Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Preterm birth: Risk factors and interventions for risk reduction

Julian N Robinson, MD
Errol R Norwitz, MD, PhD, MBA
Section Editor
Charles J Lockwood, MD, MHCM
Deputy Editor
Vanessa A Barss, MD, FACOG


Most preterm births (PTBs) are spontaneous: related to preterm labor or preterm premature rupture of membranes. The remainder are iatrogenic: performed because of medical or obstetrical complications that jeopardize the health of the mother or fetus.

There are many risk factors for PTB (table 1) and many pathways from these risk factors to the terminal cascade of events resulting in labor. Preterm labor likely occurs when local uterine factors prematurely stimulate this cascade or suppressive factors that inhibit the cascade and maintain uterine quiescence are withdrawn prematurely. The four major factors leading to preterm labor are intrauterine infection, decidual hemorrhage, excessive uterine stretch, and maternal or fetal stress. Uteroplacental vascular insufficiency, exaggerated inflammatory response, hormonal factors, cervical insufficiency, and genetic predisposition also play a role. (See "Pathogenesis of spontaneous preterm birth".)

Ideally, identification of modifiable and nonmodifiable risk factors for PTB before conception or early in pregnancy will lead to interventions that help prevent this complication. However, few interventions have been proven to prolong pregnancy in women at risk. This goal has been elusive for several reasons: two-thirds of PTBs occur among women with no risk factors, causality has been difficult to prove (eg, a cofactor may be required thus complicating the chain of causality), and no adequate animal model exists for study of spontaneous PTB (sPTB).

Risk factors for PTB and potential interventions to mitigate risk, when possible, will be reviewed here. Pathogenesis of PTB and diagnosis and treatment of preterm labor are discussed separately:

(See "Pathogenesis of spontaneous preterm birth".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jan 2017. | This topic last updated: Thu Feb 09 00:00:00 GMT+00:00 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Bloom SL, Yost NP, McIntire DD, Leveno KJ. Recurrence of preterm birth in singleton and twin pregnancies. Obstet Gynecol 2001; 98:379.
  2. Esplin MS, O'Brien E, Fraser A, et al. Estimating recurrence of spontaneous preterm delivery. Obstet Gynecol 2008; 112:516.
  3. Bhattacharya S, Raja EA, Mirazo ER, et al. Inherited predisposition to spontaneous preterm delivery. Obstet Gynecol 2010; 115:1125.
  4. Mercer BM, Goldenberg RL, Moawad AH, et al. The preterm prediction study: effect of gestational age and cause of preterm birth on subsequent obstetric outcome. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1999; 181:1216.
  5. Lykke JA, Paidas MJ, Langhoff-Roos J. Recurring complications in second pregnancy. Obstet Gynecol 2009; 113:1217.
  6. Kristensen J, Langhoff-Roos J, Kristensen FB. Implications of idiopathic preterm delivery for previous and subsequent pregnancies. Obstet Gynecol 1995; 86:800.
  7. Laughon SK, Albert PS, Leishear K, Mendola P. The NICHD Consecutive Pregnancies Study: recurrent preterm delivery by subtype. Am J Obstet Gynecol 2014; 210:131.e1.
  8. Yamashita M, Hayashi S, Endo M, et al. Incidence and risk factors for recurrent spontaneous preterm birth: A retrospective cohort study in Japan. J Obstet Gynaecol Res 2015; 41:1708.
  9. Ferrero DM, Larson J, Jacobsson B, et al. Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births. PLoS One 2016; 11:e0162506.
  10. Rafael TJ, Hoffman MK, Leiby BE, Berghella V. Gestational age of previous twin preterm birth as a predictor for subsequent singleton preterm birth. Am J Obstet Gynecol 2012; 206:156.e1.
  11. Schaaf JM, Hof MH, Mol BW, et al. Recurrence risk of preterm birth in subsequent singleton pregnancy after preterm twin delivery. Am J Obstet Gynecol 2012; 207:279.e1.
  12. Schaaf JM, Hof MH, Mol BW, et al. Recurrence risk of preterm birth in subsequent twin pregnancy after preterm singleton delivery. BJOG 2012; 119:1624.
  13. Multicenter randomized, controlled trial of a preterm birth prevention program. Collaborative Group on Preterm Birth Prevention. Am J Obstet Gynecol 1993; 169:352.
  14. Urquhart C, Currell R, Harlow F, Callow L. Home uterine monitoring for detecting preterm labour. Cochrane Database Syst Rev 2015; 1:CD006172.
  15. Committee on Practice Bulletins—Obstetrics, The American College of Obstetricians and Gynecologists. Practice bulletin no. 130: prediction and prevention of preterm birth. Obstet Gynecol 2012; 120:964.
  16. Whitworth M, Quenby S. Prophylactic oral betamimetics for preventing preterm labour in singleton pregnancies. Cochrane Database Syst Rev 2008; :CD006395.
  17. Khanprakob T, Laopaiboon M, Lumbiganon P, Sangkomkamhang US. Cyclo-oxygenase (COX) inhibitors for preventing preterm labour. Cochrane Database Syst Rev 2012; 10:CD007748.
  18. van Vliet EO, Askie LA, Mol BW, Oudijk MA. Antiplatelet Agents and the Prevention of Spontaneous Preterm Birth: A Systematic Review and Meta-analysis. Obstet Gynecol 2017; 129:327.
  19. Saccone G, Perriera L, Berghella V. Prior uterine evacuation of pregnancy as independent risk factor for preterm birth: a systematic review and metaanalysis. Am J Obstet Gynecol 2016; 214:572.
  20. Wong LF, Wilkes J, Korgenski K, et al. Risk factors associated with preterm birth after a prior term delivery. BJOG 2016; 123:1772.
  21. Rodrigues T, Barros H. Short interpregnancy interval and risk of spontaneous preterm delivery. Eur J Obstet Gynecol Reprod Biol 2008; 136:184.
  22. Rodriguez MI, Chang R, Thiel de Bocanegra H. The impact of postpartum contraception on reducing preterm birth: findings from California. Am J Obstet Gynecol 2015; 213:703.e1.
  23. Conde-Agudelo A, Rosas-Bermúdez A, Kafury-Goeta AC. Birth spacing and risk of adverse perinatal outcomes: a meta-analysis. JAMA 2006; 295:1809.
  24. Boivin A, Luo ZC, Audibert F, et al. Risk for preterm and very preterm delivery in women who were born preterm. Obstet Gynecol 2015; 125:1177.
  25. Ward K, Argyle V, Meade M, Nelson L. The heritability of preterm delivery. Obstet Gynecol 2005; 106:1235.
  26. Clausson B, Lichtenstein P, Cnattingius S. Genetic influence on birthweight and gestational length determined by studies in offspring of twins. BJOG 2000; 107:375.
  27. 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; 13:683.
  28. Treloar SA, Macones GA, Mitchell LE, Martin NG. Genetic influences on premature parturition in an Australian twin sample. Twin Res 2000; 3:80.
  29. Annells MF, Hart PH, Mullighan CG, et al. Interleukins-1, -4, -6, -10, tumor necrosis factor, transforming growth factor-beta, FAS, and mannose-binding protein C gene polymorphisms in Australian women: Risk of preterm birth. Am J Obstet Gynecol 2004; 191:2056.
  30. Winkvist A, Mogren I, Högberg U. Familial patterns in birth characteristics: impact on individual and population risks. Int J Epidemiol 1998; 27:248.
  31. Macones GA, Parry S, Elkousy M, et al. 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; 190:1504.
  32. Kistka ZA, DeFranco EA, Ligthart L, et al. Heritability of parturition timing: an extended twin design analysis. Am J Obstet Gynecol 2008; 199:43.e1.
  33. Velez DR, Fortunato S, Thorsen P, et al. Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants. Am J Obstet Gynecol 2009; 200:209.e1.
  34. Svensson AC, Sandin S, Cnattingius S, et al. Maternal effects for preterm birth: a genetic epidemiologic study of 630,000 families. Am J Epidemiol 2009; 170:1365.
  35. Wilcox AJ, Skjaerven R, Lie RT. Familial patterns of preterm delivery: maternal and fetal contributions. Am J Epidemiol 2008; 167:474.
  36. Centers for Disease Control and Prevention. Preterm birth. http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm (Accessed on April 14, 2016).
  37. Srinivasjois RM, Shah S, Shah PS, Knowledge Synthesis Group on Determinants Of Preterm/LBW Births. Biracial couples and adverse birth outcomes: a systematic review and meta-analyses. Acta Obstet Gynecol Scand 2012; 91:1134.
  38. Iams JD, Goldenberg RL, Mercer BM, et al. The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1998; 178:1035.
  39. Manuck TA, Lai Y, Meis PJ, et al. Admixture mapping to identify spontaneous preterm birth susceptibility loci in African Americans. Obstet Gynecol 2011; 117:1078.
  40. Genc MR, Onderdonk A. Endogenous bacterial flora in pregnant women and the influence of maternal genetic variation. BJOG 2011; 118:154.
  41. Tsai HJ, Hong X, Chen J, et al. Role of African ancestry and gene-environment interactions in predicting preterm birth. Obstet Gynecol 2011; 118:1081.
  42. Frey HA, Stout MJ, Pearson LN, et al. Genetic variation associated with preterm birth in African-American women. Am J Obstet Gynecol 2016; 215:235.e1.
  43. Wen A, Srinivasan U, Goldberg D, et al. Selected vaginal bacteria and risk of preterm birth: an ecological perspective. J Infect Dis 2014; 209:1087.
  44. Fettweis JM, Brooks JP, Serrano MG, et al. Differences in vaginal microbiome in African American women versus women of European ancestry. Microbiology 2014; 160:2272.
  45. Hyman RW, Fukushima M, Jiang H, et al. Diversity of the vaginal microbiome correlates with preterm birth. Reprod Sci 2014; 21:32.
  46. Vinturache AE, Gyamfi-Bannerman C, Hwang J, et al. Maternal microbiome - A pathway to preterm birth. Semin Fetal Neonatal Med 2016; 21:94.
  47. Genc MR, Witkin SS, Delaney ML, et al. A disproportionate increase in IL-1beta over IL-1ra in the cervicovaginal secretions of pregnant women with altered vaginal microflora correlates with preterm birth. Am J Obstet Gynecol 2004; 190:1191.
  48. Simhan HN, Caritis SN, Krohn MA, et al. Decreased cervical proinflammatory cytokines permit subsequent upper genital tract infection during pregnancy. Am J Obstet Gynecol 2003; 189:560.
  49. Simhan HN, Krohn MA. First-trimester cervical inflammatory milieu and subsequent early preterm birth. Am J Obstet Gynecol 2009; 200:377.e1.
  50. Shapiro-Mendoza CK, Barfield WD, Henderson Z, et al. CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth. MMWR Morb Mortal Wkly Rep 2016; 65:826.
  51. Koike T, Minakami H, Kosuge S, et al. Uterine leiomyoma in pregnancy: its influence on obstetric performance. J Obstet Gynaecol Res 1999; 25:309.
  52. Davis JL, Ray-Mazumder S, Hobel CJ, et al. Uterine leiomyomas in pregnancy: a prospective study. Obstet Gynecol 1990; 75:41.
  53. Rice JP, Kay HH, Mahony BS. The clinical significance of uterine leiomyomas in pregnancy. Am J Obstet Gynecol 1989; 160:1212.
  54. Smith GC, Wood AM, Pell JP, Dobbie R. Sudden infant death syndrome and complications in other pregnancies. Lancet 2005; 366:2107.
  55. Kiely JL. What is the population-based risk of preterm birth among twins and other multiples? Clin Obstet Gynecol 1998; 41:3.
  56. TambyRaja RL, Ratnam SS. Plasma steroid changes in twin pregnancies. Prog Clin Biol Res 1981; 69A:189.
  57. Muechler EK, Huang KE. Plasma estrogen and progesterone in quintuplet pregnancy induced with menotropins. Am J Obstet Gynecol 1983; 147:105.
  58. Weiss G, Goldsmith LT, Sachdev R, et al. Elevated first-trimester serum relaxin concentrations in pregnant women following ovarian stimulation predict prematurity risk and preterm delivery. Obstet Gynecol 1993; 82:821.
  59. Lykke JA, Dideriksen KL, Lidegaard O, Langhoff-Roos J. First-trimester vaginal bleeding and complications later in pregnancy. Obstet Gynecol 2010; 115:935.
  60. Szymusik I, Bartnik P, Wypych K, et al. The association of first trimester bleeding with preterm delivery. J Perinat Med 2015; 43:525.
  61. Lockwood CJ. Risk factors for preterm birth and new approaches to its early diagnosis. J Perinat Med 2015; 43:499.
  62. Lockwood CJ, Kayisli UA, Stocco C, et al. Abruption-induced preterm delivery is associated with thrombin-mediated functional progesterone withdrawal in decidual cells. Am J Pathol 2012; 181:2138.
  63. Mackenzie AP, Schatz F, Krikun G, et al. Mechanisms of abruption-induced premature rupture of the fetal membranes: Thrombin enhanced decidual matrix metalloproteinase-3 (stromelysin-1) expression. Am J Obstet Gynecol 2004; 191:1996.
  64. Lockwood CJ, Toti P, Arcuri F, et al. Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term decidua. Am J Pathol 2005; 167:1443.
  65. Manuck TA, Esplin MS, Biggio J, et al. Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth. Am J Obstet Gynecol 2016; 214:376.e1.
  66. Newman RB, Goldenberg RL, Iams JD, et al. Preterm prediction study: comparison of the cervical score and Bishop score for prediction of spontaneous preterm delivery. Obstet Gynecol 2008; 112:508.
  67. Norwitz ER, Robinson JN, Challis JR. The control of labor. N Engl J Med 1999; 341:660.
  68. Salafia CM, Vogel CA, Vintzileos AM, et al. Placental pathologic findings in preterm birth. Am J Obstet Gynecol 1991; 165:934.
  69. Klein LL, Gibbs RS. Use of microbial cultures and antibiotics in the prevention of infection-associated preterm birth. Am J Obstet Gynecol 2004; 190:1493.
  70. Goldenberg RL, Andrews WW, Hauth JC. Choriodecidual infection and preterm birth. Nutr Rev 2002; 60:S19.
  71. Williams MC, O'Brien WF, Nelson RN, Spellacy WN. Histologic chorioamnionitis is associated with fetal growth restriction in term and preterm infants. Am J Obstet Gynecol 2000; 183:1094.
  72. Schnarr J, Smaill F. Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Eur J Clin Invest 2008; 38 Suppl 2:50.
  73. Meis PJ, Michielutte R, Peters TJ, et al. Factors associated with preterm birth in Cardiff, Wales. I. Univariable and multivariable analysis. Am J Obstet Gynecol 1995; 173:590.
  74. Meis PJ, Michielutte R, Peters TJ, et al. Factors associated with preterm birth in Cardiff, Wales. II. Indicated and spontaneous preterm birth. Am J Obstet Gynecol 1995; 173:597.
  75. Connolly A, Thorp JM Jr. Urinary tract infections in pregnancy. Urol Clin North Am 1999; 26:779.
  76. Uncu Y, Uncu G, Esmer A, Bilgel N. Should asymptomatic bacteriuria be screened in pregnancy? Clin Exp Obstet Gynecol 2002; 29:281.
  77. Smaill F, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2007; :CD000490.
  78. Xiong X, Buekens P, Fraser WD, et al. Periodontal disease and adverse pregnancy outcomes: a systematic review. BJOG 2006; 113:135.
  79. Vergnes JN, Sixou M. Preterm low birth weight and maternal periodontal status: a meta-analysis. Am J Obstet Gynecol 2007; 196:135.e1.
  80. Offenbacher S, Jared HL, O'Reilly PG, et al. Potential pathogenic mechanisms of periodontitis associated pregnancy complications. Ann Periodontol 1998; 3:233.
  81. Newnham JP, Shub A, Jobe AH, et al. The effects of intra-amniotic injection of periodontopathic lipopolysaccharides in sheep. Am J Obstet Gynecol 2005; 193:313.
  82. Han YW, Redline RW, Li M, et al. Fusobacterium nucleatum induces premature and term stillbirths in pregnant mice: implication of oral bacteria in preterm birth. Infect Immun 2004; 72:2272.
  83. Kornman KS, di Giovine FS. Genetic variations in cytokine expression: a risk factor for severity of adult periodontitis. Ann Periodontol 1998; 3:327.
  84. Galbraith GM, Steed RB, Sanders JJ, Pandey JP. Tumor necrosis factor alpha production by oral leukocytes: influence of tumor necrosis factor genotype. J Periodontol 1998; 69:428.
  85. Kornman KS, Crane A, Wang HY, et al. The interleukin-1 genotype as a severity factor in adult periodontal disease. J Clin Periodontol 1997; 24:72.
  86. Boggess KA, Moss K, Madianos P, et al. Fetal immune response to oral pathogens and risk of preterm birth. Am J Obstet Gynecol 2005; 193:1121.
  87. Sanz M, Kornman K, Working group 3 of joint EFP/AAP workshop. Periodontitis and adverse pregnancy outcomes: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol 2013; 40 Suppl 14:S164.
  88. Polyzos NP, Polyzos IP, Zavos A, et al. Obstetric outcomes after treatment of periodontal disease during pregnancy: systematic review and meta-analysis. BMJ 2010; 341:c7017.
  89. Uppal A, Uppal S, Pinto A, et al. The effectiveness of periodontal disease treatment during pregnancy in reducing the risk of experiencing preterm birth and low birth weight: a meta-analysis. J Am Dent Assoc 2010; 141:1423.
  90. Chambrone L, Pannuti CM, Guglielmetti MR, Chambrone LA. Evidence grade associating periodontitis with preterm birth and/or low birth weight: II: a systematic review of randomized trials evaluating the effects of periodontal treatment. J Clin Periodontol 2011; 38:902.
  91. Kim AJ, Lo AJ, Pullin DA, et al. Scaling and root planing treatment for periodontitis to reduce preterm birth and low birth weight: a systematic review and meta-analysis of randomized controlled trials. J Periodontol 2012; 83:1508.
  92. Schwendicke F, Karimbux N, Allareddy V, Gluud C. Periodontal treatment for preventing adverse pregnancy outcomes: a meta- and trial sequential analysis. PLoS One 2015; 10:e0129060.
  93. Michalowicz BS, Gustafsson A, Thumbigere-Math V, Buhlin K. The effects of periodontal treatment on pregnancy outcomes. J Clin Periodontol 2013; 40 Suppl 14:S195.
  94. Valkenburg-van den Berg AW, Sprij AJ, Dekker FW, et al. Association between colonization with Group B Streptococcus and preterm delivery: a systematic review. Acta Obstet Gynecol Scand 2009; 88:958.
  95. Martin DH, Koutsky L, Eschenbach DA, et al. Prematurity and perinatal mortality in pregnancies complicated by maternal Chlamydia trachomatis infections. JAMA 1982; 247:1585.
  96. Andrews WW, Goldenberg RL, Mercer B, et al. The Preterm Prediction Study: association of second-trimester genitourinary chlamydia infection with subsequent spontaneous preterm birth. Am J Obstet Gynecol 2000; 183:662.
  97. Ryan GM Jr, Abdella TN, McNeeley SG, et al. Chlamydia trachomatis infection in pregnancy and effect of treatment on outcome. Am J Obstet Gynecol 1990; 162:34.
  98. Cohen I, Veille JC, Calkins BM. Improved pregnancy outcome following successful treatment of chlamydial infection. JAMA 1990; 263:3160.
  99. Hillier SL, Nugent RP, Eschenbach DA, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 1995; 333:1737.
  100. Meis PJ, Goldenberg RL, Mercer B, et al. The preterm prediction study: significance of vaginal infections. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1995; 173:1231.
  101. Bretelle F, Rozenberg P, Pascal A, et al. High Atopobium vaginae and Gardnerella vaginalis vaginal loads are associated with preterm birth. Clin Infect Dis 2015; 60:860.
  102. Edwards LE, Barrada MI, Hamann AA, Hakanson EY. Gonorrhea in pregnancy. Am J Obstet Gynecol 1978; 132:637.
  103. Watson-Jones D, Changalucha J, Gumodoka B, et al. Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy. J Infect Dis 2002; 186:940.
  104. Silver BJ, Guy RJ, Kaldor JM, et al. Trichomonas vaginalis as a cause of perinatal morbidity: a systematic review and meta-analysis. Sex Transm Dis 2014; 41:369.
  105. Sweeney EL, Kallapur SG, Gisslen T, et al. Placental Infection With Ureaplasma species Is Associated With Histologic Chorioamnionitis and Adverse Outcomes in Moderately Preterm and Late-Preterm Infants. J Infect Dis 2016; 213:1340.
  106. Collins S, Ramsay M, Slack MP, et al. Risk of invasive Haemophilus influenzae infection during pregnancy and association with adverse fetal outcomes. JAMA 2014; 311:1125.
  107. Andrews WW, Klebanoff MA, Thom EA, et al. Midpregnancy genitourinary tract infection with Chlamydia trachomatis: association with subsequent preterm delivery in women with bacterial vaginosis and Trichomonas vaginalis. Am J Obstet Gynecol 2006; 194:493.
  108. Mancuso MS, Figueroa D, Szychowski JM, et al. Midtrimester bacterial vaginosis and cervical length in women at risk for preterm birth. Am J Obstet Gynecol 2011; 204:342.e1.
  109. Simcox R, Sin WT, Seed PT, et al. Prophylactic antibiotics for the prevention of preterm birth in women at risk: a meta-analysis. Aust N Z J Obstet Gynaecol 2007; 47:368.
  110. Thinkhamrop J, Hofmeyr GJ, Adetoro O, et al. Antibiotic prophylaxis during the second and third trimester to reduce adverse pregnancy outcomes and morbidity. Cochrane Database Syst Rev 2015; 1:CD002250.
  111. Martin DH, Eschenbach DA, Cotch MF, et al. Double-Blind Placebo-Controlled Treatment Trial of Chlamydia trachomatis Endocervical Infections in Pregnant Women. Infect Dis Obstet Gynecol 1997; 5:10.
  112. Leitich H, Brunbauer M, Bodner-Adler B, et al. Antibiotic treatment of bacterial vaginosis in pregnancy: a meta-analysis. Am J Obstet Gynecol 2003; 188:752.
  113. Carey JC, Klebanoff MA, Hauth JC, 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; 342:534.
  114. Brocklehurst P, Hannah M, McDonald H. Interventions for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev 2000; :CD000262.
  115. Haahr T, Ersbøll AS, Karlsen MA, et al. Treatment of bacterial vaginosis in pregnancy in order to reduce the risk of spontaneous preterm delivery - a clinical recommendation. Acta Obstet Gynecol Scand 2016; 95:850.
  116. Eschenbach DA, Nugent RP, Rao AV, et al. A randomized placebo-controlled trial of erythromycin for the treatment of Ureaplasma urealyticum to prevent premature delivery. The Vaginal Infections and Prematurity Study Group. Am J Obstet Gynecol 1991; 164:734.
  117. Raynes-Greenow CH, Roberts CL, Bell JC, et al. Antibiotics for ureaplasma in the vagina in pregnancy. Cochrane Database Syst Rev 2004; :CD003767.
  118. Klebanoff MA, Regan JA, Rao AV, et al. Outcome of the Vaginal Infections and Prematurity Study: results of a clinical trial of erythromycin among pregnant women colonized with group B streptococci. Am J Obstet Gynecol 1995; 172:1540.
  119. Klebanoff MA, Carey JC, Hauth JC, et al. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med 2001; 345:487.
  120. Koss CA, Baras DC, Lane SD, et al. Investigation of metronidazole use during pregnancy and adverse birth outcomes. Antimicrob Agents Chemother 2012; 56:4800.
  121. Kigozi GG, Brahmbhatt H, Wabwire-Mangen F, et al. Treatment of Trichomonas in pregnancy and adverse outcomes of pregnancy: a subanalysis of a randomized trial in Rakai, Uganda. Am J Obstet Gynecol 2003; 189:1398.
  122. Mann JR, McDermott S, Zhou L, et al. Treatment of trichomoniasis in pregnancy and preterm birth: an observational study. J Womens Health (Larchmt) 2009; 18:493.
  123. Gülmezoglu AM, Azhar M. Interventions for trichomoniasis in pregnancy. Cochrane Database Syst Rev 2011; :CD000220.
  124. Stringer E, Read JS, Hoffman I, et al. Treatment of trichomoniasis in pregnancy in sub-Saharan Africa does not appear to be associated with low birth weight or preterm birth. S Afr Med J 2010; 100:58.
  125. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
  126. Aidoo M, McElroy PD, Kolczak MS, 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; 21:201.
  127. Luntamo M, Kulmala T, Mbewe B, et al. Effect of repeated treatment of pregnant women with sulfadoxine-pyrimethamine and azithromycin on preterm delivery in Malawi: a randomized controlled trial. Am J Trop Med Hyg 2010; 83:1212.
  128. Wolfe EB, Parise ME, Haddix AC, et al. Cost-effectiveness of sulfadoxine-pyrimethamine for the prevention of malaria-associated low birth weight. Am J Trop Med Hyg 2001; 64:178.
  129. Garner P, Gülmezoglu AM. Drugs for preventing malaria-related illness in pregnant women and death in the newborn. Cochrane Database Syst Rev 2003; :CD000169.
  130. Mozurkewich EL, Luke B, Avni M, Wolf FM. Working conditions and adverse pregnancy outcome: a meta-analysis. Obstet Gynecol 2000; 95:623.
  131. Saurel-Cubizolles MJ, Zeitlin J, Lelong N, et al. Employment, working conditions, and preterm birth: results from the Europop case-control survey. J Epidemiol Community Health 2004; 58:395.
  132. Berkowitz GS, Papiernik E. Working conditions, maternity legislation, and preterm birth. Semin Perinatol 1995; 19:272.
  133. Fox NS, Gelber SE, Kalish RB, Chasen ST. The recommendation for bed rest in the setting of arrested preterm labor and premature rupture of membranes. Am J Obstet Gynecol 2009; 200:165.e1.
  134. Goldenberg RL, Cliver SP, Bronstein J, et al. Bed rest in pregnancy. Obstet Gynecol 1994; 84:131.
  135. Sciscione AC. Maternal activity restriction and the prevention of preterm birth. Am J Obstet Gynecol 2010; 202:232.e1.
  136. Sosa CG, Althabe F, Belizán JM, Bergel E. Bed rest in singleton pregnancies for preventing preterm birth. Cochrane Database Syst Rev 2015; :CD003581.
  137. Grobman WA, Gilbert SA, Iams JD, et al. Activity restriction among women with a short cervix. Obstet Gynecol 2013; 121:1181.
  138. Fox NS, Jean-Pierre C, Predanic M, Chasen ST. Does hospitalization prevent preterm delivery in the patient with a short cervix? Am J Perinatol 2007; 24:49.
  139. Yost NP, Bloom SL, McIntire DD, Leveno KJ. Hospitalization for women with arrested preterm labor: a randomized trial. Obstet Gynecol 2005; 106:14.
  140. Kovacevich GJ, Gaich SA, Lavin JP, et al. The prevalence of thromboembolic events among women with extended bed rest prescribed as part of the treatment for premature labor or preterm premature rupture of membranes. Am J Obstet Gynecol 2000; 182:1089.
  141. Crowther CA, Han S. Hospitalisation and bed rest for multiple pregnancy. Cochrane Database Syst Rev 2010; :CD000110.
  142. Abdul Sultan A, West J, Tata LJ, et al. Risk of first venous thromboembolism in pregnant women in hospital: population based cohort study from England. BMJ 2013; 347:f6099.
  143. Convertino VA, Bloomfield SA, Greenleaf JE. An overview of the issues: physiological effects of bed rest and restricted physical activity. Med Sci Sports Exerc 1997; 29:187.
  144. Di Mascio D, Magro-Malosso ER, Saccone G, et al. Exercise during pregnancy in normal-weight women and risk of preterm birth: a systematic review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol 2016; 215:561.
  145. Berghella V, Klebanoff M, McPherson C, et al. Sexual intercourse association with asymptomatic bacterial vaginosis and Trichomonas vaginalis treatment in relationship to preterm birth. Am J Obstet Gynecol 2002; 187:1277.
  146. Read JS, Klebanoff MA. Sexual intercourse during pregnancy and preterm delivery: effects of vaginal microorganisms. The Vaginal Infections and Prematurity Study Group. Am J Obstet Gynecol 1993; 168:514.
  147. Mills JL, Harlap S, Harley EE. Should coitus late in pregnancy be discouraged? Lancet 1981; 2:136.
  148. Yost NP, Owen J, Berghella V, et al. Effect of coitus on recurrent preterm birth. Obstet Gynecol 2006; 107:793.
  149. SIMPSON WJ. A preliminary report on cigarette smoking and the incidence of prematurity. Am J Obstet Gynecol 1957; 73:807.
  150. Meyer MB, Tonascia JA. Maternal smoking, pregnancy complications, and perinatal mortality. Am J Obstet Gynecol 1977; 128:494.
  151. Shiono PH, Klebanoff MA, Rhoads GG. Smoking and drinking during pregnancy. Their effects on preterm birth. JAMA 1986; 255:82.
  152. Berkowitz GS, Papiernik E. Epidemiology of preterm birth. Epidemiol Rev 1993; 15:414.
  153. Cnattingius S, Forman MR, Berendes HW, et al. Effect of age, parity, and smoking on pregnancy outcome: a population-based study. Am J Obstet Gynecol 1993; 168:16.
  154. Harlow BL, Frigoletto FD, Cramer DW, et al. Determinants of preterm delivery in low-risk pregnancies. The RADIUS Study Group. J Clin Epidemiol 1996; 49:441.
  155. Kyrklund-Blomberg NB, Cnattingius S. Preterm birth and maternal smoking: risks related to gestational age and onset of delivery. Am J Obstet Gynecol 1998; 179:1051.
  156. http://www.cdc.gov/mmwr/volumes/65/wr/mm6532a4.htm?s_cid=mm6532a4_e.
  157. Nicholson W, Croughan-Minihane M, Posner S, et al. Preterm delivery in patients admitted with preterm labor: a prediction study. J Matern Fetal Med 2001; 10:102.
  158. Ney JA, Dooley SL, Keith LG, et al. The prevalence of substance abuse in patients with suspected preterm labor. Am J Obstet Gynecol 1990; 162:1562.
  159. Spence MR, Williams R, DiGregorio GJ, et al. The relationship between recent cocaine use and pregnancy outcome. Obstet Gynecol 1991; 78:326.
  160. Borges G, Lopez-Cervantes M, Medina-Mora ME, et al. Alcohol consumption, low birth weight, and preterm delivery in the National Addiction Survey (Mexico). Int J Addict 1993; 28:355.
  161. Wilkins-Haug L, Gabow PA. Toluene abuse during pregnancy: obstetric complications and perinatal outcomes. Obstet Gynecol 1991; 77:504.
  162. Boer K, Smit BJ, van Huis AM, Hogerzeil HV. Substance use in pregnancy: do we care? Acta Paediatr Suppl 1994; 404:65.
  163. Almario CV, Seligman NS, Dysart KC, et al. Risk factors for preterm birth among opiate-addicted gravid women in a methadone treatment program. Am J Obstet Gynecol 2009; 201:326.e1.
  164. Villar J, Gülmezoglu AM, de Onis M. Nutritional and antimicrobial interventions to prevent preterm birth: an overview of randomized controlled trials. Obstet Gynecol Surv 1998; 53:575.
  165. Bloomfield FH, Oliver MH, Hawkins P, et al. A periconceptional nutritional origin for noninfectious preterm birth. Science 2003; 300:606.
  166. Kumarasamy V, Mitchell MD, Bloomfield FH, et al. Effects of periconceptional undernutrition on the initiation of parturition in sheep. Am J Physiol Regul Integr Comp Physiol 2005; 288:R67.
  167. Rayco-Solon P, Fulford AJ, Prentice AM. Maternal preconceptional weight and gestational length. Am J Obstet Gynecol 2005; 192:1133.
  168. Stein Z, Susser M. The Dutch famine, 1944-1945, and the reproductive process. I. Effects on six indices at birth. Pediatr Res 1975; 9:70.
  169. Kramer MS. Isocaloric balanced protein supplementation in pregnancy. Cochrane Database Syst Rev 2000; :CD000118.
  170. Ota E, Tobe-Gai R, Mori R, Farrar D. Antenatal dietary advice and supplementation to increase energy and protein intake. Cochrane Database Syst Rev 2012; :CD000032.
  171. Vahratian A, Siega-Riz AM, Savitz DA, Thorp JM Jr. Multivitamin use and the risk of preterm birth. Am J Epidemiol 2004; 160:886.
  172. Fawzi WW, Msamanga GI, Urassa W, et al. Vitamins and perinatal outcomes among HIV-negative women in Tanzania. N Engl J Med 2007; 356:1423.
  173. Spinnato JA 2nd, Freire S, Pinto e Silva JL, et al. Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis. Am J Obstet Gynecol 2008; 199:433.e1.
  174. Rumbold A, Ota E, Nagata C, et al. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev 2015; :CD004072.
  175. Rumbold A, Ota E, Hori H, et al. Vitamin E supplementation in pregnancy. Cochrane Database Syst Rev 2015; :CD004069.
  176. Saccone G, Berghella V. Folic acid supplementation in pregnancy to prevent preterm birth: a systematic review and meta-analysis of randomized controlled trials. Eur J Obstet Gynecol Reprod Biol 2016; 199:76.
  177. Pérez-López FR, Pasupuleti V, Mezones-Holguin E, et al. Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 2015; 103:1278.
  178. Catov JM, Bodnar LM, Ness RB, et al. Association of periconceptional multivitamin use and risk of preterm or small-for-gestational-age births. Am J Epidemiol 2007; 166:296.
  179. Han Z, Mulla S, Beyene J, et al. Maternal underweight and the risk of preterm birth and low birth weight: a systematic review and meta-analyses. Int J Epidemiol 2011; 40:65.
  180. McDonald SD, Han Z, Mulla S, et al. Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses. BMJ 2010; 341:c3428.
  181. Cnattingius S, Villamor E, Johansson S, et al. Maternal obesity and risk of preterm delivery. JAMA 2013; 309:2362.
  182. Girsen AI, Mayo JA, Carmichael SL, et al. Women's prepregnancy underweight as a risk factor for preterm birth: a retrospective study. BJOG 2016; 123:2001.
  183. Honest H, Bachmann LM, Ngai C, et al. The accuracy of maternal anthropometry measurements as predictor for spontaneous preterm birth--a systematic review. Eur J Obstet Gynecol Reprod Biol 2005; 119:11.
  184. Carmichael SL, Abrams B. A critical review of the relationship between gestational weight gain and preterm delivery. Obstet Gynecol 1997; 89:865.
  185. Dietz PM, Callaghan WM, Cogswell ME, et al. Combined effects of prepregnancy body mass index and weight gain during pregnancy on the risk of preterm delivery. Epidemiology 2006; 17:170.
  186. Schieve LA, Cogswell ME, Scanlon KS, et al. Prepregnancy body mass index and pregnancy weight gain: associations with preterm delivery. The NMIHS Collaborative Study Group. Obstet Gynecol 2000; 96:194.
  187. Thangaratinam S, Rogozinska E, Jolly K, et al. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012; 344:e2088.
  188. Myklestad K, Vatten LJ, Magnussen EB, et al. Do parental heights influence pregnancy length?: A population-based prospective study, HUNT 2. BMC Pregnancy Childbirth 2013; 13:33.
  189. Derraik JG, Lundgren M, Cutfield WS, Ahlsson F. Maternal Height and Preterm Birth: A Study on 192,432 Swedish Women. PLoS One 2016; 11:e0154304.
  190. Han Z, Lutsiv O, Mulla S, McDonald SD. Maternal height and the risk of preterm birth and low birth weight: a systematic review and meta-analyses. J Obstet Gynaecol Can 2012; 34:721.
  191. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6409a3.htm?s_cid=mm6409a3_e.
  192. Lockwood CJ. Stress-associated preterm delivery: the role of corticotropin-releasing hormone. Am J Obstet Gynecol 1999; 180:S264.
  193. Petraglia F, Hatch MC, Lapinski R, et al. Lack of effect of psychosocial stress on maternal corticotropin-releasing factor and catecholamine levels at 28 weeks' gestation. J Soc Gynecol Investig 2001; 8:83.
  194. Lu MC, Chen B. Racial and ethnic disparities in preterm birth: the role of stressful life events. Am J Obstet Gynecol 2004; 191:691.
  195. Kramer MS, Lydon J, Séguin L, et al. Stress pathways to spontaneous preterm birth: the role of stressors, psychological distress, and stress hormones. Am J Epidemiol 2009; 169:1319.
  196. Hedegaard M, Henriksen TB, Sabroe S, Secher NJ. Psychological distress in pregnancy and preterm delivery. BMJ 1993; 307:234.
  197. Peacock JL, Bland JM, Anderson HR. Preterm delivery: effects of socioeconomic factors, psychological stress, smoking, alcohol, and caffeine. BMJ 1995; 311:531.
  198. Hedegaard M, Henriksen TB, Sabroe S, Secher NJ. The relationship between psychological distress during pregnancy and birth weight for gestational age. Acta Obstet Gynecol Scand 1996; 75:32.
  199. Dole N, Savitz DA, Hertz-Picciotto I, et al. Maternal stress and preterm birth. Am J Epidemiol 2003; 157:14.
  200. Shaw JG, Asch SM, Kimerling R, et al. Posttraumatic stress disorder and risk of spontaneous preterm birth. Obstet Gynecol 2014; 124:1111.
  201. Chen MJ, Grobman WA, Gollan JK, Borders AE. The use of psychosocial stress scales in preterm birth research. Am J Obstet Gynecol 2011; 205:402.
  202. Hodnett ED, Fredericks S. Support during pregnancy for women at increased risk of low birthweight babies. Cochrane Database Syst Rev 2003; :CD000198.
  203. Khianman B, Pattanittum P, Thinkhamrop J, Lumbiganon P. Relaxation therapy for preventing and treating preterm labour. Cochrane Database Syst Rev 2012; :CD007426.
  204. Whitworth M, Quenby S, Cockerill RO, Dowswell T. Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes. Cochrane Database Syst Rev 2011; :CD006760.
  205. Zeitlin J, Saurel-Cubizolles MJ, De Mouzon J, et al. Fetal sex and preterm birth: are males at greater risk? Hum Reprod 2002; 17:2762.
  206. Ingemarsson I. Gender aspects of preterm birth. BJOG 2003; 110 Suppl 20:34.
  207. Zeitlin J, Ancel PY, Larroque B, et al. Fetal sex and indicated very preterm birth: results of the EPIPAGE study. Am J Obstet Gynecol 2004; 190:1322.
  208. McGregor JA, Leff M, Orleans M, Baron A. Fetal gender differences in preterm birth: findings in a North American cohort. Am J Perinatol 1992; 9:43.
  209. Dolan SM, Gross SJ, Merkatz IR, et al. The contribution of birth defects to preterm birth and low birth weight. Obstet Gynecol 2007; 110:318.
  210. Purisch SE, DeFranco EA, Muglia LJ, et al. Preterm birth in pregnancies complicated by major congenital malformations: a population-based study. Am J Obstet Gynecol 2008; 199:287.e1.
  211. Lackman F, Capewell V, Richardson B, et al. The risks of spontaneous preterm delivery and perinatal mortality in relation to size at birth according to fetal versus neonatal growth standards. Am J Obstet Gynecol 2001; 184:946.
  212. Morken NH, Källen K, Jacobsson B. Fetal growth and onset of delivery: a nationwide population-based study of preterm infants. Am J Obstet Gynecol 2006; 195:154.
  213. Ott WJ. Intrauterine growth retardation and preterm delivery. Am J Obstet Gynecol 1993; 168:1710.
  214. Zeitlin J, Ancel PY, Saurel-Cubizolles MJ, Papiernik E. The relationship between intrauterine growth restriction and preterm delivery: an empirical approach using data from a European case-control study. BJOG 2000; 107:750.
  215. Gardosi JO. Prematurity and fetal growth restriction. Early Hum Dev 2005; 81:43.
  216. Wadhwa PD, Garite TJ, Porto M, et al. Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: a prospective investigation. Am J Obstet Gynecol 2004; 191:1063.
  217. Basso O, Olsen J, Christensen K. Low birthweight and prematurity in relation to paternal factors: a study of recurrence. Int J Epidemiol 1999; 28:695.
  218. Boyd HA, Poulsen G, Wohlfahrt J, et al. Maternal contributions to preterm delivery. Am J Epidemiol 2009; 170:1358.
  219. Conde-Agudelo A, Papageorghiou AT, Kennedy SH, Villar J. Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: a systematic review and meta-analysis. BJOG 2011; 118:1042.