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964 VOL. 120, NO. 4, OCTOBER 2012	 OBSTETRICS & GYNECOLOGY
P RACT I C E
BUL L E T I N
Background
Spontaneous preterm birth includes birth that follows pre-
term labor, preterm spontaneous rupture of membranes,
and cervical insufficiency, but does not include indicated
preterm delivery for maternal or fetal conditions (5).
The preterm birth rate (birth at less than 37 completed
weeks of gestation per 100 total births) increased more
than 20% from 1990 to 2006. However, decreases in
birth rates for both early preterm birth (earlier than 34
weeks of gestation) and late preterm birth (34 0/7–36 6/7
weeks of gestation) contributed to a decrease in the over-
all preterm birth rate between 2008 (12.3%) and 2009
(12.18%) (1). The risk of poor birth outcome generally
decreases with advancing gestational age. Although risks
are greatest for neonates born before 34 weeks of gesta-
tion, infants born after 34 weeks of gestation but before
37 weeks of gestation are still more likely to experience
delivery complications, long-term impairment, and early
death than those born later in pregnancy (6).
Infants born prematurely have increased risks of
mortality and morbidity throughout childhood, especially
during the first year of life. In the absence of more com-
prehensive tests of fetal and neonatal status, gestational
age is a common surrogate for presumed functional matu-
rity. Although age is related to maturity, no easily identi-
fied gestational age boundary exists between a premature
neonate and a mature neonate. The risks of perinatal,
neonatal, and infant morbidity and mortality are lowest
for infants born between 39 0/7 weeks of gestation and
40 6/7 weeks of gestation. These risks increase as gesta-
tional age at birth decreases, with morbidity reported at
37 weeks of gestation and even 38 weeks of gestation in
some series (7, 8).
Risk Factors
One of the strongest clinical risk factors for preterm birth
is a prior preterm birth (9). Maternal history of preterm
birth is commonly reported to confer a 1.5-fold to 2-fold
increased risk in a subsequent pregnancy. Importantly,
the number of prior preterm births and the gestational
age at the prior delivery significantly affect the recur-
rence risk of preterm birth (10). A preterm birth followed
by delivery at term confers lower risk than the opposite
Prediction and Prevention of
Preterm Birth
Preterm birth is the leading cause of neonatal mortality in the United States, and preterm labor precedes approxi-
mately 50% of preterm births (1, 2). Neonatal intensive care has improved the survival rate for neonates at the cusp
of viability, but it also has increased the proportion of survivors with disabilities (3). The incidence of multiple births
also has increased along with the associated risk of preterm delivery (4). The purpose of this document is to describe
the various methods proposed for identifying and treating asymptomatic women at increased risk of preterm birth and
the evidence for their roles in clinical practice.
Number 130, October 2012	 (Replaces Practice Bulletin Number 31, October 2001
	 and Committee Opinion No. 419, October 2008)
clinical management guidelines for obstetrician–gynecologists
Committee on Practice Bulletins—Obstetrics. This Practice Bulletin was developed by the Committee on Practice Bulletins—Obstetrics with the assis-
tance of Jay Iams, MD, Gary Dildy, MD, George Macones, MD, and Neil Silverman, MD. The information is designed to aid practitioners in making deci-
sions about appropriate obstetric and gynecologic care. These guidelines should not be construed as dictating an exclusive course of treatment or procedure.
Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.
The American College of
Obstetricians and Gynecologists
WOMEN’S HEALTH CARE PHYSICIANS
VOL. 120, NO. 4, OCTOBER 2012	 Practice Bulletin Prediction and Prevention of Preterm Birth 965
sequence (10, 11). For women with a prior preterm twin
birth, the risk of preterm birth in a subsequent singleton
gestation varies according to the gestational age at twin
delivery, with a recurrence risk as high as 40% when a
prior twin birth was before 30 weeks of gestation (12, 13).
Short cervical length measured by transvaginal ultra-
sonography also has been associated with an increased
risk of preterm birth (14–16). Short cervical length is
most commonly defined as less than 25 mm, usually
before 24 weeks of gestation, but up to 28 weeks of gesta-
tion in some series. It is a cutoff that has been associated
with an increased risk of preterm birth in screened popu-
lations (15, 17). Clinically, the shorter the cervical length,
the greater the risk of preterm birth.
Additional proposed risk factors for preterm birth
include aspects of obstetric and gynecologic history,
demographic characteristics, current pregnancy complica-
tions, and behavioral factors. However, data are inconsis-
tent about whether these factors are actually causative for
preterm birth. Preconception care allows an opportunity
to assess risk factors and provide counseling for women
with risk factors that can be modified, such as smoking
and optimal control of underlying chronic diseases (18).
A history of cervical surgery, including conization
and loop electrosurgical excision procedure, tradition-
ally has been thought to be a risk factor for preterm
birth because of associated cervical injury, but this rela-
tionship also may be related to environmental, factors,
behavioral factors, or both (such as smoking) that under-
lie the progression of cervical dysplasia (19, 20). Uterine
instrumentation (eg, dilation and curettage) also has been
associated with an increased risk of preterm birth in
some, but not all, studies; the mechanism is unclear, but
intrauterine microbial colonization, injury to the endo-
metrium, or both, together with host and environmental
factors, has been suggested (21).
Other factors during a current pregnancy that have
been associated with an increased risk of preterm
birth include vaginal bleeding, urinary tract infections
(UTIs), genital tract infections, and periodontal disease.
However, treatments for any of these potential risk fac-
tors have not been definitively demonstrated to result in
a decreased risk of preterm birth. Early studies of the
role of UTIs in preterm birth have demonstrated an asso-
ciation between untreated asymptomatic bacteriuria in
early pregnancy and increased rates of preterm birth (22,
23). However, subsequent meta-analyses have reported
conflicting results. One early report showed that untreat-
ed asymptomatic bacteriuria significantly increased rates
of low birth weight and preterm delivery (24). However,
later analyses, including one study of more than 25,000
births, and a Cochrane review, have failed to confirm
this finding (25, 26). Therefore, the association reported
between treating UTIs in pregnancy and preventing pre-
term birth may be related to preventing progression of
subclinical infections to pyelonephritis (25, 27). In addi-
tion, women with periodontal disease have an increased
risk of preterm birth that is not affected by periodontal
care. This suggests that the increased risk is caused by
associated traits rather than a causal linkage (28–31). In
fact, active treatment of periodontitis in pregnancy has
been shown in one study to potentially increase the risk
of spontaneous preterm birth (30).
Behavioral risk factors for preterm birth include
low maternal prepregnancy weight, smoking, substance
abuse, and short interpregnancy interval. Low maternal
body mass index (less than 19.8; calculated as weight
in kilograms divided by height in meters squared) has
been regularly found to be associated with an increased
risk of preterm birth (32, 33). Smoking is associated
with an increased risk of preterm birth and, unlike most
other risks, is amenable to intervention during pregnancy
(34, 35). An epidemiologic review of three U.S. studies
showed that the risk of adverse birth outcomes, includ-
ing preterm birth, was lowest when the interpregnancy
interval was 18–23 months and increased when the inter-
val fell outside of this range (36).
Screening Modalities
Transvaginal cervical ultrasonography has been shown
to be a reliable and reproducible way to assess the length
of the cervix (37). This is in contrast to transabdominal
ultrasound evaluation of the cervix. Unlike the transab-
dominal approach, transvaginal cervical ultrasonography
is not affected by maternal obesity, position of the cer-
vix, and shadowing from the fetal presenting part (38,
39). In addition, unlike digital examination, transvaginal
ultrasonography can help identify the presence of other
ultrasound risk markers for preterm delivery, such as
the presence of intraamniotic debris (a possible sign of
intrauterine microbial colonization) and choriodecidual
separation (40, 41).
When performed by trained operators, cervical
length screening by transvaginal ultrasonography is safe,
highly reproducible, and more predictive than transab-
dominal ultrasound screening. Using a method in which
the transvaginal probe is placed in the anterior fornix
of the vagina with an empty maternal bladder results in
measurements with interobserver variation of 5–10%
(37). Measurement of the cervical length in this manner
identifies a faint line of echodensity between internal and
external os, avoiding undue pressure on the cervix that
might increase its apparent length. The cervical length is
the shortest of three measurements taken between cali-
pers placed at the internal os and external os (15, 42). As
an independent finding, cervical funneling does not add
966 Practice Bulletin Prediction and Prevention of Preterm Birth	 OBSTETRICS & GYNECOLOGY
appreciably to the preterm delivery risk associated with a
shortened cervical length (43).
Other specific tests and monitoring modalities,
such as fetal fibronectin screening, bacterial vaginosis
testing, and home uterine activity monitoring have been
proposed to assess a woman’s risk of preterm delivery.
However, available interventional studies based on the
use of these tests for screening asymptomatic women
have not demonstrated improved perinatal outcomes
(44–46). Thus, these methods are not recommended as
screening strategies.
In addition, interventions, such as pharmacotherapy
with indomethacin or antibiotics, activity restriction, or
supplementation with omega-3 fatty acids have not been
evaluated in the context of randomized trials for women
with short cervical length, and are not recommended as
clinical interventions for women with an incidentally
diagnosed short cervical length. Although maternal dietary
fish consumption has been associated with a reduced risk
of preterm birth, supplementation with omega-3 fatty
acids was not found to reduce the risk of preterm birth in a
large randomized trial of women with a prior preterm
spontaneous birth who received 17a-hydroxyprogester-
one caproate (47, 48). Randomized placebo-controlled
trials of women taking vitamin C and vitamin E, supple-
mental calcium, and protein also have not been associ-
ated with a decreased risk of preterm birth (49–53).
Clinical Considerations and
Recommendations
	 How should women with a previous sponta-
neous preterm birth be evaluated for risk of
subsequent preterm birth?
The evaluation of women with a prior spontaneous pre-
term birth should include obtaining a detailed medical
history, reviewing comprehensively aspects of all previ-
ous pregnancies, reviewing risk factors, and determining
their candidacy for prophylactic interventions, such as
progesterone supplementation, cervical cerclage, or both.
A comprehensive review of all previous pregnancies
is an important step in the evaluation of women at risk of
preterm birth because the most important historical risk
factor for recurrent preterm birth is a prior spontaneous
preterm birth, including births in the mid-to-late second
trimester (54). It can be difficult to differentiate sponta-
neous preterm birth from indicated preterm birth, but an
effort to establish this distinction should be an integral
part of history taking. The review of medical records and
placental pathology results can be helpful in this process.
Spontaneous preterm births are those in which the onset
of parturition was spontaneous, regardless of whether
the process was later augmented. Rather than determin-
ing whether a prior preterm birth was spontaneous, it
may be easier first to exclude a prior preterm birth that
was obviously indicated (ie, initiated by the obstetric
care provider for a medical condition that threatened
maternal health, fetal health, or both).
	 How should the current pregnancy be man-
aged in a woman with a prior spontaneous
preterm delivery?
A woman with a singleton gestation and a prior spon-
taneous preterm singleton birth should be offered pro-
gesterone supplementation starting at 16–24 weeks of
gestation to reduce the risk of recurrent spontaneous
preterm birth (55–57) (Table 1). Whether such a woman
might additionally benefit from cervical cerclage place-
ment also has been studied.
A multicenter, randomized trial examined the role
of serial transvaginal cervical length screening, with cer-
clage placement for short cervical length, among women
with singleton gestations and prior spontaneous preterm
births at less than 34 weeks of gestation, including some
women who received 17a-hydroxyprogesterone caproate
(58). Women in this trial underwent serial cervical length
screening once every 2 weeks, starting at 16 weeks of
gestation until 23 weeks of gestation. If the length of
the cervix was noted to be between 25 mm and 29 mm,
the screening frequency was increased to once a week.
If the cervical length was less than 25 mm, women were
randomized to undergo cerclage or not to undergo cer-
clage. The primary study outcome was preterm birth at
less than 35 weeks of gestation, for which no significant
difference was detected (relative risk [RR], 0.78; 95%
confidence interval [CI], 0.58–1.04) (58). However,
placement of a cerclage was associated with significant
reductions in deliveries before 24 weeks of gestation
(RR, 0.44; 95% CI, 0.21–0.92) and before 37 weeks of
gestation (RR, 0.75; 95% CI, 0.60–0.93) as well as in
perinatal death (RR, 0.54; 95% CI, 0.29–0.99) when
compared with the group that did not undergo cerclage
(58). In a planned secondary analysis, cerclage for cer-
vical length less than 15 mm was associated with a sig-
nificant decrease in preterm birth at less than 35 weeks
of gestation (RR, 0.23; 95% CI, 0.08–0.66) (58). Based
on the pooled results of five clinical trials, in a singleton
pregnancy with prior spontaneous preterm birth at less
than 34 weeks of gestation and cervical length less than
25 mm before 24 weeks of gestation, cerclage was asso-
ciated with a 30% reduction in the risk of preterm birth
at less than 35 weeks of gestation (28% versus 41%; RR,
0.7; 95% CI, 0.55–0.89) and a 36% reduction in compos-
VOL. 120, NO. 4, OCTOBER 2012	 Practice Bulletin Prediction and Prevention of Preterm Birth 967
ite perinatal mortality and morbidity (16% versus 25%;
RR, 0.64; 95% CI, 0.45–0.91) (58–60).
Although the single largest trial of cerclage for pre-
term birth prevention in high-risk women did not find
benefit for the primary study outcome, available evi-
dence suggests that, in women with a current singleton
pregnancy, prior spontaneous preterm birth at less than
34 weeks of gestation and short cervical length (less
than 25 mm) before 24 weeks of gestation, cerclage
placement is associated with significant decreases in
preterm birth outcomes, offers perinatal benefits, and
may be considered in women with this combination of
history and ultrasound findings (58, 60). Insufficient
evidence exists to assess whether progesterone and cer-
clage together have an additive effect in reducing the
risk of preterm birth in women at high risk for preterm
birth (61).
No evidence exists to support the addition of an alter-
native form of progesterone to the current progesterone
treatment (eg, adding a vaginal form to an intramuscular
form), if a short cervix is identified in a woman with a
prior preterm birth who is already receiving preventive
progesterone therapy. Also, there is no evidence to sug-
gest that switching from treatment with intramuscular
progesterone to treatment with vaginal progesterone is
beneficial if a short cervix is identified.
Table 1. Selected Studies on Progesterone Supplementation for the Prevention of Preterm Delivery in Singleton Gestations
Study	Dosage	 Population
Meis, 2003*	 17a-hydroxyprogesterone caproate (250 mg 	 Women with a documented history of a spontaneous singleton preterm
	 weekly injections) 	 birth at less than 37 weeks of gestation; cervical length not measured 	
		 at entry; treatment initiated between 16 weeks of gestation and 20 		
		 weeks of gestation and continued until 36 weeks of gestation or deliv-	
		 ery, whichever occurred first
da Fonseca, 2003†
	 Vaginal progesterone (100 mg daily) 	 High-risk women with a history of spontaneous singleton preterm birth;
		 treatment initiated at 24 weeks of gestation and continued until
		 34 weeks of gestation
O’Brien, 2007‡
	 Vaginal progesterone (90 mg daily)	 Women with a history of spontaneous preterm birth randomized
		 and treated; cervical length measured at entry (mean length, 37 mm); 	
		 treatment initiated between 18 weeks of gestation and 22 6/7 weeks 		
		 of gestation and continued until 37 weeks of gestation, occurrence of 	
		 premature rupture of membranes, or preterm delivery
Fonseca, 2007§
	 Micronized progesterone gel capsules 	 Asymptomatic women with a very short cervical length (15mm or less);
	 (200 mg vaginally daily)	 90% of the women had a singleton gestation and 85% had no prior
		 preterm delivery; treatment initiated at 24 weeks of gestation and con-	
		 tinued until 34 weeks of gestation
Hassan, 2011||
	 Vaginal progesterone gel (90 mg daily)	 Women with a singleton gestation with a previous preterm birth
		 between 20 weeks of gestation and 35 weeks of gestation; patients
		 were randomized between 20 weeks of gestation and 23 6/7 weeks of
		 gestation; treatment continued until 36 6/7 weeks of gestation, rupture
		 of membranes, or delivery, whichever occurred first.
Hassan, 2011||
	 Vaginal progesterone gel (90 mg daily)	 Only women without prior preterm birth; patients were randomized
		 between 20 weeks of gestation and 23 6/7 weeks of gestation;
		 treatment continued until 36 6/7 weeks of gestation, rupture of
		 membranes, or delivery, whichever occurred first.
*Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.
National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network [published erratum appears in N Engl J Med 2003;349:1299]. N
Engl J Med 2003;348:2379–85.
†
da Fonseca EB, Bittar RE, Carvalho MH, Zagaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm
birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol 2003;188:419–24.
‡
O’Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a
randomized, double-blind, placebo-controlled trial. Ultrasound Gynecol 2007;30:687–96.
§
Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. Fetal Medicine Foundation Second
Trimester Screening Group. N Engl J Med 2007;357:462–9.
||
Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short
cervix: a multicenter, randomized, double-blind, placebo-controlled trial. PREGNANT Trial. Ultrasound Obstet Gynecol 2011;38:18–31.
968 Practice Bulletin Prediction and Prevention of Preterm Birth	 OBSTETRICS & GYNECOLOGY
tive, safe, accepted by patients, and widely available.
Opponents of this approach raise the following concerns:
quality assurance of the screening test; lack of availabil-
ity of screening and of patient access to qualified imaging
centers in some areas; and the potential for patients to
receive unnecessary or unproven interventions.
The American College of Obstetricians and Gyne-
cologists recognizes that both sides of this debate raise
valid issues. Although this document does not mandate
universal cervical length screening in women without a
prior preterm birth, this screening strategy may be con-
sidered. Practitioners who decide to implement universal
cervical length screening should follow one of the pro-
tocols for transvaginal measurement of cervical length
from the clinical trials on this subject. Protocol citations
are listed in Table 1.
	 What interventions have been shown to be
beneficial for reducing the risk of preterm
birth in women who do not have a history of
preterm birth but who are found to have a
short cervical length?
Cerclage and progesterone are the two interventions that
have been evaluated in randomized trials for effective-
ness in preventing preterm birth in women with single-
ton gestations without a prior preterm birth (Fig. 1).
Vaginal progesterone has been studied as a manage-
ment option to reduce the risk of preterm birth in asymp-
tomatic women with singleton gestations without prior
preterm birth with a very short cervical length, defined
as less than or equal to 20 mm at up to 24 weeks of gesta-
tion. In a randomized placebo-controlled trial, treatment
with vaginal micronized progesterone, 200 mg daily,
was associated with a 44% decrease in spontaneous pre-
term birth at less than 34 weeks of gestation among
asymptomatic women with a cervical length of 15 mm or
less at 20–25 weeks of gestation (19% versus 34%; RR,
0.56; 95% CI, 0.36–0.86) (62). In this study, 90% of the
women had a singleton gestation, and 85% had no prior
preterm birth (62).
In another recent randomized placebo-controlled
trial, treatment with vaginal progesterone gel, 90 mg
daily, was associated with a 45% decrease in spontane-
ous preterm birth at less than 33 weeks of gestation (9%
versus 16%; RR, 0.55; 95% CI, 0.33–0.92) and a 43%
decrease in composite neonatal morbidity and mortality
(8% versus 14%; RR, 0.57; 95% CI, 0.33–0.99) among
asymptomatic women with a cervical length of 10–20.9
mm at 19–23 6/7 weeks of gestation (16). All the women
in this study had singleton gestations, with a 16% inci-
dence of prior preterm birth. Analysis of only women
without prior preterm birth confirmed significant benefit
	 Should a woman with a current singleton
pregnancy without a history of preterm birth
be screened for a risk of preterm birth?
In general, women in this clinical scenario are at a low
risk of preterm birth. However, if second trimester
transabdominal scanning of the lower uterine segment
suggests that the cervix may be short or have some other
abnormality, it is recommended that a subsequent trans-
vaginal ultrasound examination be performed to better
visualize the cervix and establish its length (15). Until
recently, routine cervical length evaluation in women
at a low risk of preterm delivery was not advocated
because, like other factors associated with a potentially
higher preterm birth risk, no effective treatments were
available to reduce that risk. Recent randomized tri-
als that investigated the use of vaginal progesterone in
women with a short cervix diagnosed through screening
have initiated consideration of whether the current stan-
dard for evaluating the cervix should be changed.
A European trial that enrolled women with a very
short cervical length (15 mm or less) demonstrated a
lower risk of preterm birth in those treated with vaginal
progesterone suppository, 200 mg daily, compared with
those who were treated with a placebo (62). In this study,
only 1.7% of the 24,640 women screened at 20–25 weeks
of gestation (median, 22 weeks of gestation) were found
to have a cervical length less than or equal to 15 mm and,
therefore, to be eligible for the trial.
In a subsequent randomized trial, the use of vagi-
nal progesterone gel, 90 mg daily, was associated with
a decrease in spontaneous preterm birth at less than 33
weeks of gestation (9% versus 16%; RR, 0.55; 95% CI,
0.33–0.92) and a decrease in composite neonatal mor-
bidity and mortality (8% versus 14%; RR, 0.57; 95% CI,
0.33–0.99) among asymptomatic women with a cervical
length of 10–20 mm at 19–23 6/7 weeks of gestation (16).
All the women in this study had singleton gestations, with
a 16% incidence of prior preterm birth. Analysis of only
women without prior preterm birth confirmed significant
benefit of progesterone in preventing preterm birth before
33 weeks of gestation in this study (16). Even taking
into account the large number of women needed to be
screened to identify those at risk, recent decision and
economic analyses concluded that universal ultrasound
screening for short cervical length and treatment with
vaginal progesterone was cost-effective (63, 64).
Proponents of universal cervical length screening of
women without a prior preterm birth cite the following
points in support of this practice: it has the potential to
reduce the preterm birth rate; high quality evidence exists
to support efficacy of treatment for positive test results
(ie, cervical length of 20 mm or less); and it is cost effec-
VOL. 120, NO. 4, OCTOBER 2012	 Practice Bulletin Prediction and Prevention of Preterm Birth 969
of treatment with progesterone in preventing preterm
birth before 33 weeks of gestation in this study (16).
Therefore, vaginal progesterone is recommended as a
management option to reduce the risk of preterm birth in
asymptomatic women with a singleton gestation without
a prior preterm birth with an incidentally identified very
short cervical length less than or equal to 20 mm before
or at 24 weeks of gestation.
In contrast, for women in this otherwise low-risk
population, cerclage placement in women with a cervi-
cal length less than 25 mm detected between 16 weeks
of gestation and 24 weeks of gestation has not been
associated with a significant reduction in preterm birth
at less than 35 weeks of gestation [RR, 0.76; 95% CI,
0.52–1.15] (59). Even cerclage placement for detection
of a cervical length of 15 mm or less in women at 22–24
weeks of gestation has not been shown to significantly
decrease the rate of preterm birth (at less than 33 weeks
of gestation) (RR, 0.84; 95% CI, 0.54–1.31) (65).
In one trial of women with an incidentally diag-
nosed short cervix (less than or equal to 25 mm at 18–22
weeks of gestation), open-label randomization to place-
ment of a cervical pessary or expectant management (no
pessary) was studied (66). In this trial of 385 women,
the rate of spontaneous delivery at less than 34 weeks
of gestation was significantly lower in the pessary group
than in the no pessary group (6% compared with 27%;
OR, 0.18; 95% CI, 0.08–0.37). If the results of this small
trial are validated, cervical pessary placement may have
additional benefit for prevention of preterm birth in oth-
erwise low-risk women with a short cervix.
	 Does cerclage placement or progesterone
treatment decrease the risk of preterm birth
in women with multiple gestations?
Available data regarding the efficacy of cerclage place-
ment, progesterone supplementation, or both for the
reduction of preterm birth risk in women with multiple
gestations with a short cervical length with or without a
prior preterm birth do not support their use (67). Cerclage
may increase the risk of preterm birth in women with a
twin pregnancy and ultrasonographically detected cervi-
cal length less than 25 mm and is not recommended. In
a meta-analysis of randomized trials, cerclage performed
in women with a twin pregnancy and a cervical length
less than 25 mm was actually associated with a significant
twofold increase in the rate of preterm birth (RR, 2.2; 95%
CI, 1.2-4) (59). Progesterone treatment does not reduce
the incidence of preterm birth in women with twin or
triplet gestations and, therefore, is not recommended as
an intervention to prevent preterm birth in women with
multiple gestations (68–72). Currently, no data are avail-
able regarding the efficacy of any other interventions to
reduce the risk of preterm birth in women with multiple
gestations and a short cervix, and the use of any such
alternative measures cannot be recommended outside of
formal clinical trials.
Fig. 1. Algorithm for the management of short cervical length in the second trimester.
Short cervix identified with
transvaginal ultrasonography
Singleton gestation Multiple gestation
No intervention has
been shown to
improve outcomes
No prior spontaneous
preterm birth
Prior spontaneous
preterm birth and
receiving progesterone
supplementation since
16 weeks of gestation
Cerclage should be
considered if cervical
length is less than
25 mm before
24 weeks of gestation
and prior preterm birth
occurred at less than
34 weeks of gestation
Vaginal progesterone
supplementation
should be offered if
cervical length is
20 mm or less
before or at
24 weeks of gestation
970 Practice Bulletin Prediction and Prevention of Preterm Birth	 OBSTETRICS & GYNECOLOGY
Summary of
Recommendations and
Conclusions
Recommendations based on good and consistent
scientific evidence (Level A):
	 A woman with a singleton gestation and a prior
spontaneous preterm singleton birth should be
offered progesterone supplementation starting at
16–24 weeks of gestation, regardless of transvagi-
nal ultrasound cervical length, to reduce the risk of
recurrent spontaneous preterm birth.
	 Vaginal progesterone is recommended as a manage-
ment option to reduce the risk of preterm birth in
asymptomatic women with a singleton gestation
without a prior preterm birth with an incidentally
identified very short cervical length less than or
equal to 20 mm before or at 24 weeks of gestation.
	 Tests, such as fetal fibronectin screening, bacterial
vaginosis testing, and home uterine activity moni-
toring, are not recommended as screening strategies.
	 Progesterone treatment does not reduce the inci-
dence of preterm birth in women with twin or triplet
gestations and, therefore, is not recommended as an
intervention to prevent preterm birth in women with
multiple gestations.
Recommendations based on limited or inconsis-
tent scientific evidence (Level B):
	 Although this document does not mandate universal
cervical length screening in women without a prior
preterm birth, this screening strategy may be consid-
ered.
	 Insufficient evidence exists to assess if progesterone
and cerclage together have an additive effect in
reducing the risk of preterm birth in women at high
risk for preterm birth.
	 Cerclage may increase the risk of preterm birth in
women with a twin pregnancy and an ultrasono-
graphically detected cervical length less than 25 mm
and is not recommended.
Recommendations based primarily on consensus
and expert opinion (Level C):
	 Practitioners who decide to implement universal
cervical length screening should follow one of the
protocols for transvaginal measurement of cervical
length from he clinical trials on this subject. Protocol
citations are listed in Table 1.
Proposed Performance
Measure
Percentage of women with a prior spontaneous preterm
birth who are offered progesterone supplementation
References
	 1.	 Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Mathews
TJ, Osterman MJ. Births: final data for 2008. Natl Vital
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	2.	Goldenberg RL, Culhane JF, Iams JD, Romero R.
Epidemiology and causes of preterm birth. Lancet 2008;
371:75–84. (Level III)
	 3.	 Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson
AR. Neurologic and developmental disability after extremely
preterm birth. EPICure Study Group. N Engl J Med 2000;
343:378–84. (Level II-2)
	 4.	 Preterm singleton births--United States, 1989-1996. Centers
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34.	 Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley
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39.	 Leitich H, Brunbauer M, Kaider A, Egarter C, Husslein P.
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Das A, et al. The length of the cervix and the risk of
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16.	 Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK,
Khandelwal M, et al. Vaginal progesterone reduces the
rate of preterm birth in women with a sonographic short
cervix: a multicenter, randomized, double-blind, placebo-
controlled trial. PREGNANT Trial. Ultrasound Obstet
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18.	 Shih W, Rushford DD, Bourne H, Garrett C, McBain JC,
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22.	 Schieve LA, Handler A, Hershow R, Persky V, Davis F.
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with maternal morbidity and perinatal outcome. Am J
Public Health 1994;84:405–10. (Level II-3)
23.	 Klein LL, Gibbs RS. Infection and preterm birth. Obstet
Gynecol Clin North Am 2005;32:397–410. (Level III)
24.	 Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC,
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loss and subsequent pregnancy outcomes: What is the real
risk? Am J Obstet Gynecol 2007;197:581.e1–6. (Level
II-2)
55.	 Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B,
Moawad AH, et al. Prevention of recurrent preterm deliv-
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56.	 Use of progesterone to reduce preterm birth. ACOG
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vention: an evolving intervention. Am J Obstet Gynecol
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58.	 Owen J, Hankins G, Iams JD, Berghella V, Sheffield JS,
Perez-Delboy A, et al. Multicenter randomized trial of
cerclage for preterm birth prevention in high-risk women
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Gynecol 2009;201:375.e1–8. (Level I)
59.	 Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM.
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61.	Berghella V, Figueroa D, Szychowski JM, Owen J,
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one caproate for the prevention of preterm birth in women
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62.	 Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH.
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63.	Cahill AG, Odibo AO, Caughey AB, Stamilio DM,
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analysis)
64.	 Werner EF, Han CS, Pettker CM, Buhimschi CS, Copel
JA, Funai EF, et al. Universal cervical-length screening to
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40.	 Kusanovic JP, Espinoza J, Romero R, Goncalves LF,
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41.	 Faye-Petersen OM. The placenta in preterm birth. J Clin
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42.	 Owen J, Iams JD. What we have learned about cervical
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43.	 Berghella V, Roman A, Daskalakis C, Ness A, Baxter JK.
Gestational age at cervical length measurement and inci-
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(Level II-3)
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Maier JA, et al. Monitoring women at risk for preterm
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VOL. 120, NO. 4, OCTOBER 2012	 Practice Bulletin Prediction and Prevention of Preterm Birth 973
prevent preterm birth: a cost-effectiveness analysis. Ultra-
sound Obstet Gynecol 2011;38:32–7. (Cost-effectiveness
analysis)
65.	 To MS, Alfirevic Z, Heath VC, Cicero S, Cacho AM,
Williamson PR, et al. Cervical cerclage for prevention of
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cal length and risk of preterm birth in women with twin
gestations treated with 17-alpha hydroxyprogesterone
caproate. Eunice Kennedy Shriver National Institute of
Child Health and Human Development Maternal-Fetal
Medicine Units Network. J Matern Fetal Neonatal Med
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68.	 Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom
EA, Spong CY, et al. A trial of 17 alpha-hydroxyproges-
terone caproate to prevent prematurity in twins. National
Institute of Child Health and Human Development
Maternal-Fetal Medicine Units Network. N Engl J Med
2007;357:454–61. (Level I)
69.	 Norman JE, Mackenzie F, Owen P, Mactier H, Hanretty K,
Cooper S, et al. Progesterone for the prevention of pre-
term birth in twin pregnancy (STOPPIT): a randomised,
double-blind, placebo-controlled study and meta-analysis.
Lancet 2009;373:2034–40. (Level I)
70.	Combs CA, Garite T, Maurel K, Das A, Porto M.
17-hydroxyprogesterone caproate for twin pregnancy:
a double-blind, randomized clinical trial. Obstetrix
Collaborative Research Network. Am J Obstet Gynecol
2011;204:221.e1–8. (Level I)
71.	Caritis SN, Rouse DJ, Peaceman AM, Sciscione A,
Momirova V, Spong CY, et al. Prevention of preterm birth
in triplets using 17 alpha-hydroxyprogesterone caproate:
a randomized controlled trial. Eunice Kennedy Shriver
National Institute of Child Health and Human Develop-
ment (NICHD), Maternal-Fetal Medicine Units Network
(MFMU). Obstet Gynecol 2009;113:285–92.(Level I)
72.	 Combs CA, Garite T, Maurel K, Das A, Porto M. Failure
of 17-hydroxyprogesterone to reduce neonatal morbidity
or prolong triplet pregnancy: a double-blind, randomized
clinical trial. Obstetrix Collaborative Research Network
[published erratum appears in Am J Obstet Gynecol
2011;204:166]. Am J Obstet Gynecol 2010;203:248.e1–9.
(Level I)
The MEDLINE database, the Cochrane Library, and the
American College of Obstetricians and Gynecologists’
own internal resources and documents were used to con­
duct a lit­er­a­ture search to lo­cate rel­e­vant ar­ti­cles pub­lished
be­tween January 1990 and March 2012. The search was
re­strict­ed to ar­ti­cles pub­lished in the English lan­guage.
Pri­or­i­ty was given to articles re­port­ing results of orig­i­nal
re­search, although re­view ar­ti­cles and com­men­tar­ies also
were consulted. Ab­stracts of re­search pre­sent­ed at sym­po­
sia and sci­en­tif­ic con­fer­enc­es were not con­sid­ered adequate
for in­clu­sion in this doc­u­ment. Guide­lines pub­lished by
or­ga­ni­za­tions or in­sti­tu­tions such as the Na­tion­al In­sti­tutes
of Health and the Amer­i­can Col­lege of Ob­ste­tri­cians and
Gy­ne­col­o­gists were re­viewed, and ad­di­tion­al studies were
located by re­view­ing bib­liographies of identified articles.
When re­li­able research was not available, expert opinions
from ob­ste­tri­cian–gynecologists were used.
Studies were reviewed and evaluated for qual­i­ty ac­cord­ing
to the method outlined by the U.S. Pre­ven­tive Services
Task Force:
I	 Evidence obtained from at least one prop­er­ly
de­signed randomized controlled trial.
II-1	 Evidence obtained from well-designed con­trolled
tri­als without randomization.
II-2	 Evidence obtained from well-designed co­hort or
case–control analytic studies, pref­er­a­bly from more
than one center or research group.
II-3	 Evidence obtained from multiple time series with or
with­out the intervention. Dra­mat­ic re­sults in un­con­
trolled ex­per­i­ments also could be regarded as this
type of ev­i­dence.
III	 Opinions of respected authorities, based on clin­i­cal
ex­pe­ri­ence, descriptive stud­ies, or re­ports of ex­pert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and grad­ed ac­cord­ing to the
following categories:
Level A—Recommendations are based on good and con­
sis­tent sci­en­tif­ic evidence.
Level B—Recommendations are based on limited or in­con­
sis­tent scientific evidence.
Level C—Recommendations are based primarily on con­
sen­sus and expert opinion.
Copyright October 2012 by the American College of Ob­ste­
tri­cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a re­triev­al sys­tem,
posted on the Internet, or transmitted, in any form or by any
means, elec­tron­ic, me­chan­i­cal, photocopying, recording, or
oth­er­wise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
The American College of Obstetricians and Gynecologists
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Prediction and prevention of preterm birth. Practice Bulletin No. 130.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2012;120:964–73.

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Prediccion y prevencion del parto pretermino

  • 1. 964 VOL. 120, NO. 4, OCTOBER 2012 OBSTETRICS & GYNECOLOGY P RACT I C E BUL L E T I N Background Spontaneous preterm birth includes birth that follows pre- term labor, preterm spontaneous rupture of membranes, and cervical insufficiency, but does not include indicated preterm delivery for maternal or fetal conditions (5). The preterm birth rate (birth at less than 37 completed weeks of gestation per 100 total births) increased more than 20% from 1990 to 2006. However, decreases in birth rates for both early preterm birth (earlier than 34 weeks of gestation) and late preterm birth (34 0/7–36 6/7 weeks of gestation) contributed to a decrease in the over- all preterm birth rate between 2008 (12.3%) and 2009 (12.18%) (1). The risk of poor birth outcome generally decreases with advancing gestational age. Although risks are greatest for neonates born before 34 weeks of gesta- tion, infants born after 34 weeks of gestation but before 37 weeks of gestation are still more likely to experience delivery complications, long-term impairment, and early death than those born later in pregnancy (6). Infants born prematurely have increased risks of mortality and morbidity throughout childhood, especially during the first year of life. In the absence of more com- prehensive tests of fetal and neonatal status, gestational age is a common surrogate for presumed functional matu- rity. Although age is related to maturity, no easily identi- fied gestational age boundary exists between a premature neonate and a mature neonate. The risks of perinatal, neonatal, and infant morbidity and mortality are lowest for infants born between 39 0/7 weeks of gestation and 40 6/7 weeks of gestation. These risks increase as gesta- tional age at birth decreases, with morbidity reported at 37 weeks of gestation and even 38 weeks of gestation in some series (7, 8). Risk Factors One of the strongest clinical risk factors for preterm birth is a prior preterm birth (9). Maternal history of preterm birth is commonly reported to confer a 1.5-fold to 2-fold increased risk in a subsequent pregnancy. Importantly, the number of prior preterm births and the gestational age at the prior delivery significantly affect the recur- rence risk of preterm birth (10). A preterm birth followed by delivery at term confers lower risk than the opposite Prediction and Prevention of Preterm Birth Preterm birth is the leading cause of neonatal mortality in the United States, and preterm labor precedes approxi- mately 50% of preterm births (1, 2). Neonatal intensive care has improved the survival rate for neonates at the cusp of viability, but it also has increased the proportion of survivors with disabilities (3). The incidence of multiple births also has increased along with the associated risk of preterm delivery (4). The purpose of this document is to describe the various methods proposed for identifying and treating asymptomatic women at increased risk of preterm birth and the evidence for their roles in clinical practice. Number 130, October 2012 (Replaces Practice Bulletin Number 31, October 2001 and Committee Opinion No. 419, October 2008) clinical management guidelines for obstetrician–gynecologists Committee on Practice Bulletins—Obstetrics. This Practice Bulletin was developed by the Committee on Practice Bulletins—Obstetrics with the assis- tance of Jay Iams, MD, Gary Dildy, MD, George Macones, MD, and Neil Silverman, MD. The information is designed to aid practitioners in making deci- sions about appropriate obstetric and gynecologic care. These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice. The American College of Obstetricians and Gynecologists WOMEN’S HEALTH CARE PHYSICIANS
  • 2. VOL. 120, NO. 4, OCTOBER 2012 Practice Bulletin Prediction and Prevention of Preterm Birth 965 sequence (10, 11). For women with a prior preterm twin birth, the risk of preterm birth in a subsequent singleton gestation varies according to the gestational age at twin delivery, with a recurrence risk as high as 40% when a prior twin birth was before 30 weeks of gestation (12, 13). Short cervical length measured by transvaginal ultra- sonography also has been associated with an increased risk of preterm birth (14–16). Short cervical length is most commonly defined as less than 25 mm, usually before 24 weeks of gestation, but up to 28 weeks of gesta- tion in some series. It is a cutoff that has been associated with an increased risk of preterm birth in screened popu- lations (15, 17). Clinically, the shorter the cervical length, the greater the risk of preterm birth. Additional proposed risk factors for preterm birth include aspects of obstetric and gynecologic history, demographic characteristics, current pregnancy complica- tions, and behavioral factors. However, data are inconsis- tent about whether these factors are actually causative for preterm birth. Preconception care allows an opportunity to assess risk factors and provide counseling for women with risk factors that can be modified, such as smoking and optimal control of underlying chronic diseases (18). A history of cervical surgery, including conization and loop electrosurgical excision procedure, tradition- ally has been thought to be a risk factor for preterm birth because of associated cervical injury, but this rela- tionship also may be related to environmental, factors, behavioral factors, or both (such as smoking) that under- lie the progression of cervical dysplasia (19, 20). Uterine instrumentation (eg, dilation and curettage) also has been associated with an increased risk of preterm birth in some, but not all, studies; the mechanism is unclear, but intrauterine microbial colonization, injury to the endo- metrium, or both, together with host and environmental factors, has been suggested (21). Other factors during a current pregnancy that have been associated with an increased risk of preterm birth include vaginal bleeding, urinary tract infections (UTIs), genital tract infections, and periodontal disease. However, treatments for any of these potential risk fac- tors have not been definitively demonstrated to result in a decreased risk of preterm birth. Early studies of the role of UTIs in preterm birth have demonstrated an asso- ciation between untreated asymptomatic bacteriuria in early pregnancy and increased rates of preterm birth (22, 23). However, subsequent meta-analyses have reported conflicting results. One early report showed that untreat- ed asymptomatic bacteriuria significantly increased rates of low birth weight and preterm delivery (24). However, later analyses, including one study of more than 25,000 births, and a Cochrane review, have failed to confirm this finding (25, 26). Therefore, the association reported between treating UTIs in pregnancy and preventing pre- term birth may be related to preventing progression of subclinical infections to pyelonephritis (25, 27). In addi- tion, women with periodontal disease have an increased risk of preterm birth that is not affected by periodontal care. This suggests that the increased risk is caused by associated traits rather than a causal linkage (28–31). In fact, active treatment of periodontitis in pregnancy has been shown in one study to potentially increase the risk of spontaneous preterm birth (30). Behavioral risk factors for preterm birth include low maternal prepregnancy weight, smoking, substance abuse, and short interpregnancy interval. Low maternal body mass index (less than 19.8; calculated as weight in kilograms divided by height in meters squared) has been regularly found to be associated with an increased risk of preterm birth (32, 33). Smoking is associated with an increased risk of preterm birth and, unlike most other risks, is amenable to intervention during pregnancy (34, 35). An epidemiologic review of three U.S. studies showed that the risk of adverse birth outcomes, includ- ing preterm birth, was lowest when the interpregnancy interval was 18–23 months and increased when the inter- val fell outside of this range (36). Screening Modalities Transvaginal cervical ultrasonography has been shown to be a reliable and reproducible way to assess the length of the cervix (37). This is in contrast to transabdominal ultrasound evaluation of the cervix. Unlike the transab- dominal approach, transvaginal cervical ultrasonography is not affected by maternal obesity, position of the cer- vix, and shadowing from the fetal presenting part (38, 39). In addition, unlike digital examination, transvaginal ultrasonography can help identify the presence of other ultrasound risk markers for preterm delivery, such as the presence of intraamniotic debris (a possible sign of intrauterine microbial colonization) and choriodecidual separation (40, 41). When performed by trained operators, cervical length screening by transvaginal ultrasonography is safe, highly reproducible, and more predictive than transab- dominal ultrasound screening. Using a method in which the transvaginal probe is placed in the anterior fornix of the vagina with an empty maternal bladder results in measurements with interobserver variation of 5–10% (37). Measurement of the cervical length in this manner identifies a faint line of echodensity between internal and external os, avoiding undue pressure on the cervix that might increase its apparent length. The cervical length is the shortest of three measurements taken between cali- pers placed at the internal os and external os (15, 42). As an independent finding, cervical funneling does not add
  • 3. 966 Practice Bulletin Prediction and Prevention of Preterm Birth OBSTETRICS & GYNECOLOGY appreciably to the preterm delivery risk associated with a shortened cervical length (43). Other specific tests and monitoring modalities, such as fetal fibronectin screening, bacterial vaginosis testing, and home uterine activity monitoring have been proposed to assess a woman’s risk of preterm delivery. However, available interventional studies based on the use of these tests for screening asymptomatic women have not demonstrated improved perinatal outcomes (44–46). Thus, these methods are not recommended as screening strategies. In addition, interventions, such as pharmacotherapy with indomethacin or antibiotics, activity restriction, or supplementation with omega-3 fatty acids have not been evaluated in the context of randomized trials for women with short cervical length, and are not recommended as clinical interventions for women with an incidentally diagnosed short cervical length. Although maternal dietary fish consumption has been associated with a reduced risk of preterm birth, supplementation with omega-3 fatty acids was not found to reduce the risk of preterm birth in a large randomized trial of women with a prior preterm spontaneous birth who received 17a-hydroxyprogester- one caproate (47, 48). Randomized placebo-controlled trials of women taking vitamin C and vitamin E, supple- mental calcium, and protein also have not been associ- ated with a decreased risk of preterm birth (49–53). Clinical Considerations and Recommendations How should women with a previous sponta- neous preterm birth be evaluated for risk of subsequent preterm birth? The evaluation of women with a prior spontaneous pre- term birth should include obtaining a detailed medical history, reviewing comprehensively aspects of all previ- ous pregnancies, reviewing risk factors, and determining their candidacy for prophylactic interventions, such as progesterone supplementation, cervical cerclage, or both. A comprehensive review of all previous pregnancies is an important step in the evaluation of women at risk of preterm birth because the most important historical risk factor for recurrent preterm birth is a prior spontaneous preterm birth, including births in the mid-to-late second trimester (54). It can be difficult to differentiate sponta- neous preterm birth from indicated preterm birth, but an effort to establish this distinction should be an integral part of history taking. The review of medical records and placental pathology results can be helpful in this process. Spontaneous preterm births are those in which the onset of parturition was spontaneous, regardless of whether the process was later augmented. Rather than determin- ing whether a prior preterm birth was spontaneous, it may be easier first to exclude a prior preterm birth that was obviously indicated (ie, initiated by the obstetric care provider for a medical condition that threatened maternal health, fetal health, or both). How should the current pregnancy be man- aged in a woman with a prior spontaneous preterm delivery? A woman with a singleton gestation and a prior spon- taneous preterm singleton birth should be offered pro- gesterone supplementation starting at 16–24 weeks of gestation to reduce the risk of recurrent spontaneous preterm birth (55–57) (Table 1). Whether such a woman might additionally benefit from cervical cerclage place- ment also has been studied. A multicenter, randomized trial examined the role of serial transvaginal cervical length screening, with cer- clage placement for short cervical length, among women with singleton gestations and prior spontaneous preterm births at less than 34 weeks of gestation, including some women who received 17a-hydroxyprogesterone caproate (58). Women in this trial underwent serial cervical length screening once every 2 weeks, starting at 16 weeks of gestation until 23 weeks of gestation. If the length of the cervix was noted to be between 25 mm and 29 mm, the screening frequency was increased to once a week. If the cervical length was less than 25 mm, women were randomized to undergo cerclage or not to undergo cer- clage. The primary study outcome was preterm birth at less than 35 weeks of gestation, for which no significant difference was detected (relative risk [RR], 0.78; 95% confidence interval [CI], 0.58–1.04) (58). However, placement of a cerclage was associated with significant reductions in deliveries before 24 weeks of gestation (RR, 0.44; 95% CI, 0.21–0.92) and before 37 weeks of gestation (RR, 0.75; 95% CI, 0.60–0.93) as well as in perinatal death (RR, 0.54; 95% CI, 0.29–0.99) when compared with the group that did not undergo cerclage (58). In a planned secondary analysis, cerclage for cer- vical length less than 15 mm was associated with a sig- nificant decrease in preterm birth at less than 35 weeks of gestation (RR, 0.23; 95% CI, 0.08–0.66) (58). Based on the pooled results of five clinical trials, in a singleton pregnancy with prior spontaneous preterm birth at less than 34 weeks of gestation and cervical length less than 25 mm before 24 weeks of gestation, cerclage was asso- ciated with a 30% reduction in the risk of preterm birth at less than 35 weeks of gestation (28% versus 41%; RR, 0.7; 95% CI, 0.55–0.89) and a 36% reduction in compos-
  • 4. VOL. 120, NO. 4, OCTOBER 2012 Practice Bulletin Prediction and Prevention of Preterm Birth 967 ite perinatal mortality and morbidity (16% versus 25%; RR, 0.64; 95% CI, 0.45–0.91) (58–60). Although the single largest trial of cerclage for pre- term birth prevention in high-risk women did not find benefit for the primary study outcome, available evi- dence suggests that, in women with a current singleton pregnancy, prior spontaneous preterm birth at less than 34 weeks of gestation and short cervical length (less than 25 mm) before 24 weeks of gestation, cerclage placement is associated with significant decreases in preterm birth outcomes, offers perinatal benefits, and may be considered in women with this combination of history and ultrasound findings (58, 60). Insufficient evidence exists to assess whether progesterone and cer- clage together have an additive effect in reducing the risk of preterm birth in women at high risk for preterm birth (61). No evidence exists to support the addition of an alter- native form of progesterone to the current progesterone treatment (eg, adding a vaginal form to an intramuscular form), if a short cervix is identified in a woman with a prior preterm birth who is already receiving preventive progesterone therapy. Also, there is no evidence to sug- gest that switching from treatment with intramuscular progesterone to treatment with vaginal progesterone is beneficial if a short cervix is identified. Table 1. Selected Studies on Progesterone Supplementation for the Prevention of Preterm Delivery in Singleton Gestations Study Dosage Population Meis, 2003* 17a-hydroxyprogesterone caproate (250 mg Women with a documented history of a spontaneous singleton preterm weekly injections) birth at less than 37 weeks of gestation; cervical length not measured at entry; treatment initiated between 16 weeks of gestation and 20 weeks of gestation and continued until 36 weeks of gestation or deliv- ery, whichever occurred first da Fonseca, 2003† Vaginal progesterone (100 mg daily) High-risk women with a history of spontaneous singleton preterm birth; treatment initiated at 24 weeks of gestation and continued until 34 weeks of gestation O’Brien, 2007‡ Vaginal progesterone (90 mg daily) Women with a history of spontaneous preterm birth randomized and treated; cervical length measured at entry (mean length, 37 mm); treatment initiated between 18 weeks of gestation and 22 6/7 weeks of gestation and continued until 37 weeks of gestation, occurrence of premature rupture of membranes, or preterm delivery Fonseca, 2007§ Micronized progesterone gel capsules Asymptomatic women with a very short cervical length (15mm or less); (200 mg vaginally daily) 90% of the women had a singleton gestation and 85% had no prior preterm delivery; treatment initiated at 24 weeks of gestation and con- tinued until 34 weeks of gestation Hassan, 2011|| Vaginal progesterone gel (90 mg daily) Women with a singleton gestation with a previous preterm birth between 20 weeks of gestation and 35 weeks of gestation; patients were randomized between 20 weeks of gestation and 23 6/7 weeks of gestation; treatment continued until 36 6/7 weeks of gestation, rupture of membranes, or delivery, whichever occurred first. Hassan, 2011|| Vaginal progesterone gel (90 mg daily) Only women without prior preterm birth; patients were randomized between 20 weeks of gestation and 23 6/7 weeks of gestation; treatment continued until 36 6/7 weeks of gestation, rupture of membranes, or delivery, whichever occurred first. *Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network [published erratum appears in N Engl J Med 2003;349:1299]. N Engl J Med 2003;348:2379–85. † da Fonseca EB, Bittar RE, Carvalho MH, Zagaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol 2003;188:419–24. ‡ O’Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Gynecol 2007;30:687–96. § Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. Fetal Medicine Foundation Second Trimester Screening Group. N Engl J Med 2007;357:462–9. || Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. PREGNANT Trial. Ultrasound Obstet Gynecol 2011;38:18–31.
  • 5. 968 Practice Bulletin Prediction and Prevention of Preterm Birth OBSTETRICS & GYNECOLOGY tive, safe, accepted by patients, and widely available. Opponents of this approach raise the following concerns: quality assurance of the screening test; lack of availabil- ity of screening and of patient access to qualified imaging centers in some areas; and the potential for patients to receive unnecessary or unproven interventions. The American College of Obstetricians and Gyne- cologists recognizes that both sides of this debate raise valid issues. Although this document does not mandate universal cervical length screening in women without a prior preterm birth, this screening strategy may be con- sidered. Practitioners who decide to implement universal cervical length screening should follow one of the pro- tocols for transvaginal measurement of cervical length from the clinical trials on this subject. Protocol citations are listed in Table 1. What interventions have been shown to be beneficial for reducing the risk of preterm birth in women who do not have a history of preterm birth but who are found to have a short cervical length? Cerclage and progesterone are the two interventions that have been evaluated in randomized trials for effective- ness in preventing preterm birth in women with single- ton gestations without a prior preterm birth (Fig. 1). Vaginal progesterone has been studied as a manage- ment option to reduce the risk of preterm birth in asymp- tomatic women with singleton gestations without prior preterm birth with a very short cervical length, defined as less than or equal to 20 mm at up to 24 weeks of gesta- tion. In a randomized placebo-controlled trial, treatment with vaginal micronized progesterone, 200 mg daily, was associated with a 44% decrease in spontaneous pre- term birth at less than 34 weeks of gestation among asymptomatic women with a cervical length of 15 mm or less at 20–25 weeks of gestation (19% versus 34%; RR, 0.56; 95% CI, 0.36–0.86) (62). In this study, 90% of the women had a singleton gestation, and 85% had no prior preterm birth (62). In another recent randomized placebo-controlled trial, treatment with vaginal progesterone gel, 90 mg daily, was associated with a 45% decrease in spontane- ous preterm birth at less than 33 weeks of gestation (9% versus 16%; RR, 0.55; 95% CI, 0.33–0.92) and a 43% decrease in composite neonatal morbidity and mortality (8% versus 14%; RR, 0.57; 95% CI, 0.33–0.99) among asymptomatic women with a cervical length of 10–20.9 mm at 19–23 6/7 weeks of gestation (16). All the women in this study had singleton gestations, with a 16% inci- dence of prior preterm birth. Analysis of only women without prior preterm birth confirmed significant benefit Should a woman with a current singleton pregnancy without a history of preterm birth be screened for a risk of preterm birth? In general, women in this clinical scenario are at a low risk of preterm birth. However, if second trimester transabdominal scanning of the lower uterine segment suggests that the cervix may be short or have some other abnormality, it is recommended that a subsequent trans- vaginal ultrasound examination be performed to better visualize the cervix and establish its length (15). Until recently, routine cervical length evaluation in women at a low risk of preterm delivery was not advocated because, like other factors associated with a potentially higher preterm birth risk, no effective treatments were available to reduce that risk. Recent randomized tri- als that investigated the use of vaginal progesterone in women with a short cervix diagnosed through screening have initiated consideration of whether the current stan- dard for evaluating the cervix should be changed. A European trial that enrolled women with a very short cervical length (15 mm or less) demonstrated a lower risk of preterm birth in those treated with vaginal progesterone suppository, 200 mg daily, compared with those who were treated with a placebo (62). In this study, only 1.7% of the 24,640 women screened at 20–25 weeks of gestation (median, 22 weeks of gestation) were found to have a cervical length less than or equal to 15 mm and, therefore, to be eligible for the trial. In a subsequent randomized trial, the use of vagi- nal progesterone gel, 90 mg daily, was associated with a decrease in spontaneous preterm birth at less than 33 weeks of gestation (9% versus 16%; RR, 0.55; 95% CI, 0.33–0.92) and a decrease in composite neonatal mor- bidity and mortality (8% versus 14%; RR, 0.57; 95% CI, 0.33–0.99) among asymptomatic women with a cervical length of 10–20 mm at 19–23 6/7 weeks of gestation (16). All the women in this study had singleton gestations, with a 16% incidence of prior preterm birth. Analysis of only women without prior preterm birth confirmed significant benefit of progesterone in preventing preterm birth before 33 weeks of gestation in this study (16). Even taking into account the large number of women needed to be screened to identify those at risk, recent decision and economic analyses concluded that universal ultrasound screening for short cervical length and treatment with vaginal progesterone was cost-effective (63, 64). Proponents of universal cervical length screening of women without a prior preterm birth cite the following points in support of this practice: it has the potential to reduce the preterm birth rate; high quality evidence exists to support efficacy of treatment for positive test results (ie, cervical length of 20 mm or less); and it is cost effec-
  • 6. VOL. 120, NO. 4, OCTOBER 2012 Practice Bulletin Prediction and Prevention of Preterm Birth 969 of treatment with progesterone in preventing preterm birth before 33 weeks of gestation in this study (16). Therefore, vaginal progesterone is recommended as a management option to reduce the risk of preterm birth in asymptomatic women with a singleton gestation without a prior preterm birth with an incidentally identified very short cervical length less than or equal to 20 mm before or at 24 weeks of gestation. In contrast, for women in this otherwise low-risk population, cerclage placement in women with a cervi- cal length less than 25 mm detected between 16 weeks of gestation and 24 weeks of gestation has not been associated with a significant reduction in preterm birth at less than 35 weeks of gestation [RR, 0.76; 95% CI, 0.52–1.15] (59). Even cerclage placement for detection of a cervical length of 15 mm or less in women at 22–24 weeks of gestation has not been shown to significantly decrease the rate of preterm birth (at less than 33 weeks of gestation) (RR, 0.84; 95% CI, 0.54–1.31) (65). In one trial of women with an incidentally diag- nosed short cervix (less than or equal to 25 mm at 18–22 weeks of gestation), open-label randomization to place- ment of a cervical pessary or expectant management (no pessary) was studied (66). In this trial of 385 women, the rate of spontaneous delivery at less than 34 weeks of gestation was significantly lower in the pessary group than in the no pessary group (6% compared with 27%; OR, 0.18; 95% CI, 0.08–0.37). If the results of this small trial are validated, cervical pessary placement may have additional benefit for prevention of preterm birth in oth- erwise low-risk women with a short cervix. Does cerclage placement or progesterone treatment decrease the risk of preterm birth in women with multiple gestations? Available data regarding the efficacy of cerclage place- ment, progesterone supplementation, or both for the reduction of preterm birth risk in women with multiple gestations with a short cervical length with or without a prior preterm birth do not support their use (67). Cerclage may increase the risk of preterm birth in women with a twin pregnancy and ultrasonographically detected cervi- cal length less than 25 mm and is not recommended. In a meta-analysis of randomized trials, cerclage performed in women with a twin pregnancy and a cervical length less than 25 mm was actually associated with a significant twofold increase in the rate of preterm birth (RR, 2.2; 95% CI, 1.2-4) (59). Progesterone treatment does not reduce the incidence of preterm birth in women with twin or triplet gestations and, therefore, is not recommended as an intervention to prevent preterm birth in women with multiple gestations (68–72). Currently, no data are avail- able regarding the efficacy of any other interventions to reduce the risk of preterm birth in women with multiple gestations and a short cervix, and the use of any such alternative measures cannot be recommended outside of formal clinical trials. Fig. 1. Algorithm for the management of short cervical length in the second trimester. Short cervix identified with transvaginal ultrasonography Singleton gestation Multiple gestation No intervention has been shown to improve outcomes No prior spontaneous preterm birth Prior spontaneous preterm birth and receiving progesterone supplementation since 16 weeks of gestation Cerclage should be considered if cervical length is less than 25 mm before 24 weeks of gestation and prior preterm birth occurred at less than 34 weeks of gestation Vaginal progesterone supplementation should be offered if cervical length is 20 mm or less before or at 24 weeks of gestation
  • 7. 970 Practice Bulletin Prediction and Prevention of Preterm Birth OBSTETRICS & GYNECOLOGY Summary of Recommendations and Conclusions Recommendations based on good and consistent scientific evidence (Level A): A woman with a singleton gestation and a prior spontaneous preterm singleton birth should be offered progesterone supplementation starting at 16–24 weeks of gestation, regardless of transvagi- nal ultrasound cervical length, to reduce the risk of recurrent spontaneous preterm birth. Vaginal progesterone is recommended as a manage- ment option to reduce the risk of preterm birth in asymptomatic women with a singleton gestation without a prior preterm birth with an incidentally identified very short cervical length less than or equal to 20 mm before or at 24 weeks of gestation. Tests, such as fetal fibronectin screening, bacterial vaginosis testing, and home uterine activity moni- toring, are not recommended as screening strategies. Progesterone treatment does not reduce the inci- dence of preterm birth in women with twin or triplet gestations and, therefore, is not recommended as an intervention to prevent preterm birth in women with multiple gestations. Recommendations based on limited or inconsis- tent scientific evidence (Level B): Although this document does not mandate universal cervical length screening in women without a prior preterm birth, this screening strategy may be consid- ered. Insufficient evidence exists to assess if progesterone and cerclage together have an additive effect in reducing the risk of preterm birth in women at high risk for preterm birth. Cerclage may increase the risk of preterm birth in women with a twin pregnancy and an ultrasono- graphically detected cervical length less than 25 mm and is not recommended. Recommendations based primarily on consensus and expert opinion (Level C): Practitioners who decide to implement universal cervical length screening should follow one of the protocols for transvaginal measurement of cervical length from he clinical trials on this subject. Protocol citations are listed in Table 1. Proposed Performance Measure Percentage of women with a prior spontaneous preterm birth who are offered progesterone supplementation References 1. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Mathews TJ, Osterman MJ. Births: final data for 2008. Natl Vital Stat Rep 2010;59:1–72. (Level II-3) 2. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008; 371:75–84. (Level III) 3. Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR. Neurologic and developmental disability after extremely preterm birth. EPICure Study Group. N Engl J Med 2000; 343:378–84. (Level II-2) 4. Preterm singleton births--United States, 1989-1996. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep 1999;48:185–9. (Level II-3) 5. Simhan NH, Iams JD, Romero R. Preterm birth. In: Gabbe SG, Niebyl JR, Simpson JL, Landon MB, Galan HL, Jauniaux ER, et al, editors. Obstetrics: normal and problem pregnancies. 6th ed. Philadelphia (PA): Elsevier Saunders; 2012. p. 628–56. (Level III) 6. Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Kirmeyer S, Mathews TJ, et al. Births: final data for 2009. Natl Vital Stat Rep 2011;60:1–71. (Level II-3) 7. Clark SL, Miller DD, Belfort MA, Dildy GA, Frye DK, Meyers JA. Neonatal and maternal outcomes associated withelectivetermdelivery.AmJObstetGynecol2009;200: 156.e1–4. (Level II-3) 8. Fleischman AR, Oinuma M, Clark SL. Rethinking the def- inition of “term pregnancy.” Obstet Gynecol 2010;116: 136–9. (Level III) 9. Spong CY. Prediction and prevention of recurrent spon- taneous preterm birth. Obstet Gynecol 2007;110:405–15. (Level III) 10. McManemy J, Cooke E, Amon E, Leet T. Recurrence risk for preterm delivery. Am J Obstet Gynecol 2007;196:576. e1–6; discussion 576.e6–7. (Level II-3) 11. Bakketeig LS, Hoffman HJ. Epidemiology of preterm birth: results from a longitudinal study of births in Norway. In: Elder MG, Hendricks CH, editors. Preterm labor. Boston (MA): Butterworths; 1981. p. 17–46. (Level III) 12. Menard MK, Newman RB, Keenan A, Ebeling M. Prog- nostic significance of prior preterm twin delivery on sub- sequent singleton pregnancy. Am J Obstet Gynecol 1996; 174:1429–32. (Level II-3)
  • 8. VOL. 120, NO. 4, OCTOBER 2012 Practice Bulletin Prediction and Prevention of Preterm Birth 971 26. Meis PJ, Goldenberg RL, Mercer B, Moawad A, Das A, McNellis D, et al. The preterm prediction study: sig- nificance of vaginal infections. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1995;173:1231–5. (Level II-2) 27. Schnarr J, Smaill F. Asymptomatic bacteriuria and symp- tomatic urinary tract infections in pregnancy. Eur J Clin Invest 2008;38(suppl 2):50–7. (Level III) 28. Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE, et al. Treatment of periodontal disease and the risk of preterm birth. OPT Study. N Engl J Med 2006;355:1885–94. (Level I) 29. Offenbacher S, Beck JD, Jared HL, Mauriello SM, Mendoza LC, Couper DJ, et al. Effects of periodontal ther- apy on rate of preterm delivery: a randomized controlled trial. Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators. Obstet Gynecol 2009;114:551–9. (Level I) 30. Macones GA, Parry S, Nelson DB, Strauss JF, Ludmir J, Cohen AW, et al. Treatment of localized periodontal dis- ease in pregnancy does not reduce the occurrence of preterm birth: results from the Periodontal Infections and Prematurity Study (PIPS). Am J Obstet Gynecol 2010; 202:147.e1–8. (Level I) 31. Newnham JP, Newnham IA, Ball CM, Wright M, Pennell CE, Swain J, et al. Treatment of periodontal disease during pregnancy: a randomized controlled trial. Obstet Gynecol 2009;114:1239–48. (Level I) 32. Hickey CA, Cliver SP, McNeal SF, Goldenberg RL. Low pregravid body mass index as a risk factor for pre- term birth: variation by ethnic group. Obstet Gynecol 1997;89:206–12. (Level II-3) 33. Zhong Y, Cahill AG, Macones GA, Zhu F, Odibo AO. The association between prepregnancy maternal body mass index and preterm delivery. Am J Perinatol 2010; 27:293–8. (Level II-3) 34. Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L. 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(Level I) The MEDLINE database, the Cochrane Library, and the American College of Obstetricians and Gynecologists’ own internal resources and documents were used to con­ duct a lit­er­a­ture search to lo­cate rel­e­vant ar­ti­cles pub­lished be­tween January 1990 and March 2012. The search was re­strict­ed to ar­ti­cles pub­lished in the English lan­guage. Pri­or­i­ty was given to articles re­port­ing results of orig­i­nal re­search, although re­view ar­ti­cles and com­men­tar­ies also were consulted. Ab­stracts of re­search pre­sent­ed at sym­po­ sia and sci­en­tif­ic con­fer­enc­es were not con­sid­ered adequate for in­clu­sion in this doc­u­ment. Guide­lines pub­lished by or­ga­ni­za­tions or in­sti­tu­tions such as the Na­tion­al In­sti­tutes of Health and the Amer­i­can Col­lege of Ob­ste­tri­cians and Gy­ne­col­o­gists were re­viewed, and ad­di­tion­al studies were located by re­view­ing bib­liographies of identified articles. When re­li­able research was not available, expert opinions from ob­ste­tri­cian–gynecologists were used. Studies were reviewed and evaluated for qual­i­ty ac­cord­ing to the method outlined by the U.S. Pre­ven­tive Services Task Force: I Evidence obtained from at least one prop­er­ly de­signed randomized controlled trial. II-1 Evidence obtained from well-designed con­trolled tri­als without randomization. II-2 Evidence obtained from well-designed co­hort or case–control analytic studies, pref­er­a­bly from more than one center or research group. II-3 Evidence obtained from multiple time series with or with­out the intervention. Dra­mat­ic re­sults in un­con­ trolled ex­per­i­ments also could be regarded as this type of ev­i­dence. III Opinions of respected authorities, based on clin­i­cal ex­pe­ri­ence, descriptive stud­ies, or re­ports of ex­pert committees. Based on the highest level of evidence found in the data, recommendations are provided and grad­ed ac­cord­ing to the following categories: Level A—Recommendations are based on good and con­ sis­tent sci­en­tif­ic evidence. Level B—Recommendations are based on limited or in­con­ sis­tent scientific evidence. Level C—Recommendations are based primarily on con­ sen­sus and expert opinion. Copyright October 2012 by the American College of Ob­ste­ tri­cians and Gynecologists. All rights reserved. No part of this publication may be reproduced, stored in a re­triev­al sys­tem, posted on the Internet, or transmitted, in any form or by any means, elec­tron­ic, me­chan­i­cal, photocopying, recording, or oth­er­wise, without prior written permission from the publisher. Requests for authorization to make photocopies should be directed to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400. The American College of Obstetricians and Gynecologists 409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920 Prediction and prevention of preterm birth. Practice Bulletin No. 130. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012;120:964–73.