# The eXtraordinarY Babies Study: Natural History of Health and Neurodevelopment in Infants and Young Children with Sex Chromosome Trisomy

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $529,675

## Abstract

PROJECT SUMMARY 
 
Background: Sex Chromosome Trisomies (SCT) including Klinefelter (XXY), Trisomy X (XXX), and XYY syndromes occur in 1 out 
of every 500 births and are associated with a broad phenotypic spectrum including increased risk for developmental delays 
(DD), language/learning disorders, and autism spectrum disorder (ASD). XXY is also associated with testicular failure, XXX 
increases risk for ovarian failure, and disorders of insulin resistance and other medical problems resulting in increased 
morbidity and mortality occur in all 3 SCTs. Historically, less than 10% of SCT diagnoses occur in childhood, however the rate of 
newborns with SCT has markedly increased with new noninvasive prenatal cell‐free DNA (cfDNA) screening. SCT natural 
history research is limited to studies from the 1970's, and we have little knowledge of early predictors of the wide 
heterogeneity in later outcomes. Increasing research suggests that androgen therapy during infancy in XXY may improve 
developmental and health outcomes, supporting the need for newborn screening so intervention can be delivered during this 
critical period. The very high risk for DD in SCT also suggests that newborn screening may improve timely initiation of 
interventions. However, it is not clear whether all SCT infants indeed require intensive developmental assessments and therapies, or 
if primary care screenings are sufficient to identify those in need. The surge in prenatal SCT diagnoses from cfDNA methods 
provides an opportunity for longitudinal study of a cohort of infants to explore natural history, and to improve care. 
Aims: This study aims to: (1) describe and compare the natural history of neurodevelopment, health and early gonadal 
function in infants with the 3 SCT conditions through a national prospective eXtraordinarY Babies Study in partnership with the 
Newborn Screening Translational Research Network (NBSTRN), (2) identify early predictors of poor neurodevelopmental and 
cardiometabolic outcomes, and (3) evaluate the sensitivities of common primary care developmental screening measures to 
detect DD and ASD in this high‐risk population to inform recommendations for an early neurodevelopmental care protocol. 
Approach: Infants with a prenatal diagnosis of XXY (n=100), XYY (n=50), or XXX (n=50) will be followed prospectively every 
6‐12 months for 2‐4 years at 2 eXtraordinarY Kids Clinic sites. Demographics, health history, development, interventions, and 
social/family history will be collected using NBSTRN common data elements. Assessments will include: (1) measures of 
cognitive, language, social, motor, and adaptive function, (2) physical exam, gonadal function labs, cardiometabolic measures, 
and body composition, and (3) quality of life outcomes. Developmental and hormonal profiles for each SCT condition will be 
modeled, and the association between early risk factors and outcomes at 3‐4 years of age will be tested. Further, the 
sensitivities of common primar...

## Key facts

- **NIH application ID:** 10011576
- **Project number:** 5R01HD091251-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Nicole Renee Tartaglia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $529,675
- **Award type:** 5
- **Project period:** 2017-09-06 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011576

## Citation

> US National Institutes of Health, RePORTER application 10011576, The eXtraordinarY Babies Study: Natural History of Health and Neurodevelopment in Infants and Young Children with Sex Chromosome Trisomy (5R01HD091251-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10011576. Licensed CC0.

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