Letters to the Editor

Indian Pediatrics 2002; 39:1078-1080

Reply

We appreciate Locham, et al. for their keen interest in our article(1) and giving us an opportunity to update the latest literature for readers, since the time our article was submitted for publication.

1. Dexamethasone is a synthetic corticosteroid that has been used for prevention and treatment of chronic lung disease (CLD). The major mechanism of action of steroids in CLD is suppression of inflammatory cascade in the lungs. Other mechanisms as mentioned by Locham, et al. are also described. As our objective was to focus on practical aspects of steroid use in perinatology, these were deliberately not discussed. Readers may consult standard textbooks for pharmacological details(2).

2. Use of antenatal steroids is the evidence based most effective intervention for modifying the course of respiratory distress syndrome (RDS). It has substantial effect on other important morbidities of prematurity as well(1). Postnatal steroids have not been tested adequately for this purpose. In addition, postnatal steroid use has been associated with significant short and long-term side effects, hence cannot be recommended for lung maturation of preterm infants.

3-4 American Academy of Pediatrics (AAP) has recently formulated recommendations for the use of postnatal steroids (Table I)(3). It aptly clarifies the issue. At present, CLD is not a major health problem of neonatal population in developing countries because of low survival of VLBW infants and lack of ventilation facilities in majority of hospitals(4). Surfactant replacement therapy is still unaffordable by the majority and/or unavailable. Putting everything together, use of antenatal steroids must be advocated as an important low cost intervention in developing countries.

5. Dexamethasone has been found to be inferior in terms of efficacy and safety to betamethasone as an antenatal steroid(5). The dosage of postnatal dexamethasone used has been very high. Since inflammation is an important component in pathogenesis, use of steroids for modification of course of CLD makes sense(6). The side effects with postnatal steroid therapy could be related to appropriate molecule or appropriate dose(6). A few studies have tried hydrocortisone and methylpre-dnisolone(7,8). Based on experience of its use as an antenatal steroid, betamethasone can be an alternative option - but it needs to be tested in controlled trials before using in clinical practice. One is not justified to use a drug based on analogy and plausibility alone.

6. The National Institute of Child Health and Human Development (NICHD) revisited the previous statement on use of antenatal steroids to address the issue of repeat courses (Table II)(9). Again it puts the issue of repeat course of antenatal steroids, in proper perspective.

7. The large multicenter trial did not favor the use of antenatal thyroid hormone for fetal lung maturation(10). One of the studies(11) quoted by Locham, et al. is a retrospective one, which did not show any effect in babies with birth weight greater than 1500 g, while other quoted study(12) is an animal study. Therefore, based on available evidence, it is not justified to use thyroid hormones for fetal lung maturation.

Table I-American Academy of Pediatrics Recommendations on Postnatal Steroid Use (3)

Summary of existing literature

• Systemic administration of dexamethasone to preterm infants who are mechanically ventilated decreases the incidence of CLD and extubation failure but does not decrease overall mortality.

• Treatment of VLBW infants with dexamethasone is associated with an increased risk of short-and-long-term complications, including impaired growth and neurodevelopment delay.

• No substantial short-or long-term benefits have been demonstrated from the use of inhaled corticosteroids in the prevention or treatment of CLD.

Recommendations

• On the basis of limited short-term benefits, the absence of long-term benefits, and the number of serious short-and long term complications, the routine use of systemic dexamethasone for the prevention or treatment of CLD in VLBW infants is not recommended.

• Postnatal use of systemic dexamethasone for the prevention or treatment of CLD should be limited to carefully designed randomized double-masked controlled trials. The primary outcome of these trial should be survival without long-term developmental impairment and the potential confounders of contamination and crossover should be avoided.

• Long-term neurodevelopmental assessment of infants who are or have been subjects in trials of dexamethasone to prevent or treat CLD is strongly encouraged.

• Clinical trials investigating the use of alternative anti-inflammatory corticosteroids, systemic and inhaled, are required before additional recommendations can be made.

• In the context of a randomized, controlled trial, the use of corticosteroids should be limited to exceptional clinical circumstances (e.g., an infant on maximal ventilatory and oxygen support). In those circumstances, parents should be fully informed about the known short-and-long-term risks and agree to treatment.

Table II-  National Institute of Child Health and Human Development (NICHD) Consensus Statement of Repeat Course of Antenatal Steroids(9)

• The collective international data continue to support unequivocally the use and efficacy of a single course of antenatal corticosteroids using the dosage and interval of administration specified in the 1994 Consensus Developement Conference report.

• The current benefit and risk data are insufficient to support routine use of repeat or rescue courses of antenatal corticosteroids in clinical practice.

• Clinical trials are in progress to assess potential benefits and risks of various regimens of repeat courses. Until data establish a favourable benefit-to-risk ratio, repeat courses of antenatal corticosteroids, including rescue therapy, should be reserved for patients enrolled in clinical trials.

 

 

References

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

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

3. Committee on Fetus and Newborn, American Academy of Pediatrics, Fetus and Newborn Committee, Candadian Pediatric Society. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants. Pediatrics 2002; 109: 330-338.

4. NNPD Database 2000. National Neonatalogy Forum, India.

5. Whitelaw AM. Thoresen M. Antenatal steroids and the developing brain. Arch Dis Child Fetal Neonatal Ed 2000; 83: F154-F157.

6. Thebaud B, Lacaze-Marmonteil T, Watterberg K. Postnatal glucocorticoids in very preterm infants; "the good, the bad and the ugly"? Pediatrics 2001; 107: 413-415.

7. Andre P, Thebaud B, Odievre MH. Methylprednisolone, an alternative to dexamethasone in very premature infants at risk for chronic lung disease. Intensive Care Med 2000; 26: 1496-1500.

8. Watterbery KL, Gerdes JS, Gifford KL, Lin HM. Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants. Pediatrics 1999; 104: 1258-1263.

9. Antenatal Corticosteroids Revisited: Repeat Courses. National Institutes of Child Health and Human Development (NICHD) Consensus Development Conference Statement, August 17-18, 2000. http://Consensus.nih.gov/cons/112/112_statement.htm

10. Crowther CA, Hiller JE, Haslam RR, Robinson JS and the ACTOBAT Study Group. Australian collaborative trial of antenatal thyrotropin releasing hormone: Adverse effects at 12-month follow up. Pediatrics 1997; 99: 311-317.

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

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