Resource Utilization and Outcomes of Hospitalizations With Pregnancy-Associated Severe Sepsis
Variable	2001 - 2002 (n = 113)	2009 - 2010 (n = 300)	P value
^aTEP: total estimated pregnancy. ^bChronic co-morbidities included in the Deyo-Charlson index. ^cAdjusted for inflation (2,010 dollars). ^dInpatient rehabilitation, hospice, leaving against medical advice.
Age-adjusted incidence (per 10⁵ TEP^a)
All	11	27	< 0.0001
Hispanic	10	27	< 0.0001
White	10	23	< 0.0001
Black	17	37	0.0020
Age ≥ 35 years, n (%)	16 (14.2)	34 (11.3)	0.5381
Chronic co-morbidity, n (%)^b	32 (28.3)	100 (33.3)	0.3920
Deyo-Charlson score
Mean (SD)	0.38 (0.81)	0.56 (0.97)
Median (IQR)	0 (0 - 1)	0 (0 - 1)	0.1173
Obesity, n (%)	1 (0.9)	22 (7.3)	0.0211
Organ failures, n (%)
Respiratory	65 (57.7)	193 (64.3)	0.2459
Cardiovascular	36 (31.9)	181 (60.3)	< 0.0001
Renal	20 (18)	94 (31)	0.0099
Hepatic	4 (3.5)	22 (7.3)	0.2349
Hematological	28 (24.8)	83 (27.7)	0.6414
Metabolic	14 (12.4)	68 (22.7)	0.0281
Neurological	2 (1.8)	29 (9.3)	0.0152
Number of organ failures
1	73 (64.6)	106 (35.3)	< 0.0001
2	30 (26.5)	88 (29.3)	0.6626
3	7 (6.2)	59 (19.6)	0.0015
4+	3 (2.7)	47 (15.7)	0.0006
ICU admission, n (%)	88 (77.9)	270 (90)	0.0020
Procedures, n (%)
Mechanical ventilation	45 (39.8)	138 (46)	0.3099
Central venous catheterization	31 (27.4)	150 (50)	0.0001
Hemodialysis	4 (3.5)	18 (6)	0.4552
Hospital length of stay (days)
Mean (SD)	14.7 (15.3)	15.7 (21)
Median (IQR)	9 (6 - 19)	9.5 (5.5 - 18)	0.7939
Hospital charges (dollars)^c
Mean (SD)	118,219 (145,240)	191,503 (319,482)
Median (IQR)	64,034 (34,362 - 150,464)	89,895 (43,614 - 218,357)	0.0141
Disposition, n (%)
Mortality	11 (9.7)	36 (12)	0.6365
Home	80 (70.8)	191 (63.7)	0.2136
Home care	10 (8.8)	30 (10)	0.8683
Another short-term facility	8 (7.1)	17 (5.7)	0.5613
Long-term care facility	3 (2.7)	14 (4.7)	0.5224
Other^d	1 (0.9)	10 (1.3)	0.2412
Mortality rate (per 10⁵ TEP)	1.1	3.3	0.0007

Table 3. Changes in the Incidence, Patient Characteristics, Resource Utilization and Outcomes of Hospitalizations With Pregnancy-Associated Severe Sepsis

Variable

2001 - 2002 (n = 113)

2009 - 2010 (n = 300)

P value

^aTEP: total estimated pregnancy. ^bChronic co-morbidities included in the Deyo-Charlson index. ^cAdjusted for inflation (2,010 dollars). ^dInpatient rehabilitation, hospice, leaving against medical advice.

Age-adjusted incidence (per 10⁵ TEP^a)

All

< 0.0001

Hispanic

< 0.0001

White

< 0.0001

Black

0.0020

Age ≥ 35 years, n (%)

16 (14.2)

34 (11.3)

0.5381

Chronic co-morbidity, n (%)^b

32 (28.3)

100 (33.3)

0.3920

Deyo-Charlson score

Mean (SD)

0.38 (0.81)

0.56 (0.97)

Median (IQR)

0 (0 - 1)

0.1173

Obesity, n (%)

1 (0.9)

22 (7.3)

0.0211

Organ failures, n (%)

Respiratory

65 (57.7)

193 (64.3)

0.2459

Cardiovascular

36 (31.9)

181 (60.3)

< 0.0001

Renal

20 (18)

94 (31)

0.0099

Hepatic

4 (3.5)

22 (7.3)

0.2349

Hematological

28 (24.8)

83 (27.7)

0.6414

Metabolic

14 (12.4)

68 (22.7)

0.0281

Neurological

2 (1.8)

29 (9.3)

0.0152

Number of organ failures

73 (64.6)

106 (35.3)

< 0.0001

30 (26.5)

88 (29.3)

0.6626

7 (6.2)

59 (19.6)

0.0015

3 (2.7)

47 (15.7)

0.0006

ICU admission, n (%)

88 (77.9)

270 (90)

0.0020

Procedures, n (%)

Mechanical ventilation

45 (39.8)

138 (46)

0.3099

Central venous catheterization

31 (27.4)

150 (50)

0.0001

Hemodialysis

4 (3.5)

18 (6)

0.4552

Hospital length of stay (days)

Mean (SD)

14.7 (15.3)

15.7 (21)

Median (IQR)

9 (6 - 19)

9.5 (5.5 - 18)

0.7939

Hospital charges (dollars)^c

Mean (SD)

118,219 (145,240)

191,503 (319,482)

Median (IQR)

64,034 (34,362 - 150,464)

89,895 (43,614 - 218,357)

0.0141

Disposition, n (%)

Mortality

11 (9.7)

36 (12)

0.6365

Home

80 (70.8)

191 (63.7)

0.2136

Home care

10 (8.8)

30 (10)

0.8683

Another short-term facility

8 (7.1)

17 (5.7)

0.5613

Long-term care facility

3 (2.7)

14 (4.7)

0.5224

Other^d

1 (0.9)

10 (1.3)

0.2412

Mortality rate (per 10⁵ TEP)

1.1

3.3

0.0007

**Table 4.** Logistic Regression Analysis of Variables Associated With Development of Pregnancy-Associated Severe Sepsis
Covariate	Adjusted odds ratio (95% CI)^a	P value
^a95% confidence interval. ^bAge < 35 years used as referent. ^cWhite race used as referent. ^dPoverty rate ≤ 20% used as referent; modeled only for pregnancy-associated hospitalizations with zip code data (that is, excluding those with a diagnosis of HIV infection, drug or alcohol abuse). ^ePrivate insurance used as referent; significant only when modeled without including poverty level (that is, without zip code data, and including pregnancy-associated hospitalizations with a diagnosis of HIV infection, drug or alcohol abuse). ^fBased on the Deyo-Charlson index. ^gHuman immunodeficiency virus.
Age ≥ 35 years^b	1.194 (0.989 - 1.442)	0.0649
Black race^c	1.354 (1.141 - 1.607)	0.0005
Poverty level > 20%^d	1.308 (1.125 - 1.520)	0.0005
No health insurance^e	1.255 (1.010 - 1.558)	0.0403
Smoking	1.050 (0.653 - 1.689)	0.8411
Alcohol	0.631 (0.193 - 2.068)	0.4475
Drug abuse	3.365 (2.462 - 4.600)	< 0.0001
Preeclampsia/eclampsia	1.329 (1.052 - 1.679)	0.0173
Gestational diabetes	0.542 (0.357 - 0.823)	0.0040
Obesity	1.421 (1.011 - 1.996)	0.0431
Iron-deficiency anemia	0.828 (0.578 - 1.187)	0.3036
Chronic co-morbidities^f
Myocardial infarction	11.023 (5.932 - 20.484)	< 0.0001
Congestive heart failure	20.485 (15.352 - 27.334)	< 0.0001
Peripheral vascular disease	2.847 (1.212 - 6.692)	0.0164
Cerebrovascular disease	8.624 (4.710 - 15.792)	< 0.0001
Chronic pulmonary disease	1.773 (1.285 - 2.448)	0.0005
Connective tissue disease	2.251 (1.210 - 4.187)	0.0104
Peptic ulcer disease	6.500 (2.000 - 21.130)	0.0019
Chronic liver disease	41.361 (31.531 - 54.266)	< 0.0001
Diabetes	1.771 (1.217 - 2.578)	0.0028
Chronic renal disease	5.581 (3.582 - 9.559)	< 0.0001
Malignancy	4.669 (1.800 - 12.111)	0.0015
HIV infection^g	4.248 (1.518 - 11.889)	0.0059

Table 4. Logistic Regression Analysis of Variables Associated With Development of Pregnancy-Associated Severe Sepsis

Covariate

Adjusted odds ratio (95% CI)^a

P value

^a95% confidence interval. ^bAge < 35 years used as referent. ^cWhite race used as referent. ^dPoverty rate ≤ 20% used as referent; modeled only for pregnancy-associated hospitalizations with zip code data (that is, excluding those with a diagnosis of HIV infection, drug or alcohol abuse). ^ePrivate insurance used as referent; significant only when modeled without including poverty level (that is, without zip code data, and including pregnancy-associated hospitalizations with a diagnosis of HIV infection, drug or alcohol abuse). ^fBased on the Deyo-Charlson index. ^gHuman immunodeficiency virus.

Age ≥ 35 years^b

1.194 (0.989 - 1.442)

0.0649

Black race^c

1.354 (1.141 - 1.607)

0.0005

Poverty level > 20%^d

1.308 (1.125 - 1.520)

0.0005

No health insurance^e

1.255 (1.010 - 1.558)

0.0403

Smoking

1.050 (0.653 - 1.689)

0.8411

Alcohol

0.631 (0.193 - 2.068)

0.4475

Drug abuse

3.365 (2.462 - 4.600)

< 0.0001

Preeclampsia/eclampsia

1.329 (1.052 - 1.679)

0.0173

Gestational diabetes

0.542 (0.357 - 0.823)

0.0040

Obesity

1.421 (1.011 - 1.996)

0.0431

Iron-deficiency anemia

0.828 (0.578 - 1.187)

0.3036

Chronic co-morbidities^f

Myocardial infarction

11.023 (5.932 - 20.484)

< 0.0001

Congestive heart failure

20.485 (15.352 - 27.334)

< 0.0001

Peripheral vascular disease

2.847 (1.212 - 6.692)

0.0164

Cerebrovascular disease

8.624 (4.710 - 15.792)

< 0.0001

Chronic pulmonary disease

1.773 (1.285 - 2.448)

0.0005

Connective tissue disease

2.251 (1.210 - 4.187)

0.0104

Peptic ulcer disease

6.500 (2.000 - 21.130)

0.0019

Chronic liver disease

41.361 (31.531 - 54.266)

< 0.0001

Diabetes

1.771 (1.217 - 2.578)

0.0028

Chronic renal disease

5.581 (3.582 - 9.559)

< 0.0001

Malignancy

4.669 (1.800 - 12.111)

0.0015

HIV infection^g

4.248 (1.518 - 11.889)

0.0059

**Table 5.** Logistic Regression Analysis of Variables Associated With Hospital Mortality Among Hospitalizations With Pregnancy-Associated Severe Sepsis
Covariate	Adjusted odds ratio (95% CI)^a	P value
^a95% confidence interval. ^bAge < 35 years used as referent. ^cPrivate insurance used as referent. ^dBased on the Deyo-Charlson index. ^eHuman immunodeficiency virus. ^fType and number of failing organs were modeled separately. ^gOne organ failure used as referent.
Age ≥ 35 years^b	1.595 (0.888 - 2.864)	0.1185
No health insurance^c	2.934 (1.464 - 5.880)	0.0024
Smoking	0.391 (0.088 - 1.742)	0.2512
Drug abuse	3.017 (1.278 - 7.122)	0.0118
Iron-deficiency anemia	1.316 (0.263 - 6.593)	0.7385
Anemia	0.329 (0.183 - 0.593)	0.0002
Preeclampsia/eclampsia	1.063 (0.536 - 2.107)	0.8616
Stillbirth	1.371 (0.407 - 4.622)	0.6105
Operative vaginal delivery	1.589 (0.799 - 3.163)	0.1868
Hemorrhage	1.171 (0.676 - 2.030)	0.5726
Chronic co-morbidities^d
Myocardial infarction	1.888 (0.594 - 6.006)	0.2817
Connective tissue disease	2.509 (0.609 - 10.346)	0.2031
Chronic liver disease	1.872 (0.942 - 3.317)	0.0734
Malignancy	7.003 (0.898 - 54.624)	0.0633
Cerebrovascular disease	1.455 (0.483 - 4.379)	0.5047
HIV infection^e	45.465 (5.180-399.031)	0.0006
Urinary tract infection	0.300 (0.132 - 0.682)	0.0041
Genital tract infection	0.806 (0.427 - 1.522)	0.5056
Organ failures^f
Respiratory	2.577 (0.982 - 6.762)	0.0545
Cardiovascular	1.909 (1.167 - 3.122)	0.0100
Renal	1.727 (1.028 - 2.900)	0.0388
Hepatic	1.892 (0.358 - 10.004)	0.4531
Hematological	1.291 (0.731 - 2.278)	0.3791
Metabolic	0.818 (0.459 - 1.457)	0.4951
Neurological	1.637 (0.780 - 3.436)	0.1927
Number of organ failures^{f, g}
2	1.536 (0.766 - 3.076)	0.2265
3	3.827 (1.873 - 7.818)	0.0002
4	2.895 (1.239 - 6.764)	0.0141
Mechanical ventilation	4.540 (2.562 - 8.045)	< 0.0001
Hemodialysis	2.373 (1.126 - 5.000)	0.0231
Central venous catheterization	1.254 (0.781 - 2.014)	0.3496

Table 5. Logistic Regression Analysis of Variables Associated With Hospital Mortality Among Hospitalizations With Pregnancy-Associated Severe Sepsis

Covariate

Adjusted odds ratio (95% CI)^a

P value

^a95% confidence interval. ^bAge < 35 years used as referent. ^cPrivate insurance used as referent. ^dBased on the Deyo-Charlson index. ^eHuman immunodeficiency virus. ^fType and number of failing organs were modeled separately. ^gOne organ failure used as referent.

Age ≥ 35 years^b

1.595 (0.888 - 2.864)

0.1185

No health insurance^c

2.934 (1.464 - 5.880)

0.0024

Smoking

0.391 (0.088 - 1.742)

0.2512

Drug abuse

3.017 (1.278 - 7.122)

0.0118

Iron-deficiency anemia

1.316 (0.263 - 6.593)

0.7385

Anemia

0.329 (0.183 - 0.593)

0.0002

Preeclampsia/eclampsia

1.063 (0.536 - 2.107)

0.8616

Stillbirth

1.371 (0.407 - 4.622)

0.6105

Operative vaginal delivery

1.589 (0.799 - 3.163)

0.1868

Hemorrhage

1.171 (0.676 - 2.030)

0.5726

Chronic co-morbidities^d

Myocardial infarction

1.888 (0.594 - 6.006)

0.2817

Connective tissue disease

2.509 (0.609 - 10.346)

0.2031

Chronic liver disease

1.872 (0.942 - 3.317)

0.0734

Malignancy

7.003 (0.898 - 54.624)

0.0633

Cerebrovascular disease

1.455 (0.483 - 4.379)

0.5047

HIV infection^e

45.465 (5.180-399.031)

0.0006

Urinary tract infection

0.300 (0.132 - 0.682)

0.0041

Genital tract infection

0.806 (0.427 - 1.522)

0.5056

Organ failures^f

Respiratory

2.577 (0.982 - 6.762)

0.0545

Cardiovascular

1.909 (1.167 - 3.122)

0.0100

Renal

1.727 (1.028 - 2.900)

0.0388

Hepatic

1.892 (0.358 - 10.004)

0.4531

Hematological

1.291 (0.731 - 2.278)

0.3791

Metabolic

0.818 (0.459 - 1.457)

0.4951

Neurological

1.637 (0.780 - 3.436)

0.1927

Number of organ failures^{f, g}

1.536 (0.766 - 3.076)

0.2265

3.827 (1.873 - 7.818)

0.0002

2.895 (1.239 - 6.764)

0.0141

Mechanical ventilation

4.540 (2.562 - 8.045)

< 0.0001

Hemodialysis

2.373 (1.126 - 5.000)

0.0231

Central venous catheterization

1.254 (0.781 - 2.014)

0.3496