Researchers at Karolinska Institutet, Sachs Children’s Hospital, Stockholm, and Uppsala and Stockholm Universities, Sweden, analyzed the effect of moderate and extreme preterm birth on the risk for ADHD in school age children who have survived from NICUs, and allowing for genetic, perinatal, and socioeconomic confounders. Children in a Swedish national register born between 1987 and 2000 were followed up for ADHD medication in 2006 at age 6 to 19 years. Genetic confounding was estimated in a subpopulation of offspring of mothers who had given birth to preterm (<34 weeks) as well as term infants. In a total of 7,506 children in the study population with a record of ADHD medication, corresponding to 1.05% of the boys and 0.29% of girls, the most commonly prescribed drug was methylphenidate (87.8%), followed by atomoxetine (9.2%) and amphetamine (3%).
The odds ratios for ADHD medication were 2.1 for 23 to 28 weeks gestation, 1.6 for 29 to 32 weeks, 1.4 for 33 to 34 weeks, 1.3 for 35 to 36 weeks, and 1.1 for 37 to 38 weeks. The odds ratios for within-mother-between-pregnancy analysis were similar, excluding a genetic confounder effect. The effect of moderate (week 33 to 36) preterm birth on ADHD medication was higher in mothers with a low education (p<0.01). Low Apgar score had a marginal effect on the risk of ADHD medication and did not modify the effect of preterm birth. 
COMMENT. An association of preterm birth with ADHD is related to degree of immaturity and exists with moderate in addition to extreme preterm birth. The main effect is not explained by genetic, perinatal, or socioeconomic confounding, but social adversity, as expressed by low maternal education, may modify the risk of ADHD in moderately preterm births.
Low Apgar scores and increased risk of ADHD is reported in a nationwide population-based cohort study of singletons born in Denmark from 1988 to 2001 . Compared with children with Apgar scores of 9 or 10 at 5 minutes, the risk of ADHD was 75% higher in children with scores of 1 to 4 and 63% higher for those with Apgar scores of 5 to 6 (p<0.001). In this Danish study, Apgar scores are inversely associated with risk of ADHD. Low Apgar and ADHD may have a common cause or low Apgar may reflect one causal factor for ADHD.
Genetic factor in etiology of ADHD is reviewed in a report from Radboud University Nijmegen Medical Centre, the Netherlands, and Massachusetts General Hospital, Boston . A bioinformatics pathway analysis revealed 45 of 85 ADHD candidate genes that fit into a neurodevelopmental network involved in neurite outgrowth. The authors propose that since stimulants are known to regulate neurite outgrowth and network proteins, this study may be useful in the development of pharmacological therapy for ADHD.