Skip to main content
SpringerLink
Log in

Intrauterine Growth Retardation is a Risk Factor for Cisapride-Induced QT Prolongation in Preterm Infants

  • Clinical Pharmacology and Drug Studies
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Background Cisapride is a possible cause of potentially life threatening QT prolongation.

Aims We investigated these cardiac side effects in premature infants, mainly in relation to fetal growth.

Patients Forty six preterms (mean birth weight 1.350 g, mean post conceptional age 31 weeks) were studied. Thirty one of them were appropriate for gestational age (AGA) and 15 were small for gestational age (SGA). Cisapride was randomly administered at a 0.3 mg/kg or 0.6 mg/kg daily dose. Fifty preterms (15 SGA/35 AGA) not treated with Cisapride were used as control group.

Methods A pre-treatment ECG was performed and the QT-corrected (Bazzet’s formula) intervals were compared with the in-treatment values (normal values ≤440 mseconds). In the control group two different ECG were performed with a timing similar to the treated group (mean interval 5 days).

Results and Conclusions No patients showed clinical evidence of drug toxicity. In the small for gestational age group, both baseline QTc (mean 397; range 370–420 ms) and in-treatment QTc (mean 410 range 360–500 ms) were significantly higher than those found in the appropriate for gestational age group (mean 386, range 360–420 ms; mean 396, range 370–420 ms, respectively). This difference was found also in the first ECG of the control group. Moreover the mean QTc lengthening during treatment was significantly higher in small for gestational age group than in the appropriate for gestational age group.

Three infants showed a rise in the QTc interval above the value of 440 ms and all were SGA (p = 0.03). No significant correlation was found between birth weight or gestational age and the change in QTc values during Cisapride treatment in the appropriate for gestational age group. Intrauterine growth retardation is a major risk factor for Cisapride-induced QT prolongation in preterm infants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

NICU:

neonatal intensive care units

QTc:

QT-corrected

ECG:

electrocardiogram

SGA:

small for gestational age

AGA:

appropriate for gestational age

CYP3A4:

isoform 3A4 of the cytochrome P-450

References

  1. Enriquez A, Bolisetty S, Patole S, Garvey PA, Campbell PJ. Randomised controlled trial of Cisapride in feed intolerance in preterm infants. Arch Dis Child Fetal Neonatal Ed 1998;79:F110–F113.

    Article  PubMed  CAS  Google Scholar 

  2. Kimball AL, Carlton DP. Gastroesophageal reflux medications in the treatment of apnoea in premature infants. J Pediatr 2001;138:355–360.

    PubMed  CAS  Google Scholar 

  3. Ward RM, Lemons JA, Molteni RA. Cisapride: A survey of the frequency of use and adverse events in premature newborns. Pediatrics 1999;103:469–472.

    PubMed  CAS  Google Scholar 

  4. Wysowski DK, Bacsanyi J. Cisapride and fatal arrhythmia. N Engl J Med 1996;335:290–291.

    PubMed  CAS  Google Scholar 

  5. Lewin MB, Bryant RM, Fenrich AL, Griffa RG. Cisapride-induced long QT interval. J Pediatr 1996;128:279–281.

    PubMed  CAS  Google Scholar 

  6. Bernardini S, Semama DS, Huet F, Sgro C, Gouyon JB. Effects of Cisapride on QTc interval in neonates. Arch Dis Child 1997;77:F241–F243.

    CAS  Google Scholar 

  7. Hamill PV, Drizd TA, Johnson CL, Reed RB, Roche AF, Moore WM. Physical growth: National Center for Health Statistics percentiles. Am J Clin Nutr 1979;32:607–629.

    PubMed  CAS  Google Scholar 

  8. Tonini M, De Ponti F, Di Nucci A, Crema F. Review article: Cardiac adverse effects of gastrointestinal prokinetics [review]. Aliment Pharmacol Ther 1999;13:1585–1591.

    PubMed  CAS  Google Scholar 

  9. Drolet B, Khalifa M, Deleau P, Hamelin BA, Turgeon J. Block of the rapid component of the delayed rectifier potassium current by the prokinetic agent Cisapride underlies drug-related lengthening of the QT interval. Circulation 1998;97:204–210.

    PubMed  CAS  Google Scholar 

  10. Vandenplas Y, Belli DC, Benatar A, et al. The role of Cisapride in treatment of paediatric gastroesophageal reflux. J Pediatric Gastroent Nutr 1999;28:518–528.

    CAS  Google Scholar 

  11. Dubin A, Kikkert M, Mirmiran M, Ariano R. Cisapride associated with QTc prolongation in very low birth weight preterm infants. Pediatrics 2001;107:1313–1316.

    PubMed  CAS  Google Scholar 

  12. Wang L, Feng ZP, Kondo CS, Sheldon RS, Duff HJ. Developmental changes in the delayed rectifier K channel in mouse heart. Circ Res 1996;79:79–85.

    PubMed  CAS  Google Scholar 

  13. Wang L, Duff HG. Identification and characteristic of the delayed rectifier K current in fetal mouse ventricular myocytes. Am J Physiol 1996;270:H2088–H2093.

    PubMed  CAS  Google Scholar 

  14. Lacroix D, Sonnier M, Moncion A, Cheron G, Cresteil T. Expression of CYP3A in human liver: evidence that the shift between CYP3A7 and CYP3A4 occurs immediately after birth. Eur J Biochem 1997;247:625–634.

    PubMed  CAS  Google Scholar 

  15. Horsmans Y. Major cytochrome P-450 families: Implications in health and liver disease. Acta Gastroenetrol Belg 1997;60:2–10.

    CAS  Google Scholar 

  16. Cools F, Benatar A, Bruneel E, et al. A comparison of the pharmacokinetics of two dosing regimens of cisapride and their effects on corrected QT interval in premature infants. Eur J Clin Pharmacol 2003;59:17–22.

    PubMed  CAS  Google Scholar 

  17. Bergman JW, Human DE, Moor MMA, Schulz JM. Effect of kwashiorkor on the cardiovascular system. Arch Dis Child 1988;63:1359–1362.

    PubMed  CAS  Google Scholar 

  18. Thwaites BC, Bose M. Very low calorie diets and pre-fasting prolonged QT interval. A hidden potential danger. West Indian Med J 1992;41:169–171.

    PubMed  CAS  Google Scholar 

  19. Fuenmayor AJ, Mora RE, Fuenmayor AC, Fuenmayor AM. QT-interval dispersion in malnourished children. Clin Cardiol 1998;21:201–205.

    Article  PubMed  CAS  Google Scholar 

  20. Cunha DF, Cunha SF, Ferreira TP, et al. Prolonged QTc intervals on the electrocardiograms of hospitalised malnourished adults. Nutrition 2001;17:370–372.

    PubMed  CAS  Google Scholar 

  21. Cooke RA, Chambers JB, Singh R, et al. QT interval in anorexia nervosa. Br Heart J 1994;72:69–73.

    PubMed  CAS  Google Scholar 

  22. Widmark C, Jansson T, Lindecrantz K, Rosen KG. ECG waveform, short term heart rate variability and plasma catecholamine concentration in response to hypoxia in intrauterine growth retarded guinea-pig fetuses. J Dev Physiol 1991;15:161–163.

    PubMed  CAS  Google Scholar 

  23. Massin MM, Withofs N, Maeyns K, Ravet F. The influence of fetal and postnatal growth on heart rate variability in young infants. Cardiology 2001;95:80–83.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Preventive Pediatrics and Neonatology, University of Bologna, Italy

    Luigi Corvaglia MD, Giacomo Faldella, Raffaella Rotatori, Marcello Lanari, Maria Grazia Capretti & Gian Paolo Salvioli

Authors
  1. Luigi Corvaglia MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giacomo Faldella
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raffaella Rotatori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcello Lanari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Grazia Capretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gian Paolo Salvioli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luigi Corvaglia MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Corvaglia, L., Faldella, G., Rotatori, R. et al. Intrauterine Growth Retardation is a Risk Factor for Cisapride-Induced QT Prolongation in Preterm Infants. Cardiovasc Drugs Ther 18, 371–375 (2004). https://doi.org/10.1007/s10557-005-5061-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-005-5061-0

Key Words

Search

Navigation