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Promising Findings Suggest Maternal Biomarker May Help To Identify Earlier In Life Infants with Fetal Alcohol Spectrum Disorders

Tina Chambers and Rajesh Miranda

CIFASD investigators examined whether changes in the levels of circulating microRNAs (miRNAs) in mother’s plasma during pregnancy could work as a biomarker for Fetal Alcohol Spectrum Disorders (FASD) in the developing fetus. They identified 11 miRNAs that were significantly elevated in mothers who delivered infants with evidence of FASD compared to mothers who consumed similar amounts of alcohol in pregnancy and had infants without any evidence of FASD and compared to mothers who drank little or no alcohol in pregnancy. These findings suggest that maternal plasma miRNAs may be a useful and very early biomarker for FASD. Early intervention is known to improve outcomes for children with FASD. If miRNA measures in mothers during pregnancy can aid with early identification of affected children, this can help to improve outcomes.

Researchers Find That Simple Test May Help Identify Infants Who Have Been Affected By Prenatal Exposure to Alcohol So That Early Intervention Can Help

Infant CIFASD investigators, Drs. Christina Chambers, Julie Kable, and Claire Coles, found that measuring heart rate responses to stimuli (the cardiac orienting response) in infants at 6 months of age was better than the Bayley’s test of development in predicting both normal and impaired infant performance at 12 months of age. The COR, a simple test requiring few resources and minimal expertise to administer, may be an effective early measure of alcohol-related impairment in young infants. This novel screening tool could provide an early, and more accessible method for early identification leading to better outcomes for children with FASD.

Data Dictionary

Available data dictionaries:
Phase 1: Phase 1 Data Dictionary (2003-2007)

Phase 2: Phase 2 Data Dictionary (2007-2012)

Phase 3: Phase 3 Data Dictionary (2012-2017)

Phase I:

Available data from Phase I were collected across five sites:
(1) Center for Behavioral Teratology, San Diego State University, San Diego, CA;
(2) Seven Northern Plains communities, including six Indian reservations;
(3) Institute of Psychiatry, Moscow, Russia;
(4) Moscow Region Institute of Obstetrics and Gynecology, Moscow, Russia, and
(5) Omni-Net sites at the Rivne Diagnostic Center, and the Kherson Children’s Hospital, Rivne and Kherson, Ukraine.

Subject recruitment varied between the sites, and subject population was racially and ethnically diverse.

Data for Neurobehavior, Dysmorphology Demographics, 3D Facial Imaging were collected from sites 1-3 for children between the ages of 5 -18 years, although the majority were 7-18 years old.

Data on current and recent maternal alcohol consumption, demographics and pregnancy history in a prospective study of prenatal alcohol exposure were collected from mothers and their babies from sites 4-5. Dysmorphology data was collected for all participants.

Infant Data

Data collected from infants in a prospective study.

Phase II

Several variables are provided from an infant neurological exam and from the EEAC interview.

Phase III

Several variables from the Conners scale, EEAC and other neurobehavioral exams are provided. Cytokine data are available.

Neurobehavior Data

Phase 1 – data include measures from the Leiter, NES3, DKEFS, CANTAB, CBC and other scales

Phase 2 – data include measures from the Leiter, DKEFS, CANTAB, BRIEF, ASEBA, Vineland, C-DISC, and other scales

Phase 3 – data include measures from the DAS-II, NEPSY-II, CANTAB, BRIEF, ASEBA, Vineland, C-DISC and other scales

Phase I

[The => will link to detail when provided]

General Intellectual Ability=>Leiter International Performance Scale-Revised (Leiter-R)
Attention and Concentration=>NES3 – Continuous Performance Test (Animals)
Executive Function=>Delis-Kaplan Executive Function System (Verbal Fluency, Trail Making); Progressive Planning Test; Visual Discrimination Reversal Learning
Working Memory/Memory=>CANTAB (Spatial Working Memory; Spatial Span; Pattern Recognition Memory; Spatial Recognition Memory); Virtual Water Maze
Visual-Motor=>Visual-Motor Integration Test
Motor/Reaction Time: CANTAB (Motor Screening; Big/Little Circle); Grooved Pegboard Test
Interhemispheric Transfer=> Finger Localization Test
Psychological Symptomatology=> ASEBA (Child Behavior Checklist; Teacher Report Form; Youth Self Report); Disruptive Behavior Rating Scale; Sluggish Cognitive Tempo Scale; Pictorial Depression Scale

Phase II

General Intellectual Ability=>Wechsler Intelligence Scale for Children – Fourth Edition
Executive Function=> Delis-Kaplan Executive Function System (Verbal Fluency, Trail Making; Color-Word Interference; Tower; 20 Questions; Design Fluency); CANTAB (Intra/Extradimensional Shift); BRIEF (Parent Version; Child Version)
Working Memory/Memory=> CANTAB (Spatial Working Memory; Delayed Matching to Sample)
Motor/Reaction Time=> CANTAB (Motor Screening; Big/Little Circle; Simple Reaction Time; Choice Reaction Time)
Psychological Symptomatology=> ASEBA (Child Behavior Checklist; Teacher Report Form; Youth Self Report); Disruptive Behavior Rating Scale; Sluggish Cognitive Tempo Scale; Vineland Adaptive Behavior Scales, 2nd Edition (Parent/Caregiver Rating Form; Teacher Rating Form); C-DISC Psychiatric Interview (Demographics; GAD; MDD; ADHD; ODD; CD modules)

Phase III

General Intellectual Ability=> Differential Ability Scales – 2nd Ediction (DAS-II)
Attention and Concentration=> NEPSY-II (Speeded Naming; Arrows)
Executive Function=> CANTAB (Stockings of Cambridge); NEPSY-II (Word Generation; Inhibition); BRIEF (Parent Version)
Working Memory/Memory=> California Verbal Learning Test – Children’s Version (CVLT-C); NEPSY-II (Memory for Names; Memory for Designs: Memory for Faces; Narrative Memory)
Psychological Symptomatology=> ASEBA (Child Behavior Checklist; Teacher Report Form; Youth Self Report); Disruptive Behavior Rating Scale; Sluggish Cognitive Tempo Scale; Vineland Adaptive Behavior Scales, 2nd Edition (Parent/Caregiver Rating Form; Teacher Rating Form); C-DISC Psychiatric Interview (Demographics; GAD; MDD; ADHD; ODD; CD modules)

Brain Volume

MRI data were collected in Phase 2 and 3

Genetic Data

PLINK files are provided for GWAS data
VCF files are provided for whole exome sequencing data

3D Facial Imaging

3D Facial Imaging data were collected in all phases of CIFASD

Phase I

Data was acquired on an older Minolta laser system and include linear measurements for several anthropometric measures.

Phase II

Facial Data were acquired on a 3dMD system and include linear measurements as well as x, y, z coordinates for the measures.

Phase III

Data were acquired on a 3dMD system and include linear measurements as well as x, y, z coordinates for the measures.

Dysmorphology

Dysmorphology data were collected from all phases and some individuals have been examined longitudinally. These data include information on height, weight, head circumference and other physical measures, as well as philtrum score, thin vermillion border score, and palpebral figure length.

Demographics

Data include information (when known) on the birth (e.g., weight, length maternal substance use), and alcohol exposure information.

Phase III:

Available data from Phase III were collected across five sites:
(1) San Diego State University,
(2) Emory University,
(3) University of California, Los Angeles and Children’s Hospital Los Angeles, CA,
(4) University of Minnesota; and
(5) Omni-Net locations in Ukraine: the Rivne Diagnostic Center and the Khmelnytsky Perinatal Center in Rivne and Khmelnytsky, Ukraine.

Subject recruitment varied between the sites, and subject population was racially and ethnically diverse.

Data for Neurobehavior, Dysmorphology, Demographics, 3D Facial Imaging, Genetics, and Brain Volume were collected from sites 1-4 for children ages 5-7 and 10-16 years under two age-based protocols. Data from maternal blood samples were collected from pregnant women and fetal data were collected via ultrasound from mothers and babies at site 5. Live born infants were given a dysmorphology exam, facial imaging, and neurobehavioral testing. Collection of blood, urine, and cheek cell samples were also included.

Phase II:

Available data from Phase II were collected across six sites:
(1) Center for Behavioral Teratology, San Diego State University, San Diego, CA;
(2) Emory University, Atlanta, GA;
(3) the University of California, Los Angeles, Los Angeles, CA;
(4) University of New Mexico, Albuquerque, NM;
(5) Seven Northern Plains communities, including six Indian reservations; and
(6) Omni-Net locations in Ukraine: the Rivne Diagnostic Center and the Khmelnytsky Perinatal Center in Rivne and Khmelnytsky, Ukraine.

Subject recruitment varied between the sites, and subject population was racially and ethnically diverse.

Data for Neurobehavior, Dysmorphology, Demographics and Brain Volume were collected from sites 1-5 for children between the ages of 8-16 years. 3D Facial Imaging and Genetic data are also available for children from sites 1-3. Data from a longitudinal study were collected from site 6 for 350 moderately to heavily alcohol-exposed pregnant women and approximately 350 low or unexposed women.

Pregnancies were followed with serial ultrasounds and maternal blood samples were collected and analyzed for various nutrients and markers of oxidative stress and inflammation. Live born infants were given a dysmorphology exam, facial imaging, and neurobehavioral testing.