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Neurodevelopmental outcomes in infants exposed in utero to antipsychotics: a systematic review of published data

Published online by Cambridge University Press:  21 November 2016

Salvatore Gentile*
Affiliation:
Department of Mental Health ASL Salerno, Cava de’ Tirreni, Salerno, Italy Medical School “Federico II”, Department of Neurosciences, Perinatal Psychiatry, University of Naples, Naples, Italy
Maria Luigia Fusco
Affiliation:
Developmental Psychologist, Mental Health Institute, Torre Annunziata, Naples, Italy Post-graduate School of Psychology (SIPGI), Campania, Italy
*
*Address for correspondence: Salvatore Gentile, MD, PhD, Department of Mental Health ASL Salerno, Mental Health Center n. 63, Cava de’ Tirreni, Vietri sui Mare, Piazza Galdi, 841013 Cava de’ Tirreni, Salerno, Italy. (Email: [email protected])

Abstract

The proportion of pregnancies exposed to either second-generation antipsychotics (SGAs) or first-generation antipsychotics (FGAs) varies between 0.3%–2% of all pregnancies, but, until now, little is known about the potential neurobehavioral teratogenicity of antipsychotics. Assessing this safety facet is the aim of this article. PubMed, Scopus, and Google Scholar were searched for eligible articles. PubMed (1954 to May 2016) was searched using several medical subject headings, variously combined. PubMed search results were also limited using the search filter for human studies published in English. Scopus and Google Scholar searches were filtered for article title (antipsychotics/neuroleptics, pregnancy). After excluding duplicates, 9,250 articles were identified and 29 met the following inclusion criteria: only articles that provided original/primary data on neurodevelopmental outcome in human offspring older than 4 months of age, independently of the study design, were selected for review. Indeed, some relevant neurodevelopmental milestones are achieved at this time. Length of study and neurodevelopmental assessment methodology did not influence the study selection. Unfortunately, published data on neurodevelopmental teratogenicity of SGAs mainly derive from case reports and small case-series studies. Even findings emerging from case-control and prospective/retrospective studies are of limited clinical relevance because of their small sample sizes. Limited data are also available on FGAs. Hence, we have to conclude that the long-term neurodevelopmental outcomes for children exposed in utero remain unclear. Low to very low quality evidence of retrieved data makes impossible to confirm or exclude potential long-lasting untoward effects on infant neurocognitive development associate with antenatal exposure to either SGAs or FGAs.

Type
Review Articles
Copyright
© Cambridge University Press 2016 

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Footnotes

Dr. Gentile and Dr. Fusco wish to acknowledge Kay McCauley-Elsom and Christina Wichman for having kindly provided additional relevant information about their articles.

References

1. Gentile, S. SSRIs in pregnancy and lactation with emphasis on neurodevelopmental outcome. CNS Drugs. 2005; 19(7): 623633.CrossRefGoogle ScholarPubMed
2. Gentile, S. Bipolar disorder and pregnancy: to treat or not to treat? Br Med J. 2012; 345: e7367.Google Scholar
3. Toh, S, Li, Q, Cheetham, TC, et al. Prevalence and trends in the use of antipsychotic medications during pregnancy in the U.S., 2001–2007: a population-based study of 585,615 deliveries. Arch Womens Ment Health. 2013; 16(2): 149157.Google Scholar
4. Hanley, GE, Mintzes, B. Patterns of psychotropic medicine use in pregnancy in the United States from 2006 to 2011 among women with private insurance. BMC Pregnancy Childbirth. 2014; 14: 242.Google Scholar
5. Epstein, RA, Bobo, WV, Shelton, RC, et al. Increasing use of atypical antipsychotics and anticonvulsants during pregnancy. Pharmacoepidemiol Drug Saf. 2013; 22(7): 794801.CrossRefGoogle ScholarPubMed
6. Barbui, C, Conti, V, Purgato, M, et al. Use of antipsychotic drugs and mood stabilizers in women of childbearing age with schizophrenia and bipolar disorder: epidemiological survey. Epidemiol Psychiatr Sci. 2013; 22(4): 355361.Google Scholar
7. Gentile, S. Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophr Bull. 2010; 36(3): 518544.Google Scholar
8. Center for Disease Control and Prevention. Important milestones: your baby at four months. http://www.cdc.gov/ncbddd/actearly/milestones/milestones-4mo.html. January 21, 2016. Accessed March 6, 2016.Google Scholar
9. GRADE working group. Criteria for applying or using GRADE. Update 2016. http://www.gradeworkinggroup.org/intro.htm#criteria. Accessed April 15, 2016.Google Scholar
10. Uguz, F. Breastfed infants exposed to combined antipsychotics: two case-reports. Am J Ther. 2015; [Epub ahead of print]. DOI:10.1097/MJT.0000000000000376.CrossRefGoogle Scholar
11. Mervak, B, Collins, J, Valenstein, M. Case report of aripiprazole usage during pregnancy. Arch Womens Ment Health. 2008; 11(3): 249250.Google Scholar
12. Mendhekar, DN, Sharma, JB, Srilakshmi, P. Use of aripiprazole during late pregnancy in a woman with psychotic illness. Ann Pharmacother. 2006; 40(3): 575.CrossRefGoogle Scholar
13. Stoner, SC, Sommi, RW Jr, Marken, PA, Anya, I, Vaughn, J. Clozapine use in two full-term pregnancies. J Clin Psychiatry. 1997; 58(8): 364365.Google Scholar
14. Mendhekar, DN. Possible delayed speech acquisition with clozapine therapy during pregnancy and lactation. J Neuropsychiatry Clin Neurosci. 2007; 19(2): 196197.Google Scholar
15. Kirchheiner, J, Berghöfer, A, Bolk-Weischedel, D. Healthy outcome under olanzapine treatment in a pregnant woman. Pharmacopsychiatry. 2000; 33(2): 7880.Google Scholar
16. Burt, VK, Bernstein, C, Rosenstein, WS, Altshuler, LL. Bipolar disorder and pregnancy: maintaining psychiatric stability in the real world of obstetric and psychiatric complications. Am J Psychiatry. 2010; 167(8): 892897.Google Scholar
17. Stiegler, A, Schaletzky, R, Walter, G, et al. Olanzapine treatment during pregnancy and breastfeeding: a chance for women with psychotic illness? Psychopharmacology (Berl). 2014; 231(15): 30673069.CrossRefGoogle ScholarPubMed
18. Rowe, M, Gowda, BA, Taylor, D, Hannam, S, Howard, LM. Neonatal hypoglycaemia following maternal olanzapine therapy during pregnancy: a case report. Ther Adv Psychopharmacol. 2012; 2(6): 265268.Google Scholar
19. Ifteni, P, Moga, MA, Burtea, V, Correll, CU. Schizophrenia relapse after stopping olanzapine treatment during pregnancy: a case report. Ther Clin Risk Manag. 2014; 10: 901904.Google Scholar
20. Malek-Ahmadi, P. Olanzapine in pregnancy. Ann Pharmacother. 2001; 35(10): 12941295.CrossRefGoogle ScholarPubMed
21. McCauley-Elsom, KM, Cross, W, Kulkarni, J. Mental health: outcomes of 10 babies of mothers with a history of serious mental illness. J Psychiatr Ment Health Nurs. 2014; 21(7): 580586.CrossRefGoogle Scholar
22. Mendhekar, D, Lohia, D. Risperidone therapy in two successive pregnancies. J Neuropsychiatry Clin Neurosci. 2008; 20(4): 485486.CrossRefGoogle ScholarPubMed
23. Kim, SW, Kim, KM, Kim, JM, et al. Use of long-acting injectable risperidone before and throughout pregnancy in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31(2): 543545.Google Scholar
24. Yeong, CC, Worsley, R, Gilbert, H, Kulkarni, J. Gestational diabetes in women with mental illness. Aust N Z J Psychiatry. 2014; 48(10): 958.Google Scholar
25. Özdemir, AK, Pak, ŞC, Canan, F, Geçici, Ö, Kuloğlu, M, Gücer, MK. Paliperidone palmitate use in pregnancy in a woman with schizophrenia. Arch Womens Ment Health. 2015; 18(5): 739740.Google Scholar
26. Klier, MC, Mossaheb, N, Saria, A, Schloegelhofer, M, Zernig, G. Pharmacokinetics and elimination of quetiapine, venlafaxine, and trazodone during pregnancy and postpartum. J Clin Psychopharmacol. 2007; 27(6): 720722.CrossRefGoogle ScholarPubMed
27. Misri, S, Corral, M, Wardrop, AA, Kendrick, KK. Quetiapine augmentation in lactation: a series of case reports. J Clin Psychopharmacol. 2006; 26(5): 508511.Google Scholar
28. Lee, A, Giesbrecht, E, Dunn, E, Ito, S. Excretion of quetiapine in breast milk. Am J Psychiatry. 2004; 161(9): 17151716.Google Scholar
29. Gentile, S. Pharmacological management of borderline personality disorder in a pregnant woman with a previous history of alcohol addiction: a case report. Clin Drug Investig. 2015; 35(11): 761763.Google Scholar
30. Grover, S, Madan, R. Successful use of quetiapine in two successive pregnancies. J Neuropsychiatry Clin Neurosci. 2012; 24(1): E38.Google Scholar
31. Werremeyer, A. Ziprasidone and citalopram use in pregnancy and lactation in a woman with psychotic depression. Am J Psychiatry. 2009; 166(11): 1298.Google Scholar
32. Mendhekar, DM, Andrade, C. Uneventful use of haloperidol and trihehexyphenidyl during three consecutive pregnancies. Arch Womens Ment Health. 2011; 14(1): 8384.Google Scholar
33. Janjić, V, Milovanović, DR, Zecević, DR, et al. Zuclopenthixol decanoate in pregnancy: successful outcomes in two consecutive offspring of the same mother. Vojnosanit Pregl. 2013; 70(5): 526529.CrossRefGoogle ScholarPubMed
34. Štika, L, Elisová, K, Honzáková, H, et al. Effects of drug administration in pregnancy on children’s school behaviour. Pharm Weekbl Sci. 1990; 12(6): 252255.Google ScholarPubMed
35. Peng, M, Gao, K, Ding, Y, et al. Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study. Psychopharmacology (Berl). 2013; 228(4): 577584.Google Scholar
36. Johnson, KC, LaPrairie, JL, Brennan, PA, Stowe, ZN, Newport, DJ. Prenatal antipsychotic exposure and neuromotor performance during infancy. Arch Gen Psychiatry. 2012; 69(8): 787794.CrossRefGoogle ScholarPubMed
37. Wichman, CL. Atypical antipsychotic use in pregnancy: a retrospective review. Arch Womens Ment Health. 2009; 12(1): 5357.Google Scholar
38. Walker, A, Rosemberg, M, Balaban-Gil, K. Neurodevelopmental and neurobehavioral sequelae of selected substances of abuse and psychiatric medications in utero. Child Adolesc Psychiatr Clin N Am. 1999; 8(4): 845867.Google Scholar
39. Lobstein, R, Koren, G. Pregnancy outcome and neurodevelopment of children exposed in utero to psychoactive drugs: the Motherisk experience. J Psychiatry Neurosci. 1997; 22(3): 192196.Google Scholar
40. Scott, JR. In defense of case reports. Obstet Gynecol. 2009; 114(2 Pt2): 413414.Google Scholar
41. Hurd, WW. Case reports in the era of evidence-based medicine. Obstet Gynecol. 2014;2 Pt 2; 124: 409410.Google Scholar
42. Galbally, M, Snellen, M, Power, J. Antipsychotic drugs in pregnancy: a review of their maternal and fetal effects. Ther Adv Drug Saf. 2014; 5(2): 100109.Google Scholar
43. Morgan, VA, Croft, ML, Valuri, GM, et al. Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression. Br J Psychiatry. 2012; 200(4): 282289.Google Scholar
44. Ladavac, AS, Dubin, WR, Ning, A, Stuckeman, PA. Emergency management of agitation in pregnancy. Gen Hosp Psychiatry. 2007; 29(1): 3941.Google Scholar