The clinical and cost effectiveness of tight versus less tight glucose control around the time of birth in pregnancies complicated by gestational diabetes: the GILD trial

RESEARCH QUESTION: In pregnant women/birthing people with gestational diabetes (Population) around the time of birth, is less tight blood glucose control (Intervention) non-inferior to tight control (Comparison) in relation to the incidence of neonatal hypoglycaemia and neonatal unit admission (Outcome)?

BACKGROUND: Gestational diabetes (GDM) affects 8% (~50,000) of UK pregnant women/birthing people and is increasing (1). South Asian women/birthing people have a two-fold increased risk, compared to White European women/birthing people (2). If the mother/birthing person is hyperglycaemic, placental transfer of glucose leads to fetal hyperglycaemia which stimulates fetal hyperinsulinism.

At birth, the placental supply of glucose is cut-off and persistent high insulin levels can cause neonatal hypoglycaemia. Maintaining stable maternal intrapartum blood glucose could prevent this. Neonatal hypoglycaemia occurs in 7-20% of babies born to women/birthing people with GDM (3, 4).

In addition, around 10% of babies born to women/birthing people with GDM are admitted to the neonatal unit, causing anxiety, mother-baby separation and disruption to breastfeeding (5). Severe or prolonged hypoglycaemia can cause seizures and brain damage and though rare, litigation from such cases incurs a financial cost to the NHS (25 claims, total cost £162 million 2002-11).??

Intensive or ‘tight’ maternal glucose control during pregnancy could reduce adverse outcomes in mother and baby (6). However, evidence about whether intrapartum tight glucose control is beneficial is lacking (3) with some advocating for less tight control during labour despite the absence of RCT evidence (4). Tight control, and therefore greater use of insulin to reduce blood glucose levels can lead to maternal hypoglycaemia in women/birthing people with pre-existing diabetes, though there is little data on the effect in GDM women/birthing people (estimates 2-28%) (6).

The need for insulin to achieve tight control means that women/birthing people require an IV line, restricting their movement in labour. Women/birthing people have told us tight control negatively impacted on their birth experience.?Currently 10% of women with GDM require insulin during labour. Less tight control could reduce maternal hypoglycaemia, empower diabetes self-management, improve birth experience and reduce midwifery workload: put simply reduce ‘over treatment’.

There is an urgent need for an adequately powered, well designed RCT to ensure there is no harm to the baby from less tight control. OBJECTIVES

To establish whether less tight blood glucose control is non inferior to tight control around the time of birth for women/birthing people with GDM for risk of neonatal hypoglycaemia and neonatal unit admission.

To investigate the benefits and harms of less tight control compared to tight control in relation to maternal experience, other maternal outcomes (inc., admission to critical care, feeding and fluid intake during labour) and other neonatal outcomes (inc., neonatal death and breastfeeding) To undertake an economic evaluation of less tight control versus tight control

To conduct an internal pilot phase to evaluate key trial processes to inform progression from pilot to main trial

To assess the acceptability of a less tight or tight blood glucose monitoring strategy, from the perspectives of women/birthing people and health professionals, by conducting a qualitative sub-study

To conduct a Study Within a Trial (SWAT) to evaluate the effectiveness of an ‘inclusivity package’, aimed at increasing participation of South Asian women/birthing people

METHODS: Multi-centre, open-label, randomised, controlled, two-arm parallel group, non-inferiority trial, with an internal pilot phase, and economic and qualitative evaluation.

GILD will be conducted in 23 UK hospitals in areas of high ethnic and socioeconomic diversity. Study information will be freely available in community/hospital clinics. GDM women/birthing people approached between 28+0 and 36+6 weeks’ gestation (routine antenatal care), by research midwife/clinical team and given study information/link to video information.

Written informed consent sought at 36 weeks’ gestation and continuous glucose monitor (CGM) fitted to the woman/birthing person between 37-38 weeks, to facilitate real-time trial data collection. From 37 weeks’, 1630 women/birthing people will be randomised via a web-based system. Clinical teams will be informed of the randomised glucose monitoring strategy and follow this around the time of birth.

To determine acceptability of less tight glucose control, women/birthing people and health professionals (HCPs) will take part in virtual semi-structured interviews. An economic evaluation will be undertaken.

TIMELINES: Total 40 months. 1-9 set-up, 10-27 recruitment, 19 internal pilot, 31 complete data collection, 35-40 complete analyses, reporting/dissemination.

IMPACT: GILD will provide the NHS with evidence that may change policy. If less tight glucose control is non inferior to tight control AND is acceptable to HCPs and pregnant women/birthing people, it is highly likely to be introduced NHS-wide. This would reduce midwifery workload and improve the birth experience for women/birthing people.

DISSEMINATION: Share findings via a published monograph, research papers published in high-impact peer reviewed journals and presentations at clinical conferences. Findings available to study participants and wider public via PPI partners, plain English summaries, infographics, animations and videos.