Background
The American College of Obstetricians and Gynecologists currently recommends that antibiotic treatment should be considered for women with isolated maternal fevers during labor. However, there is little known about the maternal and neonatal impact of antibiotic treatment in this scenario.
Objective
We sought to assess the outcomes in women with a nonsustained, isolated maternal fever treated with antibiotics and compare it with expectant management.
Study Design
This was a retrospective cohort study of laboring women with a singleton gestation at term and a single temperature of between 38.0°C and 38.9°C without other evidence of infection (leukocytosis >15,000/mm 3 , fetal tachycardia, malodorous amniotic fluid, suspected alternate source of infection) at a tertiary teaching hospital. A contemporaneously maintained, validated obstetrical database was used to identify women for our cohort. Women with rheumatologic or renal disease, nongestational diabetes, preterm labor, placental abruption, vaginal bleeding, HIV, malpresentation, and fetal anomalies were excluded. The primary outcome was a postpartum fever above 38.0°C. Secondary maternal outcomes were treatment for postpartum endometritis, uterine atony, postpartum hemorrhage, admission to the intensive care unit, and postpartum length of stay. Secondary neonatal outcomes were neonatal intensive care unit admission, 5-minute Apgar score of <7, 5-minute Apgar score of <4, neonatal intensive care unit length of stay, and neonatal antibiotic administration. The results were compared using univariable and multivariable analyses.
Results
From January 1, 2015, to December 31, 2018, 359 women were identified; 85 received antibiotics and 274 did not. The baseline characteristics were similar between the groups, except for gestational age at the time of delivery (39.2 weeks vs 39.5 weeks for the antibiotic and no antibiotic groups, respectively; P =.02). The incidence in postpartum fever showed a downward trend in the antibiotic group (10.59% for the antibiotic group vs 18.98% for the no antibiotic group; P =.07). Significantly fewer women in the antibiotic group were treated for postpartum endometritis (3.53% vs 11.31%; P =.03). Neonatal intensive care unit admission and neonatal antibiotic administration rates were higher in the antibiotic group (41.18% vs 17.88%; P <.001 and 36.47% vs 12.41%; P <.001, respectively). The incidence of 5-minute Apgar score of <7 was higher in the antibiotic group (8.25% vs 2.19%; P =.016). After controlling for age, gestational age, body mass index, group B streptococci status, delivery method, parity, administration of epidural, and receipt of acetaminophen, the odds for postpartum fever were reduced by a factor of 0.42 (95% confidence interval, 0.18–0.99) among women who received antibiotics when compared with those who did not receive antibiotics. Outcome results are presented in Table 2 .
Conclusion
Although there was a lower rate of treatment for endometritis among women who received antibiotics for a single isolated maternal fever, there was a higher rate of neonatal intensive care unit admissions and 5-minute Apgar score of <7. This indicates that there likely is maternal benefit associated with antibiotic use, however, there are concerns about the neonatal risk.
Introduction
Intraamniotic infection and inflammation is associated with substantial maternal and neonatal morbidity. In 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the Society for Maternal-Fetal Medicine (SMFM), the American Academy of Pediatrics (AAP), and the American College of Obstetricians and Gynecologists (ACOG) convened a joint workshop to discuss the definitions of and approaches to the disease spectrum of intrauterine inflammation and infection. Isolated maternal fever was defined as a temperature of ≥39°C in the absence of additional signs of infection or a persistent temperature of between 38.0°C and 38.9°C for >30 minutes. Subsequently, ACOG Committee Opinion (#712) described isolated maternal fever as “any maternal temperature between 38.0°C and 38.9°C with no additional risk factors present, and with or without persistent temperature elevation.”
We sought to determine the impact of prescribing antibiotic treatment for mothers with an isolated maternal fever with no other evidence of intraamniotic infection on the maternal and neonatal outcomes in a large tertiary care institution.
Why was this study conducted?
Intraamniotic infections are substantial causes of maternal and neonatal morbidity. Current guidelines, based on expert opinion, recommend consideration of antibiotic treatment for nonsustained, isolated maternal fever during labor. This may lead to overtreatment or improved outcomes. We sought to investigate the maternal and neonatal effects associated with antibiotic administration for isolated maternal fever without other evidence of intraamniotic infection.
Key findings
There was a significant decrease in postpartum endometritis among women treated with intrapartum antibiotics for isolated fever. We also observed a downward trend in the incidence of postpartum fever among women treated with antibiotics. In addition, a higher rate of neonatal intensive care unit admissions, administration of neonatal antibiotics, and 5-minute Apgar score of <7 among neonates of mothers treated with antibiotics were also observed.
What does this add to what is known?
This study provides evidence for improved maternal outcomes associated with antibiotic treatment of nonsustained, isolated maternal fever in labor.
Materials and Methods
This was a retrospective cohort study conducted at a large tertiary care teaching hospital. Before initiation of the study, approval was obtained from the ChristianaCare Institutional Review Board (CCC#39096). Using vital signs recorded during these admissions, we identified all laboring women with a nonsustained (<30 minutes) elevated temperature between 38.0°C and 38.9°C before delivery between January 1, 2015, and December 31, 2018. All patients were afebrile with temperatures <38.0°C upon admission and before presenting the fever of interest. This time frame was selected because of the timing of the release of ACOG Committee Opinion #712 in 2017 and the subsequent implementation of that policy at our hospital. Hospital protocol at this time included recording of an additional temperature 30 minutes after the first by a nurse. Providers were also strongly encouraged to order a complete blood count and to administer acetaminophen at the time of the first temperature elevation. The decision to treat women with antibiotics was made by the provider.
We excluded women with additional signs or documented symptoms of intraamniotic infection (specifically maternal leukocytosis, defined as a white blood cell count >15,000/mm 3 , fetal tachycardia, fundal tenderness, or malodorous amniotic fluid). Women with a documented suspicion of an infection excluding intraamniotic infection (including the documentation of diagnosis codes or diagnoses acknowledged in provider notes such as pyelonephritis, cellulitis, or pneumonia), diagnosis of intrauterine fetal demise before fever, preterm labor or delivery (<37 weeks’ gestation), multiple gestation, known fetal anomalies, malpresentation, maternal rheumatologic or renal disease, maternal Müllerian anomalies, known pregestational diabetes, documented vaginal bleeding or concern for abruption, or HIV were also excluded. Women who were known group B streptococci (GBS) carriers and who were treated with intravenous penicillin during labor were not excluded from the study, however, a positive GBS carrier status was noted. The exclusion criteria were initially identified via the International Classification of Diseases, Ninth and Tenth Revision (ICD-9 and ICD-10) diagnosis codes and confirmed via chart review by 2 obstetricians (T.C.B. and E.N.). Through chart review, it was determined whether the women included received antibiotic treatment for a suspected intraamniotic infection before delivery.
The primary outcome was postpartum fever, defined as a maternal temperature of ≥38.0°C between delivery and discharge from the hospital. This outcome was selected owing to the clinical relevance, because all such fevers require provider notification, evaluation, and clinical investigation. Secondary maternal outcomes were treatment for postpartum endometritis (defined as a clinical diagnosis of endometritis and receipt of intravenous antibiotics), uterine atony as determined by ICD-9 or ICD-10 codes, postpartum hemorrhage (defined as an estimated blood loss ≥1000 mL), admission to the intensive care unit (ICU), and postpartum length of stay. Secondary neonatal outcomes were neonatal ICU (NICU) admission, 5-minute Apgar score of <7, 5-minute Apgar score of <4, NICU length of stay, and neonatal antibiotic administration.
Univariable analyses were conducted using Student’s t tests or chi-square tests unless nonparametric testing was indicated. The statistical significance was set at a 2-tailed P value of <.05. A multivariable logistic regression model was fitted to estimate the adjusted effect of antibiotic treatment on postpartum fever. The other covariates in the multivariable model were maternal age, gestational age, body mass index (BMI), GBS status, delivery method, parity, epidural administration, and whether the woman received acetaminophen. These covariates were selected a priori and retained in the model irrespective of their statistical significance in the final model. A similar multivariable logistic regression model was fitted to estimate the effect of antibiotic treatment on the rate of treatment of endometritis. All analyses were conducted using SAS 9.4 (SAS Institute Inc, Cary, NC).
Results
There were 24,640 deliveries that occurred at our institution between January 1, 2015, and December 31, 2018. Of these, 1226 (5.0%) were complicated by an antepartum fever that reached a maximum of between 38.0°C and 38.9°C. Following chart review and application of the remainder of the exclusion criteria, 359 women were included in the final sample. The most common reason for exclusion was documented fetal tachycardia as defined by the NICHD at the time of fever presentation. White blood cell counts were absent for 4 women; these women were included. Very few providers reported a fundal examination or described the quality of the amniotic fluid at the time of fever; these were considered to be normal in the absence of a comment. Of the women included in the final cohort, 85 received antibiotic treatment (ABX) and 274 did not (NO-ABX) ( Figure ).
The baseline characteristics and demographics are presented in Table 1 . With the exception of gestational age, there were no significant differences in the demographic characteristics between the 2 groups. A difference in gestational age was noted between the 2 groups (39.2 weeks ABX vs 39.5 weeks NO-ABX; P =.02), however, given that both values were between 39 and 40 weeks, the clinical significance of this difference is unclear.
| Description | All (N=359) | No antibiotics group (n=274) | Antibiotics group (n=85) | P value |
|---|---|---|---|---|
| Age (y) a | 28.8 (5.33) | 28.9 (5.31) | 28.3 (5.43) | .36 |
| Gestational age (wk) a | 39.5 (1.19) | 39.5 (1.12) | 39.2 (1.33) | .022 |
| Parity | .43 | |||
| Multiparous | 83 (23.12) | 66 (24.09) | 17 (20.00) | |
| BMI | 32.4 (6.55) | 32.1 (6.33) | 33.19 (7.16) | .63 |
| Race | .87 | |||
| Asian | 44 (12.26) | 34 (12.41) | 10 (11.76) | |
| Black or African American | 77 (21.45) | 60 (21.90) | 17 (20.00) | |
| Other | 38 (10.03) | 27 (9.58) | 11 (12.94) | |
| White | 200 (55.71) | 153 (55.84) | 47 (55.29) | |
| GBS status | .66 | |||
| Negative | 265 (73.82) | 202 (73.72) | 63 (74.12) | |
| Positive | 85 (23.68) | 64 (23.36) | 21 (24.71) | |
| Unknown | 9 (2.51) | 8 (2.92) | 1 (1.18) | |
| Mode of delivery | .54 | |||
| Vaginal delivery | 283 (78.83) | 214 (78.10) | 69 (81.18) | |
| Cesarean delivery | 76 (21.17) | 60 (21.90) | 16 (18.82) | |
| Epidural before fever presentation | 341 (94.99) | 258 (94.16) | 83 (97.65) | .26 |
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