Maternal Diabetes Linked to Higher ADHD Risk in Offspring

Deborah Brauser

January 03, 2012

January 3, 2012 — Maternal gestational diabetes mellitus (GDM) may increase the risk for attention-deficit/hyperactivity disorder (ADHD) in offspring, especially when combined with a low socioeconomic status (SES), new research suggests.

As part of an ongoing cohort study of more than 200 preschool children, investigators found that those with a low SES or those whose mothers had GDM were twice as likely to develop ADHD by the age of 6 years as those who had neither factor; those with both were 14 times more likely to develop ADHD.

In addition, those who experienced both factors showed a lower IQ, poorer language skills, and decreased behavioral and emotional functioning.

"It turned out that this combination really drives the risk for ADHD," lead author Yoko Nomura, PhD, MPH, assistant professor at Queens College, City University of New York in Flushing, and from the Department of Psychiatry at the Mount Sinai School of Medicine in New York City, told Medscape Medical News.

However, she noted that GDM itself might not be the problem.

"It may be that it's something having to do with that, such as an increased glucose level, which makes babies use their energy more for detoxicating from this excessive glucose and maybe less for developing their brains or other critical organs," added Dr. Nomura.

She noted that although the mechanism explaining the association between GDM and low SES with ADHD remains unknown, clinicians from internal medicine, endocrinology, pediatrics, obstetrics, and psychiatry, as well as social workers, should all be made aware of this possible link.

"Since ADHD is a disorder with high heritability, efforts to prevent exposure to environmental risks through patient education may help to reduce the nongenetic modifiable risk for ADHD and other developmental problems," write the investigators.

"Policy makers and clinicians need to get the word out that controlling glucose levels isn't just important for a healthy birth,” said Dr. Nomura. “It can also affect outcomes in offspring across the lifetime."

The study was published online January 2 in the Archives of Pediatric and Adolescent Medicine.

Paucity of Research

GDM, which is defined as glucose intolerance during pregnancy, commonly develops during the second or third trimester, the researchers write. "Approximately 7% of all pregnancies are complicated by GDM — more than 135,000 cases per year."

The researchers add that the prevalence of this disorder has increased over the past 20 years, especially in ethnic minorities and in those with low SES. This is due in part to "lifestyle changes that heighten risk including greater consumption of saturated fats, sugar, and processed foods, and sedentary working environments."

They note that the second and third trimesters are a time of rapid brain development in the fetus. However, neurobehavioral problems caused by GDM "have remained relatively unexplored."

"Gestational diabetes often produces babies that are humongous, really big because of their increased glucose,” Dr. Nomura notes. “Being too big is not good and can cause a lot of problems, so preventing this is important," she said, adding that low SES has also been shown to cause detrimental effects.

"Poverty can increase other problems. But if you have money, you are able to get good medical care and better food."

For this study, the researchers examined 212 preschool children (73.6% boys, 59% white, 12.3% black, 10.4% Asian, 18.4% mixed/other) from New York who were aged 3 or 4 years at baseline (mean age, 4.31 years). The participants were followed to the age of 6 years.

In-person interviews were conducted with mothers to obtain history of GDM, and the Socioeconomic Prestige Index was used to measure family SES. A mean score of 55.4 differentiated low from high SES.

At baseline, both parents and teachers filled out the ADHD Rating Scale–IV to report ADHD symptoms. To determine ADHD diagnosis, the children were interviewed each year of the study using the Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime Version.

In addition, the Developmental Neuropsychological Assessment was used to measure attention/executive functioning, language memory, fine motor coordination, and visuospatial processing; the Wechsler Preschool and Primary Scale of Intelligence was used to measure IQ; and the Temperament Assessment Battery for Children Revised was used to measure temperament.

Primary measurement outcomes included ADHD diagnosis, ADHD symptoms, temperament, cognitive functioning, and neurobehavioral measures. Secondary outcomes included behavioral and emotional functioning problems, as measured with the Behavior Assessment System for Children Parent and Teacher Rating Scale.

Significantly Increased Risk

Results showed that 10% of the participants' mothers had GDM during pregnancy but not low SES, and 44.5% had low SES but not maternal GDM. A total of 9 children had both low SES and maternal GDM.

There was a 2-fold higher risk for ADHD at the age of 6 years for the children exposed to GDM than for those who were unexposed (odds ratio [OR], 2.20; 95% confidence interval [CI], 1.00 - 4.82; P = .05)

There was also a 2-fold higher risk for ADHD at age 6 years for those children from low SES families (OR, 2.41; 95% CI, 1.53 - 3.79; P < .001) and an almost 2-fold higher risk for ADHD at baseline (OR, 1.87; 95% CI, 1.21 - 2.89; P = .005) compared with children from high SES families.

The risk by GDM for ADHD was also 7 times greater for the participants from low SES homes (OR, 7.0; 95% CI, 1.58 - 31.48; P = .004).

The children with mothers who had GDM during pregnancy also had significantly higher mean inattention scores at baseline than did those whose mothers did not have GDM (P = .05), but there were no significant between-group differences in hyperactivity/impulsivity scores at baseline.

The children from low SES families had significantly higher inattention scores and higher hyperactivity/impulsivity scores at baseline than those from high SES families (both, P = .01).

At baseline, those who experienced both GDM and low SES showed significantly lower neuropsychological and cognitive functioning, as evidenced in verbal, visuospatial, and full-scale IQ scores, than did any of the other groups. These children also had significantly worse temperament behaviors, including greater lack of inhibition, greater activity level, and greater lack of persistence.

At the age of 6 years, the group with both GDM and low SES also "consistently had the highest problem scores," the researchers write, including issues with functional communication, withdrawal, and attention.

Finally, a "test of additive interaction found that the risk for ADHD increased over 14-fold (P = .006)" for children at the age of 6 years when they had been exposed to both GDM and low SES compared with those who had been exposed to neither factor.

"Long-term prevention efforts should be directed at mothers with GDM to avoid suboptimal neurobehavioral development and mitigate the risk for ADHD among their offspring," write the investigators.

A "Stepping-Stone"

Joel Nigg, PhD, from Oregon Health and Science University in Portland, writes in an accompanying editorial that this study shows "additional evidence, in a retrospective design, that early developmental events are related to subsequent [ADHD] in children."

"Most of the relevant environmental risks are presumed to occur very early in development," adds Dr. Nigg. "If causal, and if able to be understood pathophysiologically, such environmental effects on ADHD are of 'game-changing' importance because they open the door to eventually preventing that portion of cases of ADHD caused by early insult to the nervous system."

He notes that if the biological mechanisms of an environmental influence can be eventually understood, "a powerful model will be created for how ADHD can develop."

"That discovery will be a crucial stepping-stone toward parsing multiple causal routes to what may be a final common pathway of the ADHD phenotype," concludes Dr. Nigg.

The study was supported by grants from the National Institute of Mental Health and the US Department of Health and Human Services. The study authors and Dr. Nigg have disclosed no relevant financial relationships.

Arch Pediatr Adolesc. Published online January 2, 2012. Abstract, Editorial


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