In a sample of over 500,000 sibling pairs, individuals with lower birth weights were significantly more likely to develop depression, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder (ADHD), and autism, reported Erik Pettersson, PhD, of Karolinska Institutet in Stockholm, Sweden, and colleagues.
Within sibling pairs, a 1-kg increment in birth weight was associated with reduced risk for neurodevelopmental disorders including ADHD and autism (β -0.159, 95% CI -0.190 to -0.128), after controlling for sex, date of birth, and birth order, they wrote in JAMA Psychiatry.
“Because the effect sizes presented herein were small, in line with past research, potential interventions are likely to have a relatively small effect on later psychiatric conditions,” they wrote.
“Nevertheless, given the sheer prevalence of mental health conditions, combating maternal malnourishment and improving prenatal care still might influence a significant number of cases.”
Joel Nigg, PhD, of the Oregon Health and Science University in Portland, Oregon, who was not involved in the study, said low birth weight can subtly impair brain development, which could in turn lead to adverse mental health outcomes.
“It’s helpful evidence that there is a causal relationship with low birth weight and certain disorders including ADHD, autism, and depression,” Nigg told MedPage Today. “That’s consistent with prior studies, but this is more clear.”
Pettersson and colleagues calculated a “general factor” (a measure of overall psychopathology) in order to control for covariance that may occur across mental health disorders.
“In doing the analysis this way, you’re able to isolate out the associations due to this general factor,” Nigg said. “Which is nice because then you can say the association of ADHD or autism is not due to what’s shared with every other disorder.”
This study linked data from several national registers covering all Swedish individuals born from January 1, 1973 to December 31, 1998. Birth weights were adjusted for gestational age and ICD (versions 8 to 10), mental health diagnoses were only included at age 12 years or later, except for autism and ADHD, which were included at 2 years or later.
The oldest sibling pair born within 5 years of each other was selected from each family and followed up until December 31, 2013. In total, 546,894 sibling pairs were included, who were 51.5% male and averaged 27.2 years old.
Researchers grouped these disorders into specific factors, which each contributed to the “general” factor. Neurodevelopmental disorders (ADHD and autism), psychotic disorders (schizophrenia and schizoaffective), anxiety disorders (OCD and anxiety), and an “externalizing factor” (violent crimes, drug use, and alcohol abuse) were all associated with fetal growth, in addition to the general factor, they reported.
Within sibling pairs, each 1-kg increment in birth weight was significantly associated with lower general psychopathology scores (β −0.047, 95% CI −0.071 to −0.023) as well as anxiety (β −0.059, 95% CI −0.114 to −0.004) and neurodevelopmental scores (β −0.159, 95% CI −0.190 to −0.128). However, higher birth weights were not associated with lower scores on the externalizing factor.
Birth weight was associated with increased risk of nine out of the 12 disorders examined:
- Depression: OR 0.96 (95% CI 0.95-0.98)
- Anxiety: OR 0.94 (95% CI 0.92-0.95)
- Post-traumatic stress disorder: OR 0.91 (95% CI 0.89-0.93)
- Bipolar disorder: OR 0.94 (95% CI 0.89-1.00)
- Alcohol abuse: OR 0.89 (95% CI 0.87-0.91)
- Drug use: OR 0.83 (95% CI 0.80-0.85)
- Violent crimes: OR 0.85 (95% CI 0.83-0.86)
- ADHD: OR 0.88 (95% CI 0.86-0.90)
- Autism: OR 0.95 (95% CI 0.92-0.97)
Pettersson and colleagues noted that the registers only included individuals diagnosed by specialists, and therefore the findings may not be generalizable to patients with less severe diagnoses. They also noted that unmeasured confounders could exist within sibling pairs, and that complete genetic matching can only be provided with a sample of identical twins. Lastly, the researchers did not account for the rate of disorder onset as a function of time.
One co-author served as a speaker for Eli Lilly and Shire and received a grant from Shire.
Another co-author served as a speaker for Medice.
Financial support was provided from the Swedish Research Council.
No other disclosures were reported
- Reviewed by
Dori F. Zaleznik, MD Associate Clinical Professor of Medicine (Retired), Harvard Medical School, Boston