NEWS WATCH

CLINICAL INSIGHTS

Highlights from the Society for Maternal-Fetal Medicine Annual Meeting

First-trimester Down syndrome screening gets a thumbs up

First-trimester screening using nuchal translucency, PAPP-A (pregnancy-associated plasma protein A), and fß-hCG (the free ß subunit of human chorionic gonadotrophin) is about as effective in detecting Down syndrome as second-trimester screening that uses QUAD testing (alpha fetoprotein, hCG, unconjugated estriol (uE3), and inhibin A) but has fewer false positives, according to results of the FASTER trial presented at the Society for Maternal Fetal Medicine's annual meeting in New Orleans.

With the first-trimester protocol, 76% of cases were detected and only 3.2% of patients received false-positive results. The second-trimester approach detected 84% of cases but had a false-positive rate of 8.4%. When investigators looked at false-positive rates for various detection levels, they found that a fully integrated screening protocol that included nuchal translucency, PAPP-A, and the components of QUAD testing generated the most impressive results: Only 1.4% of women were wrongly told they were at risk for Down syndrome when the detection rate reached 80%. When 90% of cases were caught, the false-positive rate was 5.4%.

Malone FD, Wald NJ, Canick JA et al. First and second trimester evaluation of risk (FASTER) Trial: Principal results of the NICHD multicenter Down Syndrome Screening Study. Am J Obstet Gynecol. 2003;189(6 suppl):S56-S57. (Abstract 1).

Commentary by Charles J. Lockwood, MD, Yale University School of Medicine: It is time to consider such an approach in this country. The research presented at SMFM is very consistent with those of Wald and associates (N Engl J Med. 1999; 341:461-467) who reported that when a risk cutoff of 1/120 was used to define a positive result on an integrated first- and second-trimester screening test, the rate of detection of Down syndrome was 85%, with a false-positive rate of 0.9%. Dr. Wald's data suggest that integration of first- and second-trimester screening results would lead to detection rates comparable or better than can be achieved with either first- and second-trimester screening but with an 80% reduction in the number of invasive diagnostic procedures and consequent losses of normal fetuses.

Do preconception antibiotics thwart preterm births?

Theorizing that women at risk for preterm delivery might benefit from antibiotics between pregnancies, researchers gave 124 women with a history of spontaneous preterm birth either placebo or oral azithromycin 1 g BID (4 days apart) plus sustained release metronidazole, 750 mg a day, for 7 days. The regimen was started at 3 months postpartum and repeated every 4 months until the women conceived again.

Unfortunately this "preemptive strike" did not significantly reduce preterm births. In the antibiotic group, delivery at less than 37 weeks occurred in 62% of the patients, compared to 55% in the placebo group (P=0.515). There was also no difference in miscarriages between the two groups. Of more concern was the fact that mean birthweight was significantly lower among women on the antibiotics (1,989 vs. 2,464 g, P=0.032).

Andrews W, Goldenberg R, Hauth J, et al. Interconceptional antibiotics to prevent spontaneous preterm birth (SPTB): a randomized trial. Am J Obstet Gynecol. 2003;189(6 suppl):S56-S57. (Abstract 5).

Commentary by Charles J. Lockwood, MD:This report adds to the growing body of research suggesting that while inflammation may account for 40% to 60% of preterm births, antibiotics alone don't prevent prematurity. The explanation for this paradox may lie in the immune system of affected patients. Mounting evidence suggests that a genetic predisposition to an exaggerated cytokine response to potentially innocuous bacteria or an exaggerated protease response to a given cytokine may underlie many inflammation-induced preterm births. Indeed, at the same meeting, Gravett and associates (Abstract 3) reported that in rhesus monkeys, antibiotics alone had only a modest effect in prolonging pregnancy and little effect on amniotic cytokine or protease expression after intra-amniotic injection of group B streptococcus. In contrast, combining antibiotics with the anti-inflammatory drugs dexamethasone and indomethacin suppressed preterm birth for far longer and reduced amniotic fluid cytokine, but not protease production. We need to increase our focus on modulating maternal cytokine and protease responses to see improvements in the prevention of inflammation-induced prematurity.

The pros and cons of repeat steroids

Giving weekly courses of corticosteroids to women at risk for spontaneous preterm delivery may reduce infant mortality, especially when delivery occurs before 32 weeks, according to this randomized trial presented at SMFM's annual meeting. But it also significantly reduces birthweight.

To reach that conclusion, Ronald Wapner and his associates gave at-risk women who were initially less than 32 weeks pregnant—and had already received a single course of betamethasone—either weekly courses of the drug or placebo. Among women on multiple courses who delivered before 32 weeks, the overall incidence of stillbirth, neonatal death, severe respiratory distress syndrome, and related complications was 21.3%, compared to 38.5%, a marginally significant difference (P=0.083). When the research team looked more closely at the data, however, they found that repeat doses apparently reduced the need for surfactant (12.5% vs. 18.4%, P=0.02) and mechanical ventilation (15.5% vs. 23.5%, P=0.005).

On the other hand, infants who had been exposed to four or more courses weighed significantly less at birth (2,396 g vs. 2,561 g P= 0.01). But when investigators analyzed the data for all infants on repeat steroids, including those who had been exposed to more than one and less than four courses of therapy—the drop in birthweight became statistically insignificant. That led researchers to conclude that: "...further investigation of limited repeated steroid administration to women at high risk for early preterm birth is warranted." (Italics added)

Wapner RJ for the NICHD MFMU Network. A randomized trial of single vs. weekly course of corticosteroids. (Abstract 2).

Commentary by Charles J. Lockwood, MD:Until further clinical trials are conducted, I would recommend that a second course of corticosteroids be considered only in infants at immediate risk of preterm delivery prior to 28 weeks. The research presented at the SMFM meeting parallels the work done by Guinn DA, et al., (JAMA. 2001;286:1581-1587), who compared rates of respiratory distress syndrome (RDS), necrotizing enterocolitis, severe intraventricular hemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, sepsis, and perinatal death among infants whose mothers had received single versus weekly courses of antenatal corticosteroids. These investigators observed that these complications occurred in 22.5% of the weekly-course group versus 28.0% of the single- course group. While this difference was not statistically significant overall, it was significant among neonates delivered before 28 weeks. In particular, the rate of severe RDS in neonates delivered before 28 weeks was lower in the weekly steroid group (65.6%) compared with the single-course steroid (89.3%) group. However, the weekly steroid group had significantly higher rates of preterm deliveries between 24 and 27 weeks, shorter intervals from enrollment to delivery, and trends toward lower birthweights and increased maternal infections. So there's evidence that multiple courses of corticosteroids may reduce some indices of neonatal morbidity among infants born prior to 28 to 32 weeks but may have deleterious effects on growth.

PROFESSIONAL UPDATE

We're not doing enough to get women off tobacco

1987 is a year to be ashamed of: It was the point at which the number of women dying from lung cancer exceeded the number dying from breast cancer. It probably comes as no surprise to learn that smoking was the main culprit in this situation, according to a report by the National Women's Law Center and Oregon Health and Science University.

The report, "Women and Smoking: A National and State-by-State Report Card," found that 20.7% of adult women smoke. Compared to the national health objectives set by the US Department of Health and Human Services' Healthy People 2010, the nation falls far short of the goal to reduce smoking among adults to 12%.

Although advice from physicians to quit smoking has been shown to increase cessation rates, the report found that only 61% of female smokers reported having received smoking cessation advice from a physician in the past year. The national goal is to have physicians give such advice to 75% of smokers.

Only one state—Rhode Island—exceeded the national goal with 75.7% of smokers receiving cessation advice from physicians. North Dakota ranked last with just 43.8% of smokers receiving such advice.

The report indicated that a key opportunity to discuss smoking cessation with women is during physician counseling on contraceptive risks and benefits. Because there is some evidence indicating that nicotine in tobacco can break down the estrogen in oral contraceptives, women should be counseled that smoking may make an OC less effective and increase the risk for unplanned pregnancy.

Moreover, smoking during pregnancy has serious risks. Yet, according to the report, 12.2% of women nationwide continue to do so. No state met the national goal to reduce this rate to less than 1%. However, the District of Columbia came the closest with 2.6% of women smoking during pregnancy. West Virginia had the highest percentage of women who smoke during pregnancy (26.3%).

Do restricted work hours for residents mirror the reality of practice?

Not according to one recent study. Restrictions on the work hours of residents do not reflect the actual hours put in by obstetricians and gynecologists once they enter clinical practice, according to a study in the American Journal of Obstetrics and Gynecology (9/03).

In response to legislative bills on the state and federal level to limit residents' work hours in the name of patient safety, the Accreditation Council for Graduate Medical Education implemented its own restrictions. Effective July 1, 2003, the total number of hours worked by residents must be less than 80 per week averaged over 4 weeks, and on-call duty can be no more frequent than every third night, among other restrictions.

Researchers from the University of Texas Medical School found that, while the restrictions improved the quality of life for residents, they did not reflect the life of a Houston ob/gyn after training. Specifically, the researchers found that 62 of 100 ob/gyns who returned valid surveys about their work hours put in more than 80 hours per week. Moreover, more than half of the ob/gyns surveyed (55%) said they had on-call duty more frequently than every third night. Sixteen physicians said they covered all of their own on-call duty, and 32 covered their own on-call duty during the week with shared weekends.

Female ob/gyns say they practice what they preach

When it comes to their own health practices, female ob/gyns are taking advantage of their own knowledge of women's health, according to a survey conducted by the Gallup Organization for ACOG.

For example, the survey found that female ob/gyns cite obesity as the top health concern for women, with heart disease as the top concern for women over the age of 50. The survey also found that about 81% of female ob/gyns rate their physical fitness as excellent or good, with 72% reporting that they exercise on a regular basis. Moreover, 40% say their diet is very healthy and 68% say their weight is about right.

"As women in a women's health profession, female ob/gyns may be benefiting from an 'insider's perspective' in how to address the health challenges in their own lives," said Vivian M. Dickerson, MD, president-elect of ACOG. "This puts them in a unique position to help American women have healthier lifestyles."

Among the survey's other findings:

• The majority of female ob/gyns believe menstrual suppression is safe when used long-term (69%) or occasionally (30%). More than half (53%) say they've used oral contraceptives to suppress their own menstruation.

• Among those female ob/gyns who said they had undergone a caesarean delivery, 78% said it was performed for medical reasons—not as an elective. When asked if they would perform an elective C/S if a patient requested one, 36% said they would not, 32% said they would, and another 28% said it would depend on the circumstances.

• Female ob/gyns are more likely than American women in general to be screened for cervical or breast cancer. While 89% of American women of reproductive age have had a Pap test within the past 3 years, 78% of female ob-gyns had the test within the past 18 months and 90% had one within the past 2 years. Additionally, 70% of American women over age 40 in 2002 had a mammogram in the previous 2 years, while 73% of female ob/gyns age 48 and over had one in the past year and 86% had one within the past 2 years.

• 50% of female ob/gyns use hormone therapy to treat their own menopausal symptoms, and 19% said they did not use any treatment. Other types of treatment used by female ob/gyns include antidepressants (13%) to treat hot flashes and alternative natural therapies (13%), such as botanical black cohosh.

Court says physicians should warn, but not necessarily testify

Protecting the confidentiality of patients isn't an absolute duty: When physicians believe that a patient could harm another, they should report it to proper authorities or warn the intended target. But they shouldn't testify in the patient's trial. At least that's the opinion of the Ninth US Circuit Court of Appeals in California.

According to American Medical News (9/15/03), the federal appeals court reasoned that "a physician testifying against a patient in a courtroom would have a far more damaging impact on the physician-patient relationship than a physician going to authorities to report information." Specifically, the court noted that a patient who is convicted based in part on the testimony of his or her physician would certainly be less trustful of medical professionals and, in turn, would be more reluctant to seek further treatment for her condition.

 

Clinical Insights/Professional Update. Contemporary Ob/Gyn Feb. 1, 2004;49:13-21.