In the Journals

Lower birth weight may increase risk for neurodevelopmental disorders

After controlling for family-related confounders, lower birth weight was associated with an increased risk for several psychiatric disorders, including ADHD, autism, obsessive-compulsive disorder and depression, researchers found.

Reduced fetal growth is associated with an increased level of mental health conditions,” Erik Pettersson, PhD, from the department of medical epidemiology and biostatistics, Karolinska Institutet, Sweden, and colleagues wrote in JAMA Psychiatry. “Two concerns, however, cloud causal interpretations. First, unmeasured genetic or environmental variables might confound the associations. An additional problem is the high degree of overlap among psychiatric disorders.”

In this register-based study, Pettersson and colleagues investigated the influence of fetal growth on the risk for general and specific mental health conditions, controlling for familial confounders, across adulthood in a large population-based sample of more than 500,000 sibling pairs from Sweden.

First, the researchers estimated population-based and within-sibling pair associations between fetal growth and the outcomes. Then they conducted exploratory factor analysis to derive one general factor and four specific and independent factors. After, they regressed the general and specific factors on fetal growth. Outcomes were 11 psychiatric diagnoses and violent crime convictions and the exposure was participants’ birth weight — in kilograms — adjusted for gestational age.

Analysis revealed that reduced birth weight significantly increased the risk for:

  • depression (OR = 0.96; 95% CI, 0.95-0.98);
  • anxiety (OR = 0.94; 95% CI, 0.92-0.95);
  • PTSD (OR = 0.91; 95% CI, 0.89-0.93);
  • bipolar disorder (OR = 0.94; 95% CI, 0.89-1);
  • alcohol abuse (OR = 0.89; 95% CI, 0.87-0.91);
  • drug use (OR = 0.83; 95% CI, 0.8-0.85);
  • violent crimes (OR = 0.85; 95% CI, 0.83-0.86);
  • ADHD (OR = 0.88; 95% CI, 0.86-0.9); and
  • autism (OR = 0.95; 95% CI, 0.92-0.97).

However, only depression (OR = 0.95; 95% CI 0.92-0.98), OCD (OR = 0.93; 95% CI, 0.87-0.99), ADHD (OR = 0.86; 95% CI, 0.82-0.89) and autism (OR = 0.72; 95% CI, 0.69-0.76) remained significantly linked to lower fetal growth within sibling pairs.

Further exploratory factor analysis demonstrated that one general and four specific factors — anxiety, externalizing, neurodevelopmental and psychotic — fit the outcomes well. Lower fetal growth had the strongest association with the specific neurodevelopmental factor, according to the results.

Most sensitivity analyses indicated that an increase in birth weight by 1 kg significantly lowered the general (beta = –0.047; 95% CI, –0.071 to –0.023) and specific neurodevelopmental factors (beta = –0.159; 95% CI, –0.190 to –0.128) within sibling pairs.

“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,” Pettersson and colleagues 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.” – by Savannah Demko

Disclosure: Pettersson reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

After controlling for family-related confounders, lower birth weight was associated with an increased risk for several psychiatric disorders, including ADHD, autism, obsessive-compulsive disorder and depression, researchers found.

Reduced fetal growth is associated with an increased level of mental health conditions,” Erik Pettersson, PhD, from the department of medical epidemiology and biostatistics, Karolinska Institutet, Sweden, and colleagues wrote in JAMA Psychiatry. “Two concerns, however, cloud causal interpretations. First, unmeasured genetic or environmental variables might confound the associations. An additional problem is the high degree of overlap among psychiatric disorders.”

In this register-based study, Pettersson and colleagues investigated the influence of fetal growth on the risk for general and specific mental health conditions, controlling for familial confounders, across adulthood in a large population-based sample of more than 500,000 sibling pairs from Sweden.

First, the researchers estimated population-based and within-sibling pair associations between fetal growth and the outcomes. Then they conducted exploratory factor analysis to derive one general factor and four specific and independent factors. After, they regressed the general and specific factors on fetal growth. Outcomes were 11 psychiatric diagnoses and violent crime convictions and the exposure was participants’ birth weight — in kilograms — adjusted for gestational age.

Analysis revealed that reduced birth weight significantly increased the risk for:

  • depression (OR = 0.96; 95% CI, 0.95-0.98);
  • anxiety (OR = 0.94; 95% CI, 0.92-0.95);
  • PTSD (OR = 0.91; 95% CI, 0.89-0.93);
  • bipolar disorder (OR = 0.94; 95% CI, 0.89-1);
  • alcohol abuse (OR = 0.89; 95% CI, 0.87-0.91);
  • drug use (OR = 0.83; 95% CI, 0.8-0.85);
  • violent crimes (OR = 0.85; 95% CI, 0.83-0.86);
  • ADHD (OR = 0.88; 95% CI, 0.86-0.9); and
  • autism (OR = 0.95; 95% CI, 0.92-0.97).

However, only depression (OR = 0.95; 95% CI 0.92-0.98), OCD (OR = 0.93; 95% CI, 0.87-0.99), ADHD (OR = 0.86; 95% CI, 0.82-0.89) and autism (OR = 0.72; 95% CI, 0.69-0.76) remained significantly linked to lower fetal growth within sibling pairs.

Further exploratory factor analysis demonstrated that one general and four specific factors — anxiety, externalizing, neurodevelopmental and psychotic — fit the outcomes well. Lower fetal growth had the strongest association with the specific neurodevelopmental factor, according to the results.

Most sensitivity analyses indicated that an increase in birth weight by 1 kg significantly lowered the general (beta = –0.047; 95% CI, –0.071 to –0.023) and specific neurodevelopmental factors (beta = –0.159; 95% CI, –0.190 to –0.128) within sibling pairs.

“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,” Pettersson and colleagues 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.” – by Savannah Demko

Disclosure: Pettersson reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.