Early planned delivery reduces impact of preterm pre-eclampsia

Doctors have long debated over the optimal time to deliver mothers with pre-eclampsia in late pregnancy (after 34 but before 37 completed weeks). This is because too early delivery compromises the baby’s health, while delayed action may endanger the mother’s health.

A new study by King's College London researchers shows that planning an early delivery does cut the chances of complications due to high blood pressure in such pregnancies. The research is published in The Lancet and funded by National Institute for Health Research (NIHR).

Pre-eclampsia is a unique rise of blood pressure related to pregnancy, which has implications for many organs. While one in ten pregnant women develops high blood pressure, only about 3% actually have pre-eclampsia, which is marked by damage to multiple organs. In the UK it affects about 40,000 women a year, and takes the lives of 100 women around the world each day.

Pre-eclampsia is caused by alterations in the function of both the placenta and the maternal blood vessels. It carries a high risk of complications for both the mother and the baby. These include stroke, liver damage, kidney injury, or death, in the women, while the baby is at risk of fetal growth restriction and death.

As of today, standard care means an initial assessment of the mother and the fetus, with delivery being advised once 37 weeks are complete. This is because maternal and fetal risks are minimum at this age. Between 34-37 weeks, called late preterm pre-eclampsia, the risks of immediate delivery must be considered against those of continuing expectant management.

If delivered immediately, the baby will require care for immaturity of fetal organs. If the pregnancy is continued, the mother is put at increasing risk, while the baby may suffer from increasingly poor growth, may die in utero, or may need an emergency delivery.

In the UK, women with this condition are usually watched until 37 weeks, on the condition that if the severity increases significantly the delivery will be hastened. However, is this really the best course? This trial aimed at answering this question.

How was it done?

A new study was carried out in 901 mothers at 46 centers in the UK, who were randomized to two parallel groups. All the women had high blood pressure due to pregnancy at 34 to 37 weeks, and either singleton or dichorionic diamniotic twins.

One group was managed by planned early delivery, while the other group received the usual expectant care protocol.

In the group with planned delivery, corticosteroids were given immediately and delivery was planned (though not achieved in all cases) within 48 hours of diagnosis. The steroids were given to help the fetal lungs to mature faster. Labor was induced unless Cesarean section was otherwise indicated.

In the expectant care group, women received the usual medical management under specialists, while watching for complications like uncontrolled rises in blood pressure, abnormalities in liver or kidney tests, or other blood parameters, signs of fetal oxygen deprivation, or eclampsia (convulsions). If any of these occurred, or if the woman reached 37 complete weeks, delivery was achieved.

The researchers looked for a combination of maternal complications and systolic blood pressure at or above 160 mmHg. In babies, they looked for a combination of deaths around the time of delivery with admission to the neonatal intensive care unit (NICU).
Maternal complications included the following:

• recorded systolic blood pressure of at least 160 mm
• death
• neurologic complications like eclampsia, stroke or transient ischemic attacks, cortical blindness (visual loss with normal eyes)
• cardiac complications like the need for three antihypertensive drugs, heart failure, heart attack, angina, the need for intubation, or pulmonary edema (fluid in the lungs)
• blood-related complications like a drop in platelets or bleeding complications
• liver dysfunction, liver rupture or liver hematoma
• kidney damage, acute renal failure or dialysis
• placental abruption (separation of the placenta from the uterus before birth)

Perinatal complications included:

• Death within 7 days of delivery
• Perinatal deaths (just before or after delivery)
• NICU admission

What did the study find?

Maternal complications were 14% less in the group that had a planned early delivery. Babies in this group too had a 26% improvement in the outcome. This group of mothers gave birth about 5 days earlier, on average, but the chances of spontaneous vaginal delivery were higher. The number of serious adverse events was similar in both groups.

The study shows that planning for an early delivery in late preterm pregnancy with hypertension is associated with a lower incidence of maternal and fetal complications, as well as with cost savings. While more babies were admitted to the NICU, the overall baby-related complications remained stable. That is, these babies did not require more oxygen or ventilation, neither did they have to stay in the NICU longer. While the findings might need to be adjusted for resource scarcity in low-income settings, the benefits of lower stillbirth could still outweigh the risks of prematurity in this situation.

In view of these benefits, researcher Lucy Chappell says, “Doctors and women will need to consider the trade-off between lower maternal complications and severe hypertension against more neonatal unit admissions, but the trial results tell us that these babies were not sicker from being born earlier. We suggest that these results should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery.”

Journal reference:

Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lucy C Chappell, Peter Brocklehurst, Marcus E. Green, Rachael Hunter, & Pollyanna Hardy. The Lancet. https://doi.org/10.1016/S0140-6736(19)31963-4. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31963-4/fulltext