Reduced Fetal Growth Increases Risk for Mental Health, Neurodevelopmental Disorders

Reduced fetal growth was associated with a small but significant increase in the general factor of psychopathology and a moderate increase in a specific neurodevelopmental factor, according to the results of a population-based study published in JAMA Psychiatry.

Although reduced fetal growth has been associated with an increased risk for a number of psychiatric diagnoses, the failure to account for genetic or environmental factors has prevented the establishment of causality.

Erik Pettersson, PhD, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, and colleagues conducted a register-based study that analyzed 546,894 Swedish sibling pairs born between January 1, 1973 and December 31, 1998. Birth weight was considered the exposure; the outcomes were court conviction of violent crime and 11 psychiatric diagnoses.

Researchers set out to examine the influence of fetal growth on both general and specific mental health conditions. Of the psychiatric disorders evaluated, only depression (odds ratio [OR], 0.95), obsessive-compulsive disorder (OR, 0.93), attention-deficit/hyperactivity disorder (ADHD) (OR, 0.86), and autism (OR, 0.72) remained significantly associated within sibling pairs. An increase of 1 kg significantly reduced both the general (β, −0.047) and the specific (β, −0.159) neurodevelopmental factors.

Researchers noted that one speculation is that reduced fetal growth impairs brain development during a key period, which then predisposes the individual to neurodevelopmental and psychiatric disorders. The proposed link between reduced fetal growth and ADHD is insufficient oxygen and nutrient supply for the developing fetus. However, no association between restricted fetal growth and psychotic disorders was found in the study.

Researchers argued that these findings suggest that combating maternal malnourishment and improving prenatal care could have a positive effect on fetal growth and reduce the subsequent development of neurodevelopmental and psychiatric disorders.

The study is limited by the challenge of modeling the hazard ratio of multiple outcomes simultaneously; the fact that the registers used by researchers include individuals who have been diagnosed by specialists only, which potentially misses less severe cases of neurodevelopmental and psychiatric disorders; and the failure to control for unmeasured confounders not shared by sibling pairs.

Reference

Pettersson E, Larsson H, D’Onofrio B, Almqvist C, Lichtenstein P. Association of fetal growth with general and specific mental health conditions [published online February 6, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.4342