King's College London

The latest findings from the CRADLE-4 study, led by academics in the Department of Women & Children’s Health at King’s College London, in collaboration with the University of Zambia and KLE Academy of Higher Education and Research (India), indicate that planned delivery for women with late preterm pre-eclampsia reduces risks to both mothers and babies.

Pre-eclampsia is a major cause of maternal and perinatal mortality, particularly in low and middle income countries, where few studies have been conducted on interventions that aim to reduce these adverse outcomes – despite 95% of global maternal and perinatal deaths occurring in these settings. The CRADLE-4 trial, which was carried out in nine sites across India and Zambia, compared planned delivery to  expectant management in women with pre-eclampsia from 34 to 37 weeks of pregnancy.  565 pregnant women were enrolled in this randomised trial.

Prior to this study, guidelines suggested offering delivery to women with pre-eclampsia at 37 weeks, with earlier delivery only recommended if severe complications had already developed. It was unknown if routine delivery between 34 and 37 weeks could reduce harm to the mother without increasing risk to the baby. Similar studies in the UK were unable to determine the balance of risks and benefits for the baby as complications were rare.

The study confirmed that the mother is better off if delivered early, with less severe blood pressure, which is known to be dangerous. Babies of women allocated to planned early delivery had higher birthweights, on average, and no increased risk of complications compared to babies born in the expectant management (usual care) group.

Women in the expectant management group frequently required emergency delivery, on average only 3 days later than women in the planned delivery group. When the researchers looked at the details of the babies delivered early, there was a significant reduction (75%) in stillbirths and no difference in neonatal deaths after birth – i.e. they were able to save three quarters of babies who die from pre-eclampsia at this stage of pregnancy.

Babies in the planned delivery group (born on average 3 days earlier than those in the expectant management group) were not at increased risk of breathing difficulties, neonatal unit admission, or infection. Pre-eclampsia is a progressive disease and the findings of this study suggest that babies are better off when routinely delivered early from 34 weeks.

For women, planned delivery did not increase risk of caesarean section, with women in this group just as likely to have a vaginal delivery, and spending less time in hospital.

As they have demonstrated that it is safe to routinely deliver babies for mothers who have pre-eclampsia, from 34 weeks – even when there are fewer resources for looking after the babies – the authors recommend that this intervention be rolled out across the world in low and middle-income settings.

In an accompanying editorial Catherine Cluver and Sue Walker, obstetricians from South Africa wrote: “Planned delivery in late preterm preeclampsia is an important intervention to reduce global maternal and perinatal morbidity. The observed reduction in stillbirth reinforces that the safest place for the baby in late preterm preeclampsia is- in the cradle.”

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