A Randomised Placebo-Controlled Trial of Antenatal Corticosteroids for Planned Birth in Twins: STOPPIT-3

Research question: Do antenatal corticosteroids (ACS) reduce the need for respiratory support in twins born after scheduled late preterm or early term birth and are they cost effective?

Background: Women with twin pregnancy are recommended to have scheduled birth in the late preterm (35-36 weeks gestation) or early term (37 weeks gestation) period to reduce the risk of perinatal mortality. Rates of neonatal unit admission in twins after late preterm/early term birth are disproportionately high (up to 30%), and ACS use has potential to reduce morbidity.

However, there is currently little evidence of ACS effectiveness in twins, and ACS are not devoid of harm. Late preterm/early term ACS can neonatal hypoglycaemia and reduce birthweight, and may be associated with detrimental effects on childhood educational attainment.

Aims and Objectives: Our aim is to determine the clinical and cost effectiveness of ACS prior to planned birth of twins in a multi-centre placebo-controlled trial with internal pilot. Specific objectives are:

i) To determine the effect of ACS on neonatal morbidity including the need for respiratory support within 72 hours of birth (primary outcome), and severe respiratory morbidity, NNU admission and Apgar score (secondary outcomes)

ii) To determine the effect of ACS on perinatal mortality, newborn hypoglycaemia, birthweight and head circumference, and sepsis (safety outcomes) iii) To determine the effect of ACS on maternal outcomes including infection and breastfeeding iv) To determine the cost-effectiveness of treatment with ACS compared to placebo

v) To explore the effects of ACS on childhood cognitive and language development at two years of age compared to placebo, in a subset of twins, using a validated questionnaire (PARCA-R)

vi) To establish a platform for future studies of the effects of ACS on childhood neurodevelopmental outcomes compared to placebo using record linkage of maternity data to school census data aged 4-18. vii) Within the internal pilot, to confirm our sample size, recruitment and outcome frequency estimates.

Design and setting: Multicentre, double-blinded, randomised, placebo-controlled trial with an internal pilot phase and economic evaluation in at least 50 UK Obstetric units.

Target population and sample size: 1552 women with a twin pregnancy and a planned birth between 35 and 38+6 weeks’ gestation recruited from antenatal clinics.

Health Technology being assessed: Women will be randomised (1:1) to Dexamethasone Phosphate (24mg) given by 2 IM injections 24 hours apart, or placebo, 24-72 hours prior to scheduled birth.

Outcomes: The primary outcome is respiratory support within 72 hours of birth. A number of secondary and safety outcomes will be included. Cognitive and language development at age two years will be assessed in a subset of participants using the Parent report of Children’s Abilities- Revised [PARCA-R] questionnaire.

Timelines for delivery: 48 months from February 2021 with 6 months set up, a total of 36 months recruitment over 50 sites and 6 months to final outcomes, analysis and reports. We will include an internal pilot of 10 months (159 patients).

Anticipated impact and dissemination: The proposed research will inform national guidance on the use of ACS in twin pregnancies. The results will be communicated to the scientific community via publication and conference presentation, and to the public via links with charity partners and social media.