March 19, 2003

The Problem of Preterm Delivery

By Peter Bernstein, MD, MPH

Studies concerning the problem of preterm delivery were among the highlights at this year's Annual Clinical Meeting of the Society of Maternal-Fetal Medicine (SMFM), held from February 3-8, 2003 in San Francisco, California. Some of the studies investigated mechanisms of spontaneous preterm delivery, and others attempted to determine optimal management strategies for women at risk for this potentially devastating complication of pregnancy.

Preventing Preterm Delivery

One of the more dramatic studies presented involved the resurrection of an old drug for the treatment of preterm delivery. Investigators from the National Institutes of Child Health and Human Development Maternal-Fetal Medicine Units Network reported significant results treating women at high risk of preterm delivery with 17-alpha hydroxyprogesterone (17P).^[1] This drug had largely been investigated in several small trials in the 1960s and 1970s. Studies on the use of progesterone and other progestins have yielded conflicting results regarding their effectiveness.

Pregnant women obtaining prenatal care at one of the 19 institutions that are part of the Network were invited to participate in the current study; all had a history of a prior preterm birth. Participants were carrying singleton gestations and were enrolled between 15 and 20 weeks of gestation. None had cerclages or were receiving heparin or progesterone therapy during the pregnancy. As reported by Meis and colleagues, the study entailed randomizing the women to weekly injections of 250 mg of 17P or placebo until 37 weeks of gestation or delivery.

One thousand thirty-nine women were eligible, but only 463 agreed to participate and were randomized. Most of the others declined to participate in the study. The mean gestational age of the participants' prior preterm delivery was 30.7 weeks. Subjects were randomized in a 2 to 1 fashion to receive study medication or placebo, respectively. Compliance with the regimen was 91%, and reported side effects were minor.

The study was stopped after 351 participants had delivered when an interim analysis revealed a positive effect of the study medication: Treatment with 17P significantly reduced the rate of preterm delivery. The investigators halted the study on the basis that it would be unethical to continue to enroll new subjects into the study protocol. In the placebo group, 54.9% of patients delivered prematurely (defined as less than 37 weeks of gestation), compared with 36.3% of those in the study group (a reduction in risk of one third). More importantly, however, the rate of delivery at less than 32 weeks of gestation fell from 19.6% in the placebo group to 11.4% in the 17P group (P = .018). The rate of neonatal death was 5.9% in the placebo group and 2.6% in the study group, although this finding did not reach statistical significance (P = .08). These findings held for African American and non-African American women alike. The birth rates of neonates with birth weights of less than 2500 g and less than 1500 g were also significantly reduced. The authors hypothesized that only 5-6 women with prior preterm births would need to be treated to prevent 1 recurrent preterm birth at less than 37 weeks of gestation.

These results are especially remarkable given the lack of effective treatments to date for the prevention of preterm birth. Nevertheless, this is also a fairly unique study, and caution should be used before adopting the treatment regimen. The women enrolled in this study were an extremely high-risk group. Approximately 30% had more than 1 prior preterm delivery, and the average gestational age of their previous preterm delivery that qualified them for participation in the study was 30.7 weeks of gestation. The rate of delivery prior to 37 weeks in the placebo group was unusually high at nearly 55%. Typically, the rate of recurrent preterm birth after 1 prior preterm delivery is quoted as approximately 17%, and for women with 2 prior preterm deliveries, 28%. Thus, this calls into question the generalizability of this study to all women with a single prior preterm delivery, especially in light of the fact that more than half the eligible women did not participate in the study. This treatment regimen may not be as dramatically effective in all women at risk for preterm delivery. Given that the causes of preterm birth are multifactorial, more work will need to be done to determine which patients will most benefit from this therapy. I look forward to seeing more details of this study when it is ultimately published in its entirety.

How Do Progestational Agents Prevent Preterm Delivery?

One of the presentations in the basic sciences suggested a possible role progestational agents may play in preventing preterm delivery. Elovitz and Wang^[2] utilized a model of localized intrauterine inflammation in mice that resulted in preterm delivery and death to all the pups. Mice were given intrauterine lipopolysaccharide (LPS), which induces preterm delivery through inflammation. They demonstrated that in mice treated in this fashion, there is a rise in COX-2 levels (a marker of inflammation) and a corresponding fall in serum progesterone levels. When mice treated with LPS were also given progesterone, there were fewer preterm deliveries, but again no live pups. When LPS-treated mice were instead given medroxyprogesterone acetate (MPA), there were no preterm deliveries and a significant number of live pups. Additionally, COX-2 levels were significantly lower in mice that were treated with MPA. This seems to suggest that MPA has anti-inflammatory properties as well as progestin-like effects.

Periodontal Disease and Preterm Delivery

The hypothesis that preterm delivery has an inflammatory basis has been supported by studies that have shown a relationship between periodontal disease and preterm birth. Two groups of researchers at the University of Alabama presented 2 interesting studies concerning periodontal disease. Goepfert and colleagues^[3] performed periodontal examinations on 2065 women at 21-25 weeks of gestation. Study subjects were also tested for bacterial vaginosis, fetal fibronectin, and other cervical or vaginal infections. The women were then followed through until delivery. The authors noted that 63% of the women had some form of periodontal disease and were more likely to deliver prematurely compared with women without periodontal disease. These women were also more likely to have bacterial vaginosis. Some authors have found associations between bacterial vaginosis and preterm delivery, so this study sparks further interest in this correlation in terms of a possible etiology of preterm delivery. However, the hypothesis that bacterial vaginosis predisposes to ascending infection that results in preterm delivery may not be the whole story. Indeed, bacterial vaginosis may be only a marker of some broader status of the maternal host's immune system that predisposes these women to preterm delivery and periodontal disease.

Jeffcoat and colleagues^[4] went the additional step of randomizing women to different protocols for managing the periodontal disease and then followed the subjects to see whether there was any impact on their rates of preterm delivery. This pilot study was intended only to explore the feasibility of performing a larger study to determine the effectiveness of the authors' proposed interventions. A total of 366 pregnant women with periodontitis who were between 20 and 23 weeks of gestation were randomized to 1 of 3 groups. The first had dental prophylaxis together with placebo pills for 1 week; the second group had deep cleaning and polishing of their teeth along with placebo pills for 1 week; and the third group received the deep cleaning and polishing plus metronidazole treatment for 1 week.

The authors found that the preterm delivery rates at less than 37 weeks of gestation were 8.9%, 4.1%, and 12.5% for the groups of women receiving dental prophylaxis, deep cleaning, and deep cleaning and metronidazole treatment, respectively. The preterm delivery rates at less than 35 weeks of gestation were 4.9%, 0.8%, and 3.3%, respectively. Interestingly, the rates were lowest for the group that only had deep cleaning and polishing as treatment for their periodontal disease. Additional similar intervention studies involving larger groups of patients will need to be done to determine whether these results can be confirmed for this promising treatment to prevent preterm delivery.

Management of Preterm Premature Rupture of Membranes (PPROM)

Julien (Yale University, New Haven, Connecticut) and colleagues^[5] performed a study to determine the optimal management of women who have PPROM. The use of antibiotics in women with this complication of pregnancy has become commonplace since numerous studies have shown that these therapies prolong the latency period from the time of membrane rupture until the onset of labor. In response to growing concerns about the potential complications of long-term antibiotic therapy, this study was designed to determine the appropriate duration of antibiotic therapy in women with PPROM. The authors performed a randomized, double-blinded study of 2 different antibiotic regimens. Seventy-five pregnant women with PPROM who were between 25 and 36 weeks of gestation were randomized to 1 of 2 treatment regimens. One group received intravenous ampicillin/clavulanate for 48 hours and then oral placebo until delivery. The other group received the same intravenous antibiotic regimen followed by oral ampicillin/clavulanate until delivery.

Patients in the group that received the shorter antibiotic regimen had significantly longer latency periods (17.4 days vs 7.8 days, respectively, P = .04). The gestational age at delivery, however, averaged approximately 32 weeks in both groups. The authors concluded that 48 hours of antibiotic therapy in women with PPROM may be appropriate and that prolonged therapy seemed to accrue no additional benefit. The results of this study would need to be replicated in a larger study, one in which the size of the enrolled population would be sufficient to draw conclusions about neonatal and maternal outcomes.

The larger question of whether prolonging the latency period in women with PPROM significantly improves neonatal outcomes was addressed by Ramsey and colleagues of the National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network.^[6] They performed a secondary analysis of 582 women with singleton pregnancies who had been enrolled in a multicenter trial of antibiotic use compared with placebo in women with PPROM. In a multivariate analysis, which adjusted for gestational age at delivery, the authors noted that a longer latency was associated with greater neonatal morbidity, including perinatal death and respiratory distress syndrome. Much more study is needed to explore this interesting finding given the increased morbidity of delivery at earlier gestations. These data do, however, imply that conservative management of PPROM at later gestational ages may not be optimal.

Cerclage

Several presentations focused on the potential benefits of cerclage, and the findings were at times conflicting.

Rust and colleagues^[7] (Lehigh Valley Hospital, Allentown, Pennsylvania) performed a randomized trial of pregnant women with a history of a preterm birth and a shortened cervix combined with dilation of the internal os as documented by transvaginal ultrasound examination. The impetus of their study is the common but unproven practice of diagnosing cervical incompetence with the observation of cervical shortening during second-trimester transvaginal ultrasound. In previous studies, the authors have failed to demonstrate benefits of cerclage in pregnant women with cervical shortening alone.^[8,9] In their continued effort to find patients who might benefit from cerclage who have cervical shortening, they undertook this study of a group of even higher-risk women with cervical shortening: those with a history of a prior preterm delivery.

All patients in the current study were between 16 and 24 weeks of gestation. Patients with a history of a second-trimester delivery were included as patients with a history of preterm delivery. Patients were eligible only if they had a cervical length of 25 mm or less. All patients received 48-72 hours of indomethacin or antibiotics upon entry into the study and underwent an amniocentesis to rule out chorioamnionitis. Those randomized to cerclage then had a McDonald cerclage placed in the usual fashion. All patients were subsequently treated similarly. The authors estimated that they would need to enroll a total of 70 patients in order to achieve sufficient statistical power.

The authors of this study ultimately enrolled 89 patients into the study and randomized 48 to receiving cerclages. The cerclage group and the control groups were similar for all examined baseline variables, including gestational age at enrollment and gestational age of their prior preterm births. By chance, a greater number of patients with cervical lengths less than 15 mm were assigned to receive no cerclage, and a larger number with cervical lengths of 15-25 mm were assigned to receive a cerclage.

The authors found no improvement in outcome in the cerclage group when compared with their control group for the primary outcome variables in the study: gestational age at delivery and perinatal death. The authors did note that patients with earlier presentation with a shortened cervix tended to deliver earlier, as did those with shorter cervices on ultrasound at the time of enrollment. They concluded that cerclage has yet to be demonstrated as effective in preventing preterm delivery in women with shortened cervical lengths and therefore should not be used outside research protocols.

Odibo and colleagues^[10] (University of Pennsylvania Medical Center, Philadelphia, Pennsylvania) performed a meta-analysis of 6 randomized trials of cerclage compared with expectant management for the prevention of preterm birth. In total, these trials enrolled 2190 women, with more than 1000 women randomized to receive cerclages. Among these studies, a total of 278 (12.7%) women delivered before 34 weeks of gestation. Despite these large numbers, the authors were unable to demonstrate any benefit of cerclage in preventing delivery before 34 weeks of gestation, or, more importantly, any improvement in the prevention of neonatal morbidity or mortality. They did note a trend toward fewer births before 34 weeks of gestation, but this was not significant. Instead, they found that women who received a cerclage had a greater incidence of postpartum fever. They also noted that cerclage was not demonstrated to be of benefit in women with cervical lengths of less than 25 mm or in women carrying twin gestations. However, this study is limited by the broad range of study designs in the papers that were included in their meta-analysis, which potentially limits the appropriateness of combining the studies in a meta-analysis.

In an effort to identify a specific population of women who might benefit from a cerclage, Althuisius (VU Medical Center, Amsterdam) and colleagues^[11] performed a randomized trial of women with cervical incompetence who were at less than 27 weeks of gestation and who presented with a dilated cervix and membranes protruding to the external cervical os or beyond. Patients were randomized to an emergency McDonald cerclage and bed rest or bed rest alone. All women received 1 week of antibiotics starting at the time of randomization and were kept at bed rest until 30 weeks of gestation. Patients who received cerclages were treated with indomethacin around the time of the cerclage. They enrolled 16 women with singleton gestations and 7 with twins. Thirteen women in this study received cerclages. The mean gestational age at the time of randomization was similar in the 2 groups (approximately 22-23 weeks of gestation). The authors did note a longer duration of pregnancy from randomization to delivery in the group that received cerclages compared with the bed rest alone group (54 ± 47 days vs 20 ± 28 days, respectively, P = .046), although the mean gestational age at delivery was not statistically different (29.9 ± 8.4 weeks vs 25.9 ± 4.3 weeks, respectively, P = NS). Delivery rates at less than 34 weeks of gestation were significantly less in the cerclage group (7 of 13 women with cerclages vs 10 of 10 treated with bed rest alone, P = .02). Neonatal morbidity rates were also better in the cerclage group. This study is limited, however, by its small numbers and the heterogeneous group of patients that were enrolled.

Summary

• Weekly 17 alpha hydroxyprogesterone administration may be effective in preventing preterm delivery in women who are at extremely high risk for it, such as those with a history of preterm delivery.
• Medroxyprogesterone acetate prevents preterm delivery resulting from inflammation in a mouse model.
• Pregnant women with periodontal disease are at increased risk for preterm delivery.
• Preterm delivery rates may be decreased for women with periodontal disease who receive treatment for their dental condition.
• Forty-eight hours of intravenous antibiotic therapy in women with PPROM may be sufficient to prolong the latency period.
• Conservative management of PPROM at later gestational ages may not be optimal for improving neonatal outcome.
• Cerclage does not seem to be of benefit to women with prior preterm deliveries who present with a shortened cervical length on second-trimester ultrasound examination.
• A meta-analysis of studies of cerclage found no significant benefit in preventing preterm labor.
• Rescue cerclages and bed rest seemed superior to bed rest alone in the management of women presenting with a dilated cervix and membranes to at least the external cervical os in a small study presented at the meeting.
  

References

1. Meis PJ, the NICHD MFMU Network. 17 alpha hydroxyprogesterone caproate prevents recurrent preterm birth. Am J Obstet Gynecol. 2002;187:S54.
2. Elovitz M, Wang Z. Medroxyprogesterone (MPA) -- A novel inhibitor of inflammation-induced preterm birth. Am J Obstet Gynecol. 2002;187:S66.
3. Goepfert P, Schwebke J, Andrews W, et al. Perinatal emphasis research center (PERC): periodontal disease and vaginal markers of preterm birth. Am J Obstet Gynecol. 2002;187:S127.
4. Jeffcoat M, Hauth J, Geurs N, et al. Periodontal disease and preterm birth: results of an intervention study. Am J Obstet Gynecol. 2002;187:S79.
5. Julien S, Khandelwal M, Olasewere T. Randomized trial comparing long-term versus short-term antibiotic prophylaxis in preterm premature rupture of membranes (PPROM). Am J Obstet Gynecol. 2002;187:S66.
6. Ramsay P, the NICHD MFMU Network. Preterm premature rupture of membranes (PPROM): latency and neonatal outcome. Am J Obstet Gynecol. 2002;187:S113.
7. Rust O, Atlas R, Fischl S, Depuy A, Kimmel S, Hess LW. Does cerclage therapy improve perinatal outcome in patients with a history of previous preterm birth and cervical changes on 2nd trimester transvaginal ultrasound? Am J Obstet Gynecol. 2002;187:S58.
8. Rust O, Atlas RO, Reed J, van Gaalen J, Balducci J. Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help. Am J Obstet Gynecol. 2001;187:1098-1105.
9. Rust O, Atlas O, Jones KJ, Benham BN, Balducci J. A randomized trial of cerclage versus no cerclage among patients with ultrasonographically detected second-trimester preterm dilation of the internal os. Am J Obstet Gynecol. 2000;183:830-835.
10. Odibo A, Elkousy M, Ural S, Macones G. Cervical cerclage compared with expectant management for the prevention of preterm births: a systematic review. Am J Obstet Gynecol. 2002;187:S119.
11. Althuisius SM et al. Cervical incompetence prevention randomized cerclage trial (CIPRACT): emergency cerclage with bed rest versus bedrest alone. Am J Obstet Gynecol. 2002;187:S86.

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February 28, 2003

Treating Vaginal Infections Can Reduce Pre-term Births

By Colette Bouchez

FRIDAY, Feb. 28 (HealthScoutNews) -- British researchers have cast yet another vote in the ongoing debate over whether treating certain vaginal infections during pregnancy can prevent pre-term birth.

Their study found that when treatment was rendered during the first 20 weeks of pregnancy, the rate of premature birth was cut by a dramatic 60 percent.

The study, by researchers from the Imperial College of Medicine in London, appears in the March issue of Obstetrics and Gynecology.

As impressive as those findings sound, they join the ranks of numerous other studies arriving at clearly conflicting conclusions.

"Some researchers have found that treatment reduces premature birth, others have found it does not help, and at least one study has found that treatment during pregnancy actually increased the risk of premature birth. So in my mind, this study is another piece of the puzzle, but it certainly does not offer any definitive answers," says Dr. Andrei Rebarber, director of Maternal Fetal Medicine at New York University Medical Center, who was not involved in the research.

According to the British researchers, the point of the new study was not so much to test the theory of treatment versus non-treatment, but to hone in on more specific aspects of how and when the treatment is administered.

"This study was conducted to assess whether the use of intravaginal antibiotic used early in gestation would reduce the incidence of pre-term birth," the researchers write in the journal. They also point out that in previous studies, oral antibiotics were primarily used and the timing of treatment may have been more varied.

While doctors aren't sure why certain vaginal infections can lead to pre-term birth, Rebarber says several theories exist.

"It could be that an infection encourages cervical ripening," Rebarber says. In this instance, the cervix dilates sooner than it should, setting the labor process in motion. In addition, the infecting organism may also irritate the uterus, causing contractions to begin.

"The combination of the contractions and the cervical ripening work together to encourage a pre-term birth," Rebarber says.

"What we don't know," adds Rebarber," is why some women are susceptible while others are not."

In the new study, the researchers gathered 409 pregnant women each diagnosed with abnormal genital tract flora -- indicative of one of several simple vaginal infections -- somewhere between their 13th and 20th week of pregnancy.

The women were randomly selected to receive either a three-day treatment with Clindamycin vaginal cream, or a placebo cream.

The final outcome of the study was determined after all the women had given birth: Just 4 percent of those treated with the Clindamycin cream experienced a pre-term birth, compared to 10 percent in the placebo group.

Of the babies born pre-term, 63 percent required admission to the neonatal intensive care unit, compared to just 4 percent of the full-term infants.

"A 2 percent Clindamycin vaginal cream ... administered to women with abnormal genital tract flora before 20 weeks gestation can reduce the incidence of pre-term birth by 60 percent, hence the need for neonatal intensive care," the researchers say.

While Rebarber isn't convinced that all pregnant women with vaginal infections need treatment, he says those at high risk for premature birth could benefit.

The other deciding factor can be the type of infecting organism that is diagnosed. When that organism is Strep B, for example, treatment may become necessary, he says.

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February 20, 2003

Weekly Progesterone Injections Reduce Risk of Recurrent Preterm Births

By Roberta Friedman, PhD

SAN FRANCISCO (Reuters Health) Feb 06 - New findings confirm hints from decades ago that 17-alpha-hydroxyprogesterone can prevent preterm births in women with a history of premature delivery.

Results of a trial carried out with the National Institute of Child Health and Human Development's MFMU network were reported today at the meeting of the Society for Maternal-Fetal Medicine here. A total of 19 medical centers participated in the trial.

Dr. Paul Meis, of Wake Forest University, presenting for the network, said that the network has had "a big success, to find a possible treatment to help prevent preterm birth. It's very gratifying."

Women in the study had a documented prior birth of a baby at less than 37 weeks gestation. At between 16 and 20 weeks gestation, the women were assigned randomly to receive weekly injections of 17-alpha-hydroxyprogesterone caproate, or a placebo. Injections continued until 36 weeks gestation.

Progesterone treatment gave a 0.58 relative risk to deliver at less than 32 weeks, with 11.4% of women on the active drug delivering that early compared to 19.6% on placebo. Delivery at less than 37 weeks was also less likely for women on active drug, 36.3% compared to 54.9% of women on placebo (relative risk of 0.66).

Both comparisons were statistically significant.

Dr. Meis said in his talk that the incidence of neonatal complications also declined with the treatment, compared with women who had the placebo injections. The difference was statistically significant for necrotizing enterocolitis and for intraventricular hemorrhage.

The study was halted early as the difference emerged at interim analysis.

Dr. Meis noted that 17-alpha-hydroxyprogesterone is a generic agent that will not benefit any drug company.

He added that its use in this setting would represent an off-label use of an approved drug, as this form of progesterone is approved for infertility treatment. "We examined the background and literature on this drug thoroughly," Dr. Meis said, and the investigators were able to tell study participants that 17-alpha-hydroxyprogesterone is not teratogenic and does not masculinize a female fetus.

He concluded by saying that hospitals could conceivably adopt the treatment tomorrow.

Reuters Health Information 2003. © 2003 Reuters Ltd.

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December 10, 2002

Forget the Rest

Though Widely Prescribed to Cut Risk of Premature Delivery, Bed Rest Is Not Proven to Help -- and May Hurt

By Kathleen Phalen
Special to The Washington Post

When Jessica Cannon started spotting -- having a vaginal discharge of a small amount of blood that is sometimes a sign of early labor -- late in her second trimester, her obstetrician recommended bed rest to help keep the pregnancy from ending prematurely. Unlike many women who receive this prescription, Cannon -- herself an obstetrician in Wilmington, N.C. -- knows there's little scientific support for following the advice. Still, she plans to stay away from her office and off her feet for as long as three months. "Every week I can stay pregnant is better" for her unborn second child, she says.

So ingrained is the belief that bed rest is effective and safe that each year nearly 1 million pregnant American women spend at least one week in bed. Some put themselves there with no symptoms. But most do so after their doctors detect such things as preterm labor, pregnancy-related hypertension, slow fetal growth, a multiple pregnancy or preeclampsia -- conditions that help account for the 11 percent of U.S. pregnancies that end in preterm deliveries.

For many women with such risks to their pregnancies, there is little evidence that bed rest will keep them pregnant even one day longer or make the likelihood of delivering a healthy baby any greater. "The traditional approach [to preterm labor] has always been to recommend bed rest," says Charles Lockwood, chairman of the Department of Obstetrics and Gynecology at the Yale University School of Medicine in New Haven, Conn. "Really there is scanty evidence . . . but people do it -- even I do it."

In the November issue of the journal Obstetrics & Gynecology, Robert L. Goldenberg, a professor of obstetrics at the University of Alabama at Birmingham, reports that no randomized studies have evaluated bed rest for the prevention of preterm labor in singleton pregnancies. And of the four randomized trials for twin pregnancies that he assessed, two found that bed rest and hospitalization produced no benefit and two showed that these steps actually increased the chance of preterm birth.

"For me, this says in most cases [bed rest] shouldn't be prescribed," says Goldenberg. "This seemingly innocuous treatment costs billions" in lost work time and other expenses, he says, "and forcing a woman into bed not knowing it works is potentially harmful." Reducing physical activity may benefit some women at risk of preterm birth, Goldenberg acknowledges, but there's no evidence to support its widespread use. (Nor, according to his article, is there reason to believe that other measures -- hydration, sedation and at-home monitoring of uterine activity -- are effective against preterm labor.)

The argument against bed rest includes its side effects: muscle deconditioning, depression, isolation, pulmonary embolism and blood clots. "This is an old-fashioned management," says Laura E. Riley, an obstetrician and chair of the OB Practice Committee for the American College of Obstetricians and Gynecologists. "There is no proven benefit and there are lots of downsides. . . . In the last 10 years there's been a huge effort on the part of the college to make us do things based on evidence. And we are trying to say, 'Don't do it.' "

Preterm birth -- a delivery that occurs less than 37 weeks into a pregnancy -- is the leading cause of neonatal death and can cause cerebral palsy, mental retardation, respiratory distress syndrome, sepsis and hemorrhage. For Cannon, the risks that bed rest poses for her are nothing compared with the hazards her unborn child might face from early delivery. "I've worked with extreme preemies and they've got a rough road," Cannon says. "I might lose some income; I may get deconditioned, stressed or depressed. Those are reversible risks. But what if I deliver a baby at 27 weeks with cerebral palsy?"

What's the Downside?

Bed rest may stop contractions, but it will not delay labor, says Terry Hoffman, a Baltimore obstetrician. "If someone is spotting early, some say, 'Stay off your feet.' But that doesn't keep you pregnant longer," she says. "Whether you stay off your feet or keep working, if you're going to miscarry, you're going to miscarry."

If a woman is really in labor -- experiencing contractions that change the shape of the cervix -- the most physicians can do is postpone delivery for 24 to 48 hours by using tocolytic drugs. During this window steroids are given to help the baby's lungs mature. "In 48 to 72 hours, the steroids can advance the lung maturity up to the equivalent of a 34-week baby" in some cases, says Paul Lewis, a Kaiser Permanente perinatologist who practices at the health plan's center in Kensington.

About 40 years ago, aerospace scientists used bed rest as a model for understanding the effect of weightlessness on astronauts. NASA researchers and their counterparts in the Soviet Union found widespread detrimental effects, including muscle weakness and atrophy, loss of bone density, psychological problems, sensory deprivation, fainting, dizziness and weight loss. Prompted in part by these studies, doctors started getting surgical and cardiac patients out of bed faster than before. But decades later, researcher Judith A. Maloni wondered why pregnant women were still frequently placed on bed rest. So in 1989 she began examining the side effects of bed rest in pregnancy.

Maloni, an associate professor at the Frances Payne Bolton School of Nursing at Case Western Reserve University in Cleveland, discovered that women experience muscle loss, weight loss, indigestion, dizziness, shortness of breath on exertion, depression, sleep changes, fatigue, boredom, physical deconditioning and increased family stress. Postpartum, the side effects were also troubling: muscle weakness, backache, deep muscle soreness, feeling overwhelmed, swollen feet, feelings of loss, fatigue, loneliness.

"I want to change clinical practice," says Maloni, to make bed rest less common. "If we discover that bed rest is effective, we have to know it has side effects and develop interventions [such as] planned rehabilitation and a system at home to help deal with tasks."

Take-Home Babies

"Our goal is a take-home baby," says Bonnie Campos, a nurse practitioner and director of Kaiser Permanente's TLC program, which focuses on at-risk pregnancies.

About 1,500 to 1,800 women annually go through the TLC program, which is offered at Kaiser centers in the Baltimore and Washington areas. About one-third of those women are advised to reduce their activity levels, and some in that group are assigned to bed rest, usually at home. Since the program's inception in 1995, preterm births among TLC women have declined from 7.8 percent to 4.6 percent.

But even for patients on TLC's version of complete bed rest, says Lewis, "I explain that I expect patients horizontal for 20 out of 24 hours, and they are to get up eight times a day, a half-hour at a time," he says. In addition, bed rest patients are monitored to avoid dehydration, and they do daily exercises to maintain muscle strength.

Researchers at the University of North Carolina at Chapel Hill School of Public Health recently found a link between exercise and preterm birth. While their study, which appears in the November issue of the journal Epidemiology, did not evaluate bed rest, it suggests that most pregnant women benefit from staying active.

The researchers found that 14 percent of the pregnant women they studied reported engaging in vigorous leisure activity -- such as swimming laps or moderate to fast bicycling or jogging -- during the first trimester; 8 percent stayed active into the second trimester. Preterm births were somewhat less likely for those who did first-trimester workouts than for the large majority of women who did not, and this advantage was greater for those who remained active during the second trimester. The likelihood of "early" preterm birth -- delivery at 34 to 36 weeks -- was especially lower among the exercisers than among those who did not work out at all during their pregnancies.

"We can't rule out that there is some self-selection going on," said Kelly Evenson, research assistant professor of epidemiology at UNC's School of Public Health and the study's lead author. "Women who are feeling better during pregnancy may choose to engage in regular physical activities, while those who do not feel well may choose to be less active."

"It's striking that for whatever reason, there is a fairly strong relationship between being inactive later in pregnancy and increased risk of preterm birth," said David A. Savitz, chairman of the department of epidemiology at UNC's School of Public Health. "It's especially compelling given that our ability to predict who will or won't have preterm birth is very weak overall. . . . If there is in fact a causal relationship between activity level and the risk of preterm birth, it's quite exciting, because we can do something about it. It's a risk factor amenable to intervention."

Of course, what works for most women may not be best in each case. Having discussed bed rest with her doctor, Cora Schenberg, 44, knew it might not work, but she tried it anyway after she started having contractions every three minutes at 33 weeks. "I couldn't control it," says the Charlottesville resident. "It's like trying to stop the ocean."

For whatever reason, the tide ebbed for the next month, and at 37 weeks, Schenberg got what she wanted: a healthy baby with lots of soft beautiful hair. "For me, bed rest was a good thing," she says.

© 2002 The Washington Post Company

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December 5, 2002

Bacterial Infection Raises Late Miscarriage Risk

By Patricia Reaney

LONDON (Reuters) - A common bacterial infection in women increases the risk of a late miscarriage and raises the risk of a premature birth, doctors said on Friday.

But bacterial vaginosis (BV), an imbalance between good and harmful bacteria in the vagina, is easily detected and can be treated with antibiotics.

"We didn't find a significant association with miscarriage between 10-13 weeks but there was an association with miscarriage between 13-16 weeks," Phillip Hay, of St George's Hospital Medical School in London, said in an interview.

"It kicks in at about 13 weeks as a major risk factor for miscarriage," he added.

BV develops when there is a change in the balance of bacteria but doctors do not know what triggers it. It is very common and many women may not know they have it. It can clear up on its own or with medication.

Having a new or multiple sex partners seems to increase the risk of BV. Hay believes BV could be the cause of late, unexplained miscarriage, which occurs in about two percent of pregnancies.

"About 10 percent of the women in our study miscarried between 10 to 16 weeks," he said.

Hay and his colleagues studied 1,216 pregnant women attending family planning clinics in London. In the research, reported in The British Medical Journal, they found that miscarriage was more common in the 14.5 percent, or 174 women, who had BV.

There was no raised risk of miscarriage in women with a chlamydia infection.

The researchers are planning further studies to determine whether treating BV will reduce the risk of miscarriage. They suspect the bacterial imbalance triggers something in the womb that causes the loss of the child.

"The next step of the research is to do a study of treatment with antibiotics very early in pregnancy to show whether we can improve outcome," Hay added.

Miscarriage is most common in the first three months of pregnancy. About 25 percent of pregnancies end in miscarriage but the risk decreases after eight weeks' gestation.

Chromosomal disorders and a failure of the embryo to implant in the womb are common causes of miscarriage. Having a miscarriage does not prevent a further pregnancy

Multiple pregnancy, a history of miscarriages, a high fever, smoking and poorly controlled diabetes can also increase the risk.

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November 9, 2002

Early Pregnancy Activity Cuts Risk of Preterm Labor

By Megan Rauscher

NEW YORK (Reuters Health) - Pregnant women who engage in vigorous leisure activity during the first and second trimesters may be at reduced risk of preterm delivery, new study findings suggest.

Dr. Kelly R. Evenson of the University of North Carolina at Chapel Hill and colleagues looked at the link between vigorous leisure activity and birth outcomes in nearly 1,700 pregnant women. They conducted telephone interviews with the women to determine their level of physical activity in the 3 months preceding pregnancy and during the first and second trimesters.

In the November issue of Epidemiology, Evenson's team reports that 22% of the women engaged in vigorous leisure activity 3 months before pregnancy, 14% during the first trimester, and 8% during the second trimester. The median number of hours per week of vigorous leisure activity was 4 hours, 3 hours and 3 hours, respectively, for the three time periods.

While vigorous activity before pregnancy did not influence the risk of delivering prematurely, the risk of early delivery was "somewhat reduced" with vigorous leisure activity during the first trimester, and more so during the second trimester.

This finding is consistent with the results of three other studies, the authors note.

"We found that few pregnant women participated in vigorous leisure activity, such as aerobic dance classes or swimming laps, during the first or second trimester. However, for those that did participate in these types of activities, the risk of preterm birth was not increased and may even be reduced," Evenson told Reuters Health.

Evenson's team emphasizes that the "favorable results" may be due to other factors besides exercise. "Women who feel better may choose to be more active during leisure, whereas women with less healthy pregnancies might choose not to be active during leisure." Further studies are needed.

SOURCE: Epidemiology 2002;13:653-659.

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September 9, 2002

Doc-Mom Communication Poor During Stressful Labor

By Alison McCook

NEW YORK (Reuters Health) - Delivering a premature baby is a stressful experience, during which parents may need to make some tough decisions.

Parents may have to choose, for example, whether to subject a baby to a battery of tests and interventions if there is little hope he or she will survive. They may have to decide whether a mother should undergo a risky procedure in order to increase an ailing baby's chances.

Now, new study findings suggest that doctors and patients don't communicate well during such stressful and potentially life-threatening situations.

Based on a survey of parents whose baby needed to be delivered prematurely, Dr. John A. F. Zupancic of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts, and his colleagues found a difference between what parents said they wanted from their doctors and what their doctors thought parents wanted.

While 27% of parents strongly agreed that they would rather be advised what to do by their doctors than be asked by their doctors to make a decision, physicians surveyed said 79% of patients "probably" or "definitely" wanted to be advised. The researchers found that in 45% of cases, doctors thought a parent wanted to be advised while, in fact, the parents wanted to make the decision themselves.

Zupancic told Reuters Health that, in order to make informed decisions about how best to deliver the baby, and what types of medical interventions should be performed to keep the baby alive, parents have to take in a lot of information. And in such a stressful, time-constrained environment, "I think communication (between doctors and patients) suffers," he said.

During the study, Zupancic and his team distributed a questionnaire to 49 women 24 hours after they delivered a baby at 22 to 30 weeks gestation. The mothers indicated how much they wanted to be involved in the decision-making, and their levels of anxiety during the experience. The clinicians also completed a similar questionnaire, asking them about their patients.

One third of the mothers said they were extremely anxious during delivery, the authors report in the September issue of Archives of Disease in Childhood: Fetal and Neonatal Edition.

In an interview with Reuters Health, Zupancic said that in these stressful situations, some parents clearly want to be able to call the shots, while others want their doctors to guide them through the tough choices. "We don't seem to be able to identify in these interviews, in these conditions, which patients are which," he said.

Now that he and his colleagues have identified some of the issues involved in talking parents through preterm deliveries, "we need to find a way to do a better job," Zupancic noted.

For instance, Zupancic suggested that hospital staff try to present information to parents in a clear, structured way, using methods that have helped doctors communicate tough information to patients in other situations.

"We need to come to a way of having these discussions that benefits both the parent and the babies," he said.

SOURCE: Archives of Disease in Childhood: Fetal and Neonatal Edition 2002;87:F113-F117.

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July 11, 2002

Study Explores Mouth Bacteria, Preterm Delivery Link

NEW YORK (Reuters Health) - Certain bacteria may make their way from the mouth to the amniotic fluid, possibly putting pregnant women at risk of miscarriage, preterm delivery and other complications, according to the results of a preliminary study.

The amniotic fluid that surrounds the developing fetus is normally sterile. Infection within the amniotic sac, as a result of spread from the genital tract or medical procedures such as amniocentesis, can increase the risk of premature labor. One theory is that bacteria found in the mouth might also reach the amniotic fluid via the bloodstream, especially in women with inflamed or diseased gums.

In the study, the investigators analyzed samples of dental plaque and amniotic fluid from 48 women attending a hospital for an elective cesarean section. The average age of the study volunteers was 31 years.

The researchers found the DNA of a type of bacteria commonly found in the mouth in 7 out of 48 samples tested, according to the report in a recent issue of the British Journal of Obstetrics and Gynaecology. However, they were unable to culture, or grow the bacteria in the laboratory, suggesting that although DNA was present, the bacteria were present at very low levels or were not capable of causing infection.

The researchers did find, however, an association between microbes--both mouth bacteria and other types--in the amniotic fluid and complications in the women's previous pregnancies, including miscarriage, preterm delivery, premature rupture of the amniotic sac and death of the newborn.

"It is well recognized that DNA can persist in tissues for some time and may well have remained from a previous pregnancy," write Dr. Caroline Bearfield and colleagues from Queen Mary's School of Medicine and Dentistry, University of London, UK.

More study is needed to confirm the findings.

The researchers note that they used an extremely sensitive technique called PCR to check for genetic material from microbes in the various samples. Therefore, they add, the role of infection in pregnancy complications may have been underestimated by previous research using less sensitive tests.

SOURCE: British Journal of Obstetrics and Gynaecology 2002;109:527-533.

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June 26, 2002