Few studies have examined the benefits of giving antenatal corticosteroids to women after 34 weeks of gestation to prevent RDS.11
Although administration of antenatal corticosteroids is standard of care to decrease the severe and possibly fatal consequences of respiratory distress syndrome and intraventricular hemorrhage in neonates born at less than 34 weeks of gestation,2
neonates born at 34 weeks or more of gestation with less risk of these morbidities may not incur as clear a benefit and may be exposed to undue risk. Indeed, of the 29 neonates born at greater than 34 weeks of gestation in Crowley’s original meta-analysis, corticosteroids did not decrease the incidence of RDS.2
The Antenatal Steroids for Term Elective Cesarean Section study, by Stutchfield et al,17
examined the use of antenatal corticosteroids given to women who planned to deliver at 37 weeks of gestation or greater by elective cesarean. Although the investigators found a significant difference in the rate of RDS between the treatment and control groups (1.1 and 0.2%, respectively), they had similar numbers of admissions to neonatal intensive care for both groups (26 and 32, respectively), indicating that although antenatal corticosteroids may have decreased the incidence of respiratory morbidity, other neonatal morbidities still necessitated intensive care.12
Another recent study randomized women to corticosteroids compared with no treatment after immature amniocentesis between 34 0/7 and 36 6/7 weeks of gestation.6
Steroid administration was associated with a higher mean weekly increase in TDx-FLM II than was no treatment, although the study had insufficient power to assess differences in neonatal morbidities.5
A more recent clinical trial from Brazil randomized women at 34 to 36 weeks of gestation at risk of imminent premature delivery to a two-dose course of betamethasone or placebo and found no significant difference in the incidence of respiratory disorders (which included RDS and transient tachypnea of the newborn) nor the need for ongoing respiratory support between the two groups.13
Our study evaluates differences in neonatal morbidity depending on the clinical pathway chosen after an amniocentesis documenting immature fetal lung indices. After immature amniocentesis, some physicians may consider their patient stable enough to await mature amniocentesis before delivery or to manage expectantly based on the maternal risks of prolonging pregnancy weighed against the neonatal risks of a possible premature delivery. As a secondary analysis with a small sample size, we had insufficient power to analyze individual differences between specific morbidities when comparing between groups. However, when comparing the three groups, despite no differences in major maternal morbidities such as hypertensive disease, diabetes, oligohydramnios, and preterm labor, corticosteroid-exposed neonates had higher rates of composite adverse neonatal outcome and composite adverse respiratory outcome compared with neonates born after mature amniocentesis or expectant management. Even when we attempted to account for the differences in maternal and fetal factors such as presence of labor before delivery, intrauterine growth restriction, and premature rupture of membranes through multivariable adjusted analyses, we continued to see significantly higher rates of both composite outcomes and individual neonatal morbidities in the corticosteroid-exposed group compared with the other two groups.
Not only does steroid administration appear to have no benefit when administered in the late pre-term and early term period, but our findings suggest it may actually be harmful. Specifically, our study indicates an almost twofold increased risk of hypoglycemia and a threefold increased risk of sepsis evaluation for neonates whose mothers received corticosteroids at 34 weeks of gestation or more after immature amniocentesis compared with those managed expectantly. Considering the biologic plausibility of steroids altering glycemic profiles and response to infection, these findings are certainly provocative, hypothesis-generating, and worthy of further evaluation in larger, randomized trials.
The retrospective nature of our study also may introduce bias based on inherent differences among pregnancies in which one approach was chosen over another. Performance of lung maturity amniocentesis implies that the health care provider considered the clinical scenario elective, because the health care provider had time to ponder and then act on the results. For example, a physician may desire sooner delivery in more complicated pregnancies but be willing to await mature amniocentesis or simply follow the pregnancy expectantly in those who have a more elective reason for delivery planning. Pregnancies that are allowed to continue may be inherently different, possibly at lower risk for adverse outcome, than those in which the obstetric provider chooses to administer steroids after immature lung studies and then deliver in less than 1 week. These differences in reasons for amniocentesis testing may influence the frequency of morbidities, ie, those at highest risk needing imminent delivery may be in the corticosteroid-exposed group.
Although one can never completely account for all potential confounders in a cohort study such as this, we did adjust for important factors, which are known to influence neonatal outcome such as medical comorbidities, labor onset before delivery, and pregnancy complications such as intrauterine growth restriction and prolonged rupture of membranes. After taking these factors into account, corticosteroid exposure seems to have no benefit and may possibly be harmful to neonates born at 34 weeks of gestation or more after immature amniocentesis. Our data suggest that the choice of steroid administration and then delivery if the results are immature are associated with high rates of adverse neonatal outcomes and that if the delivery is not otherwise medically indicated, either expectant management or delivery after mature fetal lung indices may be the prudent approach.
Antenatal corticosteroids have proven benefits in neonates born less than 34 weeks of gestation,14,15
and these incurred benefits certainly outweigh any theoretic maternal or neonatal risks at that gestational age. For neonates born at 34 weeks of gestation and greater, who still may have risk of neonatal morbidity as a result of prematurity, but much lower risk of more devastating morbidity such as intraventricular hemorrhage, the risks of corticosteroid administration may exceed the benefits. In a discussion of Crowley’s original meta-analysis regarding antenatal corticosteroid administration, Sinclair16
calculated that with a baseline risk of RDS of 50% in neonates at 30 weeks of gestation or less, five neonates would need to be treated to prevent one case of RDS. However, because the baseline risk of RDS in neonates at greater than 34 weeks of gestation is 15%, the number needed to treat rises to 145. Our findings agree with recent cohort studies showing that the benefit of antenatal corticosteroids varies for neonates born at either extreme of gestation and incurs the greatest benefit for neonates born between 29 to 34 weeks of gestation.17–20
Further study is needed to determine if the number needed to harm after 34 weeks gestation incurs is less than the number needed to treat for benefit.
Our work continues to support the notion that gestational maturity itself has the strongest correlation with a lack of neonatal morbidity. If delivery is able to be prolonged without undue risk to the mother, our study suggests that gestational maturity will decrease risk of subsequent neonatal morbidity. As such, we recommend that if delivery is indicated based on the maternal or fetal condition before 39 weeks of gestation, after careful consideration of the risks to the mother and fetus, the mother’s pregnancy should be managed as such without the introduction of possible additional morbidity by administration of antenatal corticosteroids until further evidence is available from randomized controlled trials.