Sun Liqun, Lee Fu-Tsuen, Milligan Natasha, Zhu Mengyuan, van Amerom Joshua F P, Saini Brahmdeep S, Lim Jessie Mei, Macgowan Christopher K, Kelly Edmond, Kingdom John C, Seed Mike
Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
JAMA Netw Open. 2025 Jun 2;8(6):e2517360. doi: 10.1001/jamanetworkopen.2025.17360.
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.
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.
Late-onset FGR diagnosed based on a composite scoring system.
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.
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.
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.
胎儿生长受限（FGR）与不良神经发育结局相关。然而，晚发型FGR神经发育后遗症的界定一直受到晚发型FGR诊断方面的挑战以及早产的混杂影响的阻碍。
描述足月暴露于晚发型FGR的婴儿的神经发育结局，并研究FGR与胎儿血流动力学、围产期脑发育和躯体生长之间的关联。
设计、地点和参与者：在这项单中心队列研究中，2010年4月1日至2016年8月31日期间纳入了孕周小于胎龄的孕妇，并随访至婴儿36个月龄。随访于2019年11月完成。数据分析于2024年6月至8月进行。
基于综合评分系统诊断的晚发型FGR。
主要结局是4、8和12月龄时通过艾伯塔婴儿运动量表（AIMS）评估的神经发育结局，以及18和36月龄时通过贝利婴幼儿发展量表第三版评估的神经发育结局。次要结局包括通过磁共振成像结果评估的胎儿血流动力学和围产期脑发育以及连续的躯体生长。
在97例单胎妊娠（平均[标准差]母亲年龄为33.5[3.
