In much of medicine, the ability to identify which patients are at increased risk for a disease or health-threatening event is half the battle, as it paves the way for timely preventive intervention. As obstetricians know all too well, however, that’s hardly the case with preterm delivery (PTD). While recent years have seen significant advances in screening modalities, those gains have not been matched by comparable improvements in our ability to prevent premature birth. In fact, instead of decreasing, the incidence of PTD in the United States has increased from 9.4% of births in 1981 to 11.8% in 1999.1
While the search for effective interventions continues, obstetricians and their patients still can derive considerable benefit from the enhanced ability to determine which women with worrisome symptoms are at low risk of PTD, thus avoiding costly and potentially harmful interventions, and which patients warrant heightened surveillance.
In October 2001, ACOG reviewed various modalities in its Practice Bulletin titled “Assessment of risk for preterm birth.” Here, Dr. Norwitz, assistant professor of obstetrics, gynecology, and reproductive sciences at Harvard Medical School and an attending Ob/Gyn in the division of maternal-fetal medicine at Brigham and Women’s Hospital in Boston, responds to OBG Management editors’ questions about the clinical implications of the bulletin and the screens and tests it discusses.
<huc>Q</huc> OBG Management: In what ways does this bulletin represent an evolution in the specialty’s thinking about preterm labor?
<huc>A</huc> NORWITZ: It represents an attempt by ACOG to synthesize the extensive and rapidly expanding body of literature on risk factors for PTD into a single, succinct, and practical document.2 As such, it replaces prior ACOG publications on preterm labor,3 home uterine-activity monitoring (HUAM),4 salivary estriol testing,5 fetal fibronectin (fFN) testing,6 and bacterial vaginosis (BV) screening and treatment.7 However, the current Practice Bulletin is a far less ambitious document than the prior review of preterm labor,3 which dealt not only with risk factors for preterm irth, but also with its management.
Nonetheless, it represents an evolution in thinking about preterm birth, as it includes a detailed discussion of fetal fibronectin screening and sonographic assessment of cervical length.
<huc>Q</huc> OBG Management: According to the bulletin, “There are no current data to support the use of salivary estriol, HUAM, or BV screening as strategies to identify or prevent preterm birth.” How widely are each of these modalities being employed by Ob/Gyns? What impact do you see this statement having on their future use?
<huc>A</huc> NORWITZ: HUAM testing had largely fallen by the wayside even before this bulletin was published. Most obstetric-care providers were already aware of the extensive literature showing that HUAM does not prevent preterm birth or improve perinatal outcome.8-11
As for salivary estriol, the development of a reliable endocrine assay to predict PTD would represent a significant advance in the field. Progesterone withdrawal is not a prerequisite for labor; nor are serum progesterone levels or progesterone/17ß-estradiol ratios predictive of preterm birth.12,1
Lower-genital-tract BV may be a marker of upper-genital-tract infection, which in turn may be the real cause of preterm birth.
On the other hand, maternal serum estriol levels accurately reflect activation of the fetal hypothalamic-pituitary-adrenal axis, which occurs in all women prior to the onset of labor, both at term and preterm.13,14 More-over, salivary estriol measurements correlate well with levels of biologically active (unconjugated) estriol in the circulation.15 The detection of elevated levels of estriol (≥2.1 ng/mL) in maternal saliva is predictive of delivery prior to 37 weeks in a high-risk population, with a sensitivity of 68% to 87% and a specificity of 77%.16,17 Serial (weekly) measurements have been shown to be more accurate in predicting preterm birth than a single measurement.17
However, salivary estriol testing to identify women at high risk of PTD has not been widely accepted. The reasons: First, maternal estriol levels show diurnal variation, peaking at night,18 making it difficult to standardize such testing. Additionally, the false-positive rate of 23% to 35% is considered unacceptably high and may lead to unnecessary intervention.16,17 Finally, salivary estriol levels may be suppressed by betamethasone administration, making the test unreliable in patients treated with corticosteroids.19 The statement in the latest ACOG bulletin that “trials with salivary estriol testing to predict preterm birth have failed to establish its usefulness for anything more than investigational purposes at present”2 is likely to further limit the use of this test, and may have the unfortunate effect of discouraging future research in the field.
In regard to BV, recent data demonstrate conclusively that screening and treating low-risk asymptomatic pregnant women for BV does not prevent preterm birth.20-22 However, the data for women at high risk for preterm birth are conflicting. Some studies suggest that the strategy of screening and treating asymptomatic BV in high-risk women may significantly decrease the incidence of preterm birth and low-birthweight infants.22-24 But the statement by ACOG that “there are insufficient data to suggest screening and treating women at…high risk will reduce the overall rate of preterm birth”2 is likely to limit the use of this strategy. The hypothesis that lower-genital-tract BV may be a marker of upper-genital-tract infection, which in turn is the real cause of preterm labor and delivery, is intriguing and deserves further attention.