Longitudinal Study of Intra-Uterine Growth Restriction

Overview

The investigation will employ a longitudinal approach in which every fetus diagnosed to be SGA (Small for Gestational Age ) will be studied at frequent intervals with sophisticated imaging techniques to assess subtle physiologic changes in the brain, heart, and placenta over time. These findings will be correlated with neurological and cardiovascular function in the newborn and early childhood. This research initiative should yield diagnostic and therapeutic templates that will improve the quality of life of IUGR babies in addition to providing important information that will better inform current diagnostic practices.

Full Title of Study: “Longitudinal Study of Intra-Uterine Growth Restriction (IUGR)”

Study Type

• Study Type: Observational
• Study Design
  • Time Perspective: Prospective
• Study Primary Completion Date: August 2023

Detailed Description

The overarching objective is to serially assess changes in the fetal circulation, heart, and brain with sophisticated ultrasound, MRI (Magnetic Resonance Imaging), and body composition techniques that will provide clues as to how growth restricted babies will tolerate life outside the uterus. Employing a longitudinal study will allow the investigators to correlate perinatal and postnatal outcomes more comprehensively than previous studies.

Interventions

• Radiation: Ultrasound
  • With 3-D and 4-D high-resolution color Doppler methods it is possible to map out the placental circulation, fetal circulation, fetal brain, and fetal cardiac function. Investigators will collect these data points prenatally.
• Radiation: MRI
  • Similar to the Ultrasound data, investigators will collect MRI images of the fetal brain and the placenta. MRI will allow investigators to collect more detailed images of both the fetal brain and placenta, and investigators will be utilizing this technique both prenatally and postnatally.
• Procedure: Blood collection
  • The maternal and cord blood will be collected for the processing of plasma and serum. There may be early biomarkers of IUGR in the maternal circulation that investigators can use to better determine the appropriate strategy for clinical management of care. Collection and subsequent analysis of molecular markers in the umbilical cord blood will be used to further confirm physiological dysfunction as detected by ultrasound and MRI techniques.
• Behavioral: Neurological Function Assessment
  • Neurological development tests including a Bayley exam, Mullen exam, Developmental Profile-3, Child Behavior Checklist, and Pediatric Stroke Outcome Measure (PSOM) will be performed.
• Procedure: Placental Analysis
  • Placentas will undergo pathological evaluation for placental function.
• Procedure: Measurement of body fat
  • The baby’s body fat will be measured in a special incubator called a PEAPOD or BODPOD when an infant.
• Radiation: Pediatric heart ultrasound
  • Children will have ultrasounds of their hearts during follow-up visits.

Arms, Groups and Cohorts

• Small for Gestational Age Pregancies (controls)
  • Small for gestational age (SGA) pregnancies that do not develop IUGR will be considered controls. Each subject will have an ultrasound, MRI, maternal blood and cord blood collection, placental analysis, neurological function assessments (infant), and body fat measurements (infant).
• IUGR Pregnancies (cases)
  • Small for gestational age (SGA) pregnancies that do develop IUGR will be considered cases. Each subject will have an ultrasound, MRI, maternal blood and cord blood collection, placental analysis, neurological function assessments (infant), and body fat measurements (infant).

Clinical Trial Outcome Measures

Primary Measures

• Characterize the sequence of neurological and cardiovascular events defining early and late IUGR pathogenesis, respectively
  • Time Frame: Every two weeks from the time of IUGR diagnosis or first visit
  • Using ultrasound and MRI to identify changes in the fetal vasculature, and fetal brain as early and late IUGR progress.

Secondary Measures

• Correlate in utero adaptations in early and late IUGR, to infant and early childhood neurodevelopment
  • Time Frame: Baseline (Day 0), 40-44 weeks gestational age (post-birth), 6 months, 1-7 years
  • Assess neurodevelopment with a series of tests (PSOM, Bayleys III, Mullen’s Scale of Early Learning, Developmental Profile-3, Child Behavior Checklist) and correlate neurological in utero findings to neurodevelopment outcomes after birth.
• Correlate in utero adaptations in early and late IUGR, to infant and early childhood cardiovascular outcomes
  • Time Frame: Baseline (Day 0), 40-44 weeks gestational age (post-birth), 6 months, 1-7 years
  • Assess cardiovascular health via heart ultrasound after birth
• Correlate in utero adaptations in early and late IUGR, to infant and early childhood metabolic outcomes
  • Time Frame: Baseline (Day 0), 40-44 weeks gestational age (post-birth), 6 months, 1-7 years
  • Correlate IUGR severity to metabolic outcomes as assessed by body composition (pea pod and bod pod with a pediatric attachment), anthropometrics, and a diet questionnaire after birth.
• Compare early IUGR, late IUGR and SGA infant and early childhood outcomes
  • Time Frame: Baseline (Day 0), 40-44 weeks gestational age (post-birth), 6 months, 1-7 years
  • Using the tests describe above compare the outcomes of each group after birth.

Participating in This Clinical Trial

Inclusion Criteria

• Patients with diagnosed SGA by an ultrasound estimated fetal weight (EFW) of less than the 10th percentile or a fetal abdominal circumference of less than the 5th percentile will be included in the study at the time of their first examination. Exclusion Criteria:

• Patients < 18 years of age, and chromosomal anomalies as identified by regular aneuploidy screening.

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 45 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • University of Colorado, Denver
• Collaborator
  • The Perelman Family Foundation
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • John Hobbins, MD, Principal Investigator, University of Colorado, Denver
• Overall Contact(s)
  • Emma Peek, BS, emma.peek@cuanschutz.edu

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