Prenatal and Perinatal Risk Factors for Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD), a highly persistent and prevalent pediatric disorder, constitutes substantial burden to affected patients, their families, and society.¹ Apart from genetics, environmental risk factors relevantly contribute to the etiology of ADHD.¹ With great interest, we read the article by Nomura et al² recently published in the Archives suggesting that the combination of maternal gestational diabetes mellitus (GDM) and low socioeconomic position (SEP) is a strong risk factor for childhood ADHD. Limitations of this study are the selected study base and the relatively small sample size.² We aimed to replicate the findings in a large population-based sample.

The German Health Interview and Examination Survey for Children and Adolescents (KiGGS) is a nationwide representative survey on the health status of German children and adolescents in 2003 to 2006 (N = 17 642; aged 0-17 years).³ We used the public use file of KiGGS, which does not contain any personal identifiers; thus, ethical approval was not required. Data from all participants aged 3 to 17 years (n = 13 488) were included. The outcome of interest was lifetime diagnosis of ADHD on the basis of medical or psychological examination as reported in standardized parental interviews conducted by trained interviewers.³ In Germany, ADHD is generally diagnosed according to the International Statistical Classification of Diseases, 10th Revision criteria of “hyperkinetic disorder” that largely correspond with the criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) definition of ADHD combined subtype.¹ Primary exposures of interest were self-reported physician-diagnosed GDM (absent/present) and SEP classified as low, medium, or high based on parental education, professional qualification, professional status, and family net income.⁴ Additionally, age, sex, and a broad set of environmental exposures in the prenatal/perinatal period and in infancy such as breastfeeding (ever vs never fully breastfed); postnatal health problems including breathing problems, maladaptation, infections, jaundice, low birth weight and/or premature delivery, and inpatient treatment (present/absent); maternal smoking/drinking during pregnancy (ever/never); and physician-diagnosed atopic eczema⁵ (ever/never) were considered as competing risk factors in multivariate logistic regression models based on 11 222 observations without missing data. Additive and multiplicative interaction was explored by combining SEP and GDM into 1 variable (reference: no GDM, high SEP). To assess the mode of interaction (additive or multiplicative), we compared the expected odds ratios (ORs) on the basis of single exposures with the observed OR of combined exposure to GDM and SEP.⁶ Data were analyzed using Stata (StataCorp).

Mean participant age was 9.9 years; 50.1% (n = 6751) were female. The prevalence of ADHD, GDM, and low SEP was 4.9% (n = 660), 2.3% (n = 280), and 25.5% (n = 3420), respectively. Both maternal GDM and low SEP were significantly related to ADHD (Table). Multivariate regression modeling indicated that not only GDM (OR, 1.91; 95% CI, 1.21-3.01) and low SEP (OR, 2.04; 95% CI, 1.56-2.68) but also perinatal health problems, maternal smoking during pregnancy, and atopic eczema are independent risk factors for ADHD, whereas fully breastfeeding appears to be protective (irrespective of the duration of breastfeeding; data not shown). Further analyses indicated the presence of additive interaction between maternal GDM and SEP on the risk of ADHD (observed OR for middle-class children exposed to GDM: 3.47; expected OR: 2.93; observed OR for lower-class children exposed to GDM: 3.68; expected OR: 3.56).

Our study confirms the previously reported² association between low SEP, maternal GDM, and ADHD and their additive interaction as risk factors for ADHD in a large population-based sample. Extending previous research, our study indicates that fully breastfeeding may have protective effects on childhood ADHD. Exposure to maternal smoking in pregnancy and perinatal health problems do seem to increase the risk for ADHD. Modification of these environmental risk factors by evidence-based prevention programs may help to decrease the burden of ADHD.

Correspondence: Dr Schmitt, Centre for Evidence-based Healthcare, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany (jochen.schmitt@tu-dresden.de).

Published Online: September 10, 2012. doi:10.1001/archpediatrics.2012.1078

Author Contributions:Study concept and design: Schmitt and Romanos. Analysis and interpretation of data: Schmitt and Romanos. Drafting of the manuscript: Schmitt and Romanos. Critical revision of the manuscript for important intellectual content: Romanos. Statistical analysis: Schmitt. Administrative, technical, and material support: Schmitt.

Additional Contributions: We thank the Robert Koch Institute for making the data of the KiGGS study available and all participants for their time and information.