Re: Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS): multicentre, open label, randomised, superiority trial
We read with interest the Swepis trial where induction at 41+0 or expectant management were compared.1 We are doubtful that the conclusions drawn are valid because; 1/. There was no difference in main outcome, only in ad-hoc analysis 2/. The incidence of stillbirth in 41st week is higher than expected. 3/. All stillbirths occurred as study violations to the predetermined published study protocol.2
We have known for more than 20 years that postdate pregnancies are at an increased risk of stillbirth, mainly attributed to a 10-fold increased risk among growth restricted fetuses.3 Therefore, women in the Swepis trial, with uncomplicated healthy singleton pregnancies were planned to be randomized after a 41+0 week ultrasound (US) scan to exclude cases small-for-gestational age (SGA) or oligohydramniosis.2 There was no difference in main outcome, i.e., a composite outcome comprising both mortality and specified morbidity (2.4% vs. 2.2%). Due to an ad-hoc analysis showing 0.36% stillbirth in the expectant management arm the study was stopped after having included 2760 out of ~10,000 planned. The authors draw the conclusion that induction ought to be offered to women no later than 41+0 week.1
After the results of the study by Divon et al.,3 the two units at Karolinska University Hospital made different changes to reduce the postdate risk.3 One unit introduced, routine 41st week US scan and the other unit, US scan based on risk factors.3 This permitted us to do a quasi-randomized assessment showing a 60% reduced risk of postterm severe adverse outcome at the unit using routine 41 week US scan.4 As a consequence, in 2014 all 6 delivery units in Stockholm area implemented a 41+0 week free of charge routine US scan. We are in the process of validating the outcome of this 41 week US scanning in terms of IUD during the years 2015 to 2018. Among the 115,636 deliveries in the Stockholm region, there were 15 stillbirths after 41+0 weeks out of 22,434 (0.067%) pregnancies. Thus, the risk of stillbirth in pregnancies passing 41+0 week in the selected low-risk pregnancies included in the Swepis trial was 5-fold higher than our pregnancy population in the Stockholm region (OR 5.4 95%CI 2.0-15.0). Thus, the stillbirth risk in Swepis is higher than expected. Our finding of a 0.067‰ incidence of stillbirth is in agreement with the prior report of 42st week US scanning in the 1990ies, showing an incidence of stillbirth in the 42nd week of 0.067%.5 In that study there was a 4-fold lower risk of severe adverse outcome, including a 6-fold lower risk of stillbirth among in–utero identified SGA cases as compared to non-identified SGA cases.5
The major strength in the Swepis study protocol was that it aimed to compare induction at 41st week, or not, in a population not growth restricted. Thus, Swepis was planned as a scientifically sound RCT with the potential to add to our knowledge. However, it is an ethical and methodological problem that none of the pregnancies with stillbirth in Swepis had performed the stipulated US scan before randomization, i.e., all occurred as study violations (ISRCTN26113652).2 Due to non-adherence to the study protocol, it is not possible to determine if the poor result in terms of stillbirth is a consequence of a missed 41 week US scan, by chance, or due to expectant management. In a study aiming to change clinical management, high standards are needed.
The authors conclude that induction at 41+0 week “could be one (of few) interventions that reduces the risk of stillbirths”. A more evidence based alternative could be to perform a late routine US scan with the aim to identify SGA pregnancies or other signs of growth restriction.4 5 In the Stockholm region, where such a regime is offered, a 5-fold lower incidence of stillbirth after 41+0 weeks is observed, as compared to the Swepis data, i.e., more than 50 stillbirths are avoided yearly.
1. Wennerholm UB, Saltvedt S, Wessberg A, Alkmark M, Bergh C, Brismar Wendel S, et al. Swepis. BMJ 2019;367:6131.
2. Elden H, Hagberg H, Wessberg A, Sengpiel V, Herbst A, Bullarbo M, et al. Study protocol of SWEPIS a Swedish multicentre register based randomised controlled trial to compare induction of labour at 41 completed gestational weeks versus expectant management and induction at 42 completed gestational weeks. BMC Pregnancy Childbirth 2016;16:49.
3. Divon MY, Haglund B, Nisell H, Otterblad PO, Westgren M. Fetal and neonatal mortality in the postterm pregnancy: the impact of gestational age and fetal growth restriction. Am J Obstet Gynecol 1998;178(4):726-31.
4. Lindqvist PG, Pettersson K, Moren A, Kublickas M, Nordstrom L. Routine ultrasound examination at 41 weeks of gestation and risk of post-term severe adverse fetal outcome: a retrospective evaluation of two units, within the same hospital, with different guidelines. BJOG 2014;121(9):1108-15.
5. Lindqvist PG, Molin J. Does antenatal identification of small-for-gestational age fetuses significantly improve their outcome? Ultrasound Obstet Gynecol 2005;25(3):258-64.
Competing interests: No competing interests