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Steroids are often unnecessarily prescribed to pregnant women thought to be at risk of preterm birth, a new evidence review contends.
As a result, millions of babies are needlessly exposed to long-term health problems associated with steroid use in gestation, such as increased risk of infection and delayed brain development, researchers say.
Steroids can't prevent preterm birth, but they can accelerate the maturation of developing organs and give preemies a fighting chance for survival, said lead researcher Dr. Sarah McDonald, a professor of obstetrics at McMaster University in Ontario, Canada.
Compared to other at-term babies not given steroids, those infants had an increased risk of requiring neonatal intensive care, being put on a respirator, and developing long-term brain development and behavioral disorders, according to the review published Aug. 2 in the BMJ.
“I like to say that steroids are powerful medications, and with great power comes great responsibility,” McDonald said. “We need to try to tailor the administration of these medications to pregnancies that are really at risk of preterm birth so we're not exposing babies who go on and be born at term to these powerful medications.”
In the same issue of the journal, a new study led by Dr. Tsung-Chieh Yao, from the Division of Allergy, Asthma, and Rheumatology Department of Pediatrics at Chang Gung Memorial Hospital, Taoyuan, Taiwan, reinforces the risk of unnecessary steroid use in pregnancy.
That study, of more than 1.9 million Taiwanese children, found that those exposed to steroids in the womb had a higher risk of serious infections during their first six to 12 months of life, including sepsis, pneumonia and gastroenteritis.
Steroids are an important tool in protecting infants at risk of being born very preterm, which is before 34 weeks of gestation, McDonald said.
“Steroids don't prevent prematurity itself, but it prevents some of the illnesses that can go with a baby being born early,” McDonald said. “Steroids improve survival, and they improve outcomes for many of the significant illnesses that small babies can face.”
Gates opened up for late-preterm babies
But a sea change occurred in 2016 regarding steroid use in pregnancy, with the publication of an article in the New England Journal of Medicine suggesting the drugs could also help late-preterm babies born at 34 to 36 weeks of gestation, said Dr. Panagiotis Kratimenos, a neonatologist at Children's National Hospital in Washington, D.C.
As a result, doctors started prescribing steroids more frequently to expecting mothers, even those closer to term, said Kratimenos, who wasn't part of the new studies.
“Even at that time, there was a lot of discussion in the community about the potential side effects on those steroids,” Kratimenos said. “My personal opinion on this is that I'm very concerned about the steroids because they have an effect on brain development, because they interfere with some signaling pathways of the brain development.”
For the evidence review, McDonald and her colleagues pooled data from seven clinical trials and 10 observational studies -- including a total 1.6 million infants. The data specifically focused on infants whose mothers took steroids at 34 weeks of gestation or earlier.
They found that about 40% of infants whose moms were given steroids were not born prematurely, and so arguably didn't need the drugs.
Those at-term babies exposed to steroids were 2.5 times more likely to need mechanical ventilation within the first six months of life, evidence showed.
McDonald said that finding was “very surprising, because in very early babies, steroids help breathing. But in babies born at term, there was a higher chance of needing to be placed on a breathing machine."
At-term babies exposed to steroids also had a 49% increased risk of requiring neonatal intensive care and a 47% increased risk of long-term neurodevelopmental or behavioral disorders.
“The head circumferences of babies born after steroid exposure are smaller, so steroids are potentially impacting the size of the infant's brain, and that's very concerning for long-term development,” McDonald said.
The Taiwanese study provided more cause for concern.
Researchers found a 32% overall increased risk of serious infection during the first six months of life; these included a 74% increased risk of sepsis, a 39% increased risk for pneumonia and a 35% increased risk for gastroenteritis.
Increased infection risk continued through a baby's first year, the researchers added.
Impact on immune cells
Steroids are known to affect immune response, Kratimenos said. They're given to organ transplant patients specifically to reduce the risk of rejection, by diminishing the recipient's immune response.\
“Babies who get steroids, they have decreased ability to fight infections because the steroids inhibit their immune cells,” Kratimenos said. “It can change the profile of the immune cells and they may develop in a different way, in a more slow or different way. They may not be able to make some immune cells because of the steroids. And it chances the ability of other tissues to ask immune cells to come and fight an infection."
These data leave doctors and expecting parents facing a real conundrum, McDonald said.
“Doctors want to help small babies, and in our enthusiasm we use these steroids because they're one of the few interventions we have to improve outcomes for small babies who are born too early,” McDonald said.
“But the challenge is that it's really difficult to predict who's going to give birth early. We don't have any good prediction models,” McDonald continued. “And that means that you either err on the side of caution and give the steroids, potentially overexposing babies, or you run the risk of not administering a medication that we think is really helpful to small babies.”
Pregnant women whose doctors recommend steroid use should voice any concerns they might have, taking into account where they are in their pregnancy, Kratimenos said.
“As physicians, we should always have this one-on-one discussion with our patients and really tailor their treatment according to their needs and priorities,” Kratimenos said. “If you are closer to term, this is something that you can really discuss with your obstetrician and make a decision based on the gestational age.”
Concerned parents also should consider enrolling in ongoing studies that are examining the use of lower doses of steroids in pregnancy, said McDonald, who is leading one of those studies.
“We've used the same dose of steroids for over 50 years, and almost nothing we do in medicine has remained unchanged, thankfully, for 50 years,” McDonald said. “Typically, we try to advance and be more precise and use the best drugs possible. But for some reason with steroids, we've kind of stayed in the dark ages and we've done the same thing for 50 years without studying the dose.
“I'd really encourage parents to think about coming into one of those studies so that we begin for the first time in 50 years to look at what are the right doses of steroids,” McDonald continued. “Can we find benefit in a lower dose and potentially decrease long-term concern?”
The March of Dimes has more on risk of preterm delivery.
SOURCES: Sarah McDonald, MD, professor, obstetrics, McMaster University, Ontario, Canada; Panagiotis Kratimenos, MD, PhD, neonatologist, Children's National Hospital, Washington, D.C; BMJ, Aug. 2, 2023
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