Does low birth weight share common genetic or environmental risk with childhood disruptive disorders?

Abstract

Although advances in neonatal care over the past century have resulted in increased rates of survival among at-risk births, including infants with low birth weight, we have much to learn about the psychological outcomes in this population. In particular, although it appears that there is growing evidence that low birth weight may be associated with an increased risk for Attention-Deficit/Hyperactive Disorder (ADHD) symptoms in childhood, few studies have examined birth weight as a risk factor for disruptive disorders that commonly co-occur with ADHD [e.g. Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD)]. In addition, the etiology of the relation between birth weight and these disorders is unknown. The current investigation aimed to better understand the putative role of birth weight in disruptive behavior disorders in the context of potentially confounding genetic and environmental influences by examining phenotypic associations between birth weight and disruptive disorder symptoms across families (using generalized linear models with generalized estimating equations) as well as within families (using linear regression) in two independent twin samples (Sample 1: N = 1676 individuals; Sample 2: N = 4038 individuals). We found negative associations between birth weight and several childhood disruptive disorder symptom dimensions, including inattentive, hyperactive-impulsive, and broad externalizing symptoms in both samples. Nonetheless, the overall magnitude of these associations was very small, contributing to less than 1% of the variance in these symptom dimensions. Within-family associations between birth weight and disruptive disorder symptoms did not differ for monozygotic and dizygotic twin pairs, suggesting that nonshared environmental influences rather than common genetic influences are responsible for these associations. These consistent albeit weak associations between birth weight and disruptive disorder symptoms suggest that, at least in the general population, low birth weight does not represent a major risk factor in the development of these symptoms.

Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison

“…Though some previous research has reported null findings (1, 5, 18), the current results build on previous co-twin control (2, 4, 10–12) and epidemiological study findings (3). The associations between birth weight and psychotic or bipolar disorder were also independent of shared familial confounds and statistical covariates, although the magnitudes of association were attenuated in fixed effects models.…”

“…In addition, it was not possible to classify ADHD cases according to subtype (i.e., combined, primarily hyperactive-impulsive and primarily inattentive type), since these were not recorded across the registers using the ICD. Offspring had to have been at least 12 years old to receive any of the following disorders: (3) psychotic or bipolar disorder was defined as first inpatient hospitalization for schizophrenia, bipolar disorder, or another non-organic psychotic disorder according to ICD-8, -9, and -10 criteria (29); (4) substance use problem was defined as first inpatient hospitalization for a primary or secondary diagnosis of alcohol or any other non-nicotine substance use disorder (30); (5) age at suicide attempt was gathered using inpatient hospitalization for a primary or secondary diagnosis (31); and (6) criminality was indicated by the first occurrence of any criminal conviction from age 15 years, the age of legal responsibility in Sweden (32). We chose not to examine broadly defined affective disorder because inpatient hospitalization for that diagnosis may indicate the presence of co-occurring suicidality or psychosis, and we had access to validated indicators of these associated possible outcomes (29, 31).…”

Concordance between maternal recall of birth complications and data from obstetrical records

“…The recommendation based on the present data would be to model continuous rather than dichotomous measures in testing hypotheses regarding the association between perinatal events and offspring development. In fact, comparing the effect sizes for continuous birthweight and low birthweight (i.e., < 2500 grams) on inattention and behavior problems in the Tennessee Twin Study resulted in the authors concluding that the continuous term for birthweight was a stronger predictor than the categorical variable [12]. …”

“…Yet, studies that utilize this methodology have reported inconsistent findings. While some studies have reported no associations between maternal report of birth complications, and low birthweight and offspring neurodevelopmental problems [10,11], others have shown that maternal recall of birth events predicts youth behavior problems [12,13,14]. For example, in two child epidemiologic studies, maternal recall of birthweight was unrelated to offspring behavior problems [15,16].…”

Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity

“…This allows for the possibility that birth weight and ADHD share a common genetic liability. Twin studies, however, demonstrate that prenatal environmental factors, rather than shared genetic factors, largely account for the relationship between birth weight and ADHD symptoms [Lehn et al, 2007;Groen-Blokhuis et al, 2011;Ficks et al, 2013;Sharp et al, 2003] or externalizing behavior [van Os et al, 2001;Wichers et al, 2002]. This suggests that environmental determinants of lower birth weight contribute to the development of ADHD.…”