The Mixed Blessing of Antenatal Corticosteroids

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An additional reason for so much interest in the potentially adverse effects of corticosteroids on the fetus is its common use in clinical practice when babies are born premature (Merill and Ballard, 2001). Given the concerns about excess fetal exposure to maternal cortisol, it may seem paradoxical that one of the more important trans-lational findings from animal research to clinical practice was the seminal finding that antenatal corticosteroid treatments are very beneficial in quickly advancing lung maturation (Liggins, 1969). Experiments in sheep showed that rising cortisol levels in the ewe signal the impending parturition and simultaneously accelerate the production of lung surfactant in the immature fetal lamb. The benefits for improving airway functioning in premature infants were soon extended to humans (Liggins and Howie, 1972). While these findings revolutionized the treatment of neonatal respiratory distress syndrome, reduced the likelihood of intraventricular hemorrhage and facilitated the management of very premature infants in the Neonatal Intensive Care Unit, there have continued to be some concerns-about prolonged dosing and the use of multiple courses of dexamethasone or betamethasone (Kay et al, 2000). When prescribed in the standard manner as a 2-day course in the premature baby or to the gravid female prior to delivery, the safety of this regimen has been reasonably well established (Roberts and Dalziel, 2009), but for some expectant women threatening to deliver early, there have been up to 10 courses administered before birthing. When treatments are repeated or prolonged, studies in rodents, sheep, and monkeys have all found adverse effects, especially on sensitive brain regions like the hippocampus (Matthews, 2000; Uno et al, 1994). When extended over many days, antenatal corti-costeroids can retard fetal growth, suppress both maternal and fetal adrenal activity, decrease thyroid activity, and affect kidney functioning in ways that would pose a long-term risk for later hypertension (Coe and Lubach, 2005; French et al, 1999; Seckl et al, 2000). One further reason for these concerns is that when administered directly to the mother before delivery, both dexamethasone and betamethasone can readily bypass the placental enzyme 116-HSD2 and then can become sequestered in fetal circulation. While examining the impact of a standard 2-day course of maternal dexamethasone in the rhesus monkey, we found fetal cortisol levels were still suppressed a full week later (Coe et al, 1993) see (Fig. 35.3).

If concerns about the potential long-term consequences of prolonged or multiple courses of

Antenatal Corticosteroids Maternal

Antenatal Corticosteroids Maternal

Fig. 35.3 Synthetic corticosteroids, including dexam-ethasone and betamethasone, are routinely administered to pregnant women who may deliver early and to premature babies in order to stimulate lung maturation. As illustrated here, Dex readily bypasses the protective barrier enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11B-HSD2), which normally limits fetal exposure to maternal cortisol by converting it to corticosterone, a less bioactive form. Some concerns linger about long-term effects of fetal exposure to high doses or sustained corticosteroid treatment

Fig. 35.3 Synthetic corticosteroids, including dexam-ethasone and betamethasone, are routinely administered to pregnant women who may deliver early and to premature babies in order to stimulate lung maturation. As illustrated here, Dex readily bypasses the protective barrier enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11B-HSD2), which normally limits fetal exposure to maternal cortisol by converting it to corticosterone, a less bioactive form. Some concerns linger about long-term effects of fetal exposure to high doses or sustained corticosteroid treatment antenatal glucocorticoid therapies are warranted, it is of considerable significance. In the United States over 12% of infants are born premature, which means that each year up to 500,000 babies could experience a jolt of high levels of glu-cocorticoids, although most would receive only the standard 2-day treatment (Martin et al, 2009; Centers for Disease Control and Prevention, 2000).

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