Risk Factors for Prematurity

Preterm birth is the greatest single cause of perinatal morbidity and mortality in the US. 70% of infant deaths are due to preterm birth.[1] While most preterm babies survive, they’re at risk of neurodevelopmental impairments and respiratory and gastrointestinal complications.[2] Avoiding premature birth is a big deal.

About 12-13% of US births are preterm, which is twice the rate in other developed countries.  Preterm births have actually increased over time.

Preterm births, defined as birth before 37 weeks, can occur either spontaneously (through early labor) or deliberately (through medical induction when something is wrong with the pregnancy such as pre-eclampsia.)  Spontaneous preterm labor is generally thought to be a syndrome involving inflammation or infection, uterine or placental hemorrhage or ischemia, stress, and other immunologically mediated processes. So we’ll see all the standard risk factors that affect systemic inflammation.

Multiple Births

Nearly 60% of twins are born preterm, for an odds ratio of 11x baseline.[2]

Vaginal Bleeding

Because premature labor is often the result of bleeding or tears in the uterus or placenta, vaginal bleeding in more than one trimester is a risk factor for premature birth, carrying an odds ratio of 7.4.[3]

Early Bacterial Vaginosis

Bacterial infection within the first 16 weeks of pregnancy is associated with an odds ratio of 7.55 of preterm birth. (Bacterial vaginosis at any time during pregnancy has an odds ratio of 2.1.) A vaginal infection may result in a uterine infection that eventually causes contractions and labor. [8]  Vaginosis is associated with a change in the composition of the vaginal flora: a drop in the number of lactobacilli, and a corresponding rise in the number of other kinds of bacteria. It is hypothesized that either through general systemic inflammation, or through the fetal immune response, these bacterial infections cause the tissue deterioration that results in rupture and preterm birth.[13]  Vaginosis at the beginning of pregnancy is also associated with a 3x risk of pregnancy loss before 22 weeks.[12] Treatment with metronidazole can cut the risk of preterm birth in half.[11]

Douching is bad for your vaginal flora.  Douching is associated with an odds ratio of 1.21 of bacterial vaginosis[16] and frequent douching has an odds ratio of 2.35[17].  Stopping douching reduces the incidence of vaginosis.[18]  The increased prevalence of douching among black women is a possible explanation for why they have higher rates of vaginosis and lower quantities of Lactobacillus species (the “good bacteria” in the vagina.)

Systemic Inflammation Markers

Elevated levels of the cytokine IL-6 and the inflammatory marker C-reactive protein had associated odds ratios of 4.60 and 4.07 respectively of premature birth.  These are also general risk factors for heart disease, stroke, and other vascular disorders.[9]

Gum disease

Mothers with severe periodontitis had odds ratios of 4.45 for preterm delivery.[5][6]  This is less crazy than it sounds; gum disease is associated with systemic inflammation. Treatment for periodontitis during pregnancy cut the incidence of preterm birth by a factor of 5 in a randomized controlled trial.[10]

Short Cervix

Women with a short cervix are at 3.7x the risk of having a premature birth.[15]  “Cervical incompetence” results in a greater risk of the cervix tearing early and causing labor.  This can be corrected by “cerclage”, or stitching the cervix shut, which reduces the incidence of preterm birth by about half.  For women with a high risk of spontaneous preterm labor, treatment with progesterone [14] can reduce their risk of preterm delivery.

Demographics

Black mothers are 2-3x as likely to have a preterm birth as mothers of other races. Low socioeconomic and educational status are also risk factors.[2] Teenage pregnancy is associated with an odds ratio of 3.4.[7]

Previous Preterm Birth

Some mothers tend to run to prematurity; a previous preterm birth has an odds ratio of 2.5 of being followed by subsequent preterm births.

Tobacco

Smoking increases the risk of preterm birth by 2x.[2]

Underweight

A BMI of < 19.8 increases the risk of preterm birth with an odds ratio of 2.0.[4]

Bottom line: things you can do to prevent prematurity

  • avoid IVF, which often results in multiple births.
  • screen for and treat vaginal infections
    • note that a drugstore test for vaginal pH is a fairly accurate indictor for bacterial vaginosis; it might be worth checking while you’re trying to get pregnant
    • don’t douche!
  • be in “general good vascular health” (more or less, have a healthy and active lifestyle)
  • treat gum disease
  • don’t smoke
  • get up to a healthy weight

 

References

[1]Pschirrer, E. Rebecca, and Manju Monga. “Risk factors for preterm labor.”Clinical obstetrics and gynecology 43.4 (2000): 727-734.

[2]Goldenberg, Robert L., et al. “Epidemiology and causes of preterm birth.”The lancet 371.9606 (2008): 75-84.

[3]Harger, James H., et al. “Risk factors for preterm premature rupture of fetal membranes: a multicenter case-control study.” American journal of obstetrics and gynecology 163.1 (1990): 130-137.

[4]Goldenberg, Robert L., et al. “The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network.” American Journal of Public Health 88.2 (1998): 233-238.

[5]Jeffcoat, Marjorie K., et al. “Periodontal infection and preterm birth: results of a prospective study.” The Journal of the American Dental Association 132.7 (2001): 875-880.

[6]Lopez, N. J., P. C. Smith, and J. Gutierrez. “Higher risk of preterm birth and low birth weight in women with periodontal disease.” Journal of Dental Research 81.1 (2002): 58-63.

[7]Martius, Joachim A., et al. “Risk factors associated with preterm (< 37+ 0 weeks) and early preterm birth (< 32+ 0 weeks): univariate and multivariate analysis of 106 345 singleton births from the 1994 statewide perinatal survey of Bavaria.” European Journal of Obstetrics & Gynecology and Reproductive Biology 80.2 (1998): 183-189.

[8]Leitich, Harald, et al. “Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis.” American journal of obstetrics and gynecology 189.1 (2003): 139-147.

[9]Sorokin, Yoram, et al. “Maternal serum interleukin-6, C-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth< 32 weeks and adverse neonatal outcomes.” American journal of perinatology27.8 (2010): 631.

[10]López, Néstor J., Patricio C. Smith, and Jorge Gutierrez. “Periodontal therapy may reduce the risk of preterm low birth weight in women with peridotal disease: a randomized controlled trial.” Journal of periodontology 73.8 (2002): 911-924.

[11]Morales, Walter J., Steve Schorr, and John Albritton. “Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study.” American journal of obstetrics and gynecology 171.2 (1994): 345-349.

[12]McGregor, James A., et al. “Prevention of premature birth by screening and treatment for common genital tract infections: results of a prospective controlled evaluation.” American journal of obstetrics and gynecology 173.1 (1995): 157-167.

[13]Pretorius, Christopher, Anilla Jagatt, and Ronald F. Lamont. “The relationship between periodontal disease, bacterial vaginosis, and preterm birth.” Journal of perinatal medicine 35.2 (2007): 93-99.

[14]Fonseca, Eduardo B., et al. “Progesterone and the risk of preterm birth among women with a short cervix.” New England Journal of Medicine 357.5 (2007): 462-469.

[15]Andersen, H. Frank, et al. “Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length.” American journal of obstetrics and gynecology 163.3 (1990): 859-867.

[16]Brotman, Rebecca M., et al. “A longitudinal study of vaginal douching and bacterial vaginosis—a marginal structural modeling analysis.” American journal of epidemiology 168.2 (2008): 188-196.

[17]Zhang, Jun, et al. “Frequency of douching and risk of bacterial vaginosis in African-American women.” Obstetrics & Gynecology 104.4 (2004): 756-760.

[18]Brotman, Rebecca M., et al. “The effect of vaginal douching cessation on bacterial vaginosis: a pilot study.” American journal of obstetrics and gynecology 198.6 (2008): 628-e1.

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