Low Birth Weight, Prematurity Can Raise ADHD Risk

Premature birth or low birth weight increase the risk of clinically verifiable hyperkinetic disorder (HKD), according to a study based on Danish medical and population registers.

Children born at fewer than 34 weeks gestational age were three times more likely to develop HKD than children born at term, said Karen Linnet, Ph.D., of the Perinatal Epidemiology Research Unit in the Department of the Obstetrics and Pediatrics at Aarhus University Hospital, Aarhus, Denmark, and colleagues. Full-term children born with birth weights below 3,000 grams also had an increased HKD risk.

Hyperkinetic disorder is the ICD-10 clinical correlate of DSM-IV's attention-deficit/hyperactivity disorder, combined type. The study was published in the June Archives of Disease in Childhood.

Cases in the study were drawn from the Danish Psychiatric Central Register, which includes records, dates, and diagnoses of all inpatient admissions and outpatient contacts at psychiatric departments in Denmark.

Exactly how preterm birth and poor intrauterine growth affect the fetal brain to cause HKD is unclear, said the researchers.

One possibility is that fetal hypoxia and hypotension injure the striatal complex of the basal ganglia and increase the number of dopamine receptors. Undernutrition during fetal brain development may also have long-term effects on attention, learning, and memory, as animal studies have shown, according to Linnet and colleagues.

Much previous research has focused on extremely premature (birth prior to 28 weeks) or very low birth weight babies— those born weighing less than 1,500 grams. Linnet's work indicates that risk remains with children born at higher gestational age or slightly underweight.

“This study shows that the relative risk persists even with mild prematurity, babies born at between 34 and 36 weeks,” said Martin Stein, M.D., a professor of pediatrics at the University of California, San Diego School of Medicine, in an interview with Psychiatric News.

Linnet and colleagues matched each of the 834 case children with 25 randomly selected children of the same gender and age. Children with autism or other pervasive developmental disorders were excluded. Gestational age was recorded by midwives at the time of birth and recorded in the Danish Medical Birth Registry. Gestational age of 40 to 42 weeks and birth weight of 3,000 to 3,999 grams were used as references.

The study benefited from the availability of a national medical system with comprehensive records and cases based on true diagnoses, not just parental reports, said Stein.

“Compared with children born at term, children with gestational ages between 34 and 36 completed weeks had an 80 percent increased risk of HKD, and children with gestational ages below 34 had a three-fold increased risk,” said the researchers. “Children born at term with birth weights between 1,500 and 2,499 grams had more than a twofold increased risk of HKD compared with children born at term with birth weights above 2,999 grams, whereas children with birth weights between 2,500 and 2,999 grams had a 70 percent increased risk.”

Single-parent families, poor social factors, and younger parental age were risk factors for HKD, as were previous psychiatric admissions for the child and parental psychopathology, but adjustment for these factors did not change the outcomes.

Maternal smoking is a known risk factor for HKD in offspring, but limiting analysis to children of nonsmoking mothers still found that preterm delivery increased risk.

“Most premature infants won't develop ADHD,” said Stein.“ But this study is a reminder of the importance of including a detailed prenatal and perinatal history when evaluating a child for possible ADHD.”

Prematurity takes on added significance with the release in July of a report for the Institute of Medicine noting that 12.5 percent of births in the United States were preterm in 2005, a 30 percent increase over 1981 rates. The report cited socioeconomic, genetic, biological, and environmental factors as possible causes. Girls under age 16 and women older than 35 have a greater chance of preterm delivery, for instance. Increased use of assisted reproductive technologies may play a role, because multiple births are common following infertility treatments. Three out of five sets of twins and nearly all triplets born following such procedures arrive prematurely. The IOM report called for more research into the causes of preterm births.

An abstract of “Gestational Age, Birthweight, and the Risk of Hyperkinetic Disorder” is posted at<http://adc.bmjjournals.com/cgi/content/abstract/adc.2005.088872v1>.▪