Neurodevelopmental disorders among term infants exposed to antenatal corticosteroids during pregnancy: a population-based study

Abstract

ObjectiveAn increasing proportion of fetuses are exposed to antenatal corticosteroids (ACS). Despite their immediate beneficial effects, the long-term safety of ACS has been an ongoing source of concern. In the current study, we assessed the likelihood of neurodevelopmental problems among term infants exposed to ACS earlier in pregnancy compared with non-exposed term infants.DesignRetrospective cohort study (2006–2011). Median duration of follow-up was 7.8 (IQR 6.4–9.2) years.SettingPopulation-based study, Ontario, Canada.ParticipantsAll live singleton infants born at term (≥370/7weeks gestation) (n=529 205).ExposureACS during pregnancy.Primary and secondary outcome measuresA composite of diagnostic or billing codes reflecting proven or suspected neurodevelopmental problems during childhood including audiometry testing, visual testing or physician service claim with a diagnosis code related to a suspected neurocognitive disorder.ResultsAt 5 years of age, the cumulative rate for the primary outcome was higher among infants exposed to ACS compared with non-exposed infants: 61.7% (3346/5423) vs 57.8% (302 520/523 782), respectively (p<0.001; number needed to harm (NNH)=25, 95% CI 19 to 38; adjusted HR (aHR) 1.12, 95% CI 1.08 to 1.16). Similar findings were observed for each of the individual components of the primary outcome: 15.3% vs 12.7% for audiometry testing (p<0.001; NNH=39, 95% CI 29 to 63; aHR 1.18, 95% CI 1.11 to 1.25); 45.4% vs 43.5% for visual testing (p=0.006; NNH=54, 95% CI 31 to 200; aHR 1.08, 95% CI 1.04 to 1.12) and 25.8% vs 21.6% for suspected neurocognitive disorder (p<0.001; NNH=24, 95% CI 19 to 33; aHR 1.16, 95% CI 1.10 to 1.21).ConclusionsWe found an association among term infants between exposure to ACS during pregnancy and healthcare utilisation during childhood related to suspected neurocognitive and neurosensory disorders.

Fetal Diagnosis and Therapy during the COVID-19 Pandemic: Guidance on Behalf of the International Fetal Medicine and Surgery Society

“…Corticosteroids should therefore not be used in asymptomatic SARS-CoV-2-positive patients or those with mild COVID-19 symptoms, unless preterm birth <34 + 0 weeks’ gestation is anticipated [2, 24]. Their use in ICU patients should be judiciously evaluated, as well as in patients at >34 + 0 weeks’ gestation [25].…”

Prophylactic antenatal corticosteroids for fetal lung maturity: Known unknowns and unknown unknowns

“…Questions remain about the balance between the risks and benefits of ACS after 34 + 6 weeks of gestation as there are no data on long-term outcomes. There are also increasing concerns about the long-term outcomes for babies exposed to ACS before 34 + 6 weeks of gestation but subsequently delivered at term [ 4 , 5 ]. This more recent evidence reveals new unknowns about ACS, only some of which are currently being actively investigated.…”

“…Combined with the current low threshold for ACS administration, this means that a large number of babies exposed to ACS before 34 + 6 weeks of gestation may not actually benefit from the intervention. There is increasing concern about the potential for harm in such babies [ 4 , 5 ]. A Finnish observational register-based study found that ACS exposure was associated with a reduction in birth weight, birth length and head circumference in babies subsequently born at pre-term, early-term and term gestations [ 4 ].…”

“…These findings on in-utero growth are consistent with reports from animal studies. In a Canadian population-based study, Melamed et al [ 5 ] found an association between exposure to ACS during pregnancy and healthcare utilisation during childhood related to suspected neurocognitive and neurosensory disorders in babies born at term. While these data are concerning, they should not deter clinicians from offering ACS to women at increased risk of giving birth before 34 + 6 weeks of gestation.…”

“…However, there are no data on long-term outcomes following the administration of ACS after 34 + 6 weeks of gestation. Based on data on animal studies and recent observational data from population studies [ 4 , 5 ], there is some concern for neurodevelopmental, cardiovascular and metabolic outcomes. Given the large number of babies born at late pre-term gestations (35 to 36 + 6 weeks) and by early (37 + 0 to 38 + 6 weeks) caesarean section, any long-term consequences of ACS are likely to impact a large number of individuals and families, with implications for health, educational and social services and the wider economy.…”