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Prevention of Pre-term Birth—A Challenge Not Yet Met
of pre-term birth in women pregnant with twins.
It is of interest to note that effective in eradicating the infection. Unfortunately, the evidence does not
applied the results of the NICHD-MFMU study to 2002 national birth suggest that treatment prevents pre-term delivery.
certificate data and concluded that use of progesterone among eligible women
would likely have a modest effect on the national pre-term birth rate. Cerclage
Cervical cerclage was introduced more than 50 years ago and uses suture
Bed Rest material to close the cervix with the goal of maintaining a pregnancy.
Bed rest has been widely used as a preventive measure. Smith and colleagues
Cervical cerclages have been placed in women with a history of
estimated that 20% of women are prescribed either partial or complete bed mid-trimester miscarriages or when cervical changes are noted on physical
rest at some point in their pregnancy. Sosa et al.
reviewed the only study that exam or by advanced ultrasound. Partly because use of cerclage is so
evaluated bed rest for women with singleton pregnancies
and found there ubiquitous, there have been a large number of trials to evaluate its
was no evidence to support or refute the use of bed rest to prevent pre-term effectiveness.
The MRC study found a slight reduction in pre-term birth
reviewed trials that evaluated hospitalization and bed rest for among the treatment group.
To and colleagues used the same definition
There was no evidence that bed rest improved the for pre-term birth (before 33 weeks’ gestation) and found no difference.
pregnancy outcome for women carrying twins (whether the pregnancy was The other studies referenced used a different definition limiting
complicated or uncomplicated) or triplets. In addition, bed rest has been
associated with increased likelihood of deep vein thrombosis,
lethargy, and isolation.
There was no evidence that bed rest
Omega-3 Fatty Acids
improved the pregnancy outcome for
It has been hypothesized that the intake of omega-3 long-chain
polyunsaturated fatty acids during pregnancy would improve outcome by
women carrying twins (whether the
preventing pre-eclampsia, preventing pre-term birth, and increasing birth
pregnancy was complicated or
weight. This hypothesis originated from a 1985 study
that found women
living in the Faroe Islands had among the highest birth weight infants in the
uncomplicated) or triplets.
world and a substantial part of this high birth weight was attributed to longer
gestation and hypothesized to be due to the high consumption of marine
Since that time, there have been a small number of studies that focused comparisons. For women at very high risk due to a cervical factor, there
on the role of omega-3 fatty acids in improving pregnancy outcomes. For may be a role for cervical cerclage. For women at low risk, cerclage will
more complete reviews of randomized controlled trials on the subject, see likely not prevent a pre-term birth. For more detailed reviews of these
Makrides, Duley, and Olsen
and Horvath, Koletzko, and Szajewska.
The studies, the reader is referred to Drakeley et al.,
Berghella et al.,
latter review focused on high-risk pregnancies. In the studies covering pre- Chervenak,
and the primary references.
only a small effect was found. The mean length of gestation for
women with singleton pregnancies was three days longer (95% CI 1.38–4.68 Prophylactic Tocolysis
days) than control women. No clear difference was seen in women with There are many pharmacological agents available to prevent or to
multiple pregnancies. Women with high-risk pregnancies benefited most treat threatened pre-term labor. These include tocolytic agents, such as
from allocation to the treatment group. These women had an increased β-mimetics, oxytocin receptor antagonists, calcium channel blockers, and
gestation of 8.5 days (95% CI 2.05–14.95 days). The evidence is not magnesium sulphate, as well at non-steroidal anti-inflammatory drugs
considered strong enough to recommend routine use of fish oil as a treatment (NSAIDs; Indomethacin and selective cyclooxygenase [COX] inhibitors). A
to prevent pre-term delivery. meta-analysis of β-mimetics concluded there was insufficient evidence to
support their use.
Studies of other agents listed above can be found in the
Antibiotics reference list.
However, none of these agents has been shown to
There is a large body of literature associating bacterial vaginosis in pregnancy effectively prevent pre-term birth.
with poor pregnancy outcomes that include low birth weight, pre-term birth,
stillbirth, and neonatal death.
Combined with the high prevalence of Conclusion
these poor outcomes made it an obvious avenue for In conclusion, only a brief review of the usual therapies suggested to reduce
study. There have been a large number of trials exploring varying therapeutic pre-term birth is presented here. Clearly there is much work still to be done,
regimes for treating vaginosis.
Evidence suggests that treatment is highly as preventing prematurity is a challenge we have not yet met. ■
1. Hamilton BE, Martin, JA, Ventura SJ, Births: Preliminary data for 5. National Center for Health Statistics, Health, United States, 2007 8. Meis PJ, Klebanoff M, Thom E, et al., Prevention of recurrent
2006, National Vital Statistics Reports, vol 56, no 7, Hyattsville, with Chartbook on Trends in the Health of Americans, Hyatsville, preterm delivery by 17 alpha-hydroxyprogesterone caproate,
MD: National Center for Health Statistics, 2007. MD: 2007. N Engl J Med, 2003;348:2379–85.
2. Saigal S, Doyle LW, An overview of mortality and sequelae of 6. Goldberg RL, Culhane JF, Iam JD, et al., Epidemiology and causes 9. Meis PJ, Klebanoff M, Dombrowski MP, Does progesterone
preterm birth from infancy to adulthood, Lancet, 2008;371:261–9. of preterm birth, Lancet, 2008; 371:75–84. treatment influence risk factors for recurrent pre-term delivery?
3. MacDorman MF, Mathews RJ, Recent trends in infant mortality in 7. da Fonseca EB, Bittar RE, Carvalho MHB, et al., Prophylactic Obstet Gynecol, 2005; 106(3):557–61.
the United States, NCHS Data Brief, no 9. Hyattsville, MD: National administration of progesterone by vaginal suppository to reduce 10. Spong CY, Meis PJ, Thom EA, Progesterone for prevention of
Center for Health Statistics, 2008. the incidence of spontaneous preterm birth in women at increased recurrent preterm birth: impact of gestational age at previous
4. Kiely JL, Kiely M, Epidemiological trends in multiple births in the risk: a randomized placebo-controlled double-blind study, Am J delivery, Am J Obstet Gynecol, 2005;193:1127–31.
US, 1971–1998, Twin Res, 2001;4:131–3. Obstet Gynecol, 2003;188:419–24. 11. Rouse, DJ., Caritis, SN, Peaceman AM, et al., A trial of 17
US OBSTETRICS & GYNECOLOGY 49
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