European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 177–183

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European Journal of Obstetrics & Gynecology and
Reproductive Biology
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Lecithin/sphingomyelin ratio and lamellar body count for fetal lung maturity:
a meta-analysis
Anouk E. Besnard a, Soetinah A.M. Wirjosoekarto b,*, Kimiko A. Broeze c, Brent C. Opmeer d,
Ben Willem J. Mol c
Faculty of Medicine, University of Amsterdam, Amsterdam, The Netherlands
Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, The Netherlands
Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands
Clinical Research Unit, Academic Medical Centre, Amsterdam, The Netherlands


Article history: Objective: To determine and compare the diagnostic accuracy of the lecithin/sphingomyelin (L/S) ratio
Received 14 September 2012 and lamellar body count (LBC) in the prediction of neonatal respiratory distress syndrome (RDS).
Received in revised form 23 January 2013 Study design: A systematic review was performed to identify studies comparing either the L/S ratio or the
Accepted 9 February 2013
LBC with the occurrence of RDS published between January 1999 and February 2009. Two independent
reviewers performed study selection and data extraction. For each study sensitivity and specificity were
Keywords: calculated. Summary receiver-operating characteristics (ROC) curves, assessing the diagnostic
Fetal lung maturity
performance of both tests, were constructed. A subgroup analysis was performed to estimate the
Lamellar body count
Lecithin/sphingomyelin ratio
sensitivity and specificity of the various cut-off values.
Neonatal respiratory distress syndrome Results: 13 studies were included. The ROC curves of the collected data illustrate that the LBC and L/S
ratio perform equally well in the prediction of RDS. Comparison of the two summary ROC curves of each
test indicates that the diagnostic performance of LBC might even have a slight advantage over L/S ratio.
Due to the wide cut-off range it was not possible to define specific cut-off values with the best accuracy.
Conclusion: We recommend replacing the L/S ratio as gold standard with the lamellar body count since
the LBC is easy to perform, rapid, inexpensive, and available to all hospitals 24 h per day.
ß 2013 Elsevier Ireland Ltd. All rights reserved.

1. Introduction strategy in favor of fetal lung maturation is still considered safe,
but which may eventually require preterm delivery [4].
Respiratory distress syndrome (RDS) is a major cause of Measurement of the lecithin/sphingomyelin (L/S) ratio in
neonatal morbidity and mortality, affecting approximately 1% of amniotic fluid by thin-layer chromatography for the prenatal
all live births and 10% of all preterm infants [1]. It is caused by prediction of FLM was first introduced in 1971 by Gluck et al. From
insufficient production of surfactant by type II pneumocytes, along 30 weeks of gestation onwards, the concentration of lecithin
with structural immaturity of the lung. The risk and severity rise begins to increase significantly, while the sphingomyelin concen-
with increasing prematurity, and infants born before 29 weeks of tration remains approximately the same. The L/S ratio has
gestation have a 60% chance of developing RDS [2]. remained the gold standard of FLM testing in the neonate, with
RDS may be prevented with antenatal steroid therapy and 2.0 as a commonly accepted cut-off value, above which the risk for
prophylactic (early) administration of exogenous surfactant [3]. In RDS is low, and which will normally be reached at a gestational age
management strategies to limit the risk of RDS, the assessment of of 35 weeks [5].
fetal lung maturity (FLM) in amniotic fluid can assist in The L/S ratio is a technically difficult test that requires trained
determining the timing of delivery, particularly in pregnancies personal to interpret. It is time-consuming, costly, prone to
with maternal and/or fetal complications for which a temporizing subjective interpretation, not universally available nor available
around the clock, and it cannot be determined in fluids
contaminated by blood or meconium.
The lamellar body count (LBC) has been proposed as a potential
* Corresponding author at: Department of Obstetrics and Gynecology, Maastricht
University Medical Centre, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
replacement of the L/S ratio. Lamellar bodies represent a storage
E-mail address: (Soetinah A.M. Wirjosoekarto). form of pulmonary surfactant within type II pneumocytes,

0301-2115/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved.

description of tests and study hospitals 24 h per day. verification. and three articles reported on the vaginal or both). this point itself is clinically not very informative. ratio and LBC as well as the used cut-off values were reported. inexpensive FLM test which is available to all on 15 items on selection. Thirteen articles were multiple pregnancies. point on the curve. In addition. whereas specificity was defined as neonatal treatment of infants at low gestational age. A pooled estimate for sensitivity and specificity was estimated with bivariate regression analysis. when a study reports sensitivity and specificity for title and abstract. the way amniotic fluid was collected (abdominal. as described by Dubin [6]. which also L/S ratio or lamellar body count or LBC and respiratory distress accommodates the inverse association between sensitivity and syndrome or RDS or hyaline membrane disease or HMD. This makes the LBC an easy-to. bias due to flawed design. inclusion eligible. In order to evaluate accuracy measures final selection was made by using pre-defined inclusion and over the whole range of reported cut-off values including all exclusion criteria. the statistical procedure to estimate the bivariate checked for additional eligible articles.2. results are based on averaged Subsequently. one reported solely on the predictive of women with ruptured membranes and use of corticosteroids. heterogeneity in sensitivity and courses. which permits the use of widely We assessed the methodological quality of the included studies available cell counters to quantify the lamellar bodies in amniotic using the QUADAS checklist. The hypothesis that 2. All accuracy estimates from different studies in terms of sensitivity and specificity were plotted in receiver-operating 2. The bivariate regression model simultaneously estimates February 2009. Literature search and study selection characteristics (ROC) space. the laboratory methods used to determine the L/S The characteristics of the included studies are listed in Table 1. and management of antenatal L/S ratio and LBC in the prediction of RDS. the time interval between amniocentesis and predictive capacity of both tests [28–30]. the prevalence of RDS was meta-analysis of Wijnberger et al. nine reported solely on the predictive Moreover. Data extraction The sROC curve corresponding with the estimated model. Data extraction radiological criteria and/or criteria for oxygen therapy) were scored. country of investigation. information was gathered on the following patient The literature search in Medline and Embase yielded 144 characteristics. was tested in the For each individual study. but data from the most calculated. Previous studies have suggested using the LBC as an initial assessment prior to the use of L/S ratio [7–13]. the accuracy of the LBC and the L/S ratio in the prediction of RDS. Of these articles. such as immaturity of the fetal lungs. but as it does not reflect the accuracy for a particular cut-off.g. language of publication. If the reported data were sufficient to construct a specificity) due to different cut-off values is accounted for by the two-by-two table of the test result (LBC and L/S ratio) the study correlation term. a tool for quality assessment of fluid. the sROC point reflects the average operating were excluded. thus 2. All studies were designed as cohort studies. (4) blinding for the test results when RDS was diagnosed and (5) 3. Results analysis [14]: (1) sampling. In the last decade there have as the proportion newborns with RDS in which the test predicted been changes in clinical management to optimize care. capacity of the LBC [19–27]. was included. (3) study design. Literature search and study selection verification bias [15]. namely the L/S ratio. inclusion of articles. Methods specificity. When in doubt. The size of lamellar bodies is similar to platelets. each of the included studies was scored on the model estimates from stratified bootstrap samples. delivery. Keywords used were lecithin/sphingomyelin ratio or sensitivity and specificity within a single model. The random-effects approach estimates and incorporates the amount of between-study variability in both sensitivity and 2. The different cut-off values. whether samples contaminated with blood or meconium were excluded. citations were detected and removed. we did not limit our analysis to a single cut-off value. e.g.178 A. different clinical subgroups. Besnard et al. of which 46 were read in full text. We pregnant women at risk for preterm delivery in whom the FLM was estimated accuracy measures for all reported cut-off values by tested by either the LBC or the L/S ratio. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 177–183 secretion of which increases with advancing gestational age. except one which was . treatment the proportion newborns without RDS in which the test predicted with antenatal corticosteroids. Secondly. e.1. Duplicate specificity due to threshold effects. capacity of the L/S ratio [18]. Cross-references were At present. Included studies were assessed perform. as well as the sensitivity and specificity of both the recent studies were not included. and changes in the diagnostic criteria for RDS. inclusion of diabetic pregnancies. the whole article was read. author. we performed an updated meta-analysis. Sensitivity was defined and neonatal care keeps developing. Two reviewers (KAB and model cannot accommodate multiple data points from the same AEB) independently screened all identified studies by reading the study. total In order to avoid the results being biased toward studies number of included patients and patients with analyzable data. rapid.E. Statistical analysis LBC is an equal or possibly better predictor for the occurrence of RDS than the gold standard. as specified in the bivariate model. diagnostic accuracy studies [16]. reporting data for multiple cut-offs. 3. single dose versus multiple mature fetal lungs. following design characteristics concurrent to the previous meta- 3. could possibly influence the outcome of the performance of the LBC Variation or heterogeneity of the results of the studies included in and L/S ratio. Finally. Study quality enabling prediction of the degree of FLM. Articles published in a language other than English Consequently. comparing the meta-analysis can be the result of differences in cut-off values.3. population. 2. minimal and maximal gestational age. however. [14]. Since these specificity between studies was explored using scatter plots. reflects the change in accuracy (sensitivity and specificity) We extracted the following data: year of publication. and how RDS was defined (clinical criteria. Studies were included if they reported on studies. first associated with a shift in positivity threshold.1. and A systematic literature search was performed in Medline and the corresponding summary ROC (sROC) curve was constructed Embase to identify articles published between January 1999 and [17]. The outcome had to be RDS assuming that the shift in accuracy (higher sensitivity and lower in the neonate. or chance.2. (2) data collection.4.

24. No No No No No No No No No No No No No To provide further information on the different cut-off values. radiological Clinical. The number of patients Clinical.28–30]. whereas the specifici- Consecutive ty varied between 60% and 100%. one study explicitly excluded women with diabetic pregnancies [23]. we combined the Roiz Hernandez (2002) studies reporting on both LBC and L/S ratio in the same population Khazardoost (2005) Abd El Aal (2005) with the studies in Wijnberger’s meta-analysis [7–12. and the clinical diagnosis of RDS as the reference test. .28–30].22.4. the prevalence of RDS and sensitivity and specificity for each individual study series are summarized in Tables 3 and 4. and two studies explicitly excluded women with multiple pregnancies [24. the sensitivity varied between 73% and 99%. 1 Yes No No No No No No No No No No No No illustrates all reported cut-off values for the L/S ratio and Blinding LBC with their corresponding sensitivity and specificity in a scatter plot.23.5.26. and for the LBC between 6000 and 79. For both tests. Most studies included a diverse group of pregnant women at risk for preterm Definition RDS and therapy and therapy and therapy and therapy and therapy and therapy and therapy delivery. radiological Clinical.29]. 2 and 3 show all the cut-off values with their corresponding sensitivity and specificity as well as summary Table 1 ROC curves for the L/S ratio and LBC respectively of this subgroup analysis.whichwascentrifuged priortothedeterminationintwostudies[28.22. resistive-pulse counting of lamellar Yes Yes Yes Yes Yes Yes Yes Yes Yes No No No No bodies with the platelet channel of a standard hematology cell counter was used in all studies. A. Statistical analysis pregnancies Unknown Unknown Unknown Unknown Unknown The prevalence of RDS varied between 6% and 32%. Fig. To assess the LBC.29]. radiological Clinical. radiological Clinical. Seven studies described more than one Abdominal/vaginal Abdominal/vaginal Abdominal/vaginal cut-off value to indicate pulmonary maturity [18– 20.3. In four studies women were treated with corticosteroids [18. data were found insufficient to execute a Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes subgroup analysis and directly compare the two most frequently Winn MacMillan (2005) used cut-off values of 2. Study quality Unknown Unknown Unknown Unknown Unknown Excluded Included Included Included Included Included Included Included PPROM Table 2 shows the quality assessment with the adjusted QUADAS tool.25. The Prospective sensitivity is 94% (95% CI 18–100%) and the specificity is Key characteristics of the included studies. 88%) with a specificity of 90% (95% CI 70–97%).000/mL to 57.25. at a range of cut-off values from bias Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 15. LBC and L/S ratio were both considered as index tests. For all studies.29].thecut-offvaluesvariedbetween Abdominal Abdominal Abdominal Abdominal Unknown Adominal 2.27. one explicitly excluded women with Therapy Therapy criteria premature rupture of the membranes [19].30]. radiological Clinical.22. Besnard et al. radiological Clinical.Fortheremaining two studies. For the LBC. the sensitivity varied between 62% and 100%. Due to the small number of studies reporting on the L/S ratio in Cohort Partly study this meta-analysis. However.whereasthe Amniotic fluid sampling other eight studies used centrifuged amniotic fluid samples [19.000 lamellar bodies per micro liter. radiological Clinical.5. Four studies assessed the LBC in Abdominal/vaginal/cesarean Abdominal/vaginal/cesarean Abdominal/vaginal/cesarean Abdominal/vaginal/cesarean uncentrifugedamnioticfluidspecimen[20. 3. whereas the specificity varied between 64% and 89%.E. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 177–183 179 a prospective clinical trial. 75% (95% CI 13–99%) when exploiting a range of cut-off Yes No No No No No No No No No No No No values from 45.000/ mL to 25. The presence of verification bias could Radiological and therapy Diagnosed by standard not be excluded in any of the studies. radiological Clinical.000/mL. Study (year) Figs. radiological included in each study varied between 73 and 833.30]. a subgroup analysis was performed to evaluate the Verification sensitivity and specificity within a specific range of cut-off values. The Bahasadri (2005) Haymond (2006) Chapman (2004) Piazze 1 (1999) Piazze 2 (2005) Beinlich (1999) Neerhof (2001) Karcher (2005) Ghidini (2005) results are shown in Table 5. it was unclear whether the specimen was centrifuged samples [18.000/mL. Therefore. respectively. For the L/ Excluded Included Included Included Included Included Included Included Diabetic S ratio.FortheL/Sratio.27]. the sensitivity is 76% (95% CI 57– PPROM = preterm premature rupture of membranes. The minimum gestational age varied between 22 and 33 weeks. Included Included Included Included Multiple 3.0 and 2. None of pregnancies Unknown Unknown Unknown Unknown Unknown Unknown Unknown Excluded Excluded the studies met all criteria. For the LBC. thin layer chromatography was used to meconium stained Exclusion blood/ determinetheL/Sratiointheamnioticfluid.0 and 2.21. sampling – Unknown Unknown Unknown whereas the maximum gestational age varied between 37 and 42 <7 days delivery Interval <72 h <72 h <72 h <48 h <24 h <72 h <72 h <48 h <72 h weeks.24.

E. A. 180 Table 2 Study quality per study of the 13 included studies assessed with the QUADAS checklist. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 177–183 Abd Bahasadri Beinlich Chapman Ghidini Haymond Karcher Khazardoost Neerhof Piazze 1 Piazze 2 Roiz Hernandez Winn El Aal (2005) (1999) (2004) (2005) (2006) (2005) (2005) (2001) (1999) (2005) (2002) MacMillan (2005) (2005) Patients representative Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes of practice Clear description Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes selection criteria Reference standard Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Unclear Yes Unclear likely to detect RDS Time between test and Yes Unclear Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes reference standard short enough Complete verification Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Consistent reference Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes standard Index test and reference Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes standard performed independently Clear description of Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes index test Clear description of Yes Yes Yes Yes Yes Unclear Yes Yes Yes Yes Unclear Yes Unclear reference standard Results index tests Yes Yes Yes No No Yes Unclear No Yes Unclear Unclear Yes Yes interpreted independent of results reference standard Results reference standard Unclear Unclear Unclear Unclear Unclear Unclear Unclear Unclear Unclear Unclear Unclear Yes Unclear interpreted independent of results index tests Clinical data same as Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes practice Uninterpretable data No No No No No Yes No No No No No No No reported Withdrawals explained Yes Yes Yes Yes Yes Yes No Yes Yes No Yes No Yes Intervention between No Unclear Unclear Yes Unclear No Unclear Yes Yes Unclear Unclear Unclear Unclear index test and <!——!>reference standard . Besnard et al.

FP = false positive. If a study reported on multiple cut-off values.000 44 17 21 96 0.94 0.60 Karcher (2005) 219 1 30. correlates with a higher sensitivity.95 0. By obtaining more data around several specific cut-off values with a small range.0 8 0 14 74 0.e.89 Neerhof (2001) 833 1 N/A 82 18 174 559 0.07 0. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 177–183 181 Table 3 Performance of the L/S ratio in the prediction of RDS. range 15.000 5 1 5 10 0.000–57.00 0.08 1.06 0.5 8 5 20 168 0. Since a small number of articles were found between 1999 and 2009. A limitation of this meta-analysis is the clinical heterogeneity. By solely analyzing studies with identical cut-off values.06 0.000 11 1 69 103 0.62 0.000– 25. we were unable to determine the cut-off value with the best accuracy. Discussion The overall results of this meta-analysis are concurrent with the meta-analysis in 2001 [14].15 0. i.22 0.75 Khazardoost (2005) 80 1 50.000. If a study reported on multiple cut-off values. Receiver-operating characteristics (ROC) of studies comparing lamellar body this analysis would cause loss of data points or may even exclude count and L/S ratio in their capacity to predict the occurrence of respiratory distress complete studies if they did not report for that cut-off value. only one is shown. this meta-analysis was obliged to compare both tests in studies with different study designs.89 0. sens = sensitivity.93 0. (p = 0.78 1.88 Ghidini (2005) 102 1 37.64 Winn-McMillan I (2005) 109 2 2. range 45.0 9 0 20 80 0.82 Roiz-Hernandez (2002) 264 3 57. The sROC curves of Fig. only one is shown.3 79.000 18 1 20 53 0.12 0. FN = false negative.7 0.74 0. which can subsequently be recommended for the clinical practice.29 0. comparing the L/S ratio and the LBC.E.08 1. Study (year) Number Number of Cut-off value RDS No RDS Prevalence of RDS Prediction of of patients cut-off values RDS TP FN FP TN Sens Spec Abd El Aal (2005) 73 4 18.18 0. The syndrome.12 0. FN = false negative.67 Chapman (2004) 88 6 25.76 Piazze (1999) 92 1 2. clinical characteristics and differences in reported cut-off values.16 0.000 18 5 0 50 0. analyzed six studies This meta-analysis demonstrates that the LBC is a good [7–12].80 Winn-McMillan II (2005) 96 1 2.32 0. 1. correlates with a high specificity.70 Neerhof (2001) 833 2 N/A 89 11 266 467 0. whereas a low cut-off value.000 36 3 65 160 0. A.82 0.92 0. As a result of the wide range of cut-off values described in the different studies.64 Haymond (2006) 184 2 50. TN = true negative. of the included studies. sens = sensitivity.71 TP = true positive. having an accuracy similar to the L/S ratio. Summary ROC curves are also given.000 16 1 31 54 0. One of the advantages of the current meta-analysis is that it provides information on the different cut-off values. spec = specificity.13). whereas the subgroup analysis calculates the accuracy of a certain cut-off value. statistical heterogeneity is taken into account by using a random .000 17 3 18 42 0.000 22. study population. as well as the statistical heterogeneity. but Fig. spec = specificity.84 TP = true positive.73 0.000 11 2 51 155 0. i.e. FP = false positive.85 0.64 Piazze I (1999) 92 1 20. the best cut-off for clinical application can eventually be derived.83 0. The subgroup analysis for the LBC showed that a high cut-off value. the heterogeneity concerning the cut-off values might be reduced. clinical characteristics and cut-off values.00 Bahasadri (2005) 104 2 45.73 Piazze II (2005) 178 1 22.34 0.000 13 1 9 65 0. and concluded that the LBC performs slightly better than the L/S ratio by comparing the ROC curves it perhaps performs slightly better. TN = true negative. Study (year) Number of patients Number of cut-off values Cut-off value RDS No RDS Prevalence of RDS Prediction of RDS TP FN FP TN Sens Spec Karcher (2005) 201 1 2. variation in results.000.3 1.92 0.25 0.17 0. Table 4 Performance of the LBC ratio in the prediction of RDS.5 14 5 26 47 0. and similarly diagnostic test. 4. Wijnberger et al. Therefore.21 0.7 0.98 Beinlich (1999) 21 1 30.00 0. Besnard et al.85 0. this analysis could not be limited to studies directly comparing the LBC and L/S ratio in the same population. 1 give a general outline on the overall accuracy combining the sensitivity and specificity points of different cut-off values.99 0.

000 0.80 0. meconium or infection or diabetic status of the heterogeneity could have influenced the results comparing both mother. an individual patient data meta-analysis should be used in the effect of the amount of amniotic fluid on LBC performance [31– which the data of all the individual patients.84 0. the presence of blood. Besnard et al. In conclusion.37–0.95 0.89 2. Nevertheless. Cut-off value Sensitivity 95% CI Specificity 95% CI LBC 5000–10.92 0.99 0.28–30].95 0. If publication bias is present.000–55.68–0. In the search for an delivery incorrectly.78 0.82 0. Since therefore possible that a certain value of LBC or L/S ratio indicates the LBC is easy to perform.97 2.182 A.60–0. performance compared to the L/S ratio.000 0.000 0. the ideal diagnostic test for FLM should have a high articles reported on the performance of the LBC versus four that sensitivity and a high negative (mature) predictive value. capacity to predict the occurrence of respiratory distress syndrome [7–12.79–0.E. but fewer studies have reported on this effect on LBC. e. inexpensive.66–0. we suggest that it should replace the L/S to this problem lies in adjusting the cut-off value according to ratio in the assessment of FLM.97 0.99 0.8–2. Publication of only those negative consequences for child and mother. It is also possible that the test performance is influenced by clinical factors.65 0.99 20. a random cut-off value was chosen good measure to predict the occurrence of RDS.e. Consequent- Another problem in this meta-analysis is that 12 of the detected ly. Previous studies show that increased gestational age has a positive effect on the performance of both L/S ratio and Conflict of interest LBC.82–0.92–1.77–0.86 0.91 50. if irrespective of clinical parameters. Future research should focus on these clinical factors and tests on accuracy.75–0.88 0.6 0. 2.73 0. This reported on the L/S ratio.70 L/S ratio 1.92 0. 3.89 Fig. effects model that estimates the amount of between-study such as fetal growth. . The authors declare that they have no conflict of interest. As stated before.93–0.2–2. in the presence of FLM. Receiver-operating characteristics (ROC) of studies comparing lamellar body Fig. and available to all FLM at one gestational age. A solution hospitals 24 h per day.83 0. but it has limitations.0 0.65–0. especially studies. the L/S ratio is currently also implies a high number of false positives. Delaying the the gold standard. characteristics and the associated results are explored. i.60–0.0 0. in cases of papers that report positive or topical results leads to publication pre-eclampsia. the accuracy of the LBC reported RDS are probably limited.95 30.73–0. the LBC is a promising option.99 0. with an equal. the total amount of amniotic fluid. This way In clinical practice.65–0. / European Journal of Obstetrics & Gynecology and Reproductive Biology 169 (2013) 177–183 Table 5 Sensitivity and specificity of the different cut-off values in studies comparing LBC and L/S ratio in the same population [7–12.59 0. in this meta-analysis was most likely overestimated. immature lungs and the associated complications.28–30].7–3. but immaturity at another. the detailed patient 33]. the variability in both sensitivity and specificity. gestational age. It is not slightly better.00 0. Receiver-operating characteristics (ROC) of studies comparing lamellar body count and L/S ratio in the same population per cut-off value of LBC in their capacity count and L/S ratio in the same population per cut-off value of L/S ratio in their to predict the occurrence of respiratory distress syndrome [7–12. but in the majority of cases the consequences of bias. such as gestational age.96 0.g.82 0.000 0. this meta-analysis illustrates that the LBC is a In all the mentioned studies. rapid. To reduce the heterogeneity of the included determine their effect on the performance of both tests.28–30]. can have alternative. it is important to predict the presence of the possible interactions between patient factors and accuracy can RDS accurately in order to prevent infants being born with be evaluated.

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