What Is the Steroid Shot to Develop Baby’s Lungs?

The steroid shot given to develop a baby’s lungs is an injection of a corticosteroid, most often betamethasone or dexamethasone, administered to a pregnant person when preterm delivery looks likely. The treatment works by crossing the placenta and speeding up the baby’s lung maturation so the lungs can function better outside the womb. A landmark Cochrane review of randomized trials found that antenatal corticosteroids cut the odds of respiratory distress syndrome by roughly half and reduced preterm infant mortality by about 40%.¹ Since its introduction in the 1970s, the treatment has become one of the most consequential interventions in perinatal medicine, yet questions about timing, repeat doses, and trade-offs still come up for every family facing a potential early delivery.

How the Shot Helps a Baby’s Lungs Mature

A baby’s lungs are not ready to breathe air on their own until late in pregnancy. One critical ingredient they need is surfactant, a slippery coating that keeps the tiny air sacs from collapsing each time the baby exhales. Corticosteroids given to the mother cross the placenta and bind to receptors in the fetal lung that are present from early in pregnancy. Once bound, they stimulate the production of surfactant-associated proteins and boost the synthesis of key fats that make up the surfactant layer.² The steroids also promote structural changes: cells in the lung walls thin out and mature, which makes gas exchange easier, and antioxidant enzymes ramp up, helping the lungs handle oxygen after birth. Fluid clearance from the lungs improves too, which matters because a baby’s lungs are filled with liquid in the womb and need to transition quickly to air breathing at delivery.

Which Steroid Is Used

Two corticosteroids dominate clinical practice worldwide: betamethasone and dexamethasone. Both are synthetic glucocorticoids that cross the placenta efficiently, which is why they were chosen over other steroids like prednisone (which the placenta largely inactivates). The standard regimen for betamethasone is two intramuscular injections of 12 mg each, given 24 hours apart. Dexamethasone is typically given as four intramuscular doses of 6 mg each, spaced 12 hours apart. Either way, the total course adds up to about 24 mg.

Whether one drug is better than the other has been debated for decades. A systematic review and network meta-analysis covering 45 trials and more than 11,000 women found no meaningful clinical difference between the two for neonatal death, neurodevelopmental disability, brain bleeds, or birth weight.³ A separate Cochrane review comparing the two drugs and various dosing schedules reached a similar conclusion: there is not enough high-quality evidence to declare a winner.⁴ In practice, betamethasone is more commonly used in many countries, partly because the two-shot schedule is simpler and partly because it was the drug used in the original 1972 trial that proved the concept.⁵ Dexamethasone, however, tends to be cheaper and more widely available in lower-income settings, which makes it the default in many parts of the world.

The Timing Window That Matters Most

The steroids need time to do their work but also lose effectiveness if delivery happens too long after the injection. The benefits peak when the baby is born between one and seven days after the first dose. A German observational study of 120 women who received the treatment illustrates how hard it is to hit that window: only about one in five delivered during the ideal one-to-seven-day period. The vast majority, nearly three-quarters, did not deliver until more than 14 days after the steroid course.⁶ That mismatch is a persistent challenge in obstetrics because predicting exactly when a preterm birth will happen is genuinely difficult. Tools like cervical length measurement and fetal fibronectin testing can help identify who is truly at risk of delivering soon, but neither is precise enough to guarantee the timing will line up.⁷

Despite the timing uncertainty, the protective effect is strong enough that clinicians still give the steroids even when they are not sure the window will be hit. A prospective study in preterm twins found that the benefit of steroids given within seven days of delivery was dramatic, with in-hospital mortality dropping by about 70%, but even courses given outside that window did not cause measurable harm.⁸ So the calculation tilts heavily in favor of treating rather than waiting for a perfect moment that may never arrive.

Benefits Beyond the Lungs

The steroid shot is most famous for preventing respiratory distress syndrome, but its protective reach extends further. A large prospective cohort study found that infants exposed to antenatal corticosteroids had lower rates of severe brain bleeds, a serious bowel disease called necrotizing enterocolitis, and severe eye problems, across nearly all gestational ages below 30 weeks and most gestational ages for babies born at 30 weeks or later.⁹ The original Cochrane review also documented a significant reduction in brain hemorrhage in preterm infants, and these benefits held regardless of the baby’s sex or racial background.¹

Research on extremely premature infants (born before 28 weeks) reinforces this picture. A study comparing babies who received no steroids, a partial course, or a complete course found a stepwise improvement: mortality was 43% in the no-steroid group versus 25% in the complete-course group, and severe brain hemorrhage among survivors fell from 23% to about 12%.¹⁰ Even a partial course was better than nothing, which is why the standard approach is to give the steroids whenever possible, even if there is not enough time to complete the full two-dose course.

What Happens at 26 to 33 Weeks Versus 34 Weeks and Beyond

The strongest evidence for antenatal steroids falls in the very preterm range, roughly 26 to 33 weeks of gestation. In that window, a population-based study of very low birth weight infants showed a clear, statistically significant reduction in respiratory distress syndrome.¹¹ At 34 weeks and beyond, the picture gets more complicated because most babies born at that stage will breathe reasonably well on their own. The question becomes whether the marginal benefit justifies the treatment.

A landmark trial published in the New England Journal of Medicine enrolled women at risk for late preterm delivery (34 to 36 weeks) and gave half of them betamethasone. Respiratory complications dropped from about 14% in the placebo group to about 12% in the steroid group, a real but modest absolute difference. Severe respiratory complications, surfactant use, and transient rapid breathing all fell in the steroid group.¹² A separate randomized trial found an even more striking difference: respiratory complications in roughly 4% of the steroid group versus 25% in the placebo group, along with fewer NICU admissions and less need for active resuscitation.¹³

However, late preterm steroid use comes with a well-documented trade-off: neonatal hypoglycemia. A meta-analysis of randomized trials found that babies exposed to late preterm steroids were about 60% more likely to develop low blood sugar after birth.¹⁴ The large NEJM trial reported the same magnitude of increased risk.¹² Neonatal hypoglycemia usually resolves with extra feeding or a glucose drip, but it can extend the hospital stay and sometimes requires NICU monitoring, which partly offsets the respiratory benefits. This is why late preterm steroid use remains somewhat more case-by-case than the near-universal recommendation at earlier gestational ages.

Repeat Courses When Delivery Does Not Come

Because so many women do not deliver within the optimal seven-day window, the question of whether to give a second (or third) course of steroids has been studied extensively. A Cochrane review of repeat-dose trials found that a repeat course reduced respiratory distress syndrome (about 17% fewer cases) and serious infant outcomes compared with no repeat treatment.¹⁵ An individual participant data meta-analysis confirmed a modest reduction in the need for respiratory support, with about 21 women needing to be treated to prevent one baby from requiring breathing assistance.¹⁶

The concern with repeat courses has always been growth. Babies exposed to multiple steroid courses tend to be born slightly lighter. The Cochrane review found a mean reduction of about 76 grams, though once birth weight was adjusted for gestational age, the difference disappeared.¹⁵ A follow-up study at about two and a half years of age found no significant differences in cognitive scores or physical measurements between children who had been exposed to repeat courses and those who had not. One concerning signal was a higher rate of cerebral palsy in the repeat-dose group, though the numbers were small and the difference was not statistically significant.¹⁷ Because of findings like these, most guidelines recommend limiting repeat courses. A single rescue course is widely accepted if the initial course was given more than a week earlier and delivery still appears imminent, but routine multiple repeat courses are discouraged.

Effects on the Mother’s Blood Sugar

One side effect that catches many pregnant people off guard is a sharp rise in blood sugar after the steroid injection. Corticosteroids are well known to raise glucose levels, and pregnancy already pushes insulin resistance higher than normal. A study measuring continuous glucose levels after betamethasone found that most women without diabetes experienced significant hyperglycemia, with average peak blood glucose around 173 mg/dL. Women who already had diabetes saw even higher peaks, averaging about 205 mg/dL.¹⁸

A prospective study at an Indian tertiary center looked at this more closely. Among women without pre-existing diabetes, about 72% developed clinically significant hyperglycemia after steroid administration. Among those who already had gestational or pre-existing diabetes, the figure was 92%. Women with pre-existing diabetes tended to need insulin within six hours of the steroid dose, while those with gestational diabetes needed it within 12 to 24 hours, and previously non-diabetic women within 24 to 48 hours. Importantly, about a third of the non-diabetic group and nearly half of the diabetic group still had elevated blood sugar a full week after the steroid course ended.¹⁹ For this reason, hospitals typically monitor blood sugar closely after the injections, and people with known diabetes should expect their insulin needs to increase temporarily.

Twin Pregnancies

Twin pregnancies are at much higher risk of preterm birth than singleton pregnancies, so antenatal steroids come up frequently. A reasonable worry is whether the standard dose is enough when there are two placentas (or one shared placenta) distributing the drug. Research so far suggests the same dose works just as well. A large study comparing outcomes in twins and singletons who received a complete course within the optimal one-to-seven-day window found nearly identical reductions in neonatal death, need for mechanical ventilation, and respiratory distress syndrome between the two groups.²⁰ Despite these encouraging results, questions remain about the best timing and whether repeat courses should be handled differently in multiples.²¹

Long-Term Outcomes for Children

One of the most common parental concerns is whether exposing a developing brain to steroids could leave lasting effects. The evidence here is mostly reassuring but not entirely settled. A study following children born at term who had been exposed to antenatal corticosteroids (cases where steroids were given but the pregnancy continued to full term) found no difference in rates of asthma, attention deficit disorder, or developmental delay compared with unexposed children.²² The Cochrane review of repeat courses also found no significant differences in disability or neurodevelopmental outcomes at early childhood follow-up.¹⁵

That said, a review article in the American Journal of Perinatology flagged the potential for long-term neurodevelopmental consequences in steroid-exposed fetuses, particularly when multiple courses are given or when the baby ends up delivering at full term (meaning the steroid exposure may not have been necessary).²³ The honest summary is that one standard course given before a genuinely preterm delivery appears safe for the child’s long-term development. Multiple courses and term exposures carry less certainty, which is part of why clinicians try to be judicious about who gets the treatment.

Steroids Before a Planned Cesarean at Term

Babies born by planned cesarean section at term, even at 37 to 39 weeks, have a slightly higher rate of breathing problems than those born vaginally. Labor itself triggers hormonal changes that help clear fluid from the lungs, and a scheduled cesarean skips that process. This has led to interest in giving steroids before an elective cesarean to reduce the chance of transient breathing difficulties. A Cochrane review on the topic found that prophylactic betamethasone before a term cesarean significantly reduced NICU admissions for respiratory problems, but the evidence for reducing specific conditions like respiratory distress syndrome or transient rapid breathing did not reach statistical significance.²⁴ This use remains much more controversial than the standard preterm indication, and most guidelines do not recommend it as routine practice.

A Cautionary Lesson from Low-Resource Settings

Nearly all the evidence showing clear benefits of antenatal steroids comes from hospitals with the capacity to monitor pregnancies closely and provide neonatal intensive care. When researchers tried to expand steroid use broadly in low-income countries through a large cluster-randomized trial called the ACT trial, the results were troubling: among the general population of births (not just preterm ones), steroid-treated communities saw higher neonatal death rates and more maternal infections.²⁵ The problem was not the steroids themselves but the difficulty of accurately identifying which women were actually going to deliver preterm. In settings where gestational age is uncertain and neonatal care is limited, giving steroids too broadly can expose term babies (who do not benefit) to unnecessary risk.

A subsequent trial, the ACTION trial, took a more targeted approach in low-resource hospitals. Women who met more stringent criteria for likely early preterm delivery received dexamethasone or placebo. This time, neonatal death was about 20% in the steroid group versus about 24% in the placebo group, a meaningful reduction, and the risk of maternal infection did not increase significantly.²⁶ The lesson from these two trials is that the steroid shot works best when it is given to the right patients in settings where babies can be cared for after birth. The drug is powerful, but its effectiveness depends on the broader system around it.

How the Discovery Happened

The story behind antenatal steroids is one of the better examples of serendipity in medicine. In the late 1960s, a New Zealand researcher named Graham Liggins was studying what triggers labor. He was injecting large doses of steroids into pregnant sheep, trying to induce labor, when he noticed something unexpected: the preterm lambs born after steroid exposure had lungs that were far more mature than they should have been for their gestational age. These lambs could breathe on their own at ages when unexposed lambs could not. Liggins teamed up with pediatrician Ross Howie to test this in humans, and in 1972 they published a randomized trial showing that two injections of betamethasone given 24 hours apart reduced the rate of respiratory distress syndrome in preterm newborns from about 16% to 10%.⁵ Despite this evidence, widespread adoption was slow. It took another two decades and a landmark NIH consensus statement in 1994 before the treatment became standard practice. That delay is estimated to have cost tens of thousands of infant lives, and it is often cited as a case study in how long it can take for strong evidence to change clinical behavior.

1
Cochrane Database of Systematic Reviews. Antenatal corticosteroids to accelerate fetal lung maturity for women at risk of preterm birth
2
PubMed. Glucocorticoids and lung development in the fetus and preterm infant
3
PubMed. Dexamethasone versus betamethasone for preterm birth: a systematic review and network meta-analysis
4
Cochrane Database of Systematic Reviews. Different corticosteroid treatments before early birth for improving outcomes for babies
5
PubMed Central. What we have learned about antenatal corticosteroid regimens
6
PubMed Central. Timing of antenatal steroid administration for imminent preterm birth: results of a prospective observational study in Germany
7
PubMed Central. Predicting preterm birth: Cervical length and fetal fibronectin
8
PubMed. Efficacy of antenatal corticosteroids in preterm twins: the EPIPAGE-2 cohort study
9
BMJ. Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study
10
JAMA Pediatrics. Association of Neurodevelopmental Outcomes and Neonatal Morbidities of Extremely Premature Infants With Differential Exposure to Antenatal Steroids
11
PubMed. The gestational effect of antenatal corticosteroids on respiratory distress syndrome in very low birth weight infants: A population-based study
12
PubMed Central. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery
13
PubMed Central. Does the use of antenatal corticosteroids reduce respiratory morbidity in babies born in late preterm period?
14
PLOS ONE. Antenatal corticosteroids for impending late preterm (34-36+6 weeks) deliveries—A systematic review and meta-analysis of RCTs
15
PubMed Central. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes
16
PubMed Central. Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis
17
PubMed. Long-term outcomes after repeat doses of antenatal corticosteroids
18
PubMed. Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes
19
PubMed Central. Antenatal Corticosteroids and Their Effects on Maternal Glycemic Status: A Prospective Observational Study From an Indian Tertiary Referral Center
20
PubMed. The role of antenatal corticosteroids in twin pregnancies complicated by preterm birth
21
PubMed Central. The role of antenatal corticosteroids in twin pregnancy
22
PubMed Central. Long-term childhood outcomes for babies born at term who were exposed to antenatal corticosteroids
23
PubMed. A Growing Dilemma: Antenantal Corticosteroids and Long-Term Consequences
24
Cochrane Database of Systematic Reviews. Prophylactic corticosteroids for elective caesarean section at term
25
The Lancet. A multifaceted intervention to implement antenatal corticosteroids at all levels of health care in low-income and middle-income countries (ACT): a cluster-randomised trial
26
New England Journal of Medicine. Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries