A wide range of studies were highlighted at this year's Annual Clinical Meeting of the Society of Maternal-Fetal Medicine (SMFM), held February 7-12, 2005 in Reno, Nevada. This report focuses on some of the key presentations made in the fields of preterm delivery and prenatal aneuploidy screening as well as in clinical obstetrics.
The meeting kicked off with an extremely promising study by Romero (Perinatology Research Branch of the National Institute of Child Health and Human Development [NICHD]) and colleagues that entailed detecting women at risk for preterm delivery. With a novel technique used to study the metabolic profile of cellular activity in the amniotic fluid (ie, determining the levels of various carbohydrates, amino acids, and other molecules using liquid and gas chromatography), the investigators of this study were able to identify, with high precision, women who delivered prematurely.
The study involved 55 women presenting with preterm contractions who fit into 1 of 3 groups. The first group consisted of women with preterm contractions, without evidence of intra-amniotic infection, who delivered at term; the second group consisted of women with preterm contractions, without evidence of intra-amniotic infection, who delivered prematurely; and the last group consisted of women who had undergone preterm labor, with evidence of intra-amniotic infection, who also delivered prematurely. Amniotic fluid metabolic profiling (termed metabolomics) was performed on each of these patients and identified which group each woman belonged to with 96.3% precision (53/55). One woman of the 16 who delivered at term was misidentified, and 1 of the 20 who delivered preterm with evidence of intra-amniotic infection was also misclassified.
In this study, an amniotic fluid white blood cell (WBC) count of > 100 cells/mm3 was considered a sign of intra-amniotic infection. Because this is a sign of significant infection, a follow-up study defined patients as having intra-amniotic infection if the amniotic fluid interleukin-6 levels were elevated (a marker of inflammation that may be more sensitive to intra-amniotic fluid infection than an elevated WBC count). Again, the technique of metabolomics was very accurate -- this time performing with 88% accuracy. In this group of patients; the test did less well separating the groups of women without evidence of intra-amniotic infection into those who delivered preterm and those who delivered at term.
The techniques in this study hold promise to identify better markers to determine which women will deliver prematurely. But first, the results will need to be repeated in a much larger group of patients in a prospective fashion.
On behalf of the NICHD's Maternal-Fetal Medicine Units (MFMU) Network, Spong presented a secondary analysis of the 2003 presentation on the use of 17-alpha hydroxyprogesterone caproate (17P) for the prevention of preterm delivery among women with a history of a prior spontaneous preterm delivery. That study had shown a significant improvement in the rates of preterm delivery among women receiving weekly injections of 17P. This secondary analysis of those data was undertaken to determine whether women whose prior preterm birth occurred earlier in gestation benefitted more from 17P. A criticism of the earlier study had been that the participants were an unusual group of women since their prior preterm births had been at a much earlier gestational age than the average preterm birth in the United States. In this secondary analysis, participants were stratified into 3 groups on the basis of when their prior preterm delivery occurred: 20.0-27.9 weeks, 28.0-33.9 weeks, or 34.0-36.9 weeks.
Benefits of the therapy with 17P were noted only for the women whose prior preterm delivery occurred at 20.0-27.9 weeks (33.5 wks vs 35.1 wks, P = .038) and for the group whose prior delivery occurred at 28.0-33.9 weeks (35.6 wks vs 36.8 wks, P = .045), but not for the group whose prior delivery occurred at 34.0-36.9 weeks (35.8 wks vs 36.3 wks, P = NS). Caution needs to be taken in drawing conclusions from these results and generalizing them to other populations. This is a secondary analysis, and, as pointed out by Dr. Spong, women in the 2 groups who had delivered earlier in their pregnancy (which qualified them for participation in the study) also were more likely to have had > 1 prior preterm delivery. So although it appears that 17P may benefit women whose prior preterm delivery occurred earlier, the women in this study who benefitted may actually belong to an even higher risk group: those with > 1 prior preterm delivery.
Other interesting studies relating to the issue of preterm delivery included the following:
Fortunato (Perinatal Research Center, Nashville, Tennessee) and colleagues explored racial differences in gene expression in fetal membranes obtained at cesarean deliveries. Using microarray technology, they exposed samples of membranes to endotoxin and found significant differences in the expression of cytokines and matrix metalloproteinases between samples taken from white and black women. The higher proinflammatory response to the same stimulus that was observed among blacks may explain higher rates of spontaneous preterm delivery in this group.
Weil (University of Texas Southwestern Medical Center, Dallas) and colleagues explored using proteomics (profiles of protein expression) from maternal serum to discriminate between women not in labor and those in preterm labor and those in labor at term. Using 25 data points of levels of various proteins in the maternal serum, they were able to differentiate the 3 groups with a sensitivity of 82% and a specificity of 76%. These researchers further theorized that the predictive value of this technique might be improved by using more homegenous racial and ethnic groups to develop a database for normal and abnormal levels of the proteins used in their analysis.
Crane (Memorial University of Newfoundland, St. John's, Canada) and colleagues examined the utility of transvaginal ultrasound performed at 24-30 weeks of gestation for predicting preterm delivery among women who had undergone loop electrical excision procedure (LEEP), cone biopsy, or cryotherapy. The authors reported the following results: (1) on average, women who had undergone one of these procedures had shorter cervical lengths than a low-risk control group; (2) their cervical lengths were similar to those obtained from women with a prior spontaneous preterm birth; (3) women who had undergone a LEEP or cone biopsy had a higher rate of spontaneous preterm delivery, and (4) a cut-off for cervical length on transvaginal ultrasound of 3 cm had a positive predictive value (PPV) of 58.3% in women who had undergone a LEEP, and a PPV of 33.3% for women who had undergone a cone biopsy.
Dolan (Albert Einstein College of Medicine, Bronx, New York) and colleagues posited that preterm birth should be classified as a "common complex disorder." A common complex disorder is one that occurs through a combination of genetic influences, environmental factors, and gene-environment interactions. Dolan and colleagues demonstrated through a review of the literature that preterm birth meets the established criteria for this classification -- and this is also demonstrated by the studies mentioned above. Dolan and colleagues suggest that this represents a paradigm shift that may allow for better use of genomics and genetic epidemiology to provide new tools for innovative research into the etiology of and therapeutic interventions for reducing preterm birth.
Medscape Ob/Gyn. 2005;10(1) © 2005 Medscape
Cite this: Highlights of the Society of Maternal-Fetal Medicine 25th Annual Clinical Meeting - Medscape - Mar 14, 2005.