Against: Expectant management for women with prelabour rupture of membranes in the presence of GBS at 34–37 weeks' gestation

A number of randomised trials have evaluated induction of labour (IoL) versus expectant management (EM) for late preterm prelabour rupture of membranes (PPROM) occurring between 34 and 37 weeks of gestation, including the PPROMEXIL-trials (van der Ham et al. 2012 PLoS Med;9:e1001208; van der Ham et al. Am J Obstet Gynecol 2012;207:276.e1–10) and the PPROMT trial (Morris et al. Lancet 2016;387:444–52). In 2018 the results of three trials were combined in an individual patient data meta-analysis (IPD-MA) (Quist-Nelson et al. Obstet Gynecol 2018:131:269–79). The IPD-MA showed that sepsis rates did not significantly differ between IoL and EM (2.6% after IoL vs. 3.5% after EM, RR 0.74, 95% CI 0.47–1.15). Therefore, both IoL and EM are considered reasonable options, through carefully balancing the benefits and the risks from both maternal and neonatal perspectives. However, the subgroup of patients with group B streptococcus (GBS) vaginal colonisation require very careful consideration. In patients testing negative for GBS the current data supports EM; however, for patients testing positive for GBS the results lean towards delivery in the late preterm period. Notably, patients who tested positive for GBS were managed differently in the PPROMEXIL and PPROMPT studies. In the Dutch PPROMEXIL-trials, 40% of patients received antibiotics during admission or labour (primarily for an active intrauterine infection or positive GBS). At study entry, GBS testing was performed and results were available after 18–72 h. Mostly patients testing positive for GBS received antibiotics, according to national guidelines, and delivery was pursued. The risk for neonatal sepsis in the GBS subgroup was significantly higher after EM (1.8% after IoL vs. 15.2% after EM, OR 0.10, 95% CI 0.01–0.84); therefore, in the PPROMEXIL-trials IoL was strongly advised (Tajik et al. 2014 BJOG;121:1263–72). In contrast, 92% of patients in the Australian PPROMT study received antibiotics before delivery and management did not differ for patients that tested positive for GBS, with the continuation of randomised treatment. In PPROMT, the risk of neonatal sepsis did not significantly increase in the case of EM (3.6% after IoL vs. 3.8% after EM, RR 0.94, 95% CI 0.20–4.54). When combining these contrasting studies in an IPD-MA, a pre-planned subgroup analysis showed a reduced risk of neonatal sepsis after IoL in patients with a positive vaginal culture (including GBS) (2.3% after IoL vs. 6.5% after EM, adjusted RR 0.35, 95% CI 0.14–0.86, interaction p = 0.04). Even in sensitivity analysis controlling for antibiotic administration the benefits of IoL still held. Although these results may be driven by the PPROMEXIL data above, in PPROMT the risk of neonatal sepsis in the case of any positive vaginal culture was nearly doubled (from 2.1% to 4.7%, RR 0.45, 95% CI 0.14–1.44). Therefore, given the morbidity of neonatal sepsis and the data showing increased neonatal sepsis rates in patients testing positive for GBS, immediate delivery should be considered. Patients should be made aware of the risk for neonatal sepsis when opting for EM. Currently, we are awaiting the results of the long-term follow-up study of the PPROMEXIL-trials, evaluating neurodevelopment in the offspring at the age of 10 years (de Ruigh et al. BMJ Open 2021;11:e046046). These results may influence the recommendations for patients with late PPROM. Based on the available evidence and depending on the use of antibiotics, in patients with PPROM at 34–37 weeks of gestation who test positive for GBS, IoL should be discussed and offered to the patient. Overall, individualised care through shared decision making is recommended, with clear counselling regarding the potential risk of neonatal sepsis resulting from GBS. BWM is supported by a National Health and Medical Research Council (NHMRC) Practitioner Fellowship (GNT1082548). BWM reports consultancy fees for ObsEva, Merck KGaA and Guerbet. Np other authors report any conflicts of interest. Completed disclosure of interests form available to view online as supporting information. Data sharing is not applicable to this article as no new data were created or analyzed in this study. Appendix S1. Appendix S2. Appendix S3. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.