Advertisement

Drug Safety

, Volume 29, Issue 6, pp 537–548 | Cite as

Herbal Medicines Used During the First Trimester and Major Congenital Malformations

An Analysis of Data from a Pregnancy Cohort Study
  • Chao-Hua Chuang
  • Pat Doyle
  • Jung-Der Wang
  • Pei-Jen Chang
  • Jung-Nien Lai
  • Pau-Chung ChenEmail author
Original Research Article

Abstract

Background: Major congenital malformations place a considerable burden on the affected child, the family and society. Any kind of medicine used during pregnancy might have a harmful impact; therefore, such practice has raised concerns. The objective of the current study was to explore the relationship between the use of herbal medicines by pregnant women during the first trimester of pregnancy and the risk of major congenital malformation in their live born infants.

Methods: This was a cross-sectional analysis of data from a prospective pregnancy cohort, which was established between 1984 and 1987. To assemble the cohort, pregnant women of ≥26 weeks of gestation who came to the Taipei Municipal Maternal and Child Hospital in Taiwan for prenatal care were enrolled in the study and interviewed using a structured questionnaire. Detailed information, including herbal medicine use during different periods of pregnancy, was obtained during the interview. Past medical history, current obstetric data and details on conventional medicines used during pregnancy were abstracted from medical records. Data on birth weight, gestational duration and characteristics of live born infants were gathered from the Taiwan national birth register. Congenital malformation information was obtained from multiple sources: the newborn examination record (1984–7); the national death register (1984–2003); and Taiwan National Health Insurance data (1996–2000). Multiple logistic regression was used to estimate the odds ratio [OR] of major congenital malformation by herbal medicines used during the first trimester.

Results: A total of 14 551 live births were analysed. After adjustment for confounding factors, taking huanglian during the first trimester of pregnancy was found to be associated with increased risk of congenital malformations of the nervous system (adjusted OR 8.62, 95% CI 2.54, 29.24). An-Tai-Yin was associated with an increased risk of congenital malformations of the musculoskeletal and connective tissues (adjusted OR 1.61, 95% CI 1.10, 2.36) and the eye (adjusted OR 7.30, 95% CI 1.47, 36.18).

Conclusion: We found evidence for a possible link between the use of specific herbal medicines during the first trimester of pregnancy and increased risks of specific groups of congenital malformations. We could not investigate whether the adverse effects were related to direct toxicity from the herbal medicines, or were from misuse, contamination or uncontrolled confounding. Nonetheless, we would advise caution regarding use of herbal medicines during pregnancy, and we suggest that further investigation of these findings is warranted.

Keywords

Pregnant Woman Herbal Medicine Prenatal Care Congenital Malformation Berberine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was supported by grants (BHP-PHRC-92-4 and D0H93-HP-1702) from the Bureau of Health Promotion, Department of Health, Taiwan.

The authors have no conflicts of interest that are directly relevant to the content of this study.

References

  1. 1.
    Anthony S, Kateman H, Brand R, et al. Ethnic differences in congenital malformations in the Netherlands: analyses of a 5-year birth cohort. Paediatr Perinat Epidemiol 2005; 19: 135–44PubMedCrossRefGoogle Scholar
  2. 2.
    Kalter H. Teratology in the 20th century: environmental causes of congenital malformations in human and how they were established. Neurotoxicol Teratol 2003; 25: 131–282PubMedCrossRefGoogle Scholar
  3. 3.
    Hoffmann W. Fallout from the Chernobyl nuclear disaster and congenital malformations in Europe. Arch Environ Health 2001; 56: 478–84PubMedCrossRefGoogle Scholar
  4. 4.
    Mone SM, Gillman MW, Miller TL, et al. Effects of environmental exposures on the cardiovascular system: prenatal period through adolescence. Pediatrics 2004; 113: 1058–69PubMedGoogle Scholar
  5. 5.
    Li SJ, Ford N, Meister K, et al. Increased risk of birth defects among children from multiple births. Birth Defects Res A Clin Mol Teratol 2003; 67: 879–85PubMedCrossRefGoogle Scholar
  6. 6.
    Becker SM, Al Halees Z, Molina C, et al. Consanguinity and congenital heart disease in Saudi Arabia. Am J Med Genet 2001; 99: 8–13PubMedCrossRefGoogle Scholar
  7. 7.
    Carmichael SL, Shaw GM. Maternal life event stress and congenital anomalies. Epidemiology 2000; 11: 30–5PubMedCrossRefGoogle Scholar
  8. 8.
    Rasmussen SA, Moore CA, Paulozzi LJ, et al. Risk for birth defects among premature infants: a population-based study. J Pediatr 2001; 138: 668–73PubMedCrossRefGoogle Scholar
  9. 9.
    Chuang CH, Lai JN, Wang JD, et al. Prevalence and related factors of Chinese herbal medicine use in pregnant women of Taipei, 1985-1987. Taiwan J Public Health 2005; 24: 335–47Google Scholar
  10. 10.
    Chuang CH, Lai JN, Wang JD, et al. Use of coptidis rhizoma and foetal growth: a follow-up study of 9895 pregnancies. Pharmacoepidemiol Drug Saf 2006; 15: 185–92PubMedCrossRefGoogle Scholar
  11. 11.
    Goldbeck-Wood S, Dorozynski A, Lie LG, et al. Complementary medicine is booming worldwide. BMJ 1996; 313: 131–3CrossRefGoogle Scholar
  12. 12.
    Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998; 280: 1569–75PubMedCrossRefGoogle Scholar
  13. 13.
    Ni H, Simile C, Hardy AM. Utilization of complementary and alternative medicine by United States adults: results from the 1999 national health interview survey. Med Care 2002; 40: 353–8PubMedCrossRefGoogle Scholar
  14. 14.
    Nordeng H, Havnen GC. Impact of socio-demographic factors, knowledge and attitude on the use of herbal drugs in pregnancy. Acta Obstet Gynecol Scand 2005; 84: 26–33PubMedGoogle Scholar
  15. 15.
    Nordeng H, Havnen GC. Use of herbal drugs in pregnancy: a survey among 400 Norwegian women. Pharmacoepidemiol Drug Saf 2004; 13: 371–80PubMedCrossRefGoogle Scholar
  16. 16.
    Tiran D. The use of herbs by pregnant and childbearing women: a risk-benefit assessment. Complement Ther Nurs Midwifery 2003; 9: 176–81PubMedCrossRefGoogle Scholar
  17. 17.
    Tsui B, Dennehy CE, Tsourounis C. A survey of dietary supplement use during pregnancy at an academic medical center. Am J Obstet Gynecol 2001; 185: 433–7PubMedCrossRefGoogle Scholar
  18. 18.
    Gibson PS, Powrie R, Star J. Herbal and alternative medicine use during pregnancy: a cross-sectional survey. Obstet Gynecol 2001; 97Suppl. 1: S44–5Google Scholar
  19. 19.
    Pinn G, Pallett L. Herbal medicine in pregnancy. Complement Ther Nurs Midwifery 2002; 8: 77–80PubMedCrossRefGoogle Scholar
  20. 20.
    Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med 1998; 338: 1128–37PubMedCrossRefGoogle Scholar
  21. 21.
    Lacroix I, Damase-Michel C, Lapeyre-Mestre M, et al. Prescription of drugs during pregnancy in France. Lancet 2000; 356: 1735–6PubMedCrossRefGoogle Scholar
  22. 22.
    Hansan WF, Peacock AE, Yankowitz J. Safe prescribing practices in pregnancy and lactation. J Midwifery Womens Health 2002; 47: 409–21CrossRefGoogle Scholar
  23. 23.
    Malm H, Martikainen J, Klaukka T, et al. Prescription of hazardous drugs during pregnancy. Drug Saf 2004; 27: 899–908PubMedCrossRefGoogle Scholar
  24. 24.
    Andrade SE, Gurwitz JH, Davis RL, et al. Prescription drug use in pregnancy. Am J Obstet Gynecol 2004; 191: 398–407PubMedCrossRefGoogle Scholar
  25. 25.
    Gallo M, Sarkar M, Au W, et al. Pregnancy outcome following gestational exposure to Echinacea: a prospective controlled study. Arch Intern Med 2000; 160: 3141–3PubMedCrossRefGoogle Scholar
  26. 26.
    Simpson M, Parsons M, Greenwood J, et al. Raspberry leaf in pregnancy: its safety and efficacy in labor. J Midwifery Womens Health 2001; 46: 51–9PubMedCrossRefGoogle Scholar
  27. 27.
    Mabina MH, Pitsoe SB, Mood LJ. The effect of traditional medicines on pregnancy outcome. The King Edward VIII Hospital experience. S Afr Med J 1997; 87: 1008–10PubMedGoogle Scholar
  28. 28.
    Murphy PA. Alternative therapies for nausea and vomiting of pregnancy. Obstet Gynecol 1998; 91: 149–55CrossRefGoogle Scholar
  29. 29.
    Conover EA. Over-the-counter products: nonprescription medications, nutraceuticals, and herbal agents. Clin Obstet Gynecol 2002; 45: 89–98PubMedCrossRefGoogle Scholar
  30. 30.
    Price CJ, George JD, Marr MC, et al. Developmental toxicity evaluation of berberine chloride dehydrate (BCD) in Sprague-Dawley (CD) rats [abstract]. Teratology 2001; 63: 279Google Scholar
  31. 31.
    Chan LY, Chiu PY, Lau TK. An in-vitro study of ginsenoside Rb1-induced teratogenicity using a whole rat embryo culture model. Hum Reprod 2003; 18: 2166–8PubMedCrossRefGoogle Scholar
  32. 32.
    Tzeng CR, Yang LL, Chien LW, et al. Effect of traditional Chinese medicine on mouse embryo development. J Taipei Med Coll 1993; 22: 43–6Google Scholar
  33. 33.
    Cosyns JP. Aristolochic acid and Chinese herbs nephropathy: a review of the evidence to date. Drug Saf 2003; 26: 33–48PubMedCrossRefGoogle Scholar
  34. 34.
    Penson RT, Castro CM, Seiden MV, et al. Complementary, alternative, integrative, or unconventional medicine? Oncologist 2001; 6: 463–73PubMedCrossRefGoogle Scholar
  35. 35.
    Angell M, Kassirer JP. Alternative medicine: the risks of untested and unregulated remedies. N Engl J Med 1998; 339: 839–41PubMedCrossRefGoogle Scholar
  36. 36.
    Ko RJ. Adulterants in Asian patent medicines. N Engl J Med 1998; 339: 847PubMedCrossRefGoogle Scholar
  37. 37.
    Ernst E. Adulteration of Chinese herbal medicines with synthetic drugs: a systemic review. J Intern Med 2002; 252: 107–13PubMedCrossRefGoogle Scholar
  38. 38.
    World Health Organization. WHO traditional medicine strategy 2002-2005. Geneva: World Health Organization, 2002 (document reference WH0/TRM/2002.1)Google Scholar
  39. 39.
    World Health Organization. General guidelines for methodologies on research and evaluation of traditional medicines. Geneva: World Health Organization, 2000: 27 (document reference WH0/EDM/TRM/2000.1)Google Scholar
  40. 40.
    Eurocat. Eurocat guide 1.2: instructions for the registration of congenital anomalies. Northern Ireland: Eurocat Central Registry, 2002Google Scholar
  41. 41.
    Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol 1993; 138: 923–36PubMedGoogle Scholar
  42. 42.
    Directorate-General of Budget, Accounting & Statistics. Manpower statistic annual report, 2004. Census Bureau, Directorate-General of Budget, Accounting & Statistics (DGBAS), Taiwan, 1985-7 [online] [in Chinese]. Available from URL: http://www.dgbas.gov.tw/census~n/four/yrtable4,5,13.xls [Accessed 2005 Jan 1]Google Scholar
  43. 43.
    Chen PC, Fu WL, Wang TR. Congenital malformation statistics in Taiwan, 1993. Taipei, Taiwan: Department of Health, The Excusive Yuan/National Taiwan University Hospital, 1995Google Scholar
  44. 44.
    Vaughan Jones SA, Hern S, Nelson-Piercy C, et al. A prospective study of 200 women with dermatoses of pregnancy correlating clinical findings with hormonal and immunopathological profiles. Br J Dermatol 1999; 141: 71–81PubMedCrossRefGoogle Scholar
  45. 45.
    Fu Q-Z, Yang S-Z, Liu D-W. Fu Qing-zhus gynecology. Boulder, (CO): Blue Poppy Press, 1999Google Scholar
  46. 46.
    Wen KC. The turnover rate of marker constituents in Chinese herbal medicines. J Food Drug Anal 2000; 8: 270–7Google Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Chao-Hua Chuang
    • 1
    • 2
  • Pat Doyle
    • 3
  • Jung-Der Wang
    • 1
    • 4
  • Pei-Jen Chang
    • 5
  • Jung-Nien Lai
    • 1
    • 6
  • Pau-Chung Chen
    • 1
    Email author
  1. 1.Institute of Occupational Medicine and Industrial HygieneNational Taiwan University College of Public HealthTaipei 100Taiwan
  2. 2.Department of NursingFooyin UniversityKaohsiung CountyTaiwan
  3. 3.Department of Epidemiology and Population HealthLondon School of Hygiene and Tropical MedicineLondonUK
  4. 4.Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
  5. 5.Department of NursingNational Taipei College of NursingTaipeiTaiwan
  6. 6.Division of Gynecology, Traditional Chinese MedicineTaipei City HospitalTaipeiTaiwan

Personalised recommendations