Longitudinal Study of Intra-Uterine Growth Restriction

Official title

Longitudinal Study of Intra-Uterine Growth Restriction (IUGR)

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.

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.

Primary outcome 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]

Secondary outcome measures (4)

• 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]
• 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]
• 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]
• 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

United States · 1 center

• University of Colorado Denver Anschutz Medical Campus — Aurora

Publications

• Barker ED, McAuliffe FM, Alderdice F, Unterscheider J, Daly S, Geary MP, Kennelly MM, O'Donoghue K, Hunter A, Morrison JJ, Burke G, Dicker P, Tully EC, Malone FD. The role of growth trajectories in classifying fetal growth restriction. Obstet Gynecol. 2013 Aug;122(2 Pt 1):248-254. doi: 10.1097/AOG.0b013e31829ca9a7. PMID 23969791
• Mongelli M, Gardosi J. Reduction of false-positive diagnosis of fetal growth restriction by application of customized fetal growth standards. Obstet Gynecol. 1996 Nov;88(5):844-8. doi: 10.1016/0029-7844(96)00285-2. PMID 8885925
• Cruz-Martinez R, Figueras F, Hernandez-Andrade E, Puerto B, Gratacos E. Longitudinal brain perfusion changes in near-term small-for-gestational-age fetuses as measured by spectral Doppler indices or by fractional moving blood volume. Am J Obstet Gynecol. 2010 Jul;203(1):42.e1-6. doi: 10.1016/j.ajog.2010.02.049. Epub 2010 May 1. PMID 20435282
• Hecher K, Bilardo CM, Stigter RH, Ville Y, Hackeloer BJ, Kok HJ, Senat MV, Visser GH. Monitoring of fetuses with intrauterine growth restriction: a longitudinal study. Ultrasound Obstet Gynecol. 2001 Dec;18(6):564-70. doi: 10.1046/j.0960-7692.2001.00590.x. PMID 11844190
• Ferrazzi E, Bozzo M, Rigano S, Bellotti M, Morabito A, Pardi G, Battaglia FC, Galan HL. Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus. Ultrasound Obstet Gynecol. 2002 Feb;19(2):140-6. doi: 10.1046/j.0960-7692.2002.00627.x. PMID 11876805
• Turan OM, Turan S, Berg C, Gembruch U, Nicolaides KH, Harman CR, Baschat AA. Duration of persistent abnormal ductus venosus flow and its impact on perinatal outcome in fetal growth restriction. Ultrasound Obstet Gynecol. 2011 Sep;38(3):295-302. doi: 10.1002/uog.9011. PMID 21465604
• Acharya G. Measurement of atrioventricular annular plane displacement has been revived: will it prove to be useful in assessing fetal cardiac function? Ultrasound Obstet Gynecol. 2013 Aug;42(2):125-9. doi: 10.1002/uog.12542. No abstract available. PMID 23775904
• Kiserud T. Re: umbilical vein flow and perinatal outcome in term small-for-gestational-age fetuses. M. Parra-Saavedra, F. Crovetto, S. Triunfo, S. Savchev, G. Parra, M. Sanz, E. Gratacos and F. Figueras. Ultrasound Obstet Gynecol 2013; 42: 189-195. Ultrasound Obstet Gynecol. 2013 Aug;42(2):130. doi: 10.1002/uog.12553. No abstract available. PMID 23893598

Identifiers

NCT: NCT02382601 · 14-1360

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗