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Original Research

Universal Cervical Length Screening and


Antenatal Corticosteroid Timing
Nicole Sahasrabudhe, MD, Catherine Igel, MD, Ghislaine C. Echevarria, MD, MS, Peer Dar, MD,
Diana Wolfe, MD, Peter S. Bernstein, MD, MPH, Robert Angert, MD, Ashlesha Dayal, MD,
Patience Gallagher, BS, and Mara Rosner, MD

OBJECTIVE: To evaluate the relationship between groups. During the study period, 64 of 69 (92.8%) of
universal transvaginal screening for short cervical patients with a short cervix and 176 of 197 (89.3%)
length in the second trimester and the timing of without a short cervix received at least one steroid
antenatal corticosteroids. injection before delivery (P5.411). Steroids were given
METHODS: We performed a retrospective cohort study within 7 days of delivery in 33 of 69 (47.8) patients with
of patients with nonanomalous singleton gestations and a short cervix compared with 126 of 197 (64%) patients in
spontaneous preterm birth between 24 and 34 weeks of the no short cervix group (P5.015; adjusted odds ratio
gestation after the initiation of a universal transvaginal 0.51, 95% confidence interval 0.290.9). Median interval
cervical length screening program between October between steroid administration and delivery was 8 days
2012 and August 2015. Our primary outcome was in patients diagnosed with a short cervix compared with
antenatal corticosteroid administration to a delivery 3 days for those without a short cervical length (P,.001).
interval of fewer than 7 days. Secondary outcomes CONCLUSION: Patients identified as having a short
were delivery 24 hours to 7 days after the initial cervical length by universal transvaginal ultrasound
steroid injection, steroid administration to delivery screening were at greater risk of delivering more than 7
interval, neonatal survival, neonatal intensive care days after the initiation of corticosteroids for fetal lung
unit length of stay, and respiratory distress syndrome. maturation compared with women without a short
Multivariable logistic regression was used to estimate cervical length.
the association between antenatal corticosteroid tim- (Obstet Gynecol 2017;129:11048)
ing and the diagnosis of a short cervix adjusted for DOI: 10.1097/AOG.0000000000002029
potential confounders.
RESULTS: Among 266 eligible patients, 69 with a short
cervical length and 197 without a short cervical length
were identified. There were no statistically significant
P reterm birth remains a leading cause of perinatal
morbidity and mortality.1
Fortunately, the rate of preterm birth in the
differences in baseline characteristics between the United States has dropped for the sixth consecutive
year to a 15-year low of 11.5% in 2013.2 This achieve-
From the Departments of Obstetrics & Gynecology and Womens Health and ment may be at least partially attributable to the iden-
Pediatrics, Albert Einstein College of Medicine/Montefiore Medical Center, tification of at-risk patients using second-trimester
Bronx, and the Departments of Anesthesiology, Perioperative Care and Pain
Medicine and Obstetrics and Gynecology, New York University School of Med-
ultrasound evaluation of the cervix along with the
icine, New York, New York. use of interventions to prevent preterm birth such as
Presented at the 36th Annual Meeting of the Society for Maternal and Fetal vaginal progesterone and in patients with a history of
Medicine, February 6, 2016, Atlanta, Georgia. prior preterm birth or cerclage.3,4 For these reasons,
Each author has indicated that he or she has met the journals requirements for many institutions have adopted a universal transvagi-
authorship. nal cervical length screening protocol (Khalifeh A,
Corresponding author: Mara Rosner, MD, 150 East 32nd Street, Suite 101, Quist-Nelson J, Berghella V. Current implementation
New York, NY 10016; email: marar01@gmail.com.
of universal cervical length screening for preterm
Financial Disclosure
The authors did not report any potential conflicts of interest.
birth prevention in the United States [19] [abstract].
Obstet Gynecol 2016;127(suppl 1):7S).
2017 by The American College of Obstetricians and Gynecologists. Published
by Wolters Kluwer Health, Inc. All rights reserved. Although antenatal corticosteroids are not an
ISSN: 0029-7844/17 intervention to reduce preterm birth, the administration

1104 VOL. 129, NO. 6, JUNE 2017 OBSTETRICS & GYNECOLOGY

Copyright by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
part of a universal transvaginal cervical length screening
protocol and the timing of administration of antenatal
corticosteroids in relation to the timing of birth.

MATERIALS AND METHODS


Our institution adopted a universal transvaginal
cervical length screening protocol in October 2012
for all women with a singleton gestation undergoing
a routine anatomy ultrasonogram between 17 0/7
weeks and 23 6/7 weeks of gestation. After obtaining
Montefiore Medical Center institutional review board
approval, we retrospectively analyzed the electronic
Fig. 1. Flow diagram. records of all women who experienced spontaneous
Sahasrabudhe. Short Cervix and Antenatal Corticosteroid. Obstet preterm delivery between 24 0/7 weeks and 34 0/7
Gynecol 2017.
weeks of gestation after the initiation of universal
transvaginal cervical length screening (October 2012)
of antenatal corticosteroids before preterm birth signif- at our institution until August 2015.
icantly reduces associated neonatal morbidity and Patients with major fetal anomalies, multiple
mortality.5 Timing of corticosteroids appears to be a crit- gestations, iatrogenic preterm deliveries resulting
ical factor in their efficacy. Although reduction of neo- from maternal or fetal indications, and patients who
natal death is seen at less than 24 hours after a first dose, did not deliver at our institution were excluded.
studies have failed to show demonstrable mortality or Maternal demographics and medical and obstetric
morbidity benefits at more than 7 days from the first history data were obtained through electronic medical
dose.6 We hypothesized that health care provider con- records. Gestational age and cervical length at the initial
cern for impending preterm labor in patients with an transvaginal ultrasonogram and on any follow-up ultra-
incidental finding of a short cervix might influence sonograms were recorded. Short cervix was defined as
hasty steroid dosing, potentially putting these patients 2.0 cm or less in the absence of prior spontaneous
at risk for suboptimal antenatal corticosteroid timing. preterm birth or less than 2.5 cm if there was a history
The aim of this study was to assess the relationship of prior spontaneous preterm birth.7 Neonatal data
between patients identified as having a short cervix as including gestational age at delivery, birth weight, gen-
der, admission to the neonatal intensive care unit, respi-
ratory distress syndrome (RDS), and neonatal demise
were also recorded. Each maternal and neonatal record
was individually reviewed by study investigators.
All episodes of antenatal corticosteroid dose
administration were identified. We considered one
dose to be an incomplete initial steroid course, two
doses a completed course, three doses an incomplete
rescue course, and four doses as a complete rescue
course. The interval of days to delivery from antenatal
corticosteroid administration was recorded. In the
event a patient received a rescue antenatal corticoste-
roid course, timing from antenatal corticosteroid
administration to delivery was based on the patients
Fig. 2. Linear regression modeling the relationship most recent (ie, rescue) antenatal corticosteroid
between cervical length at the time of second-trimester course. Optimal steroid timing was considered a ste-
transvaginal ultrasonography and antenatal corticosteroid roid to delivery interval of 24 hours to 7 days (allow-
administration to delivery interval. For every 10-mm ing for a complete steroid course).
decrease in cervical length, the predicted increase in The primary outcome was delivery within 7 days
antenatal corticosteroid administration to delivery interval
was 1.5 days. Gray area indicates 95% confidence interval. of the first dose (initial or rescue) of antenatal
Black line indicates fitted values. corticosteroid. Secondary outcomes included delivery
Sahasrabudhe. Short Cervix and Antenatal Corticosteroid. Obstet 24 hours to 7 days after the initial steroid injection,
Gynecol 2017. antenatal corticosteroid to delivery interval in days,

VOL. 129, NO. 6, JUNE 2017 Sahasrabudhe et al Short Cervix and Antenatal Corticosteroids 1105

Copyright by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Table 1. Baseline Characteristics

Characteristic Short Cervical Length (n569) No Short Cervical Length (n5197) P

Maternal age (y) 29.860.7 28.960.5 .353


Race
Hispanic 30 (43.5) 66 (33.5) .147
Black 17 (24.6) 52 (26.4) .874
Caucasian 4 (5.8) 9 (4.6) .747
Asian 4 (5.8) 8 (4.1) .515
Unknown or other 14 (20.3) 62 (31.5) .089
Nulliparous 29 (42.0) 85 (43.2) .872
History of full-term delivery 28 (40.6) 81 (41.1) .938
History of preterm delivery 24 (34.8) 57 (28.9) .300
Cervical length at anatomy (cm) 1.5 (0.81.9) 3.9 (3.34.5) ,.001
Gestational age at delivery (wk) 28.3 (26.132.3) 31.3 (28.032.9) .006
Insurance (public or private) 52/17 153/44 .695
Diabetes mellitus (including GDM) 14 (20.3) 29 (14.7) .280
GDM, gestational diabetes mellitus.
Data are mean6standard deviation, n (%), or median (interquartile range) unless otherwise specified.

the incidence of delivery after a complete steroid elimination approach, the likelihood ratio test com-
course, neonatal survival, neonatal intensive care unit paring the model including the variable with the
length of stay, and RDS. nested model excluding it was used to assess whether
We tested normality using the Shapiro-Wilk test the variable contributed significantly to the model
and Q-Q plots. We used unpaired Student t test or (P,.20). The HosmerLemeshow goodness-of-fit test
Wilcoxon rank-sum test for between-group compari- was used to assess calibration of the model.
sons, as appropriate. x2 test and Fisher exact test were Among patients with known short cervix, the
used for inferences on proportions. potential association of cerclage and the use of vaginal
A multivariable logistic regression model was progesterone on the timing of antenatal corticosteroid
used to quantify the association between optimal administration was also studied. Data are expressed as
timing of antenatal corticosteroids and a short cervix. mean (standard deviation), median (interquartile
The model building was done according to Hosmer range), or odds ratio (95% confidence interval), unless
and Lemeshow.8 Variables identified as potential con- otherwise stated. A two-sided P value ,.05 was con-
founding factors and those with a P value of ,.25 in sidered significant. All analyses were performed with
the univariable analysis were included in the multivar- STATA/SE 12.1.
iable logistic regression model. Using a backward
RESULTS
Table 2. Univariable Analysis: Odds Ratio of A total of 1,253 patients had spontaneous preterm
Receiving Antenatal Corticosteroids birth before 34 weeks of gestation within the study
Within 7 Days of Delivery (N5266)
Table 3. Multivariable Logistic Regression Analysis:
Variable OR (95% CI) P Odds Ratio of Receiving Antenatal
Corticosteroids Within 7 Days of Delivery
Age (1-y increment) 0.98 (0.941.02) .283
Gestational age (1-d increment) 1.00 (0.991.01) .637 Unadjusted Adjusted
History of preterm birth 0.56 (0.330.96) .035 Variable OR (95% CI) OR (95% CI) P
Private insurance* 1.22 (0.682.22) .500
Race Short cervical 0.50 (0.290.88) .015
Hispanic 1 length*
Black 1.04 (0.551.95) .907 Short cervical 0.51 (0.290.90) .019
Caucasian 1.60 (0.465.55) .463 length*
Asian 2.13 (0.548.37) .280 History of 0.58 (0.340.99) .045
Unknown or other 1.03 (0.561.90) .927 preterm birth
Diabetes mellitus (including GDM) 0.92 (0.671.25) .587
OR, odds ratio; CI, confidence interval.
OR, odds ratio; CI, confidence interval; GDM, gestational diabetes Hosmer and Lemeshows goodness-of-fit test for the adjusted
mellitus. model, P5.13.
* Reference group is public insurance. * Reference group is no short cervical length.

1106 Sahasrabudhe et al Short Cervix and Antenatal Corticosteroids OBSTETRICS & GYNECOLOGY

Copyright by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Table 4. Antenatal Corticosteroid Administration and Neonatal Outcomes

Short Cervical No Short Cervical


Outcome Length (n569) Length (n5197) P

Antenatal corticosteroid-to-delivery interval 7 d or less 33 (47.8) 126 (64.0) .015


Antenatal corticosteroid-to-delivery interval (d) 8 (219) 3 (19) ,.001
Any antenatal corticosteroid dose before delivery 64 (92.8) 176 (89.3) .411
Complete course of steroid 62 (89.9) 158 (80.2) .068
Optimal interval 24 h to 7-d interval or less 30 (43.5) 87 (44.2) .922
NICU stay (d) 47 (2095) 34 (1666) .011
Neonatal RDS 53 (76.8) 150 (76.1) .910
Neonatal mortality 4 (5.8) 8 (4.1) .550
NICU, neonatal intensive care unit; RDS, neonatal respiratory distress syndrome.
Data are n (%) or median (interquartile range) unless otherwise specified.
Optimal timing antenatal corticosteroid when given within the optimal 7-day window before delivery.

period, October 2012 to August 2015. Of those, 987 receiving a complete steroid course was 6.9 (1.19.9)
were excluded from the analysis for multiple gesta- hours. For the seven patients in the short cervical
tion, fetal anomalies, iatrogenic preterm birth result- length group, the median dose to delivery interval
ing from secondary causes such as preeclampsia and was 11.5 (1.618.1) hours and for those in the no short
growth restriction, or missing data. Of the remaining cervical length group (n539), the median dose to
266 patients, 69 (25.9%) had a short cervix at the time delivery interval was 5.7 (1.19.6) hours (P5.293).
of their universal transvaginal cervical length screen Within the short cervical length group, a cerclage
and 197 (74.1%) did not (Fig. 1). procedure was performed in 23 (33.3%) patients and
Patients in the short cervical length group had vaginal progesterone was used by 29 (42%). In the
a median cervical length of 1.5 (0.81.9) cm at the time subgroup analyses, no differences were seen in the
of the second-trimester transvaginal ultrasonography optimal timing of antenatal corticosteroid administra-
(Fig. 2) compared with 3.9 (3.34.5) cm in the no short tion and the presence of cerclage or use of vaginal
cervical length group (P,.001) and were more likely to progesterone (P5.610 and P5.164, respectively).
deliver at an earlier gestational age (P5.006; Table 1). Although neonates from women with short cer-
During the study period, 64 of 69 (92.8%) of vical length had a longer neonatal intensive care unit
patients with a short cervix and 176 of 197 (89.3%) stay compared with women without a short cervical
without a short cervix received at least one steroid length (47 compared with 34 days; P5.011), this dif-
injection before delivery (P5.411). At least one dose of ference was not significant after controlling for gesta-
steroids was given within 7 days of delivery in 33 of 69 tional age at delivery (P5.149). Similarly, there was
(47.8) patients with a short cervix compared with 126 of no difference in neonatal survival or RDS between the
197 (64%) patients in the no short cervix group groups (Table 4).
(P5.015). When the optimal interval of 24 hours to 7
days was considered, there was no difference between DISCUSSION
groups (30/69 [43.5%] of those with a short cervix com- In this study, we found that patients identified with
pared with 87/197 [44.2%] of those without; P5.922). a short cervix on universal transvaginal cervical
The results of the univariable and multivariable length screening and who subsequently delivered
logistic regression analysis are shown in Tables 2 and 3, prematurely had a significantly longer interval from
respectively. The adjusted odds ratio of receiving ante- antenatal corticosteroid administration (8 days com-
natal corticosteroid within 7 day before delivery was pared with 3 days) and fewer of them received
0.51 (95% confidence interval 0.290.9) when compar- antenatal corticosteroid within 7 days of birth com-
ing the short cervical length group with the no short pared with patients with spontaneous preterm birth
cervical length group. The median interval between the who were not identified as having a short cervix by
antenatal corticosteroid administration and delivery universal transvaginal cervical length screening. How-
was significantly shorter in the no short cervical length ever, a similar percentage of patients in both groups
group compared with the short cervical length group (3 delivered within the optimal interval of 24 hours to 7
days compared with 8 days, P,.001; Table 4). days. Neonatal outcomes were similar between these
The median injection to delivery interval for two groups; however, our study was not powered to
patients who delivered less than 7 days but before assess differences in neonatal outcomes.

VOL. 129, NO. 6, JUNE 2017 Sahasrabudhe et al Short Cervix and Antenatal Corticosteroids 1107

Copyright by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
This study highlights the clinical dilemma for In summary, a policy of universal transvaginal
physicians caring for patients with an incidentally cervical length screening may increase the likelihood
identified short cervix trying to balance the risk of that corticosteroids for fetal maturation are adminis-
administering corticosteroids too early with the risk of tered less than optimally.
administering them too late. Although available data
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1108 Sahasrabudhe et al Short Cervix and Antenatal Corticosteroids OBSTETRICS & GYNECOLOGY

Copyright by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.

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