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. 1997;5(2):158–164. doi: 10.1155/S1064744997000240

Biochemical Markers Predictive of Preterm Delivery

Steven R Inglis 1,2,✉
PMCID: PMC2364561  PMID: 18476169

Abstract

Preterm delivery is the leading cause of perinatal morbidity and mortality worldwide. Despite a great deal of research into this disease, we still do not understand its pathophysiology. Our treatments for this disease are only marginally effective. Biochemical markers were developed with the hope of giving us new tools to prevent preterm deliveries. Specifically the hope was that they could predict which patients were destined to have a preterm delivery. At the present time these markers perform only satisfactorily at predicting preterm labor. They are expensive and not convenient to use at present. Perhaps more importantly, though, these markers have given us insight into the complexities of preterm delivery. Preterm delivery can arise from many different etiologies. This will lead to research into new treatments as knowledge about preterm delivery is amassed. We know that any number of pathological processes may be involved in any given patient with preterm labor. Biochemical markers have the distinct advantage of being able to determine the specific pathophysiology in a given patient and may allow us to tailor therapy according to the specific problem. In the future it is likely that a careful search for specific pathophysiology will be the only way we can treat this disease effectively. For the present time the biochemical markers will be used only to predict preterm delivery. Ultrasound measurements of the cervix during the pregnancy are likely a faster and less expensive way to accomplish that goal.

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Selected References

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  1. Berkeley A. S., Killackey M. A., Cederqvist L. L. Elevated maternal serum alpha-fetoprotein levels associated with breakdown in fetal-maternal-placental barrier. Am J Obstet Gynecol. 1983 Aug 1;146(7):859–861. doi: 10.1016/0002-9378(83)91091-8. [DOI] [PubMed] [Google Scholar]
  2. Boylan P., O'Driscoll K. Improvement in perinatal mortality rate attributed to spontaneous preterm labor without use of tocolytic agents. Am J Obstet Gynecol. 1983 Apr 1;145(7):781–783. doi: 10.1016/0002-9378(83)90678-6. [DOI] [PubMed] [Google Scholar]
  3. Brazerol W. F., Grover S., Donnenfeld A. E. Unexplained elevated maternal serum alpha-fetoprotein levels and perinatal outcome in an urban clinic population. Am J Obstet Gynecol. 1994 Oct;171(4):1030–1035. doi: 10.1016/0002-9378(94)90028-0. [DOI] [PubMed] [Google Scholar]
  4. Casey M. L., Cox S. M., Beutler B., Milewich L., MacDonald P. C. Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor. J Clin Invest. 1989 Feb;83(2):430–436. doi: 10.1172/JCI113901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark I. M., Morrison J. J., Hackett G. A., Powell E. K., Cawston T. E., Smith S. K. Tissue inhibitor of metalloproteinases: serum levels during pregnancy and labor, term and preterm. Obstet Gynecol. 1994 Apr;83(4):532–537. doi: 10.1097/00006250-199404000-00008. [DOI] [PubMed] [Google Scholar]
  6. Creasy R. K. Preterm birth prevention: where are we? Am J Obstet Gynecol. 1993 Apr;168(4):1223–1230. doi: 10.1016/0002-9378(93)90373-q. [DOI] [PubMed] [Google Scholar]
  7. Darne J., McGarrigle H. H., Lachelin G. C. Increased saliva oestriol to progesterone ratio before preterm delivery: a possible predictor for preterm labor? Br Med J (Clin Res Ed) 1987 Jan 31;294(6567):270–272. doi: 10.1136/bmj.294.6567.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Darne J., McGarrigle H. H., Lachelin G. C. Saliva oestriol, oestradiol, oestrone and progesterone levels in pregnancy: spontaneous labour at term is preceded by a rise in the saliva oestriol:progesterone ratio. Br J Obstet Gynaecol. 1987 Mar;94(3):227–235. doi: 10.1111/j.1471-0528.1987.tb02359.x. [DOI] [PubMed] [Google Scholar]
  9. Eriksen N. L., Parisi V. M., Daoust S., Flamm B., Garite T. J., Cox S. M. Fetal fibronectin: a method for detecting the presence of amniotic fluid. Obstet Gynecol. 1992 Sep;80(3 Pt 1):451–454. [PubMed] [Google Scholar]
  10. Grether J. K., Nelson K. B. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA. 1997 Jul 16;278(3):207–211. [PubMed] [Google Scholar]
  11. Hillier S. L., Witkin S. S., Krohn M. A., Watts D. H., Kiviat N. B., Eschenbach D. A. The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol. 1993 Jun;81(6):941–948. [PubMed] [Google Scholar]
  12. Iams J. D., Goldenberg R. L., Meis P. J., Mercer B. M., Moawad A., Das A., Thom E., McNellis D., Copper R. L., Johnson F. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. N Engl J Med. 1996 Feb 29;334(9):567–572. doi: 10.1056/NEJM199602293340904. [DOI] [PubMed] [Google Scholar]
  13. Iams J. D., Paraskos J., Landon M. B., Teteris J. N., Johnson F. F. Cervical sonography in preterm labor. Obstet Gynecol. 1994 Jul;84(1):40–46. [PubMed] [Google Scholar]
  14. Inglis S. R., Jeremias J., Kuno K., Lescale K., Peeper Q., Chervenak F. A., Witkin S. S. Detection of tumor necrosis factor-alpha, interleukin-6, and fetal fibronectin in the lower genital tract during pregnancy: relation to outcome. Am J Obstet Gynecol. 1994 Jul;171(1):5–10. doi: 10.1016/s0002-9378(94)70069-9. [DOI] [PubMed] [Google Scholar]
  15. Jeremias J., Kalo-Klein A., Witkin S. S. Individual differences in tumour necrosis factor and interleukin-1 production induced by viable and heat-killed Candida albicans. J Med Vet Mycol. 1991;29(3):157–163. doi: 10.1080/02681219180000261. [DOI] [PubMed] [Google Scholar]
  16. Lockwood C. J., Ghidini A., Wein R., Lapinski R., Casal D., Berkowitz R. L. Increased interleukin-6 concentrations in cervical secretions are associated with preterm delivery. Am J Obstet Gynecol. 1994 Oct;171(4):1097–1102. doi: 10.1016/0002-9378(94)90043-4. [DOI] [PubMed] [Google Scholar]
  17. Lockwood C. J., Senyei A. E., Dische M. R., Casal D., Shah K. D., Thung S. N., Jones L., Deligdisch L., Garite T. J. Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. N Engl J Med. 1991 Sep 5;325(10):669–674. doi: 10.1056/NEJM199109053251001. [DOI] [PubMed] [Google Scholar]
  18. Lockwood C. J., Wein R., Lapinski R., Casal D., Berkowitz G., Alvarez M., Berkowitz R. L. The presence of cervical and vaginal fetal fibronectin predicts preterm delivery in an inner-city obstetric population. Am J Obstet Gynecol. 1993 Oct;169(4):798–804. doi: 10.1016/0002-9378(93)90008-7. [DOI] [PubMed] [Google Scholar]
  19. Main D. M., Gabbe S. G., Richardson D., Strong S. Can preterm deliveries be prevented? Am J Obstet Gynecol. 1985 Apr 1;151(7):892–898. doi: 10.1016/0002-9378(85)90667-2. [DOI] [PubMed] [Google Scholar]
  20. McGregor J. A., French J. I., Jones W., Milligan K., McKinney P. J., Patterson E., Parker R. Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream. Am J Obstet Gynecol. 1994 Apr;170(4):1048–1060. doi: 10.1016/s0002-9378(94)70098-2. [DOI] [PubMed] [Google Scholar]
  21. McGregor J. A., French J. I., Jones W., Parker R., Patterson E., Draper D. Association of cervicovaginal infections with increased vaginal fluid phospholipase A2 activity. Am J Obstet Gynecol. 1992 Dec;167(6):1588–1594. doi: 10.1016/0002-9378(92)91746-w. [DOI] [PubMed] [Google Scholar]
  22. Murakawa H., Utumi T., Hasegawa I., Tanaka K., Fuzimori R. Evaluation of threatened preterm delivery by transvaginal ultrasonographic measurement of cervical length. Obstet Gynecol. 1993 Nov;82(5):829–832. [PubMed] [Google Scholar]
  23. Novy M. J., Liggins G. C. Role of prostaglandins, prostacyclin, and thromboxanes in the physiologic control of the uterus and in parturition. Semin Perinatol. 1980 Jan;4(1):45–66. [PubMed] [Google Scholar]
  24. O'Brien J. M., Peeler G. H., Pitts D. W., Salama M. M., Sibai B. M., Mercer B. M. Cervicovaginal prolactin: a marker for spontaneous preterm delivery. Am J Obstet Gynecol. 1994 Oct;171(4):1107–1111. doi: 10.1016/s0002-9378(13)90045-4. [DOI] [PubMed] [Google Scholar]
  25. Outcomes research and cost containment. N Engl J Med. 1991 Jul 4;325(1):66–67. doi: 10.1056/NEJM199107043250118. [DOI] [PubMed] [Google Scholar]
  26. Platz-Christensen J. J., Brandberg A., Wiqvist N. Increased prostaglandin concentrations in the cervical mucus of pregnant women with bacterial vaginosis. Prostaglandins. 1992 Feb;43(2):133–134. doi: 10.1016/0090-6980(92)90082-5. [DOI] [PubMed] [Google Scholar]
  27. Romero R., Avila C., Santhanam U., Sehgal P. B. Amniotic fluid interleukin 6 in preterm labor. Association with infection. J Clin Invest. 1990 May;85(5):1392–1400. doi: 10.1172/JCI114583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Romero R., Durum S., Dinarello C. A., Oyarzun E., Hobbins J. C., Mitchell M. D. Interleukin-1 stimulates prostaglandin biosynthesis by human amnion. Prostaglandins. 1989 Jan;37(1):13–22. doi: 10.1016/0090-6980(89)90028-2. [DOI] [PubMed] [Google Scholar]
  29. Romero R., Mazor M., Brandt F., Sepulveda W., Avila C., Cotton D. B., Dinarello C. A. Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition. Am J Reprod Immunol. 1992 Apr-May;27(3-4):117–123. doi: 10.1111/j.1600-0897.1992.tb00737.x. [DOI] [PubMed] [Google Scholar]
  30. Romero R., Mazor M., Sepulveda W., Avila C., Copeland D., Williams J. Tumor necrosis factor in preterm and term labor. Am J Obstet Gynecol. 1992 May;166(5):1576–1587. doi: 10.1016/0002-9378(92)91636-o. [DOI] [PubMed] [Google Scholar]
  31. Romero R., Mazor M., Sepulveda W., Avila C., Copeland D., Williams J. Tumor necrosis factor in preterm and term labor. Am J Obstet Gynecol. 1992 May;166(5):1576–1587. doi: 10.1016/0002-9378(92)91636-o. [DOI] [PubMed] [Google Scholar]
  32. Romero R., Mazor M., Wu Y. K., Sirtori M., Oyarzun E., Mitchell M. D., Hobbins J. C. Infection in the pathogenesis of preterm labor. Semin Perinatol. 1988 Oct;12(4):262–279. [PubMed] [Google Scholar]
  33. Romero R., Sepulveda W., Kenney J. S., Archer L. E., Allison A. C., Sehgal P. B. Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity. Ciba Found Symp. 1992;167:205–223. doi: 10.1002/9780470514269.ch13. [DOI] [PubMed] [Google Scholar]
  34. Rozenberg P., Goffinet F., Malagrida L., Giudicelli Y., Perdu M., Houssin I., Safe-Femme, Nisand I. Evaluating the risk of preterm delivery: a comparison of fetal fibronectin and transvaginal ultrasonographic measurement of cervical length. Am J Obstet Gynecol. 1997 Jan;176(1 Pt 1):196–199. doi: 10.1016/s0002-9378(97)80035-x. [DOI] [PubMed] [Google Scholar]
  35. Salafia C. M., Silberman L., Herrera N. E., Mahoney M. J. Placental pathology at term associated with elevated midtrimester maternal serum alpha-fetoprotein concentration. Am J Obstet Gynecol. 1988 May;158(5):1064–1066. doi: 10.1016/0002-9378(88)90220-7. [DOI] [PubMed] [Google Scholar]
  36. Schoonmaker J. N., Lawellin D. W., Lunt B., McGregor J. A. Bacteria and inflammatory cells reduce chorioamniotic membrane integrity and tensile strength. Obstet Gynecol. 1989 Oct;74(4):590–596. [PubMed] [Google Scholar]
  37. Treatment of preterm labor with the beta-adrenergic agonist ritodrine. The Canadian Preterm Labor Investigators Group. N Engl J Med. 1992 Jul 30;327(5):308–312. doi: 10.1056/NEJM199207303270503. [DOI] [PubMed] [Google Scholar]
  38. Williams M. A., Hickok D. E., Zingheim R. W., Luthy D. A., Kimelman J., Nyberg D. A., Mahony B. S. Elevated maternal serum alpha-fetoprotein levels and midtrimester placental abnormalities in relation to subsequent adverse pregnancy outcomes. Am J Obstet Gynecol. 1992 Oct;167(4 Pt 1):1032–1037. doi: 10.1016/s0002-9378(12)80033-0. [DOI] [PubMed] [Google Scholar]
  39. Yoon B. H., Jun J. K., Romero R., Park K. H., Gomez R., Choi J. H., Kim I. O. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol. 1997 Jul;177(1):19–26. doi: 10.1016/s0002-9378(97)70432-0. [DOI] [PubMed] [Google Scholar]

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