The Effect of Antibiotics on Latency in Previable Prelabor Rupture of Membranes Between 18 0/7 and 22 6/7 Weeks Gestational Age

Throughout this detailed description, patient and subject will be used interchangeably.

Patients presenting to either an acute care setting (Woman's Hospital Assessment Center) or outpatient clinic setting with concerns for rupture of membranes will be clinically evaluated by an obstetrician (including private physicians, resident faculty and resident physicians). Exam findings including either/or 1) visualization of amniotic fluid passing from the cervical canal and pooling in the vagina via sterile speculum examination, 2) a basic pH (i.e., positive nitrazine) test of vaginal fluid, 3) arborization (ferning) of dried vaginal fluid identified via microscopic examination by the examining physician, or 4) an amniotic fluid index (AFI) of less than 4cm between 18 0/7 and 22 6/7 weeks gestation are to be diagnostic of previable, preterm premature rupture of membranes (PPROM). Eighteen weeks gestational was arbitrarily chosen as the lower limit of gestational ages included based on review of currently available retrospective studies on previable PPROM. If patient meets all inclusion and exclusion criteria as listed above specimens to be collected at the time of diagnosis include a catheterized urinalysis with reflex urine culture if indicated, wet prep (i.e., vaginitis panel), group B strep DNA recto-vaginal swab, complete blood count and PCR testing for gonorrhea, chlamydia and trichomonas via endocervical swab. An ultrasound to determine amniotic fluid index (AFI) should also be performed at this time (either by radiology or Maternal-Fetal Medicine). These will be collected according to current standard of care practices for preterm prelabor rupture of membranes. Patient will then be admitted to the Woman's Hospital Labor and Delivery unit for a 24-hour observation period. Acetaminophen and ibuprofen will be withheld during this 24-hour observation period in order to ensure that no signs or symptoms of underlying infection or preterm labor are masked. A repeat complete blood count will be performed the morning of hospital day 2, and repeat AFI on hospital day 2 to be performed with full obstetric ultrasound by Maternal Fetal medicine physicians.

If, during the 24-hour observation period, the subject is without signs of chorioamnionitis, preterm labor, or placental abruption with vaginal bleeding as determined by the MFM staff, and if patient continues to meet both inclusion and exclusion criteria, subject will then be offered enrollment in the study. The consenting process will be performed by the MFM staff physicians or by Felicia LeMoine, MD, or Kaitlyn Taylor, MD, the co-investigators. The consenting process will be performed within the patient's private hospital room (designated at the time of admission). Once the subject as agreed to voluntary participation and in-formed consent has been signed, the subject will then be assigned an individual study identifier that includes the study acronym OAPPPROM patient initials, and unique number (randomly generated using the sample () function in R statistical software). All blood samples and specimens collected prior to admission, at admission and future blood samples and specimens will be available to the treating physician and reported within the patient's chart as is current standard practice. The samples and specimens will also be referenced using the patient's unique identifier for the sake of research data collection. The enrolled subjects will then be randomized using a computer-generated sample without replacement from the patient ID numbers into either the control (no antibiotics) or treatment (antibiotics) arm.

Following the 24-hour observation period and randomization, those subjects enrolled into the treatment (antibiotics) arm of the study will be thoroughly counseled on the risks and adverse side effects associated with the use of azithromycin and amoxicillin and which of those side effects should prompt emergency evaluation at Woman's Hospital Assessment Center or the nearest emergency department with obstetrical care. The subjects of the treatment arm will also receive the first dose of antibiotics while in the hospital to ensure no immediate adverse effects.

Both arms of the study will receive, at the time of discharge, a "Patient Information Pamphlet" along with a thermometer to take home. All subjects will be instructed on proper methods to measure body temperature with the thermometer. All subjects will be thoroughly counseled on symptoms or findings which should prompt immediately follow-up at Woman's Hospital or the nearest emergency department with obstetrical care. Such symptoms include, but are not limited to, vaginal bleeding, fevers, chills, purulent vaginal discharge, contractions, pelvic pain or cramping, abdominal pain or cramping, or any other concerns. Subjects will be counseled on avoidance of sexual intercourse and avoidance of overt exertion, yet, strict bed rest will not be advised. Subjects will be instructed to keep the "Patient Information Pamphlet" with them at all times while enrolled in this study. If patient either reports a lost or misplaced pamphlet at any point during the study or presents to any scheduled follow up appointment in the MFM clinic without the pamphlet, the patient will be provided with a new copy. The pamphlet includes a daily temperature log, an adverse/side effect log, and emergency contact information for key figures involved in this study. The pamphlet also includes a table in which dates and findings (i.e., EGA, maternal heart rate, fetal heart rate, maternal blood pressure, maternal temperature, and AFI) from follow-up MFM appointments are to be logged. The initial MFM follow-up appointment will be scheduled prior to discharge from the hospital for all subjects enrolled. Documentation of scheduled time and date will be noted on patient's discharge paperwork. Follow-up for both arms of the study will be scheduled within the MFM outpatient clinic weekly until subjects either reach 23 0/7 weeks gestation or show signs of change in clinical condition. Weekly follow-up visits will consist of vital signs (maternal heart rate, maternal blood pressure, temperature and weight), a physical examination of subject, an obstetric ultrasound to assess fetal well-being, calculate amniotic fluid index, and determine fetal heart rate, and weekly complete blood counts (lab draws). Patients will also be instructed to bring the antibiotic pill bottles the initial follow up appointment. The number of pills remaining will be counted to assess degree of antibiotic compliance. The results of these assessments, along with a copy of the "Patient Information Pamphlet", will be made at each follow up visit and stored within a data collection sheet. Each patient will be assigned an individual data collection sheet which will be marked with the patient's medical record number and unique subject identifier (determined as mentioned above).