Clinical Prediction Rules for Preterm Birth in

Patients Presenting With Preterm Labor

Jamie A. Bastek, MD, MSCE, Mary D. Sammel,
Meghan A. McShea, BS, Markley N. Foreman,
and Joshua P. Metlay, MD, PhD

ScD,
BA,

OBJECTIVE: To develop prediction rules to identify

which women with preterm labor are at greatest risk for
delivery within 10 days and before 37 weeks of gestation
using demographic and clinical risk factors alone.
METHODS: We analyzed data collected for a prospective cohort study of singleton pregnancies at 2233 6/7
weeks of gestation with preterm labor. Potential risk
factors were included in multivariable logistic models for
each outcome. Using backwards regression, we identified
combinations of risk factors that generated the most
parsimonious yet predictive models. Adjusted odds ratios
of covariates in the final models were used to estimate
weights for each risk factor and were summed to generate a predictive score. The score associated with the
highest negative predictive value was defined as a positive test result for each outcome. Bootstrapping techniques internally validated the scoring systems.
RESULTS: We include data from 583 women. The risk of
delivery within 10 days was 15.4% (n90) and before 37
weeks of gestation it was 35.0% (n204). The final model
for delivery within10 days included initial cervical dilataFrom the Maternal and Child Health Research Program, Department of
Obstetrics & Gynecology, Center for Research on Reproduction and Womens
Health, the Department of Biostatistics and Epidemiology, and the Department
of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Financial support was provided by a March of Dimes grant (21-FY08-539,
Primary Investigator: Dr. Elovitz). Dr. Bastek was supported by
5T32HD7440-15 (Primary Investigator: Dr. Strom). Dr. Metlay was supported by K24 AI073957.
Presented at the Womens Reproductive Health Research symposium, September
9 10, 2011, Providence, Rhode Island, and at the Society for Maternal-Fetal
Medicine Annual Meeting, February 6 11, 2012, Dallas, Texas (abstract 482).
Corresponding author: Jamie A. Bastek, MD, MSCE, Division of MaternalFetal Medicine, Department of Obstetrics and Gynecology, Hospital of the
University of Pennsylvania, 3400 Spruce Street, 2000 Courtyard Building,
Philadelphia, PA 19104; e-mail: jbastek@obgyn.upenn.edu.
Financial Disclosure
The authors did not report any potential conflicts of interest.
2012 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/12

VOL. 119, NO. 6, JUNE 2012

Sindhu K. Srinivas, MD,

Michal A. Elovitz, MD,

MSCE,

tion, no prenatal care, and tobacco use (area under

curve0.75), and for delivery before 37 weeks of gestation it included initial cervical dilatation, obstetric history,
and tobacco use (area under the curve0.73). A positive
test result was associated with 84% sensitivity, 51%
specificity, 24% positive predictive value, and 95% negative predictive value in predicting delivery within 10
days and 79% sensitivity, 50% specificity, 46% positive
predictive value, and 82% negative predictive value in
predicting delivery before 37 weeks of gestation.
CONCLUSION: Based on their strong negative predictive values, these prediction rules could identify patients
who do not require intensive monitoring when they
present with preterm labor.
(Obstet Gynecol 2012;119:111928)
DOI: 10.1097/AOG.0b013e31825503e5

LEVEL OF EVIDENCE: II

reterm birth is defined as delivery before 37 weeks

of gestation. Although it was a goal of Healthy
People 20101 to decrease the preterm birth risk to
approximately 7%, the national incidence of preterm
birth remains greater than 12%.2 This is attributable to
both our inability to accurately predict who will
deliver preterm and our lack of universal efficacious
regimens to treat preterm labor and prevent preterm
birth.
Prematurity contributes to approximately 80% of
perinatal mortality in the United States.3 Therefore,
despite our inability to significantly decrease the rate
of preterm birth, the ability to identify patients at
greatest risk for imminent preterm birth nevertheless
is valuable to provide medical management that may
decrease the adversity associated with prematurity.
Specifically, in addition to transfer to a tertiary care
center, in patient observation, cerebral palsy prophylaxis,4 and tocolysis,5 the American College of Obstetricians and Gynecologists recommends the administration of corticosteroids to all women between 24

OBSTETRICS & GYNECOLOGY

1119

and 33 6/7 weeks of gestation at risk for delivering

within 7 days in an effort to reduce the risks of
respiratory distress syndrome, perinatal mortality,
and other morbidities.6 9
Preterm labor, defined as cervical change in the
setting of uterine contractions, is a risk factor for
imminent preterm birth. However, only 20 30% of
women with preterm labor deliver preterm.10 Although fetal fibronectin11 and transvaginal cervical
length measurements12 are oftentimes used in an
effort to risk-stratify patients symptomatic for preterm
labor, such tools are expensive and require training
and technology to use. Furthermore, they only can be
used under certain clinical circumstances. Specifically, fetal fibronectin cannot be performed when the
cervix is dilated 3 cm or more, when membranes
have ruptured, or after a digital cervical examination
has been performed.1315 Cervical length measurement is not predictive of preterm birth risk when the
cervix is dilated 2 cm or more, is inaccurate if not
performed very precisely, and is generally most useful
for predicting future rather than imminent preterm
birth.12
A validated clinical predication rule that identifies which women symptomatic for preterm labor are
at greatest risk for relatively imminent preterm birth
through use of demographic and clinical risk factors
alone could be of high clinical utility to allow for the
most judicious use of resources while being straightforward and inexpensive to perform. Based on a
PubMed search in February 2012 of articles published
in the English language using MeSH predict, preterm birth, and preterm labor, to our knowledge,
such a prediction rule in patients symptomatic for
preterm labor has not been published.
Therefore, the primary objective of this study was
to develop a prediction rule for delivery within 10
days of preterm labor using only readily obtainable
demographic and clinical risk factorsincluding gestational age at presentation with preterm labor, obstetric history, prenatal care status, initial cervical
dilatation, maternal age, obesity, race, and tobacco
use but not fetal fibronectin, transvaginal cervical
length assessment, or serum biomarkers.
Although our primary aim was delivery within 10
days, there is also clinical value to identifying which
women, presenting with preterm labor, will deliver
before 37 weeks of gestation in an effort to ensure that
these patients are more closely monitored and potentially offered corticosteroids to mitigate the risk of
prematurity. Therefore, the secondary objective of
this study was to develop a prediction rule for preterm

1120

Bastek et al

birth before 37 weeks of gestation in a cohort of

women symptomatic for preterm labor.

MATERIALS AND METHODS

We performed analyses of data that were collected for
a prospective cohort study at a single urban tertiary
care center. The cohort consisted of a sample of
women with singleton pregnancies between 22 and 33
6/7 weeks of gestation who presented to the labor and
delivery triage unit with symptoms concerning for
preterm labor, including contractions, cramping,
asymptomatic vaginal bleeding, vaginal pressure, and
abdominal or back pain.
To have preterm labor diagnosed at our institution, a patient must make documented cervical
change on sterile cervical examination in the presence
of regular uterine contractions. Patients with preterm
labor diagnosed between 24 0/7 and 33 6/7 weeks of
gestation are admitted to the hospital and receive 48
hours of magnesium sulfate tocolysis for the administration of a single course (two doses) of betamethasone. Patients with ruptured membranes at less than
34 weeks of gestation before the onset of labor are
managed conservatively with administration of a single course of betamethasone and 7 days of latency
antibiotics. Patients with preterm premature rupture
of membranes are delivered in the setting of chorioamnionitis, spontaneous labor, or achieving 34 weeks
of gestation or more. Patients who present with symptoms concerning for preterm labor or preterm premature rupture of membranes who do not meet diagnostic criteria are discharged home with instructions to
continue routine prenatal care and to return for
further evaluation as needed. Enrollment to the parent study did not influence patient care in any way. Of
note, we do not use fetal fibronectin or cervical length
measurement in the diagnosis or management of the
preterm labor patient.
A patient did not have to be admitted to the
hospital with a diagnosis of preterm labor or preterm
premature rupture of membranes to be a candidate
for enrollment. For the current study, we included all
eligible women from the parent study. Patients were
excluded from the parent study and thus from these
analyses for multiple gestation, major fetal anomaly,
intrauterine fetal demise, severe preeclampsia before
enrollment, chronic steroid or immunosuppressive
drug use, active immunologic disease, acute systemic
febrile illness, or pregestational diabetes. Patients with
unknown delivery information were also excluded
from these analyses.
Patients were enrolled in the study by trained
clinical research coordinators who obtained informed

Clinical Prediction Rules for Preterm Birth

OBSTETRICS & GYNECOLOGY

consent at the time of enrollment. The clinical research coordinators enrolled consecutive patients during daytime hours Sunday through Friday and during
evening hours Monday through Thursday. Once a
patient was enrolled in the study, all management
decisions were made by the treating physician according to the standard of care at our institution. Women
were enrolled from April 2008 through December
2010.
After enrollment, each patient was tracked for the
remainder of her pregnancy and relevant delivery
information was obtained through chart review. Previously published studies have suggested that demographic risk factors such as maternal age,16,17 low body
mass index,16,17 and obstetric history,18 as well as
modifiable traits such as no prenatal care16,17 and
tobacco use during pregnancy,19 might predispose to
preterm birth. Therefore, this information and pertinent medical, surgical, and gynecologic histories were
recorded. Initial cervical dilatation was also obtained
(0 to less than 2 cm, 2 to less than 3 cm, 3 to less than
4 cm, 4 cm or more).
The primary outcome of these analyses was delivery within 10 days of presentation to the hospital
with symptoms concerning for preterm labor. The
secondary outcome of interest was preterm birth
before 37 weeks of gestation.
Pearson 2 analyses were used to determine associations between categorical risk factors and both the
primary and secondary outcomes. Univariable logistic regression was performed to compute odds ratios
along with 95% confidence intervals (CIs) to estimate
the associations between the primary and secondary
outcomes and each demographic and clinical risk
factor.20
Variables identified as potential risk factors in
unadjusted analyses (P.2) were used to create separate multivariable logistic models for the primary and
secondary outcomes.21 After starting with the most
comprehensive model that included all potential risk
factors, a backwards selection method was performed
to determine which combination of risk factors generated the most parsimonious yet predictive model
for each outcome.22 With the successive elimination
of each variable from the model, the area under the
curve (AUC) was compared with the AUC of the
previous model containing the variable using a statistical receiver-operator curve area comparison test. If
the P value describing the comparison of consecutive
AUCs was not significant, then we concluded that
removing the variable did not significantly reduce the
predictive capability of the model.22 The AUC of each
final multivariable model was then compared with the

VOL. 119, NO. 6, JUNE 2012

AUC generated by the univariable model that generated the strongest AUC using the same statistical
receiver-operator curve area comparison test to ensure that the P value describing the comparison of
these two AUCs was significant. In that case, we
concluded that the multivariable model significantly
improved the ability to predict each adverse obstetric
outcome.
The odds ratios of each covariate in the final
multivariable model were rounded to the nearest
whole number. These rounded values were the estimated weights for each covariate that could be
summed to generate a final score that might predict
the probability of each outcome. A prediction score
was calculated for each patient in the data set and
used to determine the sensitivity, specificity, positive
predictive value, and negative predictive value for a
range of score cut points.23
For both delivery within 10 days and preterm
birth at less than 37 weeks of gestation, the AUC of
the score was compared with the AUC of the final
multivariable logistic model using a statistical receiveroperator curve area comparison test to ensure that the
P value describing the comparison of these AUCs was
not significant. In that case, we concluded that there
was no statistically significant difference between the
predictive ability of the score and the final multivariable model. The score that generated the highest
negative predictive value was defined as a positive test
result for each outcome.
Finally, bootstrapping techniques with 1,000 replications were performed to internally validate the
scoring system to estimate 95% CIs for the performance characteristics.24 STATA 10.1 was used for
data analysis. In all analyses, P.05 was considered
statistically significant.
A priori sample size calculations were computed
to allow for a specified CI around the sensitivity of
prediction.25 For the calculation, we assumed our
prediction rule would have at least 65% sensitivity for
the primary outcome. A 95% CI with a precision of
10% would require for us to observe 88 deliveries
occurring within 10 days of presentation. Based on
nonpublished data from our institution, we assumed
that the prevalence of delivery within 10 days of
presentation with preterm labor was approximately
15%. Given that the parent study recruited only
women who planned to deliver at our institution, we
assumed that a 5% loss to follow-up would be reasonable. Therefore, assuming a 15% prevalence of delivery within 10 days of presentation, a two-sided type I
error of 0.05, and allowing for 5% of patients to be lost
to follow-up, we estimated that we would need to

Bastek et al

Clinical Prediction Rules for Preterm Birth

1121

enroll approximately 614 patients to obtain data from

583 women for analysis. This study was approved by
the Institutional Review Board at the University of
Pennsylvania.

RESULTS
The actual loss to follow-up during the study period
was slightly higher than we anticipated (8.0%, not
5.0%). Therefore, we enrolled a total of 634 women
into the cohort to achieve our desired final cohort size
of 583 women. Consistent with a high-risk cohort, the
prevalence of delivery within 10 days of initial presentation with symptoms of preterm labor was 15.4%
(95% CI 12.6 18.6; n90). The prevalence of preterm birth at less than 37 weeks of gestation was
35.0% (95% CI 31.139.0; n204).
The associations between demographic variables
and both the primary and secondary outcomes were
studied to identify potential predictors. No prenatal
care, initial cervical dilatation, and tobacco use during
pregnancy were identified as potential predictors of
delivery within 10 days (Table 1). No prenatal care,
initial cervical dilatation, tobacco use, obstetric history, and African American race were identified as
potential predictors of delivery at less than 37 weeks
of gestation (Table 1). There was no significant difference between gestational age at presentation with
preterm labor and either outcome (delivery within 10

days: P.98; preterm birth at less than 37 weeks of

gestation: P.24).
The associations between the primary or secondary outcomes and each individual demographic risk
factor are summarized in Table 2. The ability of each
individual risk factor to predict the primary or secondary outcomes was quite poor, generating AUCs
between 0.47 and 0.57. Only initial cervical dilatation
was associated with a somewhat strong discriminatory
ability to predict each outcome (delivery within 10
days: AUC0.71; preterm birth at less than 37 weeks
of gestation: AUC0.70). The test characteristics of
initial cervical dilatation to predict each outcome are
depicted in Table 3.
The initial model to predict delivery within 10
days included all potential risk factors identified
through unadjusted analyses (initial cervical dilatation, no prenatal care, and tobacco use). Performing
comparative AUC analyses after serial backwards
elimination confirmed that removing any risk factor
significantly reduced the predictive capability of the
model. Therefore, the initial and final models for the
primary outcome were the same. This multivariable
model was significantly more predictive of delivery
within 10 days than initial cervical dilatation alone,
with the univariable model having the greatest individual predictive ability (AUC0.75 compared with
0.71, P.009; Fig. 1).

Table 1. Demographic Information

Delivery
Delivery
Within 10 d After 10 d
n (%)
n (%)

Demographic
Obstetric variables
Obstetric history
Primiparous
Previous preterm birth only
Previous preterm birth and
full-term birth
Previous full-term birth only
No prenatal care
Initial cervical dilatation (cm)
0 to less than 2
2 to less than 3
3 to less than
4 or more
Maternal variables
Extremes of maternal age (younger
than 17, 35 or older)
Low BMI (less than 18.5 kg/m2)
African American
Tobacco use

P*

Delivery Before
Delivery at
37 wk of Gestation 37 wk of Gestation
n (%)
or After n (%)

.72
35 (38.9)
13 (14.4)
13 (14.4)

180 (36.5)
59 (12.0)
65 (13.2)

29 (32.2)
15 (16.7)

180 (38.3)
13 (2.6)

25 (27.8)
24 (26.7)
13 (14.4)
28 (31.1)

285 (57.8)
142 (28.8)
40 (8.1)
26 (5.3)

12 (13.3)

60 (12.2)

5 (5.56)
80 (88.9)
25 (27.8)

15 (3.04)
414 (84.0)
67 (13.6)

P*
.005

66 (32.4)
38 (18.6)
30 (14.7)

149 (39.3)
34 (9.0)
48 (12.7)

70 (34.3)
19 (9.3)

148 (39.1)
9 (2.4)

67 (32.8)
64 (31.4)
29 (14.2)
44 (21.6)

243 (64.1)
102 (26.9)
24 (6.3)
10 (2.6)

.76

25 (12.3)

47 (12.4)

.96

.23
.23
.001

9 (4.41)
182 (89.2)
47 (23.0)

11 (2.90)
312 (82.3)
45 (11.9)

.34
.03
.001

.001
.001

.001
.001

BMI, body mass index.

Data are n (%) unless otherwise specified.
* Determined by 2 tests.

1122

Bastek et al

Clinical Prediction Rules for Preterm Birth

OBSTETRICS & GYNECOLOGY

Table 2. Unadjusted Odds Ratios of Risk Factors for Each Adverse Obstetric Outcome
Delivery Before 37 wk
of Gestation

Delivery Within 10 d
Risk Factor
Obstetric variables
Obstetric history
Primiparous
Previous preterm birth only
Previous preterm birth and full-term birth
Previous full-term birth only
No prenatal care
Initial cervical dilatation (cm)
0 to less than 2
2 to less than 3
3 to less than 4
4 or more
Maternal variables
Extremes of maternal age (younger
than 17, 35 or older)
Low BMI (less than 18.5 kg/m2)
African American
Tobacco use

OR

95% CI

AUC

1.00
1.13
1.03
0.79
7.38

Reference
0.562.28
0.512.06
0.461.34
3.3816.13

1.00
1.93
3.71
12.28

Reference
1.063.49
1.757.82
6.2724.05

1.11

0.572.16

1.87
1.53
2.45

0.665.29
0.763.07
1.444.15

OR

95% CI

AUC

1.00
2.52
1.41
1.07
4.22

Reference
1.464.36
0.822.42
0.711.60
1.879.51

1.00
2.28
4.38
15.96

Reference
1.513.44
2.398.02
7.6333.38

0.51

0.99

0.591.66

0.50

0.51
0.52
0.57

1.54
1.78
2.22

0.633.79
1.062.97
1.423.49

0.51
0.53
0.56

0.47

0.57
0.71

0.50

0.53
0.70

OR, odds ratio; CI, confidence interval; AUC, area under curve; BMI, body mass index.

The adjusted odds ratios of each risk factor in the

final multivariable model for delivery within 10 days
along with the weighted estimate assigned to each risk
factor are found in Table 4. The total score to predict
delivery within 10 days can be expressed as: 4(no
prenatal care)0(initial cervical dilatation: 0 to
less than 2 cm)2(initial cervical dilatation: 2 to less
than 3 cm)4(initial cervical dilatation: 3 to less
than 4 cm)10(initial cervical dilatation: 4 cm or
more)2(tobacco). The mean total score was
2.363.38 points (median 2.0, range 0 16). There was
no significant difference in the predictive ability of the
score compared with the predictive ability of the final

multivariable model (AUC0.76 compared with 0.75,

P.64).
The initial model to predict preterm birth at less
than 37 weeks of gestation included all potential risk
factors identified through unadjusted analyses (initial
cervical dilatation, no prenatal care, tobacco use,
obstetric history, and African American race). Performing serial AUC analyses after each step in backwards elimination confirmed that removing nonsignificant risk factors variables did not significantly
reduce the predictive capability of the model. The
final model for the secondary outcome included
initial cervical dilatation, obstetric history, and to-

Table 3. Test Characteristics of Initial Cervical Dilatation in Predicting Each Adverse Obstetric Outcome
Initial Cervical
Dilatation (cm)
Outcome: delivery
within 10 d
1 or more
2 or more
3 or more
4 or more
Outcome: preterm birth
before 37 wk
1 or more
2 or more
3 or more
4 or more

Sensitivity

Specificity

Positive
Predictive
Value

1.00
0.72
0.46
0.31

0.00
0.58
0.87
0.95

0.15
0.24
0.39
0.53

0.92
0.90
0.88

0.15
0.60
0.80
0.85

1.00
1.71
3.40
5.90

0.48
0.63
0.73

1.00
0.67
0.36
0.22

0.00
0.64
0.91
0.97

0.35
0.50
0.68
0.80

0.78
0.73
0.70

0.35
0.65
0.72
0.71

1.0
1.87
3.99
8.17

0.51
0.71
0.81

Bastek et al

Clinical Prediction Rules for Preterm Birth

VOL. 119, NO. 6, JUNE 2012

Negative
Predictive
Value

Correctly
Classified

Positive
Likelihood
Ratio

Negative
Likelihood
Ratio

1123

Table 4. Adjusted Odds Ratios and Weights of

Risk Factors in Final Multivariable
Models for Each Adverse Obstetric
Outcome

1.00

Sensitivity

0.75

Risk Factor

0.50

0.25

0.00
0.00

0.25

0.50

0.75

1.00

1-Specificity

Fig. 1. Models to predict delivery within 10 days of

preterm labor. P.009. Curve with triangles, multivariable model (area under the curve [AUC]0.754); curve
with circles, univariable model (AUC0.7067); dotted
line, reference line (AUC0.50). Multivariable model
includes no prenatal care, initial cervical dilatation, and
tobacco use. Univariable model includes only initial
cervical dilatation.
Bastek. Clinical Prediction Rules for Preterm Birth. Obstet
Gynecol 2012.

bacco use. This multivariable model was significantly

more predictive of preterm birth at less than 37 weeks
of gestation than initial cervical dilatation alone, with
the univariable model having the greatest individual
predictive ability (AUC0.73 compared with 0.70,
P.006; Figure 2).
The adjusted odds ratios of each risk factor in the
final multivariable model for preterm birth at less
than 37 weeks of gestation along with the weighted
estimate assigned to each risk factor are found in
Table 4. The total score to predict preterm birth at
less than 37 weeks of gestation can be expressed as:
0(initial cervical dilatation: 0 to less than 2
cm)2(initial cervical dilatation: 2 to less than
3 cm)4(initial cervical dilatation: 3 to less than 4
cm)15(initial cervical dilatation: 4 cm or more)
0(primiparous)2(previous preterm birth only)
1(previous preterm birth and previous full-term
birth)1(previous full-term birth only)2(tobacco).
The mean total score was 3.394.50 points (median 2.0,
range 0 19). There was no significant difference in the
predictive ability of the score compared with the predictive ability of the final multivariable model (AUC0.72
compared with 0.73, P.27).

1124

Bastek et al

Outcome: delivery
within 10 d
No prenatal care
Initial cervical
dilatation (cm)
0 to less than 2
2 to less than 3
3 to less than 4
4 or more
Tobacco use
Outcome: preterm birth
before 37 wk
Initial cervical
dilatation (cm)
0 to less than 2
2 to less than 3
3 to less than 4
4 or more
Obstetric history
Primiparous
Previous preterm
birth only
Previous preterm
birth and fullterm birth
Previous full-term
birth only
Tobacco use

OR

95% CI

Weight

4.33

1.8010.38

1.00
1.92
3.61
9.54
1.88

Reference
1.053.52
1.687.73
4.7419.18
1.053.38

0
2
4
10
2

1.00
2.34
4.39
14.81

Reference
1.543.57
2.378.14
7.0031.33

0
2
4
15

1.00
2.46

Reference
1.354.48

0
2

1.13

0.622.05

0.98

0.631.52

2.02

1.223.34

OR, odds ratio; CI, confidence interval.

Table 5 demonstrates the test characteristics of

different scores in predicting the risk of each adverse
obstetric outcome. Using 2 or more as the cut-point
for a positive compared with negative test result was
associated with a 94.67% negative predictive value
and 84.44% sensitivity in predicting delivery within
10 days, and an 81.54% negative predictive value and
78.92% sensitivity in predicting preterm birth at less
than 37 weeks of gestation. Using this cut-point, there
was a 55.89% prevalence of a positive test result for
the primary outcome and a 66.04% prevalence of a
positive test result for the secondary outcome. Test
characteristics and 95% CIs associated with a total
score of 2 or more generated using 1,000 bootstrap
replications of the scoring system are presented in
Table 6.

DISCUSSION
We have developed and internally validated two
clinical prediction rules in a cohort of women symptomatic for preterm labor: one to predict delivery

Clinical Prediction Rules for Preterm Birth

OBSTETRICS & GYNECOLOGY

1.00

Sensitivity

0.75

0.50

0.25

0.00
0.00

0.25

0.50
1-Specificity

0.75

1.00

Fig. 2. Models to predict preterm birth before 37 weeks of

gestation. P.006. Curve with triangles, multivariable
model (area under the curve [AUC]0.7307); curve with
circles, univariable model (AUC0.6954); dotted line,
reference line (AUC0.50). Multivariable model includes
obstetric history, initial cervical dilatation, and tobacco use.
Univariable model includes only initial cervical dilatation.
Bastek. Clinical Prediction Rules for Preterm Birth. Obstet
Gynecol 2012.

within 10 days of presentation with preterm labor and

another to predict preterm birth at less than 37 weeks
of gestation. The rule for the primary outcome included tobacco use during pregnancy, no prenatal
care, and initial cervical dilatation. The rule for the
secondary outcome included tobacco use during
pregnancy, obstetric history, and initial cervical
dilatation.
A negative test result for a particular outcome,
obtained by not having any of the risk factors contained within the final model for that outcome, was
associated with a strong ability to predict which
patients would not experience delivery within 10 days
(94.67%) and preterm birth at less than 37 weeks of
gestation (81.54%). In fact, the test characteristics
generated by our final score for delivery within 10
days were very similar to those of fetal fibronectin
to predict delivery within 7 days when performed
in patients symptomatic for preterm labor (positive
predictive value 13%, negative predictive value
99.5%).26 This suggests that patients presenting with
preterm labor could be risk-stratified for preterm
birth without the use of expensive tools and advanced technology.
We are not the first investigators to attempt to
create risk assessment systems for the prediction

VOL. 119, NO. 6, JUNE 2012

models for preterm birth based on demographic and

clinical risk factors alone.2733 However, previous investigators screened asymptomatic women and were
unable to predict gestational age at preterm delivery.
Furthermore, all studies except one were performed
between 15 and 35 years ago.
There were several strengths to our study. Based on
the results of our PubMed search described, we believe
that we are the first group to specifically study women
who presented with symptoms of preterm labor. Furthermore, whereas previous studies attempted to determine the odds of preterm birth, they did not attempt to
predict what we believe to be a clinically more relevant
outcome: the odds of relatively imminent delivery from
the time of presentation with symptoms of preterm
labor. Other strengths of our study include the fact that
the data we used were obtained from enrolling a large
number of high-risk symptomatic women in a prospective cohort study that limited misclassification bias.
Furthermore, eligibility criteria for enrollment were determined before the start of the study by the primary
and senior investigators and not by treating physician,
which minimized potential enrollment biases.
Our study was not without limitations. First,
although our rules were internally validated through
use of the bootstrapping technique, our rules have not
been externally validated in independent cohorts.
Therefore, it is possible that these rules are specific to
the population we investigated and may not be generalizeable to other populations with different demographics. Furthermore, our results may not be generalizeable for use in the outpatient or nontertiary care
settings. Although we cannot be certain of the validity
of the test characteristics of these models in the
absence of external validation, internal validation
with bootstrapping is a well-accepted technique.23,34,35
Another limitation is that, because of practice
patterns at our institution, we do not have fetal
fibronectin information for the patients in this cohort.
We recognize that this information might have had a
favorable effect on the model performance, particularly in terms of negative predictive value.
Other limitations are derived from the study
design. For example, because we enrolled only those
women who presented to the hospital (or who were
directly counseled by their physicians to come to the
hospital) because of their symptoms, our study does
not include women who have symptoms concerning
for preterm labor who chose not to present to the
hospital. In addition, the use of symptomatic women
prevents us from identifying those women who are at
risk for preterm birth before the preterm labor process has started.

Bastek et al

Clinical Prediction Rules for Preterm Birth

1125

Table 5. Test Characteristics of Each Score in Predicting Each Adverse Obstetric Outcome

Score
Outcome: delivery
within 10 d
0 or more
2 or more
4 or more
6 or more
8 or more
10 or more
12 or more
14 or more
16 or more
Outcome: preterm birth
before 37 wk
0 or more
1 or more
2 or more
3 or more
4 or more
5 or more
6 or more
7 or more
8 or more
15 or more
16 or more
17 or more
18 or more
19 or more

Sensitivity

Specificity

Positive
Predictive
Value

1.00
0.84
0.58
0.40
0.32
0.32
0.14
0.08
0.03

0.00
0.51
0.81
0.92
0.94
0.95
0.98
0.99
1.00

0.15
0.24
0.36
0.47
0.50
0.53
0.57
0.64
1.00

0.95
0.91
0.89
0.88
0.89
0.86
0.86
0.85

0.15
0.56
0.78
0.84
0.85
0.85
0.85
0.85
0.85

1.0
1.71
3.10
4.93
5.48
6.11
7.12
9.59

1.00
0.89
0.79
0.63
0.495
0.37
0.27
0.25
0.22
0.22
0.17
0.10
0.06
0.02

0.00
0.22
0.50
0.69
0.87
0.92
0.95
0.97
0.97
0.97
0.98
0.99
1.00
1.00

0.35
0.38
0.46
0.52
0.67
0.71
0.76
0.81
0.80
0.82
0.81
0.87
1.00
1.00

0.78
0.82
0.78
0.75
0.73
0.71
0.70
0.70
0.70
0.69
0.67
0.66
0.65

0.35
0.45
0.60
0.67
0.74
0.73
0.72
0.72
0.71
0.71
0.70
0.68
0.67
0.66

1.0
1.14
1.58
2.03
3.75
4.55
6.01
7.74
7.60
8.17
8.13
12.39

Patients with preterm premature rupture of membranes, a diagnosis on the spectrum of preterm labor,
were included in this study. There are circumstances at
our institution in which it is the standard of care to
induce labor in patients with preterm premature rupture
Table 6. Bootstrap Test Characteristics of Score 2
or More in Predicting Each Adverse
Obstetric Outcome
Outcome

Test Characteristic
Area under curve
Sensitivity
Specificity
Positive predictive
value
Negative predictive
value
Correctly classified
Prevalence of positive
test

Delivery
Within 10 d

Preterm Birth
Before 37 wk
of Gestation

0.76 (0.700.81)
0.84 (0.760.92)
0.51 (0.460.55)
0.24 (0.190.29)

0.72 (0.670.76)
0.75 (0.690.81)
0.56 (0.510.61)
0.48 (0.420.53)

0.95 (0.920.97)

0.80 (0.760.85)

0.56 (0.520.60)
0.55 (0.510.59)

0.62 (0.580.66)
0.55 (0.510.59)

Data are odds ratio (95% confidence interval).

1126

Bastek et al

Negative
Predictive
Value

Correctly
Classified

Positive
Likelihood
Ratio

Negative
Likelihood
Ratio

0.31
0.52
0.65
0.72
0.72
0.87
0.93
0.97

0.51
0.42
0.53
0.59
0.68
0.76
0.78
0.80
0.81
0.85
0.91
0.94
0.99

of membranes as previously described. However, there

were only five patients in the entire cohort (0.86%) who
required induction of labor within 10 days of presentation, and only four patients (0.69%) who required induction of labor at less than 37 weeks of gestation because of
our institutional management of preterm premature rupture of membranes. Therefore, although it is possible that
this inclusion may have affected our results, we do not
believe that it biased our findings in any significant
manner.
Although our clinical research coordinators were
available to enroll patients 12 hours per day for 4 days
per week and 8 hours per day on 2 additional days, our
cohort was a convenience sample. However, it is unlikely that there were relevant systematic differences
between patients who presented to the triage center for
evaluation when clinical research coordinators were
available compared with when clinical research coordinators were not available for enrollment. We acknowledge that, although our models demonstrated a statistically significant improvement in predicting each
outcome over initial cervical dilatation alone, the incorporation of demographic variables appears to improve

Clinical Prediction Rules for Preterm Birth

OBSTETRICS & GYNECOLOGY

our clinical predictive ability only marginally. Finally,

the test characteristics that we presented including the
strong negative predictive value and sensitivity are
based on our decision to use 2 or more as a cut-point for
a positive compared with negative test result. Whereas
the test characteristics would differ if we chose a different cut-point, we chose this value to maximize negative
predictive value and therefore minimize the risk of
mislabeling a patient who will experience preterm birth.
We believe that there may be situations in which
providers either do not have access to or simply
cannot use fetal fibronectin or cervical length screening. Therefore, the purpose of our study was to
present alternative and purely clinical prediction tools
with strong test characteristics that might be used by
clinicians to corroborate their decision-making regarding the appropriate management of their patients.
The widespread application of this rule will require
an understanding of the thresholds for treating compared
with not treating preterm labor in diverse settings, with
consideration of the potential risks and benefits of either
strategy in a given population. However, before such
widespread use, these rules must be validated in external
populations and studied to determine whether their test
characteristics can be significantly enhanced using additional and more detailed patient-specific data.
REFERENCES
1. U.S. Department of Health and Human Services: Office of
Disease Prevention and Health PromotionHealthy People
2010. Nasnewsletter 2000;15:3.
2. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data
for 2005. Natl Vital Stat Rep 2006;55:118.
3. Kurki T, Sivonen A, Renkonen OV, Savia E, Ylikorkala O.
Bacterial vaginosis in early pregnancy and pregnancy outcome. Obstet Gynecol. 1992;80:1737.
4. Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY,
Mercer BM, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med
2008;359:895905.
5. Lyell DJ, Pullen K, Campbell L, Ching S, Druzin ML, Chitkara
U, et al. Magnesium sulfate compared with nifedipine for acute
tocolysis of preterm labor: a randomized controlled trial.
Obstet Gynecol 2007;110:617.
6. Antenatal corticosteroids revisited: repeat courses. NIH Consens Statement 2000;17:118.
7. Antenatal corticosteroid therapy for fetal maturation. ACOG
Committee Opinion No. 475. American College of Obstetricians and Gynecologists. Obstet Gynecol 2011;117:422 4.

11. Lockwood CJ, Senyei AE, Dische MR, Casal D, Shah KD,
Thung SN, et al. Fetal fibronectin in cervical and vaginal
secretions as a predictor of preterm delivery. N Engl J Med
1991;325:669 74.
12. Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A,
Das A, et al. The length of the cervix and the risk of
spontaneous premature delivery. National Institute of Child
Health and Human Development Maternal Fetal Medicine
Unit Network. N Engl J Med 1996;334:56772.
13. Roman AS, Koklanaris N, Paidas MJ, Mulholland J, Levitz M,
Rebarber A. Blind vaginal fetal fibronectin as a predictor of
spontaneous preterm delivery. Obstet Gynecol 2005;105:2859.
14. Stafford IP, Garite TJ, Dildy GA, Colon-Lucach A, Williams
CA, Bobritchi B, et al. A comparison of speculum and nonspeculum collection of cervicovaginal specimens for fetal
fibronectin testing. Am J Obstet Gynecol. 2008;199:131e1 4.
15. McKenna DS, Chung K, Iams JD. Effect of digital cervical
examination on the expression of fetal fibronectin. J Reprod
Med 1999;44:796 800.
16. Lumley J. The epidemiology of preterm birth. Baillieres Clin
Obstet Gynaecol 1993;7:47798.
17. Wen SW, Goldenberg RL, Cutter GR, Hoffman HJ, Cliver SP.
Intrauterine growth retardation and preterm delivery: prenatal
risk factors in an indigent population. Am J Obstet Gynecol
1990;162:213 8.
18. Ekwo EE, Gosselink CA, Moawad A. Unfavorable outcome in
penultimate pregnancy and premature rupture of membranes
in successive pregnancy. Obstet Gynecol 1992;80:166 72.
19. Cnattingius S, Granath F, Petersson G, Harlow BL. The
influence of gestational age and smoking habits on the risk of
subsequent preterm deliveries. N Engl J Med 1999;341:943 8.
20. Rosner B, Alumni and Friends Memorial Book Fund. Fundamentals of biostatistics. 6th ed. Belmont (CA): ThomsonBrooks/Cole; 2006.
21. Hosmer DW, Lemeshow S. Applied logistic regression. 2nd
ed. New York (NY): Wiley; 2000.
22. Hanley JA, McNeil BJ. A method of comparing the areas
under receiver operating characteristic curves derived from the
same cases. Radiology 1983;148:839 43.
23. Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic
models: issues in developing models, evaluating assumptions
and adequacy, and measuring and reducing errors. Stat Med
1996;15:361 87.
24. Moise A, Clement B, Ducimetiere P, Bourassa MG. Comparison of receiver operating curves derived from the same
population: a bootstrapping approach. Comput Biomed Res
1985;18:12531.
25. Kelsey JL, Thompson WD, Evans AS. Methods in observational epidemiology. New York (NY): Oxford University
Press; 1986.
26. Peaceman AM, Andrews WW, Thorp JM, Cliver SP, Lukes A,
Iams JD, et al. Fetal fibronectin as a predictor of preterm birth
in patients with symptoms: a multicenter trial. Am J Obstet
Gynecol 1997;177:13 8.
27. Fedrick J. Antenatal identification of women at high risk of spontaneous pre-term birth. Br J Obstet Gynaecol 1976;83:3514.

8. Effect of corticosteroids for fetal maturation on perinatal

outcomes. NIH Consens Statement 1994;12:124.

28. Creasy RK, Gummer BA, Liggins GC. System for predicting
spontaneous preterm birth. Obstet Gynecol 1980;55:6925.

9. Berkman ND, Thorp JM Jr, Hartmann KE, Lohr KN, Idicula

AE, McPheeters M, et al. Management of preterm labor. Evid
Rep Technol Assess (Summ) 2000;18:1 6.

29. Carr-Hill RA, Hall MH. The repetition of spontaneous preterm labour. Br J Obstet Gynaecol 1985;92:921 8.

10. Berghella V, Ness A, Bega G, Berghella M. Cervical sonography in women with symptoms of preterm labor. Obstet
Gynecol Clin North Am 2005;32:38396.

VOL. 119, NO. 6, JUNE 2012

30. Mercer BM, Goldenberg RL, Das A, Moawad AH, Iams JD,
Meis PJ, et al. The preterm prediction study: a clinical risk
assessment system. Am J Obstet Gynecol 1996;174:188593;
discussion 935.

Bastek et al

Clinical Prediction Rules for Preterm Birth

1127

31. Main DM, Gabbe SG, Richardson D, Strong S. Can preterm

deliveries be prevented? Am J Obstet Gynecol 1985;151:8928.
32. Tan H, Wen SW, Chen XK, Demissie K, Walker M. Early
prediction of preterm birth for singleton, twin, and triplet pregnancies. Eur J Obstet Gynecol Reprod Biol 2007;131:1327.
33. Lazar P, Dreyfus J, Papiernik E, Winisdoerfer G, Collin D,
Gueguen S. [Prediction of prematurity as a preventive measure]. Arch Fr Pediatr 1978;35(Suppl 1):XIXXXVI.

1128

Bastek et al

34. Steyerberg EW, Harrell FE, Jr., Borsboom GJ, Eijkemans MJ,
Vergouwe Y, Habbema JD. Internal validation of predictive
models: efficiency of some procedures for logistic regression
analysis. J Clin Epidemiol 2001;54:774 81.
35. Steyerberg EW, Bleeker SE, Moll HA, Grobbee DE, Moons
KG. Internal and external validation of predictive models: a
simulation study of bias and precision in small samples. J Clin
Epidemiol. 2003;56:4417.

Clinical Prediction Rules for Preterm Birth

OBSTETRICS & GYNECOLOGY