UNSW Embryology

Abnormal Development - Intrauterine Growth Restriction (IUGR)

© Dr Mark Hill (2011)

Acknowledgements

Introduction

Intrauterine Growth Restriction or Retardation (IUGR) is a term used to describe poor fetal growth. It refers to a fetus whose weight is below the 10th percentile for gestational age and often related to very low birth weight (VLBW defined as < 1500 grams). It is thought that in addition to genetic effects that environmental programming by the uterine nutritional, oxygenation and endocrine fators may have a role in low birth weight and future health problems.

This has led to the Fetal origins hypothesis (fetal programming, barker hypothesis) that links low birth weight to postnatal development of heath problems. (More? Fetal Origins Hypothesis | Human Fetal Weight).

Page Links: Introduction | Some Recent Findings | Australian NHMRC Recommendations | WWW Links | References | Search Pubmed Now | Glossary

Some Recent Findings

Intrauterine growth restriction and placental location. Kalanithi LE, Illuzzi JL, Nossov VB, Frisbaek Y, Abdel-Razeq S, Copel JA, Norwitz ER. J Ultrasound Med. 2007 Nov;26(11):1481-9.

"Pregnancies complicated by IUGR are significantly more likely than non-IUGR pregnancies to have lateral placentation in the second trimester."

Sheridan C. Intrauterine growth restriction--diagnosis and management. Aust Fam Physician. 2005 Sep;34(9):717-23.

Ke X, Lei Q, James SJ, Kelleher SL, Melnyk S, Jernigan S, Yu X, Wang L, Callaway CW, Gill G, Chan GM, Albertine KH, McKnight RA, Lane RH. Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol Genomics. 2006 Mar 13;25(1):16-28.

"Intrauterine growth retardation (IUGR) increases the risk of neuroendocrine reprogramming. In the rat, IUGR leads to persistent changes in cerebral mRNA levels. .... We conclude that IUGR results in postnatal changes in cerebral chromatin structure and that these changes are sex specific."

AHRQ Evidence-Based Clinical Information

The information below is modified from the AHRQ (USA) publication "Criteria for Determining Disability in Infants and Children: Low Birth Weight". (More? AHRQ publication link)

Study: Retrospective and prospective studies in infants or children who weighed 2,000 grams or less, whose gestational age was 35 week or less, or whose birth weight or gestational age were below these thresholds. Preferences were given to recent studies and studies with a minimum of 6 months of follow-up.

Main Results: looked for evidence of association of very low birth weight (VLBW defined as < 1500 grams) with six outcome conditions. The evidence of the literature overwhelmingly supports that the risk of cerebral palsy (CP) and major neurologic disability is increased among VLBW infants compared to full-term infants. The literature is consistent in demonstrating that risk of CP, major neurosensory and/or neurologic disability is inversely proportional to the degree of immaturity whether measured by gestational age or by birth weight.

• VLBW have higher rates of cognitive abnormality in early childhood and a several-fold increased prevalence of IQ < 70 as adults compared with children or adults who were born normal birth weight at term. (evidence that even children who were apparently “well” VLBW infants during their neonatal course are also at significantly greater risk for both moderate and severe delay compared to larger birth weight groups)
• VLBW high risk for developing cognitive, neuromotor, and neurosensory disabilities including blindness and hearing loss. (disabilities in turn may lead to other disabilities in speech and language, behavior problems and learning disabilities affecting school performance)
• VLBW strong evidence of increased incidence of speech and language delays in and extremely premature infants, and identified clinical factors associated with the increased incidence. (short-term memory and language outcomes, preschool children who were born preterm performed at a lower level, these deficits were independent of the general IQ)
• VLBW infants, with or without retinopathy of prematurity (ROP), are at increased risk of visual impairments and disability compared to children born full term. (risk of visual disability in VLBW infants varies inversely with gestational age)
• VLBW infants with bronchopulmonary dysplasia (BPD) are at increased risk for long-term pulmonary disability. (greater the severity of BPD, the greater is the association with long-term pulmonary impairment and need for re-hospitalization)
• VLBW infants, with or without other conditions, are at high risk for poor growth during the first years of life. (due to acute neonatal illnesses, developmental delays, and chronic illnesses)

Agency for Healthcare Research and Quality USA (AHRQ) Evidence-Based Clinical Information Criteria for Determining Disability in Infants and Children: Low Birth Weight

The Australian NHMRC Recommendations

Recommendations for neonates be assessed for follow-up care under the following conditions (1988). (Please note that current guidelines may differ from those listed below)

• Birthweight less than 1500g or gestational age less than 32 weeks
• Small-for-gestational-age neonates
• Perinatal asphyxia
• Apgar score less than 3 at 5 minutes
• clinical evidence of neurological dysfunction
• delay in onset of spontaneous respiration for more than 5 minutes and requiring mechanical ventilation
• Clinical evidence of central nervous system abnormalities ie., seizures, hypotonia
• Hyperbilirubinaemia of greater than 350umol/l in full term neonates
• Genetic, dysmorphic or metabolic disorders or a family history of serious genetic disorder
• Perinatal or serious neonatal infection including children of mothers who are HIV positive
• Psychosocial problems eg., infants of drug-addicted or alcoholic mothers.

References

Reviews

• Fowden AL, Giussani DA, Forhead AJ. Intrauterine programming of physiological systems: causes and consequences. Physiology (Bethesda). 2006 Feb;21:29-37.
• Fang S. Management of preterm infants with intrauterine growth restriction. Early Hum Dev. 2005 Nov;81(11):889-900.
• Sheridan C. Intrauterine growth restriction--diagnosis and management. Aust Fam Physician. 2005 Sep;34(9):717-23.
• Maritz GS, Morley CJ, Harding R. Early developmental origins of impaired lung structure and function. Early Hum Dev. 2005 Sep;81(9):763-71.
• Ergaz Z, Avgil M, Ornoy A. Intrauterine growth restriction-etiology and consequences: what do we know about the human situation and experimental animal models? Reprod Toxicol. 2005 Sep-Oct;20(3):301-22.

Articles

• Ke X, Lei Q, James SJ, Kelleher SL, Melnyk S, Jernigan S, Yu X, Wang L, Callaway CW, Gill G, Chan GM, Albertine KH, McKnight RA, Lane RH. Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol Genomics. 2006 Mar 13;25(1):16-28.

Search Pubmed Now

Click on the listed keywords below (used to search the external database) the most current references on Medline will be displayed. Intrauterine Growth Retardation (title) + review | IUGR (title) + review

WWW Links

Glossary of Terms

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Quick Links

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- All Systems Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Renal Genital Musculoskeletal Integumentary

Finally

For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.

Movies ----------------- Embryo Growth Carnegie Stages Ultrasound Images Stage 13/14 Embryo Stage 22 Embryo Heart Septation Neural Neural Crest Other Embryos Larsen Movies

Other Embryos

The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.

Other Embryos ----------------- All Animals Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

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