Routine Assessment of Fetal Lung Maturation: A 1996 Perspective?

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OBSTETRI CS

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ROUTINE ASSESSMEN T OF FETAL LUNG MATURATI ON: A 1996 PERSPECTIVE? Z. Babay, MD, 1

I.R. Lange, MB, ChB, FRCSC, 2 1

Fellow, Perinatal Medicine, Division Chief of Obstetrics, 1 )Department of Obstetrics and Gynaecology, Foothills Hospital, University of Calgary 2

ABSTRACT

Since fetal lung maturation tests first became established in clinical practice, there have been many advances in perinatal medicine. Many clinical guidelines no longer emphasize the impartance of routine fetal lung maturation stw:lies. Despite these advances, fetal lung maturation stw:lies are commonly performed. This article reviews the development of fetal lung maturity testing, discusses the clinical value of the test when first introduced, and questions the role of the test in 1996. RESUME

Depuis la mise au point des premiers tests de la maturation des poumons du foetus en pratique clinique, la medecine perinatale a beaucoup progresse. Nombre des !ignes directrices cliniques n'insistent plus sur !'importance d'un examen regulier de la maturation des poumons du foetus. Malgre les progres realises, on procede tout de meme toujours regulierement ade tels examens. Dans le present article, nous examinons l' evolution des methodes d' evaluation de la maturite des poumons du foetus, nous traitons de la valeur clinique des tests lorsqu'ils ont ere mis en place al' origine et nous nous interrogeons sur le role de ces tests en 1996.

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1996;18:1009-15

KEY WORDS

Amniocentesis, lung maturation, surfactant. Received on May 3rd, 1996. Revised and accepted on June 3rd, 1996.

was to prove lung maturity when early delivery was considered in complicated pregnancies. As a consequence, there was considerable research focused on fetal lung development and methods to confirm lung maturity. These needs arose because of the imprecision of clinical dating as well as the wide variance in calculating

INTRODUCTION

In the recent past, lung immaturity in the preterm newborn resulted frequently in rapid death or damage as a consequence of hyaline membrane disease (HMD). 1•2 The greatest challenge to obstetricians then

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' ' ' gestational age when determined by quickening or the first fetal heart sounds. The traditional radiological markers had similar limitations. 3 Since fetal lung maturation tests first became established in clinical practice, there have been many advances in perinatal medicine. Many clinical guidelines no longer emphasize the importance of routine fetal lung maturation studies. As early as 1981, several authors began to doubt the need to confirm fetal lung maturity and they also documented a decline in the number of amniocenteses for this purpose. 4·8 Despite these advances, fetal lung maturation studies remain a relatively common test and in Calgary, for example, there is an average of two such tests performed each week. The purpose of this article is to review the development of fetal lung maturity testing, discuss the clinical value of the test when first introduced, and to question the role of this test in 1996.

assays and, on occasions, amnioscopy. Physicians were concerned that the high risk pregnancy might result in stillbirth, or following elective induction of labour, that there would be complications of prematurity. Nurseries were ill-equipped to deal with the complications of prematurity, and the perinatal morbidity and mortality were considerable. In cases of maternal or fetal complications before term, or before elective repeat Caesarean section, an obstetrician could perform an amniocentesis, and with a "mature" test result could offer the option of delivery. The routine confirmation of fetal lung maturity was viewed as a major advance and offered physicians an attractive management option in complicated pregnancies. The L/S ratio continues to be the gold standard for fetal maturity tests. There remains however, a number of drawbacks that warrant consideration, especially in 1996. Perhaps the most important issues pertain to quality control. The technician performing the test requires extensive training, there must be strict attention to laboratory technique, and the test is time consuming and expensive. The test result may be altered by such contaminants in the amniotic fluid as blood or meconium. There are also concerns about test accuracy. For example, an L/S ratio of more than or equal to two has a two percent false positive rate, while a ratio of less than 1.5 has a false negative rate of 27 percent. An L/S ratio in the intermediate range of 1.5 to two has a false negative rate of 60 percent. 14 It is important to note that in such conditions as diabetes mellitus, hypertension or renal disease where an amniocentesis could be considered, there may be a high incidence of erroneous results. 15 Perhaps the greatest drawback of fetal lung maturity testing is the need for an invasive procedure. The patient anxiety and the procedural discomfort are difficult to quantitate but cannot be underestimated. The known complications of amniocentesis are well documented, and while uncommon, include amniotic fluid embolism, placental abruption, fetal exsanguination, maternal rigors and pyrexia, chorio-amnionitis, allo-immune disease, pneumothorax of the newborn, fetal injury, and the potential to initiate preterm labour. 16 These complications are reduced with ultrasound guided needle placement techniques. Rome et al. for example, reported a fetal death rate of 0.41 percent, a failed amniocentesis rate of 13.2 percent, and a spontaneous onset of labour rate of 9. 7 percent when they used this method. 16 Other

THE DEVELOPMENT OF AMNIOCENTESIS FOR FETAL LUNG MATURITY STUDIES

Amniocentesis is one of the oldest procedures in obstetrics. Initially, it was used to treat hydramnios, 9 •10 and in the 1950s it was introduced to predict the severity of allo-immune disease. 11 Subsequently, the amniotic fluid was used as an indirect vehicle to gain access to the "fetal compartment." The association between HMD and surfactant deficiency was first demonstrated in 1959 by Avery and Mead. 12 The development of tests that detected surfactant in the amniotic fluid was not established until1971. At this time, Gluck and colleagues measured the amniotic fluid Lecithin/ Sphingomyelin ratio (L/S), and used this test to predict the subsequent onset of HMD in preterm neonatesY Other tests were soon developed to complement the L/S ratio and to improve test accuracy in certain clinical circumstances. Examples of these tests include phosphatidylglycerol and phosphatidylcholine assays, determining the lamellar body concentration as well as the foam stability index. 3 In an era where there was a limited number of accurate tests for assessing fetal wellbeing, fetal lung maturity studies were considered a milestone. Then there were few options when managing pregnancy complications as often found in the pregnant diabetic or the patient with severe pre-eclampsia. Tests for assessing fetal wellbeing were crude and were limited to urinary or plasma estriol

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That formula is Enfalac~, now compositionally closer to breast milk than ever before.

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Only Enfalac has the unique 4-oil fat blend The absorption of fat is similar to breast milk. Breast milk has a normal range of 87-98% fat absorption 1 and Enfalac has, on average, 93% fat absorption2 • Benefits of Enfalac with our 4-oil fat blend include infant visual acuity as well as mental and motor development equivalent to breast fed infants' 4 . Calcium absorption supports bone mineralization equivalent to breast fed infants 5 •

Fotty Acid Profile • Human MiJk4 •

Enfolqc

1 Fomon Nutrition of Normal Infants, 1993. 2 Data on file. Mead Johnson Nutritionals. Evansville, Indiana. 3 InnisS. et al. Development of visual acuity in relation to plasma and erythrocyte w-6 and w-3 fatty acids in healthy term gestation infants. Am J Clin Nutr. 1994; 60:347. 4 Nelson C. et al. Prospective measures of visual and cognitive development in term gestation breastfed and formula fed infants to 18 months of age. Pediatr. Res. 1995; 37:315A. 5 Hansen]. et al. Impact of palm akin in infant feedings on bone mineral content. Presented at AAP Annual Meeting, Boston, 1996. 6 Innis SM. Lipids in Infant Nutrition.). Pediatr. 1992; 120(5):556-61. 7 Bradley C. et al. Evaluation of two iron fortified, milk based formulas during infancy. Pediatrics. 1993; 91:908.

And now...

Enfalac has added nucleotides Comparison of Nucleotide Levels Found in Breast Milk vs Enfalac • • • •

l.eoclut al.• 1
Only Enfalac has 7 mg of iron Mead Jolmson has clinically proven that 7 mg of iron per litre is the appropriate amount. The iron status

Nucleotides occur naturally in breast mill{. The

among infants fed 7 mg/L is equivalent to breast fed

building blocks of RNA and DNA, nucleotides are

infants in their flrst year? Additionally, studies show

fundamental to metabolism and are integral to

the lower the iron level, the higher the percentage

cell division and replication.

absorption". This accounts for the equivalent iron

Leading experts in immunology have concluded

status in infants fed 7 mg/L vs. 12 mg/F

that claims regarding the addition of nucleotides to infant formula, in that they

Enfalac is whey predominant

enhance the baby's developing immune system,

Its whey:casein ratio of 60:40 is similar to

are not clinically substantiated.

breast mill{.

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Doctors trust the Enfalac family of formulas. 8 Saarinen UM, Siime~ .\1.A. Iron absorption from infant milk formula and the optimal level of iron supplementation. Acta Pediatr Scand, 1977; 66: 719-722. 9 Leach JL, Baxter JH. Molitor BE. et aL Total potentially available nucleosides of human milk by stage of lactation. Am J Clin :'\Jutr. 1995; 61: 1224-12:30. 10 Janas LM, Picciano MB. The nucleotide profile of human milk. Pediatr Res. 1982; 16:659-662. 11 Gil A. Sanchez-Medina E Acid-soluble nucleotides of human milk at different stages oflactation.j Dairy Res. 1982; 49:301-307. * T:\1 Authorised User. :£ 1996 Mead johnson Canada.

' ' ' authors also have reported a one percent fetal death rate and 7.5 percent risk of significant complications with ultrasound guided amniocentesis. 17 •18 A large legal settlement in Canada was a consequence of neurological complications that occurred as a result of an amniocentesis performed for lung maturity studies. 19 NEW DEVELOPMENTS IN THE 1990s

There are two changes to practice guidelines that have done the most to reduce the need for fetal lung maturation studies. These are the ability to date the pregnancy accurately and that more mothers are considering vaginal birth after Caesarean section(VBAC). Accurate dating of the pregnancy is possible because of immunologically-based pregnancy tests and routine ultrasound dating, both of which complement the accuracy of clinically determined dates. The trend to VBAC has reduced the overall number of scheduled repeat Caesarean sections. In the unusual circumstance where an elective Caesarean section is planned, the risk of neonatal HMO must be balanced against the procedural risks of an amniocentesis. If the gestational age is at or greater than 38 to 39 weeks, many obstetricians would prefer to avoid an amniocentesis for their patients. In high risk pregnancies, management decisions are often based on objective tests of maternal or fetal health. These tests offer immediate, more accurate assessments of fetal wellbeing than their biochemical predecessors. These tests include the cardiotocogram (CTG), the biophysical profile score (BPS), the amniotic fluid index (AFI), fetal growth profile, and Doppler velocimetry studies of fetal vessels. Biophysical tests used in combination permit an accurate assessment of acute and chronic fetal health. 20 Their accuracy is illustrated by the reported false negative rate of the BPS (as defined as still births occurring within a week of a last normal BPS) of 0.41 per 1,000 testsY In a recent meta-analysis of umbilical artery Doppler studies, there was a significant reduction in antenatal admissions, inductions of labour, as well as Caesarean section for fetal distress when this test was used clinically. 22 Now high risk patients with normal antenatal test results can be followed until the spontaneous onset of labour or until term is reached. In those pregnancies remote from term where there are concerns for fetal health, the use of maternal steroid administration has been shown to reduce such major neonatal complications as HMD. 21 In this clinical situation, a reasonable

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alternative to frequent amniocenteses for lung maturation studies is to consider the option of steroid administration, and to deliver the patient when an abnormal test result dictates it. In those unusual circumstances where antenatal test results are clearly abnormal, the L/S ratio result is also of limited value, as perinatal death may be the consequence of delayed intervention pending the laboratory result. It is for these reasons that the numbers of amniocenteses performed in most major institutions have fallen dramatically. It could be argued that a more central issue to this discussion is that of quality control. Are laboratories able to maintain their technical expertise when only the occasional test is performed each week? A further important question is whether those physicians who have long abandoned this test have a higher rate of HMO among their neonatal patients? In most Canadian centres the resources are available to address these important questions. No discussion on fetal lung maturation studies and HMO would be complete without acknowledging the advances in neonatal medicine. These include improvements in neonatal ventilator support as well as the general care of the premature infant. Surfactant therapy is available to assist in treating HMO and, together with antenatal steroids, has had a major effect on reducing the severity and frequency of this complication. 24 In what circumstances should fetal lung maturation studies be considered? Perhaps alternative options are available in most clinical situations. For example, the patient with unknown dates and with a previous Caesarean section could await the onset of spontaneous labour. In the difficult social situations where an expectant plan is unacceptable to the patient and where VBAC is refused, confirmation of fetal lung maturation is not unreasonable. In extreme preterm labour management, maternal steroid administration, with or without tocolytic treatment, and referral to a level three obstetrical facility for ongoing care are standard for most patients. The patient's clinical details complemented by the ultrasound findings are now used more effectively than knowledge of the L/S ratio. When the gestational age is greater than that normally required for admission to a level three nursery yet transportation is being debated, knowledge of the L/S ratio may assist in making the decision of whether or not to transport the patient to a tertiary centre . Perhaps this test could also be used in centres that do not have facilities to undertake newer

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tests for assessment of fetal health? In summary, clear guidelines for fetal lung maturation studies need to be revised to meet current Canadian practice protocols. It could be suggested that this test should only be used in limited circumstances where unusual clinical details are compounded by unusual social situations. In these patients, the L/S ratio may influence the decision making process.

8. 9. 10.

CONCLUSION

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In normal pregnancies, most fetal lungs are immature before 34 weeks. From 34 to 3 7 weeks, there is a transitional phase where varying degrees of lung maturity can be expected. As the predictive value of testing for fetal lung maturity by amniocentesis falls as the prevalence ofRDS falls near term, 25 the questions of the validity of the testing arise, especially as the procedure is invasive and carries risk. The development of such reliable, non-invasive methods of intra-uterine assessment as non-stress test (NST), BPS, and Doppler velocimetry, have changed most management guidelines. With limited fetal lung maturation tests now being performed, laboratories may have lost their technical expertise, and quality control may suffer as a consequence. This paper may encourage obstetricians to review their use of amniotic fluid to assess fetal lung maturity. If changes in clinical practice are now causing a decline in the use of the test, it is important that everyone involved in the perinatal field should be informed of the trend and of its potential benefits and hazards.

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REFERENCES 1.

2. 3. 4.

5.

6.

Claireaux A. Still Birth And First Week Deaths. In: Chamberlain R, Chamberlain G, Howlett B, Claireaux A (Eds). British Births 1970. The First Week Of Life. Heinemann Medical Books, London 1975;238. Farrell PM, Avery ME. State of the art. Hyaline membrane disease. Am Rev Respir Dis 1975;111 :657-90. Druzin ML. Methods of determining fetal maturity. Pediatr Annals 1983;12 (1):18-22. James DK, Tindall VR, Richardson T. Is Lecithin I Sphingomyelin Ratio out dated? Br J Obstet Gynaecol 1983;90:995-1 000. Schreiner RL, Hutton NM, Hannemann RE, Golichowski A. Respiratory distress associated with elective repeat caesarean section. Acta Obstet Gynecol Scand 1981 ;60:261-4. Chervenak FA, Shamsi HH. Is amniocentesis necessary before elective repeat cesarean section? Obstet Gynecol 1982;60:305-8.

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22.

23.

24.

25.

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Frigoletto FD Jr., Phillippe M, Davies IJ, Ryan KJ. Avoiding iatrogenic prematurity with elective repeat cesarean section without the routine use of amniocentesis. Am J Obstet Gynecol 1980;137:521-4. Turnbull AC. The Lecithin/Sphingomyelin Ratio in decline. Br J Obstet Gynaecol 1983;90:993-4. Lambl D. Ein Seltener Fall Von Hydramnios Zentralble. Gynaekol1881;5:329. Schantz F. Eine Besondere Art Von Ein Seitiger Oligohydramnie Bei Zwillinger. Arch Gynaecol1882;65:329. Viscarllo R, Gollin YG, Hobbins JC. Alternate methods of first trimester diagnosis. Obstet Gynecol Clin North Am 1991 ;18(4):875-90. Avery ME, Mead J. Surface properties in relation to atelactasis and hyaline membrane disease. Am J Dis Child 1959;97:517-23. Gluck L, Kulovich M, Borer RCJ, Brenner PH, Anderson GG, Spellacy WN. Diagnosis of the respiratory distress syndrome by amniocentesis. Am J Obstet Gynecol 1971; 109:440-5. Harvey D, Parkinson DC, Campbell S. Risk of respiratory distress syndrome. Lancet 1975;1:42. Savona-Ventura C. Amniocentesis for fetal lung maturity. Obstet Gynecol Surv 1987;42(12):717-23. Rome RM, Glover Jl, Simmon SC. The benefits and risks of amniocentesis for assessment of fetal lung maturity. Br J Obstet Gynaecol1975;82:662-8. Ryan GT, Ivy R, Pearson JW. Fetal bleeding as a major hazard of amniocentesis. Obstet Gynecol1972;40:702. Klein SA, Young BK, Wilson SJ eta/. Continuous fetal monitoring following third trimester amniocentesis. Obstet Gynecol1981 ;58:444. Munn I. The Knickle Case: even when you win, you lose. Can Med Assoc J 1991;144(9):1150-2. Devoe LD. The Non Stress Test. Obstet Gynecol Clin North Am 1990;17(1 ):111-28. Manning FA. Fetal Biophysical Assessment By Ultrasound. In: Creasy RK, Resnik R (Eds). Maternal Fetal Medicine: Principles and Practice. 3rd ed. WB Saunders 1994;347. Alfirevic Z, Neilson JP. Doppler ultrasonography in high risk pregnancies: systematic review with meta-analysis. Am J Obstet Gynecol1995;172:1379-87. Crowley P, Chalmers I, Keirse MJN. The effect of corticosteroid administration before preterm delivery. An overview of the evidence from controlled trials. Br J Obstet Gynaecol1990;97:11. Soli RF. Natural Surfactant Extract Treatment Of RDS. In: Chalmers I (Ed). Oxford Database Of Perinatal Trials. Version 1.2, Disk Issue 6. Autumn 1991. Whitfield CR, Sproule WB. Fetal lung maturation. Br J Hosp Med 1974;12:678.

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