Download PDF
Semin Reprod Med 2007; 25(1): 040-051
DOI: 10.1055/s-2006-956774
Copyright © 2007 by Thieme Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Genetic Influences on Preterm Birth

Emily DeFranco1 , Kari Teramo2 , Louis Muglia3
  • 1Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Center for Preterm Birth Research, Washington University School of Medicine, St. Louis, Missouri
  • 2Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland
  • 3Department of Pediatrics, Director, Division of Endocrinology & Diabetes, Director, Center for Preterm Birth Research, Washington University School of Medicine, St. Louis, Missouri
Further Information

Publication History

Publication Date:
05 January 2007 (online)

    Permissions and Reprints

ABSTRACT

The high prevalence, increasing frequency, and adverse outcomes for mothers and infants of preterm birth have led to heightened awareness of this public health concern. The causes of preterm birth are likely to be multifactorial, with genetic, infectious, nutritional, behavioral, and other environmental contributors. Because of important differences in the physiology of human pregnancy and that of nonprimate mammals, extrapolation of mechanisms from animal model systems to humans has had limited impact on the understanding of human prematurity. This review summarizes work from many groups that implicates important genetic contributions to human preterm birth. These efforts use epidemiological, classical genetic, and more recently, genomic science approaches to determine pregnancies at risk for preterm delivery and to facilitate an understanding of the substantial racial disparity in preterm birth. Data revealing racial and familial predispositions to prematurity, along with genetic polymorphisms conferring increased preterm birth, promise new insights into the understanding and treatment of this critical problem.

KEYWORDS

Preterm birth - epidemiology - genetics - polymorphism

REFERENCES

  • 1 Goldenberg R L. The management of preterm labor.  Obstet Gynecol. 2002;  100(5 pt 1) 1020-1037
    CrossrefPubMedSearch in Google Scholar
  • 2 Mattison D R, Damus K, Fiore E, Petrini J, Alter C. Preterm delivery: a public health perspective.  Paediatr Perinat Epidemiol. 2001;  15(suppl 2) 7-16
    CrossrefPubMedSearch in Google Scholar
  • 3 Martin J A, Hamilton B E, Sutton P D, Ventura S J, Menacker F, Munson M L. Births: final data for 2003.  Natl Vital Stat Rep. 2005;  54(2) 1-116
    PubMedSearch in Google Scholar
  • 4 Committee on Understanding Premature Birth and Assuring Healthy Outcomes .Preterm Birth: Causes, Consequences, and Prevention. Washington, DC; The National Academies Press 2006
    Search in Google Scholar
  • 5 Ward R M, Beachy J C. Neonatal complications following preterm birth.  BJOG. 2003;  110(suppl 20) 8-16
    CrossrefPubMedSearch in Google Scholar
  • 6 Murray C J, Lopez A D. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.  Lancet. 1997;  349(9063) 1436-1442
    CrossrefPubMedSearch in Google Scholar
  • 7 Gluckman P D, Hanson M A. Living with the past: evolution, development, and patterns of disease.  Science. 2004;  305(5691) 1733-1736
    CrossrefPubMedSearch in Google Scholar
  • 8 Adams M M, Elam-Evans L D, Wilson H G, Gilbertz D A. Rates of and factors associated with recurrence of preterm delivery.  JAMA. 2000;  283(12) 1591-1596
    CrossrefPubMedSearch in Google Scholar
  • 9 Goldenberg R L, Cliver S P, Mulvihill F X et al.. Medical, psychosocial, and behavioral risk factors do not explain the increased risk for low birth weight among black women.  Am J Obstet Gynecol. 1996;  175(5) 1317-1324
    CrossrefPubMedSearch in Google Scholar
  • 10 Kramer M S, Goulet L, Lydon J et al.. Socio-economic disparities in preterm birth: causal pathways and mechanisms.  Paediatr Perinat Epidemiol. 2001;  15(suppl 2) 104-123
    CrossrefPubMedSearch in Google Scholar
  • 11 Morken N H, Kallen K, Hagberg H, Jacobsson B. Preterm birth in Sweden 1973-2001: rate, subgroups, and effect of changing patterns in multiple births, maternal age, and smoking.  Acta Obstet Gynecol Scand. 2005;  84(6) 558-565
    CrossrefPubMedSearch in Google Scholar
  • 12 Norton M E, Merrill J, Cooper B AB, Kuller J A, Clyman R I. Neonatal complications after the administration of indomethacin for preterm labor.  N Engl J Med. 1993;  329 1602-1607
    CrossrefPubMedSearch in Google Scholar
  • 13 Copper R L, Goldenberg R L, Dubard M B, Hauth J C, Cutter G R. Cervical examination and tocodynamometry at 28 weeks' gestation: prediction of spontaneous preterm birth.  Am J Obstet Gynecol. 1995;  172(2 pt 1) 666-671
    CrossrefPubMedSearch in Google Scholar
  • 14 Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C, Husslein P. Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis.  Am J Obstet Gynecol. 2003;  189(1) 139-147
    CrossrefPubMedSearch in Google Scholar
  • 15 Carey J C, Klebanoff M A, Hauth J C et al.. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.  N Engl J Med. 2000;  342(8) 534-540
    CrossrefPubMedSearch in Google Scholar
  • 16 Lamont R F. Can antibiotics prevent preterm birth-the pro and con debate.  BJOG. 2005;  112(suppl 1) 67-73
    PubMedSearch in Google Scholar
  • 17 McDonald H, Brocklehurst P, Parsons J. Antibiotics for treating bacterial vaginosis in pregnancy.  Cochrane Database Syst Rev. 2005;  (1) CD000262
    PubMedSearch in Google Scholar
  • 18 Leitich H, Egarter C, Kaider A, Hohlagschwandtner M, Berghammer P, Husslein P. Cervicovaginal fetal fibronectin as a marker for preterm delivery: a meta-analysis.  Am J Obstet Gynecol. 1999;  180(5) 1169-1176
    PubMedSearch in Google Scholar
  • 19 Honest H, Bachmann L M, Gupta J K, Kleijnen J, Khan K S. Accuracy of cervicovaginal fetal fibronectin test in predicting risk of spontaneous preterm birth: systematic review.  BMJ. 2002;  325(7359) 301
    CrossrefPubMedSearch in Google Scholar
  • 20 Kekki M, Kurki T, Karkkainen T, Hiilesmaa V, Paavonen J, Rutanen E M. Insulin-like growth factor-binding protein-1 in cervical secretion as a predictor of preterm delivery.  Acta Obstet Gynecol Scand. 2001;  80(6) 546-551
    CrossrefPubMedSearch in Google Scholar
  • 21 Elizur S E, Yinon Y, Epstein G S, Seidman D S, Schiff E, Sivan E. Insulin-like growth factor binding protein-1 detection in preterm labor: evaluation of a bedside test.  Am J Perinatol. 2005;  22(6) 305-309
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Leitich H, Brunbauer M, Kaider A, Egarter C, Husslein P. Cervical length and dilatation of the internal cervical os detected by vaginal ultrasonography as markers for preterm delivery: a systematic review.  Am J Obstet Gynecol. 1999;  181(6) 1465-1472
    PubMedSearch in Google Scholar
  • 23 Iams J D, Goldenberg R L, Meis P J et al.. 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;  334(9) 567-572
    CrossrefPubMedSearch in Google Scholar
  • 24 Taipale P, Hiilesmaa V. Sonographic measurement of uterine cervix at 18-22 weeks' gestation and the risk of preterm delivery.  Obstet Gynecol. 1998;  92(6) 902-907
    CrossrefPubMedSearch in Google Scholar
  • 25 Rozenberg P, Goffinet F, Malagrida L et al.. Evaluating the risk of preterm delivery: a comparison of fetal fibronectin and transvaginal ultrasonographic measurement of cervical length.  Am J Obstet Gynecol. 1997;  176(1 pt 1) 196-199
    CrossrefPubMedSearch in Google Scholar
  • 26 Adams M M, Read J A, Rawlings J S, Harlass F B, Sarno A P, Rhodes P H. Preterm delivery among black and white enlisted women in the United States Army.  Obstet Gynecol. 1993;  81(1) 65-71
    PubMedSearch in Google Scholar
  • 27 Shiono P H, Klebanoff M A. Ethnic differences in preterm and very preterm delivery.  Am J Public Health. 1986;  76(11) 1317-1321
    CrossrefPubMedSearch in Google Scholar
  • 28 Zhang J, Savitz D A. Preterm birth subtypes among blacks and whites.  Epidemiology. 1992;  3(5) 428-433
    CrossrefPubMedSearch in Google Scholar
  • 29 Risch N, Burchard E, Ziv E, Tang H. Categorization of humans in biomedical research: genes, race and disease.  Genome Biol. 2002;  3(7) comment 2007;  , Epub July 1, 2002
    PubMedSearch in Google Scholar
  • 30 Goldstein D B, Tate S K, Sisodiya S M. Pharmacogenetics goes genomic.  Nat Rev Genet. 2003;  4(12) 937-947
    CrossrefPubMedSearch in Google Scholar
  • 31 Kistka ZA-F, Palomar L, Lee K A et al.. Racial disparity in the frequency of recurrence of preterm birth.  Am J Obstet Gynecol. 2007;  , In press
    PubMedSearch in Google Scholar
  • 32 Collins Jr J W, Hammond N A. Relation of maternal race to the risk of preterm, non-low birth weight infants: a population study.  Am J Epidemiol. 1996;  143(4) 333-337
    CrossrefPubMedSearch in Google Scholar
  • 33 Migone A, Emanuel I, Mueller B, Daling J, Little R E. Gestational duration and birthweight in white, black and mixed-race babies.  Paediatr Perinat Epidemiol. 1991;  5(4) 378-391
    PubMedSearch in Google Scholar
  • 34 Carlini L, Somigliana E, Rossi G, Veglia F, Busacca M, Vignali M. Risk factors for spontaneous preterm birth: a Northern Italian multicenter case-control study.  Gynecol Obstet Invest. 2002;  53(3) 174-180
    CrossrefPubMedSearch in Google Scholar
  • 35 Carr-Hill R A, Hall M H. The repetition of spontaneous preterm labour.  Br J Obstet Gynaecol. 1985;  92(9) 921-928
    PubMedSearch in Google Scholar
  • 36 Cnattingius S, Granath F, Petersson G, Harlow B L. The influence of gestational age and smoking habits on the risk of subsequent preterm deliveries.  N Engl J Med. 1999;  341(13) 943-948
    CrossrefPubMedSearch in Google Scholar
  • 37 Ekwo E E, Gosselink C A, Moawad A. Unfavorable outcome in penultimate pregnancy and premature rupture of membranes in successive pregnancy.  Obstet Gynecol. 1992;  80(2) 166-172
    PubMedSearch in Google Scholar
  • 38 Basso O, Olsen J, Christensen K. Study of environmental, social, and paternal factors in preterm delivery using sibs and half sibs. A population-based study in Denmark.  J Epidemiol Community Health. 1999;  53(1) 20-23
    PubMedSearch in Google Scholar
  • 39 Hoffman H J, Bakketeig L S. Risk factors associated with the occurrence of preterm birth.  Clin Obstet Gynecol. 1984;  27(3) 539-552
    CrossrefPubMedSearch in Google Scholar
  • 40 Porter T F, Fraser A M, Hunter C Y, Ward R H, Varner M W. The risk of preterm birth across generations.  Obstet Gynecol. 1997;  90(1) 63-67
    CrossrefPubMedSearch in Google Scholar
  • 41 Magnus P, Bakketeig L S, Skjaerven R. Correlations of birth weight and gestational age across generations.  Ann Hum Biol. 1993;  20(3) 231-238
    CrossrefPubMedSearch in Google Scholar
  • 42 Johnstone F, Inglis L. Familial trends in low birth weight.  BMJ. 1974;  3(5932) 659-661
    CrossrefPubMedSearch in Google Scholar
  • 43 Treloar S A, Macones G A, Mitchell L E, Martin N G. Genetic influences on premature parturition in an Australian twin sample.  Twin Res. 2000;  3(2) 80-82
    CrossrefPubMedSearch in Google Scholar
  • 44 Clausson B, Lichtenstein P, Cnattingius S. Genetic influence on birthweight and gestational length determined by studies in offspring of twins.  BJOG. 2000;  107(3) 375-381
    CrossrefPubMedSearch in Google Scholar
  • 45 Tucker J M, Goldenberg R L, Davis R O, Copper R L, Winkler C L, Hauth J C. Etiologies of preterm birth in an indigent population: is prevention a logical expectation?.  Obstet Gynecol. 1991;  77(3) 343-347
    PubMedSearch in Google Scholar
  • 46 Wright V C, Schieve L A, Reynolds M A, Jeng G, Kissin D. Assisted reproductive technology surveillance-United States, 2001.  MMWR Surveill Summ. 2004;  53(1) 1-20
    PubMedSearch in Google Scholar
  • 47 Ananth C V, Joseph K S, Demissie K, Vintzileos A M. Trends in twin preterm birth subtypes in the United States, 1989 through 2000: impact on perinatal mortality.  Am J Obstet Gynecol. 2005;  193(3 pt 2) 1076-1082
    PubMedSearch in Google Scholar
  • 48 Barros F C, Velez Mdel P. Temporal trends of preterm birth subtypes and neonatal outcomes.  Obstet Gynecol. 2006;  107(5) 1035-1041
    PubMedSearch in Google Scholar
  • 49 Castracane V D. Endocrinology of preterm labor.  Clin Obstet Gynecol. 2000;  43(4) 717-726
    CrossrefPubMedSearch in Google Scholar
  • 50 How H, Huang Z H, Zuo J, Lei Z M, Spinnato II J A, Rao C V. Myometrial estradiol and progesterone receptor changes in preterm and term pregnancies.  Obstet Gynecol. 1995;  86(6) 936-940
    CrossrefPubMedSearch in Google Scholar
  • 51 Karalis K, Goodwin G, Majzoub J A. Cortisol blockade of progesterone: a possible molecular mechanism involved in the initiation of human labor.  Nat Med. 1996;  2(5) 556-560
    CrossrefPubMedSearch in Google Scholar
  • 52 da Fonseca E B, Bittar R E, Carvalho M H, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study.  Am J Obstet Gynecol. 2003;  188(2) 419-424
    CrossrefPubMedSearch in Google Scholar
  • 53 Meis P J, Klebanoff M, Thom E et al.. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.  N Engl J Med. 2003;  348(24) 2379-2385
    CrossrefPubMedSearch in Google Scholar
  • 54 Romero R, Espinoza J, Goncalves L F, Kusanovic J P, Friel L A, Nien J K. Inflammation in preterm and term labour and delivery.  Semin Fetal Neonatal Med. 2006;  11(5) 317-326
    CrossrefPubMedSearch in Google Scholar
  • 55 Goncalves L F, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity.  Ment Retard Dev Disabil Res Rev. 2002;  8(1) 3-13
    CrossrefPubMedSearch in Google Scholar
  • 56 Romero R, Quintero R, Oyarzun E et al.. Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes.  Am J Obstet Gynecol. 1988;  159(3) 661-666
    PubMedSearch in Google Scholar
  • 57 Keelan J A, Blumenstein M, Helliwell R J, Sato T A, Marvin K W, Mitchell M D. Cytokines, prostaglandins and parturition-a review.  Placenta. 2003;  24(suppl A) 533-546
    PubMedSearch in Google Scholar
  • 58 Honest H, Bachmann L M, Sundaram R, Gupta J K, Kleijnen J, Khan K S. The accuracy of risk scores in predicting preterm birth-a systematic review.  J Obstet Gynaecol. 2004;  24(4) 343-359
    CrossrefPubMedSearch in Google Scholar
  • 59 Mercer B M. Preterm premature rupture of the membranes: current approaches to evaluation and management.  Obstet Gynecol Clin North Am. 2005;  32(3) 411-428
    CrossrefPubMedSearch in Google Scholar
  • 60 Mercer B M, Arheart K L. Antimicrobial therapy in expectant management of preterm premature rupture of the membranes.  Lancet. 1995;  346(8985) 1271-1279
    CrossrefPubMedSearch in Google Scholar
  • 61 Mercer B M. Preterm premature rupture of the membranes.  Obstet Gynecol. 2003;  101(1) 178-193
    CrossrefPubMedSearch in Google Scholar
  • 62 Naeye R L, Peters E C. Causes and consequences of premature rupture of fetal membranes.  Lancet. 1980;  1(8161) 192-194
    PubMedSearch in Google Scholar
  • 63 Challis J RG, Brooks A N. Maturation and activation of hypothalamic-pituitary-adrenal function in fetal sheep.  Endocr Rev. 1989;  10 182-204
    PubMedSearch in Google Scholar
  • 64 Challis J RG, Matthews S G, Gibb W, Lye S J. Endocrine and paracrine regulation of birth at term and preterm.  Endocr Rev. 2000;  21 514-550
    CrossrefPubMedSearch in Google Scholar
  • 65 Liggins G C, Forster C S, Grieves S A, Schwartz A L. Control of parturition in man.  Biol Reprod. 1977;  16 39-56
    CrossrefPubMedSearch in Google Scholar
  • 66 Gross G, Imamura T, Muglia L J. Gene knockout mice in the study of parturition.  J Soc Gynecol Investig. 2000;  7(2) 88-95
    PubMedSearch in Google Scholar
  • 67 McCormack J T, Greenwald G S. Progesterone and oestradiol-17B concentrations in the peripheral plasma during pregnancy in the mouse.  J Endocrinol. 1974;  62 101-107
    PubMedSearch in Google Scholar
  • 68 Sugimoto Y, Yamasaki A, Segi E et al.. Failure of parturition in mice lacking the prostaglandin F receptor.  Science. 1997;  277 681-683
    CrossrefPubMedSearch in Google Scholar
  • 69 Bonventre J V, Huang Z, Taheri M R et al.. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2.  Nature. 1997;  390 622-625
    CrossrefPubMedSearch in Google Scholar
  • 70 Gross G A, Imamura T, Luedke C et al.. Opposing actions of prostaglandins and oxytocin determine the onset of murine labor.  Proc Natl Acad Sci USA. 1998;  95(20) 11875-11879
    CrossrefPubMedSearch in Google Scholar
  • 71 Piekorz R P, Gingras S, Hoffmeyer A, Ihle J N, Weinstein Y. Regulation of progesterone levels during pregnancy and parturition by signal transducer and activator of transcription 5 and 20alpha-hydroxysteroid dehydrogenase.  Mol Endocrinol. 2005;  19(2) 431-440
    PubMedSearch in Google Scholar
  • 72 Gross G, Imamura T, Vogt S K et al.. Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse.  Am J Physiol Regul Integr Comp Physiol. 2000;  278(6) R1415-R1423
    PubMedSearch in Google Scholar
  • 73 Dudley D J, Branch D W, Edwin S S, Mitchell M D. Induction of preterm birth in mice by RU486.  Biol Reprod. 1996;  55(5) 992-995
    CrossrefPubMedSearch in Google Scholar
  • 74 Hirsch E, Muhle R. Intrauterine bacterial inoculation induces labor in the mouse by mechanisms other than progesterone withdrawal.  Biol Reprod. 2002;  67(4) 1337-1341
    CrossrefPubMedSearch in Google Scholar
  • 75 Condon J C, Jeyasuria P, Faust J M, Mendelson C R. Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition.  Proc Natl Acad Sci USA. 2004;  101(14) 4978-4983
    CrossrefPubMedSearch in Google Scholar
  • 76 Condon J C, Jeyasuria P, Faust J M, Wilson J W, Mendelson C R. A decline in the levels of progesterone receptor coactivators in the pregnant uterus at term may antagonize progesterone receptor function and contribute to the initiation of parturition.  Proc Natl Acad Sci USA. 2003;  100(16) 9518-9523
    CrossrefPubMedSearch in Google Scholar
  • 77 Mendelson C R, Condon J C. New insights into the molecular endocrinology of parturition.  J Steroid Biochem Mol Biol. 2005;  93 113-119
    CrossrefPubMedSearch in Google Scholar
  • 78 Mesiano S, Chan E C, Fitter J T, Kwek K, Yeo G, Smith R. Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium.  J Clin Endocrinol Metab. 2002;  87(6) 2924-2930
    CrossrefPubMedSearch in Google Scholar
  • 79 Bethin K E, Nagai Y, Sladek R et al.. Microarray analysis of uterine gene expression in mouse and human pregnancy.  Mol Endocrinol. 2003;  17(8) 1454-1469
    CrossrefPubMedSearch in Google Scholar
  • 80 Crider K S, Whitehead N, Buus R M. Genetic variation associated with preterm birth: a HuGE review.  Genet Med. 2005;  7(9) 593-604
    CrossrefPubMedSearch in Google Scholar
  • 81 Monzon-Bordonaba F, Vadillo-Ortega F, Feinberg R F. Modulation of trophoblast function by tumor necrosis factor-alpha: a role in pregnancy establishment and maintenance?.  Am J Obstet Gynecol. 2002;  187(6) 1574-1580
    CrossrefPubMedSearch in Google Scholar
  • 82 Maymon E, Ghezzi F, Edwin S S et al.. The tumor necrosis factor alpha and its soluble receptor profile in term and preterm parturition.  Am J Obstet Gynecol. 1999;  181(5 pt 1) 1142-1148
    CrossrefPubMedSearch in Google Scholar
  • 83 Raghupathy R. Th1-type immunity is incompatible with successful pregnancy.  Immunol Today. 1997;  18(10) 478-482
    CrossrefPubMedSearch in Google Scholar
  • 84 Watari M, Watari H, DiSanto M E, Chacko S, Shi G P, Strauss III J F. Pro-inflammatory cytokines induce expression of matrix-metabolizing enzymes in human cervical smooth muscle cells.  Am J Pathol. 1999;  154(6) 1755-1762
    PubMedSearch in Google Scholar
  • 85 Roberts A K, Monzon-Bordonaba F, Van Deerlin P G et al.. Association of polymorphism within the promoter of the tumor necrosis factor alpha gene with increased risk of preterm premature rupture of the fetal membranes.  Am J Obstet Gynecol. 1999;  180(5) 1297-1302
    CrossrefPubMedSearch in Google Scholar
  • 86 Moore S, Ide M, Randhawa M, Walker J J, Reid J G, Simpson N A. An investigation into the association among preterm birth, cytokine gene polymorphisms and periodontal disease.  BJOG. 2004;  111(2) 125-132
    CrossrefPubMedSearch in Google Scholar
  • 87 Aidoo M, McElroy P D, Kolczak M S et al.. Tumor necrosis factor-alpha promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX.  Genet Epidemiol. 2001;  21(3) 201-211
    CrossrefPubMedSearch in Google Scholar
  • 88 Engel S A, Erichsen H C, Savitz D A, Thorp J, Chanock S J, Olshan A F. Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms.  Epidemiology. 2005;  16(4) 469-477
    CrossrefPubMedSearch in Google Scholar
  • 89 Macones G A, Parry S, Elkousy M, Clothier B, Ural S H, Strauss III J F. A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth.  Am J Obstet Gynecol. 2004;  190(6) 1504-1508 discussion 3A
    CrossrefPubMedSearch in Google Scholar
  • 90 Kalish R B, Vardhana S, Gupta M, Chasen S T, Perni S C, Witkin S S. Interleukin-1 receptor antagonist gene polymorphism and multifetal pregnancy outcome.  Am J Obstet Gynecol. 2003;  189(4) 911-914
    CrossrefPubMedSearch in Google Scholar
  • 91 Witkin S S, Vardhana S, Yih M, Doh K, Bongiovanni A M, Gerber S. Polymorphism in intron 2 of the fetal interleukin-1 receptor antagonist genotype influences midtrimester amniotic fluid concentrations of interleukin-1beta and interleukin-1 receptor antagonist and pregnancy outcome.  Am J Obstet Gynecol. 2003;  189(5) 1413-1417
    CrossrefPubMedSearch in Google Scholar
  • 92 Genc M R, Gerber S, Nesin M, Witkin S S. Polymorphism in the interleukin-1 gene complex and spontaneous preterm delivery.  Am J Obstet Gynecol. 2002;  187(1) 157-163
    CrossrefPubMedSearch in Google Scholar
  • 93 Kalish R B, Vardhana S, Gupta M, Perni S C, Witkin S S. Interleukin-4 and -10 gene polymorphisms and spontaneous preterm birth in multifetal gestations.  Am J Obstet Gynecol. 2004;  190(3) 702-706
    CrossrefPubMedSearch in Google Scholar
  • 94 Simhan H N, Krohn M A, Roberts J M, Zeevi A, Caritis S N. Interleukin-6 promoter-174 polymorphism and spontaneous preterm birth.  Am J Obstet Gynecol. 2003;  189(4) 915-918
    CrossrefPubMedSearch in Google Scholar
  • 95 Papazoglou D, Galazios G, Koukourakis M I, Kontomanolis E N, Maltezos E. Association of -634G/C and 936C/T polymorphisms of the vascular endothelial growth factor with spontaneous preterm delivery.  Acta Obstet Gynecol Scand. 2004;  83(5) 461-465
    CrossrefPubMedSearch in Google Scholar
  • 96 Gibson C S, MacLennan A H, Janssen N G et al.. Associations between fetal inherited thrombophilia and adverse pregnancy outcomes.  Am J Obstet Gynecol. 2006;  194(4) 947 e1-10
    PubMedSearch in Google Scholar
  • 97 Hao K, Wang X, Niu T et al.. A candidate gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods.  Hum Mol Genet. 2004;  13(7) 683-691
    CrossrefPubMedSearch in Google Scholar
  • 98 Hartel C, von Otte S, Koch J et al.. Polymorphisms of haemostasis genes as risk factors for preterm delivery.  Thromb Haemost. 2005;  94(1) 88-92
    PubMedSearch in Google Scholar
  • 99 Lorenz E, Hallman M, Marttila R, Haataja R, Schwartz D A. Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population.  Pediatr Res. 2002;  52(3) 373-376
    CrossrefPubMedSearch in Google Scholar
  • 100 Landau R, Dishy V, Wood A J, Stein C M, Smiley R M. Disproportionate decrease in alpha- compared with beta-adrenergic sensitivity in the dorsal hand vein in pregnancy favors vasodilation.  Circulation. 2002;  106(9) 1116-1120
    CrossrefPubMedSearch in Google Scholar
  • 101 Ozkur M, Dogulu F, Ozkur A, Gokmen B, Inaloz S S, Aynacioglu A S. Association of the Gln27Glu polymorphism of the beta-2-adrenergic receptor with preterm labor.  Int J Gynaecol Obstet. 2002;  77(3) 209-215
    CrossrefPubMedSearch in Google Scholar
  • 102 Chen D, Hu Y, Chen C et al.. Polymorphisms of the paraoxonase gene and risk of preterm delivery.  Epidemiology. 2004;  15(4) 466-470
    CrossrefPubMedSearch in Google Scholar
  • 103 Maymon E, Romero R, Pacora P et al.. Evidence for the participation of interstitial collagenase (matrix metalloproteinase 1) in preterm premature rupture of membranes.  Am J Obstet Gynecol. 2000;  183(4) 914-920
    CrossrefPubMedSearch in Google Scholar
  • 104 McLaren J, Taylor D J, Bell S C. Increased concentration of pro-matrix metalloproteinase 9 in term fetal membranes overlying the cervix before labor: implications for membrane remodeling and rupture.  Am J Obstet Gynecol. 2000;  182(2) 409-416
    CrossrefPubMedSearch in Google Scholar
  • 105 Ferrand P E, Parry S, Sammel M et al.. A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans.  Mol Hum Reprod. 2002;  8(5) 494-501
    CrossrefPubMedSearch in Google Scholar
  • 106 Romero R, Chaiworapongsa T, Espinoza J et al.. Fetal plasma MMP-9 concentrations are elevated in preterm premature rupture of the membranes.  Am J Obstet Gynecol. 2002;  187(5) 1125-1130
    CrossrefPubMedSearch in Google Scholar
  • 107 Wang H, Parry S, Macones G et al.. Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM).  Hum Mol Genet. 2004;  13(21) 2659-2669
    CrossrefPubMedSearch in Google Scholar
  • 108 Fortunato S J, Lombardi S J, Menon R. Racial disparity in membrane response to infectious stimuli: a possible explanation for observed differences in the incidence of prematurity. Community award paper.  Am J Obstet Gynecol. 2004;  190(6) 1557-1563
    CrossrefPubMedSearch in Google Scholar
  • 109 Menon R, Velez D R, Simhan H et al.. Multilocus interactions at maternal tumor necrosis factor-alpha, tumor necrosis factor receptors, interleukin-6 and interleukin-6 receptor genes predict spontaneous preterm labor in European-American women.  Am J Obstet Gynecol. 2006;  194(6) 1616-1624
    CrossrefPubMedSearch in Google Scholar
  • 110 Wang X, Chen D, Niu T et al.. Genetic susceptibility to benzene and shortened gestation: evidence of gene-environment interaction.  Am J Epidemiol. 2000;  152(8) 693-700
    CrossrefPubMedSearch in Google Scholar
  • 111 Wang X, Zuckerman B, Pearson C et al.. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight.  JAMA. 2002;  287(2) 195-202
    CrossrefPubMedSearch in Google Scholar
  • 112 Pennell C E, Jacobsson B, Williams S M et al.. Genetic epidemiological studies of preterm birth: guidelines for research.  Am J Obstet Gynecol. 2006;  , In press
    PubMedSearch in Google Scholar
  • 113 Herbert A, Gerry N P, McQueen M B et al.. A common genetic variant is associated with adult and childhood obesity.  Science. 2006;  312(5771) 279-283
    CrossrefPubMedSearch in Google Scholar
  • 114 Austin M P, Leader L. Maternal stress and obstetric and infant outcomes: epidemiological findings and neuroendocrine mechanisms.  Aust NZJ Obstet Gynaecol. 2000;  40(3) 331-337
    PubMedSearch in Google Scholar
  • 115 Barnes D L, Adair L S, Popkin B M. Women's physical activity and pregnancy outcome: a longitudinal analysis from the Philippines.  Int J Epidemiol. 1991;  20(1) 162-172
    CrossrefPubMedSearch in Google Scholar
  • 116 Blackmore-Prince C, Kieke Jr B, Kugaraj K A et al.. Racial differences in the patterns of singleton preterm delivery in the 1988 National Maternal and Infant Health Survey.  Matern Child Health J. 1999;  3(4) 189-197
    CrossrefPubMedSearch in Google Scholar
  • 117 Cnattingius S, Lambe M. Trends in smoking and overweight during pregnancy: prevalence, risks of pregnancy complications, and adverse pregnancy outcomes.  Semin Perinatol. 2002;  26(4) 286-295
    CrossrefPubMedSearch in Google Scholar
  • 118 Iams J D. Preterm birth. In: Gabbe S, Niebyl JF, Simpson JL Obstetrics: Normal and Problem Pregnancies. New York; Churchill Livingstone 1996: 743-820
    Search in Google Scholar
  • 119 Pschirrer E R, Monga M. Risk factors for preterm labor.  Clin Obstet Gynecol. 2000;  43(4) 727-734
    CrossrefPubMedSearch in Google Scholar
  • 120 Hadley C B, Main D M, Gabbe S G. Risk factors for preterm premature rupture of the fetal membranes.  Am J Perinatol. 1990;  7(4) 374-379
    Thieme ConnectPubMedSearch in Google Scholar
  • 121 Harger J H, Hsing A W, Tuomala R E et al.. Risk factors for preterm premature rupture of fetal membranes: a multicenter case-control study.  Am J Obstet Gynecol. 1990;  163(1 pt 1) 130-137
    PubMedSearch in Google Scholar
  • 122 Mercer B M, Goldenberg R L, Meis P J et al.. The Preterm Prediction Study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.  Am J Obstet Gynecol. 2000;  183(3) 738-745
    CrossrefPubMedSearch in Google Scholar

Louis MugliaM.D. Ph.D. 

Center for Preterm Birth Research, Washington University School of Medicine

660 S. Euclid Ave., Campus Box 8208, St. Louis, MO 63110

Email: Muglia_L@kids.wustl.edu