Impaired Maternal‐Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease

Background Infants with congenital heart disease (CHD) are at risk for white matter injury (WMI) before neonatal heart surgery. Better knowledge of the causes of preoperative WMI may provide insights into interventions that improve neurodevelopmental outcomes in these patients. Methods and Results A prospective single‐center study of preoperative WMI in neonates with CHD recorded data on primary cardiac diagnosis, maternal‐fetal environment (MFE), delivery type, subject anthropometrics, and preoperative care. Total maturation score and WMI were assessed, and stepwise logistic regression modeling selected risk factors for WMI. Among subjects with severe CHD (n=183) who received a preoperative brain magnetic resonance imaging, WMI occurred in 40 (21.9%) patients. WMI prevalence (21.4%–22.1%) and mean volumes (119.7–160.4 mm3) were similar across CHD diagnoses. Stepwise logistic regression selected impaired MFE (odds ratio [OR], 2.85 [95% CI, 1.29–6.30]), male sex (OR, 2.27 [95% CI, 1.03–5.36]), and older age at surgery/magnetic resonance imaging (OR, 1.20 per day [95% CI, 1.03–1.41]) as risk factors for preoperative WMI and higher total maturation score values (OR, 0.65 per unit increase [95% CI, 0.43–0.95]) as protective. A quarter (24.6%; n=45) of subjects had ≥1 components of impaired MFE (gestational diabetes [n=12; 6.6%], gestational hypertension [n=11; 6.0%], preeclampsia [n=2; 1.1%], tobacco use [n=9; 4.9%], hypothyroidism [n=6; 3.3%], and other [n=16; 8.7%]). In a subset of 138 subjects, an exploratory analysis of additional MFE‐related factors disclosed other potential risk factors for WMI. Conclusions This study is the first to identify impaired MFE as an important risk factor for preoperative WMI. Vulnerability to preoperative WMI was shared across CHD diagnoses.