A Perinatal Pathology View of Preterm Labor

In This Article

Epidemiology of Prematurity

Most of the causes of premature labor are still unknown. Although a history of a previous preterm birth is the best single indicator of a subsequent preterm birth, a significant proportion occur in women experiencing their first pregnancy, as in our 2 case studies. Early identification of those at risk of preterm birth, even those with no obviously contributory obstetric history, is crucial to the improvement of neonatal morbidity and mortality rates.

Preterm births represent approximately 8% to 10% of all US births annually and account for an estimated 80% of perinatal losses not secondary to congenital anomalies. Of all the efforts to improve perinatal morbidity and mortality rates in the United States, prevention of preterm delivery has enjoyed the least progress in the past decade. Although complete consensus does not exist, a standard definition of preterm gestation is 20-37 weeks from the last menstrual period, with those cases of early preterm delivery (< 32 weeks) being the most significantly associated with neonatal risk. The risk indicators for premature birth are a complicated combination of psychosocial, demographic, structural, and endocrine factors, whose individual significance is not fully understood.

Reproductive History of Prior Preterm Birth

An obstetric history of at least 1 prior preterm birth remains the single best predictor of another preterm birth. In a recent NICHD Maternal-Fetal Medicine Units Network study,[1] women with a prior preterm delivery of any gestational length had a 2.5-fold increased risk of spontaneous preterm delivery in the current gestation and a 10.6-fold increased risk of spontaneous preterm delivery before 28 weeks gestation. Those women with a prior early preterm delivery (23-27 weeks) had a 22-fold increased risk of delivery before 28 weeks in the current pregnancy, giving evidence that an early prior preterm birth is more predictive of recurrence. The investigators also found that both preterm labor and premature rupture of membranes were individually associated with a similar risk of recurrence. In contrast to other recent findings, they did not find an association between a prior loss between 13 and 22 weeks and no preterm deliveries and subsequent preterm birth.

Papiernik[2] and Creasy and colleagues[3] hypothesized that preterm delivery could be predicted by the identification of multiple demographic and reproductive history factors that could be assigned arbitrarily weighted scores. Based on these factors, they proposed that all pregnancies could be dichotomously categorized as either high- or low-risk. While somewhat useful in the evaluation of multiparous women, the fact remains that approximately 40% of all preterm deliveries occur in nulliparous women with no contributory obstetric history and very few traditional risk factors.

Maternal and Fetal Characteristics

In a recent study of preterm birth, younger gestational age was found to be associated with male gender, which may indicate that the presence of increased androgen precursors of estrogen production may influence the initiation of labor.[4] The findings of this study included:


  • Second-born babies were less likely to be preterm as compared with first-borns (OR 0.875; 95% CI 0.863-0.887) (Second-borns have also been previously reported to be less prone to stillbirth.[5]).

  • Less educated mothers were slightly more likely to experience preterm delivery (OR 1.09; 95% CI 1.076-1.105).

  • Maternal age of 35years and older was associated with a greater preterm birth frequency as compared with mothers younger than 35 (4.0 vs 6.37; OR 1.635; 95% CI 1.604-1.666).

  • Male gender was associated with a significantly higher risk of preterm birth (OR 1.109; 95% CI 1.095-1.124) (Male gender has also been associated with a higher rate of late fetal death and spontaneous abortion.[4]


In a large retrospective study (1.8 million white singleton births, 103,329 black singleton births), white singleton preterm births (20-36 weeks) were 54.9% male vs 45.1% female (9.8% difference). In black singleton preterm births (20-36 weeks), there was a 2.8% gender differential (


< .001, compared with whites). A greater male fraction existed in white singleton preterms of those women in low-risk categories, namely those with a maternal age older than 20 years, those who had more than 12 years of education, and those who were married. This trend did not carry over to the black population


Any mechanistic, rather than psychosocial, origins of racial differences in preterm delivery and perinatal mortality rates are poorly understood but have been speculated to include the greater prevalence of short intrapregnancy intervals, as shown in a US military black population compared with an otherwise clinically similar military white population.


In another study,[8] other significant risk factors for preterm birth included small maternal size (stature ≤ 157.5 cm, prepregnancy body mass index [BMI] < 19.8 kg/m2) and low rate of gestational weight gain (< 0.27 kg/wk); possible risk factors included young age (< 16 yrs) and young gynecologic age (chronologic age minus age at menarche ≤ 2). Of interest, however, is that after adjustment for gestational age and other confounding variables (mode of delivery, prepregnancy BMI, height, weight gain, ethnicity, fetal sex, and smoking), infants of young adolescents were relatively larger at birth (P < .04).


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