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)


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.


  • 1 Goldenberg R L. The management of preterm labor.  Obstet Gynecol. 2002;  100(5 pt 1) 1020-1037
  • 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
  • 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
  • 4 Committee on Understanding Premature Birth and Assuring Healthy Outcomes .Preterm Birth: Causes, Consequences, and Prevention. Washington, DC; The National Academies Press 2006
  • 5 Ward R M, Beachy J C. Neonatal complications following preterm birth.  BJOG. 2003;  110(suppl 20) 8-16
  • 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
  • 7 Gluckman P D, Hanson M A. Living with the past: evolution, development, and patterns of disease.  Science. 2004;  305(5691) 1733-1736
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 16 Lamont R F. Can antibiotics prevent preterm birth-the pro and con debate.  BJOG. 2005;  112(suppl 1) 67-73
  • 17 McDonald H, Brocklehurst P, Parsons J. Antibiotics for treating bacterial vaginosis in pregnancy.  Cochrane Database Syst Rev. 2005;  (1) CD000262
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 27 Shiono P H, Klebanoff M A. Ethnic differences in preterm and very preterm delivery.  Am J Public Health. 1986;  76(11) 1317-1321
  • 28 Zhang J, Savitz D A. Preterm birth subtypes among blacks and whites.  Epidemiology. 1992;  3(5) 428-433
  • 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
  • 30 Goldstein D B, Tate S K, Sisodiya S M. Pharmacogenetics goes genomic.  Nat Rev Genet. 2003;  4(12) 937-947
  • 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
  • 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
  • 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
  • 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
  • 35 Carr-Hill R A, Hall M H. The repetition of spontaneous preterm labour.  Br J Obstet Gynaecol. 1985;  92(9) 921-928
  • 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
  • 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
  • 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
  • 39 Hoffman H J, Bakketeig L S. Risk factors associated with the occurrence of preterm birth.  Clin Obstet Gynecol. 1984;  27(3) 539-552
  • 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
  • 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
  • 42 Johnstone F, Inglis L. Familial trends in low birth weight.  BMJ. 1974;  3(5932) 659-661
  • 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
  • 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
  • 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
  • 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
  • 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
  • 48 Barros F C, Velez Mdel P. Temporal trends of preterm birth subtypes and neonatal outcomes.  Obstet Gynecol. 2006;  107(5) 1035-1041
  • 49 Castracane V D. Endocrinology of preterm labor.  Clin Obstet Gynecol. 2000;  43(4) 717-726
  • 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
  • 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
  • 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
  • 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
  • 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
  • 55 Goncalves L F, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity.  Ment Retard Dev Disabil Res Rev. 2002;  8(1) 3-13
  • 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
  • 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
  • 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
  • 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
  • 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
  • 61 Mercer B M. Preterm premature rupture of the membranes.  Obstet Gynecol. 2003;  101(1) 178-193
  • 62 Naeye R L, Peters E C. Causes and consequences of premature rupture of fetal membranes.  Lancet. 1980;  1(8161) 192-194
  • 63 Challis J RG, Brooks A N. Maturation and activation of hypothalamic-pituitary-adrenal function in fetal sheep.  Endocr Rev. 1989;  10 182-204
  • 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
  • 65 Liggins G C, Forster C S, Grieves S A, Schwartz A L. Control of parturition in man.  Biol Reprod. 1977;  16 39-56
  • 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
  • 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
  • 68 Sugimoto Y, Yamasaki A, Segi E et al.. Failure of parturition in mice lacking the prostaglandin F receptor.  Science. 1997;  277 681-683
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 77 Mendelson C R, Condon J C. New insights into the molecular endocrinology of parturition.  J Steroid Biochem Mol Biol. 2005;  93 113-119
  • 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
  • 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
  • 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
  • 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
  • 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
  • 83 Raghupathy R. Th1-type immunity is incompatible with successful pregnancy.  Immunol Today. 1997;  18(10) 478-482
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 119 Pschirrer E R, Monga M. Risk factors for preterm labor.  Clin Obstet Gynecol. 2000;  43(4) 727-734
  • 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
  • 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
  • 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

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