A
GNIESZKAS
APA1, A
RTURK
ŁÓSEK2, J
OANNAS
ZYMKOWIAK2, J
ERZYZ
ALEWSKI3,
M
AŁGORZATAC
ZYŻEWSKA2, M
IECZYSŁAWW
OŹNIAK1, 4Comparison of Two Fetal Lung Maturity Tests
– Analytical Validation and Preliminary Clinical
Assessment of the LBC Test and the TDx−FLM II Assay
Porównanie dwóch metod laboratoryjnych do oceny dojrzałości płuc
płodu – walidacja analityczna i wstępna ocena kliniczna testów LBC
i FLM II
1 Department of Clinical Chemistry, Wroclaw Medical University, Poland
2 2nd Department and Clinic of Gyneacology, Obstetrics and Neonatology, Wroclaw Medical University, Poland 3 Department of Gyneacology and Obstetrics, Wroclaw Medical University, Poland
4 Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada
Adv Clin Exp Med 2009, 18, 6, 567–573 ISSN 1230−025X
ORIGINAL PAPERS
© Copyright by Wroclaw Medical University
Abstract
Background.Respiratory distress syndrome (RDS) is connected with insufficient lung development and is dange− rous, especially in premature infants. The assessment of fetal lung maturity is critical in planning an optimal labor term properly. Implementation of the lamellar body count (LBC) in a laboratory requires a full validation proce− dure and correlation studies with some reference method.
Objectives.The aim was to validate and compare the Fetal Lung Maturity Test II (FLM II) and the LBC as pre− dictors of fetal lung maturity in pathological pregnancies. FLM II was used as the reference method.
Material and Methods.The study was performed using 112 amniotic fluid samples collected by amniocentesis from 100 patients. After proper preparation, the samples were examined by both methods. A validation procedure was performed for both tests.
Results.The correlation between LBC and FLM II was significant (r= 0.842). Both tests showed very good cor− relation with gestational age. For the investigated patient population the dispersion of results was greater for LBC than for FLM II after dividing into groups by gestational age. This study revealed a relationship between LBC test results and the amount of amniotic fluid. In cases of oligohydramnios, the results of the LBC test were higher than those of FLM II, thereby changing the clinical interpretation of results from intermediate or even immature to ma− ture. There was no RDS in the examined population. However, in 5 cases of identified respiratory disorders, none of FLM II test results were classified as mature, whereas 3 of the LBC results indicated maturity.
Conclusions.The preliminary results showed that LBC could be useful in fetal pulmonary maturity evaluation in pathological pregnancies, as it is an inexpensive and available assay. The clinician should be aware of the limita− tions of its utility and proper cutoff values should be established for specific weeks of gestation and clinical cha− racteristics (Adv Clin Exp Med 2009, 18, 6, 567–573).
Key words:fetal lung maturity, respiratory distress syndrome, amniotic fluid.
Streszczenie
Wprowadzenie.Zespół niewydolności oddechowej noworodków (RDS – respiratory distress syndrome) jest du− żym zagrożeniem dla życia noworodków urodzonych przedwcześnie. Jego występowanie jest związane z niedo− stateczną dojrzałością płuc płodu. Do podjęcia decyzji o optymalnym terminie rozwiązania ciąży jest konieczne ustalenie stanu dojrzałości płuc płodu. Wdrażanie metody oznaczania liczby ciał lamelarnych (LBC – lamellar bo− dy count) w każdym laboratorium wymaga ustalenia wartości referencyjnych i wymusza konieczność badania ko− relacji z testem referencyjnym przed wdrożeniem metody do rutynowej diagnostyki.
Respiratory distress syndrome (RDS) is dan− gerous, especially in premature infants. It is con− nected with insufficient lung tissue development. Pulmonary surfactant is a very important mixture composed of phospholipids (e.g. lecithin, sphin− gomyelin, and phosphatidylglycerol) and proteins and it possesses the ability to reduce surface ten− sion. Its production starts approximately in the 20th–24thweeks of gestation and by 34–36 weeks
the amount of lecithin present is sufficient to pre− vent alveolar collapse [1, 2]. The level of protein in the surfactant does not affect lung function and remains relatively constant throughout the later months of pregnancy. Pulmonary surfactant is pro− duced by type II pneumocytes and packed into lamellar body structures.
The chemical and physical properties of the surfactant present in amniotic fluid have been used to design several diagnostic tests. The chemical composition of surfactant changes during pregnan− cy; for example, the appearance of phosphatidyl− glycerol indicates sufficient lung maturity [3]. The assessment of fetal lung maturity is necessary to enable the clinician to make the right decision about the optimal labor term and the administra− tion of medicines that accelerate lung maturation. Amniotic fluid examination is an important part of prenatal diagnostics in spite of significant progress in noninvasive diagnostic procedures. Moreover, as the invention of artificial surfactant decreased the number of RDS cases and mortality rates, bio− chemical tests are only used to evaluate the risk of RDS. These test results do not determine the neonate’s condition, but they can confirm that lung maturation has already started.
The laboratory evaluation of fetal lung maturi− ty is not recommended for physiological pregnan−
cies after 36 weeks if the duration of pregnancy is well documented. However, lung maturity evalua− tion should be performed in pregnancies with a high risk of RDS outcome, even after 36 weeks of gestation. It is also used to verify pregnancy duration when there is a suspicion of fetal hypotrophy. According to the recommendations of the ACOG (American College of Obstetricians and Gynecologists) [1] and the guidelines of the NACB (National Academy of Clinical Bio−chem− istry) [4], the laboratory examination of fetal lung maturity should be available in every hospital with an obstetric unit. The tests should be characterized by high diagnostic value and short TAT (turn− around time) and should be inexpensive and avail− able around the clock. Of the many both commer− cially and home−made tests available, lamellar body count (LBC), surfactant−to−albumin ratio (FLM II, Abbott Laboratories, USA), and phos− phatidylglycerol (PG) semi−quantitative determi− nation (AmnioStat FLM, Irvine Scientific, USA) are commonly used and also recommended by the NACB [4]. LBC is a very cheap and simple assay and every medical laboratory equipped with a hematology counter is able to perform the test procedure. Some specialists consider the FLM II as a reference method, especially recommended in evaluating pregnancies with a high risk of RDS [1]. An important advantage of PG determination is its independence of meconium or blood contam− ination in the amniotic fluid, which disqualifies both the FLM II and LBC [5–8].
Implementation of the LBC test in every labo− ratory requires a validation procedure because of individual differences between various hematology analyzers and sample preparation procedures [4, 9, 10]. Moreover, LBC determination is recommend−
w grupie ciąż patologicznych. Jako metodę odniesienia użyto test FLM II.
Materiał i metody.Materiałem do badań było 112 próbek płynu owodniowego pobranych od 100 pacjentek me− todą amniopunkcji. Próbki, po odpowiednim przygotowaniu, zbadano testami LBC i FLM II. Dokonano walidacji analitycznej obu metod.
Wyniki. Uzyskano bardzo wysoką korelację między wynikami uzyskanymi testem LBC a testem FLM II (r = 0,842). Obydwa testy dobrze korelowały z wiekiem ciąży. W przypadku współistnienia stanów patologicznych w ciąży zaobserwowano większy, niż w przypadku FLM II, rozrzut wartości uzyskanych LBC, po podziale na gru− py w zależności od wieku ciąży. Zaobserwowano związek między występowaniem małowodzia a wynikami uzy− skanymi za pomocą testu LBC. Wyniki LBC były większe aniżeli FLM II, co zmieniało zaszeregowanie próbki z niedojrzałej lub pośredniej (FLM II) na dojrzałą (LBC). W badanej populacji nie rozpoznano przypadków RDS, wystąpiło jednak 5 przypadków zaburzeń oddychania. We wszystkich tych wypadkach wyniki testu FLM II sytu− owały się poniżej wartości odcinającej wskazującej na dojrzałość, a test LBC aż w 3 przypadkach sugerował od− powiednią dojrzałość płuc.
Wnioski. Mimo wielu ograniczeń, wysoka korelacja między testem LBC a FLM II wstępnie potwierdza możli− wość zastosowania LBC jako taniego, szeroko dostępnego testu przesiewowego w badaniu dojrzałości płuc płodu. Konieczne jest przyjęcie odpowiednich wartości odcinających dla poszczególnych grup ciężarnych (wiek ciąży i obraz kliniczny). W przypadkach współistniejącego małowodzia wyniki badań LBC są zawyżone, w związku z czym powinny być traktowane ostrożnie (Adv Clin Exp Med 2009, 18, 6, 567–573).
ed only in low−risk pregnancies, which imposes correlation studies with some reference method before its application as a routine assay [1, 2, 11].
The aim of this study was to validate the LBC (measured by Sysmex K4500) and FLM II tests. Moreover, a comparison of FLM II and lamellar body count as predictors of fetal lung maturity in a population with various pregnancy disorders was planned by determining the correlation coefficient between tests results. FLM II was used as a refer− ence method. The results of the study would allow a preliminary evaluation of the clinical usefulness of the LBC test and to verify if LBC could be applied instead of the relatively expensive FLM II test.
Material and Methods
The study was performed using 112 amniotic fluid samples collected by amniocentesis during the third trimester from 100 patients at the Department of Pathology of Fetal Development (2005–2007) and the Second Chair and Clinic of Gynecology, Obstetrics, and Neonatology (2006– 2008) of Wroclaw Medical University. The amni− otic fluid was collected for routine fetal lung matu− rity evaluation. The patients’ characteristics are shown in Table 1. Samples contaminated with vis− ible blood or meconium as well as icteric samples were excluded. Amniotic fluid was transported and stored at 2–8°C for no longer than 4 hours. Prior to analysis, all the samples were mixed thor-oughly and filtered by glass-fiber filters attached to the FLM II kit. This procedure enables the elim-ination of most solid contaminants that disturb pipetting and measurement by a hematology counter without any loss of lamellar bodies (such as during centrifugation).
Lamellar Body Count (LBC)
The test principle is the optical similarity of lamellar bodies and small platelets. Thus it is pos− sible to count lamellar bodies using the platelet channel of a hematology analyzer. The test was performed on a Sysmex K4500 part WBC 3 dif− ferential analyzer (Sysmex, Japan), which counts particles by the impedance technique. The result was taken as the mean of two measurements.FLM II Test
(Fetal Lung Maturity II)
FLM II is a second−generation test performed on a TDx analyzer (Abbott Laboratories, USA). In
the test procedure, a fluorescent dye is added to the amniotic fluid sample. The dye partitions between albumin and the aggregates formed by the surfac− tant. The fluorescence polarization measured for a sample reflects the distribution of the dye between the protein and surfactant components of the amniotic fluid and serves as a way of deter− mining the surfactant/albumin ratio present in the sample. The relationship between the surfactant/ /albumin ratio and the measured fluorescence polarization is established by generating a stan− dard curve.
Results
Tables 2 and 3 show detailed analytical char− acteristics of the LBC and FLM II tests, respec− tively (i.e. within−run and between−run impreci− sion). Between−run imprecision for the LBC test was established for platelets in control blood because there is no possibility of proper amniotic
Table 1.Patients’ clinical characteristics
Tabela 1.Charakterystyka badanej grupy, z uwzględnie− niem danych klinicznych
Parameter Number
(Cecha) of cases
(Liczebność) Maternal age – years:
(Wiek matki – lata)
– 15–20 8
– 21–30 62
– 31–40 30
Gestational age at amniocentesis – week: (Tydzień ciąży podczas amniocentezy)
– 29–32 7
– 33–34 10
– 35–36 25
– 37–42 70
Clinical characteristics: (Charakterystyka kliniczna)
– hypotrophy 35
– oligohydramnios 9
– prolonged pregnancy 9
– polyhydramnios 8
– Rh incompatibility 5
– PIH (pregnancy−induced hypertension) 5
– asthma 3
– Klinefelter’s syndrome 2
– hydrocephalus 2
– fetal esophageal occlusion 2
– hypertension 2
– fetal arrhythmia 2
– epilepsy 1
– hypothyroidism 1
– hyperthyroidism 1
– gestational diabetes 1
imprecision.
Cutoff values for the FLM II test are recom− mended by the test’s producer. For the LBC test they were taken from the literature for this type of hematology analyzer [10]. These values divided the examined population of 112 samples into three groups, as shown in Table 4.
Table 5 shows the dispersion of the results for the FLM II and LBC tests divided into four groups by week of gestation. FLM II is characterized by smaller coefficients of variation in all groups.
The correlation between LBC and FLM II was significant. Both tests showed very good correla− tion with gestational age (GA). The FLM II test presented better correlation with GA than LBC. All correlation coefficients are shown in Table 6.
A correlation study between the fetal lung maturity test results and the clinical condition of the newborns was performed on a group of 44 samples from 44 patients because only women who had delivered within 72 hrs of amniocentesis were included. None of the newborns developed RDS, but five had other respiratory disorders and their relationship with the FLM test results was observed (Table 7).
There was a specific relationship observed when oligohydramnios was present. In 8 of the 9 cases of oligohydramnios, the results of the LBC test were higher than those of FLM II. In 5 cases
showed intermediate or immature. In the cases of polyhydramnios there was no such relationship.
Discussion
Evaluation of the risk of complications involv− ing fetal lung immaturity is a very important part of antenatal diagnostics. The risk always depends on the gestational age and is also connected with many pathological factors that can retard intrauter− ine lung maturation. So far, all tests used in fetal lung maturity assessment are only able to estimate the risk of RDS; they can rather exclude than con− firm the risk of RDS. Gestational age should always be taken into account when interpreting results because there is a possibility of RDS even if the test result is mature at an early gestational age, and there is a low risk of RDS even if the result indicates immaturity in later weeks of gesta− tion. All the tests are better at predicting the likely absence rather than the presence of RDS; thus they have high negative predictive value (usually 95–100%) and low positive predictive value, depending on the test and applied cutoff values (13–60%) [1, 9, 12–15].
None of the known methods has been estab− lished as a reference method so far because they do not met the criteria for a reference method. In
Table 2.Imprecision of the lamellar body count test – LBC [×103/µl] Tabela 2. Nieprecyzyjność pomiaru liczby ciał lamelarnych – LBC [×103/µl]
Within−run imprecision for three different amniotic fluid samples, n = 10 measurements
(Nieprecyzyjność w obrębie serii dla 3 różnych próbek płynu owodniowego, liczba pomiarów n = 10) Sample 1: mean = 14 Sample 2: mean = 76.6 Sample 3: mean = 156
SD = 1.25 SD = 2.27 SD = 3.48
CV = 8.9% CV = 2.9% CV = 2.2%
Between−run imprecision for platelets in control blood sample, mean = 100 ×103/µl, CV < 4% (Nieprecyzyjność między seriami dla płytek we krwi kontrolnej, średnia = 100 ×103/µl, CV < 4%)
Table 3.Imprecision of the FLM II test [mg/g] Tabela 3.Nieprecyzyjność testu FLM II [mg/g]
Within−run imprecision for three different amniotic fluid samples, n = 10 measurements
(Nieprecyzyjność w obrębie serii dla 3 różnych próbek płynu owodniowego, liczba pomiarów n = 10) Sample 1: mean = 20.5 Sample 2: mean = 49.9 Sample 3: mean = 55.1
SD = 0.84 SD = 1.72 SD = 1.30
CV = 4.1% CV = 3.4% CV = 2.4%
Between−run imprecision for three control samples FLM II, n = 30 measurements
(Nieprecyzyjność między seriami dla 3 próbek kontrolnych FLM II, liczba pomiarów n = 30)
Level 25 Level 50 Level 100
Mean = 25.52 Mean = 51.75 Mean = 107.75
SD = 0.88 SD = 2.20 SD = 5.68
spite of this, some specialists consider lecithin/sphingomyelin ratio determination by HPLC (high−pressure liquid chromatography) as a reference method [4, 8].
The choice of a test in a laboratory is based on its cost, availability, turnaround time (TAT), and negative predictive value. The comparison of FLM II and LBC according to these criteria showed LBC to be superior as it is less expensive, has shorter TAT, and is much more available than the FLM II test, which requires a specific analyzer.
There have been many publications that com− pared all available tests, among others the lecithin− to−sphingomyelin ratio (L/S), PG determination, FLM II, and LBC [12–15]. Most studies revealed relatively high diagnostic sensitivity of these tests, but their diagnostic specificity was poor. In spite of the many studies and a great improvement in laboratory diagnostic technology, there is still a problem in interpreting result. The commonly used differentiation of immature, intermediate, and mature results is no longer recommended or
Table 4.Cut−off values for LBC [10] and FLM II (recommended by test producer). The number of results for each group is in parenthesis
Tabela 4.Przyjęte wartości odcinające dla testów LBC [10] i FLM II (zgodnie z zaleceniami producenta testu). W nawia− sach podano uzyskaną liczbę wyników należących do danej grupy
Test Immaturity Intermediate Maturity
(Test) (Niedojrzałość) (Pośrednie) (Dojrzałość)
LBC [×103/µl] ≤15 (20) 16–49 (28) ≥50 (64)
FLM II [mg/g] ≤39 (38) 40–54 (27) ≥55 (47)
Table 5.The dispersion of results of LBC and FLM II divided into four groups by gestational age
Tabela 5.Rozproszenie wyników uzyskanych dla testów LBC i FLM II z podziałem na 4 grupy badane w zależności od tygodnia ciąży
Group FLM II [mg/g] LBC [×103/µl]
(Grupa)
1. 29–34 weeks of gestation: n = 17 (29.–34. tydz. ciąży)
– mean 15.9 27
– SD 16.1 49.2
– min–max 4.6–61.2 0–162
2. 35–36 weeks of gestation: n = 25 (35.–36. tydz. ciąży)
– mean 35.4 42.9
– SD 16.8 36.0
– min–max 7.0–73.7 5–160
3. 37–38 weeks of gestation: n = 35 (37.–38. tydz. ciąży)
– mean 51.4 78.8
– SD 21.6 58.6
– min–max 9.9–111.3 0–303
4. 39–43 weeks of gestation: n = 35 (39.–43. tydz. ciąży)
– mean 86.0 110.1
– SD 27.2 49.0
– min–max 42.8–157.9 26–257
Table 6.Correlation between the tests and between the tests and week of gestation (hbd) (for 112 samples of amniotic fluid) Tabela 6.Korelacja między badanymi testami oraz między testami a tygodniem ciąży (hbd) (dla 112 badanych próbek płynu owodniowego)
FLM II / LBC FLM II / hbd LBC / hbd
Spearman correlation coefficient 0.842 0.773 0.609
functional. According to ACOG guidelines, the risk of RDS should always be evaluated with ref− erence to gestational age [1]. Fetal pulmonary maturity assessment is recommended between 34 and 36 weeks of gestation, when the risk of RDS is 2–14%. More than 50% of immature results after 34 weeks are, in fact, false positive for RDS, and this is the reason for the low diagnostic specificity of most tests. However, before 34 weeks the risk of RDS and other disorders is so high that pulmonary maturity evaluation is meaningless. Many authors even question the legitimacy of per− forming amniocentesis to assess lung maturity before 34 and after 39 weeks of gestation [13, 16–18]. This does not apply to a situation in which fetal hypotrophy is suspected or if it is necessary to confirm a prolonged pregnancy. Fetal lung maturity assessment is most important in pregnancies com− plicated by gestational diabetes, fetal hypotrophy, and other pathologies that may disturb intrauterine growth [1]. In this study, there was very good cor− relation of both tests’ results with gestational age in a high−risk patient population.
The aim of the study was primarily an analy− tical validation and assessment of the usefulness of FLM II and LBC in a high−risk population. LBC precision was worse at lower values (i.e. those indicating immaturity) and was comparable with FLM II’s imprecision at “mature” values. How− ever, the analytical validation of both tests still revealed their high precision and accuracy.
The high correlation between these tests sug− gests that they could possibly have similar diag− nostic significance when appropriate cutoff values are applied. When interpreting results, one must take into account that LBC is recommended pri− marily in a low−risk population and FLM II in a high−risk population and is sometimes consid− ered a reference method [1, 2, 4, 8, 11, 13, 19]. Karcher et al. [13] reported high correlation between LBC and FLM II (r= 0.79, p< 0.001). Own data revealed similar high correlation (r= 0.842, p< 0.0001).
Among other things, this results from the rela− tionship between LBC test results and the amount of amniotic fluid. This study revealed such a con− nection as well. There were 9 cases of oligohy− dramnios in the examined group of patients, in 8 of which the result of the LBC test was higher than that of FLM II, thereby changing the clinical inter− pretation of results from intermediate or even immature to mature in 5 cases. This was probably the effect of the reduction of the amount of amnio− tic fluid which caused its concentration. This may confirm the restricted usefulness of LBC in cases of oligohydramnios observed by other investiga− tors [8]. In the study there was no such connection observed in the cases of polyhydramnios.
In the investigated population, some patholog− ical factors occurred in most cases during gesta− tion that could disturb intrauterine fetus matura− tion. This is probably the reason for the consider− able dispersion of results after the patients were divided into groups by gestational age. The disper− sion was greater with the LBC than the FLM II test and, similarly, the correlation of LBC with gesta− tional age was weaker. Moreover, in 5 cases of identified respiratory disorders, none of the FLM II test results were classified as mature, whereas 3 of the LBC results indicated maturity. This may suggest that LBC results should be considered unreliable when a high−risk patient is examined, but can still be used as screening, especially with gestational diabetes [20].
The results of this study indicate that LBC could be useful for fetal pulmonary maturity eval− uation in a high−risk population on the condition that the clinician is aware of the limitations of its utility. Because of its advantages, such as low price and availability, it should always be used when other tests are unavailable. Furthermore, there is a necessity to increase the number of stud− ies to establish proper cutoff values for specific weeks of gestation and the clinical condition of pregnant women.
Tabela 7.Opis przypadków rozpoznanych zaburzeń oddychania (hbd – tydzień ciąży podczas amniocentezy) Case hbd FLM II [mg/g] LBC [×103/µl] Clinical data
(Przypadek) (Dane kliniczne)
1. 36 12.7 10 fetal esophageal occlusion
2. 36 16.8 10 maternal asthma, fetal bradycardia
3. 36 41.5 50 polyhydramnios, fetal hypotrophy
4. 36 51.6 88 hydrocephalus
References
[1]American College of Obstetricians and Gynecologists: Clinical management guidelines for obstetrician−gynecol− ogists. Fetal lung maturity. Obstet Gynecol 2008, 112, 717–726.
[2] Abd El Aal D, Elkhirshy A, Atwa S, El−Kabsh M:Lamellar body count as a predictor of neonatal lung maturi− ty in high−risk pregnancies. Int J Gynaecol Obstet 2005, 89, 19–25.
[3] Krasomski G, Sałacińska B, Broniarczyk D, Świątkowska E:Prenatalna ocena dojrzałości płuc płodu poprzez oznaczanie stężenia fosfatydyloglicerolu (PG) w płynie owodniowym. Gin Pol 2001, 72, 688–692.
[4] Shrewin J, Lockitch G, Rosenthal P, Ashwood E, Geaghan S, Magee L et al.:National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Maternal−fetal risk assessment and reference values in pregnancy. Washington, DC: AACC Press, 2006.
[5] Towers C, Garite T:Evaluation of the new AmnioStat−FLM test for the detection of phosphatidylglycerol in con− taminated fluids. Am J Obstet Gynecol 1989, 160, 298–303.
[6] Grenache D, Parvin C, Gronowski A:Preanalytical factors that influence the Abbott TDx Fetal Lung Maturity II assay. Clin Chem 2003, 49, 935–939.
[7] Albright T, Colombo D, Euscher E, Samuels P:Evaluation of the effect of meconium on assessment of fetal lung maturity status by TDxFLM II testing. Obstet Gynecol 2004, 104, 952–956.
[8] Ashwood E:Standards of laboratory practice. Evaluation of fetal lung maturity. Clin Chem 1997, 43, 211–214.
[9] Chapman J, Ashwood E, Feld R, Wu A:Evaluation of two−dimensional cytometric lamellar body counts on the ADVIA®120 hematology system for estimation of fetal lung maturation. Clin Chim Acta 2004, 340, 85–92.
[10] Szallasi A, Gronowski A, Eby C:Lamellar body count in amniotic fluid: a comparative study of four different hematology analyzers. Clin Chem 2003, 49, 994–997.
[11] Ghidini A, Poggi S, Spong C, Goodwin K, Vink J, Pezzullo J:Role of lamellar body count for the prediction of neonatal respiratory distress syndrome in non−diabetic pregnant women. Arch Gynecol Obstet 2005, 271, 325–328.
[12] Winn−McMillan T, Karon B:Comparison of the TDx−FLM II and lecithin to sphingomyelin ratio assays in pre− dicting fetal lung maturity. Am J Obstet Gynecol 2005, 193, 778–782.
[13] Karcher R, Sykes E, Batton D, Uddin Z, Ross G, Hockman E, Shade G: Gestational age−specific predicted risk of neonatal respiratory distress syndrome using lamellar body count and surfactant−to−albumin ratio in amni− otic fluid. Am J Obstet Gynecol 2005, 193, 1680–1684.
[14] Wijnberger L, Kleine M, Voorbij H, Arabin B, van de Leur J, Bruinse H, Visser G, Bossuyt P, Mol W:The effect of clinical characteristics on the lecithin/sphingomyelin ratio and lamellar body count: a cross−sectional study. J Matern Fetal Neonatal Med 2003, 14, 373–382.
[15] Neerhof M, Haney E, Silver R, Ashwood E, Lee I, Piazze J:Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity. Obstet Gynecol 2001, 97, 305–309.
[16] Parvin C, Kaplan L, Chapman J, McManamon T, Gronowski A:Predicting respiratory distress syndrome using gestational age and fetal lung maturity by fluorescent polarization. Am J Obstet Gynecol 2005, 192, 199–207.
[17] Luo G, Norwitz E: Revisiting amniocentesis for fetal lung maturity after 36 weeks’ gestation. Rev Obstet Gynecol 2008, 1, 61–68.
[18] Richardson D, Heffner L: Fetal−lung maturity: Tests mature, interpretation not. Lancet 2001, 358, 684–686.
[19] Fantz C, Powell C, Karon B, Parvin C, Hankins K, Dayal M, Sadovsky Y, Johari V, Apple F, Gronowski A:
Assessment of the diagnostic accuracy of the TDx−FLM II to predict fetal lung maturity. Clin Chem 2002, 48, 761–765.
[20] DeRoche M, Ingardia C, Guerette P, Wu A, LaSala C, Mandavilli S:The use of lamellar body counts to pre− dict fetal lung maturity in pregnancies complicated by diabetes mellitus. Am J Obstet Gynecol 2002, 187, 908–912.
Address for correspondence:
Agnieszka Sapa
Department of Medical Laboratory Diagnostics Wroclaw Medical University
Pasteura 2 50−367 Wrocław Poland
Tel. +48 71 784 12 08
E−mail: [email protected] Conflict of interest: None declared Received: 6.04.2009
