Fetal Growth Factors : MD137 Lecture VII PDF

MD137 Factors that Control Growth In Utero  Fetal Growth Birth weight is a What controls it? significant predictor of neonatal and infant survival Universi...

MD137 Factors that Control Growth In Utero  Fetal Growth Birth weight is a What controls it? significant predictor of neonatal and infant survival Universi ofGalwa ty y.i e  Fetal Growth Birth Weight is a critical determinant of neonatal morbidity and mortality Intrauterine growth retardation/small for gestational age Predisposed to hypoglycemia, hypocalcemia, hypothermia, asphyxia, and cognitive dysfunction IUGR with rapid catch-up weight gain in early childhood Increased risk for adult-onset type 2 diabetes, hypertension, preeclampsia, dyslipidemia, and ischemic heart disease Large for gestational age (LGA) infants Predisposed to childhood weight gain, type 2 DM, metabolic University ofGalway. syndrome ie Fetal Growth University ofGalway. ie University ofGalway. ie  Symmetric I.U.G.R. 1/3 of all cases Fetus is proportionally small Head circumference (HC), Abdominal circumference (AC) and femur length (FL) Diagnosed early Early insult affecting cell number (intrauterine infection, karyotype anomaly, genetic syndrome) University ofGalway. ie Asymmetric I.U.G.R. “Nutritional” Placental insufficiency, late 2nd/3rd trimesters Lower AC growth vs normal HC and FL Glycogen utilization by liver, liver shrinkage, decreased AC Preferential shunting to brain thus maintained HC University ofGalway. ie Factors that affect foetal growth Genetics 30-70% of variability due to genetics Two-Fold Increased risk of IUGR in women who were SGA Physical Environment Placental Capacity Nutrient Availability Interaction Between The Two Altered foetal gene expression by the maternal University ofGalway. ie uterine environment Factors that affect foetal growth University ofGalway. ie  Some Observations in Knockout Mice: GH Knockout of the GH gene results in normal fetal growth, and normal birth-weight. However, after birth, growth is impaired. Together these results indicate that IGF-I and IGF-II are NOT regulated by GH during fetal development. Some Observations in Knockout Mice: IGF-I Knockout of the IGF-I gene also results in slow fetal development and low birth weights. However, these mice also display marked lack of growth after birth as well. Thus, IGF-I is important for growth at all stages of development (before and after birth). Some Observations in Knockout Mice: IGF- II Knockout of IGF-II gene results in slower fetal development, with low birth weights. However, after birth these mice grow at normal rates. This finding suggests that IGF-II is an important fetal growth factor, with unclear role in growth after birth.  Correlation Correlation Hormon Effect of Foetal with(CW) with(CW) e Deficiency or Excess Birth Length Birth Weight Large decrease in birth Weak CW weight Insulin Low in Strong CW Lesser decrease in birth SGA/IUGR length Strong CW Low birth weight *high CW fat-free Strong CW IGFBP-1 IGF-1 mass Low in Increased in LGA Severe IUGR - IGF-1 or SGA/IUGR IGF-1 receptor mutations Severe IUGR in Russell– Silver syndrome - loss of paternal expression of Weak CW IGF-2 Variably IGF-2 BUT Low in Foetal Overgrowth in correlated SGA/IUGR. Beckwith–Wiedemann syndrome- Overexpression of IGF-2  U The regulation of fetal growth n i v e r s i t Early gestation IGF-II y o f G a l w a GH IGFBP-1 y. i IGF-I e IGFBP-3 Late gestation Insulin Glucose and amino acid availability  Hormone levels in fetuses IGF-I (mcg/L) IGFBP-3 (mcg/L) IGFBP-1 (mcg/L) Insulin (mcU/ml) Control IUGR Langford KS, J Clin Endocrinol Metab 1994  Correlation Correlation with(CW) Hormone with(CW) Birth Weight Birth Length Negatively CW Glucocorticoid Xs Cortisol (endogenous or (Stress, exogenous) Reduces Variably increased in IUGR Prescribed) IGF-1 Increases IGFBP-1 Inhibits linear growth Birth length slightly Birth weight slightly greater Sex steroids greater in boys than in boys than girls. girls.  Thyroid hormones Essential for normal fetal growth and development Required for general fetal increased size Discrete developmental events in brain and somatic tissues Act directly through anabolic effects on fetal metabolism Act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors ofGalway. that University ie influence fetal development Catecholamines and insulin-like growth factors