UTILITY OF PLACENTAL LEUCINE AMINOPEPTIDASE/OXYTOCINASE IN THE PREDICTION OF PRETERM DELIVERY IN PREGNANT WOMEN WITH THREATENED PRETERM LABOR
Objective: The study objective was to assess the utility of placental leucine aminopeptidase (P-LAP) marker for the prediction of delivery in patients presented with threatened preterm labor (TPL).
Setting: This study was conducted at the Obstetrics and Gynaecology Department of Al-Yarmouk Teaching Hospital in the period from March 2017 to June 2018.
Type of Study: This is a prospective case control study.
Methods: This study included 90 pregnant women with gestational age from (28-36+6) weeks; 45 of them who presented with preterm uterine contractions were considered as the study group which was further subdivided into three subgroups according to gestational age 28–31+6 weeks, 32– 33+6 weeks, and 34–36+6 weeks. The other 45 pregnant women who presented to the hospital for regular antenatal care visit at comparable gestational age to the study group were considered as the control group. Hence, this study aimed to assess the serum level of P-LAP in both groups and compare it between those delivered preterm from term to assess its applicability as a predictor of preterm labor.
Results: Serum level of P-LAP in pregnant women presented with TPL was found to be significantly lower in those delivered preterm (p<0.001), compared to those continued to term and control group especially in gestational ages ≥32 weeks, while the study found P-LAP level to be statistically insignificant in gestational age <32 weeks (p=0.052). The cutoff point for P-LAP serum level was = 21 (IU/ml) that below it, the pregnant women with TPL most probably deliver before 37 weeks of gestation with Sensitivity (85.7%) Specificity (90.3%), Positive predictive value (80.0%) Negative predictive (93.3%).
Conclusion: The serum level of P-LAP was lower in women delivered preterm than those delivered at term, so it can be used as one of the markers for the prediction of preterm delivery, especially at gestational age >32 weeks.
2. Svigos JM, Dodd JM, Robinson JS. Threatened and actual preterm labor including mode of delivery high risk pregnancy. In: James D, Steer PJ, Weiner CP, editors. High Risk Pregnancy Management Options. 4th ed. Philadelphia, PA: Elsevier Saunders Health Sciences; 2011. p. 1052.
3. Roman AS. Late pregnancy complications. In: Decherney AH, Lauren N, Laufer N, Roman AS. Current Diagnosis and Treatment Obstetrics and Gynecology. 11th ed. United States: The McGraw-Hill Companies; 2013. p. 463.
4. Patel HV, Patel NH, Sodagar NR. Vitamin D receptor (VDR) gene polymorphism and maternal Vitamin D deficiency in Indian women with preterm birth (PTB). Asian J Pharm Clin Res 2017;10:219-23.
5. WHO. EMRO|Prematurity|New-Born Health|Child and Adolescent Health. Available from: http://www.emro.who.int/child-adolescent-health/newborn-health/prematurity.html. [Last cited on 2018 Jun 06].
6. Farhan FS, Hameed BH, Zghair MA. The effect of rectal progesterone on Doppler parameters of the uterine arteries for the prevention of preterm delivery in Iraqi population. Asian J Pharm Clin Res 2018;11:545-8.
7. Esplin MS, Varner MW. Genetic factors in preterm birth-the future. BJOG 2005;112 Suppl 1:97-102.
8. Simhan HN, Iams JA, Romero R. Preterm labor and birth. In: Obstetrics Normal and Problem Pregnancies E-Book. 7th ed. Philadelphia, PA: Elsevier Health Science; 2017. p. 618.
9. Behrman RE, Butler AS. Prematurity at birth: Determinants, consequences, and geographic variation. In: Preterm Birth: Causes, Consequences and Prevention. Washington, DC: The National Academic Press; 2007. p. 772.
10. Swaggart KA, Pavlicev M, Muglia LJ. Genomics of preterm birth. Cold Spring Harb Perspect Med 2015;5:a023127.
11. Zhang G, Feenstra B, Bacelis J, Liu X, Muglia LM, Juodakis J, et al. Genetic associations with gestational duration and spontaneous preterm birth. N Engl J Med 2017;377:1156-67.
12. Bennett P. Preterm labour. In: Dewhurst J, Edmonds DK, editors. Dewhurst’s Textbook of Obstetrics and Gynaecology. 8th ed. London, UK: Wiley-Blackwell; 2012. p. 338.
13. Sullivan SA, Hoffman M, Elliott J. Preterm birth: Can we do better? Proc Obstet Gynaecol 2016;6:1-7.
14. Rasmussen TE, Pedraza-Díaz S, Hardre R, Laustsen PG, Carríon AG, Kristensen T. Structure of the human oxytocinase/insulin-regulated aminopeptidase gene and localization to chromosome 5q21. FEBS J 2000;267:2297-306.
15. Rogi T, Tsujimoto M, Nakazato H, Mizutani S, Tomoda Y. Human placental leucine aminopeptidase/oxytocinase. A new member of Type II membrane-spanning zinc metallopeptidase family. J Biol Chem 1996;271:56-61.
16. Mizutani S, Wright JW, Kobayashi H. Placental leucine aminopeptidase-and aminopeptidase a-deficient mice offer insight concerning the mechanisms underlying preterm labor and preeclampsia. BioMed Res Int 2010;2011:286947.
17. Nomura S, Ito T, Yamamoto E, Sumigama S, Iwase A, Okada M, et al. Gene regulation and physiological function of placental leucine aminopeptidase/ oxytocinase during pregnancy. Biochim Biophys Acta 2005;1751:19-25.
18. Kenkel WM, Yee JR, Carter CS. Is oxytocin a maternal-foetal signalling molecule at birth? Implications for development. J Neuroendocrinol 2014;26:739-49.
19. Mizutani S, Yoshino M, Oya M. Placental and non-placental leucine aminopeptidases during normal pregnancy. Clin Biochem 1976;9:16-8.
20. Mizutani S, Hayakawa H, Akiyama H, Sakura H, Yoshino M, Oya M, et al. Simultaneous determinations of plasma oxytocin and serum placental leucine aminopeptidase (P-LAP) during late pregnancy. Clin Biochem 1982;15:141-5.
21. Matsui M, Fowler JH, Walling LL. Leucine aminopeptidases: Diversity in structure and function. Biol Chem 2006;387:1535-44.
22. McLaurin KK, Hall CB, Jackson EA, Owens OV, Mahadevia PJ. Persistence of morbidity and cost differences between late-preterm and term infants during the first year of life. Pediatrics 2009;123:653-9.
23. Lisonkova S, Sabr Y, Butler B, Joseph KS. International comparisons of preterm birth: Higher rates of late preterm birth are associated with lower rates of stillbirth and neonatal death. BJOG 2012;119:1630-9.
24. Di Renzo GC, Pacella E, Di Fabrizio L, Giardina I. Preterm birth: Risk factors, identification and management. In: Malvasi A, Tinelli A, Carlo G, Renzo D, editors. Management and Therapy of Late Pregnancy Complications. 1st ed. Italy: Springer; 2017. p. 81
25. Honest H, Hyde CJ, Khan KS. Prediction of spontaneous preterm birth: No good test for predicting a spontaneous preterm birth. Curr Opin Obstet Gynecol 2012;24:422-33.
26. Waldenström U, Cnattingius S, Vixner L, Norman M. Advanced maternal age increases the risk of very preterm birth, irrespective of parity: A population-based register study. BJOG 2017;124:1235-44.
27. Fuchs F, Monet B, Ducruet T, Chaillet N, Audibert F. Effect of maternal age on the risk of preterm birth: A large cohort study. PLoS OneA 2018;13:e0191002.
28. Goisis A, Remes H, Barclay K, Martikainen P, Myrskylä M. Advanced maternal age and the risk of low birth weight and preterm delivery: A within-family analysis using Finnish population registers. Am J Epidemiol 2017;186:1219-26.
29. Lisonkova S, Janssen PA, Sheps SB, Lee SK, Dahlgren L. The effect of maternal age on adverse birth outcomes: Does parity matter? J Obstet Gynaecol Can 2010;32:541-8.
30. Shaikh K, Premji SS, Rose MS, Kazi A, Khowaja S, Tough S, et al. The association between parity, infant gender, higher level of paternal education and preterm birth in Pakistan: A cohort study. BMC Pregnancy Childbirth 2011;11:88.
31. Kozuki N, Lee AC, Silveira MF, Sania A, Vogel JP, Adair L, et al. The associations of parity and maternal age with small-for-gestational-age, preterm, and neonatal and infant mortality: A meta-analysis. BMC Public Health 2013;13:S2.
32. Kuzniewicz MW, Black L, Walsh EM, Li SX, Greenberg M. Outcomes of admissions for preterm labor. AJP Rep 2017;7:e106-13.
33. Teoh PJ, Ridout A, Seed P, Tribe RM, Shennan AH. Gender and preterm birth: Is male fetal gender a clinically important risk factor for preterm birth in high-risk women? Eur J Obstet Gynecol Reprod Biol 2018;225:155-9.
34. Peelen MJ, Kazemier BM, Ravelli AC, De Groot CJ, Van Der Post JA, Mol BW, et al. Impact of fetal gender on the risk of preterm birth, a national cohort study. Acta Obstet Gynecol Scand 2016;95:1034-41.
35. Brettell R, Yeh PS, Impey LW. Examination of the association between male gender and preterm delivery. Eur J Obstet Gynecol Reprod Biol 2008;141:123-6.
36. Svenvik M, Brudin L, Blomberg M. Preterm birth: A prominent risk factor for low Apgar scores. BioMed Res Int 2015;2015:978079.
37. Lee HC, Subeh M, Gould JB. Low Apgar score and mortality in extremely preterm neonates born in the United States. Acta Paediatr 2010;99:1785-9.
38. Kozaki H, Itakura A, Okamura M, Ohno Y, Wakai K, Mizutani S, et al. Maternal serum placental leucine aminopeptidase (P-LAP)/oxytocinase and preterm delivery. Int J Gynaecol Obstet 2001;73:207-13.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.