Prevention of Preterm Parturition: Jay D. Iams, M.D

PREVENTION OF PRETERM
PARTURITION
JAY D. IAMS, M.D.
Pamangin Yandry
A woman presents for prenatal care in the first
trimester of her third pregnancy. Her first child was
born at 30 weeks of gestation after preterm labor.
Her second pregnancy ended in delivery at 19
weeks of gestation. How would you recommend
reducing the risk of preterm birth in this pregnancy?
The Clinical Problem
In the United States, the annual rate of preterm births (before

37 weeks of gesta-tion) reached a peak of 12.8% in 2006
and was 11.7% in 2011.
The rate in the United States remains nearly twice the rate in
European nations
Premature birth in the United States accounts for 35% of
deaths in the first year of life and estimated annual costs
exceeding $26 billion
Risk Factors
Factors associated with a risk of preterm birth may be
identified before pregnancy, at conception, or during
pregnancy.
Major risk factors for spontaneous preterm birth in cases of
singleton pregnancies include black maternal race, previous
pregnancy with an adverse outcome, genitourinary infection,
smoking, extremes of body weight, and social disadvantage.
Maternal depression, pre /pregnancy stress, poor diet,
assisted fertility, and periodontal disease are also associated
with pre-term birth
A previous preterm birth is a strong and easily identified risk
factor for future preterm births; a preterm birth increases the
risk of future pre-term births by a factor of 1.5 to 2
Short cervical length (i.e., values below the 10th percentile for
gestational age), as measured with the use of transvaginal
ultrasonography at 18 to 24 weeks of gestation is a consistent
predictor of an increased risk of preterm delivery
Key Clinical points
Prevention of Preterm Parturition
Despite advances in neonatal care, preterm birth remains a

leading cause of infant death in the United States, especially
among blacks.
Systemic changes in reproductive health care to reduce the
incidence of multifetal pregnancies and scheduled births
before 39 weeks of gestation that lack a medical indication
have been temporally associated with decreased preterm
birth rates.
Strategies to identify and treat medical risk factors in early
pregnancy (e.g., genitourinary infection and poor nutrition)
have not been effective in reducing preterm birth rates.
Previous preterm birth and a short cervix (20 mm, as
measured by transvaginal ultrasonography) are major risk
factors for preterm birth.
The use of progesterone supplementation in women with a
previous preterm birth, a short cervix, or both wasshown in
randomized trials to reduce the frequency of preterm birth
and is recommended for women with these risk factors.
Cervical cerclage reduces the risk of recurrent preterm birth
among women with a short cervix.
Strategies and Evidence
Strategies to prevent preterm birth have traditionally

emphasized early prenatal care as providing an opportunity
to identify and treat prematurity-related risk factors, but this
approach has not reduced the incidence of preterm birth.
Improved access to prenatal care is associated with lower
rates of preterm birth, but the linkage is apparently related
more to the high rates among women who receive no prenatal
care than to the content of care received
Adequately powered randomized trials of interventions aimed
at nutritional deficiencies (vitamins C and E,calcium, and n3
fatty acids), genital tract microorganisms (bacterial vaginosis
and Trichomonas vaginalis), or treatment of periodontal
disease have not shown reductions in preterm births among
women with risk factors or those without risk factors
Nevertheless, the rate of preterm births in the United States
has fallen annually since 2006; the percentage of births
before 34 weeks of gestation declined from 3.7% in 2006 to
3.4% in 2011.
Progesterone Therapy
Treatment with progesterone was initially stud-ied because of

evidence that labor begins when the ratio of progesterone
activity to estrogen activity is reversed or when progesterone
activity is blocked, resulting in cervical ripening and uterine
contractility.
Progesterone causes inhibition of cervical ripening, reduction of
myometrial contractility through suppression of oxytocin-
receptor synthesis and function, and modulation of
inflammation.
Cervical Cerclage
Cerclage, an encircling suture placed around the

cervix before or during pregnancy to correct
structural weakness or defects, has been a
controversial treatment for a short cervix
Available studies suggest that vaginal progesterone
and cervical cerclage are similarly effective in
reducing the risk of preterm birth among high-risk
women
Clinical Care
Ultrasonographic Screening for a Short Cervix
At or soon after the initial prenatal visit, a thorough review of

a womans previous pregnancies and risk factors for
prematurity and an ultrasonographic examination to document
the location of the gestational sac, the number of fetuses, and
the number of weeks of gestation are customarily performed.
Women with a previous spontaneous birth at 16 to 36 weeks
of gestation, including stillbirth before 24 weeks, are
candidates for prophylaxis beginning at 16 weeks of
gestation.
Such women should undergo cervical ultrasonography between
16 weeks and 24 weeks of gestation to determine whether
they are candidates for cerclage
Prescription of Progesterone
Vaginal progesterone is available as manufactured capsules

and gel and as compounded supposi-tories;
None of these formulations are currently approved by the
Food and Drug Administration (FDA) to reduce the risk of
preterm birth among women with a short cervix.
Manufactured (FDA-approved) and compounded 17OHPC
formulations are available for women who have had a
previous preterm birth.
Areas of Uncertainty
The pathophysiology of preterm parturition and the basis of its
association with risk factors such as black race are poorly
understood.
The mechanism of action of progestogens and the optimal
route of administration and dose of progestogen
supplementation for reducing the risk of preterm birth are also
uncertain.
More research is needed to identify women who give birth
prematurely but do not have a short cervix and to determine
the relative benefit of treatment with progesto-gens in women
with a short cervix.
Guidelines
The Society for Maternal-Fetal Medicine andthe American

College of Obstetricians and Gynecologists have issued
guidelines recommendingthat women with a previous
spontaneous preterm birth be offered treatment with weekly
injections of 17OHPC and that women with a shortcervix (20
mm) be offered treatment with vaginal progesterone.
The guidelines highlight the importance of obtaining a
thorough obstetricalhistory and the need for proper training to
obtain satisfactory ultrasonographic images.
Universal ultrasonographic screening is supported but not
considered mandatory.
Although the published guidelines agree on treatment, they
leave open the question of how best to identify eligiblewomen.
Recommendations in this article are generally concordant with
these guidelines
Conclusions and Recommendations
The woman described in the vignette has had two early

preterm births.
Her risk of recurrent preterm birth is at least 35% and is
higher if she is black. Her first prenatal visit should include
ultrasonography to determine the number of weeks of
gestation, and a careful history taking to identify other risk
factors, such as cigarettesmoking, nutritional deficits, and
genitourinary infections (even though trials have not shown the
efficacy of nutritional supplementation and treatment of
genitourinary infection in reducing preterm birth rates).
She should receive supplemental progestogen treatment, with
either 17OHPCinjections or vaginal progesterone.
She should also undergo regular transvaginal ultrasonographic
surveillance of cervical length, beginning at 16 weeks of
gestation, with consideration ofcerclage if the cervix measures
less than 25 mm before 24 weeks of gestation.
Finally, she should be educated about the signs and symptoms
of early cervical change that warrant prompt evaluation.

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PREVENTION OF PRETERM

In the United States, the annual rate of preterm births (before

Despite advances in neonatal care, preterm birth remains a

Strategies to prevent preterm birth have traditionally

Treatment with progesterone was initially stud-ied because of

Cerclage, an encircling suture placed around the

At or soon after the initial prenatal visit, a thorough review of

Vaginal progesterone is available as manufactured capsules

The Society for Maternal-Fetal Medicine andthe American

The woman described in the vignette has had two early

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