Correlation of CXCR4 Expression in Premature Infants With a Diagnosis of Autism at 24 Months (ASD-CXCR4)

This study is not yet open for participant recruitment.
Verified September 2012 by Hadassah Medical Organization
Sponsor:
Information provided by (Responsible Party):
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT01686685
First received: September 13, 2012
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

Extremely 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 a variety of proteins that change the course of cell development.

In this study, our investigators plan to measure changes in the expression of 3 different proteins that may be affected by changes in oxygen level at birth. The investigators 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 to be investigated are:

  1. VEGF (Vascular Endothelial Growth Factor), a protein that takes part in creating new blood vessels during embryonic development.
  2. Hypoxia-inducible factor -1(HIF-1), a key protein that coordinates expression of different genes, many with developmentally critical functions.
  3. CXCR4, a cell surface protein (receptor) 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.

The investigators' hypothesis that changes in oxygen tension in premature babies initiates a cascade of events that lead to changes in cell mobility via abnormal CXCR4 expression. This change leads to abnormal neurodevelopment.

The investigators' primary aim is to find if there is a correlation between postnatal levels of expression of HIF-1, CXCR4 and VEGF and a diagnosis of autism at age 24 months. The investigators' secondary aim is to find if there is a correlation between postnatal levels of expression of HIF-1, CXCR4 and VEGF and a language or neurocognitive delay.

Methods:

  1. Premature babies will be recruited in the first day post delivery.
  2. Blood samples will be collected at 3 time points during their hospitalization, and the expression of HIF-1, CXCR4 and VEGF will be determined.
  3. Infants will undergo a complete developmental evaluation at 18-24 months of age .
  4. Postnatal levels of HIF, CXCR4 and VEGF will be plotted against the results of the developmental evaluation.

Condition
Autism Spectrum Disorder
Prematurity

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Study of Correlation Between Expression of Proteins That Are Essential for Embryonic Brain Development and Neurodevelopmental Outcomes at 2 Years of Age in Premature Infants.

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Diagnosis of ASD at 24 months corrected age [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Language or cognitive delay at 24 months corrected age [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Participants will be screened by questionnaires at 18 and 24 months. all positive screens will be referred for a full developmental evaluation using the Mullen Scales of Early learning


Biospecimen Retention:   Samples Without DNA

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


Estimated Enrollment: 400
Study Start Date: April 2013
  Eligibility

Ages Eligible for Study:   up to 1 Day
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

neonatal intensive care units newborn ward

Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01686685

Contacts
Contact: Michal Begin, MD 972-2-505172414 mbegin@leumit.co.il
Contact: Hadas Lemberg, PhD 972-2-6777572 lhadas@hadassah.org.il

Locations
Israel
Hadassah Medical Center Not yet recruiting
Jerusalem, Israel
Sponsors and Collaborators
Hadassah Medical Organization
  More Information

No publications provided

Responsible Party: Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT01686685     History of Changes
Other Study ID Numbers: begin1HMO-CTIL
Study First Received: September 13, 2012
Last Updated: September 20, 2012
Health Authority: Israel: Ministry of Health- Director General

Keywords provided by Hadassah Medical Organization:
ASD
autism
prematurity
oxygen-dependant gene activation
CXCR4
Language delay
Cognitive delay

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders

ClinicalTrials.gov processed this record on April 15, 2014