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Low Birthweight PORT publishes recent findings

The Low Birthweight in Minority and High-Risk Women Patient Outcomes Research Team (PORT) was supported by the Agency for Health Care Policy and Research (PORT contract 290-92-0055) to examine the factors contributing to low birthweight, particularly among low-income black women who are at increased risk for delivering low birthweight babies. In addition, PORT researchers studied practices aimed at preventing low birthweight and its major sequelae. Led by Robert L. Goldenberg, M.D., of the University of Alabama at Birmingham, the researchers recently published three studies, as well as the PORT final report. All are summarized here.

The first study demonstrates success with a five-step approach to increase doctors' use of corticosteroids, which are known to improve outcomes in preterm babies. The second study recommends that the routine screening of pregnant women for thrombocytopenia be discontinued. The third study concludes that maternal serum levels of metalloproteinase-9 do not appear to predict spontaneous preterm birth.

Leviton, L.C., Goldenberg, R.L., Baker, C.S., and others (January 1999). "Methods to encourage the use of antenatal corticosteroid therapy for fetal maturation. A randomized controlled trial." Journal of the American Medical Association 281(1), 46-52.

A multipart intervention to improve the quality of care that physicians give to pregnant women has been successful and shows promise of decreasing infant mortality and disability in preterm infants. The goal of the intervention was to increase the appropriate use of corticosteroids, which when given prior to a preterm birth can reduce the risk of complications. According to Dr. Goldenberg and colleagues, this intervention resulted in a 33 percent increase in the use of corticosteroids.

The study focused on minority and other high-risk women who tend to deliver preterm babies because of poor pregnancy weight gain, low prepregnancy weight, and other related lifestyle issues. Corticosteroid use is known to be one of the most effective ways to improve the outcomes of babies born preterm and reduce infant mortality and disability in preterm babies.

The AHCPR Low Birthweight PORT researchers used a five-step intervention to increase doctors' use of corticosteroids. The quality improvement program included enlisting local medical opinion leaders to encourage doctors to administer corticosteroids, lectures for doctors on corticosteroids, reminders in medical charts to use them, regular discussions with doctors on the various preterm scenarios, and ongoing feedback on their use of corticosteroids.

Although a National Institutes of Health Consensus Conference and several medical societies have endorsed the use of corticosteroids to reduce the complications of preterm delivery, this treatment continues to be underused by the medical community. According to the researchers, the reasons for this low use include the fact that many obstetricians underestimate the benefits of corticosteroids, and hospital obstetrical practices for preterm labor do not always allow for the most optimal timing of corticosteroid administration.

Rouse, D.J., Owen, J., and Goldenberg, R.L. (1998). "Routine maternal platelet count: An assessment of a technologically driven screening practice." American Journal of Obstetrics and Gynecology 179, pp. 573-576.

Routine screening of pregnant women for thrombocytopenia—or a low blood platelet count—a cause of bleeding disorders, should be discontinued. This practice fails to meet established pregnancy screening criteria. Also, it may actually be harmful because it may place unaffected fetuses of thrombocytopenic women and the women themselves at risk from invasive procedures. The researchers reviewed the literature to determine the potential for maternal thrombocytopenia screening to detect fetal thrombocytopenia and prevent fetal or neonatal mortality.

Autoimmune thrombocytopenia occurs in about 2 in 1,000 pregnancies and is estimated to result in neonatal intracranial hemorrhage in about 2 in 100,000 births. Gestational thrombocytopenia, which occurs in 4 percent to 7 percent of pregnancies, is 40 to 70 times as prevalent in pregnancy as the autoimmune form, but it poses negligible risk to the fetus. What's more, maternal thrombocytopenia has been shown to be a relatively insensitive indicator of severe fetal thrombocytopenia. The positive predictive value of such a screening test, that is, its ability to predict an infant who will sustain an intracranial hemorrhage based on identifying mothers with the condition, is 0.1 percent, calculate the researchers.

A maternal history of nongestational thrombocytopenia should identify nearly all of the about 2 in 1,000 women at presumed risk of delivering a severely thrombocytopenic infant. Also, women with gestational thrombocytopenia, which carries no risk to the fetus, may be diagnosed with autoimmune thrombocytopenia, and subjected needlessly to invasive diagnostic and therapeutic interventions such as cordocentesis and cesarean delivery. This screening test has an unacceptably high false-positive rate and is insensitive, that is, it fails to identify many at-risk fetuses, conclude the researchers.

Tu, F.F., Goldenberg, R.L., Tamura, T., and others (1998). "Prenatal plasma matrix metalloproteinase-9 levels to predict spontaneous preterm birth." Obstetrics and Gynecology 92, pp. 446-449.

The ability to identify biomarkers that can predict the onset of preterm labor or premature rupture of membranes would be invaluable in designing a therapy to prevent these problems. The Low Birthweight PORT was hopeful that a zinc-dependent proteinase, plasma matrix metalloproteinase-9, might be such a marker. However, this study shows that although levels of this substance remain unchanged throughout pregnancy and then rise three-fold at the onset of spontaneous labor, levels obtained just prior to delivery do not appear to predict spontaneous preterm birth.

The research team used an enzyme-linked immunosorbent assay to measure matrix metalloproteinase-9 levels in plasma samples from 35 nonpregnant women and in stored plasma samples obtained during a randomized trial of zinc supplementation in pregnant women. They then periodically sampled plasma levels of women who eventually delivered following spontaneous labor or premature rupture of membranes at 24 to 32 weeks, 33 to 36 weeks, and greater than 37 weeks.

They found that plasma matrix metalloproteinase-9 levels averaged about 19 ng/mL from 19 weeks until 36 weeks and did not change significantly as the gestational age increased. This remained true regardless of whether women ultimately delivered at 24 to 32, 33 to 36, or after 37 weeks. Levels obtained prior to, but within 1 week of, presentation for delivery were not significantly different from those obtained earlier in pregnancy. Finally, levels for women in spontaneous labor were similar regardless of gestational age and were increased three-fold compared with those drawn at each prenatal visit.

Low Birthweight in Minority and High-Risk Women Patient Outcomes Research Team. Final Report. (AHCPR Publication No. 98-N005).

In this final report, the researchers provide detailed findings on topics such as bacterial vaginosis, preeclampsia and low-dose aspirin therapy, biochemical predictors of preterm birth, prevention-based findings, and neonatal intensive care. The report also includes an extensive cumulative bibliography. Key findings from the 5½-year PORT project are summarized for clinicians in a two-page clinical highlight which is available from the AHCPR Publication Clearinghouse (AHCPR Publication No. 98-N005).

A limited supply of free copies of the complete report (AHCPR Publication No. 99-N005) are available from AHCPR Publication Clearinghouse. Select to access online copies of the abstract, cumulative bibliography, and the clinical highlight.

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