Results
The P5 trial screened 8168 women, of whom 7857 were singleton and 1081
had CL ≤30mm. In a CL distribution curve including only singleton
pregnancies, 1081 women corresponds to 13.7% of total. For this study,
we excluded 310 twins, 14 women without CL data and 3 women in
progesterone group without gestational age at birth. We included 430
singleton women with CL ≤30 mm randomized to progesterone alone and we
projected this group to correspond to 13.7% of CL ≤30mm for our
analysis. To complete our final sample and reach the complementary
86.3% of CL >30mm, we randomly selected 2709 singleton
women with CL >30 mm, comprising a total of 3139 women
(Figure S1).
Among women with CL ≤30mm receiving progesterone, compliance was 82%.
Regarding obstetric history, 46.2% (1449) of our sample were
nulliparous, 10.1% (318) had at least one previous PTB and 24.4% had a
previous abortion. The prevalence of PTB at <37 weeks was
14.43%: sPTB at <37 weeks was found in 7.1% (223/3139); and
sPTB at <37 weeks in women with CL ≤30mm receiving
progesterone was 16.7% (72/430). Of all 223 women who had a sPTB,
32.3% (72/223) had a CL ≤30mm. Sociodemographic information is listed
in Table 1.
Logistic univariate regression analysis for PTB at <37 weeks
identified the following risk factors: low body mass index (BMI ≤ 18.5)
(OR = 1.95, 95%CI = 1.05–3.43,); hypertension (OR 2.15, 1.5–3.02);
endocrinopathies (OR = 1.73, 1.27–2.33); previous PTB (OR = 2.51,
1.88–3.32); previous abortion (OR = 1.43, 1.15–1.78); cervical length
≤30mm (CL 25-≤ 30mm OR 2.10, 1.47 - 2.95; CL 20-25mm OR 2.55, 1.71 -
3.72; CL 15-20mm OR 3.33, 1.74 - 6.11; CL 10-15 mm OR = 6.40,
2.53–5.99, and CL ≤10mm OR 11.17, 4.37–30.55); funneling at
measurement (OR = 5.03, 3.36–7.49); and sludge at measurement (OR =
3.50, 2.24–5.39). Considering only sPTB at <37 weeks, these
factors presented an even higher association except for comorbidities
and low BMI. A comparison between sPTB at < 34 weeks and ≥ 34
weeks illustrates that there is a robust association among risk factors
and sPTB<34 weeks, highlighting CL≤10mm (OR 44.9,
15.45–125.87) and 10–15mm (OR13.32, 2.98–43.09), funneling at
measurement (OR 10.22, 5.57–17.95) and sludge at measurement (OR =
5.61, 2.63–10.86) (Table 2).
A multivariate logistic regression analysis also identified an
association between CL ≤30mm and PTB (CL 25-≤30mm ORa 1.80, 1.23-2.63;
CL 20-25mm ORa 1.93, 1.22-3.06; CL 10-20mm ORa 3.04, 1.54-5.71, and CL
≤10mm ORa 3.82, 1.12-13.06). The ORa for cervical length <30mm
increased when considered only sPTB <37 (CL 25-≤30mm ORa 2.2,
1.35-3.57; CL 20-25mm ORa 2.07, 1.14-3.76; CL 10-20mm ORa 4.59,
2.12-9.94, and CL≤10mm ORa 6.71, 1.79-25.27). For sPTB<34,
there was an association with CL ≤25 mm (Table S2). We also performed a
multivariate analysis for cervical length and PTB <37, sPTB
<37 and sPTB<34 weeks with adjusted odds ratios for
BMI, comorbidities, obstetrical history, funneling and sludge and the
association between CL<30mm and PTB and sPTB<37 was
also significant. Again, moderate sPTB (sPTB<34) where
associated with CL ≤25mm (Table S3).
We identified an inverse association between CL and sPTB at
<37 weeks (OR = 7.84, 5.5–11.1). The ROC curve analysis to
predict PTB at < 37 weeks and sPTB at <37 weeks
showed low performance, with area under the curve (AUC) of 0.598
(0.57–0.63) and 0.643 (0.60–0.68), respectively. For sPTB at
<34 weeks and sPTB at <32 weeks the ROC curve
presented a moderate performance with AUC of 0.665 (0.59–0.74) and
0.718 (0.62–0.81), respectively; and for sPTB at <28 weeks
the ROC curve demonstrated good performance, with AUC of 0.820
(0.63–0.95) (Table S4 and Figure 1).
The best cutoff point to predict PTB at <37 weeks was 31.75
mm, with 31.3% sensitivity and 84.4% specificity. To predict sPTB at
<37 weeks the best cutoff point was 31.75mm, with 37.2%
sensitivity and 84.3% specificity. TVU provided good prognostic results
combining: AUC (0.82), high sensitivity (73.7%) and acceptable
specificity (91.3%) rates for sPTB at <28 weeks’ gestation
(Table S4). The best cutoff points to predict sPTB at <34,
<32 and <28 weeks were 28.05, 28.05 and 26.55 mm,
respectively.
Kaplan-Meyer survival analysis demonstrated an association between
extremely severe, severe, moderate and late PTB and CL ≤25 mm, and an
association between CL of 25–30mm and late PTB (p<0.001) (Figure 2). The number needed to screen (NNS) to
detect one true positive sPTB <34 weeks in women with CL ≤25mm
is 121. To prevent one sPTB <34 weeks among women with CL
≤25mm, the number needed to treat (NNT) with vaginal progesterone
prophylaxis is 1812. Assuming that all women with CL
≤25mm are treated with vaginal progesterone, we estimated that the
number of TVU necessary to identify 18 women with CL ≤25mm and prevent
one sPTB <34 weeks is 248.