Fetal Growth Restriction

Chapter 36. Fetal Growth Restriction


December 1. 1st year of resident Cho. S. B.

• < 2,500 g => low birthweight
  
• Intra-uterine growth retardation -> fetal growth resriction

I. Definition

• Small for gestational age ; 10th percentile for their gestational age
  
  => increased risk for neonatal death (1967, Battalgia and Lubchencho)
  
  
  
  
• < 5th percentile
  
  2 standard deviation => 3 % of birth ; growth restriction
  
  -> most meaningful from a clinical standpoint
  
  
  
• Figure 36-1
  
  
  
  
• Manning and Hohler (1991)
  
  ; 25 to 60 % of infants conventionally diagnosed to be small for gestational age
  
  => in fact appropriately grown when determinants of birthweight such as
  
  maternal ehtnic group, parity, weight and height are considered

1. Normal Infants Birthweight

• Figure 36-2

2. Mortality and Morbidity

1. Fetal growth restriction is associated with substantive perinatal morbidity and
   mortality ; fetal demise, birth asphyxia, neonatal hypoglycemia, hypodermia,
   abnormal neurologic problems
   
   
   
   
2. Long-term prognosis -> related to etiologies of fetal growth restriction
   viral or congenital abnormality Vs placental insufficiency

3. Accelarated Maturation

1. Accelrated fetal pulmonary maturation in complicated pregnancy associated with
   growth restriction (Perelman and colleagues, 1985)
   by reponding to stressed condition by increasing adrenal glucocorticoid secretion (Laatikainen 1988).
   
   
   
   
2. Owen and associates (1990)
   
   
   
   
3. 178 pregnancies delivered primariliy because of hypertention Vs 159 pregnancies delivered because of preterm labor or ruptured membranes
   
   => no difference of survival rate
   
   
   
   
4. Friedmann and colleagues (1995)

4. Symmetric Versus Asymmetric Fetal Growth Restriction

1. Fetal growth phases
   
   first phase ; conception to early second trimester
   
   => cellular hyperplasia
   
   second phase ; to late second trimester
   
   => cellular hyperplasia and hypertrophy
   
   third phase ; cellular hypertrophy
   
   
   
   
2. The head and abdominal proportions in growth restricted fetus would reveal
   both timing and nature of the insult of abnormal growth.
   
   
   
   
3. Symmetric growth restriction
   
   
   
   
   
   
   • Due to chemical exposure, viral infection in early pregnancy, anueploidy
     
     -> theoretically result in a relative reduction in cell number and size
     
     asymmetric growth restriction
     
     
     
     
   • Due to late pregnancy insult (placental insufficiency by hypertention)
     
     -> diminished glucose transfer and preferential shunting of oxygen and
     
     nutrients to brain ; abnormal hesd to abdominal circumference ratio
   
   
   
   
4. Nicolades and co-authors (1991)
   
   
   
   
   
   • The ratio of fetal head to abdominal circumferences in 376 growth restricted person with aneuplody ; asymmetrical pattern
     
     
     
     
   • Salafia and co-authors (1995)
     
     with uteroplacental insufficency ; symmetric pattern
   
   
   
   
5. Crane and Kopta (1980)
   
   the concept of brain sparing was erraneous and could not be used to diagnose
   
   the cause of indivisual fetal growth restriction

II. Risk Factors for Fetal Growth Restriciton



1. Constituionally Small Mothers

• small women typically have small babies -> not pathological event

2. Poor Maternal Weight Gain and Nutrition

1. average or low weight , lack of weight gain throghout pregnancy
   
   => associated with fetal growth restriction (Simpson and colleagues)
   
   lack of weight gain in second trimester
   
   => strongly correlated with decreased birthweight (Abrams and Selvin, 1995)
   
   
   
   
2. restriction of calories => affect fetal growth minimally

3. Social Deprivation

• associated with lifestyle factors such as smoking, alcohol, substanse abuse
  poor nutrition

4. Fetal Infection

1. Viral, bacterial, protozoal, and spirochetal infections => 20 % of fetal growth
   restrictions
   
   
   
   
   
2. Rubella
   
   Cytomegalovirus
   
   Hepatitis A and B
   
   Listeriosis, tuberculosis and syphilis
   
   Toxoplasmosis
   
   Malaria

5. Congenital Malformations

1. 13,000 infants with major structural anomalies, 22 percent had accompanying
   growth restriction (Khoury and associates 1988)
   
   
   
   
2. Especially in fetuses with chromosomal abnormalities or those with serious
   cardiovascular malformations

6. Chromosomal Abnormalities

1. Placentas of fetuses with autosomal trisomies have a reduced number
   of
   small muscular arteries in the tertiary stem villi (Rochelson and associate, 1990)
   
   -> placental insufficiency and primary celluar growth and differentiation
   
   
   
   
2. Trisomy 21
   
   
   
   
   
   • Fetal growth restriction is mild and postnatal growth failure is prominent
     
     
   • After first trimester, the length of all long bones in fetuses with trisomy 21
     lags behind those of normal fetuses
     
     
   • Shortend femur length and hypoplasia of the middle phlanx
   
   
   
   
3. Trisomy 18
   
   
   
   
   
   • Significant fetal growth restriction
     
     
   • Growth failure has been noted as early as the first trimester
     
     
   • In the second trimester, all long bones
     
     -> below the third percentile and upper extremities are more affected
     
     
   • Visceral organ growth is also abnormal

7. Trisomy 16

1. Most common trisomy in spontaneous abortions and usually lethal to fetuses in
   nonmosaic state
   
   
   
   
2. The spots of trisomy in the placenta -called confined placental mosaicism -
   
   lead to placental insufficiency that account for many cases of previously unexplained fetal growth restriction (Kalousek and colleauges, 1993)
   
   => chromosomal abnormalities confined to placenta

8. Primary Disorders of Cartilage and Bone

• Osteogenesis imperfecta and other chondrodystrophies
  
  => fetal growth restriction (+)

9. Chemical Teratogens

anticonvulsants

Tobacco

Narcotics

Alcohol

Coccaine

10. Vascular Disease

• Chronic vascular disease, especially superimposed preeclampsia
  
  -> commonly cause fetal growth restriction

11. Chronic Renal Disease

• Renal insufficiency -> accompanied by fetal growth restriction

12. Chronic Hypoxia

1. Fetuses of women who reside at high altitude usually weigh than those born to
   women who live at a lower altitude
   
   
   
   
2. Fetuses of women with cyanotic heart disease are also frequently growth restricted

13. Maternal Anemia

1. Generally does not cause growth restriction exept in those with sickle cell anemia or other inherited anemias associated with serious maternal disease
   
   
   
2. Deficient maternal total blood volume early in pregnancy
   
   -> fetal growth restriction

14. Placental and Cord Abnomalities

1. Chronic partial placental seperation, extensive infarction, chorioangioma,
   a curcumvallate or a placenta previa, marginal insertion of the cord and
   especially velamentous insertion
   
   -> more likely to be accompanied by fetal growth restriction
   
   
   
   
2. Uteroplacental insufficiency
   
   
   
   
   
   • women with otherwise unexplained fetal growth restriction demonstrated fourfold
     reduction in uteroplacental blood flow compared with normally grown fetuses
     (Lunell and Lylund, 1992)
     
     
     
   • macrosomic infants do not have increased uteroplacental blood flow
     

15. Multiple Fetuses



- Fetal growth restriction -> 10 to 50 % of twins




16. Antiphospholipid Antibody Syndrome

• Anticardiolipin antibodies and lupus anticoagulant -> associated with fetal growth restriction
  
  
  
• Poor pregnancy outcome, early onset preeclampsia, and second or third trimester
  fetal demise
  
  
  
• Maternal placental aggregation and placental thrombosis

17. Extrauterine Pregnancy

- Usually growth restricted

some uterine malformations

III. Additional Insights into Human Fetal Growth Restrction




1. Soothill and colleuges (1987)

1. Measurement of umbilical venous pO2, pCO2, pH, lactate and glucose concentration
   nucleated red cell count, and hemoglobin concentrations
   
   
   
2. The severity of fetal hypoxia corelated with fetal hypercapnia, acidosis, lactic
   acidosis, hypoglycemia, and erythroblastosis.

2. Economides and colleagues (1989)

1. Major cause of hypoglycemia in small-for-gestational-age fetuses is reduced supply rather than increased consumption or decreased endogenous glucose production
   
   
   
   
2. Hypoinsulinemia and hypoglycemia the degree of growth restriction did not correlate with plasma insulin level
   
   
   
   
3. Glycine/valine ratio measurement -> same as Kwashiorkor patient and protein
   deprivation is correlated with fetal hypoxia
   
   
   
   
4. Plasma triglyceride concentration
   
   -> elevated and correlated with the degree of fetal hypoxemia

3. Van den Hof and Nicolades (1990)

1. Thrombocytopenia in growth restricted fetuses
   
   
   
2. Platelet abnormalities is correlated the degree of growth restriction, hypoxemia, and acidemia

4. Elevated adenosine concentrations, interleukin-10, placental atrial natriuretic peptide plasma endothelin-1

• Defect in epidermal growth factor function
  
• Chronic reduction in nitrous oxide

5. Fetal heart rate monitoring and fetal blood gases (Visser and collegues)

1. Repetitive fetal heart rate decelerations -> best identified fetal growth restrictions
   
   
   
   
2. Low normal pO2 and fetal heart rate acceleration -> indicate the abscence of
   potenially degrees of hypoxemia and acidosis

6. Elevated concentrations of cellular fibronectin




IV. Screening and Identification of Fetal Growth Restriction



1. Uterine Fundal Height

1. A simple, safe, inexpensive, and reasonably accurate screening method
   
   
2. Correctly identified 40 % of such infants
   
   
3. Jimenez and colleagues 1983
   
   
   
   
   
   • from the top of the symphysis to top of the uterine fundus
     
     
   • 18 to 30 weeks, uterine fundal height coincides with weeks of gestations
     
     
   • more than 2 to 3 cm from the expected height -> inappropriate fetal growth may
     be suspected

2. Ultrasonic Measurement

1. Abdominal circumference measurement -> most reliable index of fetal size
   
   
   
2. Ultrasonic estimate of fetal growth during the third trimester significantly increased diagnosis of small-for-gestational-age fetuses.
   
   Elective delivery increased without overall improvement of neonatal mortality
   and morbidity
   
   
   
3. Oligohydroamnios and fetal growth restriction

• Figure 36-5.6.7.8

3. Doppler Velocimetry in Fetal Growth Restriction

1. Umblical artery S/D ratio, fetal growth restriction and adverse perinatal outcome in high risk populations -> 75 to 95 % ranged sensitivities
   
   in screening programs involoving general obstetrical populations -> 15 to 30 %
   
   
   
   
   
2. Alstrom and collegues (1992)
   
   a randomized, controlled trial compared Doppler velocimetry with standard
   nonstressing testing in fetuses with presumed growth restrictions
   
   -> did not improve perinatal outcome but did demonstrate significantly fewer
   cesarian delivery

V. Manegement of Fetal growth Restriction



1. Growth Restricion Near Term

1. Prompt delivery
   
   
   
   
2. In the prescence of significant oligohydroamnios
   
   -> vaginal delivery Vs Cesarean delivery
   
   
   
   
3. Uncertainty about the diagnosis of fetal restriction should preclude intervention until fetal lung maturity is assured
   
   
   
   
4. Expectant management

2. Growth Restriction Remote from Term

1. Diagnosed prior to 34 weeks, and amniotic fluid volume and antepartum fetal
   surveillance test is normal -> observation
   
   ; amniocentesis is helpful in clinical decsion making
   
   
   
   
2. In fetal growth restriction remote from term, there is no specific treatment that will ameliorate the condition
   
   
   
   
3. Weiner and collegues (1996)
   
   nonstress test, biophysical profiles, and umblical artery velocimetry within 3 days of delivery in 135 growth restricted fetuses
   
   ; morbidity and mortality primarily by gestational age and birthweight and not
   by abnormal fetal testing
   
   
   
   
4. Low dose aspirin, oxygen therapy

VI. Labor and Delivery

1. Throughout labor, should be monitored for evidence of compromise
   
2. Placental insuficiency and cord compression -> aggravated by labor
   
3. Infant needs a expert assistance in making a successful transition to air breathing

VII. Subsequent Deveolpment of the Growth-restricted Fetus

1. Symmetric case => slow growth rate
   
   asymmetric case => catch up normal growth
   
   
   
2. Neurological development

VIII. Fetal Growth Restriction in Subsequent Pregnancies

• Increased particulary in a women with a history of fetal growth restriction and a continuing medical problems.