Although individuals born at extremely low birth weight (ELBW; ≤1000 g) are known to be at greater risk for mental health problems than individuals born at normal birth weight (NBW; ≥2500 g), contributions of postnatal growth to these relations have not been fully explored. We compared individual differences in the Ponderal Index [(PI; weight(kg)/height(m3)] and head circumference (HC) in predicting internalizing and externalizing behaviors in childhood and adolescence in a cohort of ELBW survivors (N = 137) prospectively followed since birth. Baseline models indicated that infants who were born thinner or with smaller HC showed greater PI or HC growth in the first 3 years. Latent difference score (LDS) models showed that compensatory HC growth in the first year (ΔHC = 20.72 cm), controlled for birth HC, predicted ADHD behaviors in adolescence in those born with smaller HC. LDS models also indicated that the PI increased within the first year (ΔPI = 1.568) but decreased overall between birth and age 3 years (net ΔPI = −4.597). Modeling further showed that larger increases in the PI in the first year and smaller net decreases over 3 years predicted more internalizing behaviors in adolescence. These findings suggest early growth patterns prioritizing weight over height may have negative effects on later mental health in ELBW survivors, consistent with developmental programming theories.

Effects of stresses associated with extremely preterm birth may be biologically “recorded” in the genomes of individuals born preterm via changes in DNA methylation (DNAm) patterns. Genome-wide DNAm profiles were examined in buccal epithelial cells from 45 adults born at extremely low birth weight (ELBW; ≤1000 g) in the oldest known cohort of prospectively followed ELBW survivors (Mage = 32.35 years, 17 male), and 47 normal birth weight (NBW; ≥2500 g) control adults (Mage = 32.43 years, 20 male). Sex differences in DNAm profiles were found in both birth weight groups, but they were greatly enhanced in the ELBW group (77,895 loci) versus the NBW group (3,424 loci), suggesting synergistic effects of extreme prenatal adversity and sex on adult DNAm profiles. In men, DNAm profiles differed by birth weight group at 1,354 loci on 694 unique genes. Only two loci on two genes distinguished between ELBW and NBW women. Gene ontology (GO) and network analyses indicated that loci differentiating between ELBW and NBW men were abundant in genes within biological pathways related to neuronal development, synaptic transportation, metabolic regulation, and cellular regulation. Findings suggest increased sensitivity of males to long-term epigenetic effects of extremely preterm birth. Group differences are discussed in relation to particular gene functions.