722 - Neurodevelopment in Small-for-Gestational-Age Preterm Infants: Distinguishing the Impact of Birthweight and Gestational Age in a Cohort Study

Publication Number: 2704.722

Maria G. Alda, Mercy Hospital for Women, Caulfield East, Victoria, Australia; Teresa M. MacDonald, University of Melbourne/Mercy Hospital for Women, Melbourne, Victoria, Australia; Julia K. Charlton, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Amanda Wood, Deakin University, Parkville, Victoria, Australia

Background: Preterm birth increases the risk of developmental delay, particularly among small for gestational age (SGA) infants. Evidence is inconsistent, and few studies assess outcomes within the first year, a critical window for early intervention. Fetal growth restriction (FGR), often due to placental insufficiency, alters brain development despite apparent "brain sparing." Gestational age (GA) and birthweight (BW) are distinct but complementary risk factors, with GA linked to motor and BW to cognitive outcomes.

Objective: To assess neurodevelopmental outcomes at 3-, 6-, and 12-month corrected age in preterm SGA versus appropriate for gestational age (AGA) infants, and to determine whether differences are explained by BW or GA.

Design/Methods: As part of the CONFIGR project, preterm infants (24-36+6 weeks GA) born at Mercy Hospital for Women, Melbourne (Apr 2023-Feb 2024), were prospectively enrolled. SGA ( < 10th centile) and AGA (10th-90th centile) were defined using GROW charts. Neurodevelopment was assessed using ASQ-3 (3 and 6 months), and Bayley™-4 A&NZ and PEDI (12 months). The primary outcome was Bayley-4 Cognitive score at 12 months. Analyses included t-tests, χ² tests, and regression models adjusted for sex and socioeconomic status. Mediation analyses assessed whether GA or BW explained associations with outcomes.

Results: Of 150 enrolled infants, 143 (50 SGA, 93 AGA) had follow-up data. Completion rates were 91% (3 months), 82% (6 months), and 80% (12 months). Maternal characteristics were similar. SGA infants had higher rates of FGR, pre-eclampsia, and lower BW (1327g vs 1889g, p< 0.01). ASQ-3 scores were comparable at 3 and 6 months. At 12 months, Bayley-4 cognitive, language, and motor scores did not differ by group (Table 1), though both scored below the normative mean. Moderate-to-severe delays were more common in SGA infants (~5% vs 0-1%). PEDI scores showed similar mobility and social function. SGA infants had slightly higher self-care (p=0.04). Regression models found GA and BW-but not SGA status-independently predicted cognitive and motor scores (Figure 1). Mediation analysis showed BW, not GA, explained the effect of SGA on outcomes (Figure 2).

Conclusion(s): At 12 months' corrected age, preterm SGA and AGA infants had similar, mildly delayed development. GA and BW independently influenced outcomes, but BW best explained SGA-related risk. Findings highlight the need for close follow-up of infants with significant growth restriction.

Table 1: Bayley-4 assessment 12 months


Figure 1. Associations between gestational age, birthweight, and neurodevelopmental outcomes
Cognitive and Motor standard scores at 12 months corrected age are plotted against adjusted gestational age (left panels) and adjusted birthweight (right panels). Lines represent fitted values for SGA and AGA groups with 95% confidence intervals.

Figure 2. Mediation of the association between SGA and 12-month
Causal mediation models showing indirect effects of birthweight and gestational age on cognitive (A), language (B), and motor (C) outcomes. Arrows indicate indirect pathways with β coefficients (Bayley-4 points) and exact p-values. Birthweight significantly mediated cognition and motor outcomes (p = 0.012), with weaker evidence for language (p = 0.086); gestational age showed no mediation.