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Maternal pre-pregnancy overweight/obesity and the risk of attention-deficit/hyperactivity disorder in offspring: a systematic review, meta-analysis and quasi-experimental family-based study
Örebro University, School of Medical Sciences.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Psychology, University of Southampton, Southampton, UK.
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2020 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 49, no 3, p. 857-875Article, review/survey (Refereed) Published
Abstract [en]

BACKGROUND: Previous studies are inconclusive concerning the association between maternal pre-pregnancy overweight/obesity and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. We therefore conducted a systematic review and meta-analysis to clarify this association. To address the variation in confounding adjustment between studies, especially inadequate adjustment of unmeasured familial confounding in most studies, we further performed cousin and sibling comparisons in a nationwide population-based cohort in Sweden.

METHODS: We searched PubMed, Embase and PsycINFO during 1975-2018. We used random-effects models to calculate pooled risk ratios (RRs) with 95% confidence interval. In the population-based study, Cox proportional hazard models were used to calculate the unadjusted hazard ratios (HRs) and HRs adjusted for all confounders identified in previous studies. Stratified Cox models were applied to data on full cousins and full siblings to further control for unmeasured familial confounding.

RESULTS: Eight cohorts with a total of 784 804 mother-child pairs were included in the meta-analysis. Maternal overweight [RRoverweight = 1.31 (1.25-1.38), I2 = 6.80%] and obesity [RRobesity = 1.92 (1.84-2.00), I2 = 0.00%] were both associated with an increased risk of ADHD in offspring. In the population-based cohort of 971 501 individuals born between 1992 and 2004, unadjusted Cox models revealed similar associations [HRoverweight = 1.30 (1.28-1.34), HRobesity = 1.92 (1.87-1.98)]. These associations gradually attenuated towards the null when adjusted for measured confounders [HRoverweight = 1.21 (1.19-1.25), HRobesity = 1.60 (1.55-1.65)], unmeasured factors shared by cousins [HRoverweight = 1.10 (0.98-1.23), HRobesity = 1.44 (1.22-1.70)] and unmeasured factors shared by siblings [HRoverweight = 1.01 (0.92-1.11), HRobesity = 1.10 (0.94-1.27)].

CONCLUSION: Pre-pregnancy overweight/obesity is associated with an increased risk of ADHD in offspring. The observed association is largely due to unmeasured familial confounding.

Place, publisher, year, edition, pages
Oxford University Press, 2020. Vol. 49, no 3, p. 857-875
Keywords [en]
ADHD, confounding, cousin comparison, meta-analysis, obesity, sibling comparison
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:oru:diva-81395DOI: 10.1093/ije/dyaa040ISI: 000593364900020PubMedID: 32337582Scopus ID: 2-s2.0-85089130058OAI: oai:DiVA.org:oru-81395DiVA, id: diva2:1428779
Funder
Swedish Research Council, 2018-02599
Note

Funding Agencies:

Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) 340-2013-5867

European Union (EU)667302

Available from: 2020-05-06 Created: 2020-05-06 Last updated: 2022-03-14Bibliographically approved
In thesis
1. Somatic and occupational outcomes in adult ADHD: epidemiology studies based on real-world data
Open this publication in new window or tab >>Somatic and occupational outcomes in adult ADHD: epidemiology studies based on real-world data
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by inattention or hyperactivity–impulsivity, or both. ADHD is a multifactorial disorder influenced by the complex interplay between genetic and environmental risk factors, but a detailed understanding of the causal status of these factors is lacking. ADHD is associated with many psychiatric disorders, but somatic comorbidity in ADHD has received less attention in the research literature. Pharmacological treatment is effective in reducing the core symptoms of ADHD, but the effects on occupational outcomes remain unclear. The overarching aim of this thesis is to extend previous knowledge on the early risk factors of ADHD, and to increase the awareness and the understanding on somatic and occupational outcomes of ADHD in adults.

In Study I, we combined a systematic review and mate-analysis with a population based cohort of 971,501 individuals born between 1992 and 2004 in Sweden. The meta-analysis revealed a positive association between maternal pre-pregnancy overweight/obesity and risk of ADHD in offspring. However, these associations gradually attenuated toward the null when adjusted for measured confounders,unmeasured factors shared by cousins and unmeasured factors shared by siblings. In Study II, by using a Swedish population-based twin study with 17,999 individuals aged 20–47 years, we found both inattention and hyperactivity/impulsivity was associated with higher consumption of high-sugar food and unhealthy dietary habits, although these associations were generally weak. Further, the observed associations was explained by both genetic and non-shared environmental factors.In Study III, we explored the prospective associations between ADHD and a broad range of cardiovascular diseases in 5,389,519 adults from Sweden, and found that ADHD may be a novel and independent risk factor for cardiovascular diseases. In Study IV, based on the longitudinal cohort of 12,875 middle-aged adults with ADHD, we found the use of ADHD medications during the previous two years was associated with a 10% reduction in the risk of long-term unemployment in the following year.

Taken together, findings from the thesis highlight the need of future studies with various study designs, to fully understand the aetiology and long-term health outcomes of ADHD across the lifespan.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2022. p. 76
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 257
Keywords
ADHD, Comorbidities, Obesity, Dietary habits, ADHD medication, Cardiovascular disease, Epidemiology, Casual inference, Adults
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-97402 (URN)9789175294292 (ISBN)
Public defence
2022-04-08, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2022-02-10 Created: 2022-02-10 Last updated: 2022-03-18Bibliographically approved

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