This chapter reports the results of the C-STICH trial. Some text in this chapter has been reproduced from our study results paper,22 published under the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited (https://creativecommons.org/licenses/by/4.0/).
Recruitment
The trial opened to recruitment on 30 August 2015 and recruited its first participant on 22 September 2015, completing recruitment to its revised sample size on 28 January 2021. The trial completed follow-up and subsequently the database was locked for statistical analysis on 26 January 2022. There was a pause in recruitment between 26 March 2020 and 5 May 2020 as a result of COVID-19 restrictions and further impacts on recruitment numbers were seen throughout 2020 and 2021 (see Figure 3). However, due to the emergency nature of the situation and the continued support of the non-redeployed clinicians, COVID-19 had minimal impact on the assessments and resulting data. Recruitment occurred across a large preterm-birth-prevention network of 56 trusts relating to 75 individual sites. Figure 4 is a geographical representation of the C-STICH network. Table 3 demonstrates the number of women recruited at each C-STICH trust with the top three sites being Guys and St Thomas, Birmingham Women’s Hospital and Leeds, recruiting 29% of the total sample.
FIGURE 3 Monthly recruitment into the C-STICH trial. (Figure not reproduced here; see the original article.)
FIGURE 4 Map of C-STICH recruiting centres. (Figure not reproduced here; see the original article.)
| Trust, n (%) | All participants(N = 2049) |
|---|---|
| Guy’s and St Thomas’ NHS Foundation Trust | 248 (12) |
| Leeds Teaching Hospitals NHS Trust | 178 (9) |
| Birmingham Women’s and Children’s NHS Foundation Trust | 161 (8) |
| University College London Hospitals NHS Foundation Trust | 99 (5) |
| University Hospitals of Leicester NHS Trust | 92 (5) |
| Chelsea and Westminster Hospital NHS Foundation Trust | 88 (4) |
| Barts Health NHS Trust | 84 (4) |
| Central Manchester University Hospital NHS Trust | 81 (4) |
| Heart of England NHS Foundation Trust | 78 (4) |
| NHS Lothian | 71 (4) |
| East Lancashire Hospitals NHS Trust | 70 (3) |
| University Hospitals Coventry and Warwickshire NHS Trust | 50 (2) |
| Imperial College Healthcare NHS Trust | 48 (2) |
| The Newcastle Upon Tyne NHS Foundation Trust | 46 (2) |
| Kingston Hospital NHS Foundation Trust | 37 (2) |
| Kettering General Hospital NHS Trust | 36 (2) |
| Portsmouth Hospitals NHS Trust | 35 (2) |
| Barking, Havering and Redbridge Hospitals NHS Trust | 32 (2) |
| Lewisham and Greenwich NHS Trust | 32 (2) |
| Aneurin Bevan University Health Board | 31 (2) |
| Sandwell and West Birmingham Hospitals NHS Trust | 28 (1) |
| Nottingham University Hospitals NHS Foundation Trust | 25 (1) |
| Liverpool Women’s NHS Foundation Trust | 24 (2) |
| Milton Keynes University Hospital NHS Foundation Trust | 24 (1) |
| NHS Fife | 19 (1) |
| City Hospitals Sunderland NHS Foundation Trust | 18 (1) |
| Royal free London NHS Foundation Trust | 18 (1) |
| University Hospitals Bristol NHS Foundation Trust | 18 (1) |
| Burton Hospitals NHS Foundation Trust | 17 (1) |
| Betsi Cadwaladr University Health Board | 16 (1) |
| Epsom and St Helier University Hospitals NHS Trust | 16 (1) |
| NHS Grampian | 16 (1) |
| Pennine Acute Hospitals NHS Trust | 16 (1) |
| The Mid Yorkshire Hospitals NHS Trust | 16 (1) |
| Cardiff and Vale | 15 (1) |
| Calderdale and Huddersfield NHS Trust | 14 (1) |
| NHS Greater Glasgow and Clyde | 14 (1) |
| The Royal Wolverhampton NHS Foundation Trust | 14 (1) |
| Bradford Teaching Hospital NHS Foundation Trust | 13 (1) |
| Wirral University Teaching Hospital NHS Foundation Trust | 13 (1) |
| Lancashire Teaching Hospitals NHS Foundation Trust | 12 (1) |
| Blackpool Teaching Hospitals NHS Foundation Trust | 9 (< 1) |
| The Shrewsbury and Telford Hospital NHS Trust | 9 (< 1) |
| Luton and Dunstable University Hospital NHS Foundation Trust | 8 (< 1) |
| Worcestershire Acute Hospitals NHS Trust | 8 (< 1) |
| Bolton NHS Foundation Trust | 6 (< 1) |
| North Bristol NHS Trust | 6 (< 1) |
| University Hospital Southampton NHS Foundation Trust | 6 (< 1) |
| The Dudley Group NHS Foundation Trust | 5 (< 1) |
| Warrington and Halton Hospitals NHS Foundation Trust | 5 (< 1) |
| York Teaching Hospital NHS Foundation Trust | 5 (< 1) |
| Northern Devon Healthcare NHS Trust | 4 (< 1) |
| Mid Essex Hospital Services NHS Trust | 4 (< 1) |
| Western Sussex University Hospitals NHS Trust | 3 (< 1) |
| Countess of Chester NHS Trust | 3 (< 1) |
| Princess Alexandra Hospital NHS Trust | 3 (< 1) |
| Abertawe Bro Morgannwg University Health Board | 1 (< 1) |
| Bedford Hospital NHS Trust | 1 (< 1) |
Participant flow
The participant flow is illustrated in Figure 5. A total of 2937 women were screened for eligibility. Of these, 326 women were not eligible to be randomised and 526 women were not randomised. In total, 2049 women were randomised to C-STICH, with 1025 women allocated to a monofilament suture thread and 1024 women allocated to a braided suture thread. Seven women were withdrawn from the study and a further 40 women were lost to follow-up, meaning that 2002 women (97.7% of those randomised) were available for analysis of the primary outcome. The reasons for withdrawal are provided in Table 4.
FIGURE 5 CONSORT diagram representing the flow of women through the C-STICH trial. (Figure not reproduced here; see the original article.)
| Monofilament suture(N = 1025) | Braided suture(N = 1024) | |
|---|---|---|
| Withdrawals, n (%) | 4 (< 1) | 3 (< 1) |
| Reason for withdrawal, n | ||
| Withdrawn consent, no reason provided | 1 | 2 |
| Ineligible, multiple pregnancy | 3 | 0 |
| Ineligible, no consent (randomised in error) | 0 | 1 |
Monthly recruitment into the C-STICH trial was consistent across the developed preterm birth network following the start-up phase.
Baseline data
The baseline demographic characteristics of women in the monofilament suture group and the braided suture group were comparable, with the minimisation algorithm ensuring balance across indication for cerclage, intended bladder dissection and concomitant progesterone intended use.
The randomised women had a mean age of 32.9 years (SD 5.0 years). Ethnicity, as documented within the maternity booking records, was similar across both groups: 57% were white, 19% were Asian, 19% were black and 5% were from other ethnic groups demonstrating a good representation of ethnicity. The mean body mass index (BMI) at booking was 27.7 kg/m2.
The majority of women (70%) had a cervical length scan prior to cerclage placement, with a mean shortest cervical length of 23.1 mm (SD 9.4 mm). The majority of women (61%) in whom a cerclage was placed were deemed at-risk on the basis of their history or the results of ultrasound. A total of 439 women (21%) had had a CC placed in a previous pregnancy and then opted for a repeat cerclage; 324 (16%) of women had a history of a mid-trimester loss and/or preterm birth and a short cervix in this pregnancy. Previous cervical surgery as a risk factor for preterm birth was present in 538 women (27%), of which the majority had undergone a single previous large loop excision of the cervical transformation zone (LLETZ) treatment. Further details are provided in Table 5.
| Monofilament suture(N = 1025) | Braided suture(N = 1023a) | |
|---|---|---|
| Participant characteristics | ||
| Gestational age at randomisation (weeks), mean (SD, N) | 16.5 (3.7, 1025) | 16.6 (3.8, 1023) |
| Maternal age (years), mean (SD, N) | 32.8 (5.0, 1025) | 33.0 (5.1, 1023) |
| Ethnicity, n (%) | ||
| White | 592 (58) | 566 (56) |
| Asian | 197 (19) | 196 (19) |
| Black | 181 (18) | 205 (20) |
| Mixed | 36 (4) | 37 (4) |
| Other | 13 (1) | 10 (1) |
| Missing | 6 | 9 |
| BMI at bookingb (kg/m2), mean (SD, N) | 27.2 (6.3, 347) | 28.1 (6.5, 337) |
| Pregnancy history | ||
| Gravida, median [IQR, N] | 2.0 [1.0–4.0, 1025] | 2.0 [1.0–4.0, 1023] |
| Parity, n (%) | ||
| Nulliparous | 307 (30) | 309 (30) |
| 1–3 | 661 (64) | 661 (65) |
| > 3 | 57 (6) | 53 (5) |
| Median [IQR, N] | 1.0 [0–2.0, 1025] | 1.0 [0–2.0, 1023] |
| Number of 1st trimester losses, median [IQR, N] | 0 [0–1.0, 1025] | 0 [0–1.0, 1023] |
| Number of mid-trimester losses, median [IQR, N] | 1.0 [0–1.0, 1025] | 1.0 [0–1.0, 1023] |
| Number of termination of pregnancies, median [IQR, N] | 0 [0–0, 1025] | 0 [0–0, 1023] |
| Number of live births ≤ 33 + 6 weeks, median [IQR, N] | 0 [0–1.0, 1025] | 0 [0–1.0, 1023] |
| Number of live births 34 to 36 + 6 weeks, median [IQR, N] | 0 [0–0, 1025] | 0 [0–0, 1023] |
| Number of live births ≥ 37 weeks, median [IQR, N] | 0 [0–1.0, 1025] | 0 [0–1.0, 1023] |
| Clinical characteristics | ||
| Cervical length ultrasound scan performed, n (%) | 709 (69) | 718 (70) |
| Shortest cervical length before cerclage,c mean (SD, N) | 23.2 (9.8, 709) | 23.1 (9.0, 718) |
| Cervical funnelling, n (%) | ||
| Yes | 239 (34) | 248 (34) |
| No | 419 (59) | 435 (61) |
| Do not know | 51 (7) | 35 (5) |
| Primary indication for cerclage,d n (%) | ||
| Deemed at risk of preterm birth through history or ultrasound | 620 (61) | 619 (61) |
| Insertion of cervical sutures in previous pregnancies | 219 (21) | 220 (21) |
| History of mid-trimester loss/premature birth with a shortened cervix | 164 (16) | 160 (16) |
| History of ≥ 3 previous mid-term losses/premature births | 22 (2) | 24 (2) |
| Planned cerclage technique includes bladder dissection,d n (%) | 174 (17) | 175 (17) |
| Intention to commence patient on progesterone,d n (%) | 415 (40) | 414 (40) |
| Previous cervical surgery, n (%) | 258 (26) | 280 (28) |
| Missing | 19 | 28 |
| Type of previous cervical surgery,e n (%) | ||
| 1 × previous LLETZ | 123 (48) | 131 (47) |
| 2 × previous LLETZ | 45 (18) | 53 (19) |
| Knife cone biopsy | 29 (11) | 32 (11) |
| Otherf | 59 (23) | 64 (23) |
| Missing | 2 | 0 |
Adherence
The CC was placed in 98% of women in both the monofilament and braided arms. In the women where the CC was not placed, the reasons included change of decision for cerclage, cervix too short, membranes ruptured and cervical bleeding. Most women (87%) had their cerclage placed within 3 days of randomisation. Adherence to the randomised allocation was 94% in the monofilament arm and 96% in the braided arm, as detailed in Table 6.
| Monofilament suture(N = 1025) | Braided suture(N = 1023a) | |
|---|---|---|
| Cerclage placed, n (%) | 999 (98) | 999 (98) |
| Cerclage not placed, n (%) | 23 (2) | 22 (2) |
| Missing | 3 | 2 |
| Reason cerclage not placed,b n | ||
| Participant refused/did not attend | 6 | 3 |
| Cervix too short | 7 | 14 |
| Cervix too dilated | 0 | 1 |
| Membranes ruptured | 5 | 1 |
| Cervical bleeding | 3 | 4 |
| Infection | 0 | 0 |
| Otherc | 10 | 6 |
| Time to cerclage placement (days),d,e n (%) | ||
| ≤ 3 | 866 (87) | 868 (87) |
| > 3 | 133 (13) | 131 (13) |
| Median [IQR, N] | 0 [0–1.0, 999] | 0 [0–1.0, 999] |
| Minimum–maximum | 0–48.0 | 0–51.0 |
| Suture material placed,d n (%) | ||
| Monofilament suture | 963 (96) | 23 (2) |
| Braided suture | 36 (4) | 976 (98) |
| Second suture placed following primary cerclage,d n (%) | 20 (2) | 9 (1) |
| Missing | 48 | 62 |
| Adherent, n (%) | 963 (94) | 976 (96) |
| Missing | 3 | 2 |
Primary outcome: pregnancy loss
Overall, 155 out of 1996 women (8%) had a pregnancy loss. The pregnancy loss rate in the monofilament suture group was 8% (80/1003) and the rate in the braided suture group was 8% (75/993) (RR 1.05, 95% CI 0.79 to 1.40). Full details of the components of pregnancy loss are detailed in Table 7.
| Monofilament suture(N = 1025) | Braided suture(N = 1023a) | RRb(95% CI) | RDc(95% CI) | p-value | |
|---|---|---|---|---|---|
| Pregnancy loss, n (%) | |||||
| Yes | 80 (8) | 75 (8) | 1.05 (0.79 to 1.40) | 0.002 (−0.02 to 0.03) | 0.73 |
| No | 923 (92) | 918 (92) | |||
| Missing | 22 | 30 | |||
| Type of pregnancy loss, n (%) | |||||
| Miscarriage | 44/80 (55) | 36/75 (48) | – | – | – |
| Spontaneous | 37 | 34 | |||
| Missed | 5 | 1 | |||
| Septic | 2 | 1 | |||
| Termination | 9/80 (11) | 14/75 (19) | |||
| Fetal anomaly | 4 | 3 | |||
| Maternal medical condition | 1 | 1 | |||
| Maternal sepsis | 2 | 6 | |||
| Otherd | 2 | 4 | |||
| Stillbirth | 8/80 (10) | 11/75 (15) | |||
| Othere | 0/80 (–) | 1/75 (1) | |||
| Neonatal death < 7 days | 19/80 (24) | 13/75 (17) | |||
Sensitivity and supportive analyses
In the per-protocol analysis of the primary outcome comparison, including only the 1939 women defined as adherent to their allocated suture thread, the rates of pregnancy loss remained similar across the two arms. Similarly, when women were analysed as per what suture thread they primarily received, there were no significant differences in pregnancy loss rates between the suture threads, as detailed in Table 8.
| Monofilament suture | Braided suture | RRa(95% CI) | RDb(95% CI) | |
|---|---|---|---|---|
| Pregnancy loss, n/N (%) | ||||
| Per-protocol analysisc | 67/946 (7) | 68/949 (7) | 0.99 (0.71 to 1.37) | −0.01 (−0.03 to 0.02) |
| As-treated analysisd | 67/968 (7) | 73/984 (7) | 0.93 (0.68 to 1.28) | −0.01 (−0.03 to 0.01) |
The sensitivity analyses to assess the impact of missing data using a ‘tipping point’ approach are summarised in Figures 6 and 7 and support the conclusion that our primary outcome analysis was robust to the small amount of missing data. In the first scenario, Figure 6 demonstrates that if we assume no cases of pregnancy loss (i.e. pregnancy loss = no) in all women with missing data in the braided arm, we must assume > 95% of the women with missing data in the monofilament arm had a pregnancy loss in order to change the conclusion of the outcome (in favour of a braided suture). In the second scenario, Figure 7 shows that even if we assume no cases of pregnancy loss (i.e. pregnancy loss = no) in all women with missing data in the monofilament arm and assume all women with missing data in the braided arm had a pregnancy loss, we do not change the conclusion of the outcome (i.e. under the most extreme assumptions the conclusion will not change in favour of a monofilament suture).
FIGURE 6 Tipping point analysis in the monofilament suture group. Risk ratios < 1 favour monofilament suture. a, In the base case, the estimate is derived from the model where we assume the event rate in the missing data is equal to the event rate in the non-missing data in the monofilament arm. All missing data in the braided arm are assumed to be non-events. (Figure not reproduced here; see the original article.)
FIGURE 7 Tipping point analysis in the braided suture group. Risk ratios <1 favour monofilament suture. a, In the base case, the estimate is derived from the model where we assume the event rate in the missing data is equal to the event rate in the non-missing data in the braided arm. All missing data in the monofilament arm are assumed to be non-events. (Figure not reproduced here; see the original article.)
Subgroup analyses
The output from the subgroup analyses for the primary outcome can be seen in Table 9. For indication for cerclage and current or intended progesterone use, there was no evidence of a differential treatment effect within these subgroups. For the key subgroup of bladder dissection, there was evidence of a potential differential treatment effect (p = 0.05 test for interaction). In women where it was planned to dissect their bladder during the CC, the rate of pregnancy loss was lower in the monofilament suture group than in the braided suture group [6/169 (4%) vs. 14/172 (8%)]; however, the numbers were small and the effect within this stratum was not statistically significant.
| Monofilament suture | Braided suture | Interactionp-value | RRa(95% CI) | Ratiob(95% CI) | |
|---|---|---|---|---|---|
| Key subgroup | |||||
| Planned bladder dissection, n/N (%) | |||||
| Yes | 6/169 (4) | 14/172 (8) | 0.05 | 0.44(0.17 to 1.12) | 0.37(0.01 to 0.74)c |
| No | 74/834 (9) | 61/821 (7) | 1.19(0.86 to 1.64) | ||
| Exploratory subgroups | |||||
| Indication for cerclage, n/N (%) | |||||
| A history of three or more previous mid-term losses or premature births (≤ 28 weeks) | 1/22 (5) | 2/24 (8) | 0.56 | 0.55(0.05 to 5.65) | 0.46(0.00 to 1.56)d |
| Insertion of cervical sutures in previous pregnancies | 14/213 (7) | 19/212 (9) | 0.72(0.37 to 1.39) | 0.60(0.14 to 1.07)e | |
| A history of mid-trimester loss or premature birth with a (current) shortened (≤ 25 mm) cervix | 16/163 (10) | 13/160 (8) | 1.20(0.60 to 2.41) | 1.01(0.20 to 1.82)f | |
| Women whom clinicians deem to be at risk of preterm birth either because of their history or because of the results of an ultrasound scan | 49/605 (8) | 41/597 (7) | 1.19(0.80 to 1.76) | REF | |
| Progesterone treatment (either current or intention to commence), n/N (%) | |||||
| Yes | 31/402 (8) | 27/403 (7) | 0.66 | 1.15(0.70 to 1.89) | 1.15(0.43 to 1.87)g |
| No | 49/601 (8) | 48/590 (8) | 1.00(0.68 to 1.46) | ||
Secondary outcome results
The secondary maternal outcomes are reported in Table 10. There was no evidence of any difference between the groups in any of the outcomes, apart from maternal sepsis and chorioamnionitis, which was lower in the monofilament group than in the braided group (RR 0.58, 95% CI 0.40 to 0.82 and RR 0.45, 95% CI 0.29 to 0.71, respectively).
| Maternal outcome | Monofilament suture | Braided suture | Estimate(95% CI) | RD(95% CI) |
|---|---|---|---|---|
| Time from conception to pregnancy end (weeks), median [IQR, N] | 37.9[35.6–39.1, 1008] | 38.0[35.4–39.1, 998] | 1.04a(0.95 to 1.14) | – |
| Miscarriage and previable neonatal death, n/N (%) | 60/1003 (6) | 49/993 (5) | 1.21b(0.84 to 1.74) | 0.01c(−0.01 to 0.03) |
| Still birth, n/N (%) | 8/1003 (1) | 11/993 (1) | 0.72b(0.29 to 1.77) | 0.00d(−0.01 to 0.01) |
| Gestational age at deliverye (weeks). mean (SD, N) | 37.2 (3.3, 926) | 37.2 (3.4, 919) | 0.02f(−0.29 to 0.32) | – |
| Gestational age at delivery < 28 weeks,e n/N (%) | 34/926 (4) | 35/919 (4) | 0.96g(0.61 to 1.53) | 0.00d(−0.02 to 0.02) |
| Gestational age at delivery < 32 weeks,e n/N (%) | 77/926 (8) | 86/919 (9) | 0.89b,h(0.66 to 1.19) | −0.01c,h(−0.03 to 0.02) |
| Gestational age at delivery < 37 weeks,e n/N (%) | 258/926 (28) | 265/919 (29) | 0.96b,h(0.83 to 1.11) | −0.01c,h(−0.05 to 0.03) |
| Time from conception to onset of spontaneous vaginal deliveryi (weeks), median [IQR, N] | 37.9[35.6–39.4, 342] | 38.0[35.7–39.6, 420] | 1.07a(0.91 to 1.26) | - |
| Maternal sepsis, n/N (%) | 39/1000 (4) | 67/988 (7) | 0.58j(0.40 to 0.82) | −0.03c(−0.05 to −0.01) |
| PPROM, n/N (%) | 199/1006 (20) | 201/997 (20) | 0.98b(0.82 to 1.16) | −0.01c (−0.04 to 0.03) |
| Mode of initiation of birth, n/N (%) | ||||
| Spontaneous | 446/957 (47) | 437/951 (46) | 0.99b(0.91 to 1.07) | −0.01c(−0.05 to 0.04) |
| Induced | 327/957 (34) | 338/951 (36) | ||
| Caesarean section | 184/957 (19) | 176/951 (18) | ||
| Mode of delivery, n/N (%) | ||||
| Vaginal | 490/953 (51) | 513/943 (54) | 0.94k(0.86 to 1.02) | −0.03l(−0.08 to 0.01) |
| Operative vaginal | 112/953 (12) | 81/943 (9) | ||
| Caesarean | 351/953 (37) | 349/943 (37) | ||
| Vaginal bleeding, n/N (%) | 142/995 (14) | 154/988 (16) | 0.91j(0.74 to 1.13) | −0.01c(−0.04 to 0.02) |
| Steroid use, n/N (%) | 294/1000 (29) | 303/993 (31) | 0.97b(0.85 to 1.10) | −0.01c(−0.05 to 0.03) |
| Chorioamnionitis, n/N (%) | 26/956 (3) | 57/957 (6) | 0.45j(0.29 to 0.71) | −0.03d(−0.05 to −0.01) |
| Maternal pyrexia (intrapartum), n/N (%) | 22/1003 (2) | 35/992 (4) | 0.98j(0.65 to 1.48) | 0.00c(−0.02 to 0.02) |
| Maternal pyrexia (postnatal), n/N (%) | 44/1001 (4) | 44/989 (4) | 0.80j(0.43 to 1.51) | −0.01c(−0.02 to 0.01) |
| Admission to HDU (pre delivery), n/N (%) | 17/1003 (2) | 21/996 (2) | 0.80j (0.43 to 1.51) | −0.01c(−0.02 to 0.01) |
| Admission to ITU (pre delivery), n/N (%) | 0/1002 (–) | 1/995 (< 1) | – | – |
| Admission to HDU (post delivery), n/N (%) | 52/999 (5) | 50/986 (5) | 1.02j(0.70 to 1.49) | 0.00c(−0.02 to 0.02) |
| Admission to ITU (post delivery), n/N (%) | 1/998 (< 1) | 5/986 (1) | 0.20b(0.02 to 1.69) | 0.00d(−0.01 to 0.00) |
For conception to pregnancy end, no difference was demonstrated between a monofilament suture thread and a braided suture thread (see Figure 8).
FIGURE 8 Kaplan–Meier plot for time from conception to pregnancy end. (Figure not reproduced here; see the original article.)
The neonatal outcomes are presented in Table 11. There was no evidence of a difference between any of the outcomes collected.
| Neonatal outcomea | Monofilament suture | Braided suture | Estimate(95% CI) | RD(95% CI) |
|---|---|---|---|---|
| Early neonatal death (< 7 days), n/N (%) | 5/920 (1) | 3/913 (< 1) | 1.63b(0.39 to 6.80) | 0.00c(0.00 to 0.01) |
| Late neonatal death (≥ 7 and < 28 days), n/N (%) | 1/920 (< 1) | 0/913 (–) | – | – |
| Birth-weight (centile), mean (SD, N) | 41.0 (29.2, 923) | 42.4 (28.8, 912) | −1.44d(−4.09 to 1.21) | – |
| Small for gestational age, n/N (%) | 147/923 (16) | 132/912 (14) | 1.10e(0.84 to 1.45) | 0.02f(−0.02 to 0.05) |
| Resuscitation at birth, n/N (%) | 61/916 (7) | 62/911 (7) | 0.98b(0.70 to 1.38) | 0.00f(−0.02 to 0.02) |
| Additional care, n/N (%) | 265/920 (29) | 268/912 (29) | 0.98b(0.85 to 1.13) | 0.00f(−0.05 to 0.04) |
| Length of stay in additional care, median [IQR, N] | ||||
| SCBU | 4.0 [0–15.0, 243] | 4.0 [0–16.0, 258] | – | – |
| NICU | 0 [0–7.0, 231] | 0 [0–6.0, 247] | – | – |
| HDU | 0 [0–4.0, 233] | 0 [0–4.0, 244] | – | – |
| Transitional care | 0 [0–1.5, 220] | 0 [0–1.0, 241] | – | – |
| Antibiotics within 72 hours after birth, n/N (%) | 236/915 (26) | 249/906 (27) | 0.94e(0.81 to 1.09) | −0.01f(−0.06 to 0.03) |
| Sepsis (clinically diagnosed), n/N (%) | 102/909 (11) | 113/904 (13) | 0.90e(0.71 to 1.14) | −0.01f(−0.04 to 0.02) |
| Sepsis (confirmed), n/N (%) | 15/908 (2) | 19/904 (2) | – | – |
| Early neurodevelopmental morbidity, n/N (%) | 13/912 (1) | 19/903 (2) | – | – |
| Respiratory support, n/N (%) | 130/915 (14) | 144/910 (16) | 0.90e(0.72 to 1.11) | −0.01f(−0.05 to 0.02) |
| Days on respiratory support, median [IQR, N] | 5.0[1.0–28.0, 125] | 4.0[1.0–27.0, 142] | – | – |
| Supplementary oxygen requirements, n/N (%) | 27/910 (3) | 30/914 (3) | 0.91b(0.54 to 1.52) | 0.00f(−0.02 to 0.01) |
| Necrotising enterocolitis (Bell’s stage 2 or 3), n/N (%) | 7/908 (1) | 11/909 (1) | – | – |
| Retinopathy of prematurity requiring laser treatment, n/N (%) | 4/906 (< 1) | 5/908 (1) | – | – |
| Disabilities, n/N (%) | 1/910 (< 1) | 5/904 (1) | – | – |
| Details of disabilities, n | ||||
| Brachial plexus injury | 0 | 2 | – | – |
| Hypoxic-ischemic encephalopathy (grade one) | 0 | 1 | ||
| Feeding difficulty | 0 | 1 | ||
| Retinopathy of prematurity | 1 | 1 | ||
| Hearing disability | 0 | 1 | ||
| Congenital anomalies, n/N (%) | 18/914 (2) | 18/909 (2) | – | – |
| Details of congenital anomalies, n | ||||
| Chromosomal abnormalities | 2 | 4 | – | – |
| Cleft lip and cleft palate | 3 | 3 | ||
| Congenital malformations and deformations of the musculoskeletal system | 5 | 4 | ||
| Congenital malformations of genital organs | 2 | 0 | ||
| Congenital malformations of the circulatory system | 5 | 5 | ||
| Congenital malformations of the digestive system | 2 | 0 | ||
| Congenital malformations of the nervous system | 0 | 1 | ||
| Congenital malformations of the urinary system | 1 | 2 | ||
Cervical cerclage is known to be associated with both insertion and removal risks (see Table 12). Within C-STICH, 4% of women in the monofilament group and 3% in the braided group experienced insertion complications. There were two cases of ruptured membranes during CC and these both occurred within the monofilament group. The most common insertion complication was bleeding from the cervix, which occurred in 4% of women in the monofilament group and 3% of women in the monofilament group. With regard to cerclage removal complications, there was a higher proportion of women who experienced a removal complication in the monofilament group compared with the braided group RR 1.25 (95% CI 1.15 to 1.36). Removal complications comprised clinician-judged difficulty in suture removal and an increased need for anaesthetic, with 41% of women requiring an anaesthetic for removal in the monofilament group compared with 32% in the braided group. There were no statistically significant differences in the number of women who experienced a SAE between the two treatment groups. There was a small increase in the number of neonates who experienced a SAE in the braided group but overall, the numbers were small. Twelve maternal SAEs and one neonatal SAE were considered to be related to the trial allocation and classified as unexpected.
| Monofilament suture | Braided suture | RR(95% CI) | RD(95% CI) | |
|---|---|---|---|---|
| Cerclage complications | ||||
| Cerclage placement complication,a n/N (%) | 43/999 (4) | 30/999 (3) | 1.44b(0.91 to 2.27) | 0.01c(0.00 to 0.03) |
| Details of cerclage placement complications,a n/N (%) | ||||
| Cervical laceration | 5/999 (1) | 2/999 (< 1) | – | |
| Bleeding from cervix | 39/999 (4) | 29/999 (3) | – | |
| Ruptured membranes | 2/999 (< 1) | 0/999 (–) | – | |
| Bladder injury | 0/999 (–) | 0/999 (–) | – | |
| Cerclage removal complication,d n/N (%) | 506/896 (56) | 373/883 (42) | 1.25c(1.15 to 1.36) | 0.14e(0.10 to 0.18) |
| Details of cerclage removal complications,d n/N (%) | ||||
| Cervical tears | 20/863 (2) | 8/865 (1) | – | |
| Difficulty in removal | 276/885 (31) | 128/875 (15) | – | |
| Need for anaesthetic | 382/934 (41) | 293/922 (32) | – | |
| Adverse events | ||||
| Total number of women experiencing a SAE, n/N (%) | 108/1025 (11) | 99/1023f (10) | – | |
| Number of maternal SAEs reported, n | 126 | 115 | – | |
| Total number of neonates experiencing a SAE, n/N (%) | 8/1025 (1) | 19/1023f (2) | – | |
| Number of neonate SAEs reported, n | 15 | 25 | – | |
| Total number of women experiencing a SUSAR, n/N (%) | 6/1025 (1) | 3/1023f (< 1) | – | |
| Number of maternal SUSAEs reported, n | 9 | 3 | – | |
| Total number of neonates experiencing a SUSAR, n/N (%) | 1/1025 (< 1) | 0/1023f (–) | – | |
| Number of neonate SUSARs reported, n | 1 | 0 | – | |