1. Intrauterine Growth Restriction
Natasha Lopez, MD
September 19th, 2019

2. Definition
Rate of fetal growth that is less than normal for the growth potential of a specific infant
Any aberration of biological activity in fetus may cause impaired growth

3. Symmetric vs Asymmetric
Early onset
Constitutional or normal small
Normal maternal and fetal arterial waveform velocity
Glycogen and fat content relative
Low risk for hypoglycemia
Asymmetric (70-80%)
Late onset
Environmental
Decreased maternal and fetal arterial waveform velocity
Decreased glycogen and fat content
Increased risk for hypoglycemia

4. Ponderal Index Useful tool to detect IUGR
Especially asymmetric
PI = [weight (g) x 100] ÷ [length (cm)]3
PI less than 10th percentile = fetal malnutrition
PI less than 3rd percentile = severe wasting
Normal in symmetric IUGR (2-2.5)
Low in asymmetric IUGR (<2)
PI >2.5 in AGA term babies

5. Ponderal Index Ex: PI = [weight (g) x 100] ÷ [length (cm)]3

6. Neonatal Problems
Perinatal mortality in IUGR is 10-20x higher than AGA infants
Increased morbidity related to:
Perinatal asphyxia
Neonatal hypoglycemia
Hypothermia
Polycythemia

7. IUGR vs SGA Are they interchangeable??No
IUGR signifies pathology of some sort….
SGA simply means <10th percentile, which could be their full growth potential (small parents)

8. Causes Symmetric Asymmetric Genetics Infection Chromosomal
Placental insufficiency
Pre-eclampsia
Maternal nutritional deficiency
Poor caloric intake
Diabetes class D to F
Chronic fetal distress

9. Maternal Genetic Factors
History of growth restricted baby
Risk increases with every IUGR baby mom has
History of mother being a growth restricted baby (2x risk)

10. Fetal Genetic Abnormalities
Account for 5-20% of IUGR
Aneuploidy
Uniparental disomy
Single gene mutations
Partial deletions or duplications
Symmetric IUGR prior to 20 weeks suggests aneuploidy with Trisomy 18 being the most common

11. Fetal Infection Accounts for 5-10% of IUGR Rubella CMV Toxoplasmosis
Parvo B19

12. Multiple Gestation
Inability of environment to meet the nutritional needs of multiple fetuses
Pregnancy complications more common in multiples (pre-eclampsia, TTTS)
Placental and umbilical cord anomolies

13. Gross Cord and Placental Abnormalities
Single umbilical artery
Velamentous umbilical cord insertion
Marginal cord insertion
Bilobate placenta
Circumvallate placenta
Placental hemangioma
Courtesy of the Pathology Department at The Valley Hospital in Ridgewood, New Jersey

14. Maternal medical and obstetric conditions
Pre-eclampsia
Abruptio placenta
Chronic hypertension
Chronic kidney disease
Pregestational diabetes
Uterine malformations
Use of alcohol, drugs, cigarettes
Illustration by James A. Cooper, MD, San Diego, CA. Obtained from

15. Complications

16. Prematurity
Early delivery is often performed because the risks of staying in utero outweigh the risks of prematurity
IUGR preterm babies are higher risk of many morbidities related to prematurity (NEC, RDS, BPD, and ROP) than AGA preterm babies are
23+3 weeks
245 g
December 2018 in San Diego. Discharged to home at 5 months of age.

17. Perinatal asphyxia
Particularly for infants with IUGR due to placental pathology
Often times, do not tolerate contractions well
Can result in:
Hypoxia and metabolic acidosis
HIE
Meconium aspiration
PPHN
Acute kidney injury

18. Impaired thermoregulation
Reduced subcutaneous fat
Reduced heat production
Poor nutrient reserves
Depletion of cathecolamines
The infant has the characteristic appearance of an infant with intrauterine growth restriction. Note the loose, peeling skin, decreased subcutaneous tissue and muscle mass, and meconium staining.
Courtesy of George T Mandy, MD.

19. Hypoglycemia Due to decreased reserves of fat, protein, and glycogen
Typically occurs within the first 10 hours after birth

20. Polycythemia and Hyperviscosity
Increased erythropoietin secondary to fetal hypoxia
By FetalTherapyLUMC at English Wikipedia, CC BY-SA 3.0,

21. Hypocalcemia Usually occurs within the first 2-3 days after birth
Due to decreased stores

22. Initial Management Delivery room Airway Thermoregulation
Provide normal NRP resuscitation in timely fashion to help avoid PPHN and/or limit effects of meconium aspiration
Thermoregulation
Radiant warmer
Polyethylene bag (<32 weeks)
Chemical mattress (<32 weeks or EFW <1500 grams)

23. Management Glucose check within first 1-2 hours of life
Goal glucoses in first 24 hours of life >45
After first 24 hours, goal > 55-60
Ionized calcium check at 12 hours of life
CBC at 6-12 hours of life to look for polycythemia
PO feeds should be started if greater than 36 weeks. Gavage feeds should started slowly and increased cautiously in IUGR babies.

24. Further Evaluation Take a detailed maternal history
Send placenta to pathology for evaluation
Comprehensive physical examination of baby for dysmorphic features
Rule out congenital infections
Rubella
CMV
Toxoplasmosis
Parvo B19

25. Trisomy 18 Second most common Trisomy after Trisomy 21
Live born prevalence of 1 in 6,000
Babies born with :
IUGR
Overlapping fingers
Congenital heart disease

26. Infections Causing IUGR
CMV
Screened through urine CMV test
Toxoplasmosis
Send infant and maternal serology
CT to evaluate for calcifications
Rubella
Check mom’s Rubella status
If Rubella immune, this is unlikely
If Rubella non-immune, may consider further Rubella congenital infection work up
Parvo B19
Send fluid for serology (serum or tissue, including amniotic fluid)

27. Outcomes
Mortality
Increased in neonates with IUGR versus those born AGA
Most significant at <5th percentile
This is especially true in preterm infants
French EPIPAGE (1997)
24-28 weeks
62% (<10th percentile))
42% (10-20th)
30% (>20th percentile)

28. Outcomes Long term morbidity Physical growth
Growth patterns depend on etiology of IUGR
Many times growth accelerated 6-12 months resulting in normal size
Severely affected babies (BW <3rd percentile)
Average height at 17 years was less than AGA controls
5’6” vs 5’9” cm in boys
5’3” vs 5’4” cm in girls

29. Outcomes Long term morbidity Neurodevelopment
Possible increased risk for neurodevelopmental abnormalities and decreased cognitive function
Though the evidence is difficult to extrapolate
Systematic review
Poor neurodevelopmental outcomes in 11 of 16 studies
10 of the studies showed motor delay
8 studies showed cognitive delay
7 studies showed language delay

30. Outcomes Long term morbidity Neurodevelopment EPIPAGE study
26 weeks to 32 weeks
Survivors with symmetric growth restriction vs AGA controls
BW and HC <20th percentile
Cognitive difficulties at 5 years
Poor school performance at 8 years
Other studies
Behavioral problems, such as ADHD
Gross motor dysfunction
Growth failure

31. Outcomes Long term morbidity Adult chronic disorders
Coronary artery disease
Hypertension
Chronic kidney disease

32. References
Anderson MS, Hay WW. Intrauterine growth restriction and the small-for-gestational-age infant. In: Neonatology Pathophysiology and Management of the Newborn, 5th ed, Avery GB, Fletcher MA, MacDonald MG (Eds), Lippincott Williams and Wilkins, Philadelphia p.411.
Barker DJ. Early growth and cardiovascular disease. Arch Dis Child 1999; 80:305.
Bernstein IM, Horbar JD, Badger GJ, et al. Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. The Vermont Oxford Network. Am J Obstet Gynecol 2000; 182:198.
Chard T, Costeloe K, Leaf A. Evidence of growth retardation in neonates of apparently normal weight. Eur J Obstet Gynecol Reprod Biol 1992; 45:59.
Doctor BA, O'Riordan MA, Kirchner HL, et al. Perinatal correlates and neonatal outcomes of small for gestational age infants born at term gestation. Am J Obstet Gynecol 2001; 185:652.
Guellec I, Lapillonne A, Renolleau S, et al. Neurologic outcomes at school age in very preterm infants born with severe or mild growth restriction. Pediatrics 2011; 127:e883.
Holtrop PC. The frequency of hypoglycemia in full-term large and small for gestational age newborns. Am J Perinatol 1993; 10:150.
Lapillonne A, Braillon P, Claris O, et al. Body composition in appropriate and in small for gestational age infants. Acta Paediatr 1997; 86:196.
Levine TA, Grunau RE, McAuliffe FM, et al. Early childhood neurodevelopment after intrauterine growth restriction: a systematic review. Pediatrics 2015; 135:126.
Mandy, GT. Infants with fetal (intrauterine) growth restriction. UpToDate. Last updated: Sept 2019
Miller HC, Hassanein K. Diagnosis of impaired fetal growth in newborn infants. Pediatrics 1971; 48:511.
Paz I, Seidman DS, Danon YL, et al. Are children born small for gestational age at increased risk of short stature? Am J Dis Child 1993; 147:337.

33. Thank you!
Questions/comments???