STOPPIT-3 and STOPPIT-M

STOPPIT-3 is a twin study trying to find out if steroid injections given to the mother or gestational parent just before birth reduces the need for admission to the neonatal unit for breathing help.

Around 2-3% of births in the UK are twins. However, admission rates of twins to neonatal units is around 15-20%, and remains high even among twin babies born in the recommended late preterm (35-36 weeks gestation) or early term (37 weeks gestation) period. (In twin pregnancies with no complications, birth is recommended at 36+0-36+6 in twins that share a placenta, and at 37+0-37+6 in twins that don’t share a placenta.)

To reduce the risk of breathing difficulties after birth, antenatal corticosteroids (ACS) are often given to women at risk of preterm birth (24-34 weeks gestation) to help mature babies’ lungs and reduce the need for high levels of respiratory (breathing) support. These are given by injection to women at risk of an early (preterm) birth. There is good evidence of their benefit for babies born at 24-34 weeks.

In the past 10+ years ACS have also been given to some women who are more than 34 weeks pregnant if there is a higher chance their baby or babies might need to go to the neonatal unit for help with breathing, for example babies born by planned caesarean birth, or twins.

However, there is currently little evidence of ACS effectiveness in twins, and little evidence of their use after 34 weeks of pregnancy.

As part of the STOPPIT-3 study, we plan to recruit 1,552 women from 50+ centres across the UK. We will invite women and pregnant people to consent to participate in the study who are expecting twins. We will ask the women to have a single course of dexamethasone 6.6mg/2ml (an antenatal corticosteroid) given in two divided doses by intramuscular (IM) injection 24 hours apart. We will follow women and their babies for two years after delivery.

The proposed research will generate much needed evidence on the use of ACS prior to a planned birth (a birth after induction of labour of planned caesarean) of twins. If ACS reduces the chance that twins need to go to the neonatal unit for help with breathing and they are cost-effective over placebo, this will provide evidence to help standardise the advice and care offered before birth in twin pregnancies. If ACS does not prove to be effective over placebo this will also be very important in creating standardised care in twin and may result in important cost savings to the NHS.

Women will be eligible for inclusion in the study if they are:

• >16 years old;
• with a viable twin pregnancy;
• and a planned caesarean birth or induction of labour scheduled between 35+0 -38+6 weeks gestation.

See the funding award.

In addition to the central study STOPPIT-3, we will be running STOPPIT-M: a mechanistic study. We know that steroids work well for most babies in preventing breathing difficulties, but for some babies they don’t work and we can see side effects like low blood sugar levels. In STOPPIT-M we are trying to understand why ACS (antenatal corticosteroids) work for some babies and not for others. For babies who do not benefit from ACS, we think it might affect their own stress-response systems – called the hypothalamic-pituitary-adrenal axis or HPA axis.

STOPPIT-3 participants undergoing elective caesarean section will be eligible to participate and donate samples at delivery for analysis.

In STOPPIT-M we will collect a maternal blood sample as well as cord blood samples from each twin, amniotic fluid and placenta from each twin and will use these to explore whether infant HPA activity underpins side effects like low blood sugar and breathing difficulties in some babies.

See below for videos giving more information about steroids in pregnancy.