Developmental, Endocrine, and Ophthalmologic Outcomes in Children Prenatally Diagnosed With Midline Brain Malformations

Abstract

Background: Midline brain malformations (MBMs) are commonly prenatally diagnosed and associated with endocrinologic, ophthalmic, and adverse developmental outcomes.

Methods: A retrospective review was conducted of all neonates identified prenatally with suspected MBMs between 2018 and 2022 at the only multidisciplinary referral center in a multistate region. Abnormalities were categorized as isolated versus complicated absent cavum septum pellucidum (ASP) (N = 11 vs N = 13) or corpus callosum abnormalities (AgCC) (N = 11 vs N = 43) or holoprosencephaly spectrum (N = 12). We assessed subsequent diagnoses and outcomes using a standardized assessment pathway.

Results: Infants with holoprosencephaly were significantly more likely to die than patients with isolated ASP or AgCC (P = 0.02). Surviving infants with holoprosencephaly had universal developmental delay, significantly more than the 10% seen in isolated ASP or AgCC (P = 0.007), and infants with isolated MBMs were significantly more likely to be alive and without endocrine, ophthalmologic, developmental, or epileptic diagnoses at last follow-up than other groups (isolated ASP = 67%, AgCC 82%). The median time to diagnosis of optic nerve hypoplasia was 3 days and initial identification of endocrine concerns was 7 days. There were no significant differences between rates of diagnosis for endocrine, ophthalmologic, or epileptic complications between groups, with all MBMs demonstrating a risk for complications.

Conclusions: Our study shows the importance of multidisciplinary screening in all infants with midline brain defects. Most infants with isolated ASP or AgCC did not have MBM-associated diagnoses at last follow-up, but all groups had comorbidities and would benefit from multispecialty postnatal monitoring.

Keywords: Absence of the corpus callosum; Absent septum pellucidum; Corpus callosum dysplasia; Midline brain defect; Midline brain malformation; Optic nerve hypoplasia; Septo-optic dysplasia.