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Amniotic fluid indices of fetal pulmonary maturity with preterm premature rupture of membranes
Amniotic Fluid Indices of Fetal Pulmonary Maturity With Preterm Premature Rupture of Membranes RODNEY K. EDWARDS, MD, PATRICK DUFF, MD, AND KELLI C. ROSS, MD Objective: To evaluate the performance of the TDx/TDxFLx fetal lung maturity II assay (Abbott Laboratories; Abbott Park, IL) on amniotic fluid (AF) specimens collected vaginally from women with preterm premature rupture of membranes (PROM). Methods: We reviewed charts of patients with preterm PROM treated at Shands Hospital at the University of Florida from January 1, 1995, to June 30, 1999. Negative predictive values (prediction of the absence of neonatal respiratory distress) of mature (at or above 55 mg/g) and borderline (40 –54 mg/g) test results were calculated for 153 women. Results: Respiratory distress syndrome (RDS) occurred with frequencies of one in 42 and three in 29 cases with mature and borderline test results, respectively. All cases of RDS were mild, defined as sustained tachypnea with or without need for supplemental oxygen. With an immature (less than 40 mg/g) test result, 20 of 82 infants developed RDS, and half of those cases were severe, defined as needing mechanical ventilation. Negative predictive values of mature and borderline tests were 97.6% (95% confidence interval [CI] 92.9, 100) and 89.7% (95% CI, 78.3, 100), respectively. Conclusion: Mature results from fetal lung maturity tests of vaginally collected AF predict the absence of RDS with a high degree of accuracy. (Obstet Gynecol 2000;96:102–5. © 2000 by The American College of Obstetricians and Gynecologists.)
Preterm premature rupture of membranes (PROM) complicates more than 130,000 pregnancies in the United States every year and is associated with at least one third of all preterm births.1 Infant morbidity in those cases is related primarily to gestational age at delivery. Respiratory distress syndrome (RDS) is the most common complication suffered by preterm inFrom the Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida. The authors affirm that they have no financial support from Abbott Laboratories relating to this study or otherwise.
102 0029-7844/00/$20.00 PII S0029-7844(00)00866-8
fants. However, there is evidence that, at gestational ages of 32 weeks or above, with proven fetal pulmonary maturity, maternal and neonatal outcomes are better with delivery than expectant management.2 Therefore, assessment of fetal pulmonary maturity is important for planning treatment of many women with preterm PROM. Many tests to assess fetal pulmonary maturity have been developed, of which the standard seems to be lecithin-sphingomyelin (L/S) ratio. However, L/S ratio is expensive, time consuming, and labor intensive.3 The fluorescence polarization assay (TDx/TDxFLx fetal lung maturity [FLM] II assay; Abbott Laboratories, Abbott Park, IL) is an automated, reproducible measurement that avoids interobserver and intraobserver variability in sample preparation and measurement.4 –7 Although most literature on this test deals with an earlier version (TDx FLM; Abbott Laboratories, Abbott Park, IL), the newer version differs only in packaging of the reagents, the sample volume required (0.25 mL rather than 0.5 mL), and the value of the low control (25 mg/g versus 15 mg/g). The test uses a fluorescent dye that partitions between albumin and phospholipid and measures fluorescence polarization.8 Results are expressed as mg of surfactant per g of albumin. Most investigators of this method have used amniotic fluid (AF) specimens mainly collected by amniocentesis. A MEDLINE search using the terms “fluorescence polarization” and “fetal lung maturity” for articles from 1966 through October 1999 found that the only study that specifically evaluated fluorescence polarization results from vaginally collected AF had only 19 subjects, and each was at term.9 Other reports included preterm gravidas from whom specimens were collected vaginally, but two thirds or more of the subjects in these studies had specimens collected by amniocentesis rather than from the vaginal pool.3,6,10,11 The purpose of this study was to evaluate the performance of the
Obstetrics & Gynecology
TDx/TDxFLx FLM II assay for predicting neonatal clinical outcomes when used on AF collected vaginally from women with preterm PROM.
Materials and Methods We analyzed women treated at Shands Hospital at the University of Florida with preterm PROM between January 1, 1995, and June 30, 1999, who had vaginally collected AF samples submitted for testing of fetal lung maturity. Specimens were analyzed initially with the TDx/TDxFLx FLM II assay which is a quantitative measurement of the ratio of surfactant to albumin in AF. The level of albumin and other proteins in AF is independent of lung maturation. In contrast, the amount of phospholipids increases relative to other components of AF as pulmonary maturation occurs; Thus as the fetal lungs mature, the ratio of surfactant to albumin increases. The TDx/TDxFLx FLM II assay uses a fluorescent dye that is added to AF and partitions between albumin and dispersed phospholipid.4 The dye associated with the surfactant has a lower fluorescence polarization than the dye associated with albumin. The overall fluorescence polarization measured for a sample determines the ratio of surfactant to albumin, expressed in mg/g. According to the manufacturer, results of 55 mg/g or greater indicate mature lungs, and results less than 40 mg/g are immature. Test results of 40 –54 mg/g are considered borderline. Women who had mature tests did not have further testing, and those results were used to formulate a plan of clinical management. Amniotic fluid specimens of women with borderline or immature FLM II test results were analyzed for L/S using thin-layer chromatography. The charts of mother-infant pairs were reviewed for demographic factors, diabetic status, betamethasone administration, and neonatal respiratory complications. Respiratory distress syndrome was considered mild if only tachypnea occurred or supplemental oxygen therapy was required, and severe if mechanical ventilation was necessary. The neonatologist’s subsequent reclassification of four cases as transient tachypnea of the newborn was noted, and those infants were considered not to have RDS for test performance calculations. Negative predictive values were calculated for mature and borderline FLM II results. The negative predictive values of L/S in women with borderline or immature FLM II results also were evaluated, and the incidence of RDS stratified by gestational age was analyzed.
VOL. 96, NO. 1, JULY 2000
Results During the study period, 618 women with preterm PROM were treated at Shands Hospital at the University of Florida. Our tertiary care medical center serves a largely rural population. Most patients are insured under Medicaid. During that time, there were 10,877 deliveries at our institution, with a 5.7% incidence of preterm PROM. When delivery was not clearly indicated (eg, because of nonreassuring fetal heart rate tracings or chorioamnionitis), gravidas had vaginally collected AF samples submitted for testing for fetal lung maturity. There were 211 such women during the study period. Patients were excluded from analysis for multiple gestations (n ⫽ 20), inadequate sample volumes of AF (n ⫽ 12), unsatisfactory samples (ie, grossly bloody, highly mucoid) (n ⫽ 13), delivery more than 7 days after fluid analysis (n ⫽ 10), and infant charts unavailable for review (n ⫽ 3). The remaining 153 motherinfant pairs composed our historical cohort. We did not collect samples routinely from women at less than 30 weeks’ gestation because the probability of a mature fetal lung profile is so low in that group. We would not deliver such patients routinely even if fetal pulmonary maturity could be shown because other forms of morbidity are so common among them. The gestational ages of those infants ranged from 30 to 36 weeks. Racial composition of the subjects was 113 (73.9%) white and 36 (23.5%) black. Mean maternal age was 26.0 years with a standard deviation (SD) of 6.2 years. Subjects delivered at a mean gestational age of 32.9 weeks (SD 1.5 weeks). Fifty-nine (38.6%) women delivered between 48 hours and 7 days of first of two doses of betamethasone, 12 mg intramuscularly (IM) every 24 hours. However, most subjects received at least one dose. Women did not receive full courses of betamethasone if spontaneous preterm labor resulting in delivery occurred before 48 hours from the first dose, or if mature fetal pulmonary status was shown on testing, and delivery was based on those results. The cohort included 21 women (13.8%) with diabetes; and all but three had gestational diabetes. Of the women with gestational diabetes, four needed insulin and 14 had diabetes controlled by diet alone. The results of cases of RDS stratified by FLM II result are presented in Table 1. There were five cases of RDS among infants of diabetic subjects, and all of those had immature FLM II values. There were no neonatal deaths in our cohort. The negative predictive values (prediction of the absence of RDS) of the FLM II test for mature and borderline results were 97.6% (95% CI 92.9, 100) and 89.7% (95% CI 78.3, 100), respectively. The incidence of RDS depends on gestational age, so we also analyzed cases of RDS stratified by gestational
Edwards et al
Fetal Lung Maturity Testing
103
Table 1. RDS Cases by Test Result FLM II (mg/g) ⱖ 55 40 –54 ⱕ 39
Discussion
RDS absent
RDS mild
RDS severe
Total cases
41 26 62
1 3 10
0 0 10
42 29 82
RDS ⫽ respiratory distress syndrome; FLM II ⫽ TDx/TDxFLx fetal lung maturity II assay (Abbott Laboratories, Abbott Park, Illinois); mg ⫽ milligrams of surfactant; g ⫽ grams of albumin.
age (Table 2). The negative predictive value of a gestational age of 34 weeks or greater was 94.4% (95% CI 89.0, 99.8). One case of severe RDS occurred in that group, in which the infant required ventilator support for 36 hours and had a chest radiograph consistent with hyaline membrane disease after being born at 34 weeks’ gestation by cesarean delivery for breech presentation and labor. The infant’s mother had received two doses of betamethasone 3 and 4 days before delivery. The FLM II result was 33; there was an insufficient quantity of AF submitted for L/S analysis. The negative predictive value of a gestational age of at least 32 but less than 34 weeks was only 77.2% (95% CI 66.1, 88.3), and five of 13 cases of RDS at gestational ages of 32 or 33 weeks were severe. Women with borderline or immature FLM II results had L/S tests done on their AF samples. Nineteen of 29 in the borderline group had L/S of 2.0 or greater. In one of those infants, mild RDS developed. Five infants in the group had L/S less than 2.0, and none developed RDS. The L/S test was cancelled in three cases, and two samples were of insufficient volume for that test. Among 82 women with immature FLM II results, 22 had L/S of 2.0 or greater. In four of those 22 infants, RDS developed, all severe cases. Thirty-nine women in the group had L/S less than 2.0. There were 15 cases of RDS in that group, five of which were severe. Of the remaining 21 cases, 12 L/S tests were cancelled because other factors mandated delivery, five had insufficient amounts of fluid for the test, and four specimens were deemed unsatisfactory for analysis. Overall, an L/S greater than 2.0 had a negative predictive value of 94.7% (95% CI 83.9, 100) for women with borderline FLM II results, and 81.8% (95% CI 64.7, 98.9) for women with immature FLM II results. Table 2. RDS Cases by Gestational Age Gestational age (wk)
RDS absent
RDS mild
RDS severe
Total cases
68 44 17
3 8 3
1 5 4
72 57 24
34 –36 32–33 ⬍ 32
RDS ⫽ respiratory distress syndrome.
104 Edwards et al
Fetal Lung Maturity Testing
Treatment decisions about women with preterm PROM beyond 32 weeks’ gestation require consideration of fetal pulmonary maturity. Collection of AF for analysis by amniocentesis is more expensive than collecting it from the vaginal pool. At our institution, the charge for the FLM II test is $96.50. The charge for amniocentesis is an additional $458.40, which includes supplies and physicians’ fees. No separate charge is assessed for collection of AF from the vaginal pool, so using this method to collect it for FLM II analysis decreases hospital charges in excess of $450.00 per patient. Amniocentesis in those women is often technically challenging and potentially dangerous because of oligohydramnios. In certain cases, analysis of AF collected by amniocentesis might be advantageous. Assessment for subclinical chorioamnionitis with Gram stain, glucose concentration, or interleukin-6 concentration in the AF clearly is most accurate when AF is collected by amniocentesis. Despite our study’s limitations because of its retrospective nature and relatively small sample, our investigation indicated that the results of the TDx/TDxFLx FLM II assay on AF collected vaginally correlate well with clinical outcomes, so the results can be used reliably to formulate clinical treatment plans. When the results in this study indicated fetal lung maturity, the likelihood of neonates needing mechanical ventilation was zero. No infants required supplemental oxygen; one had tachypnea for less than 48 hours. No infants in this study who had borderline FLM II results needed mechanical ventilation. This investigation lacked sufficient numbers of diabetic women to evaluate the correlation of FLM II test on AF collected vaginally with neonatal outcomes. There was no suggestion that the test performed less well in that subgroup because all infants of diabetic mothers with RDS had immature FLM II values. Our results indicate that the risk of significant neonatal pulmonary complications is minimal with an FLM II result of 55 or greater, and is unlikely with a result of at least 40. Others also have noted that the manufacturer’s suggested reference range was overly conservative with the original TDx FLM assay.3,5 In our sample, an L/S of 2.0 or greater had an unexpectedly low negative predictive value in women with immature FLM II results, lower than generally noted in the literature for the L/S test, likely because of the highly selected nature of this group with immature FLM II values. Our data indicate that the risk of serious pulmonary complications in neonates of women with preterm PROM is minimal when the FLM II test results indicate mature fetal lungs. The assay is inexpensive and repro-
Obstetrics & Gynecology
ducible, and the results can be available in less than an hour.
References 1. Meis PJ, Ernest JM, Moore ML. Causes of low birth weight births in public and private patients. Am J Obstet Gynecol 1987;156: 1165– 8. 2. Mercer BM, Crocker LG, Boe NM, Sibai BM. Induction versus expectant management in premature rupture of the membranes with mature amniotic fluid at 32 to 36 weeks: A randomized trial. Am J Obstet Gynecol 1993;169:775– 82. 3. Steinfeld JD, Samuels P, Bulley MA, Cohen AW, Goodman DBP, Senior MB. The utility of the TDx test in the assessment of fetal lung maturity. Obstet Gynecol 1992;79:460 – 4. 4. Russell JC. A calibrated fluorescence polarization assay for assessment of fetal lung maturity. Clin Chem 1987;33:1177– 84. 5. Herbert WNP, Chapman JF, Schnoor MM. Role of the TDx FLM assay in fetal lung maturity. Am J Obstet Gynecol 1993;168:808 –12. 6. Ragosch V, Jurgens S, Lorenz U, Stolowsky C, Arabin B, Weitzel HK. Prediction of RDS by amniotic fluid analysis: A comparison of the prognostic value of traditional and recent methods. J Perinat Med 1992;20:351– 60. 7. Russell JC, Cooper CM, Ketchum CH, Torday JS, Richardson DK, Holt JA, et al. Multicenter evaluation of TDx test for assessing fetal lung maturity. Clin Chem 1989;35:1005–10.
VOL. 96, NO. 1, JULY 2000
8. Shinitzky M, Goldfisher A, Bruck A, Goldman B, Stern E, Barkai G, et al. A new method for assessment of fetal lung maturity. Br J Obstet Gynaecol 1976;83:838 – 44. 9. Schneider EP, Fox HE, Barad D, Farber RS. Fluorescence polarization values of amniotic fluid collected from the vagina after rupture of the membranes. Am J Obstet Gynecol 1985;152:572–3. 10. Bayer-Zwirello LA, Jertson J, Rosenbaum J, Moccio R, O’Grady JP, Kanaan CM, et al. Amniotic fluid surfactant-albumin ratio as a screening test for fetal lung maturity: Two years of clinical experience. J Perinatol 1993;13:354 – 60. 11. Apple FS, Bilodeau L, Preese LM, Benson P. Clinical implementation of a rapid, automated assay for assessing fetal lung maturity. J Reprod Med 1994;39:883–7.
Reprints are not available.
Received November 19, 1999. Received in revised form February 22, 2000. Accepted March 2, 2000.
Copyright © 2000 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Edwards et al
Fetal Lung Maturity Testing
105
Preterm premature rupture of membranes (PROM) complicates more than 130,000 pregnancies in the United States every year and is associated with at least one third of all preterm births.1 Infant morbidity in those cases is related primarily to gestational age at delivery. Respiratory distress syndrome (RDS) is the most common complication suffered by preterm inFrom the Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida. The authors affirm that they have no financial support from Abbott Laboratories relating to this study or otherwise.
102 0029-7844/00/$20.00 PII S0029-7844(00)00866-8
fants. However, there is evidence that, at gestational ages of 32 weeks or above, with proven fetal pulmonary maturity, maternal and neonatal outcomes are better with delivery than expectant management.2 Therefore, assessment of fetal pulmonary maturity is important for planning treatment of many women with preterm PROM. Many tests to assess fetal pulmonary maturity have been developed, of which the standard seems to be lecithin-sphingomyelin (L/S) ratio. However, L/S ratio is expensive, time consuming, and labor intensive.3 The fluorescence polarization assay (TDx/TDxFLx fetal lung maturity [FLM] II assay; Abbott Laboratories, Abbott Park, IL) is an automated, reproducible measurement that avoids interobserver and intraobserver variability in sample preparation and measurement.4 –7 Although most literature on this test deals with an earlier version (TDx FLM; Abbott Laboratories, Abbott Park, IL), the newer version differs only in packaging of the reagents, the sample volume required (0.25 mL rather than 0.5 mL), and the value of the low control (25 mg/g versus 15 mg/g). The test uses a fluorescent dye that partitions between albumin and phospholipid and measures fluorescence polarization.8 Results are expressed as mg of surfactant per g of albumin. Most investigators of this method have used amniotic fluid (AF) specimens mainly collected by amniocentesis. A MEDLINE search using the terms “fluorescence polarization” and “fetal lung maturity” for articles from 1966 through October 1999 found that the only study that specifically evaluated fluorescence polarization results from vaginally collected AF had only 19 subjects, and each was at term.9 Other reports included preterm gravidas from whom specimens were collected vaginally, but two thirds or more of the subjects in these studies had specimens collected by amniocentesis rather than from the vaginal pool.3,6,10,11 The purpose of this study was to evaluate the performance of the
Obstetrics & Gynecology
TDx/TDxFLx FLM II assay for predicting neonatal clinical outcomes when used on AF collected vaginally from women with preterm PROM.
Materials and Methods We analyzed women treated at Shands Hospital at the University of Florida with preterm PROM between January 1, 1995, and June 30, 1999, who had vaginally collected AF samples submitted for testing of fetal lung maturity. Specimens were analyzed initially with the TDx/TDxFLx FLM II assay which is a quantitative measurement of the ratio of surfactant to albumin in AF. The level of albumin and other proteins in AF is independent of lung maturation. In contrast, the amount of phospholipids increases relative to other components of AF as pulmonary maturation occurs; Thus as the fetal lungs mature, the ratio of surfactant to albumin increases. The TDx/TDxFLx FLM II assay uses a fluorescent dye that is added to AF and partitions between albumin and dispersed phospholipid.4 The dye associated with the surfactant has a lower fluorescence polarization than the dye associated with albumin. The overall fluorescence polarization measured for a sample determines the ratio of surfactant to albumin, expressed in mg/g. According to the manufacturer, results of 55 mg/g or greater indicate mature lungs, and results less than 40 mg/g are immature. Test results of 40 –54 mg/g are considered borderline. Women who had mature tests did not have further testing, and those results were used to formulate a plan of clinical management. Amniotic fluid specimens of women with borderline or immature FLM II test results were analyzed for L/S using thin-layer chromatography. The charts of mother-infant pairs were reviewed for demographic factors, diabetic status, betamethasone administration, and neonatal respiratory complications. Respiratory distress syndrome was considered mild if only tachypnea occurred or supplemental oxygen therapy was required, and severe if mechanical ventilation was necessary. The neonatologist’s subsequent reclassification of four cases as transient tachypnea of the newborn was noted, and those infants were considered not to have RDS for test performance calculations. Negative predictive values were calculated for mature and borderline FLM II results. The negative predictive values of L/S in women with borderline or immature FLM II results also were evaluated, and the incidence of RDS stratified by gestational age was analyzed.
VOL. 96, NO. 1, JULY 2000
Results During the study period, 618 women with preterm PROM were treated at Shands Hospital at the University of Florida. Our tertiary care medical center serves a largely rural population. Most patients are insured under Medicaid. During that time, there were 10,877 deliveries at our institution, with a 5.7% incidence of preterm PROM. When delivery was not clearly indicated (eg, because of nonreassuring fetal heart rate tracings or chorioamnionitis), gravidas had vaginally collected AF samples submitted for testing for fetal lung maturity. There were 211 such women during the study period. Patients were excluded from analysis for multiple gestations (n ⫽ 20), inadequate sample volumes of AF (n ⫽ 12), unsatisfactory samples (ie, grossly bloody, highly mucoid) (n ⫽ 13), delivery more than 7 days after fluid analysis (n ⫽ 10), and infant charts unavailable for review (n ⫽ 3). The remaining 153 motherinfant pairs composed our historical cohort. We did not collect samples routinely from women at less than 30 weeks’ gestation because the probability of a mature fetal lung profile is so low in that group. We would not deliver such patients routinely even if fetal pulmonary maturity could be shown because other forms of morbidity are so common among them. The gestational ages of those infants ranged from 30 to 36 weeks. Racial composition of the subjects was 113 (73.9%) white and 36 (23.5%) black. Mean maternal age was 26.0 years with a standard deviation (SD) of 6.2 years. Subjects delivered at a mean gestational age of 32.9 weeks (SD 1.5 weeks). Fifty-nine (38.6%) women delivered between 48 hours and 7 days of first of two doses of betamethasone, 12 mg intramuscularly (IM) every 24 hours. However, most subjects received at least one dose. Women did not receive full courses of betamethasone if spontaneous preterm labor resulting in delivery occurred before 48 hours from the first dose, or if mature fetal pulmonary status was shown on testing, and delivery was based on those results. The cohort included 21 women (13.8%) with diabetes; and all but three had gestational diabetes. Of the women with gestational diabetes, four needed insulin and 14 had diabetes controlled by diet alone. The results of cases of RDS stratified by FLM II result are presented in Table 1. There were five cases of RDS among infants of diabetic subjects, and all of those had immature FLM II values. There were no neonatal deaths in our cohort. The negative predictive values (prediction of the absence of RDS) of the FLM II test for mature and borderline results were 97.6% (95% CI 92.9, 100) and 89.7% (95% CI 78.3, 100), respectively. The incidence of RDS depends on gestational age, so we also analyzed cases of RDS stratified by gestational
Edwards et al
Fetal Lung Maturity Testing
103
Table 1. RDS Cases by Test Result FLM II (mg/g) ⱖ 55 40 –54 ⱕ 39
Discussion
RDS absent
RDS mild
RDS severe
Total cases
41 26 62
1 3 10
0 0 10
42 29 82
RDS ⫽ respiratory distress syndrome; FLM II ⫽ TDx/TDxFLx fetal lung maturity II assay (Abbott Laboratories, Abbott Park, Illinois); mg ⫽ milligrams of surfactant; g ⫽ grams of albumin.
age (Table 2). The negative predictive value of a gestational age of 34 weeks or greater was 94.4% (95% CI 89.0, 99.8). One case of severe RDS occurred in that group, in which the infant required ventilator support for 36 hours and had a chest radiograph consistent with hyaline membrane disease after being born at 34 weeks’ gestation by cesarean delivery for breech presentation and labor. The infant’s mother had received two doses of betamethasone 3 and 4 days before delivery. The FLM II result was 33; there was an insufficient quantity of AF submitted for L/S analysis. The negative predictive value of a gestational age of at least 32 but less than 34 weeks was only 77.2% (95% CI 66.1, 88.3), and five of 13 cases of RDS at gestational ages of 32 or 33 weeks were severe. Women with borderline or immature FLM II results had L/S tests done on their AF samples. Nineteen of 29 in the borderline group had L/S of 2.0 or greater. In one of those infants, mild RDS developed. Five infants in the group had L/S less than 2.0, and none developed RDS. The L/S test was cancelled in three cases, and two samples were of insufficient volume for that test. Among 82 women with immature FLM II results, 22 had L/S of 2.0 or greater. In four of those 22 infants, RDS developed, all severe cases. Thirty-nine women in the group had L/S less than 2.0. There were 15 cases of RDS in that group, five of which were severe. Of the remaining 21 cases, 12 L/S tests were cancelled because other factors mandated delivery, five had insufficient amounts of fluid for the test, and four specimens were deemed unsatisfactory for analysis. Overall, an L/S greater than 2.0 had a negative predictive value of 94.7% (95% CI 83.9, 100) for women with borderline FLM II results, and 81.8% (95% CI 64.7, 98.9) for women with immature FLM II results. Table 2. RDS Cases by Gestational Age Gestational age (wk)
RDS absent
RDS mild
RDS severe
Total cases
68 44 17
3 8 3
1 5 4
72 57 24
34 –36 32–33 ⬍ 32
RDS ⫽ respiratory distress syndrome.
104 Edwards et al
Fetal Lung Maturity Testing
Treatment decisions about women with preterm PROM beyond 32 weeks’ gestation require consideration of fetal pulmonary maturity. Collection of AF for analysis by amniocentesis is more expensive than collecting it from the vaginal pool. At our institution, the charge for the FLM II test is $96.50. The charge for amniocentesis is an additional $458.40, which includes supplies and physicians’ fees. No separate charge is assessed for collection of AF from the vaginal pool, so using this method to collect it for FLM II analysis decreases hospital charges in excess of $450.00 per patient. Amniocentesis in those women is often technically challenging and potentially dangerous because of oligohydramnios. In certain cases, analysis of AF collected by amniocentesis might be advantageous. Assessment for subclinical chorioamnionitis with Gram stain, glucose concentration, or interleukin-6 concentration in the AF clearly is most accurate when AF is collected by amniocentesis. Despite our study’s limitations because of its retrospective nature and relatively small sample, our investigation indicated that the results of the TDx/TDxFLx FLM II assay on AF collected vaginally correlate well with clinical outcomes, so the results can be used reliably to formulate clinical treatment plans. When the results in this study indicated fetal lung maturity, the likelihood of neonates needing mechanical ventilation was zero. No infants required supplemental oxygen; one had tachypnea for less than 48 hours. No infants in this study who had borderline FLM II results needed mechanical ventilation. This investigation lacked sufficient numbers of diabetic women to evaluate the correlation of FLM II test on AF collected vaginally with neonatal outcomes. There was no suggestion that the test performed less well in that subgroup because all infants of diabetic mothers with RDS had immature FLM II values. Our results indicate that the risk of significant neonatal pulmonary complications is minimal with an FLM II result of 55 or greater, and is unlikely with a result of at least 40. Others also have noted that the manufacturer’s suggested reference range was overly conservative with the original TDx FLM assay.3,5 In our sample, an L/S of 2.0 or greater had an unexpectedly low negative predictive value in women with immature FLM II results, lower than generally noted in the literature for the L/S test, likely because of the highly selected nature of this group with immature FLM II values. Our data indicate that the risk of serious pulmonary complications in neonates of women with preterm PROM is minimal when the FLM II test results indicate mature fetal lungs. The assay is inexpensive and repro-
Obstetrics & Gynecology
ducible, and the results can be available in less than an hour.
References 1. Meis PJ, Ernest JM, Moore ML. Causes of low birth weight births in public and private patients. Am J Obstet Gynecol 1987;156: 1165– 8. 2. Mercer BM, Crocker LG, Boe NM, Sibai BM. Induction versus expectant management in premature rupture of the membranes with mature amniotic fluid at 32 to 36 weeks: A randomized trial. Am J Obstet Gynecol 1993;169:775– 82. 3. Steinfeld JD, Samuels P, Bulley MA, Cohen AW, Goodman DBP, Senior MB. The utility of the TDx test in the assessment of fetal lung maturity. Obstet Gynecol 1992;79:460 – 4. 4. Russell JC. A calibrated fluorescence polarization assay for assessment of fetal lung maturity. Clin Chem 1987;33:1177– 84. 5. Herbert WNP, Chapman JF, Schnoor MM. Role of the TDx FLM assay in fetal lung maturity. Am J Obstet Gynecol 1993;168:808 –12. 6. Ragosch V, Jurgens S, Lorenz U, Stolowsky C, Arabin B, Weitzel HK. Prediction of RDS by amniotic fluid analysis: A comparison of the prognostic value of traditional and recent methods. J Perinat Med 1992;20:351– 60. 7. Russell JC, Cooper CM, Ketchum CH, Torday JS, Richardson DK, Holt JA, et al. Multicenter evaluation of TDx test for assessing fetal lung maturity. Clin Chem 1989;35:1005–10.
VOL. 96, NO. 1, JULY 2000
8. Shinitzky M, Goldfisher A, Bruck A, Goldman B, Stern E, Barkai G, et al. A new method for assessment of fetal lung maturity. Br J Obstet Gynaecol 1976;83:838 – 44. 9. Schneider EP, Fox HE, Barad D, Farber RS. Fluorescence polarization values of amniotic fluid collected from the vagina after rupture of the membranes. Am J Obstet Gynecol 1985;152:572–3. 10. Bayer-Zwirello LA, Jertson J, Rosenbaum J, Moccio R, O’Grady JP, Kanaan CM, et al. Amniotic fluid surfactant-albumin ratio as a screening test for fetal lung maturity: Two years of clinical experience. J Perinatol 1993;13:354 – 60. 11. Apple FS, Bilodeau L, Preese LM, Benson P. Clinical implementation of a rapid, automated assay for assessing fetal lung maturity. J Reprod Med 1994;39:883–7.
Reprints are not available.
Received November 19, 1999. Received in revised form February 22, 2000. Accepted March 2, 2000.
Copyright © 2000 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Edwards et al
Fetal Lung Maturity Testing
105