Blood Pressure at 6 Years of Age After Prenatal Exposure to Betamethasone: Follow-up Results of a Randomized, Controlled Trial

Dalziel, Stuart R; Liang, Allen; Parag, Varsha; Rodgers, Anthony; Harding, Jane E.

doi:10.1542/peds.2004-0196

Cited by 43 publications

(32 citation statements)

References 14 publications

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“…In the report of Doyle et al (5), a small but significant elevation in BP was evident at 14 y of age in a cohort who received betamethasone at an average of 28 wk gestation. In contrast, no elevations in BP were found when antenatal glucocorticoids were administered at an average of 32 wk gestation (38).…”

Section: Discussionmentioning

confidence: 77%

Alterations in Fetal Kidney Development and Elevations in Arterial Blood Pressure in Young Adult Sheep after Clinical Doses of Antenatal Glucocorticoids

et al. 2005

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Epidemiologic studies have yielded controversial information regarding an association between antenatal steroid administration and elevations in arterial blood pressure (BP). The aim of the study was to determine whether antenatal administration of a clinically relevant dose of steroids at a time when fetal nephrogenesis is at its highest results in abnormal kidney development and adult hypertension. Pregnant sheep were treated with either vehicle or betamethasone. Maternal injections were given 24 h apart at 80 d of gestational age (dGA; 0.55 of gestation). Animals were studied either as fetuses or as immature adults. Fetuses were delivered by cesarean section at 135 dGA. Adults were studied at 6 mo of age. Betamethasone administration did not induce premature labor or intrauterine growth restriction. In the betamethasone-exposed group, we found at 135 dGA a 25.5% decrease in the number of glomeruli with no differences in fetal kidney weight. In adults, mean, systolic, and diastolic arterial BPs were significantly higher, whereas there were no significant differences in heart rate over the same study period. The major finding of this study is that a single course of antenatal steroids alters renal development and is associated with elevations in arterial BP in lambs at 6 mo of age. We conclude that antenatal glucocorticoid administration under the National Institutes of Health consensus guidelines may alter human fetal renal development. (Pediatr Res 58: 510-515, 2005) Abbreviations AT, angiotensin receptor BP, blood pressure dGA, days of gestational age PAH, para aminohippuric acid RAS, renin-angiotensin systemThe pioneering work of Liggins and Howie (1) resulted in antenatal steroid treatment's becoming standard of care for enhancing fetal lung maturation in pregnancies that are threatened by premature labor between 24 and 34 wk of gestation. Following the National Institutes of Health consensus conference recommendation (2), the use of corticosteroid therapy in the United States has increased from Ͻ15% of individuals who threatened to deliver prematurely in 1990 to Ͼ75% now (3). However, the growing use of glucocorticoids in the perinatal period has become an issue of extreme concern because of the potential for untoward effects found only with long-term outcome studies (3,4). A recent epidemiologic study shows an association between antenatal glucocorticoid administration and elevations in systolic and diastolic blood pressure (BP) at 14 y of age (5). Studies in animals have also associated administration of glucocorticoids during pregnancy with hypertension in the adult offspring (6 -10). However, in these studies, either the dose of glucocorticoids or the developmental stage at which the fetus was exposed does not parallel the clinical use.Fetal exposure to excess glucocorticoids of maternal origin seems to play a central role in the development of hypertension after fetal undernutrition. Maternal adrenalectomy (11) and inhibition of adrenal function with metyrapone (12) negate the effect of protein restr...

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Section: Discussionmentioning

confidence: 77%

Alterations in Fetal Kidney Development and Elevations in Arterial Blood Pressure in Young Adult Sheep after Clinical Doses of Antenatal Glucocorticoids

et al. 2005

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“…Moreover, glucocorticoid administration preceding premature delivery has only become routine in the last 30-40 years, so the longer term effects on cardiovascular outcomes may yet unfold. Nonetheless, most studies to date do not report any deleterious effects of antenatal glucocorticoid therapy on blood pressure, heart rate or overall cardiac performance (systolic or diastolic) in neonates, children, adolescents or in adults at 30 years of age (Dalziel et al 2004, de Vries et al 2008. A few follow-up studies report that children exposed to antenatal corticosteroids have moderately heightened systolic and diastolic blood pressures at the age of 7 (Wilson et al 2006) and 14 (Doyle et al 2000), although none were in the hypertensive range.…”

Section: Precocious or Excessive Glucocorticoid Actionmentioning

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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“…In the report of Doyle et al (6), a small but significant elevation in blood pressure was evident at 14 y of age in a cohort who received betamethasone at an average of 28 wk gestation. In contrast, no elevations in blood pressure were found when antenatal glucocorticoids were administered at an average of 32 wk gestation at either 6 or 30 y of age (18,19). Gestational age at treatment and birth weight are strikingly different in these cohorts and may hold the answer for the different findings.…”

Section: Discussionmentioning

confidence: 86%

“…Limited information exists regarding the long-term effects of prenatal glucocorticoids exposure on arterial blood pressure levels in humans. Furthermore, the association between antenatal glucocorticoid administration and elevations in arterial blood pressure is not a universal finding (6,18,19). In the report of Doyle et al (6), a small but significant elevation in blood pressure was evident at 14 y of age in a cohort who received betamethasone at an average of 28 wk gestation.…”

Section: Discussionmentioning

confidence: 99%

Antenatal Betamethasone Administration Has a Dual Effect on Adult Sheep Vascular Reactivity

Pulgar

Figueroa

2006

Pediatr Res

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ABSTRACT:The effect of antenatal steroids on blood pressure in humans remains an unresolved question. Here we report the effects of prenatal exposure to clinically relevant doses of betamethasone on endothelial and/or vascular smooth muscle function. Pregnant sheep were randomly treated with betamethasone (0.17 mg/kg) or vehicle at 80 and 81 d of gestation. We studied arterial segments (4th-5th generation) of the right brachial artery obtained at 1-2 y of age under general anesthesia. We demonstrate that in brachial arteries of steroid exposed offspring: KCl induced contraction is increased after endothelium removal or incubation with inhibitors of nitric oxide synthase or cyclooxygenase; acetylcholine-induced relaxation is increased; sensitivity to endothelin-1 (ET-1) is increased and this effect is decreased by the ET B antagonist BQ-788. These data suggest that, in sheep treated with clinically relevant doses of betamethasone at a gestational stage when human fetuses are routinely exposed to glucocorticoids, there is a dual effect of betamethasone on the adult sheep brachial artery, i.e. endothelial dysfunction with an impairment of endothelin-1 ET B receptor-induced release of nitric oxide and an increased contribution of the ET B receptor in smooth muscle to the contractile effects of ET-1. (Pediatr Res 60: 705-710, 2006)

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Blood Pressure at 6 Years of Age After Prenatal Exposure to Betamethasone: Follow-up Results of a Randomized, Controlled Trial

Cited by 43 publications

References 14 publications

Alterations in Fetal Kidney Development and Elevations in Arterial Blood Pressure in Young Adult Sheep after Clinical Doses of Antenatal Glucocorticoids

Alterations in Fetal Kidney Development and Elevations in Arterial Blood Pressure in Young Adult Sheep after Clinical Doses of Antenatal Glucocorticoids

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

Antenatal Betamethasone Administration Has a Dual Effect on Adult Sheep Vascular Reactivity

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