Fetal Endocrine and Autocrine/Paracrine-Acting Growth Factor Effects on Fetal Growth In IUGR.

 Fetal Endocrine and Autocrine/Paracrine-Acting Growth Factor Effects on Fetal Growth In IUGR.

Fetal hormones promote growth (and development) in utero by altering both the metabolism and gene expression of fetal tissues.

A.    Insulin:

Insulin has direct mitogenic effects on cellular development and cell number. It also enhances glucose consumption and limits protein breakdown. The latter effects are associated with reduced fetal growth when insulin concentration is low.

Thus, insulin deficiency, directly and indirectly, results in a decrease in fetal nutrient supply.

 

B.    Insulin-Like Growth Factor-I:

IGF-1 is a major anabolic hormone in fetal development. IGF-I is positively regulated by glucose supply in the fetus.

IGF-I probably can regulate metabolic processes that affect fetal protein balance and growth, but these have been difficult to measure.

Human IUGR fetuses have decreased plasma IGF-I concentrations.

Mutations in the Igf1 and Igf1r genes in humans cause both intrauterine and postnatal growth restriction.

C.    Thyroid Hormones:

In all species, fetal thyroid hormone deficiency or reduced free thyroxine (T4) produces developmental abnormalities in certain tissues and reduced growth.

Fetal hypothyroidism decreases oxygen consumption and oxidation of glucose, thereby potentially decreasing fetal energy supply for growth. Hypothyroidism also can decrease circulating and tissue concentrations of IGF-I.

FETAL NUTRIENT UPTAKE AND METABOLISM AND REGULATION OF FETAL GROWTH IN IUGR.

 FETAL NUTRIENT UPTAKE AND METABOLISM AND REGULATION OF FETAL GROWTH  In IUGR .

1. Glucose Uptake, Metabolism:

First, relative fetal hypoglycemia is an important and natural compensatory mechanism that helps to maintain the maternal-to-fetal glucose concentration gradient and thus the transport of glucose across the placenta to the fetus.

Despite this compensation, fetal hypoglycemia limits tissue glucose uptake directly by diminished mass action and indirectly by limiting fetal insulin secretion and thus the effect of insulin to promote tissue glucose uptake by skeletal muscle, heart, adipose tissue, and liver.

Reduced glucose supply alone decreases fetal growth rate and oxygen consumption rate (metabolic rate) proportionally.

Insulin also normally suppresses hepatic glucose production and release, and it acts as an anabolic hormone that increases net protein balance by inhibiting protein breakdown. Thus, a decrease in fetal plasma insulin concentration initially may allow fetal glucose production to take place, thereby providing glucose for both fetal and placental needs, but subsequently, combined with hypoglycemia, results in increased protein breakdown and decreased protein accretion.

Circulating concentrations and tissue-specific expression of growth factors such as IGF-I also are decreased during fetal hypoglycemia, which may contribute to increased fetal protein breakdown and decreased rates of fetal growth.

Thus, fetal hypoglycemia in response to a decrease in maternal glucose supply acts to maintain fetal glucose supply, but it also leads to lower anabolic hormone concentrations, which limit the rate of fetal growth, thereby decreasing fetal nutrient needs.

Patterns of Intrauterine Growth Restriction.

 Patterns of Intrauterine Growth Restriction.

1.  Symmetric or non-symmetric:

	Symmetric	Non-symmetric
Onset	Early	Late
Incidence	less common ≈ 30% of FGR cases	more common ≈ 70%–80% of cases
Pattern of retardation	Symmetric, Infants have reductions in all organ systems with the body, head, and length proportionally affected.	Asymmetric, Infants have disproportionate growth restriction in which head circumference is preserved, length is somewhat affected but may be spared, and weight is compromised to a greater degree. The weight deficit is principally due to a reduction in fat deposition, particularly during the 3rd trimester of pregnancy. The disproportion is due to the redistribution of blood flow during fetal development with preferential perfusion of the brain, heart and adrenal glands at the expense of the kidney, GIT and liver, limbs and SC tissues.
	Reduction in cell number.	Reduction of cell size.
Head size	Decreased	Normal
Ponderal index	Normal	Decreased
Catch up growth	Less	More
Genetic growth potential	Not attainable	Attainable
Amniotic fluid	typically accompanied by normal amniotic fluid volume but may be accompanied by polyhydramnios if there is reduced fetal swallowing of amniotic fluid, e.g. trisomy 21 or GIT anomalies.	often oligohydramnios, which is a result of chronic stress on the fetus and reduced urine production.
Causes	usually is caused by intrinsic factors such as congenital   infections or chromosomal abnormalities, maternal drug and alcohol abuse or a chronic medical condition or malnutrition.	usually is caused by Extrinsic factors such as   disorders of the placenta or from maternal problems e.g uteroplacental dysfunction secondary to maternal pre-eclampsia, multiple pregnancy, maternal smoking or may be idiopathic.
Prognosis	poor prognosis, these infants are more likely to remain small permanently, decreased nutrient supply early in development can restrict growth of all organs.	good prognosis, these infants rapidly put on weight after birth.

- Placental factors Causing IUGR.

 Placental factors Causing Intrauterine Growth
Restriction

· Placental insufficiency due to maternal disorders, such as pre-eclampsia and eclampsia, or due to post-term gestation.

Ü Presence of asymmetrically grown fetus, low amniotic fluid index, and umbilical artery abnormalities (abnormal waveforms, absent or reversed end-diastolic flows) together suggests placental insufficiency.

·     Gross cord and placental abnormalities:

–       Single umbilical artery.

–       Abnormal umbilical vascular insertions (marginal cord insertion, circumvallate, velamentous).

–       bilobed placenta

–       circumvallate placenta.

–       multiple infarcts

–       umbilical vascular thrombosis and hemangiomas.

–       Infectious villitis (as with TORCH infections)

·     Placental mesenchymal dysplasia is a rare placental abnormality characterized by placentomegaly and grape-like vesicles resembling a partial mole. The euploid fetus with these findings is at increased risk for FGR, perinatal death, and Beckwith-Wiedemann syndrome.

·     Multiple gestations may be associated with significant placental problems such as abnormal vascular anastomoses and inability of the uteroplacental environment to meet the nutritional needs of multiple fetuses.

·     Abruption (chronic, partial).

·     Placenta previa