Research

Nutrition and Neurodevelopment Activity

Nutrition and Infant Neurodevelopment

Nutrition has profound impact on neurodevelopment, but the mechanisms are only partly understood. In collaboration with other researchers at the Fetal-Neonatal Neuroimaging Developmental Science Center, we are studying the connections between maternal diet, breastmilk contents, infant brain development and child neurodevelopment. We also have a pilot study on the trajectory of infant develop the important skill of oral feeding with the goal of improving diagnosis and personalized care through quantitative EMG assessment of infant feeding, advanced computational analytics, and identifying biomarkers of neonatal outcomes.

Neurodevelopment FreeSurfer

Modifiers of Neurodevelopment among Patients with Congenital Heart Disease

Congenital heart disease (CHD) is the most common severe malformation. As improvements in medical and surgical management have led to increased survival, patients with congenital heart disease face additional lifelong health risks. Neurodevelopmental delay or impairment is the most common extracardiac complication of CHD. To better understand the mechanisms of neurodevelopmental risk in patients with CHD, we have recently participated a clinical trial that collected genetic, clinical, and neuropsychological testing data. Ongoing projects include further analysis of that trial data, and local pilot studies.

Gene Discovery Data

Gene Discovery in Congenital Heart Disease

We study the genetics of congenital heart disease with the goal of improving diagnosis and personalized care through gene discovery, functional analysis of patient variants, and identifying biomarkers of neonatal outcomes. Approaches include computational biology projects, cell culture projects, and multi-omic analysis of patient samples.

Publications

  • Penner, Y., Sabir, S., Quirk, K., Foster, J., Lindamood, K. E., Mello, J., Ortega, J. G., Tate, S., Leeman, K. T., Rudie, C., & Morton, S. U. (2025). Increasing length board use in a neonatal intensive care unit: a quality improvement initiative.. Journal of Perinatology : Official Journal of the California Perinatal Association. https://doi.org/10.1038/s41372-025-02286-1 (Original work published 2025)

    OBJECTIVE: To increase length board use for eligible neonatal intensive care unit (NICU) infants.

    STUDY DESIGN: We implemented a quality improvement study involving 704 infants in our level IV NICU. A multidisciplinary workgroup developed guidelines for length measurement technique and completed Plan-Do-Study-Act cycles. Outcome measure was the weekly proportion of eligible infants who received a length board measurement. Process measures were the weekly proportion of infants with any length measurement or had method documented. Balancing measure was the incidence of unplanned dislodgements of drains, tubes, or catheters.

    RESULTS: After the guideline launch, both process measure proportions increased. Weekly mean percentage of length board increased from 11 to 63%. There were no dislodgement events. Length board measurements were less likely to demonstrate a negative change week-to-week (10% vs 18%, 16/161 vs 59/326, Fisher p = 0.02).

    CONCLUSION: In a level IV NICU, a quality improvement initiative increased the safe use of length boards.

  • Cohen, J. L., Duyzend, M., Adelson, S. M., Yeo, J., Fleming, M., Ganetzky, R., Hale, R., Mitchell, D. M., Morton, S. U., Reimers, R., Roberts, A., Strong, A., Tan, W., Thiagarajah, J. R., Walker, M. A., Green, R. C., & Gold, N. B. (2025). Advancing precision care in pregnancy through a treatable fetal findings list.. American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2025.03.011 (Original work published 2025)

    The use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade. Fetal GS also offers an opportunity to identify incidental genomic variants that are unrelated to the fetal phenotype but may be relevant to fetal and newborn health. There are currently no guidelines for reporting incidental findings from fetal GS. In the United States, GS for adults and children is recommended to include a list of "secondary findings" genes (ACMG SF v.3.2) that are associated with disorders for which surveillance or treatment can reduce morbidity and mortality. The genes on ACMG SF v.3.2 predominantly cause adult-onset disorders. Importantly, many genetic disorders with fetal and infantile onset are treatable as well. A proposed solution is to create a "treatable fetal findings list," which can be offered to pregnant individuals undergoing fetal GS or, eventually, as a standalone cell-free fetal DNA screening test. In this integrative review, we propose criteria for a treatable fetal findings list, then identify genetic disorders with clinically available or emerging fetal interventions and those for which clinical detection and intervention in the first week of life might lead to improved outcomes. Finally, we synthesize the potential benefits, limitations, and risks of a treatable fetal findings list.

  • Mondragon-Estrada, E., & Morton, S. U. (2025). Protocol to analyze deep-learning-predicted functional scores for noncoding de novo variants and their correlation with complex brain traits.. STAR Protocols, 6(2), 103738. https://doi.org/10.1016/j.xpro.2025.103738 (Original work published 2025)

    Functional impact of noncoding variants can be predicted using computational approaches. Although predictive scores can be insightful, implementing the scores for a custom variant set and associating scores with complex traits require multiple phases of analysis. Here, we present a protocol for prioritizing variants by generating deep-learning-predicted functional scores and relating them with brain traits. We describe steps for score prediction, statistical comparison, phenotype correlation, and functional enrichment analysis. This protocol can be generalized to different models and phenotypes. For complete details on the use and execution of this protocol, please refer to Mondragon-Estrada et al.1.

  • Sierant, M. C., Jin, S. C., Bilguvar, K., Morton, S. U., Dong, W., Jiang, W., Lu, Z., Li, B., López-Giráldez, F., Tikhonova, I., Zeng, X., Lu, Q., Choi, J., Zhang, J., Nelson-Williams, C., Knight, J. R., Zhao, H., Cao, J., Mane, S., … Lifton, R. P. (2025). Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes.. Proceedings of the National Academy of Sciences of the United States of America, 122(13), e2420343122. https://doi.org/10.1073/pnas.2420343122 (Original work published 2025)

    Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent-offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to 4 subtypes. Seven genes were only associated with isolated CHD, while 37 were associated with 1 or more extracardiac abnormalities. Genes selectively expressed in the cardiomyocyte lineage were associated with isolated CHD, while those widely expressed in the brain were also associated with neurodevelopmental delay (NDD). Missense variants introducing or removing cysteines in epidermal growth factor (EGF)-like domains of NOTCH1 were enriched in tetralogy of Fallot and conotruncal defects, unlike the broader CHD spectrum seen with loss of function variants. Transmitted damaging missense variants in MYH6 were enriched in multiple CHD phenotypes and account for  1% of all probands. Probands with characteristic mutations causing syndromic CHD were frequently not diagnosed clinically, often due to missing cardinal phenotypes. CHD genes that were positively or negatively associated with development of NDD suggest clinical value of genetic testing. These findings expand the understanding of CHD genetics and support the use of molecular diagnostics in CHD.