Extremely Preterm Births Linked to Increase Risk of Psychiatric Disorders

Jean A. Frazier, MD

Preterm birth and family history result in an increased risk of developing a psychiatric disorder by age 15, with many also suffering from 2 or 3 disorders, mainly anxiety, attention deficit/hyperactivity disorder (ADHD), and major depression.

A team, led by Jean A. Frazier, MD, Eunice Kennedy Shriver Center at the University of Massachusetts Medical School, evaluated the prevalence, co-occurrence, sex differences, and functional correlates of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) psychiatric disorders in 15-year-old adolescents born extremely preterm.

The Trial

In the Extremely Low Gestational Age Newborns (ELGAN) trial, the investigators examined children born at less than 28 weeks gestation at age 15. The team identified 670 children who completed the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), the Youth Self Report, a disability scale of participation in social roles and cognitive testing.

The investigators also had parents complete a family psychiatric history questionnaire.

Overall, anxiety, ADHD, and major depression emerged as the most prevalent psychiatric disorders. The results also show females met the criteria for anxiety than males.

The Link to Psychiatric Disorders

However, 66% of participants did not meet the criteria for a psychiatric disorder, while 15% met the criteria for 1, 9% met the criteria for 2, and 8% met the criteria for at least 3 psychiatric disorders.

The participants with at least 2 psychiatric disorders were more likely to have repeated a grade in school, as well as have an individualized educational program (IEP) and have a lower Non-Verbal IQ than the participants with no psychiatric disorders.

In addition, individuals with any psychiatric disorder were more likely to use psychotropic medications, have greater cognitive and functional impairment, and have mothers were single, on public health insurance, and have less than a high school education.

Using the parent questionnaires, the investigators learned a positive family history of psychiatric disorders more frequently occurred in adolescents with at least 3 psychiatric disorders.

“Among adolescents born extremely preterm anxiety, major depression and ADHD were the most prevalent psychiatric disorders at age 15,” the authors wrote. “Adolescents with > 1 psychiatric disorder were at increased risk for multiple functional and participatory challenges.”

Forecasting Psychiatric Disorders

For some psychiatric disorders, genetic copy number variations (CNV) can help predict risk, while for others are more narrow forecasts.

Recently, a team, led by Xabier Calle Sanchez, MS, Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, produced an unbiased, population-based estimate of the prevalence, disease risks and trajectories, fertility, and mortality of genetic copy number variants implicated in neuropsychiatric disorders.

Overall, copy number variants were broadly associated with an increased risk for ASD and ADHD. However, risk estimates for schizophrenia for most genetic copy number variants were lower than what was previously reported.

For the 1q21.1 deletion, there was a significant risk found for MDD (HR, 5.8; 95% CI, 1.5-22.2) and sex-specific risk of bipolar disorder (HR, 17; 95% CI, 1.5-189.3 for men only).

While both 1q21.1 and 15q13.3 were linked to increased risks for most of the diagnoses, the 17p12 deletion consistently resulted in less of a risk for psychiatric disorders (HR, 0.4-0.8). However, none of the estimates differed significantly from the general population.

After conducting a trajectory analysis, the investigators found while diagnostic risk profiles differed across loci, they were similar for deletions and duplications within each locus and sex-stratified analyses suggest pathogenicity of many genetic copy number variants could be modulated by sex.

The study, “Psychiatric Outcomes, Functioning, and Participation in Extremely Low Gestational Age Newborns at Age 15 Years,” was published online in the Journal of the American Academy of Child & Adolescent Psychiatry.