Impact of Fetal Growth Restriction on Early Childhood Growth and Development in Very Low Birthweight Infants

Background: Very low birthweight ( <1500 grams; VLBW) and fetal growth restriction ( <10th percentile weight for gestational age; FGR) have each been studied and associated with poor growth and development in early childhood. Few studies address the combined effect of VLBW and FGR on early development, as well as how catch-up growth during early childhood affects these outcomes.

Methods: We conducted a retrospective cohort review of VLBW infants born over a 2-year period at either of our two level 3 NICUs and completing follow-up at 24 months corrected age. Our cohort was divided into FGR and non-FGR subgroups based on birthweight percentile using Fenton Growth Chart. At 24 months, we examined growth parameters (weight, height, BMI, head circumference), catch-up growth (defined as weight attainment >10th percentile on the WHO growth charts 0-2 years at 24 months), and developmental scores using Bayley Scales of Infant Development-III. Chi square and t-test were used for descriptive statistics. 24-month growth and developmental data were analyzed using linear mixed model regression and multiple linear regression respectively.

Results: 224 VLBW infants were evaluated, 41 of which had FGR. At birth, non-FGR infants had significantly lower gestational age (p < 0.01), but groups did not otherwise differ significantly. At 24 months, FGR infants showed significantly lower weight (p < 0.0001), height (p=0.0004), BMI (p < 0.0001), and head circumference (p=0.0002) compared to their non-FGR counterparts (Fig 1). FGR infants showed lower scores in all developmental domains at 24 months (p=0.001 for MDI, p=0.002 for PDI, p=0.001 for language). Catch-up growth was seen in 42% of FGR infants. Within the FGR group, there was no difference in developmental scores at 24 months between those who attained catch-up growth and those who did not attain catch-up growth. However, when compared independently to their non-FGR peers, both FGR subgroups (catch-up growth vs. no catch-up growth) showed significantly lower 24 month developmental scores (catch-up growth group: p=0.01 for MDI, p=0.05 for PDI, p=0.004 for language; no-catch-up growth group: p=0.01 for MDI, p=0.01 for PDI), with the exception of similar language scores between the no-catch-up growth group and non-FGR group (p=0.09) (Fig 2).

Conclusion: The combination of FGR with VLBW had a significant impact on both growth and developmental outcomes at 24 months corrected age, regardless of whether catch-up growth was attained. Catch-up growth on its own, however, had little to no impact on developmental outcomes. Our findings provide new insight into the broad risks associated with this combination of conditions, and highlight the role of good growth during the fetal period as a more useful marker of developmental potential.