Impact of Antenatal Glucocorticoid Therapy and Risk of Preterm Delivery on Intelligence in Term-Born Children

Alexander, Nina; Rosenlöcher, Franziska; Dettenborn, Lucia; Stalder, Tobias; Linke, Julia; Distler, W.; Morgner, J; Miller, Robert; Kliegel, Matthias; Kirschbaum, Clemens

doi:10.1210/jc.2015-2453

Cited by 35 publications

(36 citation statements)

References 64 publications

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“…Betamethasone (BM), a synthetic glucocorticoid, is considered the glucocorticoid of choice for this antenatal treatment (Alexander et al, 2016;Lindsley et al, 2015) being used for pregnant women between 24 and 34 weeks of gestation ( Jobe & Soll, 2004;Rayburn et al, 1997;Wapner, 2013), promoting fetal lung maturation and thus reducing the incidence of respiratory distress syndrome, neonatal mortality and morbidity (Gyamfi-Bannerman et al, 2016;Lindsley et al, 2015). However, the prenatal exposure to BM demonstrated several systemic long-term deleterious effects on offspring in different experimental protocols (Alexander et al, 2016;Belanoff et al, 2001;Bertram & Hanson, 2002;Pascual et al, 2014;Su et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Reproductive disorders in female rats after prenatal exposure to betamethasone

Borges

Pacheco

Guerra

et al. 2017

J of Applied Toxicology

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Betamethasone is the drug of choice for antenatal treatment, promoting fetal lung maturation and decreasing mortality. Previous studies in rats reported male programming and alteration in sperm parameters and sexual behavior following intrauterine betamethasone exposure. The impact on the female reproductive development is not known. In this study, rat female offspring was assessed for sexual development, morphophysiology of the reproductive tract and fertility after maternal exposure to 0.1 mg kg of betamethasone or vehicle on gestational days 12, 13, 18 and 19. The treatment promoted reduction of litter weight on postnatal day 1, morphological masculinization in females, delay in the age of puberty onset, reduction in estrus number, increase in estrous cycle length and increase in luteinizing hormone serum levels and uterus weight. The females from the betamethasone group showed an increase of myometrial uterine area and decrease in endometrial uterine area. These animals also performed less lordosis during the sexual behavior test and showed impaired reproductive performance. The uterus showed higher contraction in the treated group as shown by a pharmacological assay. In conclusion, prenatal betamethasone exposure in rats promoted female masculinization, altered sexual development and reproductive parameters. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Reproductive disorders in female rats after prenatal exposure to betamethasone

Borges

Pacheco

Guerra

et al. 2017

J of Applied Toxicology

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“…60 A Finnish birth cohort study revealed that prenatal exposure to a single course of sGC was associated with adverse mental health outcomes, including ADHD symptomology in childhood (8 years) and adolescence (16 years). 62 This highlights the importance of factoring the presence of pregnancy complications into these types of study, as well as acknowledging the potential limitations of retrospective analysis. However, subsequent analysis revealed that the effect on IQ was linked to the risk of being born preterm, rather than the sGC exposure.…”

Section: Neurodevelopment and Behavioursmentioning

confidence: 99%

Prenatal programming of stress responsiveness and behaviours: Progress and perspectives

Hamada

Matthews

2019

J Neuroendocrinology

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Parental exposure to stress or glucocorticoids either before or during pregnancy can have profound influences on neurodevelopment, neuroendocrine function and behaviours in offspring. Specific outcomes are dependent on the nature, intensity and timing of the exposure, as well as species, sex and age of the subject. Most recently, it has become evident that outcomes are not confined to first‐generation offspring and that there may be intergenerational and transgenerational transmission of effects. There has been intense focus on the mechanisms by which such early exposure leads to long‐term and potential transgenerational outcomes, and there is strong emerging evidence that epigenetic processes (histone modifications, DNA methylation, and small non‐coding RNAs) are involved. New knowledge in this area may allow the development of interventions that can prevent, ameliorate or reverse the long‐term negative outcomes associated with exposure to early adversity. This review will focus on the latest research, bridging human and pre‐clinical studies, and will highlight some of the limitations, challenges and gaps that exist in the field.

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“…Ascertainment bias likely occurs as well. Since pregnancy complications such as threatened preterm delivery are stressful for mothers, Alexander et al [38, 39] used an innovative experimental approach to separate the consequences of maternal stress and sGC use. They recruited three distinct groups of term infants: group 1 consisted of infants of mothers with a complicated pregnancy who had received a single course of sGC (PP/GC); group 2 consisted of infants of mothers with a complicated pregnancy who had not received sGC (PP/non-GC); and group 3 were infants of mothers without pregnancy complications.…”

Section: Antenatal Gc Exposurementioning

confidence: 99%

“…Using the paradigm of an acute psychosocial stress situation, 6- to 11-year-old term-born children exposed to antenatal sGC manifested significantly increased cortisol reactivity compared to both the control children and the maternally stressed group that did not receive sGC; this effect was more pronounced in females [38]. After controlling for potentially confounding factors, IQ scores were lower in both the PP/GC and PP/non-GC groups; this finding was primarily driven by the results in males and suggests that the stress of threatened preterm delivery independent of sGC exposure can have deleterious consequences on postnatal cognitive function [39]. …”

Section: Antenatal Gc Exposurementioning

confidence: 99%

The Hypothalamic-Pituitary-Adrenal Axis and the Fetus

2018

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Glucocorticoids (GCs), cortisol in humans, influence multiple essential maturational events during gestation. In the human fetus, fetal hypothalamic-pituitary-adrenal (HPA) axis function, fetal adrenal steroidogenesis, placental 11β- hydroxysteroid dehydrogenase type 2 activity, maternal cortisol concentrations, and environmental factors impact fetal cortisol exposure. The beneficial effects of synthetic glucocorticoids (sGCs), such as dexamethasone and betamethasone, on fetal lung maturation have significantly shifted the management of preterm labor and threatened preterm birth. Accumulating evidence suggests that exposure to sGCs in utero at critical developmental stages can alter the function of organ systems and that these effects may have sequelae that extend into adult life. Maternal stress and environmental influences may also impact fetal GC exposure. This article explores the vulnerability of the fetal HPA axis to endogenous GCs and exogenous sGCs.

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Impact of Antenatal Glucocorticoid Therapy and Risk of Preterm Delivery on Intelligence in Term-Born Children

Cited by 35 publications

References 64 publications

Reproductive disorders in female rats after prenatal exposure to betamethasone

Reproductive disorders in female rats after prenatal exposure to betamethasone

Prenatal programming of stress responsiveness and behaviours: Progress and perspectives

The Hypothalamic-Pituitary-Adrenal Axis and the Fetus

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