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Cited by 7,801Preterm Birth and ChorioamnionitisInfant Development and Preterm CareMaternal and Perinatal Health Interventions

Epidemiology and causes of preterm birth

Open access
Goldenberg, Robert L, Culhane, Jennifer F, Iams, Jay D, Romero, Roberto·2008·The Lancet
DOI 10.1016/s0140-6736(08)60074-4PMC PMC7134569
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Abstract

This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM-together called spontaneous preterm births-are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.

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Crossref · 10.1016/s0140-6736(08)60074-4

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Claims the paper makes

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  • Premisecitation

    Black women are three to four times more likely to have a very early preterm birth than women from other racial or ethnic groups.

    “Black women are also three to four times more likely to have a very early preterm birth than women from other racial or ethnic groups.”
    • Also stated in: § Maternal risk factors · plain
      “Black women are also three to four times more likely to have a very early preterm birth than women from other racial or ethnic groups.22, 23”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Goldenberg, 1996, Medical, psychosocial, and behavioral risk factors do not explain the increased risk for low birth weight among black women, Am J Obstet Gynecol source

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    • cites [23] Fiscella, 1996, Race, perinatal outcome, and amniotic infection, Obstet Gynecol Surv source

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  • Premisecitation

    Singleton pregnancies after in-vitro fertilisation are at increased risk of preterm birth.

    “Singleton pregnancies after in-vitro fertilisation are also at increased risk of preterm birth.10”
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    • cites [10] Jackson, 2004, Perinatal outcomes in singletons following in vitro fertilization: a meta–analysis, Obstet Gynecol source

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  • Premisecitation

    Much of the increase in the singleton preterm birth rate is explained by rising numbers of indicated preterm births.

    “Much of the increase in the singleton preterm birth rate is explained by rising numbers of indicated preterm births (figure 3 ).9”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Ananth, 2005, Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000, Obstet Gynecol source

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  • Premisecitation

    Inflammatory decidual activation is an important pathway leading to labour initiation.

    “An important pathway leading to labour initiation implicates inflammatory decidual activation.19”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Romero, 2006, The preterm parturition syndrome, BJOG source

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  • Premisenone given

    In many USA immigrant groups, a longer time spent living in the USA is associated with a higher preterm birth rate.

    “What does seem clear, however, is that in many USA immigrant groups, the greater the length of time spent living in the USA, the higher the preterm birth rate; the explanation for this finding is also unknown.”
    Quote in the paperNot a substantial claim
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    Premisecitation

    About 30-35% of preterm births are indicated, 40-45% follow spontaneous preterm labour, and 25-30% follow PPROM.

    “About 30–35% of preterm births are indicated, 40–45% follow spontaneous preterm labour, and 25–30% follow PPROM;”
    • Also stated in: § Epidemiology · plain
      “About 30–35% of preterm births are indicated, 40–45% follow spontaneous preterm labour, and 25–30% follow PPROM; births that follow spontaneous labour and PPROM are together designated spontaneous preterm births.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Premisenone given

    Nearly 60% of twins are born preterm.

    “Nearly 60% of twins are born preterm.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    About 40% of twins have spontaneous labour or PPROM before 37 weeks, with others having an indicated preterm delivery because of pre-eclampsia or other maternal or fetal disorders.

    “About 40% of twins will have spontaneous labour or PPROM before 37 weeks' gestation, with others having an indicated preterm delivery because of pre-eclampsia, or other maternal or fetal disorders.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Spontaneous preterm birth is most commonly caused by preterm labour in white women, but by PPROM in black women.

    “Spontaneous preterm birth is most commonly caused by preterm labour in white women, but by PPROM in black women.8”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Ananth, 2006, Epidemiology of preterm birth and its clinical subtypes, J Matern Fetal Neonatal Med source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The preterm delivery rate is about 12-13% in the USA and generally 5-9% in Europe and other developed countries.

    “In the USA, the preterm delivery rate is 12–13%; in Europe and other developed countries, reported rates are generally 5–9%.1, 2”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Slattery, 2002, Preterm delivery, Lancet source

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    • cites [2] Hamilton

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    Interpretationreasoning

    A decrease in local progesterone concentrations or receptor number is a plausible mechanism for labour initiation, because progesterone antagonists initiate preterm labour and progestational agents prevent it.

    “however, because progesterone antagonists—such as RU486—initiate preterm labour and progestational agents prevent preterm labour, a decrease in local progesterone concentrations or in the number of receptors is a plausible mechanism for initiation of labour.16, 17, 18”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [16] Sfakianaki, 2006, Mechanisms of progesterone action in inhibiting prematurity, J Matern Fetal Neonatal Med source

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    • cites [17] Garfield, 1987, Effects of the antiprogesterone RU 486 on preterm birth in the rat, Am J Obstet Gynecol source

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    • cites [18] Meis, 2003, Prevention of recurrent preterm delivery by 17 alpha–hydroxyprogesterone caproate, N Engl J Med source

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    Premisecitation

    Obese women are more likely to have infants with congenital anomalies such as neural-tube defects, and these infants are more likely to be delivered preterm.

    “Obese women are more likely to have infants with congenital anomalies, such as neural-tube defects, and these infants are more likely to be delivered preterm.39”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Goldenberg, 1996, Prepregnancy weight and pregnancy outcome, JAMA source

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    Premisecitation

    Vaginal bleeding caused by placental abruption or placenta preavia is associated with a very high risk of preterm delivery, and first- or second-trimester bleeding not associated with either is also associated with subsequent preterm birth.

    “Vaginal bleeding caused by placental abruption or placenta preavia is associated with a very high risk of preterm delivery, but bleeding in the first and second trimesters that is not associated with either placental abruption or placenta preavia is also associated with subsequent preterm birth.43”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Krupa, 2006, Predictors of preterm birth, Int J Gynaecol Obstet source

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  • May combine two claims.

    Premisenone given

    Multiple gestations account for only 2-3% of infants but carry a substantial risk of preterm delivery and result in 15-20% of all preterm births.

    “Multiple gestations—accounting for only 2–3% of infants—carry a substantial risk of preterm delivery, and result in 15–20% of all preterm births.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The preterm birth rate has increased in most industrialised countries, with the USA rate rising from 9.5% in 1981 to 12.7% in 2005.

    “The preterm birth rate has risen in most industrialised countries, with the USA rate increasing from 9·5% in 1981 to 12·7% in 2005 (figure 1 ),2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Hamilton

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    Premisecitation

    The disparity in preterm birth rates between black and white women has remained largely unchanged and unexplained.

    “Over time, the disparity in preterm birth rates between black and white women has remained largely unchanged and unexplained, and contributes to a cycle of reproductive disadvantage with far-reaching social and medical consequences.24”
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    • cites [24] Collins, 1997, Racial differences in post-neonatal mortality in Chicago: what risk factors explain the black infant's disadvantage?, Ethn Health source

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    Premisecitation

    Women with early spontaneous preterm births are far more likely to have subsequent spontaneous preterm births, while women with indicated preterm births tend to repeat such births.

    “but women with early spontaneous preterm births are far more likely to have subsequent spontaneous preterm births; women with indicated preterm births tend to repeat such births.41, 42”
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    • cites [41] Goldenberg, 2006, The Alabama preterm birth project: placental histology in recurrent spontaneous and indicated preterm birth, Am J Obstet Gynecol source

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    • cites [42] Ananth, 2006, Recurrence of spontaneous versus medically indicated preterm birth, Am J Obstet Gynecol source

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    Premisecitation

    Risk factors for PPROM are generally similar to those for preterm spontaneous labour with intact membranes, although infections and tobacco exposure play important parts.

    “Risk factors for PPROM are generally similar to those for preterm spontaneous labour with intact membranes, although infections and tobacco exposure play important parts.12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Mercer, 2000, The preterm prediction study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing, Am J Obstet Gynecol source

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    Premisecitation

    Other maternal demographic characteristics associated with preterm birth include low socioeconomic and educational status, low and high maternal ages, and single marital status.

    “Other maternal demographic characteristics associated with preterm birth include low socioeconomic and educational status, low and high maternal ages, and single marital status.25, 26, 27”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [25] Smith, 2007, Socioeconomic inequalities in very preterm birth rates, Arch Dis Child Fetal Neonatal Ed source

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    • cites [26] Brett, 1997, Employment, job strain, and preterm delivery among women in North Carolina, Am J Public Health source

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    • cites [27] Thompson, 2006, Secular trends in socio-economic status and the implications for preterm birth, Paediatr Perinat Epidemiol source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In developed countries, preterm birth is the main contributor to perinatal illness and death.

    “Preterm births account for 75% of perinatal mortality and more than half the long-term morbidity.5”
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    • cites [5] McCormick, 1985, The contribution of low birth weight to infant mortality and childhood morbidity, N Engl J Med source

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    Premisecitation

    A low prepregnancy BMI is associated with a high risk of spontaneous preterm birth, whereas obesity can be protective.

    “For example, a low prepregnancy BMI is associated with a high risk of spontaneous preterm birth, whereas obesity can be protective (figure 4 ).35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Hendler, 2005, The preterm prediction study: association between maternal body mass index (BMI) and spontaneous preterm birth, Am J Obstet Gynecol source

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    Premisecitation

    Nicotine and carbon monoxide are powerful vasoconstrictors and are associated with placental damage and decreased uteroplacental blood flow.

    “however, both nicotine and carbon monoxide are powerful vasoconstrictors, and are associated with placental damage and decreased uteroplacental blood flow.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Benowitz, 2000, The use of pharmacotherapies for smoking cessation during pregnancy, Tob Control

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    Interpretationcitation

    Smoking is associated with a systemic inflammatory response and can increase spontaneous preterm birth through that pathway.

    “Smoking is also associated with a systemic inflammatory response and can increase spontaneous preterm birth through that pathway.64, 65”
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    • cites [64] Tracy, 1997, Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects, Arterioscler Thromb Vasc Biol source

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    • cites [65] Bermudez, 2000, Relation between markers of systemic vascular inflammation and smoking in women, Am J Cardiol source

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    Premisecitation

    Prostaglandins stimulate uterine contractility, whereas degradation of extracellular matrix in fetal membranes leads to PPROM.

    “Prostaglandins stimulate uterine contractility, whereas degradation of extracellular matrix in the fetal membranes leads to PPROM.67, 68”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [67] Goldenberg, 2000, Intrauterine infection and preterm delivery, N Engl J Med source

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    • cites [68] Romero, 2006, The preterm parturition syndrome, Br J Obstet Gynaecol source

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    Premisecitation

    History of cervical cone biopsy or loop electrocautery excision procedures and various uterine anomalies are associated with an increase in spontaneous preterm delivery.

    “History of cervical cone biopsy sample or loop electrocautery excision procedures secondary to premalignant cervical disorders have also been associated with an increase in spontaneous preterm delivery, as have various anomalies of the uterus itself—such as the presence of a septum.44”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Jakobsson, 2007, Preterm delivery after surgical treatment for cervical intraepithelial neoplasia, Obstet Gynecol source

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    Premisecitation

    Microbiological studies suggest intrauterine infection might account for 25-40% of preterm births, and this might be a minimum estimate because intrauterine infection is difficult to detect with conventional culture techniques.

    “Microbiological studies suggest that intrauterine infection might account for 25–40% of preterm births;67 however, 25–40% might be a minimum estimate because intrauterine infection is difficult to detect with conventional culture techniques.69”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [67] Goldenberg, 2000, Intrauterine infection and preterm delivery, N Engl J Med source

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    • cites [69] Relman, 1990, The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens, N Engl J Med source

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    Premisecitation

    In the USA, about 20-25% of pregnant women smoke, and 12-15% continue throughout pregnancy.

    “In the USA, about 20–25% of pregnant women smoke, and, of these, 12–15% continue throughout pregnancy.60, 61, 62”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [60] Ebrahim, 2000, Trends in pregnancy related smoking rates in the United States, 1987–1996, JAMA source

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    • cites [61] Andres, 2000, Perinatal complications associated with maternal tobacco use, Semin Neonatol source

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    • cites [62] Cnattingius, 2004, The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes, Nicotine Tob Res source

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  • May combine two claims.

    Premisecitation

    Depressed mood is associated with a reduction in natural killer cell activity and higher plasma concentrations of proinflammatory cytokines and their receptors.

    “Although, the mechanism(s) underlying the association of depression and preterm birth is unknown, there is an association between depressed mood and a reduction in natural killer cell activity, and higher plasma concentrations of proinflammatory cytokines and their receptors.59”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] Gennaro, 1997, Caregiving to very low birthweight infants: a model of stress and immune response, Brain Behav Immun source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Clinical depression during pregnancy has been reported in up to 16% of women, with up to 35% having some depressive symptoms.

    “Clinical depression during pregnancy has been reported in up to 16% of women, with up to 35% having some depressive symptoms.52, 53”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [52] Gavin, 2005, Perinatal depression: a systematic review of prevalence and incidence, Obstet Gynecol source

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    • cites [53] Dayan, 2006, Prenatal depression, prenatal anxiety, and spontaneous preterm birth: a prospective cohort study among women with early and regular care, Psychosom Med source

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  • May combine two claims.

    Interpretationreasoning

    In some studies adjusted for smoking and drug and alcohol use, the association between depression and preterm birth persisted, suggesting the relationship might be caused by more than confounding.

    “Nevertheless, in some studies that adjusted for smoking and drug and alcohol use, the association between depression and preterm birth persisted, suggesting that this relationship might be caused by more than confounding.”
    Quote in the paperSubstantial claim

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    Interpretationcitation

    Genital mycoplasmas and other organisms detected in the uterus before membrane rupture are typically of low virulence, probably accounting for the chronicity of intrauterine infections and the frequent absence of overt clinical signs.

    “The genital mycoplasmas and other organisms detected in the uterus before membrane rupture are typically of low virulence, probably accounting for both the chronicity of intrauterine infections and the frequent absence of overt clinical signs of infection.67”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Goldenberg, 2000, Intrauterine infection and preterm delivery, N Engl J Med source

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    Premisecitation

    Several reports suggest a relation between depression and preterm birth, with risks generally less than 2-fold.

    “Although the results are inconsistent, several reports suggest a relation (risks generally rose <2–fold) between depression and preterm birth.54, 55”
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    • cites [54] Orr, 1995, Maternal depressive symptoms and the risk of poor pregnancy outcome: review of the literature and preliminary findings, Epidemiol Rev source

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    • cites [55] Hoffman, 1996, Stress, social support and pregnancy outcome: a reassessment based on recent research, Paediatr Perinat Epidemiol source

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  • May combine two claims.

    Premisenone given

    Heavy alcohol consumption has been associated with preterm birth, but mild or moderate alcohol use is not generally regarded as a risk factor.

    “Although heavy alcohol consumption has been associated with preterm birth, neither mild nor moderate alcohol use is generally regarded as a risk factor for preterm birth.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    With a cervical length greater than 30 mm, the likelihood of delivering in the next week is about 1%, and most women can be safely discharged without treatment.

    “With a cervical length greater than 30 mm, the likelihood of delivering in the next week is about 1%, and most women can be safely discharged without treatment.124”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Leitich, 1999, Cervical length and dilation of the internal as detected by vaginal ultrasonography as markers for preterm delivery: a systematic review, Am J Obstet Gynecol source

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  • May combine two claims.

    Interpretationcitation

    Viral DNAs in the amniotic fluid of asymptomatic women undergoing genetic amniocentesis were generally unrelated to subsequent preterm births, so it seems unlikely that maternal viral infection plays an important part in preterm birth.

    “In several studies, the viral DNAs—identified by PCR techniques—in the amniotic fluid of asymptomatic women undergoing genetic amniocentesis were generally unrelated to subsequent preterm births;115 therefore, it seems unlikely that maternal viral infection plays an important part in preterm birth, but controversy persists, and with little information, further study is needed.116”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [115] Wenstrom, 1998, Intrauterine viral infection at the time of second trimester genetic amniocentesis, Obstet Gynecol source

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    • cites [116] Srinivas, 2006, Placental inflammation and viral infection are implicated in second trimester pregnancy loss, Am J Obstet Gynecol source

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  • May combine two claims.

    Premisecitation

    Periodontal disease has received widespread scrutiny, with some case-control studies suggesting an increased risk independent of other factors.

    “Periodontal disease has received widespread scrutiny with some case-control studies suggesting an increased risk independent of other factors.109, 110”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [109] Offenbacher, 1996, Periodontal infection as a possible risk factor for preterm low birth weight, J Periodontol source

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    • cites [110] Jeffcoat, 2001, Periodontal infection and preterm birth: results of a prospective study, J Am Dent Assoc source

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  • May combine two claims.

    Premisecitation

    Cervical insufficiency caused by congenital cervical weakness, surgery, or trauma has been implicated as causal for some preterm births, but its exact contribution to preterm birth is unknown.

    “Cervical insufficiency caused by congenital cervical weakness, surgery, or trauma has been implicated as causal for some preterm births; however, distinguishing cervical insufficiency from cervical shortening attributable to other causes has proven difficult, and the exact contribution to preterm birth is unknown.125”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [125] Iams, 1995, Cervical competence as a continuum: a study of ultrasonographic cervical length and obstetric performance, Am J Obstet Gynecol source

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  • May combine two claims.

    Premisecitation

    The fetal inflammatory response has been linked to the onset of preterm labour, fetal injury, and long-term handicap including periventricular leucomalacia, cerebral palsy, and chronic lung disease.

    “The fetal inflammatory response has been linked to the onset of preterm labour, and fetal injury and long-term handicap—including periventricular leucomalacia, cerebral palsy, and chronic lung disease.92, 93, 94”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [92] Yoon, 1996, Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia, Am J Obstet Gynecol source

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    • cites [93] Yoon, 2000, Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years, Am J Obstet Gynecol source

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    • cites [94] Yoon, 1999, A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia, Am J Obstet Gynecol source

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  • May combine two claims.

    Premisecitation

    Chlamydia is probably associated with preterm birth only in the presence of a maternal immune response, and most probably with a relative risk of about 2.

    “Chlamydia is probably associated with preterm birth only in the presence of a maternal immune response, and most probably with a RR of about 2.106”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Sweet, 1987, Chlamydia trachomatis infection and pregnancy outcome, Am J Obstet Gynecol source

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  • May combine two claims.

    Premisecitation

    Uterine contraction frequency is associated with preterm birth, but contractions do not predict preterm birth well in singletons because of wide variation in normal pregnancy and large overlap between women who do and do not deliver preterm.

    “Several studies have shown an association between uterine contraction frequency and preterm birth;117, 118, 119 however, uterine contractions do not predict preterm birth well in singletons because of the wide variation in frequency in normal pregnancy and the large overlap in frequency between women who do and do not deliver preterm.119”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [117] Moore, 1994, Diurnal and gestational patterns of uterine activity in normal human pregnancy, Obstet Gynecol source

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    • cites [118] Nageotte, 1988, Quantitation of uterine activity preceding preterm, term, and postterm labor, Am J Obstet Gynecol source

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    • cites [119] Iams, 2002, Frequency of uterine contractions and the risk of spontaneous preterm delivery, N Engl J Med source

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  • May combine two claims.

    Premisecitation

    In asymptomatic women at 24 weeks' gestation, a cervical length of less than 25 mm defines increased risk of preterm birth, and the shorter the cervix, the greater the risk.

    “In asymptomatic women, at 24 weeks' gestation, a cervical length of less than 25 mm defines increased risk of preterm birth. The shorter the cervix, the greater the risk.122, 123”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [122] Iams, 1996, The length of the cervix and the risk of spontaneous premature delivery, N Engl J Med source

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    • cites [123] Andrews, 2000, Second-trimester cervical ultrasound: associations with increased risk for recurrent early, spontaneous delivery, Obstet Gynecol source

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  • May combine two claims.

    Premisecitation

    Salivary oestriol concentration predicts late preterm birth quite well, but is not especially useful for predicting earlier preterm births.

    “Salivary oestriol concentration predicts late preterm birth quite well, but is not especially useful for the prediction of earlier preterm births.128”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [128] Ramsey, 2003, Biochemical predictors of preterm labor: fetal fibronectin and salivary estriol, Clin Perinatol source

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  • May combine two claims.

    Premisecitation

    Vaginal group B streptococcus, U urealyticum, and M hominus colonisations are not associated with increased risk of preterm birth.

    “Vaginal group B streptococcus, U urealyticum, and M hominus colonisations are not associated with increased risk of preterm birth.103, 104”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [103] Goldenberg, 2005, Maternal infection and adverse fetal and neonatal outcomes, Clin Perinatol source

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    • cites [104] Goldenberg, 1997, Sexually transmitted diseases and adverse outcomes of pregnancy, Clin Perinatol source

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  • May combine two claims.

    Premisecitation

    There is sparse evidence that viral infections predispose to preterm birth, but when the mother is severely ill, such as with varicella pneumonia or severe acute respiratory syndrome, a preterm delivery might occur.

    “Compared with bacterial infections, there is sparse evidence that viral infections predispose to preterm birth; however, when the mother is severely ill, such as with varicella pneumonia or severe acute respiratory syndrome, a preterm delivery might occur.113, 114”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [113] Hardy, 1961, The effect of Asian influenza on the outcome of pregnancy. Baltimore 1957–1958, Am J Public Health source

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    • cites [114] Horn, 1955, Poliomyelitis in pregnancy. A twenty-year report from Los Angeles County, California, Obstet Gynecol

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  • May combine two claims.

    Interpretationcitation

    Black women in the USA and UK are three times more likely to have bacterial vaginosis than white women, and this difference might explain 50% of the excess preterm births in black women.

    “Black women in both the USA and the UK are three times more likely to have bacterial vaginosis than are white women, and this difference might explain 50% of the excess preterm births in black women.21, 99, 100”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [21] Goldenberg, 2005, Biochemical markers for the prediction of preterm birth, Am J Obstet Gynecol source

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    • cites [99] Goldenberg, 1996, Bacterial colonization of the vagina during pregnancy in four ethnic groups, Am J Obstet Gynecol source

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    • cites [100] Fiscella, 1996, Racial disparities in preterm births. The role of urogenital infections, Public Health Rep

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  • May combine two claims.

    Premisecitation

    Microorganisms can gain access to the amniotic cavity by ascending from the vagina and cervix, haematogenous dissemination through the placenta, accidental introduction at invasive procedures, and retrograde spread through the fallopian tubes.

    “Microorganisms can gain access to the amniotic cavity by: (1) ascending from the vagina and the cervix; (2) haematogenous dissemination through the placenta; (3) accidental introduction at the time of invasive procedures; and (4) by retrograde spread through the fallopian tubes (figure 5 ).67, 86”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [67] Goldenberg, 2000, Intrauterine infection and preterm delivery, N Engl J Med source

      Not checked in the free run.

    • cites [86] Gomez, 1997, The role of infection in preterm labor and delivery

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fetal fibronectin is typically absent from cervicovaginal secretions from 24 weeks until near term, but 3-4% of women undergoing routine screening at 24-26 weeks are positive and are at substantially increased risk of preterm delivery.

    “Typically, fetal fibronectin is absent from cervicovaginal secretions from 24 weeks' until near term; however, 3–4% of women undergoing routine screening at 24–26 weeks' are positive, and are at substantially increased risk of preterm delivery.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A gene-environment interaction has been shown with maternal carriage of an allele of the TNFα gene and bacterial vaginosis; neither characteristic alone was associated with spontaneous preterm birth, but the combination increased risk.

    “A gene-environment interaction has been shown with maternal carriage of an allele of the TNFα gene and bacterial vaginosis.136 Although neither characteristic alone was associated with spontaneous preterm birth, the combination increased the risk of preterm birth.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [136] Macones, 2004, 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 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Maternal carriage of an IL6 polymorphism did not increase risk of spontaneous preterm birth for white or black women, but black carriers with bacterial vaginosis had a two-fold greater risk than carriers without infection.

    “Similarly, maternal carriage of a polymorphism in the IL6 gene did not result in increased risk of spontaneous preterm birth for white or black women;137 however, black women who were carriers of the IL6 allele and had bacterial vaginosis had a two-fold greater risk of preterm birth than did those who carried the variant but did not have such infection.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [137] Engel, 2005, Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms, Epidemiology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Improved understanding of the mechanisms by which risk factors relate to preterm birth should allow clinicians to design interventions that reduce the incidence of preterm birth and related fetal and neonatal morbidity and mortality.

    “Improved understanding of these mechanisms should allow clinicians to design appropriate interventions so that the incidence of preterm birth and related fetal and neonatal morbidity and mortality will be reduced.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    High-density arrays now allow simultaneous examination of 500,000 or more DNA variants in the same individual.

    “High-density arrays now allow simultaneous examination of 500 000 or more DNA variants in the same individual.”
    Quote in the paperNot a substantial claim
46 of 46

  • The authors state this as an assumption.

    Oxytocin plays a part in labour initiation.

    “Because intravenous oxytocin increases the frequency and intensity of uterine contractions, the assumption is that oxytocin plays a part in labour initiation.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The risk of preterm birth in the next pregnancy is about 15% to more than 50%.

    “The risk of preterm birth in the next pregnancy is about 15% to more than 50% [2].”

    From The association between parity, infant gender, higher level of paternal education and preterm birth in Pakistan: a cohort study (2011) · cites this paper as [2]

    The Pregnancy history section gives a recurrence risk of 15% to more than 50% in the next pregnancy, but only for women with a previous preterm delivery. The citing sentence omits that condition and reads as though the range applies to pregnancies generally. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Women with medical or obstetrical histories were excluded, and limitations in medical records and poor health literacy precluded classification into subtypes of preterm birth.

    “In our study women with medical or obstetrical histories were excluded from this study, and limitations in medical records and poor health literacy of the mothers precluded classification into the other two subtypes of preterm birth - spontaneous preterm labour without premature rupture of chorioamniotic membranes (PROM), and preterm PROM with vaginal or caesarean section delivery [2,56].”

    From The association between parity, infant gender, higher level of paternal education and preterm birth in Pakistan: a cohort study (2011) · cites this paper as [2]

  • Maternal stress has been identified as a potential causal factor for preterm birth.

    “Although, the etiology of preterm birth likely involves numerous factors, maternal stress has been identified as a potential casual factor for preterm birth [72].”

    From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [72]

Cites

Flagged first, then by citations

13 of the 163 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. Romero, 2006, The preterm parturition syndrome, Br J Obstet Gynaecol, 113, 17, 10.1111/j.1471-0528.2006.01120.x · DOI · Paper page
  2. Russell, 1979, Inflammatory lesions of the human placenta. I. Clinical significance of acute chorioamnionitis, Diagn Gynecol Obstet, 1, 127
  3. Horn, 1955, Poliomyelitis in pregnancy. A twenty-year report from Los Angeles County, California, Obstet Gynecol, 6, 121
  4. Engel, 2005, Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms, Epidemiology, 16, 469, 10.1097/01.ede.0000164539.09250.31 · DOI · Paper page

Cited by

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Related

Authors
Goldenberg, R. L., Culhane, J. F., Iams, J. D., & Romero, R.
Affiliations
  • Drexel University (US)
  • The Ohio State University (US)
  • National Institutes of Health (US)
Corresponding author
Goldenberg, Robert L
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2008-01
Volume
371
Issue
9606
Pages
75-84
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(08)60074-4
PMC
PMC7134569
OpenAlex
W1975755498
Cited by
7,801
References
163
Citations by year
2026: 318 · 2025: 438 · 2024: 519 · 2023: 553 · 2022: 544 · 2021: 552 · 2020: 591 · 2019: 433 · 2018: 459 · 2017: 510 · 2016: 441 · 2015: 474 · 2014: 425 · 2013: 396 · 2012: 354
FWCI
27.76
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
  • Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
Keywords
preterm birth, preterm labour, preterm premature rupture of membranes, labor induction, cesarean section, preeclampsia, fetal growth restriction, multiple pregnancy, preterm birth risk factors, periodontal disease, maternal body mass index, cervical length, fetal fibronectin, perinatal morbidity and mortality
MeSH terms
Female, Fetal Membranes, Premature Rupture, Premature Rupture of Fetal Membranes, Humans, Infant, Newborn, Obstetric Labor, Premature, Pre-Eclampsia, Pregnancy, Risk Factors, Body Mass Index, Racial Groups, Premature Birth

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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