1. INTRAUTERINE GROWTH RESTRICTION (IUGR)
Selçuk Özden MD, Prof

2. INTRAUTERINE GROWTH RESTRICTION
IUGR, is the second most important cause of perinatal mortality after preterm delivery.
Perinatal mortality is increased 6 to 10 times (120/1000)

3. INTRAUTERINE GROWTH RESTRICTION
53 percent of preterm stillbirths and,
26 percent of term stillbirths
Intrapartum asphyxia is increased (50%)
It is possible to prevent prenatal complications by appropriate diagnosis and management.

4. FETAL GROWTH AGA: Appropriate for gestational age (10-90.p)
SGA: Small for gestational age (<10.p)
LGA: Large for gestational age (>90.p)

5. FETAL GROWTH
characteristics

6. FETAL GROWTH
Fetal weight normogram according to gestational age. Lubchencho et al.
characteristics

7. DEFINITIONS Low Birth Weight (LBW) <2500 g
Very Low Birth Weight (VLBW) <1500 g
Extremely Low Birth weight (ELBW) <1000 g
Macrosomia >4000 g

8. TERMINOLOGY
Normal Small Fetuses: (Small Happy Babies): There is no structural anomaly; Doppler findings and amniotic fluid volume normal; fetal weight is low. These babies are not risky, and no need special care
Abnormal Small Fetuses- There is genetic or structural anomaly. Pregnancy termination is offered.
Intrauterine Growth Restriction (= IUGR)- Placental function is impaired. These fetuses need appropriate management and observation.

9. INTRAUTERINE GROWTH RESTRICTION
Cut-off values for diagnosis:
<10.th percentile
<5 th. percentile
Mean±2 SD (3.th percentile)

10. INTRAUTERINE GROWTH RESTRICTION
Growth normograms are based on different ethnic and geographic regions.

11. Growth normograms are based on different ethnic and geographic regions

12. PHASES OF FETAL GROWTH Cellular hyperplasia (first 16 weeks)
Cellular hyperplasia + hypertrophy (until 32.th weeks)
Cellular hypertrophy (after 32 weeks).

13. PHASES OF FETAL GROWTH Impaired dynamics of fetal growth effects
number of cells,
size of cells or both and
cause abnormal fetal weight, body mass or body ratios

14. CLASSIFICATION of IUGR
Symmetric IUGR
Asymmetric IUGR
Head and body of the baby are proportionately small
May be caused by an event during early pregnancy
Head of the baby is abnormally bigger than the body
May be caused by an event during late pregnancy

15. CLASSIFICATION of IUGR

16. SYMMETRIC IUGR Baby is small proportionally
Early events (chemical, viral, chromosomal) ↓
Size and number of cells are decreased
Size of head and body are small propotionately

17. ASYMMETRIC IUGR 2/ 3 of the IUGR
Abdominal growth is disproportionately small.
Late pregnancy pathologies (e.g. Preeclampsia) effect primarily size of cell.
Hepatic storage ↓ → Abdominal circumference ↓
Development of head and brain are not effected (brain sparing effect)
In severe cases, ratio of head circumference to abdominal circumference increase to 1/5

18. ASYMMETRIC IUGR
20 percent of fetuses with IUGR, growth of head is asimetrical with respect to abdomen
Intrapartum and neonatal complications
However, adverse pregnancy outcomes are different from normal fetuses

19. MORTALITY & MORBIDITY
Fetal dead, asphyxia, meconium aspiration, neonatal hypoglycemia and hypothermia ↑
Abnormal neurologic development ↑
Preterm IUGR de long-term mortalite ↑

20. ACCELERATION OF MATURATION
Lung maturation is accelerated in IUGR.
Adrenal glucocorticoid secretion is increased in response to stress
Babies with IUGR has no advantage than preterm babies

21. ETIOLOGY of IUGR General – Ethnicity, small parents, fetal gender.
Maternal causes
Fetal causes
Placental causes
Idiopathic- (40 percent of cases) – Cause ? – probably due to placental insufficiency.

22. ETIOLOGY of IUGR Maternal Causes Chronic medical disorders
Vascular diseases
Hypertensive diseases of pregnancy
Diabetic vasculopathies
Chronic renal diseases
Collagen vascular diseases
Thrombophilia
Antiphospholipid antibody synd.
These problems decreases uteroplacental blood flow
Eating disorders
Poor maternal nutrition
Poor gestational weight gain
Anemia
High altitude
Social deprivation
Illicit drugs
Cocaine
Smoking
Warfarine, hydantoine
Maternal age >35

23. ETIOLOGY of IUGR Fetal Causes Constitutional Multiple gestation
Aneuploidies (trisomi 13, 18, 21)
Congenital abnormalities
Diseases of cartilage and bone
Genetic syndromes
Infectious causes
Herpes,
Cytomegalovirus,
Rubella,
Toxoplasma gondii

24. ETIOLOGY of IUGR Placental Causes
Anormal placental development (1/3 of cases)
Circumvallate plasenta,
Partial abruption,
Pl. Acrreta,
Placental infarcts,
Hemangioma
Single umbilical artery
Placental mosaisism
Placenta previa

25. FETAL AND MATERNAL EFFECTS of IUGR
The effects depend on the gestational week at the onset of placental insufficiency
If placental insufficiency start early, clinical feature is severe, and results in miscarriage or stillbirth

26. MATERNAL EFFECTS of IUGR
Resistance to placental blood flow increases
Active placental mass decreases

27. FETAL EFFECTS of IUGR Appears early, Nutrient flow to fetus decrease,
Glucose mobilize from the hepatic storage,
Physical findings of growth restriction appear,
Metabolic, endocrine, hematological, cardiovascular and behavioral manifestations appear depending on the duration and severity of placental insufficiency

28. FETAL EFFECTS of IUGR Transfer of nutrients to fetus ↓
Size of placenta and fetus ↓
Fetal hypoglycemia
Gluconeogenesis from the hepatic storage
Transfer of amino acids ↓
Breakdown of the muscle proteins
Oxidative metabolism ↓ → Lactat accumulation → Acidemia

29. FETAL EFFECTS of IUGR Fetal hypoxia → erythropoietin secretion ↑
Polycythemia → hemoglobin ↑
Viscosity of blood ↑
Placental dysfunction
Immune system is effected
Immunoglobulins, B-cell count, WBC ↓
Risk of infectious complications ↑

30. FETAL EFFECTS of IUGR Early fetal cardiovascular effects
Transport of nutrients by umbilical vein decrease,
Nutrient flow to vital organs increase,
Umbilical blood flow much more shunts to fetal hearth by ductus venosus

31. FETAL EFFECTS of IUGR
Resistance to blood flow of cerebral artery decrease
Blood flow to myocardium and brain increase
Decrease in renal perfusion result in oligohydramnios.
Fetal movements and breathing decrease

32. FETAL CIRCULATION

33. DIAGNOSIS of IUGR Differential diagnosis: Maternal diseases
Placental insufficiency
Aneupoidy and non-aneuploid syndromes
Viral infections.

34. DIAGNOSIS of IUGR Determination of gestational age in early gestation,
Maternal weight gain,
Measurement of the symphysis-fundal height
Serial ultrasonography,
Definitive diagnosis may be impossible until delivery.

35. DIAGNOSIS of IUGR Measurement of the symphysis-fundal height
Simple, cheaper, reliable
Able to diagnose 40 percent of cases.
Between 18 and 30 weeks’ gestation, the uterine fundal height in centimeters coincides within 2 weeks of gestational age.
If the measurement is more than 2 to 3 cm from the expected height, inappropriate fetal growth is suspected.

36. DIAGNOSIS of IUGR-ULTRASONOGRAPHY
Fetal biometry:
CRL (Crown-rump length)
BPD (Biparietal diameter), HC (Head circumference), TCD (Trans cerebellar Diameter)
Serial AC (Abdominal circumference) measurement in two week interval is the most invaluable measurement (<10 p).
Sonography fetal weight estimation
Ultrasound is not able to diagnose 30 percent of cases.

37. DIAGNOSIS of IUGR-ULTRASONOGRAPHY

38. DIAGNOSIS of IUGR-ULTRASONOGRAPHY
Initial sonography examination—usually at 16 to 20 weeks’ gestation establishes gestational age and identify anomalies.
Anatomical defects, markers of aneuploidies and non-aneuploid syndromes are detected by ultrasonography
Combining head, abdomen, and femur dimensions has been shown to optimize accuracy
Fetal growth is evaluated by repeat sonography evaluation at 32 to 34 weeks

39. DIAGNOSIS of IUGR-ULTRASONOGRAPHY
Amniotic Fluid Volume measurement:
Hypoxia and diminished renal blood flow has been hypothesized as an explanation for oligohydramnios.
Oligohydramnios increases prenatal mortality.
Single vertical pocket > 2 cm is normal,
<1 cm ↓(oligohydramnios)
Four quadrant amniotic Fluid index (AFI)
<5 cm ↓ (oligohidramnios)

40. DOPPLER VELOCIMETRY Is both diagnostic and observation method
Fetal arterial and venous blood flow is evaluated.
Arterial Doppler: vascular resistance is evaluated
Blood flow velocity Waveform is evaluated by:
Ratio of Systolic/Diastolic velocities (S/D),
Resistance index (RI) and
Pulsatility index (PI)

41. DOPPLER VELOCIMETRY Umbilical artery Doppler velocimetry:
As resistance to flow increase, end-diastolic flow decreases and disappears (absent end-diastolic flow)
Reversed arterial flow during diastole (negative S/D ratio) is an ominous sign that may precede fetal demise.

42. DOPPLER VELOCIMETRY Uterine artery Doppler velocimetry: Indexes ↑
Early diastolic notch is observed
Normal
Early diastolic notch

43. DOPPLER VELOCIMETRY Other vessels: Doppler of Ductus venosus
Middle cerebral artery
Abdominal aorta
Renal artery

44. MANAGEMENT
If fetal-growth restriction is suspected, then efforts are made
to confirm the diagnosis,
To assess fetal condition, and
To search for possible causes.

45. MANAGEMENT
If there is a strong suspicion of fetal anomalies, patient counseling and prenatal diagnostic testing are indicated
The timing of delivery is crucial, and the risks of fetal death versus the hazards of preterm delivery must be considered.

47. MANAGEMENT Important factors for management
Gestational age and fetal maturity
Basic pathology and associated medical pathologies
Type of IUGR
Presence of congenital defects
Oligohydramnios
Results of fetal surveillance tests: (Echography, CTG, acoustic stimulation test, fetal movements, umbilical Doppler, fetal hemodynamic pattern, biophysical profile,etc)

48. PREVENTION OF IUGR Important factors for management Primary prevention
Secondary prevention
Tertiary prevention

49. PRIMARY PREVENTION
Primary prevention is applied during periconceptional period:
Smoking cessation,
Counseling about Toxoplasmosis,
Vaccination to prevent Rubella,
Early diagnosis of associated abnormalities
Prevention of multiple gestation during ART
Preventive strategies to prevent IUGR associated preeclampsia (contact to sperm, prevention of obesity and insuline resistance)

50. SECONDARY PREVENTION
Aim is to detect and treat the disease during preclinical period
Maternal serum screenings are disappointing: Increased AFP and hCG accompanies IUGR, but are poor screening tests.
Increased Uterine artery resistance : plays a significant role in the management.

51. TERTIARY PREVENTION Aim is to decrease fetal mortality and morbidity:
Therapeutic strategies,
Timing of delivery

52. THERAPEUTIC STRATEGIES
Nutritional supplementation
Bed rest
Dextrose and amino acid perfusion
Maternal hemodilution
Beta mimetics
Sedative agents
Heparine and anticoagulants
Oxygen
Asetyl salisilic acid, dipridamole
Sex steroids
Atrial natriuretic peptid
Intra amniotic therapy
Giving nutrient directly to fetus
Nitric oxide liberators
Immunological treatments

53. THERAPEUTIC STRATEGIES
Therapeutic strategies are dissapointing
There is no specific treatment
Frequently, modified bed rest is offered

54. TIMING of DELIVERY There is no definitive treatment of IUGR,
So, timing of delivery is important
Risks of prematurity must be balanced against to fetal risks.
After 24 to 28 weeks, neonatal mortality ↓
After 32 weeks, morbidity ↓

55. TIMING of DELIVERY Management of IUGR near term
Immediate delivery is the best approach,
If there is oligohydramniosis, delivery is recommended
If fetal heart rate is normal, vaginal delivery is preferable.
The fetus can not tolerate delivery, cesarean section is recommended.

56. TIMING of DELIVERY Preterm IUGR >34 weeks:
If fetal growth stops, delivery is planned.
Fetal lung maturity is confirmed by amniocentesis
To accelerate fetal lung maturity, corticosteroid therapy is recommended.

57. TIMING of DELIVERY Preterm IUGR <34 weeks:
If fetal anatomy and fetal tests are normal, observation is preferable.
If fetal growth progress and fetal test are normal, fetus is observed until fetal maturity
Fetal growth is evaluated by serial sonography

58. TIMING of DELIVERY Between 27-34 weeks:
If there is fetal risk, delivery may be planned.
To accelerate fetal lung maturity, corticosteroid therapy is recommended
Between weeks:
Fetus is immature during this period.
Perinatal mortality is 50%
So, maternal condition is the most important to choose interventions (e.g: preeclampsia)

59. LABOR AND DELIVERY
Oligohydramnios causes compression of umbilical cord
Fetus must be observed closely in the intrapartum period.
Rate of cesarean delivery ↑
Fetal hypoxia and meconium aspiration ↑
Staff proficient in resuscitative techniques must be available.

60. LABOR AND DELIVERY Conditions Requiring Birth
If fetal growth does not progress during 3 weeks period.
Oligohydramnios
Abnormal venous Doppler, reverse diastolic flow in umbilical artery , low score of biophysical profile, or deceleration in cardiotocography
Disorders of acid-base balance in fetal blood drawn by cordocentesis

61. ROUTE of DELIVERY
Two of 3 fetus with IUGR are able to tolerate vaginal delivery
Rate of cesarean delivery: %
Decision about labor induction or cesarean depends on:
Conditions of the fetus,
Special obstetric characteristics (Parity, presentation, cervical ripening)

62. REFERENCES
Williams Obstetrics 24.th edition-Cunningham et al. The McGraw-Hill Companies-2014
Gabbe: Obstetrics: Normal and Problem Pregnancies, 6th ed., 2013
Current Obstetrics & Gyneacology , McGrawHill, LANGE, 12 th edition 2015