1. The Small for Gestational Age Infant
Perinatology Division
Department of Child Health
Medical School
University of Sumatera Utara

2. Small For Gestational Age (SGA)
Definition
Birth weight or birth crown-heel length
<2 SD for gestational age, based on data derived from a reference population
SGA has also been defined as birth weight or length below the 10th, 5th, or 3rd percentile for gestational age
International SGA Advisory Board Consensus Development Conference Statement: PEDIATRICS Vol. 111 No. 6 June 2003, pp

4. SGA vs. IUGR SGA and IUGR are not synonymous
SGA refers to the size of the infant at birth and not fetal growth
IUGR suggests diminished intrauterine growth velocity
IUGR indicates the presence of a pathologic process in-utero that inhibits fetal growth

5. SGA vs. IUGR A child who is born SGA is not always IUGR
Infants born after a short period of IUGR are not always SGA
SGA:
IUGR
Constitutionally small infant

6. Fetal Growth
Up to 20 wk, fetal growth is due primarily to increase in cell number with rapid mitosis and an increase in DNA content (hyperplastic stage)
20-28 wk: declining mitosis and an increase in cell size
After 28 wks: rapid increase in cell size and accumulation of fat, muscle and connective tissue (hypertrophic stage)

7. Fetal Growth
Eighty-five percent of fetal weight gain occurs during the second half of pregnancy
Fat deposition mainly in 3rd trimester
Fetal weight gain is constant in 1st and 2nd trimesters
Fetal weight gain accelerates in 3rd trimester and then declines near term

8. Etiology Maternal factors Reduced uteroplacental blood flow
Preeclampsia-eclampsia
Chronic renovascular disease
Chronic hypertensive vascular disease
Maternal Malnutrition
Multiple pregnancy
Maternal hypoxemia

9. Maternal factors Drugs
Cigarettes: Infants of smokers weigh 150g to 200g less than non-smokers
Alcohol abuse: Fetal alcohol syndrome
Heroin/cocaine/methamphetamines:
55% of neonates born to heroin addicted mothers weigh <2500g
Antiepileptics, Antimetabolites, Steroids,
also smaller in all dimensions including length,
head circumference, abdominal circumference and
chest circumference. They are usually symmetrical
IUGR. Smokers have a three times greater risk of
IUGR than nonsmokers. A study in 1998 by Scott,
Moar, and Ounsted attributed as much as 40% of all
cases of IUGR in the industrialized world on
cigarette smoking. Smoking more than 20
cigarettes coupled with increased maternal age
(>28 years) is associated with the greatest risk
of IUGR.
b. Alcohol abuse: Fetal alcohol syndrome (FAS)
consists of malformations including growth
restriction, abnormal facies, CNS effects, limb
deformations and heart anomalies. The incidence
of FAS varies from 11% in mild drinkers, 19% in
moderate, 32% in heavy drinkers. The effects of
alcohol appear to be dose related.
c. Heroin/cocaine/metamphetamines and other elicit
drug use. Up to 55% of neonates born to heroin
addicted mothers weigh <2500 grams, with a higher
incidence of both growth retarded fetuses and
preterm deliveries. Heroin usually produces
symmetrical IUGR.
d. Use of other drugs or chemical agents such as
antileptics, antimetabolites, steroids, and
coumadin.
e. Other maternal factors are short stature, young
age, and grand multiparity

10. Others maternal factors
Maternal short stature
Young maternal age
Short interpregnancy interval
Uterine anomalies
Low sosioeconomic class
Primiparity
Grand multiparity

11. 2. Placental Factors Utero-placental insufficiency resulting from:
Improper / inadequate trophoblastic invasion and placentation in the first trimester
Aberrant placental insertion
Reduced maternal blood flow to the placental bed (thrombosis, infarcts, hemangioma)
The etiologic role of micronutrients in IUGR remains to be clarified. The best evidence concerning their importance derives from randomized trials and from systematic overviews of those trials contained in the Cochrane Collaboration Pregnancy and Childbirth database. Unfortunately, there are few supplementation or fortification trials in developing country settings where deficiencies in these micronutrients are prevalent. Trials are required to define the possible etiologic roles of iron, calcium, vitamin D, and vitamin A, especially in developing countries. The evidence concerning folate, magnesium, and zinc also looks sufficiently promising to justify further investigation.
The physiologic and molecular mechanisms by which nutritional or other determinants affect fetal growth are incompletely understood. Growth is determined not only by substrate availability but also by the integrity of physiologic processes necessary to ensure transfer of nutrients and oxygen to the developing fetus. Expansion of maternal plasma volume, maintenance of uterine blood flow, and development of adequate placentation are key physiologic mechanisms required for optimal fetal growth. All substances used by the fetus are transported by the placenta: some (like oxygen and most other gases) by passive diffusion, others by facilitated transport proteins (e.g., Glut 1 for glucose), and still others (e.g., amino acids) by active energy-dependent transport processes. Insulin-like growth factors (IGFs) are important mediators of substrate incorporation into fetal tissue. IGF1 appears to induce cell differentiation, including (perhaps) oligodendrocyte development in the brain, whereas IGF2 may function to stimulate mitosis. It remains uncertain whether these physiologic and molecular mechanisms are merely the final common pathways for genetic or environmental determinants of IUGR, or whether they themselves vary (favorably or pathologically) independently of those determinants.

12. Placental Factors Feto-placetal insufficiency due to:
Vascular anomalies of placenta and cord
Decreased placental functioning mass:
Small placenta, abruptio placenta, placenta previa, post term pregnancy.
The etiologic role of micronutrients in IUGR remains to be clarified. The best evidence concerning their importance derives from randomized trials and from systematic overviews of those trials contained in the Cochrane Collaboration Pregnancy and Childbirth database. Unfortunately, there are few supplementation or fortification trials in developing country settings where deficiencies in these micronutrients are prevalent. Trials are required to define the possible etiologic roles of iron, calcium, vitamin D, and vitamin A, especially in developing countries. The evidence concerning folate, magnesium, and zinc also looks sufficiently promising to justify further investigation.
The physiologic and molecular mechanisms by which nutritional or other determinants affect fetal growth are incompletely understood. Growth is determined not only by substrate availability but also by the integrity of physiologic processes necessary to ensure transfer of nutrients and oxygen to the developing fetus. Expansion of maternal plasma volume, maintenance of uterine blood flow, and development of adequate placentation are key physiologic mechanisms required for optimal fetal growth. All substances used by the fetus are transported by the placenta: some (like oxygen and most other gases) by passive diffusion, others by facilitated transport proteins (e.g., Glut 1 for glucose), and still others (e.g., amino acids) by active energy-dependent transport processes. Insulin-like growth factors (IGFs) are important mediators of substrate incorporation into fetal tissue. IGF1 appears to induce cell differentiation, including (perhaps) oligodendrocyte development in the brain, whereas IGF2 may function to stimulate mitosis. It remains uncertain whether these physiologic and molecular mechanisms are merely the final common pathways for genetic or environmental determinants of IUGR, or whether they themselves vary (favorably or pathologically) independently of those determinants.

13. 3. Fetal Factors Genetic Chromosomal anomalies:10% of SGA infants
Congenital malformations
Congenital infection: TORCH
Fetal cardiovascular anomalies
Inborn error of metabolism
Genetic factors: Potential for growth is influenced by
racial, ethnic, sexual, and parental endowment
(familial short stature and familial slow maturation).
Recent studies have shown that maternal genes exert the
main influence of fetal growth in utero. There are
also environmental differences including socioeconomic
factors which can influence growth including
nutritional status and exposure to teratogens.
2. Chromosomal diseases: Fetal retarded growth is a
feature of trisomies (21,18, and 13) and many
syndromes, (Turner syndrome, X polysomy, dwarfism,
chondrodystrophies, Osteogenesis Imperfecta, etc..)
Chromosomal disorders occur in approximately 10% of
IUGR neonates.
3. Congenital anomalies: Anomalies of almost any organ
system can be associated with IUGR. CNS,
gastrointestinal, renal abnormalities, Pituitary growth
hormone deficiency, Hypothyroidism, metabolic disorders
such as hypercalcemia, hypophosphatemic rickets,
hypokalemia, galactosemia, glycogen storage disease,
salt-losing congenital adrenal hyperplasia. Also
cardiovascular abnormalities such has left to right
shunting and renal dysfunction can cause restriction.
4. Congenital infection: There are usually anatomic
findings and certain abnormal lab findings also
associated with these infections.
Feto-fetal transfusion

15. Classification Symmetrical Asymmetrical
Baby's head and body are proportionately small
May occur when the fetus experiences a problem during early development
Baby's head and length are preserved
Occur when the fetus experiences a problem later in pregnancy
Application of the international foetal growth reference curve will vary according to its specific clinical and public health uses or purposes. Criteria for diagnosis of foetal growth restriction (e.g., SGA) should be related to evidence of increased risk for perinatal mortality and/or other indices of adverse outcomes. The new reference should provide percentiles [(e.g., 3rd, 5th, 10th, 15th, 25th, 50th (median), 75th, 85th, 90th, 95th, and 97th)] as well as z-scores [(e.g., -3, -2, -1, 0 (mean), 1, 2, and 3 SD)], so that health planners and practitioners can use the most appropriate cut off based on local circumstances.
Proportionality at birth may be related to adverse outcomes. Thus there is a need to develop reference data for birth length and head circumference in relation to GA, and for birth weight in relation to birth length. Because the concepts of 'wasting' and 'stunting' have proven useful for categorizing undernourished infants and older children, an attempt should be made to quantify the mortality and morbidity risks associated with 'wasted' and 'stunted' newborns and to develop indicators for their classification.
In a normal infant, the brain weighs about three times more than the liver. In asymmetrical IUGR, the brain can weigh five or six times more than the liver.

16. Types of SGA / IUGR Early onset growth restriction
Symmetric IUGR Type I
Early onset growth restriction
Uniform growth restriction
Long-term growth failure
Associated with decreased cell number
Associated with less catch-up growth in the first year of life
Asymmetric IUGR Type II
Late onset growth restriction
Head Sparing
Potentially reversible
Associated with decreased cell size
Infants demonstrate more catch-up growth than symmetric IUGR in first year of life

17. Diagnosis Antenatal Presence of risk factors
Inadequate growth detected by serial measurement of weight, abdominal girth and fundal height
Ultrasound evaluation of fetal growth
Inadequate fetal growth
Placental calcification
IUGR can be difficult to diagnose and in many cases doctors are not able to make an exact diagnosis until the baby is born. A mother who has had a growth restricted baby is at risk of having another during a later pregnancy. Such mothers are closely monitored during pregnancy. The length in weeks of the pregnancy must be carefully determined so that the doctor will know if development and weight gain are appropriate. Checking the mother's weight and abdomen measurements can help diagnose cases when there are no other risk factors present. Measuring the girth of the abdomen is often used as a tool for diagnosing IUGR. During pregnancy, the healthcare provider will use a tape measure to record the height of the upper portion of the uterus (the uterine fundal height). As the pregnancy continues and the baby grows, the uterus stretches upward in the direction of the mother's head. Between 18 and 30 weeks of gestation, the uterine fundal height (in cm.) equals the weeks of gestation. If the uterine fundal height is more than 2-3 cm below normal, then IUGR is suspected. Ultrasound is used to evaluate the growth of the baby. Usually, IUGR is diagnosed after week 32 of pregnancy. This is during the phase of rapid growth when the baby should be gaining more weight. IUGR caused by genetic factors or infection may sometimes be detected earlier.

18. Diagnosis Neonatal Low ponderal index ([weight(g)/length³ (cm)] x 100)
Decreased subcutaneous fat with soft tissue, desquamated skin, meconium stained
Widened cranial sutures with large fontanelles
IUGR can be difficult to diagnose and in many cases doctors are not able to make an exact diagnosis until the baby is born. A mother who has had a growth restricted baby is at risk of having another during a later pregnancy. Such mothers are closely monitored during pregnancy. The length in weeks of the pregnancy must be carefully determined so that the doctor will know if development and weight gain are appropriate. Checking the mother's weight and abdomen measurements can help diagnose cases when there are no other risk factors present. Measuring the girth of the abdomen is often used as a tool for diagnosing IUGR. During pregnancy, the healthcare provider will use a tape measure to record the height of the upper portion of the uterus (the uterine fundal height). As the pregnancy continues and the baby grows, the uterus stretches upward in the direction of the mother's head. Between 18 and 30 weeks of gestation, the uterine fundal height (in cm.) equals the weeks of gestation. If the uterine fundal height is more than 2-3 cm below normal, then IUGR is suspected. Ultrasound is used to evaluate the growth of the baby. Usually, IUGR is diagnosed after week 32 of pregnancy. This is during the phase of rapid growth when the baby should be gaining more weight. IUGR caused by genetic factors or infection may sometimes be detected earlier.

19. Neonatal Thin umbilical cord Skin and sole creases more mature than GA
‘‘alert-looking’’ and jittery
Congenital malformations
Stigmata of congenital infections

20. Neonate and Placenta in IUGR
Normal & IUGR Newborn babies
Normal & IUGR Placentas

21. Small for gestational age

22. Problems Associated With Impaired Fetal Growth
Short-term morbidity
Long-term outcomes

23. Short-term morbidity Still birth Prematurity Fetal distress in labor
MAS
Perinatal depression / Asphyxia
Persistent Pulmonary Hypertension
RDS

24. Short-term morbidity Hypoglycemia: 12-24%
Hyperviscosity-polycythemia Syndrome: 15-17%
Poor Thermoregulation
Hypocalcemia
Thrombocytopenia/Neutropenia
Poor humoral and cellular immunity
NEC

25. Long term morbidity Cognitive & Neuro-developmental outcome
Effects on childhood growth
Predisposition to adult onset diseases

26. Cognitive & Neuro-Developmental Outcome
Strong association between poor prenatal head growth (symmetric IUGR) and poor developmental outcome
However, neurodevelopmental outcome in infants with ‘fetal brain sparing’ (asymmetrical IUGR) is less clear cut

27. Prevention Prenatal intervention strategies include:
Protein/energy supplementation
Treatment of anaemia
Vitamin/mineral supplementation
Fish oil supplementation
Prevention and treatment of
Hypertensive disorders,
Fetal compromise
Infection
A systematic review of 126 available randomized controlled trials (RCTs) has been carried out to summarize the efficacy of 36 prenatal interventions aimed at reducing IUGR. Strategies include prenatal care modalities, protein/energy supplementation, treatment of anemia, vitamin/mineral supplementation, fish oil supplementation, and prevention and treatment of hypertensive disorders, fetal compromise, and infection. Based on this review, few statistically significant reductions in the risk of IUGR have been demonstrated with these interventions. However, the point estimate (average effect) associated with some interventions suggests a potential effect of considerable magnitude; these interventions should be further evaluated by targeting populations at risk for IUGR, increasing sample size, and addressing coexisting factors limiting growth. Studies should be conducted in developed as well as developing countries.

28. Prevention
Strong evidence of benefit only for the following interventions:
Balanced protein/energy supplementation
Strategies to reduce maternal smoking,
Treatment of TB and urinary tract infections
Anti-malarial prophylaxis
A systematic review of 126 available randomized controlled trials (RCTs) has been carried out to summarize the efficacy of 36 prenatal interventions aimed at reducing IUGR. Strategies include prenatal care modalities, protein/energy supplementation, treatment of anemia, vitamin/mineral supplementation, fish oil supplementation, and prevention and treatment of hypertensive disorders, fetal compromise, and infection. Based on this review, few statistically significant reductions in the risk of IUGR have been demonstrated with these interventions. However, the point estimate (average effect) associated with some interventions suggests a potential effect of considerable magnitude; these interventions should be further evaluated by targeting populations at risk for IUGR, increasing sample size, and addressing coexisting factors limiting growth. Studies should be conducted in developed as well as developing countries.

29. thank you