Wilson Siân, Yun Hyuk Jin, Sadhwani Anjali, Feldman Henry A, Jeong Seungyoon, Hart Nicholas, Pujols Kaysi Herrera, Newburger Jane W, Grant P Ellen, Rollins Caitlin K, Im Kiho
Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Boston, MA, 02115, USA; Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Boston, MA, 02115, USA; Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
EBioMedicine. 2025 Apr;114:105679. doi: 10.1016/j.ebiom.2025.105679. Epub 2025 Mar 29.
In adolescents and adults with complex congenital heart disease (CHD), abnormal cortical folding is a putative predictor of poor neurodevelopmental outcome. However, it is unknown when this relationship first emerges. We test the hypothesis that it begins in utero, when the brain starts to gyrify and folding patterns first become established.
We carried out a prospective, longitudinal case-control study, acquiring foetal MRIs at two timepoints in utero, (Scan 1 = 20-30 Gestational Weeks (GW) and Scan 2 = 30-39 GW), then followed up participants at two years of age to assess neurodevelopmental outcomes. We used normative modelling to chart growth trajectories of surface features across 60 cortical regions in a control population (n = 157), then quantified the deviance of each foetus with CHD (n = 135) and explored the association with neurodevelopmental outcomes at two years of age.
Differences in cortical development between CHD and Control foetuses only emerged after 30 GW, and lower regional cortical surface area growth was correlated with poorer neurodevelopmental outcomes at two years of age in the CHD group.
This work highlights the third trimester specifically as a critical period in brain development for foetuses with CHD, where the reduced surface area expansion in specific cortical regions becomes consequential in later life, and predictive of neurodevelopmental outcome in toddlerhood.
This research was supported by the NINDS (R01NS114087, K23NS101120) and NIBIB (R01EB031170) of the NIH, PHN Scholar Award, AAN Clinical Research Training Fellowship, BBRF Young Investigator Awards, and the Farb Family Fund.
在患有复杂先天性心脏病（CHD）的青少年和成年人中，皮质折叠异常被认为是神经发育不良结局的一个预测指标。然而，这种关系何时首次出现尚不清楚。我们检验了这样一个假设，即这种关系始于子宫内，此时大脑开始形成脑回，折叠模式首次确立。
我们开展了一项前瞻性纵向病例对照研究，在子宫内的两个时间点获取胎儿磁共振成像（MRI）（扫描1 =妊娠20 - 30周（GW），扫描2 =妊娠30 - 39周），然后在参与者两岁时进行随访以评估神经发育结局。我们使用规范建模来绘制对照组（n = 157）中60个皮质区域表面特征的生长轨迹，然后量化每个患有CHD的胎儿（n = 135）的偏差，并探讨其与两岁时神经发育结局的关联。
CHD胎儿与对照胎儿之间的皮质发育差异仅在30周后出现，并且CHD组中较低的区域皮质表面积增长与两岁时较差的神经发育结局相关。
这项研究特别强调了妊娠晚期是患有CHD胎儿大脑发育的关键时期，在此期间特定皮质区域表面积扩张减少在以后的生活中会产生影响，并可预测幼儿期的神经发育结局。
本研究由美国国立卫生研究院（NIH）的国立神经疾病和中风研究所（NINDS）（R01NS114087，K23NS101120）、国立生物医学成像和生物工程研究所（NIBIB）（R01EB031170）、PHN学者奖、美国神经病学学会临床研究培训奖学金、BBRF青年研究者奖以及法布家族基金资助。
