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Editorial SEPTEMBER 2008

Ischemic Placental Disease Is the Main Cause For Indicated Preterm Births

Anthony M. Vintzileos, MD

Preterm birth complicates 12.9% of US pregnancies (year 2006 statistics) and remains a major contributor to perinatal mortality (75% to 80%) and major neurological morbidity (50%). The frequency of preterm births is alarming, with approximately one preterm birth per minute in the United States. This rate is rising, reflecting a concurrent increase in medically indicated preterm births. Although older data show that approximately 20% to 30% of preterm births are indicated, more recent data suggest that they account for up to 35% to 40% of all preterm births in the United States.1,2 Despite the temporal increase in indicated preterm births, little attention has been paid to researching their etiology and/or prevention. To date, the overwhelming majority of resources and research efforts have been allocated to studying spontaneous preterm birth. In my view, this may have been the unintended consequence of the belief that spontaneous preterm birth is a “more or less” homogeneous condition since the clinical presentation in these patients is usually either preterm labor or preterm premature rupture of membranes. However, subsequent research has shown that spontaneous preterm birth is a very heterogeneous condition in terms of etiologic/pathophysiologic mechanisms with the most common pathways including intra-amniotic infection, inflammation, maternal-fetal stress, ischemia, and uterine over distention. However, in the presence of any of the aforementioned processes, the preterm patient may present with either spontaneous or indicated preterm birth. For instance, a pregnant woman with preterm placental abruption can present with vaginal bleeding and preterm labor and have a vaginal delivery (classified under the “spontaneous preterm birth” group), or she can present with vaginal bleeding without labor, intrauterine growth restriction (IUGR) and nonreassuring fetal status, necessitating medical intervention (classified under the “indicated preterm birth” group). Moreover, research from our group has revealed a crossover recurrence between spontaneous and indicated preterm birth, an observation that suggests that there is considerable etiologic overlap between the two conditions.3

Our group has recently reported on the type and frequency of the maternal and fetal conditions leading to indicated preterm birth.4 Preeclampsia, IUGR, and placental abruption were the most frequent conditions. More than 1 of every 2 patients (54%) with indicated preterm births have one or more of these conditions present. Since these conditions share several similarities—as evidenced by uterine and umbilical Doppler studies, placental histology, and biochemical placental (angiogenic and antiangiogenic) factors—we have introduced the term “ischemic placental disease” under which we include these 3 clinical conditions. This terminology may facilitate research operating under the hypothesis that these conditions may be different clinical manifestations of a common etiology (ie, defective/inadequate placentation).

Epidemiologic evidence in support of a common etiologic mechanism present in both conditions is the recent observation of crossover recurrence in successive pregnancies.5 We recently reported that if a woman develops preeclampsia in the first pregnancy, she is at risk not only for preeclampsia, but also for IUGR and abruption in a subsequent pregnancy. Similarly, women who develop any of the other two conditions (IUGR or abruption) are at risk for developing the same clinical complication, along with any of the other two conditions, in a subsequent pregnancy.

Medically indicated preterm births, especially ischemic placental disease, are now recognized as major contributors to preterm birth. If we are to reduce preterm births, future research should also focus on ischemic placental disease, as it seems to be less heterogeneous than previously believed. Lastly, the crossover recurrence between spontaneous and indicated preterm birth underscores that in order for preterm birth prevention programs to be effective, investigators should use as primary outcome reduction of total (spontaneous and indicated) preterm births, rather than studying each as an isolated entity.

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Anthony M. Vintzileos, MD, Board Member

REFERENCES

1. Tucker JM, Goldenberg RL, Davis RO, Copper RL, Winkler CL, Hauth JC. Etiologies of preterm birth in an indigent population: is prevention a logical expectation? Obstet Gynecol. 1991;77(3):343¨347.
2. Ananth CV, Joseph KS, Oyelese Y, Demissie K, Vintzileos AM. Trends in preterm birth and perinatal mortality among singletons: United States, 1989 though 2000. Obstet Gynecol. 2005;105 (5 Pt 1): 1084¨1091.
3. Ananth CV, Getahun D, Peltier MR, Salihu HM, Vintzileos AM. Recurrence of spontaneous versus medically indicated preterm birth. Am J Obstet Gynecol. 2006; 195(3):643¨650.
4. Ananth CV, Vintzileos AM. Maternal-fetal condition necessitating a medical intervention resulting in preterm birth. Am J Obstet Gynecol. 2006; 195(6):1557¨1563.
5. Ananth CV, Peltier MR, Chavez MR, Kirby RS, Getahun D, Vintzileos AM. Recurrence of ischemic placental disease. Obstet Gynecol. 2007;110(1):128¨133.