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Systematic Review

Universal cervical length screening and risk of


spontaneous preterm birth: a systematic
review and meta-analysis
Kamran Hessami, MD; Elena D’Alberti, MD; Daniele Di Mascio, MD; Vincenzo Berghella, MD

Introduction

G lobally, preterm birth (PTB) is the


leading cause of neonatal morbid-
ity and mortality.1,2 In more than two-
OBJECTIVE: To evaluate the risk of spontaneous preterm birth with or without universal trans-
vaginal ultrasound cervical length screening at the time of midtrimester scan.
DATA SOURCES: Medline, Embase, ClinicalTrials.gov, and Web of Science were systemati-
thirds of cases, PTB occurs spontane- cally searched from the inception of the databases to November 12, 2023, using combina-
ously (sPTB), following either preterm tions of the relevant medical subject heading terms, key words, and word variants that were
labor (PTL) or preterm prelabor rup- considered suitable for the topic.
ture of membranes (PPROM).3 The STUDY ELIGIBILITY CRITERIA: Studies including individuals with singleton gestations at 16
research of effective screening strategies −25 weeks of gestation screened or not screened with universal transvaginal ultrasound cer-
for sPTB in asymptomatic individuals is vical length screening were considered eligible. Primary outcome was spontaneous preterm
of paramount importance because there birth <37 weeks; secondary outcomes were spontaneous preterm birth <34 and <32 weeks.
are evidence-based preventive strategies, METHODS: Random effect head-to-head analyses were used to directly compare each out-
such as progesterone supplementation come, expressing the results as summary odds ratio and relative 95% confidence interval.
and cervical cerclage, that can be offered The quality of the included studies was independently assessed by 2 reviewers, using the
to patients at high risk.2,4−10 Newcastle-Ottawa scale for cohort studies and the Cochrane risk-of-bias tool for randomized
Transvaginal ultrasound (TVU) cer- controlled studies. The study was registered on the prospective register of systematic reviews
vical length (CL) evaluation has been database (PROSPERO) (registration number: CRD42022385325).
shown to be one of the main predictors RESULTS: Eight studies, including 447,864 pregnancies, were included in the meta-analysis
of sPTB,2 as cervical shortening is one (213,064 screened with transvaginal ultrasound cervical length and 234,800 unscreened). In
of the first asymptomatic before later the overall analysis, universal transvaginal ultrasound cervical length did not significantly
symptomatic PTL or PPROM. decrease the spontaneous preterm birth rates <37 weeks (odds ratio, 0.92 [95% confidence
interval, 0.84−1.01], P=.07) and <34 weeks (odds ratio, 0.87 [95% confidence interval,
0.73−1.04], P=.12), but was significantly associated with a lower risk of spontaneous pre-
Cite this article as: Hessami K, D’Alberti E, Mascio DD, term birth <32 weeks (odds ratio, 0.84 [95% confidence interval, 0.76−0.94], P=.002). Indi-
et al. Universal cervical length screening and risk of viduals without a prior spontaneous preterm birth had a significantly lower risk of spontaneous
spontaneous preterm birth: a systematic review and preterm birth <37 weeks (odds ratio, 0.88 [95% confidence interval, 0.79−0.97], P=.01)
meta-analysis. Am J Obstet Gynecol MFM
2024;6:101343.
and a lower trend of spontaneous preterm birth <32 weeks (odds ratio, 0.82 [95% confidence
interval, 0.66−1.01], P=.06) when screened with transvaginal ultrasound cervical length,
From the Maternal Fetal Care Center, Boston compared with no screening.
Children’s Hospital, Harvard Medical School, CONCLUSION: Universal transvaginal ultrasound cervical length screening usually <24 weeks
Boston, MA (Dr Hessami); Department of in singletons without a prior spontaneous preterm birth, is associated with a significant reduc-
Maternal and Child Health and Urological
Sciences, Sapienza University of Rome, Rome,
tion in spontaneous preterm birth <37 weeks, compared with no screening.
Italy (Drs D’Alberti and Di Mascio); Division of Key words: cervical length, preterm birth, preterm labor, short cervix, transvaginal ultrasound,
Maternal-Fetal Medicine, Department of
universal screening
Obstetrics and Gynecology, Thomas Jefferson
University Hospital, Philadelphia, PA (Dr
Berghella).
Received January 24, 2024; revised February Although midtrimester TVU CL screen- universal TVU CL screening in such
20, 2024; accepted March 4, 2024. ing is recommended by United States patients,2 despite the fact that this pop-
K.H. and E.D.A. share first authorship. and international societies in individu- ulations of singletons without prior
The authors report no conflict of interest. als with singleton gestations and prior sPTB represents almost 90% of PTBs
Corresponding author: Vincenzo Berghella, sPTB,11−13 TVU CL screening in <34 weeks. Some of the main obstacles
MD. vincenzo.berghella@jefferson.edu asymptomatic individuals with no prior to TVU CL implementation are the
2589-9333/$36.00 sPTB is not universally recommended, uncertainty of cost-effectiveness across
© 2024 Elsevier Inc. All rights reserved. and only the International Society of the entire population and the lack of
http://dx.doi.org/10.1016/j. Ultrasound in Obstetrics and Gynecol- conclusive results confirming a signifi-
ajogmf.2024.101343 ogy (ISUOG) guidelines recommend cant decrease in the risk of PTB by

May 2024 AJOG MFM 1


Systematic Review

AJOG MFM at a Glance Data extraction


A systematic literature search was per-
Why was this study conducted? formed by 2 independent authors (K.H.
The role of universal midtrimester transvaginal ultrasound (TVU) cervical and E.D.A.), and all abstracts were
length (CL) assessment is still a matter of debate. reviewed independently by 2 authors
Key findings (K.H. and E.D.A.). Agreement regard-
Universal TVU CL screening usually <24 weeks in singletons without a prior ing potential relevance was reached by
spontaneous preterm birth (SPTB) is associated with a significant reduction in consensus. Full-text copies of the rele-
SPTB <37 weeks, compared to no screening. vant papers were obtained, and relevant
data regarding study characteristics and
What does this add to what is known? pregnancy outcomes were extracted
Our findings support the implementation of a universal TVU CL screening at independently by the same 2 reviewers.
around 18−23 weeks for singletons without a prior SPTB. Inconsistencies were discussed by the
reviewers until a consensus was reached
or resolved by discussion with other
screening pregnant individuals without Study selection authors (D.D.M. and V.B.). For those
a prior sPTB.11−15 This systematic review aimed to evalu- articles in which the relevant informa-
Thus, this study aimed to ascertain ate the risk of sPTB with and without tion was not reported but the methodol-
the risk of sPTB with and without uni- universal TVU CL screening at the time ogy was such that the information
versal TVU CL screening at the time of of midtrimester scan, in particular in might have been recorded initially, the
midtrimester scan, in particular in indi- singletons without a prior sPTB. Selec- authors were contacted requesting the
viduals with singleton gestations and no tion criteria included either observa- data. Data abstraction was performed
prior sPTB. tional or interventional studies directly using a standardized collection form.
comparing the risk of sPTB between
pregnant individuals undergoing vs not Assessment of risk of bias
undergoing universal TVU CL in the Quality assessment of the observational
Materials and Methods midtrimester of pregnancy (screening studies included was performed using
Eligibility criteria, information vs not screening over the same period the Newcastle-Ottawa scale (NOS) for
sources, and search strategy or 2 different periods [after vs before cohort studies.22 According to the NOS,
This systematic review was performed the implementation of TVU CL]). Stud- each study is judged on 3 broad per-
according to an a-priori-designed pro- ies were excluded if designed as case spectives: selection of the study groups,
tocol recommended for systematic reports, case series, or review articles. comparability of the groups, and ascer-
reviews and meta-analyses.16−18 Med- Studies considering only overall PTB as tainment of the outcome of interest.
line, Embase and Cochrane databases outcome and cases with cervical cerc- Assessment of the selection of a study
were searched electronically until lage performed before screening includes evaluation of the representa-
November 2023 using the following key because of obstetric history were tiveness of the exposed cohort, selection
words: (“cervical length”[TIAB] OR excluded from the meta-analysis. Stud- of the nonexposed cohort, ascertain-
(“cervi*”[TIAB] AND (“ultrasound”[- ies using transabdominal ultrasound ment of the exposure, and demonstra-
TIAB] OR “sonograph*”[TIAB]))) (TAU) for CL screening were excluded, tion that the outcome of interest was
AND (“preterm delivery”[TIAB] OR even when TVU followed the TAU. not present at the start of the study.
“preterm birth”[TIAB] OR “prematur- The primary outcome was sPTB <37 Assessment of the comparability of the
e”[TIAB]) AND (“universal”[TIAB] OR weeks; secondary outcomes were sPTB study includes evaluation of the compa-
“routine”[TIAB] OR “worldwide”[- <34 weeks and sPTB <32 weeks. rability of cohorts on the basis of the
TIAB] OR “screening”[TIAB]). Because of the presence of 2 different design or analysis. Ascertainment of the
The search and selection criteria were design methods evaluating the effect of outcome of interest includes evaluation
restricted to the English language. Ref- TVU CL on the risk of sPTB, we of the type of assessment of the out-
erence lists of relevant articles and planned to perform 2 subgroup analy- come of interest and the length and ade-
reviews were hand-searched for addi- ses, 1 evaluating the screening program quacy of follow-up. According to the
tional reports. Preferred Reporting offered over the same period and 1 eval- NOS, a study can be awarded a maxi-
Items for Systematic Reviews and Meta- uating CL assessment over 2 different mum of one star for each numbered
analysis (PRISMA) guidelines were fol- periods, after and before the implemen- item within the selection and outcome
lowed.19−21 The study protocol for this tation of TVU CL screening. In addi- categories, and a maximum of 2 stars
systematic review was registered in the tion, we planned to perform a subgroup can be given for comparability. A score
prospective register of systematic analysis that considered only individu- of ≥7 was considered as high quality.
reviews database (PROSPERO) (regis- als without previous sPTB, which was In addition, we included a random-
tration number: CRD42022385325). our main aim. ized controlled trial (RCT) in the

2 AJOG MFM May 2024


Systematic Review

analysis, and the quality assessment of test (in such cases, the power is too low Canada.32 Five studies were designed
this study was performed using the to distinguish chance from real asym- retrospectively,26,27,29,31,32 2 studies
Cochrane risk-of-bias (RoB2) tool for metry).24 The statistical analysis was were prospective,25,30 and 1 was an
RCTs. It consists of 5 domains for conducted using Review Manager (Rev- RCT.28 By design, all pregnancies were
assessing bias in randomized trials: (1) Man, version 5.4.1; The Cochrane Col- singleton gestations. About half of the
bias arising from the randomization laboration, London, United Kingdom). population was represented by primipa-
process, (2) bias because of deviations rous individuals, whereas a prior sPTB
from intended interventions, (3) bias Results was present in 5% of pregnancies
because of missing outcome data, (4) Study selection (Table 125−32). TVU CL screening usu-
bias in the measurement of the out- A total of 1030 articles were retrieved. ally occurs between 18 and 23 weeks,
come, and (5) bias in the selection of Of those, 238 articles were excluded for with a range from 16 to 25 weeks.
the reported result. Each domain is duplication. The remaining 792 studies Vaginal progesterone was recom-
assessed using a set of signaling ques- were screened for eligibility. Title and mended for cervical length ≤25 mm in
tions to evaluate the risk of bias for each abstract screening resulted in 13 poten- 4 studies,28,30−32 ≤20 mm in 3 studies,25
−27
domain.23 tially eligible studies. After a full-text and ≤15 mm in 1 study.29 Cervical
assessment was conducted, 8 studies cerclage was placed according to physi-
Data synthesis met the inclusion criteria defined in our cal examination changes,26,27 and short
We used random effect head-to-head methodology (Figure 1, Supplemental CL and history of sPTB.26 In 1 study,
analyses to directly compare each out- Table 1). These 8 included studies com- cervical cerclage was placed for CL ≤15
come, expressing the results as sum- prised 447,864 patients at the mid- mm; further cervical shortening
mary odds ratio (OR) and relative 95% trimester of the pregnancy; of these, occurred during follow-up despite pro-
confidence interval (CI). The statistical 213,064 underwent TVU CL screening, gesterone treatment,29 and in 1 study
heterogeneity was evaluated through whereas 234,800 did not. for ≤10 mm (Table 2).25−32 In the
the heterogeneity measure (I2). For each screened group, short cervix defined as
outcome, the total number of publica- Study characteristics ≤25 mm and ≤20 mm was found in
tions included in the meta-analyses was The included studies were published 0.81% of cases and 0.78%, respectively.
<10. Thus, we were unable to assess between 2014 and 2023 (Table 125−32). Among screened individuals with a
publication bias, either graphically, Three studies were conducted in the diagnosis of short CL, about 62% of
through funnel plots, or formally, United States25−27; the others were in patients overall received progesterone,
through Egger’s regression asymmetry India,28 Greece,29 France,30 Spain31 and and 15% of patients with no previous
PTB received cerclage (Table 225−32).
The overall quality of the included
FIGURE 1 studies was moderate to high.25−28,30−32
PRISMA 2020 flow diagram Only 1 study had a NOS score <7
(Tables 3 and 4).25−27,29−32

Synthesis of results
Overall, the rate of sPTB <37 weeks was
not significantly different between the
TVU CL screened and unscreened pop-
ulation (OR, 0.92 [95% CI, 0.84−1.01],
P=.07, I2=52%) (Figure 2). Similarly,
there was no significant difference for
the rate of sPTB <34 weeks (OR, 0.87
[95% CI, 0.73−1.04], P=.12, I2=35%)
(Figure 3), whereas the rate of sPTB
<32 weeks was significantly lower in
the TVU CL screened group (OR, 0.84
[95% CI, 0.76−0.94], P=.002 I2=0%)
(Figure 4, Table 525−32).
When focusing on studies comparing
screening vs no screening for TVU CL
over the same period, we found no sig-
PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analysis. PTL, preterm labor; sPTB, spontaneous preterm birth. nificant difference either for the rate of
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024. sPTB <37 weeks (OR, 0.91 [95% CI,
0.76−1.09], P=.30, I2=0%), <34 weeks

May 2024 AJOG MFM 3


4 AJOG MFM May 2024

Systematic Review
TABLE 1
Characteristics of the included studies
Eligibility criteria
Study Number Primiparous Prior PTB GA at TVU Definition of Outcomes of Variables for
Study (first author) Country design Screeninga,b Total population size of fetuses rate, n (%) rate, n (%) CL screening short CL, mm interest, wk adjustment
Orzechowski et al,25 United States P A 2171 (1569/602) SP 997 (45.9) Excluded 18 wk 0 d−23 wk 6 d ≤20 sPTB: <37, <34, and <32 Ethnicity, prior conization,
2014 and nulliparity
Temming et al,26 2016 United States R A 12,740 (10,871/1869) SP 4010 (31.5) 1209 (9.5) 17 wk 0 d−23 wk 6 d ≤20 sPTB: <37, <34, and <32 Ethnicity, smoking, and
history of PTB
Son et al,27 2016 United States R B 64,207 (17,609/46,598) SP 34,856 (54.3) Excluded 18 wk 0 d−23 6 d ≤20 PTB and sPTB: <37, <34, Ethnicity, BMI, and history
and <32 of the following: cervical
excision procedure,
smoking, chronic
hypertension, and
pregestational diabetes
Mishra et al,28 2018 India RP A 296 (147/149) SP 150 (50.67) Excluded 16 wk 0 d−23 6 d ≤25 sPTB: <37, and <32 NA
Souka et al,29 2019 Greece R B 15,298 (10,506/4792) SP 6860 (65.3)c 108 (1.0)c 20 wk 0 d−23 6 d ≤15 sPTB: <37, <34, and <32 NA
Figarella et al,30 2023 France Pd B 336,603 (165,524/171,079) SP 1595 (46)e 98 (2.8)e 16 wk 0 d−25 6 d ≤25 PTB and sPTB: <37 and Age, BMI, smoking
<32
Melchor Corcostegui et Spain R B 10,536 (4158/6378) SP NRf Excluded 19 wk 0 d−22 6 d ≤25 sPTB: <37, <34, and <32 NA
al,31 2023
Stratulat et al,32 2024 Canada R B 6013 (2680/3333) SP 2525 (42) 288 (4.8) 18 wk 0 d−23 6 d ≤25 PTB and sPTB: <37, <34, NA
and <32
Total − − A (n=3) 447,864 (213,064/234,800) SP 50,993/100,543 (50.7) 1703/32, 16 wk 0 d−25 6 d 4 studies ≤25 − −
B (n=5) 738 (5.2) 3 studies ≤20
1 study ≤15
BMI, body mass index; CL, cervical length; GA, gestational age; NA, not applicable; NR, not reported; P, prospective; PTB, preterm birth; R, retrospective; RP, randomized prospective; SP, Singleton pregnancies; sPTB, spontaneous preterm birth; tPTL, threatened pre-
term labor; TVU, transvaginal ultrasound; US, United States.
a
Screening assessment A: primary and secondary outcomes compared between screened and unscreened populations over the same periods; b Screening assessment B: primary and secondary outcomes compared between pregnant women over 2 different periods,
after and before TVU CL screening implementation; c Reported among screened women only; d Data from the French Programme de me dicalisation des syste mes d’information national database and the ECHOCOL (“echo”=“ultrasound” and “col”=“cervix” in French)
prospective cohort; e Reported for the ECHOCOL population only; f Reported only among women with tPTL.
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024.
TABLE 2
Preventive strategies after identifying short cervix during universal TVU CL screening
Short cervix treated with cerclage
Recommended Short cervix treated
Study (first author) vaginal PG Cervical cerclage Cervical pessary Short cervix, n/N (%) with PG, n/N (%) Overall No prior PTB
Orzechowski et al,25 2014 CL ≤20 mm Not indicated because of a low-risk Unspecified 17/1569 (1.1) 13/17 (76.5) 0/17 (0) 0/17 (0)
population without previous PTB
Temming et al,26 2016 CL ≤20 mm and no Those with a history of PTB and Unspecified 131/10,871 (1.2) 56/115 (48.7)a 35/115 (30.4)a NR
history of PTB CL≤25 mm or based on physical
examination
Son et al,27 2016 Recommended for CL Recommended when there is a cervical Not indicated 87/17609 (0.47) 40/87 (46) 31/87 (35.6) 31/87 (35.6)
≤20 mm dilatation on digital examination at <24
wk of gestation
Mishra et al,28 2018 Recommended for CL Unspecified Unspecified 2/147 (1.3) 1/2 (50) 1/2 (50) 1/2 (50)
≤25 mm
Souka et al,29 2019 CL ≤15 mm In the short-cervix (CL ≤15 mm) group, if Unspecified 113/10,506 (1.07) NR 14/113 (12.4) 12/113 (10.6)
further cervical shortening occurred
during follow-up despite PG treatment,
cervical cerclage was performed at the
discretion of the obstetrician
Figarella et al,30 2023 CL ≤25 mm Unspecified Unspecified 38/3468 (1.1)b 25/38 (65.8)b 1/38 (2.63) 1/38 (2.63)
Melchor Corcostegui et al, 2023
31
CL ≤25 mm Indicated for CL ≤10 mm Unspecified NR c
NRc NR NR
Stratulat et al,32 2024 Unspecified Unspecified Unspecified CL <25mm: 74/2680 (2.8) 74/74d 23/74 (31.1) 7/74 (9.45)
Total 4 studies: CL ≤25 mm Usually only for dilated cervix if no prior No report of use CL ≤25 mm (4 studies): 114/14,121 (0.81) 209/333 (62) 105/429 (24.4) 52/331 (15.7)
3 studies: ≤20 mm sPTB CL ≤20 mm (3 studies): 235/30,049 (0.78)
1 study: CL ≤15 mm CL ≤15 mm (1 study): 113/10,506 (1.07)
CL, cervical length; NR, not reported; PG, progesterone; PTB, preterm birth; sPTB, spontaneous preterm birth; tPTL, threatened preterm labor; TVU, transvaginal ultrasound.
a
Temming et al,26 2016 delivery outcome available only in 115/131 cases; b Reported in the ECHOCOL (“echo”=“ultrasound” and “col”=“cervix” in French) cohort study only; c Not reported for the whole population, only for those women presented with tPTL; d PG
among screened women was recommended in 98 women, whereas 74 women were diagnosed with a short cervix.
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024.

Systematic Review
May 2024 AJOG MFM
5
Systematic Review

(Tables 525−32 and 6,25−28,31,32 Supple-


TABLE 3
mentary Tables 3 and 4) showed that
Quality assessment of the included studies according to the Newcastle-
TVU CL screening was associated
Ottawa scale for cohort studies
with about an 8% to 22% decrease in
Author Y Selection Comparability Outcome sPTB compared with no screening.
Orzechowski et al, 2014 25
2014 $$$ $ $$$
Strengths and limitations
Temming et al,26 2016 2016 $$$ $ $$$
Our study has several strengths. By
Son et al,27 2016 2016 $$$ $$ $$$ selecting studies carried out over the
29
Souka et al, 2019 2019 $$$ − $$$ last decade, we could consistently pro-
30
Figarella et al, 2023 2023 $$$$ $ $$$
vide a preliminary estimate of the per-
formance of TVU CL as a routine
Melchor Corcostegui et al,31 2023 2023 $$$ $$ $$$ screening for sPTB. In general, the
Stratulat et al,32 2024 2024 $$$ $$ $$$ included studies are of good quality and
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024. have an overall low risk of bias, accord-
ing to the NOS scale and RoB2.
Moreover, because of the extensive sys-
tematic literature search, this is the first
(OR, 0.78 [95% CI, 0.52-1.16], P=.22, P=.01, I2=16%; Figure 5). No significant study that reports on a notable number
I2=22%), and <32 weeks (OR, 1.04 differences were found for sPTB <34 of patients undergone a universal mid-
[95% CI, 0.40−2.73] P=.93, I2=0%) weeks (OR, 0.85 [95% CI, 0.68−1.06], trimester TVU CL screening
(Supplemental Table 3). P=.14, I2=37%; Figure 6), and for sPTB (n=213,064). Another strength is that
When considering only studies com- <32 weeks (OR, 0.82 [95% CI, 0.66 all studies used only TVU as the
paring rates of sPTB after vs before a −1.01], P=.06, I2=0%; Figure 7) method for CL screening.
policy of implementation of TVU CL, (Table 625−28,31,32). Another strength is the rigorous
there was no significant difference for methodology of our statistical analysis.
sPTB <37 weeks (OR, 0.92 [95% CI, Comment In addition to the main results obtained
0.82−1.04], P=.20 I2=75%) and sPTB Main findings from the overall study population, we
<34 weeks (OR, 0.92 [95% CI, 0.73 The findings from this systematic performed 2 subgroup analyses to assess
−1.15], P=.46, I2=49%), whereas there review showed that, overall, universal results from different designs and meth-
was a significant decrease of the rate of midtrimester TVU CL screening signifi- ods. In one, universal TVU CL was
sPTB <32 weeks after the implementa- cantly decreased the risk of sPTB <32 compared with a nonscreening group
tion of TVU CL screening (OR, 0.84 weeks compared with unscreened over the same period; in the other, it
[95% CI, 0.75−0.94], P=.003, I2=4%) patients in an unselected risk popula- was compared with the period before its
(Supplemental Table 4). tion, whereas when performed in single- implementation. Once the similarities
In the focus of our study, in the sub- ton individuals without prior sPTB, between the data of subgroups and the
group of individuals with singleton ges- which was the focus of our study, TVU overall population were assessed, the
tations and without a prior sPTB, there CL screening was associated with a sig- feasibility of the analysis, including all
was a significant reduction of sPTB <37 nificant reduction in sPTB <37 weeks. the studies, was effectively established.
weeks (OR, 0.88 [95% CI, 0.79−0.97], Interestingly, 11 out of 12 analyses Furthermore, the subgroup analysis we

TABLE 4
The RoB2 tool for assessment of risk of bias in randomized controlled trials

D, domain; RoB2, Cochrane risk-of-bias.


Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024.

6 AJOG MFM May 2024


Systematic Review

FIGURE 2 reflects different recommendations


Forest plot for the risk of sPTB <37 weeks among national guidelines and local
protocols, but universal screening might
have had an increased effect in reducing
the rate of sPTB if all the included stud-
ies had considered CL 25 mm as a cutoff
to define a short cervix.2 Thus, out-
comes in the group of individuals
screened with TVU CL might have been
influenced by different preventive strat-
egies adopted after identifying a short
sPTB, spontaneous preterm birth. cervix. Moreover, only 60% of patients
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024. received progesterone after a diagnosis
of a short cervix, underestimating the
potential benefit of TVU CL implemen-
tation.
FIGURE 3 Another limitation is that, in some of
Forest plot for the risk of sPTB <34 weeks the included studies, individuals under-
going TVU CL were more likely to have
a prior cervical excision procedure and
to have other risk factors for sPTB.25
−27,30
After adjusting for these factors,
aORs were significant for PTB <37,
<34, and <32 weeks in the study with
the most prominent population.27

Comparison with existing literature


sPTB, spontaneous preterm birth.
This meta-analysis demonstrated that
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024.
universal TVU CL screening detected
short CL, defined mostly as ≤25 or
≤20 mm and detected in nearly 1% of
patients with singleton pregnancies, and
FIGURE 4 was associated with a significant risk
Forest plot for the risk of sPTB <32 weeks reduction of sPTB <32 weeks, when
prematurity most likely leads to worse
perinatal and neonatal outcomes,33,34
with an overall reduction of 16% in the
subset of patients screening with TVU
CL, than those not undergoing CL
screening.
Although there is a consensus for
TVU CL screening in singleton preg-
nancies with prior sPTB, the role of uni-
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024. versal midtrimester TVU CL
assessment in singleton gestations with-
out a prior sPTB is still a matter of
were focused on had a considerable that iatrogenic PTB inclusion might debate, with controversial recommen-
sample of patients with singleton gesta- have induced. dations provided from both national
tions and without prior sPTB screened In addition, we acknowledge our lim- and international guidelines (Supple-
with TVU CL in the midtrimester itations. The individual studies differ mentary Table 2). However, our results
(n=92,821). somewhat in the CL cutoff to define a showed that there was a significant
Moreover, considering as outcomes short cervix requiring preventive strate- reduction of 12% for sPTB <37 weeks
the occurrence of sPTB <37, <34, and gies, such as vaginal progesterone or and a lower trend of severe PTBs
<32 weeks, we provided a more accu- cerclage. For instance, 3 studies used a (namely <32 weeks) among patients
rate impact of TVU CL on the sponta- CL cutoff of 25 mm, 3 studies used with singleton gestations and no prior
neous onset of PTB, reducing the bias 20 mm, and 1 study used 15 mm. This PTB screened with TVU CL.

May 2024 AJOG MFM 7


8 AJOG MFM May 2024

Systematic Review
TABLE 5
Results for primary and secondary outcomes
Melchor
Stratulat Corcostegui Figarella Souka Mishra Son Temming Orzechowski
et al,32 2024 et al,31 2023 et al,30 2023 et al,29 2019 et al,28 2018 et al,27 2016 et al,26 2016 et al,25 2014 Total OR (95% CI) I2 P value
sPTB <37 wk 105/2441 (4.3) 77/4158 (1.85) 2944/165,524 (1.7) NA 15/147 (10.2) 701/17,609 (3.98) 639/9731(6.56) 65/1569 (4.14) 4546/201,179 (2.26) 0.92 (0.84−1.01) 52% .07
vs vs vs vs vs vs vs vs
140/3112 (4.5) 105/6378 (1.64) 3179/171,079 (1.85)a 12/149 (8.1) 2258/46,598 (4.85) 121/1661(7.28) 28/602 (4.65) 5843/229,579 (2.54)
sPTB <34 wk 32/2441 35/4158 (0.84) NA 89/7116 (1.25) NA 176/17609 (1.00) 207/9731 (2.13) 24/1569 (1.53) 563/42,624 (1.32) 0.87 (0.73−1.04) 35% .12
vs vs vs vs vs vs vs
33/3112 (1.1) 44/6378 (0.68) 73/4792 (1.52) 594/46,598 (1.3) 50/1661 (3.01) 8/602 (1.33) 729/58,351 (1.27)
sPTB <32 wk 19/2441 (0.78) 12/4158 (0.28) 423/165,524 (0.25) 36/7116 (0.51) 2/147 (1.36) 94/17,609 (0.53) NA 12/1569 (0.76) 598/198,564 (0.30) 0.84 (0.76−0.94) 0% .002
vs vs vs vs vs vs vs vs
20/3112 (0.6) 13/6378 (0.20) 513/171,079 (0.30)a 33/4792 (0.69) 1/149 (0.7) 328/46,598 (0.58) 5/602 (0.83) 913/232,720 (0.39)
Presented values are shown as n/N (%).
CI, confidence interval; NA, not applicable; OR, odds ratio; sPTB, spontaneous preterm birth
a
Figarella et al,30 2023 provided data as rates of PTB <37 wk, broken down by causes of PTB. To assess sPTB only, we considered only cases of preterm labor because it is not clear whether pPROM received induction or if an sPTB occurred; thus, considering preterm
prelabor rupture of membranes (PPROM) could also have biased our analysis, particularly for PTB <37 weeks. The authors requested the total number of PPROM cases that received induction; we are waiting for a reply.
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024.

TABLE 6
Subgroup analysis for sPTB in individuals without a history of sPTB
Melchor
Corcostegui
Subgroup 32
Stratulat et al, 2024 et al,31 2023 Mishra et al,28 2018 Son et al,27 2016 Temming et al,26 2016 Orzechowski et al,25 2014 Total OR (95% CI) I2 P value
sPTB <37 wk 79/2314 (3.4) 77/4158 (1.85) 15/147 (10.2) 701/17,609 (3.98) 507/8837 (5.7) 65/1569 (4.14) 1444/34,634 (4.16) 0.88 (0.79−0.97) 16% .01
vs vs vs vs vs vs vs
110/2969 (3.7) 105/6378 (1.64) 12/149 (8.1) 2258/46,598 (4.85) 96/1491 (6.4) 28/602 (4.65) 2609/58,187 (4.5)
sPTB <34 wk 18/2314 (0.8) 35/4158 (0.84) NA 176/17,609 (1.00) 162/8837 (1.8) 24/1569 (1.53) 415/34,487 (1.20) 0.85 (0.68−1.06) 37% .14
vs vs vs vs vs vs
23/2969 (0.8) 44/6378 0-68) 594/46,598 (1.05) 42/1491 (2.8) 8/602 (1.33) 711/58,038 (1.26)
sPTB <32 wk 10/2314 (0.4) 12/4158 (0.28) 2/147 (1.36) 94/17,609 (0.53) NA 12/1569 (0.76) 130/25,797 (0.50) 0.82 (0.66−1.01) 0% .06
vs vs vs vs vs vs
13/2969 (0.4) 13/6378 (0.20) 1/149 (0.7) 328/46,598 (0.58) 5/602 (0.83) 360/56,696 (0.63)
Presented values are shown as n/N (%).
CI, confidence interval; NA, not applicable; OR, odds ratio; sPTB, spontaneous preterm birth
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024.
Systematic Review

FIGURE 5 evidence to recommend routine univer-


Forest plot for the risk of sPTB <37 weeks among women without a history sal TVU CL screening, mostly because
of sPTB of the limitations inherent to the
included studies and the high heteroge-
neity of the study population that could
considerably affect the strength of the
results.36 In contrast to the 2019
Cochrane meta-analysis, we showed a
significant reduction of sPTB <32
weeks in an unselected risk population
and a significant 12% decrease in sPTB
in singletons without a prior sPTB
sPTB, spontaneous preterm birth.
screened with TVU CL.
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024.

Conclusions and Implications


Universal midtrimester TVU CL
FIGURE 6 screening in asymptomatic singleton
Forest plot for the risk of sPTB <34 weeks among women without a history gestations, of which >95% were without
of sPTB a prior sPTB, was associated with a sig-
nificant reduction in the risk of sPTB
<32 weeks; moreover, universal TVU
CL screening usually <24 weeks, specifi-
cally in asymptomatic singletons with-
out a prior SPTB, which was the focus
of our study, was associated with a sig-
nificant reduction in sPTB <37 weeks,
compared with no screening. These
sPTB, spontaneous preterm birth. results occurred despite the facts that
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024. patients with TVU CL screening were at
higher risk for sPTB, that CL was
defined as short as 25 mm in only 3 out
of 8 studies, and that only 60% of those
FIGURE 7 with a short CL were treated with vagi-
Forest plot for the risk of sPTB <32 weeks among women without a history nal progesterone as currently recom-
of sPTB mended. Given these results, our
systematic review supports guidelines,
such as those by ISUOG,2 that recom-
mend the implementation of a universal
TVU CL in asymptomatic singletons
without a prior sPTB at around 18−22
weeks, the time of the anatomy scan.
Well-designed RCTs with an adequate
sample size can also better elucidate this
issue. TVU CL screening between 16
sPTB, spontaneous preterm birth. and 23 weeks is already recommended
Hessami. Universal cervical length screening and risk of preterm birth. Am J Obstet Gynecol MFM 2024.
by the American College of Obstetricians
and Gynecologists, Society for Maternal-
Fetal Medicine, and other societies for
asymptomatic singletons with prior
TVU CL fulfills all the conditions effective. However, those opposing uni- sPTB11,12 (Supplemental Table 2). &
required by World Health Organization versal screening claim that the epidemi-
for a successful screening, as it clearly ology of PTB is such that the screening CRediT authorship contribution
detects individuals at risk for sPTB, and will not appreciably reduce its preva- statement
there is an effective preventive strategy lence in the population.35 Kamran Hessami: Conceptualization.
with vaginal progesterone once a short A previous Cochrane meta-analysis Elena D’Alberti: Writing − original
cervix is diagnosed that is also cost- published in 2019 failed to show enough draft. Daniele Di Mascio: Writing −

May 2024 AJOG MFM 9


Systematic Review

review & editing, Supervision. Vin- 11. Prediction and prevention of spontaneous 25. Orzechowski KM, Boelig RC, Baxter
cenzo Berghella: Writing − review & preterm birth: ACOG practice bulletin, number JK, Berghella V. A universal transvaginal
234. Obstet Gynecol 2021;138:e65–90. cervical length screening program for pre-
editing, Supervision. &
12. Society for Maternal-Fetal Medicine term birth prevention. Obstet Gynecol
(SMFM)McIntosh J, Feltovich H, Berghella V, 2014;124:520–5.
Supplementary materials Manuck T. The role of routine cervical length 26. Temming LA, Durst JK, Tuuli MG, et al.
screening in selected high- and low-risk women Universal cervical length screening: implemen-
Supplementary material associated with
for preterm birth prevention. Am J Obstet tation and outcomes. Am J Obstet Gynecol
this article can be found in the online ver- Gynecol 2016;215:B2–7. 2016;214. 523.e1−8.
sion at doi:10.1016/j.ajogmf.2024.101343. 13. Shennan AH, Story L. Royal College of 27. Son M, Grobman WA, Ayala NK, Miller ES.
Obstetricians, Gynaecologists. Cervical cerc- A universal mid-trimester transvaginal cervical
lage: Green-Top guideline no. 75. BJOG length screening program and its associated
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10 AJOG MFM May 2024

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