Letters to the Editor

Indian Pediatrics 2002; 39:1075-1077

Steroids in Perinatology

We offer our comments on a recent article on this subject(1).

1. In the scientific basis for the use of postnatal steroids, the authors mention that steroids suppress or abolish the inflammatory responses that lead to bronchopulmonary dysplasia. However, apart from anti-inflammatory effects, steroids also stabilize cell and lysosomal membranes, increase serum vitamin A concentration and surfactant synthesis, stimulate antioxidant enzyme activity, break granulocyte aggregates with improvement in pulmonary microcirculation, reduce pulmonary oedema and enhance beta-adrenergic activity in chronic lung disease (CLD)(2).

2. Under the same heading, authors note that the practice of early postnatal dexamethasone in respiratory distress syndrome (RDS) has been abandoned (paragraph 1). In a study done by Mukhopadhyay, et al. early postnatal dexamethasone given for 3 days, starting within 6 hours of birth, reduced morbidity due to RDS by decreasing FiO2 and alveolar arterial oxygen gradient, and decreased the mean duration of ventilation(3). It stands to reason that a baby who develops less severe RDS will have lesser and shorter requirements for ventilation and oxygenation, thereby reducing the severity of barotrauma and incidence of CLD(4). It takes only 1-2 days following birth for an immature lung to mature both anatomically and biochemically as it responds to the surge of glucocorticoids and beta-adrenergic compounds that are released by the stress of delivery(5).

3. It is well established that the use of antenatal steroids decrease the incidence of CLD(6). Similarly, postnatal administration of dexamethasone (before 7 days of life) reduces the incidence and severity of CLD at 28 days of life and 36 weeks post-conceptional age(7). The infants who develop CLD have lower basal and stimulated cortisol values but elevated cortisol precursors and precursor to product ratios(8). The decreased cortisol response to stress increases the risk of CLD secondary to inflammatory lung injury(9).

4. The authors mention that surfactant does not have other benefits like reduction in intraventricular hemorrhage and patent ductus arteriosus, which are provided by use of antenatal steroids. Also, though administration of surfactant reduces the mortality from hyaline membrane disease, it does not alter the incidence of CLD, which is reduced by postnatal steroids(10).

5. According to authors betamethasone is a better choice than dexamethasone antenatally. Why is the same not true postnatally? Since several studies suggest an increased risk of neurological disability with dexamethasone compared to betamethasone, it seems prudent to use betamethasone antenatally as well as postnatally whenever indicated(11).

6. Authors have recommended a single course of antenatal steroids. As antenatal steroids have been shown to be beneficial as soon as 23 weeks of gestation, repeat courses at an interval of 10-15 days can be carefully evaluated since side effects appear to overcome the benefits after 3 courses of treatment(11). Glucocorticoid treatment has been shown to improve lung function in premature lambs without a detectable increase in surfactant components(12). Longer exposure to antenatal glucocorticoids increases surfactant lipids and proteins in a coordinated fashion. The enhanced response with a repetitive dosing indicates that the process of glucocorticoid induced lung maturation is either reversible and/or gestational age dependent(12). Babies delivered after multiple courses of corticosteroids and within 7 days of dosing have demonstrated improved respiratory compliance compared with untreated and remotely treated infants. This suggests that the enzymes responsible for surfactant production can be repetitively induced despite prior treatment with corticosteroid(13).

7. Antenatal administration of thyrotrophin releasing harmone has not been recommended by the authors. In a recent study, the greatest effectiveness with reduced requirement for surfactant, reduction of oxygenation index and duration of artificial ventilation was achieved by a combination of betamethasone and thyrotrophin releasing hormone in neonates weighing 500-999 g. This combination had beneficial effect only on the oxygenation index and grade of RDS in neonates weighing 1000-1499 g. The combination was without any effect in those weighing 1500 g or more(14). The intra-amniotic injection of betamethasone and thyroxine enhanced the lung maturation of preterm rhesus fetal monkey compared with maternal injections(15).

References

1. Narayan S, Deorari AK. Steroids in perinatology. Indian Pediatr 2002; 39: 347-361.

2. Davis JM, Rosenfeld WN. Chronic lung disease. In: Neonatology Pathophysiology and Management of the Newborn, 5th edn. Eds. Avery GB, Fletcher MA, Mac Donald MG. Philidelphia, Lippincott Williams Wilkins, 1999; pp 509-531.

3. Mukhopadhyay K, Kumar P, Narang A. Role of early postnatal dexamethasone in respiratory distress syndrome. Indian Pediatr 1998; 35: 117-122.

4. Nagesh NK. Antenatal and postnatal corticosteroids in the prevention of chronic lung disease in preterm neonates - risk and benefits. J Neonatal 2001; 15: 56-58.

5. Tooley WH. Hyaline membrane disease. In: Rudolph’s Pediatrics; 20th edn. Eds. Rudolph AM, Hoffman JIE, Rudolph CD. Connecticut, Appleton Lange, 1996; pp 1598-1605.

6. Narang A, Kumar P, Kumar R. Chronic lung disease in neonates: emerging problem in India. Indian Pediatr 2002; 39: 158-162.

7. Cherry A, Marrakchi Z, Chaouachis, Boukef S, Sfar R. Bronchopulmonary dysplasia and corticosteroid therapy. Arch Pediatr 2002; 9: 159-168.

8. Watterberg KL, Gerdes JS, Cook KL. Impaired glucocorticoid synthesis in premature infants developing chronic lung disease. Pediatr Res 2001; 50: 190-195.

9. Banks BA, Stouffer N, Cnaan A, Ning Y, Merrill JD, ballard RA, et al. Association of plasma cortisol and chronic lung disease in preterm infants. Pediatrics 2001; 107: 494-498.

10. Stoll BJ, Kliegman RM. The foetus and the neonatal infant. In: Nelson Textbook of Pediatrics, 16th edn. Eds. Behrman RE, Kliegman RM, Jenson HB. Philadelphia, WB Saunders, 2000; pp 451-551.

11. Hamon I, Hascoet JM. Perinatal corticotherapy: updates. J Gynecol Obstet Biol Reprod 2001; 30 (6 Suppl): S 50-53.

12. Ballard PL, Ning Y, Polk D, Ikegami M, Jobe AH. Glucocorticoid regulation of surfactant components in immature lambs. Am J Physiol 1997; 273: L1048-L1057.

13. McEvoy C, Bowling S, Williamson K, Collins J, Tolaymat L, Maher J. Timing of antenatal corticosteroids and neonatal pulmonary mechanics. Am J Obstet Gynecol 2000; 183: 895-899.

14. Roztocil A, Svojanovska K, Matuskova D, Borek I, Juren T, Unzertig V, et al. Prenatal induction of lung maturation in the fetus. Betamethasone versus betamethsone + thyrotrophin - releasing hormone. Ceska Gynekol 1999; 64: 147-152.

15. Gilbert WM, Eby-Wilkens E, Plopper C, Whitsett JA, Tarantal AF. Fetal monkey surfactants after intramniotic or maternal administration of betamethasone and thyroid hormone. Obstet Gynecol 2001; 98: 466-470.