http://informahealthcare.com/rnf ISSN: 0886-022X (print), 1525-6049 (electronic) Ren Fail, 2014; 36(6): 951–952 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/0886022X.2014.900403
CASE REPORT
Transient nephrogenic diabetes insipidus caused by fetal exposure to haloperidol Melek Akar, C¸ig˘dem Seher Kasapkara, Mehmet Nuri O¨zbek, Heybet Tu¨zu¨n, Bedri Aldudak, and Berat Kanar
Ren Fail Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 02/12/15 For personal use only.
Department of Neonatology, Diyarbakir Children Hospital, Diyarbakir, Turkey
Abstract
Keywords
Haloperidol is commonly used in the treatment of psychiatric disorders. Data from animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in high doses. For the first time, we report a neonate with transient nephrogenic diabetes insipidus (DI) caused by fetal exposure to haloperidol. The magnitude of risk associated with the use of haloperidol during pregnancy appears to be small, but nephrogenic DI secondary to haloperidol is a serious condition with the risk of hypernatremic dehydration. Haloperidol can have adverse effects on the fetus and newborn infant, that’s why one should prevent the use of haloperidol during pregnancy and lactation.
Haloperidol, neonate, nephrogenic diabetes insipidus
Introduction Haloperidol is commonly used in the treatment of psychiatric disorders. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. Haloperidol should be given during pregnancy only if the benefit to the mother clearly outweighs the potential fetal risk.1 In this report, we present a case of transient nephrogenic DI whose mother was on haloperidol treatment within pregnancy.
Case The mother has used haloperidol alone because of psychosis since she was 29 years old. The daily dose of haloperidol was 20 mg. At 31 years of age she experienced her first pregnancy while on haloperidol treatment. The mother had not received prenatal attention by a physician. The baby was delivered vaginally on term. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. Birth weight was 3100 g. She discontinued haloperidol after giving birth. The baby was exclusively breastfed and referred to our hospital after 3 days of fever, irritability, and feeding difficulties. On neurological evaluation, she was hypotonic especially in the trunk. All neonatal reflexes including Moro were depressed along with decreased movements. She was phenotypically normal but the baby was hypoactive and appeared to be dehydrated. Her weight was 2300 g, temperature of 98 F rectally, heart rate 125/min, respiratory rate 42/min, and blood pressure 62/30 mmHg. Serum sodium level was 164 mmol/L, Address correspondence to Melek Akar, MD, Department of Neonatology, Diyarbakir Children Hospital, NICU Yenisehir, Diyarbakir, Turkey. E-mail: [email protected]
History Received 3 December 2013 Revised 17 February 2014 Accepted 23 February 2014 Published online 27 March 2014
potassium was 4.8 mmol/L, blood urea nitrogen 117 mg/dL, creatinine 1.28 mg/dL, glucose 84 mg/dL, calcium 10.2 mg/ dL. Initial complete blood count revealed a white blood cell of 16,900/mm3, hemoglobin 18.6 g/dL, hematocrit 56.2%, likely due to hemoconcentration. Urine output was 6.5 mL/kg/h (normal, 2–4 mL/kg/h). Serum osmolality was 373 mOsm/kg H2O (normal, 280–300 mOsm/kg H2O). Urine sodium concentration was 15 mmol/L. Urine osmolality and urine specific gravity were 112 mOsm/kg H2O (normal, 600– 800 mOsm/L) and 1004 mg/mL, respectively. The patient was evaluated for other endocrine abnormalities but no additional hormonal pathology was found. A renal ultrasound scan was normal. By 6th day of life, the urine output gradually decreased to 3–4 mL/kg/h on an intake of 140 mL/kg/day. At that time, urine osmolality increased to 192 mOsm/kg H2O, with a specific gravity of 1010 mg/mL. She made steady recovery before discharge. Follow up examination at three weeks of age with endocrinologic examination revealed a thriving infant.
Discussion In breast-fed neonates, hypernatremia may occur from inadequate breast milk production, central or nephrogenic DI, gastroenteritis, or salt poisoning. Close follow up of infants during the first days after hospital discharge, particularly in breast-fed infants, is essential for the primary care physician to detect early weight loss. Even in the infant who looks well, weight loss of 10% or more deserves an immediate investigation, including evaluation of the serum electrolytes for possible hypernatremia.2,3 This case was admitted to our hospital with large water losses in the urine and hypernatremic dehydration. The mother had no history of lactation
Ren Fail Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 02/12/15 For personal use only.
952
M. Akar et al.
failure or this exclusively breast-fed infant had no history of diarrhea. Paradoxical hypernatremic dehydration and polyuria were believed to be a result of nephrogenic diabetes insipidus secondary to haloperidol treatment. Neonatal DI is extremely rare and its etiology has not been documented extensively.4 Urine output is not a good indicator of hydration status in children with DI and can lead to an inappropriate reassurance. In addition, patients with hypernatremic dehydration may clinically appear relatively well; and therefore, laboratory investigation is necessary to make the diagnosis. Once recognized, hypernatremic dehydration in the neonate must be evaluated expeditiously to investigate the possibility of DI and other causes. It is important to check paired serum and urine osmolarity, urine specific gravity, and urine electrolytes. The combination of hypernatremia, inappropriately low urine specific gravity and low urinary sodium concentration will confirm a diagnosis of DI. A simultaneous measurement of serum antidiuretic hormone (ADH) or the response to ADH will indicate whether the DI is central or nephrogenic.5 This patient had severe hypernatremia, low urine density and low urine sodium concentration. Nephrogenic diabetes insipidus was considered, because of this serum ADH level was not measured. Haloperidol is a dopamine inverse agonist of the typical antipsychotic class of medications. Haloperidol has a half-life of 13–35 h in adults. In humans, no controlled studies exist. Unconfirmed studies in pregnant woman revealed possible damage to the fetus, although most of the women were exposed to multiple drugs during pregnancy. Haloperidol, when given to lactating women, is found in significant amounts in their milk. Breast-fed children sometimes show extrapyramidal symptoms. Following accepted general principles, haloperidol should be given during pregnancy and lactation only if the benefit to the mother clearly outweighs the potential risk.6 The patient’s symptoms such as hypernatremia, abnormal renal function tests, serum and urine osmolalities resolved spontaneously by six days of hospitalization suggested that the newborn had experienced haloperidol induced nephrogenic DI. We suggest that haloperidol delivery to baby by milk or crossed the placenta into the fetal circulation, causing
Ren Fail, 2014; 36(6): 951–952
increased pituitary antidiuretic hormone release or increased pituitary ADH release or increased tubular sensitivity to ADH, or both. After delivery the infant underwent drug withdrawal, which left her with a transient ADH deficiency. We cannot be certain that haloperidol withdrawal was the only factor contributing to the hypernatremia but suggests that it was the major one. For the first time, we report a neonate with transient nephrogenic DI caused by fetal exposure to haloperidol. The magnitude of risk associated with the use of haloperidol during pregnancy appears to be small, but acquired nephrogenic DI secondary to haloperidol is a serious condition with the risk of hypernatremic dehydration. The present case illustrates an extremely rare consequence of haloperidol induced nephrogenic diabetes insipidus. Haloperidol can have adverse effects on the fetus and newborn infant, because of whichone should prevent the use of haloperidol during pregnancy and lactation.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Klinger G, Stahl B, Fusar-Poli P, Merlob P. Antipsychotic drugs and breastfeeding. Pediatr Endocrinol Rev. 2013;10:308–317. 2. Fleischer LM, Wilson TA, Parker MM. Hypernatremic dehydration diabetes insipidus, and cerebral venous sinus thrombosis in a neonate: a case report. J Med Case Rep. 2007;1:66. doi: 10.1186/ 1752-1947-1-66. 3. Zaki SA, Mondkar J, Shanbag P, Verma R. Hypernatremic dehydration due to lactation failure in an exclusively breastfed neonate. Saudi J Kidney Dis Transpl. 2012;23:125–128. 4. Karadag A, Erdeve O, Atasay B, et al. Isolated central diabetes insipidus in a newborn with congenital toxoplasmosis. J Pediatr Endocrinol Metab. 2006;19:173–175. 5. Rivas-Crespo MF, Min˜ones-Sua´rez L, G-Gallarza SS. Rare neonatal diabetes insipidus and associated late risks: case report. BMC Pediatr. 2012;12:56. doi: 10.1186/1471-2431-12-56. 6. Iqbal MM, Aneja A, Rahman A, et al. The potential risks of commonly prescribed antipsychotics: during pregnancy and lactation. Psychiatry (Edgmont). 2005;2:36–44.
CASE REPORT
Transient nephrogenic diabetes insipidus caused by fetal exposure to haloperidol Melek Akar, C¸ig˘dem Seher Kasapkara, Mehmet Nuri O¨zbek, Heybet Tu¨zu¨n, Bedri Aldudak, and Berat Kanar
Ren Fail Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 02/12/15 For personal use only.
Department of Neonatology, Diyarbakir Children Hospital, Diyarbakir, Turkey
Abstract
Keywords
Haloperidol is commonly used in the treatment of psychiatric disorders. Data from animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in high doses. For the first time, we report a neonate with transient nephrogenic diabetes insipidus (DI) caused by fetal exposure to haloperidol. The magnitude of risk associated with the use of haloperidol during pregnancy appears to be small, but nephrogenic DI secondary to haloperidol is a serious condition with the risk of hypernatremic dehydration. Haloperidol can have adverse effects on the fetus and newborn infant, that’s why one should prevent the use of haloperidol during pregnancy and lactation.
Haloperidol, neonate, nephrogenic diabetes insipidus
Introduction Haloperidol is commonly used in the treatment of psychiatric disorders. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. Haloperidol should be given during pregnancy only if the benefit to the mother clearly outweighs the potential fetal risk.1 In this report, we present a case of transient nephrogenic DI whose mother was on haloperidol treatment within pregnancy.
Case The mother has used haloperidol alone because of psychosis since she was 29 years old. The daily dose of haloperidol was 20 mg. At 31 years of age she experienced her first pregnancy while on haloperidol treatment. The mother had not received prenatal attention by a physician. The baby was delivered vaginally on term. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. Birth weight was 3100 g. She discontinued haloperidol after giving birth. The baby was exclusively breastfed and referred to our hospital after 3 days of fever, irritability, and feeding difficulties. On neurological evaluation, she was hypotonic especially in the trunk. All neonatal reflexes including Moro were depressed along with decreased movements. She was phenotypically normal but the baby was hypoactive and appeared to be dehydrated. Her weight was 2300 g, temperature of 98 F rectally, heart rate 125/min, respiratory rate 42/min, and blood pressure 62/30 mmHg. Serum sodium level was 164 mmol/L, Address correspondence to Melek Akar, MD, Department of Neonatology, Diyarbakir Children Hospital, NICU Yenisehir, Diyarbakir, Turkey. E-mail: [email protected]
History Received 3 December 2013 Revised 17 February 2014 Accepted 23 February 2014 Published online 27 March 2014
potassium was 4.8 mmol/L, blood urea nitrogen 117 mg/dL, creatinine 1.28 mg/dL, glucose 84 mg/dL, calcium 10.2 mg/ dL. Initial complete blood count revealed a white blood cell of 16,900/mm3, hemoglobin 18.6 g/dL, hematocrit 56.2%, likely due to hemoconcentration. Urine output was 6.5 mL/kg/h (normal, 2–4 mL/kg/h). Serum osmolality was 373 mOsm/kg H2O (normal, 280–300 mOsm/kg H2O). Urine sodium concentration was 15 mmol/L. Urine osmolality and urine specific gravity were 112 mOsm/kg H2O (normal, 600– 800 mOsm/L) and 1004 mg/mL, respectively. The patient was evaluated for other endocrine abnormalities but no additional hormonal pathology was found. A renal ultrasound scan was normal. By 6th day of life, the urine output gradually decreased to 3–4 mL/kg/h on an intake of 140 mL/kg/day. At that time, urine osmolality increased to 192 mOsm/kg H2O, with a specific gravity of 1010 mg/mL. She made steady recovery before discharge. Follow up examination at three weeks of age with endocrinologic examination revealed a thriving infant.
Discussion In breast-fed neonates, hypernatremia may occur from inadequate breast milk production, central or nephrogenic DI, gastroenteritis, or salt poisoning. Close follow up of infants during the first days after hospital discharge, particularly in breast-fed infants, is essential for the primary care physician to detect early weight loss. Even in the infant who looks well, weight loss of 10% or more deserves an immediate investigation, including evaluation of the serum electrolytes for possible hypernatremia.2,3 This case was admitted to our hospital with large water losses in the urine and hypernatremic dehydration. The mother had no history of lactation
Ren Fail Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 02/12/15 For personal use only.
952
M. Akar et al.
failure or this exclusively breast-fed infant had no history of diarrhea. Paradoxical hypernatremic dehydration and polyuria were believed to be a result of nephrogenic diabetes insipidus secondary to haloperidol treatment. Neonatal DI is extremely rare and its etiology has not been documented extensively.4 Urine output is not a good indicator of hydration status in children with DI and can lead to an inappropriate reassurance. In addition, patients with hypernatremic dehydration may clinically appear relatively well; and therefore, laboratory investigation is necessary to make the diagnosis. Once recognized, hypernatremic dehydration in the neonate must be evaluated expeditiously to investigate the possibility of DI and other causes. It is important to check paired serum and urine osmolarity, urine specific gravity, and urine electrolytes. The combination of hypernatremia, inappropriately low urine specific gravity and low urinary sodium concentration will confirm a diagnosis of DI. A simultaneous measurement of serum antidiuretic hormone (ADH) or the response to ADH will indicate whether the DI is central or nephrogenic.5 This patient had severe hypernatremia, low urine density and low urine sodium concentration. Nephrogenic diabetes insipidus was considered, because of this serum ADH level was not measured. Haloperidol is a dopamine inverse agonist of the typical antipsychotic class of medications. Haloperidol has a half-life of 13–35 h in adults. In humans, no controlled studies exist. Unconfirmed studies in pregnant woman revealed possible damage to the fetus, although most of the women were exposed to multiple drugs during pregnancy. Haloperidol, when given to lactating women, is found in significant amounts in their milk. Breast-fed children sometimes show extrapyramidal symptoms. Following accepted general principles, haloperidol should be given during pregnancy and lactation only if the benefit to the mother clearly outweighs the potential risk.6 The patient’s symptoms such as hypernatremia, abnormal renal function tests, serum and urine osmolalities resolved spontaneously by six days of hospitalization suggested that the newborn had experienced haloperidol induced nephrogenic DI. We suggest that haloperidol delivery to baby by milk or crossed the placenta into the fetal circulation, causing
Ren Fail, 2014; 36(6): 951–952
increased pituitary antidiuretic hormone release or increased pituitary ADH release or increased tubular sensitivity to ADH, or both. After delivery the infant underwent drug withdrawal, which left her with a transient ADH deficiency. We cannot be certain that haloperidol withdrawal was the only factor contributing to the hypernatremia but suggests that it was the major one. For the first time, we report a neonate with transient nephrogenic DI caused by fetal exposure to haloperidol. The magnitude of risk associated with the use of haloperidol during pregnancy appears to be small, but acquired nephrogenic DI secondary to haloperidol is a serious condition with the risk of hypernatremic dehydration. The present case illustrates an extremely rare consequence of haloperidol induced nephrogenic diabetes insipidus. Haloperidol can have adverse effects on the fetus and newborn infant, because of whichone should prevent the use of haloperidol during pregnancy and lactation.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Klinger G, Stahl B, Fusar-Poli P, Merlob P. Antipsychotic drugs and breastfeeding. Pediatr Endocrinol Rev. 2013;10:308–317. 2. Fleischer LM, Wilson TA, Parker MM. Hypernatremic dehydration diabetes insipidus, and cerebral venous sinus thrombosis in a neonate: a case report. J Med Case Rep. 2007;1:66. doi: 10.1186/ 1752-1947-1-66. 3. Zaki SA, Mondkar J, Shanbag P, Verma R. Hypernatremic dehydration due to lactation failure in an exclusively breastfed neonate. Saudi J Kidney Dis Transpl. 2012;23:125–128. 4. Karadag A, Erdeve O, Atasay B, et al. Isolated central diabetes insipidus in a newborn with congenital toxoplasmosis. J Pediatr Endocrinol Metab. 2006;19:173–175. 5. Rivas-Crespo MF, Min˜ones-Sua´rez L, G-Gallarza SS. Rare neonatal diabetes insipidus and associated late risks: case report. BMC Pediatr. 2012;12:56. doi: 10.1186/1471-2431-12-56. 6. Iqbal MM, Aneja A, Rahman A, et al. The potential risks of commonly prescribed antipsychotics: during pregnancy and lactation. Psychiatry (Edgmont). 2005;2:36–44.
