Timing is Everything: New UCSF Study Offers Hope for Reducing Brain Bleeds in Preterm Babies

For extremely preterm infants, a severe brain bleed (called sIVH) can lead to long-term complications.  Doctors can reduce this risk by administering steroids to the pregnant mother, but the protective effect starts to wane after the first week, making it difficult for healthcare teams to determine the best timing to ensure the treatment works effectively.

A new UC San Francisco study published in the American Journal of Obstetrics and Gynecology has found that a timely second dose of BMZ, the steroid commonly used to prevent sIVH, can restore the benefit temporarily and effectively reduce risk in infants born before 28 weeks’ gestation.

“This study builds off previous findings that the benefits of BMZ start after 24 hours and wane after nine days, which led to a 2016 update of our clinical practice at UCSF to encourage retreatment with BMZ after nine days for pregnant women still at high risk of delivering before 28 weeks,” said Ron Clyman, MD, first author of the study and Emeritus Professor of Pediatrics at UCSF in the Division of Neonatology.

The Power of Retreatment

The current study, which reviewed data from over 400 preterm infants born before 28 weeks, found that only 3% of infants who received a second dose developed sIVH, compared to nearly 20% of those who did not.

“Importantly, sIVH rates stayed consistent for infants born 1-9 days after the first dose of BMZ. This means that the remarkable difference in sIVH rates can be attributed to BMZ retreatment rather than other care improvements accumulating over the study period,” said Clyman.

“While the benefits on sIVH are relatively straightforward, the decision on steroid retreatment is quite complex. They also have beneficial effects on the lungs that peak at 29-32 weeks’ gestation, but more than three courses can cause decreased fetal growth and head circumference,” said Clyman.

Timing Is Everything

Predicting when preterm delivery will occur is an imprecise science. Up to half of pregnant women who are given a course of steroids remain undelivered 14 days later. Some even end up delivering close to term, months later.

Due to the risks of frequent steroid dosing, regularly scheduled repetitive courses are not recommended by the American College of Obstetricians and Gynecologists. Care teams instead make informed decisions based on the specific pregnancy and the perceived risk of preterm birth.

“If you retreat with BMZ too early, the infant may miss out on the benefits to the lungs if the delivery happens around 30 weeks’ gestation. If you are too hesitant about BMZ retreatment, you could be opening a significant risk for sIVH if the delivery happens before 28 weeks,” said Clyman.

As the field of neonatal care continues to evolve, research from the UCSF Department of Pediatrics highlights the need for ongoing adjustments in treatment protocols to ensure the best possible outcomes for preterm infants. By prioritizing the prevention of sIVH through well-timed steroid retreatments, healthcare providers can help reduce the risk of long-term complications and improve the chances of healthy development for these newborns.

This study marks a significant step forward in the care of preterm infants, providing clinicians with critical insights to enhance their approach to steroid treatment timing, ultimately saving lives and reducing the risk of lifelong challenges for the tiniest patients.

Authors: Co-authors from the UCSF Department of Pediatrics are Elizabeth Rogers, MD, Professor of Pediatrics, and Katelin Kramer, MD, Assistant Professor of Pediatrics. Please see the paper for all authors.