Association of Fetal Growth With General and Specific Mental Health Conditions

Association of Fetal Growth With General and Specific Mental Health Conditions. Erik Pettersson, Henrik Larsson, Brian D’Onofrio, et al. JAMA Psychiatry, doi:10.1001/jamapsychiatry.2018.4342

Key Points

Question  Do the associations between fetal growth and later mental health conditions remain after controlling for familial confounding factors and psychiatric comorbidity?

Findings  This register-based study including more than 1 million participants and using a within-sibling pair design found that higher birth weight (statistically adjusted for gestational age) significantly lowered the risk for attention-deficit/hyperactivity disorder, autism, obsessive-compulsive disorder, and depression. Furthermore, an increase in birth weight by 1 kg significantly decreased a general factor of psychopathology by 0.047 SDs and a specific neurodevelopmental factor by 0.159 SDs.

Meaning  After controlling for familial factors and psychiatric comorbidity, fetal growth was most strongly associated with specific neurodevelopmental disorders.
Abstract

Importance  It is unclear if the associations between fetal growth and later mental health conditions remain after controlling for familial factors and psychiatric comorbidity.

Objective  To examine the associations between fetal growth and general and specific mental health conditions, controlling for familial factors.

Design, Setting, and Participants  This register-based study conducted in Sweden analyzed 546 894 pairs of full siblings born between January 1, 1973, and December 31, 1998. Sibling pairs were followed up through December 31, 2013. First, population-based and within-sibling pair associations (which controlled for time-invariant familial confounders) between fetal growth and the outcomes were estimated. Second, exploratory factor analysis was applied to the outcomes to derive 1 general factor and 4 specific and independent factors. Third, the general and specific factors were regressed on fetal growth. Statistical analysis was performed from March 27, 2017, to October 27, 2018.

Main Outcome and Measures  The outcomes were 11 psychiatric diagnoses (depression, anxiety, obsessive-compulsive disorder, posttraumatic stress disorder, bipolar disorder, alcohol abuse, drug use, attention-deficit/hyperactivity disorder, autism, schizophrenia, and schizoaffective disorder) and court convictions of violent crimes. Birth weight (in kilograms) statistically adjusted for gestational age was the exposure.

Results  The mean (SD) age of the 1 093 788 participants was 27.2 (6.8) years (range, 15.1-40.9 years) and 51.5% were male. Nine outcomes were significantly associated with birth weight in the population at large: depression (odds ratio [OR], 0.96; 95% CI, 0.95-0.98), anxiety (OR, 0.94; 95% CI, 0.92-0.95), posttraumatic 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), attention-deficit/hyperactivity disorder (OR, 0.88; 95% CI, 0.86-0.90), and autism (OR, 0.95; 95% CI, 0.92-0.97). Only depression (OR, 0.95; 95% CI 0.92-0.98), obsessive-compulsive disorder (OR, 0.93; 95% CI, 0.87-0.99), attention-deficit/hyperactivity disorder (OR, 0.86; 95% CI, 0.82-0.89), and autism (OR, 0.72; 95% CI, 0.69-0.76) remained significantly associated within sibling pairs. An exploratory factor analysis indicated that 1 general and 4 specific factors (capturing anxiety, externalizing, neurodevelopmental, and psychotic conditions) fit the outcomes well. Across almost all sensitivity analyses, an increase in birth weight by 1 kg significantly reduced the general (β, −0.047; 95% CI, −0.071 to −0.023) and the specific neurodevelopmental factors (β, −0.159; 95% CI, −0.190 to −0.128) within sibling pairs.

Conclusions and Relevance  Controlling for familial confounders, 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.