Tools
Lecithin Sphingomyelin Ratio
Introduction
The Lecithin-to-Sphingomyelin Ratio (L/S ratio) is one of several methods for clinicians to assess fetal lung maturation. This biochemical test was first introduced in the 1970s, where a sample of amniotic fluid was collected via amniocentesis to determine the risk of the neonate developing respiratory distress syndrome (RDS). The sample was then evaluated, utilizing thin-layer chromatography to assess the size of lecithin relative to sphingomyelin.[1] Historically, this test was useful for clinicians to attempt to time the delivery of infants prior to 39 weeks gestation in hopes of minimization of RDS. In recent years, the test has had a decline in use due to guidelines and recommendations from major medical societies.[2]
Fetal lung development occurs as a gradual process in which the maturation of the pulmonary system progresses with increasing gestational age. There are five stages of lung development, listed in sequential order: embryonic (3 to 7 weeks), pseudo glandular (5 to 17 weeks), canalicular (16 to 26 weeks), saccular (26 to 36 weeks), and alveolar (32 weeks through childhood). The major maturation of the fetal lungs occurs during the alveolar stage when the maturation of type II pneumocytes occurs. Type II pneumocytes are responsible for the production of surfactant, which is critical for the support of alveoli in the lungs to combat surface tension.
The effect of the surfactant prevents the collapse of the alveoli during expiration. The composition of the surfactant includes phospholipids, proteins, and lipids. Of notable importance is the composition of the phospholipids. Phosphatidylcholine, also referred to as lecithin, is one of the phospholipids present in mature surfactant. It is stored and secreted by organelles called lamellar bodies.[3]
These organelles appear after 22 to 24 weeks gestation. Before the 28th week of gestation, the fetal lung primarily synthesizes sphingomyelin, a nonpulmonary lipid. At approximately 32 weeks gestation, the number of lamellar bodies increases, which translates into increased surfactant present in the fetal lungs and amniotic fluid. At this point in lung maturity, the ratio of lecithin and sphingomyelin are relatively equal in concentration. By 35 weeks of gestation, the mature surfactant has been produced and is marked by a sharp increase in the concentration of lecithin in the fetal lungs and amniotic fluid. The lecithin to sphingomyelin ratio of 2:1 or greater is characteristic of mature fetal lungs. Fetuses delivered prior to this gestational age are at increased risk of neonatal respiratory distress syndrome.
Specimen Collection
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Specimen Collection
Obtaining a sample of amniotic fluid can occur via amniocentesis after 34 weeks of gestation or from vaginal pooling in the preterm premature rupture of membranes (PPROM). In the case of amniocentesis, an ultrasound is used to determine an adequately sized pocket of amniotic fluid that is away from the fetus. Local anesthesia can be used for the sampling site. A stylet is introduced through the abdomen under ultrasound guidance, and a syringe is attached to obtain the sample. In the case of PPROM, the sample can be collected from the vagina. However, if blood were to be present within the sample or in the vagina, the results of the L/S ratio would be invalidated.
Procedures
A thin layer chromatography is performed on the sample, which can determine the ratio of lecithin to sphingomyelin in the amniotic fluid.[4]
Indications
Historically, indications for amniocentesis for fetal lung maturity included maternal comorbidities, uterine and placental complications, and obstetric concerns. Some of these conditions included diabetes, chronic hypertension, preeclampsia, placenta previa, preterm labor, preterm premature rupture of the membranes, fetal heart rate abnormalities, and several other concerns. Based on new guidelines, these indications no longer warrant testing the L/S ratio or performing other fetal lung testing modalities. One possible exception relates to inaccurate dating of the gestational age. If there is poor dating of the pregnancy and the delivery is to be planned between 32 to 39 weeks gestation, the clinician may consider testing for fetal lung maturity.[5]
Potential Diagnosis
The main focus of testing the L/S ratio is to determine fetal lung maturity in an effort to decrease the risk of delivering a neonate with respiratory distress syndrome (RDS). RDS predominantly occurs in preterm infants less than 39 weeks gestation with increased risk with lesser gestational age.
Normal and Critical Findings
The normal L/S ratio is 2.0 to 2.5 and is significant for appropriate fetal lung development. An L/S ratio of less than 2.0 is significant for immature fetal lung development. For patients who have poorly controlled diabetes, there was a discussion for the L/S ratio to be 3.0 due to elevated maternal glucose impacting the maturity of the developing fetal lungs. However, it was later found that there was no significant difference in the L/S ratio between diabetic and non-diabetic patients.[6] Some institutions use 3.0 as the cutoff for pregnancies with poorly controlled diabetes.
Interfering Factors
The presence of meconium and blood in the sample can alter the result of the L/S ratio. The presence of meconium in the sample can invalidate the final result.[7] The presence of blood can decrease the result of the L/S ratio leading to alterations in the interpretation of the test. If a result of the L/S ratio were to be read initially as less than 2.0, the presence of blood would further decrease the value obtained, leading to an interpretation as an immature result. On the other hand, if the result were to be read as more significant than 2.0, in the presence of blood, the sample would still be lead to the interpretation as mature despite the decrease in the value.[8]
Complications
Major complications of delivery of a neonate before 39 weeks gestation have focused on the consequences of incomplete pulmonary development such as respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary hypertension, and the need for respiratory support.[9]
Patient Safety and Education
Risks of performing an amniocentesis for determining an L/S ratio are rare but include maternal sepsis, intrauterine rupture, maternal-fetal hemorrhage, and fetal heart rate abnormalities.[5]
Clinical Significance
The L/S ratio was a test used to help guide clinicians in determining the timing of delivery of neonates to minimize the risk of developing respiratory distress syndrome.[10] The evidence of immature fetal lungs by this biochemical test had been used to support the administration of glucocorticoids for promoting lung maturation. Other fetal lung maturity testing options have been developed since the advent of the L/S ratio. They include lamellar body count, phosphatidylglycerol test (PG), foam stability test, and surfactant/albumin ratio. Over the last several years, the need to test for fetal lung maturity has diminished. In many circumstances, if there is a maternal or fetal indication to deliver before term, performing an L/S ratio test would not be necessary.
References
Gluck L, Kulovich MV, Borer RC Jr, Brenner PH, Anderson GG, Spellacy WN. Diagnosis of the respiratory distress syndrome by amniocentesis. American journal of obstetrics and gynecology. 1971 Feb 1:109(3):440-5 [PubMed PMID: 5107880]
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Veldhuizen R, Nag K, Orgeig S, Possmayer F. The role of lipids in pulmonary surfactant. Biochimica et biophysica acta. 1998 Nov 19:1408(2-3):90-108 [PubMed PMID: 9813256]
Level 3 (low-level) evidenceSharma L, Desai A, Sharma A. A thin layer chromatography laboratory experiment of medical importance. Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology. 2006 Jan:34(1):44-8. doi: 10.1002/bmb.2006.49403401044. Epub [PubMed PMID: 21638633]
Varner S, Sherman C, Lewis D, Owens S, Bodie F, McCathran CE, Holliday N. Amniocentesis for fetal lung maturity: will it become obsolete? Reviews in obstetrics & gynecology. 2013:6(3-4):126-34 [PubMed PMID: 24826202]
Moore TR. A comparison of amniotic fluid fetal pulmonary phospholipids in normal and diabetic pregnancy. American journal of obstetrics and gynecology. 2002 Apr:186(4):641-50 [PubMed PMID: 11967485]
Level 2 (mid-level) evidenceTabsh KM, Brinkman CR 3rd, Bashore R. Effect of meconium contamination on amniotic fluid lecithin: sphingomyelin ratio. Obstetrics and gynecology. 1981 Nov:58(5):605-8 [PubMed PMID: 7301236]
Cotton DB, Spillman T, Bretaudiere JP. Effect of blood contamination on lecithin to sphingomyelin ratio in amniotic fluid by different detection methods. Clinica chimica acta; international journal of clinical chemistry. 1984 Mar 13:137(3):299-304 [PubMed PMID: 6697534]
Bates E, Rouse DJ, Mann ML, Chapman V, Carlo WA, Tita ATN. Neonatal outcomes after demonstrated fetal lung maturity before 39 weeks of gestation. Obstetrics and gynecology. 2010 Dec:116(6):1288-1295. doi: 10.1097/AOG.0b013e3181fb7ece. Epub [PubMed PMID: 21099593]
St Clair C, Norwitz ER, Woensdregt K, Cackovic M, Shaw JA, Malkus H, Ehrenkranz RA, Illuzzi JL. The probability of neonatal respiratory distress syndrome as a function of gestational age and lecithin/sphingomyelin ratio. American journal of perinatology. 2008 Sep:25(8):473-80. doi: 10.1055/s-0028-1085066. Epub 2008 Sep 4 [PubMed PMID: 18773379]