BREAKING NEWS: ADHD-medication use during pregnancy poses no increased risk of any negative effects on offspring!

ADHD-medication use is safe during pregnancy: New findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

The Danish Way …

For years now, strong proponents against ‘Big Pharma’ (like Scientology etc.) have used the argument that ADHD-medication is harmful, especially when your pregnant, suggesting scenarios from ‘giving your child ADHD before birth’, or ‘making your child addicted to drugs’ along with other far-fetched, yet catchy and creative slogans.

Although it have never been scientific proven to be the case, neither have it been specially disproven – until now!

In this article I can report from the latest scientific research from the National Centre for Register-based Research in Denmark, where Kathrine Bang Madsen and colleagues have just released their findings from the largest study to date on this topic.

In Denmark, every person is given a CPR-number (Social Security Number) at birth, and this acts a primary key for lifelong registration of usage within the social- and health related services, as well as for medicinal prescriptions. Since we are only around 6 mio. people here in Denmark, all of our services are run as what Americans call ‘socialized medicine’, meaning that we do not pay for GP, hospital, or medication for chronic diseases. This means that everything is run from a centrally managed health care system, which all entities that needs to access registry data, prescriptions, or medical journals on a patient, is all registered from birth to death.

As such, the Danish cohort-studies are wellknown for their high level of accuracy and specificity, and world renowned researcher like Prof. Søren Dalsgaard, PhD. have published numerous groundbreaking studies on ADHD, amongst others on increased mortality rates (+50% for people with ADHD), increased risk of injury in childhood when unmedicated (+43%), and lastly looked at high school graduation for people with ADHD, on or off, medication, which showed that 6 out of 10 did not even get a basic diploma, when unmedicated!.

So it is with great pleasure, and some national pride, that I can now add this new study to that list of esteemed priors!

ADHD: Medication use during pregnancy does not pose any risk to your child!

ABSTRACT

Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy. (Bang Madsen et al., 2023)

INTRODUCTION

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder affecting individuals across the lifespan. In parallel to the increasing number of women of reproductive age using ADHD medication, a steep increase in ADHD medication use during pregnancy has been observed. With treatment prevalence recently estimated above 1% of pregnant women, ADHD medications now rank among the most commonly prescribed medications during pregnancy. Meanwhile, no specific guidelines exist for using ADHD medication during pregnancy due to the lack of empirical evidence for the safety and consequences of in utero exposure to these medications. Thus, out of concern for the unborn child, most women currently choose to discontinue their use of ADHD medication around conception. While the consequences of discontinuation are limited in daily life for some women; others struggle to maintain employment and are at higher risk for serious health outcomes, including motor vehicle crashes, accidents, injuries, and suicidality. (Bang Madsen et al., 2023)

Studies have assessed short-term offspring outcomes associated with prenatal exposure to ADHD medication, including congenital malformations, and outcomes related to labor and delivery with conflicting findings. Recent systematic reviews suggested no convincing evidence to indicate that in utero exposure to ADHD medication results in teratogenic effects. Potential effects on cardiac malformations (Modafinil exposure), gestational age and weight cannot be ruled out, but the risk differences appears small. It should be noted that due to the observational nature of existing studies, the possibility of drawing causal inferences is limited. In particular, confounding by indication is challenging in observational treatment studies due to the high heritability of ADHD an because patients in medical treatment for ADHD are likely to be more severely affected by their disorder and other comorbid conditions than those who are not. (Bang Madsen et al., 2023)

The medications most commonly used to treat ADHD are stimulants, which act by increasing the release of catecholamines into the synaptic cleft. Catecholamine synthesis begins mid-gestation, and catecholamine signaling activity is required for the completion of normal fetal development. Thus, it is possible that chronic alterations in catecholamine signaling in the fetus could result in alterations in neural development and growth later in life. Moreover, given that growth restriction is one of the major clinical concerns when ADHD medication is prescribed in children and adolescents, there is a need to study in utero exposure to these medications. (Bang Madsen et al., 2023)

In this population-based register study, we examined whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental outcomes and/or growth impairment. We used multiple rigorous study designs to address different potential sources of biases, including confounding by indication. (Bang Madsen et al., 2023)

CONCLUSIONS

Our results are important because stimulant medications are critical for many adults, including women of childbearing age, to perform their essential functions at work, home, and school. Pregnant women who depend on stimulants for daily functioning must weigh the potential of exposing their fetus to unknown developmental risks against potential medical, financial, and other consequences to both mother and child that are associated with exacerbation of ADHD symptoms when stopping the medication, such as inability to maintain employment and unsafe driving. The present study provides reassurance that several essential categories of child outcomes that could reasonably be suspected to be affected by stimulants, including body growth, neurodevelopment, and seizure risk, do not differ based on antenatal stimulant exposure. Future studies would benefit from larger sample sizes making it possible to conduct stratified analyses on ADHD medication type. Further investigation in other health care systems and of other types of outcomes, such as psychiatric diagnoses in older age groups, would also be of interest. The addition of other types of studies, such as clinical cohort studies, could be used to investigate subtler neurodevelopmental outcomes not accessible in the registers. (Bang Madsen et al., 2023)

Reference

Bang Madsen, K., Robakis, T. K., Liu, X., Momen, N., Larsson, H., Dreier, J. W., Kildegaard, H., Groth, J. B., Newcorn, J. H., Hove Thomsen, P., Munk-Olsen, T., & Bergink, V. (2023). In utero exposure to ADHD medication and long-term offspring outcomes. Molecular Psychiatry. https://doi.org/10.1038/s41380-023-01992-6

Other interesting publications based on the Danish Register …

Dalsgaard, S., Thorsteinsson, E., Trabjerg, B. B., Schullehner, J., Plana-Ripoll, O., Brikell, I., Wimberley, T., Thygesen, M., Madsen, K. B., Timmerman, A., Schendel, D., McGrath, J. J., Mortensen, P. B., & Pedersen, C. B. (2020). Incidence Rates and Cumulative Incidences of the Full Spectrum of Diagnosed Mental Disorders in Childhood and Adolescence. JAMA psychiatry, 77(2), 155–164. https://doi.org/10.1001/jamapsychiatry.2019.3523

Momen, N. C., Plana-Ripoll, O., Agerbo, E., Benros, M. E., Børglum, A. D., Christensen, M. K., Dalsgaard, S., Degenhardt, L., de Jonge, P., Debost, J. P. G., Fenger-Grøn, M., Gunn, J. M., Iburg, K. M., Kessing, L. V., Kessler, R. C., Laursen, T. M., Lim, C. C. W., Mors, O., Mortensen, P. B., Musliner, K. L., … McGrath, J. J. (2020). Association between Mental Disorders and Subsequent Medical Conditions. The New England journal of medicine, 382(18), 1721–1731. https://doi.org/10.1056/NEJMoa1915784

Plana-Ripoll, O., Pedersen, C. B., Holtz, Y., Benros, M. E., Dalsgaard, S., de Jonge, P., Fan, C. C., Degenhardt, L., Ganna, A., Greve, A. N., Gunn, J., Iburg, K. M., Kessing, L. V., Lee, B. K., Lim, C. C. W., Mors, O., Nordentoft, M., Prior, A., Roest, A. M., Saha, S., … McGrath, J. J. (2019). Exploring Comorbidity Within Mental Disorders Among a Danish National Population. JAMA psychiatry, 76(3), 259–270. https://doi.org/10.1001/jamapsychiatry.2018.3658

Dalsgaard, S., Nielsen, H. S., & Simonsen, M. (2014). Consequences of ADHD medication use for children’s outcomes. Journal of health economics, 37, 137–151. https://doi.org/10.1016/j.jhealeco.2014.05.005

Wimberley, T., Brikell, I., Pedersen, E. M., Agerbo, E., Vilhjálmsson, B. J., Albiñana, C., Privé, F., Thapar, A., Langley, K., Riglin, L., Simonsen, M., Nielsen, H. S., Børglum, A. D., Nordentoft, M., Mortensen, P. B., & Dalsgaard, S. (2022). Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder. The Journal of clinical psychiatry, 83(1), 21m14033. https://doi.org/10.4088/JCP.21m14033

Dalsgaard S. (2021). More Evidence Linking Autoimmune Diseases to Attention-Deficit/Hyperactivity Disorder. JAMA pediatrics, 175(3), e205502. https://doi.org/10.1001/jamapediatrics.2020.5502

Özgen, H., Spijkerman, R., Noack, M., Holtmann, M., Schellekens, A., Dalsgaard, S., van den Brink, W., & Hendriks, V. (2021). Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review. Journal of clinical medicine, 10(17), 3908. https://doi.org/10.3390/jcm10173908

Thygesen, M., Holst, G. J., Hansen, B., Geels, C., Kalkbrenner, A., Schendel, D., Brandt, J., Pedersen, C. B., & Dalsgaard, S. (2020). Exposure to air pollution in early childhood and the association with Attention-Deficit Hyperactivity Disorder. Environmental research, 183, 108930. https://doi.org/10.1016/j.envres.2019.108930

Ottosen, C., Larsen, J. T., Faraone, S. V., Chen, Q., Hartman, C., Larsson, H., Petersen, L., & Dalsgaard, S. (2019). Sex Differences in Comorbidity Patterns of Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 58(4), 412–422.e3. https://doi.org/10.1016/j.jaac.2018.07.910

Wimberley, T., Horsdal, H. T., Brikell, I., Laursen, T. M., Astrup, A., Fanelli, G., Bralten, J., Poelmans, G., Gils, V. V., Jansen, W. J., Vos, S. J. B., Bertaina-Anglade, V., Camacho-Barcia, L., Mora-Maltas, B., Fernandez-Aranda, F., Bonet, M. B., Salas-Salvadó, J., Franke, B., & Dalsgaard, S. (2022). Temporally ordered associations between type 2 diabetes and brain disorders – a Danish register-based cohort study. BMC psychiatry, 22(1), 573. https://doi.org/10.1186/s12888-022-04163-z

Fitzgerald, C., Dalsgaard, S., Nordentoft, M., & Erlangsen, A. (2019). Suicidal behaviour among persons with attention-deficit hyperactivity disorder. The British journal of psychiatry : the journal of mental science, 1–6. Advance online publication. https://doi.org/10.1192/bjp.2019.128

Brikell, I., Wimberley, T., Albiñana, C., Pedersen, E. M., Vilhjálmsson, B. J., Agerbo, E., Demontis, D., Børglum, A. D., Schork, A. J., LaBianca, S., Werge, T., Mors, O., Hougaard, D. M., Thapar, A., Mortensen, P. B., & Dalsgaard, S. (2021). Genetic, Clinical, and Sociodemographic Factors Associated With Stimulant Treatment Outcomes in ADHD. The American journal of psychiatry, 178(9), 854–864. https://doi.org/10.1176/appi.ajp.2020.20121686

Dalsgaard, S., Leckman, J. F., Nielsen, H. S., & Simonsen, M. (2014). Gender and injuries predict stimulant medication use. Journal of child and adolescent psychopharmacology, 24(5), 253–259. https://doi.org/10.1089/cap.2013.0101

Bikic, A., & Dalsgaard, S. (2018). Pharmacological treatment reduces the risk of motor vehicle crashes among men and women with ADHD. Evidence-based mental health, 21(2), 79. https://doi.org/10.1136/eb-2017-102816

Chen, Q., Hartman, C. A., Haavik, J., Harro, J., Klungsøyr, K., Hegvik, T. A., Wanders, R., Ottosen, C., Dalsgaard, S., Faraone, S. V., & Larsson, H. (2018). Common psychiatric and metabolic comorbidity of adult attention-deficit/hyperactivity disorder: A population-based cross-sectional study. PloS one, 13(9), e0204516. https://doi.org/10.1371/journal.pone.0204516

Hvolby, A., Christensen, J., Gasse, C., Dalsgaard, S., & Dreier, J. W. (2021). Cumulative incidence and relative risk of sleep problems among children and adolescents with newly diagnosed neurodevelopmental disorders: A nationwide register-based study. Journal of sleep research, 30(3), e13122. https://doi.org/10.1111/jsr.13122

Dalsgaard, S., Mortensen, P. B., Frydenberg, M., & Thomsen, P. H. (2013). Long-term criminal outcome of children with attention deficit hyperactivity disorder. Criminal behaviour and mental health : CBMH, 23(2), 86–98. https://doi.org/10.1002/cbm.1860