Associations Between Maternal Antenatal Corticosteroid Treatment and Psychological Developmental and Neurosensory Disorders in Children

Räikkönen, Katri; Gissler, Mika; Tapiainen, Terhi; Kajantie, Eero

doi:10.1001/jamanetworkopen.2022.28518

Cited by 29 publications

(37 citation statements)

References 28 publications

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“…5,6 In studies considering longer-term neonatal follow-up, exposure to antenatal corticosteroids has been associated with differences in childhood neurocognitive development, particularly when delivery occurs at term. [9][10][11] In some studies, exposure to antenatal corticosteroids has also been found to increase maternal infection morbidity. 6 These findings raise concerns that the American College of Obstetricians and Gynecologists guidelines recommending antenatal corticosteroid administration in the late-preterm period for those at risk for preterm delivery may not be universally appropriate.…”

Section: Resultsmentioning

confidence: 99%

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Late-Preterm Antenatal Steroids for Reduction of Neonatal Respiratory Complications

Yenuberi,

Ross,

Sasmita Tirkey

et al. 2024

Obstetrics &Amp; Gynecology

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OBJECTIVE: To evaluate the efficacy of antenatal corticosteroids in reducing neonatal respiratory complications when administered to those at risk of preterm delivery between 34 and 36 6/7 weeks of gestation. METHODS: This was a single-center, triple-blind, randomized, placebo-controlled trial in southern India enrolling pregnant participants at risk of preterm delivery between 34 and 36 6/7 weeks of gestation. Computer-generated block randomization was used with participants randomized to either one course of intramuscular betamethasone or placebo. The primary outcome was a composite of treatment for respiratory distress in the neonate, defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life. Neonatal secondary outcomes were transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, hypoglycemia, stillbirth, and early neonatal death; maternal secondary outcomes were chorioamnionitis, postpartum hemorrhage, puerperal fever, and length of hospitalization. All analyses were based on intention to treat. A sample size of 1,200 was planned with 80% power to detect a 30% reduction in rates of respiratory distress. After a planned interim analysis, enrollment was stopped for futility. RESULTS: From March 2020 to August 2022, 847 participants were recruited, with 423 participants randomized to betamethasone and 424 participants randomized to placebo. There were 22 individuals lost to follow-up. There was no statistically significant difference in the primary outcome (betamethasone 4.9% vs placebo 4.8%, relative risk 1.03, 95% CI, 0.57–1.84, number needed to treat 786). There were no statistically significant differences in secondary neonatal or maternal outcomes. CONCLUSION: Betamethasone administered in the late preterm period to those at risk for preterm delivery did not reduce the need for treatment of neonatal respiratory distress. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry of India, CTRI/2019/09/021321.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Late-Preterm Antenatal Steroids for Reduction of Neonatal Respiratory Complications

Yenuberi,

Ross,

Sasmita Tirkey

et al. 2024

Obstetrics &Amp; Gynecology

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“…Recent research hints at potential long‐term neurodevelopmental challenges in children who have been exposed to corticosteroids 3 . There is also growing concern about severe infections, pointing to heightened risks.…”

Section: Introductionmentioning

confidence: 99%

Editorial: Antenatal corticosteroids for pregnancy and risk of serious infection—Revisiting the role of antenatal corticosteroids

Chiu,

Yii,

Yong

2024

Int J of Rheum Dis

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Previous research suggested a heightened risk of sepsis and congenital pneumonia in newborns exposed to ACS. 5 When weighing the pros of ACS, such as decreasing neonatal respiratory distress syndrome by 4.3% and reducing neonatal death rates between 2.3% and 2.6%, 6 against the amplified risk of severe infection (0.4%, 0.9%, and 1.7% the first 3, 6, and 12 months, respectively), medical professionals must decide judiciously regarding their application.Additionally, the varied risk in full term compared to preterm babies implies that while antenatal corticosteroids can be advantageous for preterm infants, they should be used with discretion in full-term pregnancies. On a biological level, these results may be linked to how corticosteroids affect lung cell differentiation and surfactant production, combined with the potential hidden risk of severe infections in early life. Corticosteroids alter Th1/Th2 immune reactions may also play a role in influencing inflammatory scenarios in infants during their formative months. | CON CLUS IONIn conclusion, a single regimen of ACS notably increased the risk of severe infection in children by 1.2-1.7 times during their first year of life, 4 emphasizing the importance of closely observing children who have been exposed to these corticosteroids. While these medications undeniably benefit preterm infants, their administration in full-term pregnancies should be approached with prudence given the distinct risk factors. More studies are essential to understand the underlying biological causes of these outcomes and to evaluate the enduring impacts past the newborn phase, especially in full-term babies.

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“…However, recent studies revealed the potential adverse effects of antenatal corticosteroid on fetal neurodevelopment and even contributed to mental and behavioral disorders in children. 12 , 13 Therefore, there is an urgent need to explore the exact aetiology and pathogenesis of GDM-induced FLUD.…”

Section: Introductionmentioning

confidence: 99%

Gestational Diabetes Mellitus Impedes Fetal Lung Development Through Exosome-Dependent Crosstalk Between Trophoblasts and Lung Epithelial Cells

Chen¹,

Gu²,

Wan³

et al. 2023

IJN

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Background Fetal lung underdevelopment (FLUD) is associated with neonatal and childhood severe respiratory diseases, among which gestational diabetes mellitus (GDM) play crucial roles as revealed by recent prevalence studies, yet mechanism underlying GDM-induced FLUD, especially the role of trophoblasts, is not all known. Methods From the perspective of trophoblast-derived exosomes, we established in vitro, ex vivo, in vivo and GDM trophoblast models. Utilizing placenta-derived exosomes (NUB-exos and GDMUB-exos) isolated from normal and GDM umbilical cord blood plasma and trophoblast-derived exosomes (NC-exos and HG-exos) isolated from HTR8/SVneo trophoblasts medium with/without high glucose treatment, we examined their effects on fetal lung development and biological functions. Results We found that, compared with the NUB-exos group, the exosome concentration increased in GDMUB-exos group, and the content of exosomes also changed evidenced by 61 dysregulated miRNAs. After applying these exosomes to A549 alveolar type II epithelial cells, the proliferation and biological functions were suppressed while the proportion of apoptotic cells was increased as compared to the control. In ex vivo studies, we found that GDMUB-exos showed significant suppression on the growth of the fetal lung explants, where the number of terminal buds and the area of explant surface decreased and shrank. Besides, the expression of Fgf10, Vegfa, Flt-1, Kdr and surfactant proteins A, B, C, and D was downregulated in GDMUB-exos group, whilst Sox9 was upregulated. For in vivo studies, we found significant suppression of fetal lung development in GDMUB-exos group. Importantly, we found consistent alterations when we used NC-exos and HG-exos, suggesting a dominant role of trophoblasts in placenta-derived exosome-induced FLUD. Conclusion In conclusion, GDM can adversely affect trophoblasts and alter exosome contents, causing crosstalk disorder between trophoblasts and fetal lung epithelial cells and finally leading to FLUD. Findings of this study will shine insight into the theoretical explanation for the pathogenesis of FLUD.

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Associations Between Maternal Antenatal Corticosteroid Treatment and Psychological Developmental and Neurosensory Disorders in Children

Cited by 29 publications

References 28 publications

Late-Preterm Antenatal Steroids for Reduction of Neonatal Respiratory Complications

Late-Preterm Antenatal Steroids for Reduction of Neonatal Respiratory Complications

Editorial: Antenatal corticosteroids for pregnancy and risk of serious infection—Revisiting the role of antenatal corticosteroids

Gestational Diabetes Mellitus Impedes Fetal Lung Development Through Exosome-Dependent Crosstalk Between Trophoblasts and Lung Epithelial Cells

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