Fetal Growth and Genetics Quiz

Fetal Growth Factors

• Birth weight is a crucial factor for neonatal survival and infant health
• Energy reserves are significantly influenced by birth weight, with a correlation between weight and non-protein kcal and total kcal intake.
• Birth weight is a critical determinant of neonatal morbidity and mortality.
• Intrauterine growth retardation (IUGR)/small for gestational age (SGA) fetuses develop many complications. They're predisposed to hypoglycemia, hypocalcemia, hypothermia, asphyxia, and cognitive dysfunction
• Intrauterine growth retardation (IUGR) with rapid catch-up weight gain in early childhood may correlate with increased risks of adult-onset type 2 diabetes, hypertension, preeclampsia, dyslipidemia, and ischemic heart disease
• Large for gestational age (LGA) infants are also at risk. They're predisposed to childhood weight gain, type 2 diabetes mellitus (DM), and metabolic syndrome.
• Fetal growth is characterized by distinct stages of hyperplasia, hyperplasia/hypertrophy, and hypertrophy based on weeks of gestation

Fetal Growth & Development

• The femur's growth velocity and length correlate with gestational weeks, with peak velocity occurring around weeks 16-32.
• Growth hormone (GH) affects fetal growth post-birth, not pre-birth. Fetal growth is normal if GH is knocked out. IGF-1 and IGF-2 are not regulated by GH during fetal development.
• IGF-I plays a role in fetal development and impacts birth weight, and also affects growth after birth.
• Knockout of the IGF-I gene leads to slow fetal development and low birth weights that exhibit continued growth impairment after birth.
• IGF-II plays a key role in fetal growth, impacting development and showing a normal growth rate post-birth after knockout of this gene.

Types of IUGR

• Symmetrical IUGR: affects all body parts equally (head circumference, abdominal circumference, femur length), one-third of cases, associated with early insult affecting cell number (e.g., intrauterine infection, karyotype anomaly, or genetic syndrome).
• Asymmetrical IUGR (often referred to as "nutritional"): Body parts are not equally affected with the abdominal circumference growth impaired in relation to head circumference growth. This is associated with placental insufficiency late in the 2nd or 3rd trimesters, with lower abdominal circumference vs head circumference and femur length. Glycogen utilization by the liver, liver shrinkage, and decreased abdominal circumference may be observed in this type of IUGR.

Factors Affecting Fetal Growth

• Genetics: Account for 30-70% variability. A two-fold increased risk of IUGR is associated with women who were small for gestational age (SGA) themselves
• Physical Environment:
• Placental Capacity: Essential for proper nutrient transfer to the fetus
• Nutrient Availability: Maternal nutritional status impacts fetal development
• Interaction Between Genetics and Environment: Altered fetal gene expression by the maternal uterine environment
• Adverse Conditions: Preeclampsia, maternal/fetal malnutrition, smoking, alcohol use, high/low salt intake, certain drugs, and hypo/hyper-vitaminosis are factors negatively affecting fetal growth. Adverse conditions lead to epigenetic modifications impacting DNA and affect fetal development, including birth weight (and potential low nephron number). Also correlated to renal disease, cardiovascular disease, or metabolic disease.

Hormonal Regulation & Effects

• Insulin: Weak correlation with birth length, strong correlation with birth weight, low levels observed in SGA/IUGR fetuses.
• IGF-1: Strong correlation with both birth length and weight, Low levels observed in SGA/IUGR fetuses.
• IGF-2: Weak correlation with birth length, variable correlation with birth weight, low levels of IGF-2 observed in SGA/IUGR fetuses.
• IGFBP-1: Decreased levels related to negatively impacting birth weight and linear growth
• IGFBP-3: Increased levels observed in IUGR fetuses.
• Cortisol (Stress, Prescribed): Negatively correlates with birth length. Increased glucocorticoids can lead to increased IGFBP-1 levels and inhibit linear growth.
• Sex Steroids: Slightly greater birth length and weight in boys compared to girls.
• Thyroid Hormones: Crucial for normal fetal growth and development. They influence overall fetal size and contribute to discrete developmental events in the brain and somatic tissues. Thyroid hormones directly and indirectly affect fetal metabolism and impact the bioavailability of other hormones affecting fetal development.

Hormone Levels in Fetuses

• Hormone levels (IGF-1, IGFBP-3, IGFBP-1, insulin) differ between control fetuses and IUGR fetuses. Data available from 1994 study.

This quiz explores the intricate relationship between genetics and fetal growth, focusing on factors that affect intrauterine growth restriction (IUGR). It delves into the roles of specific genes like GH and IGF-I in development, as well as the implications of nutritional issues and other conditions on neonatal health. Test your knowledge on the predictors of survival, growth patterns, and potential risks associated with fetal growth abnormalities.