Jcrpe ic sayfalar 2011-3baski

Fetal Adrenal Suppression Due to Maternal Selim Kurto¤lu1, Dilek Sar›c›1, Mustafa Ali Ak›n1, Ghaniya Daar2, Levent Korkmaz1, fieyma Memur1 1Erciyes University Faculty of Medicine, Department of Pediatrics Division of Neonatology, Kayseri, Turkey 2Nevflehir Government Hospital, Deparment of Pediatrics, Nevflehir, Turkey Introduction
Corticosteroids administered during pregnancy or maternal Cushing’s syndrome can cause suppression of fetal adrenalglands (1,2,3,4,5,6,7). Maternal use of corticosteroids is needed in case of fetal congenital adrenal hyperplasia, as wellas in maternal diseases such as idiopathic thrombocytopenicpurpura (ITP), Crohn’s disease, systemic lupus erythematosus,Addison’s disease and rheumatological problems (3,8,9). ABSTRACT
Short-term corticosteroid treatment is given in case of preterm During pregnancy, steroids are usually used in maternal diseases labor to enhance fetal lung maturation (8). When using such as adrenal failure or other autoimmune diseases, e.g. idiopathic corticosteroids during pregnancy, the choice of preparation thrombocytopenic purpura (ITP), Crohn’s disease, systemic lupus type and dose is of utmost importance - steroids crossing the erythematosus, dermatomyositis, scleroderma, Addison’s disease and placenta freely should be given if the target is fetus, while hyperemesis gravidarum, HELLP syndrome. Endogenous or exogenous those passing across the placenta should be used in smaller maternal steroids are metabolized by the placental enzyme 11 beta-hydroxy steroid dehydrogenase type 2. Prednisolone and amount if maternal disorders are being treated (1).
methylprednisolone are highly sensitive to this enzyme, while In this article, adrenal suppression pattern in a newborn dexamethasone and betamethasone are less well metabolized. Steroids exposed to long-term maternal methylprednisolone therapy which can cross the placental barrier are administered in cases like fetal were presented with special emphasis on short term follow up lupus, congenital adrenal hyperplasia and for enhancement of fetal lung maturation, whereas steroids used in maternal diseases are usually theones with low affinity to the placenta; however, in case of long-term useor in high doses, placental enzyme saturation occurs and thus, resulting in fetal adrenal suppression. Antenatal steroids can lead to low birthweight, as observed in our patient. Here, we report a case with fetal A 20-minute-old newborn, whose mother used 64 mg adrenal suppression due to maternal methylprednisolone use presenting methylprednisolone per day during her pregnancy due to ITP, with early hypoglycaemia and late hyponatremia in neonatal period and was hospitalized for follow-up. Pregnancy duration was 39 requiring three-month replacement therapy. Key words: Pregnancy, exsogenous corticosteroids, fetal adrenal weeks. The neonate was 2680 grams (3-10th percentile) at birth with head circumference of 36 cm (75-90th percentile) andheight of 50 cm (25-30th percentile). Whole blood examination Conflict of interest: None declaredReceived: 03.05.2011 showed hemoglobin level of 19.1 g/dL, leukocyte count of 10530/mm3, and platelet count of 10 000/mm3. Biochemistry Address for Correspondence
Levent Korkmaz MD, Erciyes University Faculty of Medicine, Department of Pediatrics Division of Neonatology, Kayseri, Turkey GSM: +90 535 255 82 55 E-mail: [email protected] Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing. profile revealed the following: blood glucose 29 mg/dL, steroid, is metabolized to cortisone. Similarly, synthetic sodium level 138 mEq/L, potassium 4.5 mEq/L, ALT 18 U/L, glucocorticosteroids are metabolized to inactive AST 62 U/L, calcium 9.5 mg/dL, phosphorus 4.8 mg/L, alkaline metabolites in the placenta. Prednisolone-related drugs are phosphatase 100 U/L, parathormone 13.91 pg/mL. On adrenal mostly degraded to inactive forms by the placental ultrasonographic examination, the adrenal glands were small enzymes and, approximately 10% of the total amount will measuring 10x2 mm in size for the right and 12x2 mm for the ultimately reach the fetus and among this whole, about left one. Since the patient was thrombocytopenic, 0.8 g/kg 33% of betamethasone and 50% of dexamethasone will IVIG infusion was given and repeated platelet count was 30 enter the fetal circulation (11,12). Besides this, when taken 000 mm3. On the third day of follow-up, sodium level became in high doses and for long period of time, prednisolone and 123 mEq/L, potassium 3.9 mEq/L, and urinary sodium level methylprednisolone themselves can saturate the placental was 26 mEq/L. On the fourth day, cortisol level was 16.22 enzymes and, as a result, large amount of corticosteroids μg/dL, ACTH was 44.4 pg/mL, 17-OH progesterone was 2.58 can cross the placental barrier causing significant ng/mL. On the 10th day, rechecking the adrenal functions, suppression of the fetal glands, as observed in our case (5).
cortisol level was found to be 0.194 μg/dL and ACTH 20.9 Fetal adrenal suppression develops approximately within 14 pg/mL. After administration of 1 μg of ACTH i.v. (low-dose days after maternal steroid use, therefore, the neonate may ACTH test), the cortisol level increased to 9.69 μg/dL at 30 be born with ACTH suppression (5). Adrenal gland minute. Then, the patient was given 3 mg/m2/day p.o. insufficiency becomes prominent on postnatal day methylprednisolone as physiological replacement. The result 3 - the neonate develops hyponatremia, hypoglycemia and of low-dose ACTH test on the 40th day postpartum was as hypotension. Since there is central adrenal insufficiency follows: basal cortisol level of 4.29 μg/dL and 30th minute due to long-term steroid effect, potassium level is within cortisol level of 11.29 μg/dL. Therefore, methylprednisolone normal limits, or even low. It is well known that therapy was continued and stopped by slowly tapering at the long-term steroid use can cause low birth weight, as in end of the 3rd month (Table 1). Low-dose ACTH test was repeated in the 4th posnatal month and the results were as In our patient, high-dose methylprednisolone saturated follows: basal cortisol 4.75 μg/dL, ACTH 19.5 pg/dL. After 30 the placental enzymes, the steroids crossed the placenta minutes, cortisol level was 19.9 μg/dL. Hormone tests and more significantly and in higher amounts, thus, causing fetal their results are summarized in Table 1. These results showed adrenal suppression. On the fourth day, cortisol level was that the patient was relived from adrenal suppression. within normal ranges, but we consider that there might be an interference between crossed maternal steroids, their Discussion
metabolites and fetal cortisol. Since on the 10th day ACTHand cortisol levels were found to be suppressed, this shows Corticosteroids are given during pregnancy if needed in the importance of measuring cortisol and ACTH levels during maternal diseases or other pregnancy-related problems as well as to treat certain fetal diseases; in the latter cases, Thus, steroids crossing the placenta in small amount should corticosteroids capable of crossing the placenta are be preferred during pregnancy in case of maternal disorders administered to the mother (5,6,7,8,9).
necessitating steroid use. The newborns should be followed As side effects to the mother, steroids used during postnatally. On postnatal day 4, basal cortisol and ACTH levels pregnancy can cause weight gain, dyslipidemia, should be measured, and if needed, adrenal reserves should be hypertension, cushingoid appearance, acne, hypertrichosis, checked by conducting low-dose ACTH test. Although there are psychological problems (8). Corticosteroids are metabolized many references for threshold of cortisol response to low-dose in the placenta by the help of the enzyme 11-β-hydroxylase ACTH test, for term newborns, levels of 20 μg/dL and above steroid dehydrogenase-2 (10). Cortisol, a physiologic should be accepted as normal response (13). Table 1. Hormone levels and treatment of the patient during follow-up
Response to
low-dose ACTH test
Continued methylprednisolone therapy until the end of the 3rd month For patients with adrenal insufficiency, physiological 6. Saulnier PJ, Piguel X, Perault-Pochat C, Csizmadia-Bremaud C, replacement should be started. Moreover, in case of stressful Saulnier JP. Hypoglycaemic seizure and neonatal adrenal conditions, the dose of steroid should be increased 2-3 times, insufficiency after maternal exposure to prednisone during because it has been shown that antenatal steroids can change pregnancy : a case report. Eur J Pediatr 2010;169:763-765.
7. Kreines K, Devaux WD. Neonatal adrenal insufficiency the response to neonatal stress (14). Low-dose ACTH test associated with maternal Cushing syndrome. Pediatrics should be repeated at specified intervals and, as soon as adrenal response returns to normal, replacement therapy 8. Eventov-Friedman S, Shinwell ES. Current controversies in perinatal steroid therapy. Acta Paediatr 2008;97:1492-1501. 9. Mc Gee DC. Steroid use during pregnancy. J Perinat Neonat References
10. Murphy VE, Fittock RJ, Zarzycki PK, Delahunty MM, Smith Tegethoff M, Pryce C, Meinlschmidt G. Effects of intrauterine R, Clifton VL. Metabolism of synthetic steroids by the human exposure to synthetic glucocorticoids on fetal, newborn, and infant hypothalamic-pituitary-adrenal axis function in humans: 11. Beitins IZ, Bayard F, Ances IG, Kowarski A, Migeon CJ. a systematic review. Endocr Rev 2009;30:753-789.
The placental passage of prednisone and prednisolone in 2. Mesogitis S, Daskalakis G, Papapetrou P, Mavroudis K, Papandraulaki F, Papantoniou N, Antsaklis A. The effect on the pregnancy near term. J Pediatr 1972;81:936-945. fetal pituitary-adrenal axis of dexamethasone administration 12. Khan AA, Rodrigues A, Kaakinen M, Pouta A, Hartikainen AL, early in the second trimester of pregnancy. J Matern Fetal Jarvelin MR. Does in utero exposure to synthetic glucocorticoids influence birtahweight, head circumference Trainer PJ. Corticosteroids and pregnancy. Semin Reprod and birth lenght: a systematic review of current evidence in humans. Pediatr Perinat Epidemiol 2011;25:20-36. Manabe M, Nishida T, Imai T, Kusaka T, Kawada K, Okada H, 13. Lomenick JP, Smith WJ. Low dose adrenocorticotropic Okubo K, Isobe K, Itoh S. Cortisol levels in umbilical vein and hormone stimulation testing in term infants. J Pediatr umbilical artery with or without antenatal corticosteroids.
Pediatr Int 2005;47:60-63. 5. Homar V, Grosek S, Battelino T. High dose methylprednisolone 14. Schaffer L, Luzi F, Burkhardt T, Rauh M, Beinder E. Antenatal in a pregnant woman with Crohn’s disease and adrenal betamethasone administration alters stres physiology in suppression in her newborn. Neonatology 2008;94:306-309.
healthy neonates. Obstet Gynecol 2009;113:1082-1088.

Source: http://www.jcrpe.org/sayilar/38/buyuk/160-162.pdf