Assessment of fetal lung maturity
- Jonathan Gillen-Goldstein, MD
Jonathan Gillen-Goldstein, MD
- Director of Prenatal Diagnosis and Therapy
- for Madonna Perinatal Associates
- Mineola, NY
- Andrew P MacKenzie, MD
Andrew P MacKenzie, MD
- Assistant Professor of Obstetrics and Gynecology
- University of Connecticut
- Director of Maternal Fetal Medicine
- St Francis Hospital and Medical Center
- Edmund F Funai, MD
Edmund F Funai, MD
- Professor and Chief Operating Officer
- USF Health
The pulmonary system is among the last of the fetal organ systems to mature, both functionally and structurally. Fetal sex and race/ethnicity appear to play a role in this process; respiratory problems near term are more common among white male fetuses than among female fetuses, blacks, and South Asians [1,2].
Because the immature pulmonary system may not oxygenate the neonate adequately, preterm birth can lead to significant neonatal morbidity or mortality. Therefore, fetal lung maturity is sometimes assessed before iatrogenic preterm delivery and can be a factor in determining the timing of delivery in these cases. Several laboratory tests are available for this purpose. All involve testing amniotic fluid and provide an indirect assessment of the likelihood of lung maturity; direct studies of fetal lung function are not possible.
This topic will discuss tests for assessment of fetal lung maturity. Clinical manifestations, diagnosis, treatment, sequelae, and prevention of neonatal pulmonary immaturity are reviewed separately. (See "Pathophysiology and clinical manifestations of respiratory distress syndrome in the newborn" and "Prevention and treatment of respiratory distress syndrome in preterm infants" and "Antenatal corticosteroid therapy for reduction of neonatal morbidity and mortality from preterm delivery".)
WHEN IS FETAL LUNG MATURITY TESTING PERFORMED?
A test for fetal lung maturity is performed before semielective but medically indicated births <39 weeks when this information significantly impacts assessment of the balance between the maternal-fetal risks of continuing the pregnancy versus the maternal-fetal risks of preterm birth. This is a rare occurrence. In most clinical settings, the test is omitted because (1) delaying delivery because of lung immaturity would place the mother or fetus at significant risk, or (2) the fetus would benefit from delaying delivery, even if lung maturity is documented, and delaying delivery does not place the mother at significant risk .
Tests for fetal lung maturity are generally not performed before 32 weeks of gestation, given the high prevalence of fetal pulmonary immaturity and the lower predictive value of a mature test result at this gestational age.
- Balchin I, Whittaker JC, Lamont RF, Steer PJ. Timing of planned cesarean delivery by racial group. Obstet Gynecol 2008; 111:659.
- Anadkat JS, Kuzniewicz MW, Chaudhari BP, et al. Increased risk for respiratory distress among white, male, late preterm and term infants. J Perinatol 2012; 32:780.
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 97: Fetal lung maturity. Obstet Gynecol 2008; 112:717.
- Bates E, Rouse DJ, Mann ML, et al. Neonatal outcomes after demonstrated fetal lung maturity before 39 weeks of gestation. Obstet Gynecol 2010; 116:1288.
- ACOG Committee on Practice Bulletins -- Obstetrics. ACOG Practice Bulletin No. 107: Induction of labor. Obstet Gynecol 2009; 114:386.
- Neerhof MG, Haney EI, Silver RK, et al. Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity. Obstet Gynecol 2001; 97:305.
- Winn-McMillan T, Karon BS. Comparison of the TDx-FLM II and lecithin to sphingomyelin ratio assays in predicting fetal lung maturity. Am J Obstet Gynecol 2005; 193:778.
- Haymond S, Luzzi VI, Parvin CA, Gronowski AM. A direct comparison between lamellar body counts and fluorescent polarization methods for predicting respiratory distress syndrome. Am J Clin Pathol 2006; 126:894.
- Karcher R, Sykes E, Batton D, et al. Gestational age-specific predicted risk of neonatal respiratory distress syndrome using lamellar body count and surfactant-to-albumin ratio in amniotic fluid. Am J Obstet Gynecol 2005; 193:1680.
- Neerhof MG, Dohnal JC, Ashwood ER, et al. Lamellar body counts: a consensus on protocol. Obstet Gynecol 2001; 97:318.
- Ventolini G, Neiger R, Hood DL, Belcastro MR. Changes in the threshold of fetal lung maturity testing and neonatal outcome of infants delivered electively before 39 weeks gestation: implications and cost-effectiveness. J Perinatol 2006; 26:264.
- Khazardoost S, Yahyazadeh H, Borna S, et al. Amniotic fluid lamellar body count and its sensitivity and specificity in evaluating of fetal lung maturity. J Obstet Gynaecol 2005; 25:257.
- Dalence CR, Bowie LJ, Dohnal JC, et al. Amniotic fluid lamellar body count: a rapid and reliable fetal lung maturity test. Obstet Gynecol 1995; 86:235.
- Ghidini A, Poggi SH, Spong CY, et al. Role of lamellar body count for the prediction of neonatal respiratory distress syndrome in non-diabetic pregnant women. Arch Gynecol Obstet 2005; 271:325.
- Janicki MB, Dries LM, Egan JF, Zelop CM. Determining a cutoff for fetal lung maturity with lamellar body count testing. J Matern Fetal Neonatal Med 2009; 22:419.
- Zhao Q, Zhao Z, Leung-Pineda V, et al. Predicting respiratory distress syndrome using gestational age and lamellar body count. Clin Biochem 2013; 46:1228.
- Wijnberger LD, Huisjes AJ, Voorbij HA, et al. The accuracy of lamellar body count and lecithin/sphingomyelin ratio in the prediction of neonatal respiratory distress syndrome: a meta-analysis. BJOG 2001; 108:583.
- http://clsi.org/blog/2011/12/07/clsi-publishes-new-guideline-assessment-of-fetal-lung-maturity-by-the-lamellar-body-count-c58-a/ (Accessed on December 08, 2014).
- Gluck L, Kulovich MV, Borer RC Jr, et al. Diagnosis of the respiratory distress syndrome by amniocentesis. Am J Obstet Gynecol 1971; 109:440.
- Ashwood ER. Standards of laboratory practice: evaluation of fetal lung maturity. National Academy of Clinical Biochemistry. Clin Chem 1997; 43:211.
- Whitsett JA, Pryhuber GS, Rice WR. Acute respiratory disorders. In: Neonatology pathophysiology and the management of the newborn, Avery GB, Fletcher MA, MacDonald MG (Eds), JB Lippincott, Philadelphia 1994. p.429.
- Gluck L, Kulovich MV, Borer RC Jr, Keidel WN. The interpretation and significance of the lecithin-sphingomyelin ratio in amniotic fluid. Am J Obstet Gynecol 1974; 120:142.
- Hallman M, Kulovich M, Kirkpatrick E, et al. Phosphatidylinositol and phosphatidylglycerol in amniotic fluid: indices of lung maturity. Am J Obstet Gynecol 1976; 125:613.
- Coapman-Hankin RA, Kiechle FL, Epstein E, et al. Three methods compared for determining phosphatidylglycerol in amniotic fluid. Clin Chem 1985; 31:1374.
- Halvorsen PR, Gross TL. Laboratory and clinical evaluation of a rapid slide agglutination test for phosphatidylglycerol. Am J Obstet Gynecol 1985; 151:1061.
- Eisenbrey AB, Epstein E, Zak B, et al. Phosphatidylglycerol in amniotic fluid. Comparison of an "ultrasensitive" immunologic assay with TLC and enzymatic assay. Am J Clin Pathol 1989; 91:293.
- Lockitch G, Wittmann BK, Mura SM, Hawkley LC. Evaluation of the Amniostat-FLM assay for assessment of fetal lung maturity. Clin Chem 1984; 30:1233.
- Knight JA, Miya T, Wu JT. Standard lecithin/sphingomyelin and phosphatidylglycerol techniques compared with immunologic slide test. Obstet Gynecol 1985; 65:840.
- Bernstein LH, Stiller R, Menzies C, et al. Amniotic fluid polarization of fluorescence and lecithin/sphingomyelin ratio decision criteria assessed. Yale J Biol Med 1995; 68:101.
- Standards of Laboratory Practice: Guidelines for the Evaluation and Management of the Newborn. National Acadamy of Clinical Biochemisry, 1998.
- Kesselman EJ, Figueroa R, Garry D, Maulik D. The usefulness of the TDx/TDxFLx fetal lung maturity II assay in the initial evaluation of fetal lung maturity. Am J Obstet Gynecol 2003; 188:1220.
- Hagen E, Link JC, Arias F. A comparison of the accuracy of the TDx-FLM assay, lecithin-sphingomyelin ratio, and phosphatidylglycerol in the prediction of neonatal respiratory distress syndrome. Obstet Gynecol 1993; 82:1004.
- Dubin SB. The laboratory assessment of fetal lung maturity. Am J Clin Pathol 1992; 97:836.
- Clements JA, Platzker AC, Tierney DF, et al. Assessment of the risk of the respiratory-distress syndrome by a rapid test for surfactant in amniotic fluid. N Engl J Med 1972; 286:1077.
- Sher G, Statland BE, Freer DE, Kraybill EN. Assessing fetal lung maturation by the foam stability index test. Obstet Gynecol 1978; 52:673.
- Jobe AH. Fetal lung development, tests for maturation, induction of maturation and treatment. In: Maternal-Fetal Medicine, Creasy RK, Resnik R (Eds), WB Saunders, Philadelphia 1999. p.418.
- Parvin CA, Kaplan LA, Chapman JF, et al. Predicting respiratory distress syndrome using gestational age and fetal lung maturity by fluorescent polarization. Am J Obstet Gynecol 2005; 192:199.
- Kaplan LA, Chapman JF, Bock JL, et al. Prediction of respiratory distress syndrome using the Abbott FLM-II amniotic fluid assay. Clin Chim Acta 2002; 326:61.
- Kamath BD, Marcotte MP, DeFranco EA. Neonatal morbidity after documented fetal lung maturity in late preterm and early term infants. Am J Obstet Gynecol 2011; 204:518.e1.
- Carlan SJ, Gearity D, O'Brien WF. The effect of maternal blood contamination on the TDx-FLM II assay. Am J Perinatol 1997; 14:491.
- Albright TS, Colombo DF, 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.
- Wong SS, Schenkel O, Qutishat A. Strategic utilization of fetal lung maturity tests. Scand J Clin Lab Invest 1996; 56:525.
- Srouji SS, Carr DB, Gardella CM, et al. The effect of common clinical contaminants on amniotic fluid fluorescence polarization results. Obstet Gynecol 2004; 104:1237.
- Grenache DG, Parvin CA, Gronowski AM. Preanalytical factors that influence the Abbott TDx Fetal Lung Maturity II assay. Clin Chem 2003; 49:935.
- Spillman T, Cotton DB. Current perspectives in assessment of fetal pulmonary surfactant status with amniotic fluid. Crit Rev Clin Lab Sci 1989; 27:341.
- Jobe AH. Fetal lung development, tests for maturation, induction of maturation and treatment. In: Maternal-Fetal Medicine, Creasy RK, Resnik R (Eds), WB Saunders, Philadelphia 1999. p.417.
- Piazze JJ, Maranghi L, Cosmi EV, Anceschi MM. The effect of polyhydramnios and oligohydramnios on fetal lung maturity indexes. Am J Perinatol 1998; 15:249.
- Wijnberger LD, de Kleine M, Voorbij HA, et al. 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.
- Dombroski RA, MacKenna J, Brame RG. Comparison of amniotic fluid lung maturity profiles in paired vaginal and amniocentesis specimens. Am J Obstet Gynecol 1981; 140:461.
- Lambers DS, Brady K, Leist PA, et al. Ability of normal vaginal flora to produce detectable phosphatidylglycerol in amniotic fluid in vitro. Obstet Gynecol 1995; 85:651.
- Schumacher RE, Parisi VM, Steady HM, Tsao FH. Bacteria causing false positive test for phosphatidylglycerol in amniotic fluid. Am J Obstet Gynecol 1985; 151:1067.
- Tanasijevic MJ, Winkelman JW, Wybenga DR, et al. Prediction of fetal lung maturity in infants of diabetic mothers using the FLM S/A and disaturated phosphatidylcholine tests. Am J Clin Pathol 1996; 105:17.
- Livingston EG, Herbert WN, Hage ML, et al. Use of the TDx-FLM assay in evaluating fetal lung maturity in an insulin-dependent diabetic population. The Diabetes and Fetal Maturity Study Group. Obstet Gynecol 1995; 86:826.
- Curet LB, Tsao FH, Zachman RD, et al. Phosphatidylglycerol, lecithin/sphingomyelin ratio and respiratory distress syndrome in diabetic and non-diabetic pregnancies. Int J Gynaecol Obstet 1989; 30:105.
- Berkowitz K, Reyes C, Saadat P, Kjos SL. Fetal lung maturation. Comparison of biochemical indices in gestational diabetic and nondiabetic pregnancies. J Reprod Med 1997; 42:793.
- Melanson SE, Jarolim P, McElrath TF. Fetal lung maturity testing in diabetic mothers. Lab Med 2007; 38:553.
- WHEN IS FETAL LUNG MATURITY TESTING PERFORMED?
- FETAL MATURITY TESTS
- Lamellar body count
- Lecithin/sphingomyelin ratio
- Surfactant/albumin ratio
- Optical density at 650 nm
- Foam stability index
- FACTORS THAT MAY AFFECT INTERPRETATION
- Gestational age
- Blood, meconium
- Oligohydramnios and polyhydramnios
- Vaginal pool samples
- Antenatal corticosteroids
- Maternal diabetes mellitus
- Twin pregnancy
- SUMMARY AND RECOMMENDATIONS