Abstract
This study uses National Readmissions Database data to characterize incidence of and mortality due to maternal sepsis within 42 days of delivery hospitalization discharge in the United States between 2013 and 2016.
Maternal sepsis is a leading cause of maternal morbidity and mortality. However, population-based estimates of maternal sepsis occurring after delivery hospitalization have been limited because previous studies have focused on select populations or have not followed up patients longitudinally.1,2 Thus, the burden of maternal sepsis and sepsis-related deaths may be underestimated. We assessed the nationwide incidence and outcomes of maternal sepsis within 42 days of delivery hospitalization discharge using all-payer data.
Methods
We analyzed data from 2013 to 2016 from the National Readmissions Database (NRD), which aggregates all-payer hospital discharges from 27 states, representing 57.8% of the US population, and allows for measurement of readmissions, even across insurance changes. We identified single or multiple live-birth and stillbirth delivery hospitalizations, excluding ectopic pregnancies, molar pregnancies, and abortions.3 We further limited index hospitalizations to those with a January through October discharge to allow for 42-day follow-up in the yearly data sets.
We identified sepsis using diagnosis codes for severe sepsis and septic shock or concurrent codes for sepsis and acute organ dysfunction.2 For both delivery hospitalizations and sepsis, we updated International Classification of Diseases, Ninth Revision, Clinical Modification identification methods to International Classification of Diseases, Tenth Revision, Clinical Modification methods. Acute organ dysfunctions were identified using criteria based on the methods of Dombrovskiy et al,4 which have been used in previous studies of maternal sepsis.2 Site of infection was classified based on the highest-ranking diagnosis indicating an infectious site, and comorbidities were identified using a weighted index from Bateman et al.5 Maternal sepsis was defined as sepsis occurring during delivery hospitalization or during a readmission within 42 days of delivery discharge. The 42-day end point was selected in accordance with the World Health Organization definition of maternal sepsis.6 Maternal death was defined as in-hospital mortality occurring during index delivery hospitalization or within 42 days of delivery hospitalization discharge. Maternal deaths were considered sepsis-related if they occurred during a hospitalization with sepsis. The NRD does not include data on out-of-hospital deliveries or deaths.
The primary outcomes were the incidence of maternal sepsis and sepsis-related mortality (overall and during and after delivery hospitalization). All-cause maternal deaths were also measured and the proportion that were sepsis-related was determined. Weighted characteristics of maternal sepsis episodes occurring during vs after delivery hospitalization were compared using the F statistic with significance set at a 2-sided P < .05. Nationwide estimates were generated using NRD sampling weights. Results are presented as unweighted numbers and weighted proportions, means, or incidences per 100 000 deliveries. Analyses were performed with Stata/MP15 (StataCorp). This study was deemed exempt by the University of Michigan’s institutional review board.
Results
From 63 665 593 hospitalizations in the NRD (2013-2016), there were 5 957 678 delivery hospitalizations with discharges in January through October, of which 32.5% were cesarean deliveries. There were 2905 deliveries complicated by sepsis (0.038%; 95% CI, 0.037%-0.040%); 49.8% (95% CI, 47.7%-52.0%) were complicated during delivery hospitalization and 50.3% (95% CI, 48.1%-52.4%) after delivery discharge. Sepsis readmissions occurred a mean of 13.6 (SD, 11.2) days after discharge from delivery hospitalization.
Maternal sepsis episodes after delivery discharge, compared with during delivery hospitalization, occurred in women with fewer comorbidities (mean, 1.9 vs 2.6; difference, −0.7 [95% CI, −0.8 to −0.5]; P < .001), were less frequently associated with cesarean deliveries (49.6% vs 63.7%; difference, −15.7% [95% CI, −19.2% to −12.1%]; P < .001), had a higher percentage of acute kidney dysfunction (35.2% vs 23.9%; difference, 10.6% [95% CI, 7.3%-13.9%]; P < .001), and had a lower percentage of genitourinary infection (39.8% vs 49.2%; difference, −7.5% [95% CI, −11.1% to −3.9%]; P < .001) (Table 1).
Table 1. Characteristics of Maternal Sepsis Episodes Occurring During vs After Index Delivery Hospitalization.
| Patient and Hospitalization Characteristics | Maternal Sepsis Episodes | P Valuea | |||||
|---|---|---|---|---|---|---|---|
| Total | During Delivery Hospitalization | After Delivery Discharge | |||||
| National Readmissions Data (n = 2905) | Weighted Estimates, % (95% CI) | National Readmissions Data (n = 1463) | Weighted Estimates, % (95% CI) | National Readmissions Data (n = 1442) | Weighted Estimates, % (95% CI) | ||
| Age, mean (SD), y | 28.6 (6.4) | 28.4 (6.6) | 28.8 (6.5) | 28.6 (6.8) | 28.4 (6.4) | 28.1 (6.4) | .09 |
| Bateman Comorbidity Index, mean (SD)b | 2.3 (2.3) | 2.3 (2.4) | 2.6 (2.4) | 2.6 (2.4) | 1.9 (2.2) | 1.9 (2.2) | <.001 |
| Obesity, No. | 445 | 15.9 (14.4-17.5) | 208 | 14.0 (12.2-16.1) | 237 | 17.9 (15.7-20.3) | .01 |
| Chronic kidney disease, No. | 371 | 12.0 (10.8-13.4) | 182 | 12.3 (10.6-14.2) | 189 | 11.7 (10.1-13.7) | .71 |
| Asthma, No. | 297 | 10.2 (9.0-11.6) | 141 | 9.6 (8.0-11.5) | 156 | 10.9 (9.3-12.9) | .35 |
| Chronic hypertension, No. | 294 | 10.5 (9.3-11.8) | 111 | 7.6 (6.2-9.3) | 183 | 13.3 (11.4-15.3) | <.001 |
| Tobacco use, No. | 271 | 10.3 (9.1-11.7) | 126 | 9.3 (7.7-11.1) | 145 | 11.3 (9.6-13.4) | .11 |
| Severe preeclampsia, No. | 202 | 7.1 (6.1-8.2) | 176 | 12.5 (10.7-14.5) | 26 | 1.9 (1.3-2.9) | <.001 |
| Drug abuse, No. | 197 | 6.8 (5.8-8.0) | 96 | 6.3 (5.1-7.8) | 101 | 7.3 (5.8-9.2) | .38 |
| Acute organ dysfunctions, mean (SD)c | 1.2 (1.0) | 1.3 (0.99) | 1.3 (1.0) | 1.3 (1.0) | 1.2 (1.0) | 1.2 (0.99) | .20 |
| Cardiovascular, No. | 1121 | 38.3 (36.4-40.4) | 570 | 38.3 (35.6-41.2) | 551 | 38.3 (35.6-41.1) | .98 |
| Kidney, No. | 848 | 29.6 (27.6-31.7) | 350 | 23.9 (21.5-26.5) | 498 | 35.2 (32.4-38.0) | <.001 |
| Pulmonary, No. | 734 | 26.0 (24.2-28.0) | 398 | 27.5 (25.0-30.1) | 336 | 24.6 (22.1-27.3) | .10 |
| Hematologic, No. | 725 | 25.3 (23.5-27.1) | 456 | 31.8 (29.1-34.6) | 269 | 18.7 (16.5-21.2) | <.001 |
| Neurologic, No. | 103 | 3.5 (2.8-4.3) | 62 | 4.3 (3.3-5.6) | 41 | 2.7 (2.0-3.7) | .03 |
| Hepatic, No. | 83 | 2.9 (2.3-3.8) | 34 | 2.3 (1.6-3.2) | 49 | 3.6 (2.6-4.9) | .04 |
| Site of infection, No. | |||||||
| Genitourinary | 1316 | 44.5 (42.4-46.6) | 717 | 49.2 (46.2-52.3) | 599 | 39.8 (37.1-42.6) | <.001 |
| Respiratory | 450 | 16.0 (14.6-17.6) | 236 | 16.4 (14.3-18.7) | 214 | 15.8 (13.8-18.0) | .61 |
| Gastrointestinal | 266 | 9.6 (8.4-11.0) | 42 | 2.8 (2.1-3.9) | 224 | 16.3 (14.2-18.7) | <.001 |
| Skin/soft tissue | 206 | 7.0 (6.1-8.1) | 79 | 5.0 (4.0-6.3) | 127 | 8.9 (7.4-10.7) | <.001 |
| Otherd | 62 | 2.3 (1.8-3.0) | 29 | 2.0 (1.4-3.0) | 33 | 2.5 (1.8-3.7) | .34 |
| Unknown | 605 | 20.6 (19.0-22.3) | 360 | 24.5 (22.0-27.1) | 245 | 16.7 (14.8-18.7) | <.001 |
| Method of delivery, No.e | |||||||
| Cesarean | 1643 | 56.7 (54.6-58.8) | 940 | 63.7 (60.9-66.5) | 703 | 49.6 (46.7-52.6) | <.001 |
| Vaginal | 1232 | 42.2 (40.1-44.3) | 502 | 34.5 (31.8-37.3) | 730 | 49.7 (46.8-52.7) | <.001 |
| Mortality | 95 | 3.2 (2.6-4.0) | 52 | 3.7 (2.6-4.8) | 43 | 2.8 (2.1-3.8) | .18 |
P values calculated using the F statistic comparing maternal sepsis episodes during delivery hospitalization vs after delivery hospitalization.
Bateman Comorbidity Index5 (range, 0-46) is a maternal comorbidity index for predicting severe maternal morbidity (ie, severe organ injury or death) used in prior studies of maternal sepsis.2 The weighted index includes the following comorbidities: alcohol abuse, asthma, cardiac valvular disease, congestive heart failure, ischemic heart disease, chronic kidney disease, congenital heart disease, cystic fibrosis, drug abuse, gestational hypertension, gestational diabetes, HIV, mild preeclampsia, multiple gestation, obesity, placenta previa, previous cesarean delivery, preexisting diabetes, preexisting hypertension, pulmonary hypertension, severe preeclampsia, sickle cell disease, systemic lupus erythematosus, and tobacco use.
Acute organ dysfunction score (range, 0-6) is the sum of 6 acute organ dysfunctions, based on the methods of Dombrovskiy et al,4 which has been used in previous studies of maternal sepsis.2 Percentages of individual organ dysfunctions total more than 100% because patients may have more than 1 acute organ dysfunction.
Other site of infection includes bacteremia, osteomyelitis, infective arthritis, meningitis, encephalitis, central nervous system infections not otherwise specified, endocarditis, and septic thrombophlebitis, which occurred in ≤11 patients.
Thirty deliveries (1%) did not have an identifiable delivery type, so percentages total less than 100%.
There were 408 delivery hospitalizations (0.007%; 95% CI, 0.006%-0.007%) that were followed by maternal death; 74.4% (95% CI, 69.6%-78.6%) during delivery hospitalization and 25.6% (95% CI, 21.4%-30.4%) after delivery discharge (Table 2). Overall, 95 (22.6%; 95% CI, 18.7%-27.1%) of the maternal deaths were sepsis-related; 17.3% (95% CI, 13.2%-22.4%) occurred during delivery hospitalization and 38.1% (95% CI, 29.0%-48.1%) occurred after delivery discharge.
Table 2. Nationwide Estimates of Maternal Sepsis Incidence, Maternal Deaths, and Sepsis-Related Maternal Deaths.
| Outcome | No. in National Readmissions Database (2013-2016) | Weighted Incidence per 100 000 Deliveries in the United States (95% CI) | Weighted Percentage of Delivery Hospitalizations With the Outcome (95% CI) |
|---|---|---|---|
| Maternal Sepsis Episodes | |||
| Total | 2905 | 38.3 (36.6-40.2) | 0.038 (0.037-0.040) |
| During delivery hospitalization | 1463 | 19.0 (17.8-20.4) | 0.019 (0.018-0.020) |
| After delivery discharge | 1442 | 19.3 (18.2-20.4) | 0.019 (0.018-0.020) |
| Maternal Deaths | |||
| Total | 408 | 6.6 (5.9-7.4) | 0.007 (0.006-0.007) |
| During delivery hospitalization | 300 | 4.9 (4.4-5.6) | 0.005 (0.004-0.006) |
| After delivery discharge | 108 | 1.7 (1.4-2.1) | 0.002 (0.001-0.002) |
| Sepsis-Related Maternal Deaths | |||
| Total | 95 | 1.5 (1.2-1.9) | 0.002 (0.001-0.002) |
| During delivery hospitalization | 52 | 0.8 (0.6-1.1) | 0.001 (0.001-0.001) |
| After delivery discharge | 43 | 0.7 (0.5-0.9) | 0.001 (0.001-0.001) |
Discussion
Maternal sepsis occurred in 0.04% of deliveries in the United States, and 23% of all maternal deaths were sepsis-related. Substantial percentages of both outcomes occurred after discharge from delivery hospitalization. Study limitations include lack of data on home births and out-of-hospital deaths. The findings highlight the importance of sepsis in maternal mortality, particularly after discharge, and the need for awareness of this condition.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
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