Abstract
The increasing proportion of women conceiving later in life, associated with the higher probability of contracting a chronic disease, highlights an increasing need to understand the impact of drug use for chronic diseases pre- and postpartum. In this study, the authors report the results of systematic reviews of drug use during pregnancy by focusing on pregnant women with a chronic disease, specifically, epilepsy, rheumatoid arthritis (RA), or schizophrenia. The authors studied the clinical impact of drug use in these chronic diseases on the mother and fetus, as well as the ethical issues and socioeconomic impact of drug use during pregnancy for women with these conditions. The results indicate that treatment discontinuation in epilepsy and schizophrenia can lead to serious adverse effects, whereas pregnancy can have an ameliorating effect on RA symptoms. Delivery and neonatal complications were associated with the use of older generation drugs across the 3 diseases. Newer generation drugs were deemed safer but more expensive. Ethical considerations for physicians and patients involved mainly the potential risks of drug use for the fetus. In conclusion, treatment guidelines need to be developed in the future; additionally, better insight into the economics of pregnancy for women with chronic diseases will improve value for money in obstetric care.
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References
Organisation for Economic Co-operation and Development. Society at a Glance 2009: OECD Social Indicators. Paris, France: OECD Publishing; 2009.
Organisation for Economic Co-operation and Development. Mean Age of Mothers at First Child Birth. OECD Family Database. Paris, France: OECD Social Policy Division; 2012.
World Health Organization. Global Status Report on Noncommunicable Diseases 2010. Geneva, Switzerland: World Health Organization; 2011.
Golding A, Haque UJ, Giles JT. Rheumatoid arthritis and reproduction. Rheum Dis Clin N Am. 2007;33(2):319–343.
Beghi E. Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines. Lancet Neurol. 2004;3(10):618–621.
Grimaccia F, Kanavos P. Treating epilepsy during pregnancy: a systematic literature review of the impact of drug treatment on mother and foetus. LSE Health Working Paper Series in Health Policy and Economics. Working Paper 39. London: London School of Economics.
Østensen M, Förger F. Management of RA medications in pregnant patients. Nat Rev Rheumatol. 2009;5(7):382–390.
Toh S, Li Q, Cheetham TC, et al. Prevalence and trends in the use of antipsychotic medications during pregnancy in the US, 2001–2007: a population-based study of 585,615 deliveries. Arch Womens Ment Health. 2013;16(2):149–157.
Grepstad M, Tzouma V, Grimaccia F, Kanavos P. Treating schizophrenia during pregnancy: a systematic literature review on the impact of drug treatment on mother and foetus. LSE Health Working Paper Series in Health Policy and Economics. Working Paper 41. London: London School of Economics.
Viinikainen K, Heinonen S, Eriksson K, Kälviäinen R. Community-based, prospective, controlled study of obstetric and neonatal outcome of 179 pregnancies in women with epilepsy. Epilepsia. 2006;47(1):186–192.
Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoid arthritis rising? Results from Olmsted County, Minnesota, 1955–2007. Arthritis Rheum. 2010;62(6):1576–1582.
Black DW, Andreasen NC. Introductory Textbook of Psychiatry. Arlington, Virginia: American Psychiatric Publishing; 2011.
Mecacci F, Pieralli A, Bianchi B, Paidas MJ. The impact of autoimmune disorders and adverse pregnancy outcome. Semin Perinatol. 2007;31(4):223–226.
Castle D, Sham P, Murray R. Differences in distribution of ages of onset in males and females with schizophrenia. Schizophr Res. 1998;33(3):179–183.
Wyllie E, Cascino GD, Gidal E, Goodkin HP, eds. Wyllie’s Treatment of Epilepsy: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins; 2012.
Tzouma V, Grepstad M, Kanavos P. Treating rheumatoid arthritis during pregnancy: a systematic literature review of the impact of drug treatment on mother and foetus. LSE Health Working Paper Series. Working Paper 40. London: London School of Economics.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–1012.
NHS Centre for Reviews and Dissemination. Systematic Reviews: CRD’s Guidance for Undertaking Reviews in Health Care. York, United Kingdom: University of York, NHS Centre for Reviews and Dissemination; 2008.
Doherty M. What value case reports? Ann Rheum Dis. 1994;53(1):1.
Østensen M, Fuhrer L, Mathieu R, Seitz M, Villiger PM. A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments. Ann Rheum Dis. 2004;63(10):1212–1217.
De Man YA, Dolhain RJ, van de Geijn FE, Willemsen SP, Hazes JM. Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study. Arthritis Rheum. 2008;59(9):1241–1248.
Förger F, Vallbracht I, Helmke K, Villiger PM, Østensen M. Pregnancy mediated improvement of rheumatoid arthritis. Swiss Med Wkly. 2012;142:w13644.
El-Taweel El-Ebyary MM, El-Motayam AS, Agban EL. Seizures profile during pregnancy in women with epilepsy. Egypt J Neurol Psychiatry Neurosurg. 2009;46(1):119–127.
Hironaka M, Kotani T, Sumigama S, et al. Maternal mental disorders and pregnancy outcomes: a clinical study in a Japanese population. J Obstet Gynaecol Res. 2011;37(10):1283–1289.
US Food and Drug Administration. Information for healthcare professionals: risk of neural tube birth defects following prenatal exposure to valproate. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm192649.htm. Accessed April 9, 2015.
Epilepsy Research UK. Leaving epilepsy untreated during pregnancy “can be dangerous.” Available at: http://www.epilepsyresearch.org.uk/leaving-epilepsy-untreated-during-pregnancy-can-be-dangerous/. Accessed April 9, 2015.
Coppola D, Russo LJ, Kwarta RF Jr., Varughese R, Schmider J. Evaluating the postmarketing experience of risperidone use during pregnancy. Drug Safety. 2007;30(3):247–264.
Almarzouqi M, Scarsbrook D, Klinkhoff A. Gold therapy in women planning pregnancy: outcomes in one center. J Rheumatol. 2007;34(9):1827–1831.
Cassina M, Johnson DL, Robinson LK, et al. Pregnancy outcome in women exposed to leflunomide before or during pregnancy. Arthritis Rheum. 2012;64(7):2085–2094.
Chambers CD, Johnson DL, Robinson LK, et al. Birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum. 2010;62(5):1494–1503.
Mawer G, Briggs M, Baker GA, et al. Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study. Seizure. 2010;19(2):112–119.
Vajda FJ, O’Brien TJ, Hitchcock A, Graham J, Lander C. The Australian registry of anti-epileptic drugs in pregnancy: experience after 30 months. J Clin Neurosci. 2003;10(5):543–549.
Østensen M, von Esebeck M, Villiger PM. Therapy with immunosuppressive drugs and biological agents and use of contraception in patients with rheumatic disease. J Rheumatol. 2007;34(6):1266–1269.
Hajdyla-Banaś I, Banas T, Rydz-Stryszowska I, et al. Pregnancy course and neonatal outcome after exposure to leflunomide—2 cases report and review of literature. Przegl Lek. 2009;66(12):1069–1071.
Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62(6):385–392.
Sinha A, Patient C. Rheumatoid arthritis in pregnancy: successful outcome with anti-TNF agent (etanercept). J Obstet Gynaecol. 2006;26(7):689–691.
Umeda N, Ito S, Hayashi T, Goto D, Matsumoto I, Sumida T. A patient with rheumatoid arthritis who had a normal delivery under etanercept treatment. Inter Med. 2010;49(2):187–189.
Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011;117(5):1499–1506.
Dudzinski DM, Sullivan M. When agreeing with the patient is not enough: a schizophrenic woman requests pregnancy termination. Gen Hosp Psychiatry. 2004;26(6):475–480.
Kim SW, Kim KM, Kim JM, et al. Use of long-acting injectable risperidone before and throughout pregnancy in schizophreniai. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(2):543–545.
Yaeger D, Smith H, Altshuler L. Atypical antipsychotics in the treatment of schizophrenia during pregnancy and the postpartum. Am J Psychiatry. 2006;163(12):2064–2070.
Ružić K, Dadić-Hero E, Knez R, Medved P, Petrić D. Pregnancy and atypical antipsychotics. Psychiatr Danub. 2009;21(3):368–370.
Vučić-Peitl M, Petrić D, Peitl V. Ziprasidone as a possible cause of cleft palate in a newborn. Psychiatr Danub. 2010;22(1):117–119.
Janjić V, Milovanovic D, Ruzic-Zecevic D, Loncar D, et al. Zuclopenthixol decanoate in pregnancy: Successful outcomes in two consecutive off springs of the same mother. Vojnosanitetski Pregled. 2013;70(5):526–529.
American College of Obstetricians and Gynecologists. Use of Psychiatric Medications During Pregnancy and Lactation. ACOG Practice Bulletin No. 92. Washington, District of Columbia: American College of Obstetricians and Gynecologists; 2008.
Coverdale JH, McCullough LB, Chervenak FA. Assisted and surrogate decision making for pregnant patients who have schizophrenia. Schizophr Bull. 2004;30(3):659–664.
Oates M. Psychiatric services for women following childbirth. Int Rev Psychiatry. 1996;8(1):87–98.
Muqtadir S, Hamann MW, Molnar G. Management of psychotic pregnant patients in a medical-psychiatric unit. Psychosomatics. 1986;27(1):31–33.
Chambers CD, Polifka JE, Friedman JM. Drug safety in pregnant women and their babies: Ignorance not bliss. Clin Pharmacol Ther.2008;83(1):181–183.
Charlton RA, Weil JG, Cunnington MC, Ray S, de Vries CS. Comparing the General Practice Research Database and the UK Epilepsy and Pregnancy Register as tools for postmarketing teratogen surveillance: anticonvulsants and the risk of major congenital malformations. Drug Saf. 2011;34(2):157–171.
Dewulf L. Medicines in pregnancy—women and children first? Time for a coalition to address a substantial patient need. Ther Innov Regulat Sci. 2013;47(5):528–532.
Clemow DB, Dewulf L, Michaels DL, et al. A proposed framework to address needs of clinical data for informed medication use in pregnancy. Ther Innov Regulat Sci. 2014;48(2):145–154.
US Food and Drug Administration. Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation final labeling rule. Available at: https://www.federalregister.gov/articles/2014/12/04/2014-28241/content-and-format-of-labeling-for-human-prescription-drug-and-biological-products-requirements-for. Accessed April 10, 2015.
Vajda FJE, Lander CM, Hitchcock A, et al. Changing Australian prescribing patterns for antiepileptic drugs in pregnancy and their possible consequences. J Clin Neurosci. 2007;14(7):611–617.
Jentink J, Loane MA, Dolk H, et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med. 2010;362(23):2185–2193.
Vajda FJE, Graham JE, Hitchcock AA, O’Brien TJ, Lander CM, Eadie MJ. Is lamotrigine a significant human teratogen? Observations from the Australian Pregnancy Register. Seizure. 2010;19(9):558–561.
Physicians Committee for Responsible Medicine, ed. Birth Defect Statistics. Washington, District of Columbia: Physicians Committee for responsible Medicine; 2014.
Russell RB, Green NS, Steiner CA, et al. Cost of hospitalization for preterm and low birth weight infants in the United States. Pediatrics. 2007;120(1):e1–e9.
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Tzouma, V., Grepstad, M., Grimaccia, F. et al. Clinical, Ethical, and Socioeconomic Considerations for Prescription Drug Use During Pregnancy in Women Suffering From Chronic Diseases. Ther Innov Regul Sci 49, 947–956 (2015). https://doi.org/10.1177/2168479015589820
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DOI: https://doi.org/10.1177/2168479015589820