Abstract
Background
Preterm labour associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.
Methods and findings
We conducted an open label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1st April 2015 to 14th February 2019, 2228 women with a twin pregnancy underwent cervical length screening between 18 weeks, 0 days and 20 weeks, 6 days of gestation. 503 women with cervical length ≤35mm were randomly assigned to pessary in addition to standard care (n=250, mean age 32.4 years, mean cervical length 29mm, with pessary inserted in 230 women [92·0%]) or standard care alone (n=253, mean age 32.7 years, mean cervical length 30mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation was present in 46/250 (18·4%) in the pessary group compared to 52/253 (20·6%) standard care alone (adjusted odds ratio [aOR] 0·87 [95% CI 0·55–1·38], p=0.54). The primary neonatal outcome, a composite of any of: stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis or proven sepsis, from birth to 28 days after the expected date of delivery, was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0·54–1.36] p=0·50). The positive and negative likelihood ratios (LR) of a short cervix ≤ 35 mm to predict preterm birth before 34 weeks were 2·14 and 0·83 respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT 2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (RR: 0·74 [95% CI 0·50–1·11], p=0.15). No women died in either arm of the study, 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p=0.53). Study limitations include lack of power either to exclude a smaller than 40% reduction in preterm labour associated preterm birth, or to be conclusive about subgroup analyses.
Conclusions
These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.
Preterm labour associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.
Methods and findings
We conducted an open label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1st April 2015 to 14th February 2019, 2228 women with a twin pregnancy underwent cervical length screening between 18 weeks, 0 days and 20 weeks, 6 days of gestation. 503 women with cervical length ≤35mm were randomly assigned to pessary in addition to standard care (n=250, mean age 32.4 years, mean cervical length 29mm, with pessary inserted in 230 women [92·0%]) or standard care alone (n=253, mean age 32.7 years, mean cervical length 30mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation was present in 46/250 (18·4%) in the pessary group compared to 52/253 (20·6%) standard care alone (adjusted odds ratio [aOR] 0·87 [95% CI 0·55–1·38], p=0.54). The primary neonatal outcome, a composite of any of: stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis or proven sepsis, from birth to 28 days after the expected date of delivery, was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0·54–1.36] p=0·50). The positive and negative likelihood ratios (LR) of a short cervix ≤ 35 mm to predict preterm birth before 34 weeks were 2·14 and 0·83 respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT 2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (RR: 0·74 [95% CI 0·50–1·11], p=0.15). No women died in either arm of the study, 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p=0.53). Study limitations include lack of power either to exclude a smaller than 40% reduction in preterm labour associated preterm birth, or to be conclusive about subgroup analyses.
Conclusions
These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.
| Original language | English |
|---|---|
| Article number | e1003506 |
| Number of pages | 18 |
| Journal | PLoS Medicine |
| Volume | 18 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 29 Mar 2021 |
Bibliographical note
Publisher Copyright:© 2021 Norman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords
- Twin -pregnancy
- preterm birth
- preterm labour
- cervical pessary
- randomised trial