Timing of birth to improve outcomes in chronic or gestational hypertension: the WILL RCT.

BACKGROUND: For women with chronic or gestational hypertension who remain well, early term birth (at 37-38 weeks' gestation) may reduce maternal complications, caesareans and stillbirths, but it may increase neonatal morbidity compared with expectant care. Expectant care may increase costs. There are no high-quality data to guide care, which currently involves maternal-fetal surveillance and intervention for maternal or fetal compromise, which may be rapid or unexpected. OBJECTIVE: To investigate optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well. DESIGN: Pragmatic, unmasked, multicentre randomised trial with a health economic analysis. SETTING: Fifty United Kingdom hospitals. PARTICIPANTS: Inclusion: maternal age ≥ 16 years, chronic or gestational hypertension, singleton pregnancy, live fetus, 36+0-37+6 weeks' gestation and able to give documented informed consent. Exclusion: contraindication to either trial arm (e.g. pre-eclampsia), blood pressure ≥ 160/110 mmHg until controlled, major fetal anomaly anticipated to require neonatal care unit admission or participation in another timed birth trial. INTERVENTIONS: Planned early term birth at 38+0-3 weeks' (intervention) or 'usual care at term' (control, revised from 'expectant care until at least 40+0 weeks', August 2022). MAIN OUTCOME MEASURES: Maternal coprimary: composite of 'poor maternal outcome' (severe hypertension, maternal death or maternal morbidity and superiority hypothesis). Neonatal coprimary: neonatal care unit admission ≥ 4 hours (non-inferiority hypothesis). Each coprimary is measured until primary hospital discharge or 28 days post birth (whichever is earlier). Key secondary: caesarean birth. RANDOMISATION: 1 : 1 ratio, minimised for key prognostic variables: site, hypertension type and prior caesarean. BLINDING: It was not possible to mask care providers or participants to the intervention. For the coprimary maternal outcome, there was local site principal investigator/delegate sign-off based on review, masked to allocated group, of primary case notes. RESULTS: From 2019 to 2022, 403 participants were randomised (37% of target 1080) to intervention (n = 201) or control (n = 202). The funder stopped the trial during the coronavirus disease discovered in 2019 pandemic for delayed recruitment. In the intervention (vs. control) group, birth was a median of 0.9 weeks earlier (38.4, interquartile range 38.3-38.6 vs. 39.3, interquartile range 38.7-39.9 weeks). There was no evidence of a difference in 'poor maternal outcome' (13% vs. 12%, respectively; adjusted risk ratio 1.16, 95% confidence interval 0.72 to 1.87). For 'neonatal care unit admission ≥ 4 hours', the intervention was considered to be non-inferior to control, as the adjusted risk difference, 95% confidence interval upper bound did not cross the 8% pre-specified non-inferiority margin (7% vs. 7%, respectively; adjusted risk difference 0.003, 95% confidence interval -0.05 to +0.06), although event rates were lower than estimated. There was no evidence of a difference in caesarean (29% vs. 36%, respectively; adjusted risk ratio 0.81, 95% confidence interval 0.61 to 1.08). LIMITATIONS: Recruitment was 37% of the anticipated sample size (as above). CONCLUSIONS: Despite being unable to recruit to target in this study, we observed that most women with chronic or gestational hypertension required labour induction and planned birth at 380-3 weeks (vs. usual care), which resulted in birth an average of 6 days earlier and there were no differences in poor maternal outcome or neonatal morbidity. Our findings provide reassurance about planned birth at 380-3 weeks as a clinical option for these women. FUTURE WORK: An individual participant data meta-analysis is planned to address whether the intervention (vs. control) reduces caesarean; low adverse event rates would make unfeasible mounting another randomised trial. FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/167/123.