Effects of Intrauterine Exposure to Synthetic Glucocorticoids on Fetal, Newborn, and Infant Hypothalamic-Pituitary-Adrenal Axis Function in Humans: A Systematic Review

Tegethoff, Marion; Pryce, Christopher R.; Meinlschmidt, Gunther

doi:10.1210/er.2008-0014

Cited by 118 publications

(108 citation statements)

References 250 publications

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“…A meta-analysis of 49 human studies assessed the impact of antenatal treatment with synthetic glucocorticoids and concluded that although basal HPA axis function recovered within 2 weeks of delivery, there was a sustained (O4-8 weeks) suppression of the cortisol response to pain (Tegethoff et al 2009), suggesting that antenatal glucocorticoid treatment itself may cause a persistent inability to mount a cortisol stress response. Thus, both immaturity and antenatal glucocorticoid therapy may result in a similar limited adrenal reserve in premature birth.…”

Section: Insufficient Glucocorticoid Action: Prematuritymentioning

confidence: 99%

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Rog-Zielinska¹,

Richardson²,

Denvir³

et al. 2013

Journal of Molecular Endocrinology

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Glucocorticoids are steroid hormones, essential in mammals to prepare for life after birth. Blood levels of glucocorticoids (cortisol in most mammals including humans; corticosterone in rats and mice) rise dramatically shortly before birth. This is mimicked clinically in the routine administration of synthetic glucocorticoids to pregnant women threatened by a preterm birth or to preterm infants to improve neonatal survival. Whilst effects on lung are well documented and essential for postnatal survival, those on heart are less well known. In this study, we review recent evidence for a crucial role of glucocorticoids in late gestational heart maturation. Either insufficient or excessive glucocorticoid exposure before birth may alter the normal glucocorticoid-regulated trajectory of heart maturation with potential life-long consequences.

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Section: Insufficient Glucocorticoid Action: Prematuritymentioning

confidence: 99%

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Rog-Zielinska¹,

Richardson²,

Denvir³

et al. 2013

Journal of Molecular Endocrinology

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“…57,58 Third, the hypothalamicpituitary-adrenal (HPA) axis is another candidate mechanism linking maternal asthma during pregnancy with offspring diseases, as dysregulation of the HPA axis is a frequently observed feature of asthma 59 and changes in intrauterine glucocorticoid exposure have been shown to take effect in the fetus. 60 Fourth, one may speculate that asthma medication adversely affects the fetus. However, children of mothers with asthma taking asthma medication were at similar risk for diseases as children of mothers with asthma but without asthma medication, indicating that asthma medication does not play an important role in the offspring' s risk of diseases.…”

Section: Figurementioning

confidence: 99%

Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

Tegethoff¹,

Olsen

Schaffner

et al. 2013

Pediatrics

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WHAT'S KNOWN ON THIS SUBJECT: Asthma is a common medical complication during pregnancy that is associated with an increased risk of adverse obstetric outcomes. WHAT THIS STUDY ADDS:This study adds knowledge on potential long-term consequences of maternal asthma during pregnancy for offspring health, demonstrating that maternal asthma during pregnancy is linked to a wide spectrum of offspring diseases during childhood. abstract BACKGROUND AND OBJECTIVE: Maternal asthma is a common pregnancy complication, with adverse short-term effects for the offspring. The objective was to determine whether asthma during pregnancy is a risk factor of offspring diseases. METHODS:We studied pregnant women from the Danish National Birth Cohort (births: 1996Cohort (births: -2002; prospective data) giving birth to live singletons (n = 66 712 mother-child pairs), with 4145 (6.2%) women suffering from asthma during pregnancy. We estimated the associations between asthma during pregnancy and offspring diseases (International Classification of Diseases, 10th Revision diagnoses from national registries), controlling for potential confounders and validating findings by secondary analyses. RESULTS:Offspring median age at end of follow-up was 6.2 (3.6-8.9) years. Asthma was associated with an increased offspring risk of infectious and parasitic diseases (hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.23-1.46), diseases of the nervous system (HR 1.43; CI 1.18-1.73), ear (HR 1.33; CI 1.19-1.48), respiratory system (HR 1.43; CI 1.34-1.52), and skin (HR 1.39; CI 1.20-1.60), and potentially (not confirmed in secondary analyses) of endocrine and metabolic disorders (HR 1.26; CI 1.02-1.55), diseases of the digestive system (HR 1.17; CI 1.04-1.32), and malformations (odds ratio 1.13; CI 1.01-1.26), but not of neoplasms, mental disorders, or diseases of the blood and immune system, circulatory system, musculoskeletal system, and genitourinary system. CONCLUSIONS:To the best of our knowledge, this is the first comprehensive study of the associations between asthma during pregnancy and a wide spectrum of offspring diseases. In line with previous data on selected outcomes, asthma during pregnancy may be a risk factor for numerous offspring diseases, suggesting that careful monitoring of women with asthma during pregnancy and their offspring is important. Dr Tegethoff conceptualized and designed the study, carried out the statistical analyses, interpreted data, drafted the initial manuscript, critically reviewed the manuscript, and obtained funding; Dr Olsen acquired data, interpreted data, critically reviewed the manuscript, and obtained funding; Mr Schaffner carried out the statistical analyses, interpreted data, and critically reviewed the manuscript; Dr Meinlschmidt conceptualized and designed the study, carried out the statistical analyses, interpreted data, critically reviewed the manuscript, and obtained funding; and all authors approved the final manuscript as submitted. Asthma is a frequently occurring medical condition in pregnancy, ...

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“…Unfortunately treatment options remain very limited, especially in preterm newborns. Therapeutic limitations are mainly due to: (i) the lack of non-invasive and reliable diagnostic markers enabling the detection of placental and fetal insults prenatally, and (ii) uncertainties about drug metabolism and benefit/risk balance of drug administration, to both the pregnant mother and fetus (Kenyon et al, 2008;King et al, 2002;Perlman, 2006;Tegethoff et al, 2009). In contrast, postnatal treatment is a more clinically attractive option since diagnosis of prenatal inflammation and HI are most often made postnatally due to clinical investigations routinely performed in human neonates.…”

Section: Introductionmentioning

confidence: 99%

Postnatal administration of IL-1Ra exerts neuroprotective effects following perinatal inflammation and/or hypoxic-ischemic injuries

Girard¹,

Sébire²,

Brochu³

et al. 2012

Brain, Behavior, and Immunity

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New therapeutic strategies are needed to protect neonates, especially premature newborns, against brain injury and associated neurobehavioral deficits. The role of pro-inflammatory cytokines, especially IL-1β, in the pathophysiological pathway leading to neonatal brain damage is increasingly recognized and represents an attractive therapeutic target. We investigated the therapeutic potential of postnatal systemic administration of the interleukin (IL)-1 receptor antagonist (IL-1Ra) in an animal model of perinatal brain injury using the insults most common to human neonates, i.e. prenatal exposure to inflammation and/or postnatal hypoxia-ischaemia (HI). We found that postnatal administration of IL-1Ra preserved motor function and exploratory behavior after either prenatal exposure to inflammatory agent lipopolysaccharide (LPS) or postnatal HI insult. The deleterious effect of combined prenatal LPS and postnatal HI on brain development was also alleviated by administration of IL-1Ra, as seen by the protected neural stem cell population, prevention of myelin loss in the internal capsule, decreased gliosis, and decreased neurobehavioral impairment. This study showed the distinct pattern of functional deficits induced by prenatal inflammation as compared to postnatal HI and the therapeutic potential of IL-1Ra administration against neonatal brain injury. Furthermore, our results highlight the potential for postnatal treatment of prenatal inflammatory stressors.

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Effects of Intrauterine Exposure to Synthetic Glucocorticoids on Fetal, Newborn, and Infant Hypothalamic-Pituitary-Adrenal Axis Function in Humans: A Systematic Review

Cited by 118 publications

References 250 publications

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

Postnatal administration of IL-1Ra exerts neuroprotective effects following perinatal inflammation and/or hypoxic-ischemic injuries

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