Steroid Shots for Threatened Preterm Birth: A New Debate About Timing, Dosing, and What It Means for Mothers and Babies

Table of Contents

• Key Points
• Why This Research Matters
• The APOSTEL 8 Trial: What Researchers Did
• Key Findings: What the Trial Showed
• The Bigger Debate: Are Antenatal Corticosteroids Still Needed After 30 Weeks?
• What the Evidence Says About Steroid Benefits and Risks
• Clinical Implications: What These Findings Mean for Patients
• Study Limitations
• Recommendations for Patients and Doctors
• What the Original Trial Authors Said in Reply
• Frequently Asked Questions
• Source Information

Key Points

• In 752 women with threatened preterm birth at 30–34 weeks, atosiban delayed delivery beyond 48 hours more often than placebo but did not improve baby outcomes.
• Nearly 98% of APOSTEL 8 participants received at least one corticosteroid dose, making the steroid effect difficult to isolate.
• Experts argue the uniform steroid regimen from 24 to 34 weeks needs re-evaluation because babies at 30–34 weeks have lower baseline risks.
• A meta-analysis of over 1.25 million children linked antenatal corticosteroid exposure to elevated mental and behavioral disorder risks, including late-preterm and term infants.
• A non-inferiority trial could not prove a single 11.4 mg betamethasone dose works as well as the standard two-dose course.

Why This Research Matters

Babies born too early — before 37 weeks of pregnancy — can face serious health problems. The earlier a baby is born, the higher the risk of complications like breathing difficulties, infections, and even death. Fortunately, the risk drops steeply as pregnancy progresses, particularly between 28 weeks and 30 weeks of gestation.

Doctors have a powerful tool to help babies born early: antenatal corticosteroids (steroid medications given to the mother before birth). These medications help speed up the development of the baby's lungs and other organs. The current standard regimen is based on landmark clinical trials from the 1970s and 1980s, and it is generally given to women at risk of preterm birth anywhere between 24+0 and 33+6 weeks of gestation (roughly 24 to 34 weeks of pregnancy).

However, whether that broad, one-size-fits-all approach still makes sense — particularly for babies at 30+0 to 33+6 weeks, whose risk of complications is much lower than for very premature babies — has become a subject of intense debate.

This correspondence, published in the medical journal The Lancet, discusses how the results of the APOSTEL 8 trial — a study of a drug called atosiban for threatened preterm birth — shine new light on this question.

The APOSTEL 8 Trial: What Researchers Did

The APOSTEL 8 trial was a randomised clinical trial (a study in which participants are randomly assigned to receive one treatment or another, ensuring that the groups are comparable). It was a multicentre, placebo-controlled study — meaning it was conducted at multiple hospitals and some participants received an inactive substance (placebo) for comparison.

Researchers, led by Larissa I van der Windt and colleagues, enrolled 752 participants diagnosed with threatened preterm birth — meaning they were experiencing early labor symptoms and were at risk of delivering too soon.

The women were between 30+0 and 33+6 weeks of gestation (30 to just under 34 weeks of pregnancy). They were randomly assigned to receive either:

• Atosiban: a medication called a tocolytic, which is designed to relax the uterine muscles and stop or delay contractions, or
• Placebo: an identical-looking inactive substance.

Atosiban is sometimes used to delay delivery long enough to allow the full course of antenatal corticosteroids to be completed. The study was designed to determine whether atosiban could delay birth and improve babies' health outcomes in this specific group of women.

Key Findings: What the Trial Showed

The results revealed a clear split between short-term effects and longer-term outcomes:

Atosiban did delay delivery. The proportion of women whose pregnancy was prolonged beyond 48 hours was higher in the atosiban group:

• Atosiban group: 78% of women remained pregnant beyond 48 hours
• Placebo group: 69% of women remained pregnant beyond 48 hours

In statistical terms, this was expressed as a relative risk (RR) of 1.13 (95% confidence interval [CI] 1.03–1.23). The confidence interval indicates that researchers are 95% confident the true effect lies within this range. The lower end of the range (1.03) is still above 1.0, meaning the difference was statistically significant — there is a real effect.

More women in the atosiban group completed their full course of corticosteroids. The study found:

• Atosiban group: 76% of women received completed courses of antenatal corticosteroids
• Placebo group: 68% completed their steroid courses

This was expressed as a relative risk of 1.11 (95% CI 1.02–1.22). Again, the difference was statistically significant.

Crucially, however, atosiban did not improve neonatal outcomes. In other words, delaying birth and completing more steroid courses did not translate into measurably healthier babies in the atosiban group.

Another key observation: nearly 98% of all participants in the trial received at least one dose of antenatal corticosteroids. This is a strikingly high number and helps explain why the research team's attention turned to the corticosteroids themselves.

The Bigger Debate: Are Antenatal Corticosteroids Still Needed After 30 Weeks?

The findings of APOSTEL 8 raise a fundamental question: since almost everyone got steroids, and babies born at 30 to 34 weeks already have dramatically lower risks of severe complications compared to those born before 28 weeks, is the standard corticosteroid regimen still offering meaningful benefit at this later stage?

The correspondence highlights that preterm-related illness and death decline steeply between 28 weeks and 30 weeks of gestation. This improvement is partly thanks to advances in modern neonatal intensive care. Even though antenatal corticosteroids likely contribute to better outcomes for early preterm babies, the benefit–risk profile of this medication after 30 weeks is unclear.

Experts are particularly concerned about whether the uniform dosing strategy — the same dose and regimen given to all women from 24 to 34 weeks — is appropriate. The current regimen of antenatal corticosteroids is built on evidence from trials conducted decades ago, and the babies born today, with access to far more advanced neonatal care, are a different population in some ways.

The correspondents, Ruben Ramirez Zegarra, Beatrice Valentini, and Tullio Ghi, argue that modern obstetrics needs to shift toward more personalised approaches. They suggest the continued use of a single uniform corticosteroid regimen across all early preterm stages (24+0 to 33+6 weeks) warrants critical re-evaluation.

Given the lower baseline risk of severe complications faced by infants born between 30+0 and 33+6 weeks, these babies might benefit from reduced or individualised corticosteroid dosing. However, the researchers are quick to note that robust evidence to support such a change is still lacking.

What the Evidence Says About Steroid Benefits and Risks

The correspondences carefully reviewed the existing scientific literature to evaluate both sides of the argument.

Evidence questioning benefit after 30 weeks

Reliable data examining the effectiveness of antenatal corticosteroids specifically between 30+0 and 33+6 weeks are sparse. However, the available evidence raises doubts:

• One observational study of over 13,000 infants born between 23 weeks and 32 weeks found no survival benefit and no respiratory benefit from corticosteroids among the babies born later in that range.
• The APOSTEL 8 trial itself hinted that a partial course of antenatal corticosteroids could be safe after 30 weeks, adding to the suggestion that a smaller dose might be sufficient.

Evidence from non-inferiority trials

A separate non-inferiority trial (a trial designed to test whether a new treatment is not worse than the standard treatment) tested a single 11.4 mg dose of betamethasone — a common antenatal corticosteroid — against the standard two-dose regimen.

The trial involved 3,244 participants. However, it failed to show non-inferiority, meaning the researchers could not prove that a single dose works as well as the standard two-dose course. Despite methodological limitations — especially in how outcomes were selected — this trial emphasized the need for further research in this field.

An ongoing trial called the SNACS trial (NCT05114096) is expected to provide additional insights into whether reduced antenatal corticosteroid dosing is sufficient.

Evidence on safety risks

Safety concerns regarding antenatal corticosteroids are not new, but they are becoming harder to ignore:

• Risks appear to be dose-dependent, meaning higher or repeated doses are associated with greater risks.
• Repeated courses of antenatal corticosteroids have been associated with increased short-term and long-term adverse outcomes for the child.
• Animal studies found that corticosteroids caused delayed fetal brain growth and impaired cortical development (the cortex is the brain's outer layer, responsible for higher functions like thought and memory).
• Human cohort studies (studies that follow groups of people over time) have reported increased rates of mental and behavioural disorders in children who were born preterm and had been exposed to antenatal corticosteroids.
• A recent meta-analysis of over 1.25 million children (a statistical combination of many studies) found elevated risks of such disorders, even in late-preterm and term infants following antenatal corticosteroid exposure. In other words, the increased risk was seen in babies who were not severely premature.

These findings suggest the long-term neurological safety of this widely used medication deserves serious consideration, particularly when the short-term benefits are less certain.

Clinical Implications: What These Findings Mean for Patients

For women who experience threatened preterm birth between 30 and 34 weeks of pregnancy, these findings have direct relevance:

• Atosiban is effective at buying time. Women who received atosiban were more likely to remain pregnant past the critical 48-hour mark, which is the window needed to complete a full course of steroids.
• Buying time did not change outcomes. Despite more completed steroid courses and delayed delivery, the babies born to mothers in the atosiban group were not healthier than those in the placebo group. This raises the possibility that the extra delay — and the extra steroids — may not provide the kind of benefit doctors have assumed.
• Steroid use was nearly universal. With 98% of participants receiving at least one dose of corticosteroids, the trial could not separate the effect of atosiban from the effect of steroids. It also highlights how standard practice has made steroids almost automatic in this setting.

Study Limitations

The correspondences openly acknowledge the limitations of the evidence discussed:

• Subgroup analyses from randomised clinical trials are inconsistent for the 30 to 34 week window. Some analyses show benefits, while others show no benefit.
• The non-inferiority trial comparing a single 11.4 mg dose of betamethasone to the standard two-dose regimen had methodological limitations, especially in outcome selection. This means the outcomes chosen to measure success may not have been the most appropriate, which could affect the reliability of the results.
• Data specifically addressing corticosteroid efficacy between 30+0 and 33+6 weeks remain sparse, making it difficult to draw firm conclusions.
• The observational studies and meta-analyses regarding long-term risks are associations — they cannot prove that corticosteroids directly caused the mental and behavioural disorders observed.
• Animal study findings, while concerning, do not always translate directly to humans.

Recommendations for Patients and Doctors

Based on this exchange of expert opinions, the authors propose several directions:

1. Re-evaluate the uniform corticosteroid regimen. Doctors should critically assess whether the same steroid dosing is appropriate for all pregnancies from 24 to 34 weeks, or whether it should be tailored by gestational age.
2. Consider reduced or individualised dosing. Infants born between 30+0 and 33+6 weeks have a lower baseline risk of severe complications. They might benefit from reduced or individually adjusted corticosteroid doses, which could preserve benefits while reducing potential harms.
3. Await the SNACS trial results. The ongoing SNACS trial (NCT05114096) is expected to clarify whether reduced dosing of antenatal corticosteroids is sufficient to protect babies' lungs while minimising long-term risks.
4. Continue to use atosiban judiciously. The trial confirms atosiban prolongs pregnancy, which may still be valuable in specific clinical situations — for example, to allow transfer to a hospital with a higher level of neonatal care, or to complete steroid treatment when it is clearly indicated.
5. Weigh benefits against risks together with patients. For women in the 30 to 34 week window, the conversation about steroids should ideally include an honest discussion of the uncertain benefits at this stage and the emerging safety questions.

What the Original Trial Authors Said in Reply

The article also includes a response from the original APOSTEL 8 trial authors (van der Windt and colleagues). They thanked Lola Loussert and colleagues, and Ruben Ramirez Zegarra and colleagues, for their thoughtful responses to the study. The trial authors acknowledged that both correspondences raise important questions regarding the standard regimen of antenatal corticosteroids.

The exchange of views indicates that this is a live scientific conversation, with leading researchers actively debating whether common obstetric practices need updating. Notably, the article also contains a note about infants born after 29 weeks, and states that subgroup analyses from randomised trials are inconsistent — with some showing benefits from corticosteroids between 30 and 34 weeks and others showing none.

Frequently Asked Questions

I am 31 weeks pregnant and had threatened preterm labor. Do the APOSTEL 8 findings change whether I should get steroid shots?

The APOSTEL 8 trial studied women between 30 and 34 weeks. Nearly all received steroids, and babies' outcomes were not improved by delaying birth. Experts debate whether the standard steroid dose is still appropriate at this stage, but they say solid evidence is lacking. Talk with your doctor about your specific situation and current recommendations.

Did atosiban help delay birth, and did it improve baby outcomes?

In the trial, 78% of women receiving atosiban remained pregnant beyond 48 hours, compared with 69% receiving placebo. More women in the atosiban group completed steroid courses. However, babies in the atosiban group were not healthier than those in the placebo group. Delaying birth and completing more steroids did not lead to measurable improvements in neonatal outcomes.

Why are experts questioning the standard antenatal corticosteroid regimen for 30 to 34 weeks?

Nearly 98% of APOSTEL 8 participants received steroids, yet babies born at 30 to 34 weeks already have much lower risks than those born before 28 weeks. Some research suggests no clear benefit for later preterm babies, and long-term safety concerns have been raised. Experts call for re-evaluation of uniform steroid dosing across all preterm stages.

What does the research say about the risks of antenatal corticosteroids?

Some animal studies found delayed fetal brain growth. Human studies have reported increased rates of mental and behavioral disorders in children exposed to steroids, and a meta-analysis of over 1.25 million children found elevated risks even in late-preterm and term infants. Risks appear dose-dependent, with higher or repeated doses linked to greater risks.

Is a single lower dose of betamethasone as effective as the standard two-dose course?

A non-inferiority trial tested a single 11.4 mg betamethasone dose against the standard two-dose course in 3,244 participants. It failed to show that the single dose works as well as the standard course. Researchers noted limitations in how outcomes were selected, and they emphasize more research is needed.

Should women at 30 to 34 weeks avoid atosiban or steroids based on this debate?

No. The article says atosiban may still be valuable in specific situations, such as allowing transfer to a higher-level neonatal unit or completing clearly indicated steroid treatment. The authors advise weighing uncertain benefits and emerging safety questions with your healthcare provider. Recommendations are not to stop treatments but to individualize care and await further trial results.

I'm 30 to 34 weeks pregnant with threatened preterm labor. Doctors recommend atosiban and steroid shots, but I've heard steroids may not be needed this late. When should I get a second opinion?

Between 30 and 34 weeks, babies have much lower risks of severe complications than earlier preterm infants, and the standard one-dose-fits-all steroid course used from 24 to 34 weeks is now under debate. In a large trial, atosiban delayed birth beyond 48 hours and allowed more steroid courses to be completed, yet babies were no healthier. Experts now suggest reduced or individualized steroid dosing may be appropriate for this group, but solid evidence is still lacking. A second opinion can help weigh those uncertain benefits against emerging safety questions. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

This patient-friendly article is based on peer-reviewed research.

• Original article title: Atosiban for threatened preterm birth — the APOSTEL 6 (correspondence discussing the APOSTEL 8 trial)
• Correspondence authors: Ruben Ramirez Zegarra, Beatrice Valentini, Tullio Ghi (with a reply from the original trial authors)
• Affiliation: Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; and Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
• Journal: The Lancet, Vol 406, September 27, 2025, page 1339
• Original trial referenced: van der Windt LI, Klumper J, Duijnhoven RG, et al. "Atosiban versus placebo for threatened preterm birth (APOSTEL 8): a multicentre, randomised controlled trial." Lancet 2025; 405: 1004–13.
• Note: This patient-friendly article is based on peer-reviewed research. It is intended for informational purposes only and does not constitute medical advice. Pregnant women and their families should discuss treatment options — including the risks and benefits of antenatal corticosteroids and tocolytic drugs — with their healthcare providers.