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. 2025 Jun 2;8(6):e2517360.
doi: 10.1001/jamanetworkopen.2025.17360.

Neurodevelopment Among Infants With Late-Onset Fetal Growth Restriction

Liqun Sun  1   2   3 , Fu-Tsuen Lee  3   4   5 , Natasha Milligan  3   4 , Mengyuan Zhu  3   4 , Joshua F P van Amerom  3   4 , Brahmdeep S Saini  3   4 , Jessie Mei Lim  3   4 , Christopher K Macgowan  4   6 , Edmond Kelly  7 , John C Kingdom  8 , Mike Seed  3   4   5   9
Affiliations

Neurodevelopment Among Infants With Late-Onset Fetal Growth Restriction

Liqun Sun et al. JAMA Netw Open. .

Abstract

Importance: Fetal growth restriction (FGR) is associated with adverse neurodevelopmental outcomes. However, the delineation of neurodevelopmental sequela in late-onset FGR has been hampered by challenges in diagnosing late-onset FGR and the confounding influence of prematurity.

Objective: To characterize neurodevelopmental outcomes in full-term infants exposed to late-onset FGR and to examine the association of FGR with fetal hemodynamics, perinatal brain development, and somatic growth.

Design, setting, and participants: In this single-center cohort study, pregnant persons with fetuses small for gestational age were enrolled between April 1, 2010, and August 31, 2016, and followed up until the infant was 36 months of age. Follow-up was completed November 2019. Data analysis was performed from June to August 2024.

Exposures: Late-onset FGR diagnosed based on a composite scoring system.

Main outcomes and measures: The primary outcomes were neurodevelopmental outcomes at 4, 8, and 12 months of age assessed by the Alberta Infant Motor Scale (AIMS) and at 18 and 36 months of age assessed by the Bayley Scales of Infant and Toddler Development, Third Edition. Secondary outcomes included fetal hemodynamics and perinatal brain development assessed by magnetic resonance imaging findings and serial somatic growth.

Results: Among 97 singleton pregnancies (mean [SD] maternal age, 33.5 [3.8] years; 50 [52%] male neonates), 41 neonates (42%) were exposed to late-onset FGR. At 12-month follow-up, motor development was significantly delayed among full-term infants exposed to late-onset FGR compared with neonates appropriate for gestational age (AIMS mean difference, -4.5; 95% CI, -8.6 to -0.3). At all other time points, neurodevelopmental outcomes were similar between the groups. In models adjusted for covariates, gestational age at birth was associated with 18-month cognitive outcomes (coefficient, 4.13 [95% CI, 0.54-7.72]), while the diagnosis of late-onset FGR was not. Preterm infants exposed to FGR exhibited higher fetal combined ventricular output, higher ratio of cerebral to pulmonary blood flow, and lower oxygen saturation compared with full-term infants exposed to FGR and infants with no FGR exposure. In general, neonatal brain maturation and somatic growth by 12 months of age were similar between full-term infants exposed to FGR and those with no exposure. However, head circumference was smaller from birth until the 36-month follow-up in infants exposed to FGR.

Conclusions: In this cohort study, full-term infants exposed to late-onset FGR exhibited normal neurodevelopmental outcomes by 18 and 36 months of age, and longer gestation was associated with improved outcomes. These findings suggest that early delivery is unlikely to offer neurodevelopmental benefit, and any adverse impact on neurodevelopmental outcomes of late-onset FGR among full-term infants is likely to be modest.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Macgowan reported receiving grant support from the Canadian Institutes for Health Research and the National Science and Engineering Research Council of Canada during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
Among participants born appropriate for gestational age (AGA), 56 were invited for follow-up. Loss to follow-up was due to participant decline. Among participants exposed to fetal growth restriction (FGR), those with term FGR were invited for neurodevelopmental follow-up. Of the 25 participants in the term FGR group, loss to follow-up was due to participant decline. AIMS indicates Alberta Infant Motor Scale; BSID-III, Bayley Scales of Infant and Toddler Development, Third Edition.
Figure 2.
Figure 2.. Somatic Growth Trajectories of Full-Term Infants With and Without Late-Onset Fetal Growth Restriction (FGR)
Each z score at each time point is represented as mean (95% CI).
See this image and copyright information in PMC

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