Volume 171, Number 2 Am J Obstet Gynecol

20% of tests not assayable. Accurate fetal lung maturity testing remains a critical issue in spite of the advent of surfactant.

Douglas K. Rlchardson, MD, MBA, and Milenko Tanasijevic, MD

Jomt Program in Neonatology, Hunnewell 4, 300 Longwood Ave., Boston, MA 02115

REFERENCES

1. Russell lC, Cooper CM, Ketchum CH, et al. Multicenter evaluation ofTDx test for assessing fetal lung maturity. Clm Chern 1989;35:1005-10.

2. Steinfeld lD, Samuels P, Bulley MA, Cohen AW, Goodman DBP. Senior MB. "Ine utility of the TDx test in the assess­ment of fetal lung matunty. Obstet GynecoI1991;79:460-4.

3. Richardson DK, Schwartz lS, Weinbaum P, Gabbe SG. Diagnostic tests in obstetrics: a method for improved evalu­atIon. AMl OBSTET GYNECOL 1985;152:613-8.

4. Van Marter Ll, Berwick DM, Torday lS, Frigoletto FD, Wise PH, Epstein MF. Interpretation of indices of fetal pulmo­nary maturity by gestational age. Pediatr Perinat Epidemiol 1988;2:360-4.

5. Hunink MGM. Richardson DK, Doubilet PM, Begg CB. Te~ting for fetal maturity: an ROC analysis involving cova­riates, verification bias and combination testing. Med Deci­sion Making 1990;10:3:201-11.

6. Weinbaum P, Richardson DK, Schwartz lS, Gabbe SG. Amniostat FLM: a new technique for detection of phos­phatidylglycerol in amniotic fluid. Am 1 Perinatol 1985;2: 88-92.

6/8/56512

Reply To the Editors: We appreciate the interest Richardson and Tanasijevic have shown in our work, which is only the second report of the fetal lung maturity assay in the obstetrics and gynecology literature. They have several concerns about our paper that apply, in general, to all reports involving fetal maturation tests. Many other limitations in this field of study can be cited, including modifications of testing procedures (especially for the lecithin/sphingomyelin ratio), uncertainty in gestational age, interval between fluid collection and delivery, use of test results to determine patient care (thereby modi­fying outcome), influence of pregnancy complications that modify maturation, difficulty in diagnosis of respi­ratory distress syndrome, prenatal glucocorticoid use, neonatal exogenous surfactant therapy, vaginal versus abdominal collection of fluid, type of delivery, and contamination of amniotic fluid.

With respect to the specific concerns expressed about our work, however, we offer the following responses.

1. Statistical tools. It is correct that there is a spec­trum of positivity that reflects the probability of matu­rity. In clinical practice, though, a single cutoff point is

Letters 585

used for virtually all tests of fetal lung maturity. For this reason we did not include a receiver-operator charac­teristic curve.

2. Gestational age considerations. Certainly gesta­tional age is a critical determinant of the incidence of respiratory distress syndrome, and ideally predictive values should be calculated for each week of gestation. However, to do so would require an extraordinarily large database, particularly in light of the other vari­ables noted above. Again we followed the traditional reporting approach, with its recognized limitations.

3. Inadequate sample size. What is an adequate sample size? Any new test must be evaluated in the anticipated clinical setting in which it will be used. The gestational age range of our patients, as stated, was from 28 to 40 weeks. The mean gestational age was 34.5 weeks, with the 25th and 75th percentiles being 32 and 37 weeks, respectively. This population is typical of clinical settings for fetal lung maturity testing and included a large proportion of infants who had res­piratory distress syndrome. With regard to McNemar's test, we in fact used this calculation but did not specifically say so; rather, we simply said that we used X" analysis, which McNemar's test uses as the test statistic.

Interestingly, the three "flaws" cited in our paper are also present in the Weinbaum et al. reference, in which Richardson was a coauthor. In that work specific cutoff points were used for the tests involved, and the spec­trum of gestational ages and respiratory outcomes were not stratified (percentages of mature results were used!). In addition, the number of cases used to evalu­ate clinical outcome for the Amniostat-FLM test was less than the number we reported and contained one half (11 vs 22) the number of infants who had respiratory distress syndrome. Finally, although their letter men­tions use of McNemar's test in that paper, it is not so stated in the manuscript itself.

Because the authors mention diabetes specifically, we are provided an opportunity to mention a study group underway to address fetal lung maturity testing, specifi­cally the TDx FLM assay, in this population. This study group was described at the 1993 meeting of the Society of Perinatal Obstetricians, and participants from vari­ous centers are involved. Perhaps Richardson and Ta­nasijevic, and others, would like to join in this effort; if so, they should contact us as soon as possible.

Wilham N.P. Herbert, MD

Dmmon of Maternal-Fetal Medu'lIZe, Department of Obstffrtr< and Gynecology, DUMC 3967, Duke Un/vemty Medlwl Center, Durham, NC 27710

John F. Chapman, DrPH, and Melame M. Schnoor, AB Department of Pathology, Univenity of North Caroll11a School of Medlcme, Chapel HIll, NC 27514

6/8/56514