Comparison of Two Fetal Lung Maturity Tests
Comparison of Two Fetal Lung Maturity Tests
The investigators wish to compare the difference in both cost and time to result for
 determining fetal lung maturity for the Lamellar Body Count method and the Fetal Lung
 Maturity II. Our hypothesis is that the time to result will be significantly less using the
 Lamellar Body Count method, and the cost associated with this method over the traditional FLM
 II will be favorable.
Rationale/Background: This pilot study is a prospective cohort analysis of two methods
 currently available at our institution for the determination of fetal lung maturity (FLM)
 using amniotic fluid. The investigators wish to explore a cost and time savings potential
 between these two available tests. The test most utilized for the determination of FLM is the
 evaluation of phospholipids from the amniotic fluid. In our particular institution, the
 relationship of surfactant to albumin (S/A ratio) is analyzed using a measured fluorescent
 polarization called the FLM II procedure performed on the TDx or TDxFLx chemical analyzer
 which is commercially available from Abbott Labs. This test is time-consuming and not
 available at all institutions.

 Lamellar bodies are lamellated phospholipids that represent a storage form of surfactant (1).
 Because lamellar body diameter (range, 1-5 µm) is similar to that of small platelets,
 lamellar body counts (LBCs) can be obtained rapidly with use of the platelet channel of a
 hematology analyzer. The investigators wish to compare the difference in both cost and time
 to result for determining FLM for the LBC method and the FLM II. Our hypothesis is that the
 time to result will be significantly less using the LBC method, and the cost associated with
 this method over the traditional FLM II will be favorable.

 Extensive research has shown the efficacy of analyzing fetal lung maturity using lamellar
 bodies (2-11). Since the efficacy of this method has been established, the adequacy of the
 lamellar body count in comparison to the FLM II is not in question in this study. While other
 studies have speculated that a cost and time savings would exist, no literature was found to
 answer this precise question. The authors feel this information could benefit the medical
 community from an economic standpoint.

 Amniotic fluid collected at the time of amniotomy on term cesarean sections will be sent to
 OSUMC laboratory for FLM analysis using both a LBC and the FLM II. Our hypothesis is that
 both the time to result and cost using the LBC method will be substantially less.

 Methodology Mechanism of Testing At present, FLM testing at Oklahoma State University Medical
 Center (OSUMC) is performed by TDx-FLM chemical analyzer manufactured by Abbott Labs. Most
 laboratories using the Abbott FLM-II assay for assessing fetal lung maturity follow the
 manufacturer's recommendations for interpreting the surfactant to albumin ratio. Thus, values
 greater than 55 mg/g are considered mature and values less than 40 mg/g immature. McElrath et
 al., reported a probability of respiratory distress syndrome (RDS) of 15% or less can be
 achieved with a S/A ratio cutoff of 60 mg or more at 28 weeks of gestation, 50 or more at 30
 weeks, 40 or more at 33 weeks, 30 or more at 35 weeks, and 20 or more at 37 weeks (12).

 Lamellar bodies have been tested on many hospital instruments that are used for the
 hematology testing at their institutions. The ADVIA 2120 (Siemens Medical Solutions
 Diagnostics, Tarrytown, NY), which is a flow cytometry system that functions to identify and
 count specific cells in body fluid, is used in the OSUMC laboratory for hematology and other
 body fluids. Although it has not been used for LBC in our institution, it certainly has that
 capability according to the manufacturer (13). Neerhof et. al, recently described a change in
 the threshold at their particular institution. The level of maturity was increased from
 30,000 to 50,000 LB/ul. This resulted in significantly fewer neonatal intensive care unit
 admissions for RDS (14).

 An algorithm to FLM testing first utilizing the LBC has been published by Ventolini et al.
 This algorithm is pictured in Figure 1 (15). We will incorporate this algorithm into our cost
 analysis as indeterminate LBC values would have required the FLM II procedure, thus elevating
 the cost for that patient.

 Amniotic fluid will be obtained by the operating surgeon or assistant once amniotomy is made.
 At least 2 ml of amniotic fluid is required for both tests. The fluid will them be handed off
 to waiting nursing personnel. Once the amniotic fluid is obtained, LBC and S/A ratios will be
 sent to the laboratory as a stat order. Laboratory personnel will record the time that the
 specimen is checked into lab and the time the result is available, which is their standard
 protocol. These times will be used to calculate the time differences between LBC and S/A
 ratios. The patient will be identified by their assigned medical record number in the
 hospital. Details of the LBC protocol using the ADVIA 2120 can be found in Table 1.

 We will record results of both studies. When an indeterminate level is obtained using the
 lamellar body count, a cost for performing the FLM II procedure will be added to the lamellar
 body count cost for that particular patient. The amount that would have been charged to the
 patient will be used to calculate the cost savings in our sample size. We will then compare
 the cost of the LBC, LBC and TDxFLM (if required by our algorithm), and the TDxFLM alone.

 Study Population:

 The study population will include ten term gestations scheduled for either repeat cesarean
 section (C/S) or primary C/S for malpresentation. Term will be defined as 37 completed weeks
 based on a sure last menstrual period or first trimester ultrasound crown rump length
 measurement.

 Consent will be obtained either in the resident clinic or on the morning of the scheduled
 procedure. The resident investigator or one of the obstetrical residents at OSUMC will
 consent the patient.. The residents participating in consenting will be given instructions
 regarding the consent process as well as inclusion/exclusion criteria.

 The cost for both laboratory tests will be approximately $45 per patient. The sample size
 will be limited by a research grant of $500.00 provided by the Osteopathic Founders
 Foundation. Other funding is in application and expansion of this project will be likely in
 the future.

 Inclusion Criteria:

 -  Term intrauterine gestations beyond 37 completed weeks with dating calculated by their
 sure last menstrual period (LMP) using Negel's rule or utilizing a first trimester crown
 rump length ultrasound.

 -  Women with a previous C/S scheduled for repeat C/S.

 -  Women who are undergoing a scheduled C-Section for malpresentation

 Exclusion Criteria:

 -  Presence of gross blood in amniotic sample

 -  Hematocrit count greater than 1% on ADVIA 2120

 -  Presence of meconium in sample

 -  Patients with oligohydramnios defined as an amniotic fluid index of less than 5 cm or
 polyhydramnios defined as an amniotic fluid index of more than 24 cm.

 Early Termination Criteria:

 If for any reason the investigators or the obstetrician performing the C/S believe the
 patient or fetus may be harmed by the extra time required for amniotic fluid collection
 (albeit short), the patient may be removed from the study without her consent. The volunteer
 would also have the right to terminate her participation in the study and to terminate the
 investigators' rights to use the collected fluid or analyzed result at any time.

 Collection Sheet Appendix C "Lamellar Body Data Collection Sheet" will be used for the
 collection and storage of data. All information will be de-identified for the collection,
 storage and retrieval of information.

 Data Collection Only the principle investigator(s) will have access to the patients' data
 collection sheet. Individual physicians involved in the care of a specific patient will have
 access to that patient's information. All individuals will be in compliance with HIPPA
 guidelines as set forth by the university and the medical center. Treatment decisions will
 not be based on the results of data collected for this study.

 The following information will be obtained from the patients chart for entry on the data
 collection sheet.

 1. Maternal age

 2. Gravity/Parity

 3. Estimated Gestational Age and how that was figured

 4. Maternal complications - diabetes, hypertension, PIH, coronary vascular disease, thyroid
 disease, thrombophilia,

 5. Date collected

 6. Time collected

 7. Time received

 8. Time reported - FLM, LB

 9. Difference in total times

 10. FLM result - mature, intermediate or immature

 11. LB result - mature, intermediate or immature

 12. Cost for FLM

 13. Cost for LB No other data will be collected from any patient charts. The resident
 investigator will assist in the collection of data and will have qualifications for
 basic human research and HIPPA training as they fall under the OSU - CHS community of
 individuals with this privilege. Further, physicians and residents which have direct
 access to current patients chart in their medical management will determine needs for
 fluid collections and assist in patient consents.

 Analysis: An algebraic expression will be used to determine which procedure is the most time
 and cost effective. Let P be the proportion of LBC's that have conclusive results. Let X
 denote an attribute of LBC (say cost or time) and let Y denote the same attribute for FLM II.
 The following equation asks the question "when are the costs associated with just performing
 FLM II greater than the costs associated with LBC with the FLM II backup?"

 Cost (or time) of LBC with FLM II back up < Cost (or time) of FLM II

 when

 X < P*Y

 In other words: Using LBC is beneficial when the proportion of conclusive results is greater
 than the proportion of cost of LBC over FLM II.

 Confidentiality: All records and lab results will be maintained at Oklahoma State University
 Medical Center, department of medical records and laboratory storage on the hospital's
 Meditech system. Research analysis data collection sheets will be de-identified and will be
 maintained by the Department of Ob/Gyn in a secured location at 717 South Houston Ave, Tulsa
 OK 74127.
Inclusion Criteria:

 -  Term intrauterine gestations beyond 37 completed weeks with dating calculated by their
 sure last menstrual period (LMP) using Negel's rule or utilizing a first trimester
 crown rump length ultrasound.

 -  Women with a previous C/S scheduled for repeat C/S.

 -  Women who are undergoing a scheduled C-Section for malpresentation

 Exclusion Criteria:

 -  Presence of gross blood in amniotic sample

 -  Hematocrit count greater than 1% on ADVIA 2120

 -  Presence of meconium in sample

 -  Patients with oligohydramnios defined as an amniotic fluid index of less than 5 cm or
 polyhydramnios defined as an amniotic fluid index of more than 24 cm.