G M Maher1,2, C Dalman3,4, G W O'Keeffe1,5, P M Kearney2, F P McCarthy1, L C Kenny6, A S Khashan1,2. 1. INFANT Research Centre, Cork, Ireland. 2. School of Public Health, University College Cork, Cork, Ireland. 3. Department of Public Health Sciences, Division of Public Health Epidemiology, Karolinska Institutet, Stockholm, Sweden. 4. Center for Epidemiology and Community Medicine, Stockholm County Council, Stockholm, Sweden. 5. Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland. 6. Department of Women's and Children's Health, Institute of Translational Medicine, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
Abstract
OBJECTIVE: To examine the association between preeclampsia and attention-deficit hyperactivity disorder (ADHD), using a large Swedish-based registry cohort. METHODS: This study comprised 2 047 619 children, with 114 934 (5.6%) cases of ADHD. Preeclampsia was based on two alternate definitions: (i) preeclampsia (using ICD-9/ICD-10) and (ii) preeclampsia and small for gestational age (SGA) combined. ADHD was determined in one of two ways: (i) if a diagnosis of ADHD was present in the National Patient Register or (ii) if an individual was in receipt of ADHD medication in the Prescribed Drug Register. Multivariate Cox proportional hazards regression analysis allowed adjustment for several perinatal/sociodemographic factors. Sibling-matched analysis further controlled for shared genetic and familial confounding. RESULTS: In the adjusted Cox model, preeclampsia was associated with an increase in likelihood of ADHD (HR: 1.15, 95% CI: 1.12, 1.19). The HR for preeclampsia and those born SGA was 1.43 (95% CI: 1.31, 1.55) in the adjusted model, compared to those unexposed to preeclampsia/SGA. The sibling-matched analysis did not materially change these associations (HR: 1.13, 95% CI: 1.05, 1.22) and 1.55 (95% CI: 1.28, 1.88). CONCLUSIONS: Exposure to preeclampsia or preeclampsia/SGA was associated with ADHD, independent of genetic/familial factors shared by siblings. However, it is important to note that sibling-matched analysis can only adjust for factors that are constant between pregnancies; therefore, residual confounding cannot be ruled out. Further research is needed to explore modifiable risk factors and identify those most-at-risk babies following delivery.
OBJECTIVE: To examine the association between preeclampsia and attention-deficit hyperactivity disorder (ADHD), using a large Swedish-based registry cohort. METHODS: This study comprised 2 047 619 children, with 114 934 (5.6%) cases of ADHD. Preeclampsia was based on two alternate definitions: (i) preeclampsia (using ICD-9/ICD-10) and (ii) preeclampsia and small for gestational age (SGA) combined. ADHD was determined in one of two ways: (i) if a diagnosis of ADHD was present in the National Patient Register or (ii) if an individual was in receipt of ADHD medication in the Prescribed Drug Register. Multivariate Cox proportional hazards regression analysis allowed adjustment for several perinatal/sociodemographic factors. Sibling-matched analysis further controlled for shared genetic and familial confounding. RESULTS: In the adjusted Cox model, preeclampsia was associated with an increase in likelihood of ADHD (HR: 1.15, 95% CI: 1.12, 1.19). The HR for preeclampsia and those born SGA was 1.43 (95% CI: 1.31, 1.55) in the adjusted model, compared to those unexposed to preeclampsia/SGA. The sibling-matched analysis did not materially change these associations (HR: 1.13, 95% CI: 1.05, 1.22) and 1.55 (95% CI: 1.28, 1.88). CONCLUSIONS: Exposure to preeclampsia or preeclampsia/SGA was associated with ADHD, independent of genetic/familial factors shared by siblings. However, it is important to note that sibling-matched analysis can only adjust for factors that are constant between pregnancies; therefore, residual confounding cannot be ruled out. Further research is needed to explore modifiable risk factors and identify those most-at-risk babies following delivery.
Authors: Stephen V Faraone; Tobias Banaschewski; David Coghill; Yi Zheng; Joseph Biederman; Mark A Bellgrove; Jeffrey H Newcorn; Martin Gignac; Nouf M Al Saud; Iris Manor; Luis Augusto Rohde; Li Yang; Samuele Cortese; Doron Almagor; Mark A Stein; Turki H Albatti; Haya F Aljoudi; Mohammed M J Alqahtani; Philip Asherson; Lukoye Atwoli; Sven Bölte; Jan K Buitelaar; Cleo L Crunelle; David Daley; Søren Dalsgaard; Manfred Döpfner; Stacey Espinet; Michael Fitzgerald; Barbara Franke; Manfred Gerlach; Jan Haavik; Catharina A Hartman; Cynthia M Hartung; Stephen P Hinshaw; Pieter J Hoekstra; Chris Hollis; Scott H Kollins; J J Sandra Kooij; Jonna Kuntsi; Henrik Larsson; Tingyu Li; Jing Liu; Eugene Merzon; Gregory Mattingly; Paulo Mattos; Suzanne McCarthy; Amori Yee Mikami; Brooke S G Molina; Joel T Nigg; Diane Purper-Ouakil; Olayinka O Omigbodun; Guilherme V Polanczyk; Yehuda Pollak; Alison S Poulton; Ravi Philip Rajkumar; Andrew Reding; Andreas Reif; Katya Rubia; Julia Rucklidge; Marcel Romanos; J Antoni Ramos-Quiroga; Arnt Schellekens; Anouk Scheres; Renata Schoeman; Julie B Schweitzer; Henal Shah; Mary V Solanto; Edmund Sonuga-Barke; César Soutullo; Hans-Christoph Steinhausen; James M Swanson; Anita Thapar; Gail Tripp; Geurt van de Glind; Wim van den Brink; Saskia Van der Oord; Andre Venter; Benedetto Vitiello; Susanne Walitza; Yufeng Wang Journal: Neurosci Biobehav Rev Date: 2021-02-04 Impact factor: 9.052