Skip to main content

Unilateral multicystic dysplastic kidney in infants exposed to antiepileptic drugs during pregnancy

Pediatric Nephrology volume 22, pages 1054–1057 (2007)Cite this article

Abstract

Prenatal exposure to antiepileptic drugs (AEDs) increases the risk of major congenital malformations (MCM) in the fetus. AED-related abnormalities include heart and neural tube defects, cleft palate, and urogenital abnormalities. Among the various congenital anomalies of the kidney and urinary tract (CAKUT), multicystic dysplastic kidney (MCDK) disease is one of the most severe expressions. Although prenatal ultrasound (US) examination has increased the prenatal diagnosis of MCDK, the pathogenesis is still unclear. We report on four cases of MCDK in infants of epileptic women treated with AEDs during pregnancy. From October 2003 to June 2006, we observed four infants with unilateral MCDK born to epileptic women. Three patients were considered to have typical features of multicystic dysplastic kidney, and one infant was operated because of a cystic pelvic mass in the absence of a kidney in the left flank. The macroscopic appearance of this mass showed an ectopic multicystic kidney confirmed by histological findings. All patients have been studied by US scans, voiding cystourethrogram (VCUG), and radionuclide screening isotope imaging. The prenatal exposure to AEDs increases the risk of major congenital malformations from the background risk of 1–2% to 4–9%. AEDs may determine a defect in apoptosis regulation that could lead to abnormal nephrogenesis, causing MCDK. Carbamazepine (CBZ) and phenobarbital (PHB) during pregnancy should be used at the lowest dosage compatible with maternal disease. The reduction, or even suspension, of drug dosage should be achieved from the periconceptional period to the first 8 weeks of gestation to avoid any interference with organogenesis.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S, Hayes AM, Ryan LM (2001) The teratogenicity of anticonvulsant drugs. N Eng J Med 344:1132–1138

    CAS  Article  Google Scholar 

  2. Pennel PB (2004) Pregnancy in women who have epilepsy. Neurol Clin 22:799–820

    Article  Google Scholar 

  3. Fried S, Kozer E, Nulman I, Einarson TR, Koren G (2004) Malformation rates in children of women with untreated epilepsy; a meta-analysis. Drug Saf 27:197–202

    PubMed  Article  Google Scholar 

  4. Canger R, Battino D, Canevini MP, Fumarola C, Guidolin L, Vignoli A, Mamoli D, Palmieri C, Molteni F, Granata T, Hassibi P, Zamperini P, Pardi G, Avanzino G (1999) Malformations in offspring of women with epilepsy: a prospective study. Epilepsia 40:1231–1236

    CAS  PubMed  Article  Google Scholar 

  5. Fairgrieve SD, Jackson M, Jonas P, Walshaw D, White K, Montgomery TL, Burn J, Lynch SA (2000) Population based, prospective study of the care of woman with epilepsy in pregnancy. BMJ 321:674–675

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. Yerby MS (2001) The use of anticonvulsants during pregnancy. Semin Perinatol 25:153–158

    CAS  PubMed  Article  Google Scholar 

  7. Stumpf DA, Frost M (1978) Seizures, anticonvulsants, and pregnancy. Am J Dis Child 132:746–748

    CAS  PubMed  Google Scholar 

  8. Samren EB, van Duijn CM, Christiaens GCML, Hofman A, Lindhout D (1999) Antiepileptic drug regimens and major congenital abnormalities in the offspring. Ann Neurol 46:739–746

    CAS  PubMed  Article  Google Scholar 

  9. Wide K, Winbladh B, Kallen B (2004) Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepin and valproic acid: a nation-wide, population-based register study. Acta Pediatr 93:174–176

    CAS  Article  Google Scholar 

  10. Matalon S, Schechtman S, Godzweig G, Ornoy A (2002) The teratogenic effect of carbamazepine: a meta-analysis of 1255 exposures. Reprod Toxicol 16:9–17

    CAS  PubMed  Article  Google Scholar 

  11. Janz D (1994) Are anti epileptic drugs harmful when taken during pregnancy? J Perinat Med 22:367–375

    CAS  PubMed  Article  Google Scholar 

  12. Lindhout D, Hoppener RJ, Meinardi H (1984) Teratogenicity of antiepileptic drug combinations with special emphasis on epoxidation (of carbamazepine). Epilepsia 25:77–83

    CAS  PubMed  Article  Google Scholar 

  13. Arpino C, Brescianini S, Robert E, Castilla EE, Cocchi G, Cornel MC, de Vigan C, Lancaster PA, Merlob P, Sumiyoshi Y, Zampino G, Renzi C, Rosano A, Mastroiacovo P (2000) Teratogenic effects of antiepileptic drugs: use of an International Database on Malformations and Drug Exposure (MADRE). Epilepsia 41:1436–1443

    CAS  PubMed  Article  Google Scholar 

  14. Hernandez-Diaz S, Werler MM, Walker AM, Allen A (2000) Folic acid antagonists during pregnancy and the risk of birth defects. N Eng J Med 343:1608–1614

    CAS  Article  Google Scholar 

  15. Pope JC, Brock JW, Adams MC, Douglas Stephens F, Ichikawa I (1999) How they begin and how they end: classic and new theories for the development and deterioration of congenital anomalies of the kidney and urinary tract, CAKUT. J Am Soc Nephrol 10:2018–2028

    PubMed  PubMed Central  Google Scholar 

  16. Chandler D, El-Naggar AK, Brisbay S, Redline RW, McDonnel TJ (1994) Apoptosis and expression of the bcl-2 proto-oncogene in the fetal and adult human kidney: evidence for the contribution of bcl-2 expression to renal carcinogenesis. Human Pathol 25:789–796

    CAS  Article  Google Scholar 

  17. Trudel M, Lanoix J, Barisoni L, Bloudin M, Desforges M, L’Italien C, D’Agati V (1997) C-MYC-induced apoptosis in polycystic kidney disease is Bcl-2 and p53 independent. J Exp Med 186:1873–1884

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. Sorenson CM, Padanilam BJ, Hammerman MR (1996) Abnormal postpartum renal development and cystogenesis in the bcl-2 (−/−) mouse. Am J Physiol 271:F184–F193

    CAS  PubMed  Google Scholar 

  19. Winyard PJD, Risdon RA, Sams VR, Dressler GR, Woolf AS (1996) The PAX2 transcription factor is expressed in cystic and hyperprofilerative dysplastic epithelia in human kidney malformations. J Clin Invest 98:451–459

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Worner W, Schrenk D (1996) Influence of liver tumor promoters on apoptosis in rat hepatocytes induced by 2-acetylaminofluorene, ultraviolet light, or transforming growth factor beta 1. Cancer Res 56:1272–1278

    CAS  PubMed  Google Scholar 

  21. Sanders S, Thorgeirsson SS (1999) Phenobarbital promotes liver growth in c-myc/TGF-a transgenic mice by inducing hypertrophy and inhibiting apoptosis. Carcinogenesis 20:41–49

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

  1. UTIN e Pediatria, Università di Palermo, Palermo, Italy

    Maurizio Carta, Mario Giuffrè & Giovanni Corsello

  2. Unità di Chirurgia Pediatrica, Dipartimento Materno Infantile, Università di Palermo, Palermo, Italy

    Marcello Cimador, Maria Sergio, Maria Rita Di Pace & Enrico De Grazia

  3. Dipartimento Materno-Infantile, Università di Palermo, Via Cardinale Rampolla 1, 90100, Palermo, Italy

    Maurizio Carta

Authors
  1. Maurizio Carta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcello Cimador
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mario Giuffrè
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Sergio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Rita Di Pace
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Enrico De Grazia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giovanni Corsello
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maurizio Carta.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Carta, M., Cimador, M., Giuffrè, M. et al. Unilateral multicystic dysplastic kidney in infants exposed to antiepileptic drugs during pregnancy. Pediatr Nephrol 22, 1054–1057 (2007). https://doi.org/10.1007/s00467-007-0446-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-007-0446-x

Keywords

  • Multicystic dysplastic kidney
  • Antiepileptic drugs
  • Major congenital anomalies
  • Infant