Objective
Chorioamnionitis can cause severe complications for the infant; therefore, characterization of the risk of recurrence and identification of the factors that modify it are clinically relevant to pregnant women and their providers.
Study Design
The risk of recurrence was examined in a retrospective population-based cohort study with the use of birth certificate and delivery hospitalization discharge data from Washington State for the years 1989–2008.
Results
Women who had chorioamnionitis in their first deliveries were 3.43 times as likely to have chorioamnionitis in their second deliveries as were women who did not have chorioamnionitis in their first deliveries (95% confidence interval [CI], 2.67–4.42; P < .001). Smoking status modified this association (smokers: odds ratio, 1.38 [95% CI, 0.62–3.08]; nonsmokers: odds ratio, 3.80 [95% CI, 2.88–5.00]).
Conclusion
These data provide strong evidence for the occurrence of repeat chorioamnionitis; the association is strongest in women who do not smoke during pregnancy.
Chorioamnionitis or intraamniotic infection is an inflammation of the amniotic fluid, membranes, placenta, and/or decidua. Diagnosis can be made histologically but is generally diagnosed clinically based on the finding of fever (>100.4°F) plus 2 of the following occurrences: uterine tenderness, maternal or fetal tachycardia, elevated maternal leukocytosis (>15,000 cells/mm 3 ), or foul odor of the amniotic fluid. Chorioamnionitis usually results from ascending polymicrobial infection from the lower genital tract into the amniotic cavity with subsequent invasion of the fetus ; however, transmission is also possible after invasive procedures by retrograde seeding from the peritoneal cavity or by hematogenous spread. Although usually acute, chronic cases have been documented and associated with preterm birth. Factors that are associated with chorioamnionitis include prolonged rupture of membranes (ROM), prolonged labor, multiple digital examinations with ROM, nulliparity, group B streptococcus colonization, bacterial vaginosis, alcohol or tobacco use, meconium-stained amniotic fluid, internal monitoring, and epidural anesthesia.
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With the use of antibiotics, severe maternal complications are rare in the United States; however, maternal bacteremia may occur in up to 10% of cases, with other potential complications that include increased risk of postpartum hemorrhage, cesarean delivery, and associated surgical complications. In contrast, the infant faces increased risk for more severe complications that include cerebral palsy, neonatal sepsis, and pneumonia. In term infants, intraamniotic infection increases the incidence of cerebral palsy from 3 per 1000 to 8 per 1000 live births. In preterm premature rupture of membranes (PROM), chorioamnionitis increases the neonatal morbidity rate from 18-55%. In light of these complications, mothers who previously have had clinical chorioamnionitis with a poor birth outcome may express hesitation about future pregnancies. Further, preventive methods are available for high-risk women; thus, characterization of the risk of recurrent chorioamnionitis and identification of factors that modify this risk are of interest.
To date, 2 hospital-based studies have shown evidence for an increased risk of repeat clinical chorioamnionitis. The purpose of this study was to use a population-based data set to compare the risk of clinical chorioamnionitis in the second delivery among women whose first deliveries were complicated by clinical chorioamnionitis, relative to that of women whose first deliveries were not complicated by clinical chorioamnionitis. Additionally, because decreased host resistance has been associated with chorioamnionitis, we assessed whether smoking, which is a controllable cause of decreased host resistance, modified the risk of recurrence. Furthermore, because preterm PROM is associated strongly with chorioamnionitis, we sought to assess whether it modified the risk.
Materials and Methods
We conducted a retrospective population-based cohort study using maternally linked longitudinal birth certificate data from Washington State that were linked to maternal hospital discharge data from the Birth Events Records Database. We selected “exposed” and “comparison” women from among 306,769 women who had a first pregnancy from 1989–2008 and at least 2 consecutive live singleton births. Previous studies have shown a higher incidence of chorioamnionitis in the first pregnancy, compared with the second pregnancy, so we restricted our search to women who were nulliparous at first recorded birth. The exposed cohort consisted of women whose first birth resulted in clinical chorioamnionitis. For completeness, clinical chorioamnionitis was defined by maternal and infant International Classification of Diseases (ICD-9) codes (658.40, 658.41, 658.43 and 762.7). However, all but 3 women were coded with the ICD-9 code 658.41. From here on, the phrase chorioamnionitis will refer to this clinical diagnosis of intraamniotic infection or chorioamnionitis.
The comparison group was a subset of women who did not have chorioamnionitis in their first deliveries. Based on power calculations, we selected 4 comparison women for each exposed woman. Because of changes in the birth certificate data over time and potential temporal trends, we frequency matched on birth year but otherwise randomly selected from women with ≥2 live singleton births who did not have chorioamnionitis in their first deliveries. In both groups, we further excluded women who were reported to be either nulliparous (711 women) or multiparous (2305 women) for their second birth on record (total, 3016/34,530 women) because these indicate data-recording errors or women who had intervening births outside of Washington State. Our final sample size was 6219 exposed women and 25,294 unexposed women (N = 31,514).
The odds ratio (OR) for chorioamnionitis in the second delivery was estimated with logistic regression. Because factors from the second pregnancy are related more directly to the outcome, we present descriptive information on variables from the second pregnancy. Potential confounders included maternal and paternal age (years), maternal and paternal ethnicity (white, black, Native American, Asian, Hispanic, Pacific Islander), marital status (married, not married), maternal years of education, Medicaid enrollment, infant’s sex, interpregnancy interval (months), chronic or gestational diabetes mellitus, chronic hypertension, gestational age (weeks), prolonged labor ≥20 hours, medium or heavy meconium-stained amniotic fluid, internal monitoring during labor (based on ICD-9 codes 74.32, 75.34, 75.35; yes, no), genital herpes (no, active, established), and syphilis. Observations with missing data were dropped from the multivariable analyses. Only maternal education, paternal age, and paternal ethnicity had >10% missing in either type of pregnancy; none of these characteristics were included in our final models.
We decided a priori to include maternal age, maternal ethnicity, PROM, and internal monitoring as confounders. We assessed other variables from both pregnancies and year of birth as potential confounders, with a confounder defined as altering the OR by ≥10%. Because black race and decreased host resistance are risk factors for chorioamnionitis, we also conducted a sensitivity analysis of women who self-reported as white without chronic hypertension or diabetes mellitus.
We evaluated smoking during pregnancy (self-reported on the birth certificate, any or none) and PROM (categorized as no PROM, PROM at term [≥37 weeks’ gestation], and preterm PROM [<37 weeks’ gestation]; based on ICD-9 codes 658.1, 658.10, 658.11, 658.13, and 761.1 and gestational age from birth certificate) as potential effect modifiers by including an interaction term in the regression model. For significant interactions, we performed stratified analysis, calculating stratum-specific ORs directly from the regression model.
All probability values were 2-sided, and the significance level was set at .05. Statistical analysis was performed with STATA software (release 11; StataCorp, College Station, TX).
The institutional review board of the University of Washington approved this study.
Results
Demographic, medical, and obstetric characteristics of the cohort at time of first and second pregnancies are given in Table 1 . The characteristics of exposed and unexposed women were generally similar. We observed 131 cases of chorioamnionitis in the second delivery among women with chorioamnionitis in their first deliveries (2.11%) and 139 cases of chorioamnionitis in the second delivery among women without chorioamnionitis in their first deliveries (0.59%; unadjusted OR, 3.60; 95% confidence interval [CI], 2.84–4.57). Adjustment for the a priori factors of maternal age, maternal ethnicity, PROM, internal monitoring, and year of birth to address the possibility of a temporal trend or other variables ( Table 1 ) did not substantially alter the risk estimate, so the final model included only our a priori factors (adjusted OR, 3.43; 95% CI, 2.67–4.42).
| Characteristic | First pregnancy b | Second pregnancy b | ||
|---|---|---|---|---|
| Chorioamnionitis (n = 6220) | No chorioamnionitis (n = 25,294) | Chorioamnionitis (n = 270) | No chorioamnionitis (n = 31,234) | |
| Mean maternal age, y c , d | 25.4 ± 5.7 | 24.6 ± 5.6 | 28.1 ± 5.9 | 28.0 ± 5.7 |
| Maternal ethnicity, n (%) | ||||
| White | 4360 (70.1) | 19,633 (77.6) | 201 (72.0) | 24,100 (77.2) |
| Black | 313 (5.0) | 708 (2.8) | 17 (6.1) | 1039 (3.3) |
| Native American | 159 (2.6) | 601 (2.4) | 9 (3.2) | 739 (2.4) |
| Asian | 663 (10.7) | 1622 (6.4) | 33 (11.8) | 2249 (7.2) |
| Hispanic | 556 (8.9) | 2122 (8.4) | 15 (5.4) | 2322 (7.4) |
| Pacific Islander | 31 (0.5) | 88 (0.4) | 0 | 126 (0.4) |
| Mean maternal education, y c , e | 13.3 ± 2.7 | 13.3 ± 2.7 | 13.2 ± 2.6 | 13.5 ± 2.7 |
| Mean paternal age, y c , f | 28.4 ± 6.3 | 27.7 ± 6.1 | 31.7 ± 6.9 | 30.8 ± 6.2 |
| Paternal ethnicity, n (%) | ||||
| White | 3938 (66.3) | 17,328 (68.5) | 179 (65.2) | 22,057 (70.6) |
| Black | 329 (5.3) | 810 (3.2) | 23 (8.2) | 1237 (4.0) |
| Native American | 120 (1.9) | 426 (1.7) | 4 (1.4) | 511 (1.6) |
| Asian | 456 (7.3) | 1343 (5.3) | 23 (8.2) | 1844 (5.9) |
| Hispanic | 502 (8.1) | 2143 (8.5) | 15 (5.4) | 2489 (8.0) |
| Pacific Islander | 24 (0.4) | 95 (0.4) | 0 | 135 (0.4) |
| Married, n (%) | 4136 (66.5) | 16,898 (66.8) | 193 (69.2) | 24,105 (77.2) |
| Infant’s sex, n (%) | ||||
| Female | 2818 (45.3) | 12,401 (49.0) | 126 (45.2) | 15,390 (49.3) |
| Male | 3402 (54.7) | 12,893 (51.0) | 153 (54.8) | 15,845 (50.7) |
| Smoker, n (%) | 633 (10.2) | 2776 (11.0) | 39 (14.0) | 3470 (11.1) |
| Medicaid, n (%) | 2413 (38.8) | 9489 (37.5) | 100 (35.8) | 10,332 (33.1) |
| Chronic hypertension, n (%) | 65 (1.0) | 214 (0.9) | 1 (0.36) | 331 (1.1) |
| Diabetes mellitus, n (%) g | 189 (3.0) | 695 (2.8) | 5 (1.8) | 1238 (4.0) |
| Mean gestational age, wk c , h | 38.6 ± 3.4 | 39.2 ± 1.8 | 36.8 ± 4.6 | 39.0 ± 1.6 |
| Premature rupture of membranes, n (%) | ||||
| None | 4638 (74.6) | 21,675 (85.7) | 214 (76.7) | 28,322 (90.7) |
| Term | 794 (12.8) | 1591 (6.3) | 16 (5.7) | 929 (3.0) |
| Preterm | 351 (5.6) | 397 (1.6) | 29 (10.4) | 345 (1.1) |
| Prolonged labor: >20 hr, n (%) | 462 (7.4) | 641 (2.5) | 14 (5.0) | 189 (0.6) |
| Meconium staining, n (%) i | 815 (13.1) | 1,575 (6.2) | 17 (6.1) | 1225 (3.9) |
| Internal monitoring, n (%) | 968 (15.6) | 3383 (13.4) | 36 (12.9) | 2902 (9.3) |
| Herpes, n (%) | ||||
| No | 5559 (89.4) | 22,977 (90.8) | 246 (89.3) | 23,323 (92.2) |
| Active | 13 (0.2) | 102 (0.4) | 0 | 71 (0.2) |
| Established | 138 (2.2) | 554 (2.2) | 8 (2.9) | 820 (2.6) |
| Syphilis, n (%) | 2 (0.03) | 7 (0.03) | 0 | 8 (0.03) |
a Because this is a descriptive summary, we did not include probability values;
b Percentages include missing data;
c Data are given as mean ± SD;
d 6/31,514 records were missing maternal age at first pregnancy; 9/31,514 records were missing maternal age at second pregnancy;
e 6,295/31,514 records were missing maternal education at first pregnancy; 2077/31,514 records were missing maternal education at second pregnancy;
f 3,465/31,514 records were missing paternal age at first pregnancy; 2,381/31,514 records were missing paternal age at second pregnancy;
h 589/31,514 records were missing gestational age at first delivery; 386/31,514 records were missing gestational age at second delivery;
Smoking status modified the risk of recurrence ( P interaction = .02; Table 2 ), with the adjusted risk of recurrence being higher in nonsmokers than smokers ( Table 3 ). We did not observe statistical evidence for the risk of recurrence being modified by PROM ( P interaction = .41).
| Variable | Model A a , b | Model B a , c | ||||
|---|---|---|---|---|---|---|
| Odds ratio | 95% CI | P value | Odds ratio | 95% CI | P value | |
| Chorioamnionitis | 3.43 | 2.67–4.42 | < .001 | 3.80 | 2.88–5.00 | < .001 |
| Maternal age | 1.00 | 0.98–1.02 | .956 | 1.00 | 0.98–1.03 | .793 |
| Maternal ethnicity | 1.01 | 0.92–1.11 | .844 | 1.01 | 0.92–1.11 | .850 |
| White | Reference | Reference | ||||
| Black | 1.52 | 0.88–2.61 | .133 | 1.39 | 0.78–2.47 | .267 |
| Native American | 1.40 | 0.71–2.79 | .333 | 1.12 | 0.52–2.42 | .771 |
| Asian | 1.59 | 1.08–2.32 | .018 | 1.57 | 1.07–2.32 | .023 |
| Hispanic | 0.62 | 0.34–1.12 | .116 | 0.65 | 0.36–1.19 | .163 |
| Pacific Islander | — | — | — | — | — | — |
| Premature rupture of membranes | 2.92 | 2.39–3.58 | < .001 | 2.83 | 2.30–3.50 | < .001 |
| Internal monitoring | 1.56 | 1.08–2.25 | .018 | 1.59 | 1.10–2.32 | .015 |
| Maternal smoking status | — | — | — | 1.74 | 1.12–2.72 | .015 |
| Chorioamnionitis × smoker d | — | — | — | 0.36 | 0.16–0.85 | .019 |
a Adjusted for maternal age (y), ethnicity (white, black, Native American, Asian, Hispanic, Pacific Islander), premature rupture of membranes (none, term, preterm), and internal monitoring (yes, no);
d The coefficient for this interaction term should not be considered an odds ratio.
| Smoked in second pregnancy a | Total, n | Second deliveries complicated by chorioamnionitis, n | Odds ratio b | 95% CI | P value |
|---|---|---|---|---|---|
| Yes | 3509 | 40 | 1.38 | 0.62–3.08 | .428 |
| No | 27,388 | 229 | 3.80 | 2.88–5.00 | < .001 |
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