Letters to the Editor

Indian Pediatrics 2000;37: 1390-1392

Effect of Antenatal Steroids on Lung Maturity and Brain Development

The recent article on the effects of antenatal corticosteroids implies that there is a beneficial effect on hypotension and respiratory distress syndrome (RDS) related morbidities in preterm neonates. What remains unclear, however, is whether repeat doses should be given if delivery does not occur shortly after the initial course. Some data suggests that 74% of UK maternity units give repeated doses on a weekly basis to such women(2). Are these preterm infants prone for cerebral palsy like those who receive postnatal steroids(3)?

B.R. Santhanakrishnan
28, Cathedral Garden Road,
Chennai 600 034, India.

1. Aggarwal R, Downe L. Effects of antenatal corticosteroids on blood pressure support in premature infants Indian Pediatr 2000; 37: 639-646.

2. Brocklehurst P, Gates S, Mc Kenzie - Ma Harg K. Are we prescribing multiple courses of antenatal corticosteroids? A survey of practice in the UK. Br J Obstet Gynecol 1999; 106: 977-979.

3. Tarnow-Modi WA, Mitra A. Postnatal dexamethasone in preterm infants. BMJ 1999; 319: 1385-1386.

Liggins and Howie were the first to describe the beneficial effects of antenatal corticosteroids (ANCS) on lung maturity in preterm neonates(1). Use of ANCS have been associated with a decrease in Respiratory Distress Syndrome (RDS) related mortality and morbidity in infants <34 weeks of gestation. Additionally long term follow up studies have ruled out any harmful effect on the lungs, growth and development(2,3). The NIH consensus statement (1995) endorsed the use of ANCS and since then, this has become standard practice in the management of preterm labor (<34 weeks of gestation)(4).

The beneficial therapeutic effects of ANCS to enhance lung maturity seem to decrease after 7 days and this has prompted clinicians to use multiple courses to maintain the effect(5). The NIH consensus statement (1955) did not resolve the issue of multiple courses and suggested repeated doses may be used after 7-10 days of the last course. Two questions need to be answered regarding multiple courses of ANCS. Firstly are they effective in enhancing lung maturity? Since 1995, various retrospective studies have documented that mortality and morbidity related to respiratory distress syndrome (RDS) continues to improve with multiple courses of ANCS(6,7). Therefore it seems that the effect on lung maturity can be sustained effectively by repeated courses of ANCS. The second issue with the use of multiple courses is the potential side effects of steroids on the fetal hypothalamic-pituitary-adrenal (HPA) axis and future growth and development.

The effect of multiple doses of ANCS on growth and development is of some concern. Animal stuides have shown that gluco-corticoids although essential for normal brain development can be detrimental in higher doses(8). Sustained elevation of these hor-mones can permanently modify the structure and function of the brain. Within the developing brain, the limbic system (primarily the hippocampus) is particularly sensitive to high levels of steroids. Perhaps the most striking observation has been the reduction in hippocampal volume with chronically ele-vated glucocorticoids. The hypothalamus-pituitary-adrenal (HPA) axis which is central to the integration of an individuals endocrine and behavioral response, also appears to be affected by high steroids. However, this retardation in brain development with the use of steroids was associated with significantly higher doses, for a longer duration and at an earlier gestation as compared to its clinical use in humans. It is unknown whether any of the structural changes that have been described in the animal brains can occur in humans resulting in neurodevelopmental problems.

A retrospective analysis of 710 infants enrolled in the North American Thyrotrophin-Releasing Hormone Trial(7), has shown that more than 2 courses of ANCS was associated with a small decrease in fetal growth and lower plasma cortisol levels at 2 hours of age but no change in head circumference or neonatal mortality. Another study has documented a decrease in birth weight by 9% and smaller head circumference by 4%(9). Similar reduction effects on the head circum-ference have been reported by others(76). Infants in these studies had received multiple courses ranging from 2 to 12 in number!! However, the information gathered from retrospective data analysis has inherent problems and prospective randomized trials are required before recommendations can be made. Until then it may be prudent to use multiple doses of ANCS with a caution. However, this should in no way deter us from offering the benefit of the first course of ANCS to all pregnant mothers with imminent preterm delivery <34 weeks of gestation.

Our study involving 161 infants did not address this question(10). Only four of babies in the steroid group had received 2 courses of steroids. Their immediate outcome in terms of morbidity and mortality was not different when compared to babies with a single course of ANCS.

Rajiv Aggarwal,
Assistant Professor,
Department of Pediatrics,
All India Institute of Medical Sciences,
New Delhi 110 029, India.

Lynette Downe,
Director,
Neonatal Intensive Care Unit,
Nepean Hospital, Penrith,
NSW 2750, Australia.

1. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for the prevention of the respiratory distress syn-drome in premature infants. Pediatrics 1972; 50: 515-523.

2. NIH Consensus Development Panel on the effects of cortiocosteroids for fetal maturation on perinatal outcomes. JAMA 1995; 273: 413-418.

3. Doyle LW, Ford GW, Richards AL, Kelly EA, Davis NM, Callanan C, et al. Antenatal cortiocosteroids and outcome at 14 years of age in children with birth weight less than 1501 grams. Pediatrics 20000; 106: e2.

4. Dessens AB, Haas HS, Koppe JG. 20 year follow up of antenatal corticosteroids Pediatrics 2000; 105: e77.

5. Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet Gynecol 1995; 173: 254-262.

6. Abbasi S, Hirsch D, Davis J, Tolosa J, Stouffer N, Debbs R, et al. Effect of single versus multiple courses of steroids on maternal and neonatal outcome. Am J Obstet Gynecol 2000; 182: 1243-1249.

7. Banks BA, Cnaan A, Morgan MA, Parer JT, Merrill JD, Ballard PL, et al. Multiple courses of antenatal corticosteroids and outcome of premature neonates. North American Thyro-trophin-Releasing Hormone Study Group. Am J Obstet Gynecol 1999; 181: 709-717.

8. Matthews SG. Antenatal glucocorticoids and programming of the developing CNS. Pediatr Res 2000; 47: 291-300.

9. French NP, Hagan R, Evans SF, Godfrey M, Newnham JP. Repeated antenatal cortico-steroids: Size at birth and subsequent development. Am J Obstet Gynecol 1999; 180: 114-121.

10. Aggarwal R, Downe L. Effects of antenatal corticosteroids on the blood pressure support in premature infants. Indian Pediatr 2000; 37: 639-646.