Lin Li1, Ayesha C Sujan2, Agnieszka Butwicka3,4,5, Zheng Chang3, Samuele Cortese6,7,8,9,10, Patrick Quinn11, Alexander Viktorin3, A Sara Öberg3,12, Brian M D'Onofrio13,14, Henrik Larsson1,3. 1. School of Medical Sciences, Örebro University, Örebro, Sweden. 2. Department of Psychological and Brain Sciences, Indiana University, 1101 E. 10th St., Bloomington, IN, 47405, USA. 3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 4. Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Stockholm, Region Stockholm, Sweden. 5. Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland. 6. Centre for Innovation in Mental Health, School of Psychology, Life and Environmental Sciences, University of Southampton, Southampton, UK. 7. Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK. 8. Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK. 9. National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham, UK. 10. New York University Child Study Center, New York, NY, USA. 11. Department of Applied Health Science, School of Public Health, Indiana University, Bloomington, IN, USA. 12. Department of Epidemiology, T.H. Chan School of Public Health, Harvard, Boston, MA, USA. 13. Department of Psychological and Brain Sciences, Indiana University, 1101 E. 10th St., Bloomington, IN, 47405, USA. bmdonofr@indiana.edu. 14. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. bmdonofr@indiana.edu.
Abstract
BACKGROUND: Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring. OBJECTIVES: The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding. METHODS: We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle-Ottawa Scale to rate the quality of the included studies. RESULTS: Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers. CONCLUSION: The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman's specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.
BACKGROUND: Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring. OBJECTIVES: The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding. METHODS: We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle-Ottawa Scale to rate the quality of the included studies. RESULTS: Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers. CONCLUSION: The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman's specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.
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Authors: Ayesha C Sujan; Martin E Rickert; A Sara Öberg; Patrick D Quinn; Sonia Hernández-Díaz; Catarina Almqvist; Paul Lichtenstein; Henrik Larsson; Brian M D'Onofrio Journal: JAMA Date: 2017-04-18 Impact factor: 56.272
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