Length of Pregnancy Prolongation in Hours
Conditions
Keywords
Preterm birth, antibiotics, preterm labor, respiratory distress, pergnancy
Brief summary
Preterm birth remains a major health concern affecting up to 12% of all live births prior to 37 weeks gestation. As preterm birth can often be associated with infection our proposal is to evaluate in a randomized fashion antibiotics for women with advanced cervical exams.
Detailed description
Preterm birth, its causes, prevention, complications and ramifications persist as an important focus of obstetrical research. In the United States 11.8% of all live births occur prior to 37 weeks gestation. As many as 45% of these deliveries will have been proceeded by preterm labor with intact membranes.(2) Both preterm labor and preterm premature rupture of membranes have both been associated with evidence intrauterine infection. While antibiotic treatment in conservative management of preterm PROM remote from term has been shown to significantly prolong pregnancy and reduce infant morbidity, (16) data regarding the effectiveness of antibiotics for pregnancy prolongation in preterm labor are inconsistent. (3-15) Currently, narrow spectrum antibiotics (penicillin or clindamycin) are given prior to delivery to reduce the risk of neonatal Group B Beta Streptococcus (GBS) sepsis, however broad spectrum antibiotic treatment of women with preterm labor for pregnancy prolongation is not recommended. Review of the literature regarding antibiotic treatment for pregnancy prolongation in preterm labor reveals that most studies utilized single agent therapy, and no study has evaluated the use of antibiotics for pregnancy prolongation in women with an advanced cervical exam (\>4cm). While a number of studies have shown significant pregnancy prolongation in unselected populations,(5,12,13) only one study of 12 reviewed was able to show a neonatal benefit to adjunctive antibiotic use.(12,20) Norman, et al was able to show a reduction in the incidence of necrotising enterocolitis with the use of antibiotics. Given the number of studies in this area, and the lack of supporting evidence, this likely represents an alpha error. Another study by Svare et al was able to show a significant decrease in NICU admissions for women treated with antibiotics in the setting of preterm labor, however no change was reported in neonatal morbidities. Our proposed study is designed to evaluate patients at particular risk for preterm delivery; those with advanced cervical exam. In this randomized prospective controlled study, we intend to examine the influence of adjunctive antibiotic use in preterm labor complicated by a cervical exam of 4 cm or greater. We plan to compare a study group receiving broad-spectrum antibiotics with a control group that will not receive antibiotics for pregnancy prolongation. Both groups will receive antibiotics for GBS prophylaxis as indicated. We hope to see a delay in delivery in the study group as a primary outcome. Secondary outcomes will include the use of steroids, neonatal complications including sepsis, intraventricular hemorrhage, periventricular leukomalacea, mechanical ventilation and respiratory distress syndrome, retinopathy of prematurity and necrotizing enterocolitis, and neonatal ICU stay.
Interventions
DRUGerythromycin and metronidazole (antibiotics)
Erythromycin 250 mg IV q 6 hours x 8 doses, followed erythromycin 250 mg tabs, 1 PO q 8 hours for five days. Metronidazole, 1 gm IV loading dose followed by 500 mg IV q 12 hours x 4 doses, followed by metronidazole 500 mg tabs, 1 PO q 8 hours for five days
DRUGplacebo
IV and pill placebo
Sponsors
MetroHealth Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. All patients admitted with the diagnosis of preterm labor between 24 0/7 and 33 6/7 weeks gestation. Preterm labor will be defined by regular contractions and/or cervical change from last documented exam. 2. Cervical exam 4 cm or greater 3. Intact membranes
Exclusion criteria
1. Multiple gestation (\>2) 2. Clinical evidence of chorioamnionitis, such as maternal fever, uterine tenderness, fetal tachycardia 3. Lethal fetal anomaly 4. Persistent vaginal bleeding, abruption, or placenta previa 5. Rupture of membranes 6. Maternal illness or fetal indication requiring delivery 7. Inability to give informed consent 8. Serious allergy to study medications. GI discomfort will not be considered a drug allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of Pregnancy Prolongation | Measured from randomization to delivery in hours | The length of time (in hours) from initiation of therapy to delivery will establish the latency |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory Distress | newborn nursery | Respiratory distress will be defined by the clinical record documentation of the neonatal team. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Antibiotic group | 10 |
| Group B Non antibiotic group | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Customized | 10 Participants | 10 Participants | 20 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Length of Pregnancy Prolongation
The length of time (in hours) from initiation of therapy to delivery will establish the latency
Time frame: Measured from randomization to delivery in hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group A | Length of Pregnancy Prolongation | 4 hours |
| Group B | Length of Pregnancy Prolongation | 4 hours |
Secondary
Respiratory Distress
Respiratory distress will be defined by the clinical record documentation of the neonatal team.
Time frame: newborn nursery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Respiratory Distress | 2 Participants |
| Group B | Respiratory Distress | 1 Participants |