ESPE Abstracts (2019) 92 P1-303

Hypothalamo-Pituitary-Adrenal (HPA) Axis in Infants Exposed to Corticosteroids During Fetal Life

Morgane Auriche1, Muriel Houang1, Eloise Giabicani1,2, Delphine Mitanchez3,2, Irène Netchine1,2


1Explorations Fonctionnelles Endocriniennes -APHP- Hôpital Armand Trousseau, Paris, France. 2Sorbonne University, Paris, France. 3service de néonatalogie, APHP Hôpital Armand Trousseau, Paris, France


Background: Prednisolone, prednisone, and hydrocortisone, are used during pregnancy, in women with thrombocytopenia, auto immune or inflammatory diseases. The current belief speculates on the absence of adverse effects on the hypothalamo-pituitary-adrenal (HPA) axis of the fetus, thanks to placental 11BHSD2 inactivation.

Objective and Hypotheses: We analyzed the results of ATCH tests routinely performed in neonates exposed to corticosteroids during fetal life, with the hypothesis that HPA function would be normal in most cases.

Patients and Methods: We retrospectively collected all ACTH tests performed from 2012 to 2018 in neonates exposed in utero to corticosteroids, in our laboratory database. Twenty six files were retained for analysis. The infants had ACTH tests in the first 15 days of life and then every two months until HPA axis recovered. Meanwhile they had adequate glucocorticoid replacement in case of stress.

Results: Twenty-one mothers (80.8%) received prednisone, two (7.7%) prednisolone, and three (11.5 %) hydrocortisone. Mean dose of the treatment was 44 mg/day (2.5-80) and mean duration was 78 days (7-272). Mean cumulative dose was 1370 mg (525-4680). Six (23.1%) women received over 60 mg/day for at least two weeks, and eight (30.1%) were treated for more than 100 days. Mean Z-score at birth was -0.29 SDS for weight, -0.49 SDS for length and -0.43 SDS for head circumference. Three (12.5%) were born small for gestational age, and three had transient hypoglycemia. Twenty neonates (76.9%) had an abnormal first ATCH test. The cumulative dose of 1300 mg was the threshold, beyond which all children had a low abnormal response (n=7), but no least dose was safe. The result of the ACTH test was not correlated to the cumulative dose, or to the duration of the exposition. At mean age of two months, 19 infants had a second ACTH test with a low response in nine cases. Six were tested again, of which five had a normal ACTH test at the mean age of 4.4 months and a last child at 5.5 months. The mean delay to recover a normal HPA function was 76 days.

Conclusion: We found a surprisingly high amount of HPA axis anomalies (76.9 %) in neonates exposed during fetal life to corticosteroids. Although rare, acute adrenal insufficiency has been reported in this situation. We propose to educate caregivers and parents to adequate stress glucocorticoid replacement in the first months of life. These results should be confirmed by a large prospective study.

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