Correlation of CXCR4 Expression in Premature Infants With a Diagnosis of Autism at 24 Months

NCT01686685 | Completed

• 1 other identifier: begin1HMO-CTIL
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Preterm children are at increased risk for autism spectrum disorders, with an estimated rate of 10%. In the US, about 1 in 8 pregnancies ends with a premature birth. Therefore, individuals with ASD who were born prematurely form a substantial body of children diagnosed with ASD. Premature birth confers an insult to the newborn at a neurologically vulnerable stage. Prematurity associated changes in oxygen tension can be detrimental to developing organs, the brain being one of the most rapidly developing organs in the second half of the pregnancy. Changes in oxygen tension mediate activation of proteins that change the course of cell development. In this study, we plan to measure changes in the expression of 3 proteins that may be affected by changes in oxygen level at birth. We will study the interaction between the proteins' levels in the first few days after premature birth with a diagnosis of ASD at 2 years of age. The proteins are:

1. 1.VEGF (Vascular Endothelial Growth Factor), a protein that takes part in creating new blood vessels during embryonic development.
2. 2.Hypoxia-inducible factor -1(HIF-1), a key protein that coordinates expression of different genes, many with developmentally critical functions.
3. 3.CXCR4, a cell surface protein that is activated by SDF-1. SDF- 1 is a molecule that regulates migration of cells to their target destination during embryonic life. CXCR4 is expressed in areas of the brain and on cells that are known to be associated with ASD.
4. 4.Premature babies will be recruited in the first day post delivery.
5. 5.Blood samples will be collected at 3 time points during their hospitalization, and the expression of HIF-1, CXCR4 and VEGF will be determined.
6. 6.Infants will undergo a complete developmental evaluation at 18-24 months of age .
7. 7.Postnatal levels of HIF, CXCR4 and VEGF will be plotted against the results of the developmental evaluation.

Conditions

Autism Spectrum Disorder; Complication of Prematurity

Keywords

ASD; autism; prematurity; oxygen-dependant gene activation; CXCR4; Language delay; Cognitive delay

Outcome Measures

Primary Outcomes (1)

• Diagnosis of ASD at 24 months corrected age

  Participants will be screened at 18 and 24 months for autism using the MCHAT questionnaire all positive screens will be referred for a complete developmental evaluation by child psychologist and developmental pediatrician: History, assessment (ADOS) and clinical judgement based on DSM criteria

  30 months

Secondary Outcomes (1)

• Language or cognitive delay at 24 months corrected age

  30 months

Eligibility Criteria

• Age: 1 Hour - 1 Day
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

neonatal intensive care units newborn ward

You may qualify if:

• Parents gave informed consent approved by the Institutional Review Board
• Gestational week 28-34 as determined by an ultrasound during the first trimester
• Singleton or twin pregnancy

You may not qualify if:

• Major anatomical abnormalities as detected on prenatal US
• Genetic syndrome as detected by prenatal US, MRI or chorioamniocentesis
• Obvious anatomical abnormalities or dysmorphic features detected on physical examination immediately following birth
• Triplet pregnancy
• Mother known or suspected to consume alcohol or illegal drugs during pregnancy
• Mother took medications during pregnancy that are known to have adverse affects on development (e.g. anti-epileptics)
• Family history of genetic syndrome related to developmental delays, that was not ruled out during current pregnancy (e.g. sibling with Tuberous Sclerosis or fragile X)

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Medical Center

Jerusalem, Israel

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood samples. expression of proteins or RNA will be determined from the blood.

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder; Premature Birth; Language Development Disorders

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michal Begin, MD

  Hadassah HMO

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: September 18, 2012
• Study Start: September 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: April 12, 2018

Record last verified: 2012-09

Locations

IL (1)