On the Spectrum

A Prospective Study of Fetal Head Growth in Children, Autistic Traits and Autism Spectrum Disorder
Prenatal head growth and autistic traits
We examined whether fetal HC growth trajectories were related to later autistic traits (Table
2A). This was addressed in a separate model for each of the cohorts, in which autistic trait
scores were regressed on the latent growth parameters of gestational-age-adjusted SD
scores of HC. Models were adjusted for sex, ethnicity of the child, maternal educational
level, maternal age, maternal alcohol use and maternal smoking during pregnancy. These
models had good fit indices: comparative fit index = 0.987 and root mean square error of
approximation = 0.021 for the Generation R Study and comparative fit index = 0.966 and root
mean square error of approximation = 0.029 for the Raine Study. We found evidence for a
consistent negative association of the slope of growth (i.e., growth rate) with autistic traits
when the results for both cohorts were pooled (pooled z = -2.20, p = .03).
For the Generation R Study, in the fully adjusted model, the intercept and slope of HC
growth during pregnancy were negatively associated with autistic traits: children with growth
trajectories characterized by a lower slope and intercept had more autistic traits at age 6 (β
slope= -0.043, p = .04, β intercept= -0.049, p = .03). For the Raine Study, we found the same
direction of effect for the association of the slope of growth with autistic traits, although not
statistically significant (β slope= -0.075, p = .41). Since postnatal studies of children with ASD
have found both larger and smaller HC, we tested whether the relation between growth and
autistic traits was nonlinear. For both studies, the addition of quadratic terms of the growth
parameters did not add significantly to the models. In a sensitivity analysis, we assessed
whether this effect was specific to HC by examining trajectories of HC-FL difference scores.
Results were broadly consistent (pooled z = -2.11, p = .04).
In separate cross-sectional analyses for each cohort, HC in mid- and late pregnancy, but
not early pregnancy, were related to autistic traits (Table 2B). Pooled results indicate that
children with smaller HC in mid- and late pregnancy had higher levels of autistic traits later
in life (mid pregnancy: pooled z = -2.19, p = .03, late pregnancy pooled z = -2.11, p =.04).
When examining difference scores, results were consistent (pooled z = -2.79, p