Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder: a population-based cohort study using a sibling-comparison design.
BACKGROUND
High maternal pre-pregnancy body mass index (BMI) is associated with increased risk of offspring attention deficit hyperactivity disorder (ADHD). However, the role of unmeasured familial confounding for this association remains unclear.


METHODS
We conducted a population-based cohort study via linkage of Swedish national and regional registers to investigate maternal pre-pregnancy BMI (underweight: BMI <18.5; overweight: 25≤ BMI <30; obesity: BMI ≥30) in relation to offspring ADHD. We followed 673 632 individuals born in Sweden between 1992 and 2000, with prospectively collected information on maternal pre-pregnancy BMI, until they received an ADHD diagnosis or ADHD medication, death, emigration or 31 December 2009. Hazard ratios (HRs) were estimated by Cox proportional hazards models. Stratified Cox proportional hazards models were applied to data on full siblings to control for unmeasured familial confounding.


RESULTS
At the population level, pre-pregnancy overweight/obesity was associated with increased risk of offspring ADHD (HR(overweight) = 1.23, 95% CI = 1.18-1.27, P = 0.01; HR(obesity) = 1.64, 95% CI = 1.57-1.73, P = 0.01), after adjustment for measured covariates. In full sibling comparisons, however, previously observed associations no longer remained (HR(overweight) = 0.98, 95% CI = 0.83-1.16, P = 0.82; HR(obesity) = 1.15, 95% CI = 0.85-1.56, P = 0.38).


CONCLUSIONS
The results suggested that the association between maternal pre-pregnancy overweight/obesity and offspring ADHD could be ascribed to unmeasured familial confounding.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Department of Social Sciences-Psychology, Mid Sweden University, Östersund, Sweden, Department of Epidemiology and Biostatistics, Imperial College London, London, UK, Medical Research Council Social Genetic Developmental Psychiatry Centre, King's College London, London, UK, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
Qi
Q
Chen
Arvid
A
Sjölander
Niklas
N
Långström
Alina
A
Rodriguez
Eva
E
Serlachius
Brian M
BM
D'Onofrio
Paul
P
Lichtenstein
Henrik
H
Larsson
D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology*; D015992:Body Mass Index; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008425:Maternal Behavior / Q000523:psychology*; D009034:Mother-Child Relations; D009035:Mothers / Q000706:statistics & numerical data*; D009765:Obesity / Q000453:epidemiology*; D011159:Population Surveillance; D011247:Pregnancy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D035781:Siblings; D011795:Surveys and Questionnaires; D013548:Sweden / Q000453:epidemiology
ADHD; confounding; maternal BMI; prenatal; sibling comparison