Intrapartum Fever: Antibiotics Versus no Treatment

Study Overview
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Brief Summary
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The purpose of this study is to determine whether antibiotics can be safely avoided in women who develop a fever during labor. Because investigators have no accurate tests to determine whether women who develop fever during labor have intra-amniotic infection, antibiotics are often used to prevent spread of infection to the fetus.

Detailed Description
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A fever > 100.4 F during labor (intrapartum fever) complicates up to 14% of term deliveries, and is commonly considered a sign of intrauterine infection. Despite studies showing that most causes of maternal intrapartum fever are non-infectious, intrapartum fever often prompts the diagnosis of chorioamnionitis/intrauterine infection, or what is now known as 'triple I' (intra-amniotic infection or inflammation). Diagnosis of triple I is primarily based on clinical findings such as maternal fever, maternal leukocytosis, uterine tenderness, foul-smelling or purulent amniotic fluid, and fetal tachycardia. A minimum of two of these criteria for diagnosis, although this distinction is somewhat artificial as fetal tachycardia is highly associated with maternal fever. The poor performance of clinical signs and lack of effective biomarkers to identify neonatal infection results in over treatment of both mothers and infants. Avoiding antibiotic use in mothers and infants is desirable in order to avoid unnecessary separation after birth, decreasing cost and interventions in newborns, and to avoid altering the infant's microbiome (the bacteria newborns carry on their skin, mucosal membranes, and in their gut at the time of birth). Infants with altered microbiomes may be at risk for skin, pulmonary, and gastrointestinal disorders. The investigators in this trial are randomizing women with fever during labor who are felt to be a low risk for true infection to antibiotic treatment compared to no antibiotics in order to determine if antibiotics can be safely avoided for these women and their infants.

Official Title
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A Randomized Trial in Intrapartum Fever Of No Antibiotics for Low-risk Women (RATIONAL)

Conditions
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Chorioamnionitis, Intrapartum Fever, Intra-amniotic Infection

Intervention / Treatment
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* Drug: Standard Antibiotic Treatment
* Other: No Antibiotic Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women between 34-42 weeks gestation Singleton fetus Admitted for labor management & develops a fever of 100.4 F or greater Exclusion Criteria: Known fetal anomaly Other indication for intrapartum antibiotics (endocarditis prophylaxis, other known maternal infection)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Low risk women will be randomized to standard antibiotic treatment versus no antiobiotics.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Antibiotic Treatment<br>Standard antibiotic treatment provided to patient. Placenta submitted for pathologic exam. Maternal and neonatal outcomes collected. | Drug: Standard Antibiotic Treatment<br>* Participants randomized to this intervention will receive standard antibiotic treatment. The placenta will be submitted for pathologic exam after delivery and investigators will collect maternal and neonatal outcomes<br>|
| Experimental: No Antibiotic Treatment<br>No Antibiotic treatment given. Placenta submitted for pathologic exam. Maternal and neonatal outcomes collected. | Other: No Antibiotic Treatment<br>* Participant randomized to this arm of the study will not receive antibiotics. The placenta will be submitted for pathologic exam after delivery and investigators will collect maternal and neonatal outcomes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal antibiotic treatment as recommended by the EONS (Early Onset Neonatal Sepsis) calculator. | All newborns will have a screening assessment including physical exam and vital signs, and this data along with maternal and delivery data is entered into the Kaiser Permanente Early Onset Neonatal Sepsis (EONS) calculator. The EONS calculator estimates the risk of sepsis and recommends observation, additional evaluation, or empiric antibiotic treatment. | Within 2 hours of delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive blood culture | For infants who have a blood culture obtained by recommendation of the EONS calculator, the presence of significant bacterial growth will be considered a positive culture. | Up to 4 days after birth | 
| Need for NICU admission | Admission of the infant to the Newborn Intensive Care Unit | Up to 4 weeks after birth | 
| Newborn length of stay | Days hospitalized after birth | Up to 4 weeks after birth | 
| Maternal endometritis | The diagnosis of endometritis made by the patient's OB provider requiring treatment with antibiotics. | Up to 4 weeks after birth | 
| Maternal length of stay | Days hospitalized after delivery | Up to 4 weeks after birth | 
| Patient satisfaction | Satisfaction with maternal and newborn care using a standardized survey administered by phone at 6-8 weeks after delivery | 6-8 weeks after delivery | 
| Cost | The hospital charges for mother and infant | Up to 4 weeks after birth |