Article summary with Hormonal changes associated with intra-uterine growth restriction: Impact on the developing brain and future neurodevelopment by Baud & Berkane - 2019

What is intra-uterine growth restriction?

Intra-uterine growth restriction (IUGR) is the inability of a fetus to reach its genetically determined size. Fetal growth depends on several maternal, fetal, and placental factors, in particular genetic background, nutrients, and oxygen supply to the fetus, maternal nutrition, and various growth factors and hormones.

How is IUGR related to brain development?

Suboptimal fetus growth is a key factor of disruption in brain development. Many neurodevelopmental disorders of motor and cognitive dysfunction have their origins in the antenatal period. Infants exposed to IUGR conditions are at high risk for neonatal death and cerebral palsy, neurodevelopmental morbidities (such as mental retardation), learning disabilities, and developmental behavioral disorders associated with the onset of neuropsychiatric disorders later in life.

What role do hormones play in fetal development?

Hormonal balance is very important in fetal growth and maturation, neonatal adaptation, parturition, and brain development. Hormones act as maturational and nutritional signals that control tissue development and differentiation and they interact closely with the in utero environment. Hormonal imbalance impairs fetal maturation and growth, and can also induce obstetrical, perinatal, and neonatal complications. Six dysregulated hormones are identified that are closely related to brain development and future neurobehavioral outcomes, namely glucocorticoids, oxytocin, estrogens, progesterone, insulin growth factor, and thyroid hormones.

How do glucocorticoids influence fetal development?

Glucocorticoids are key mediators of stress responses involved during fetal development in the regulation of fetal growth and maturation of fetal tissues and organs. Research results indicate that increased exposure of the fetus to glucocorticoids is associated with IUGR, postnatal hypertension, cardiovascular disease, increased postnatal activity in the HPA axis, postnatal glucose intolerance, and interference with fetal brain development.

How does oxytocin influence fetal development?

Oxytocin is an essential hormone during the perinatal period and parturition and is balanced against glucocorticoids. Oxytocin has been associated with autism and, in combination with IUGR, can lead to defective myelination and abnormal brain function.

How does sex steroid hormones influence fetal development?

Estriol and estradiol are two different forms of the female hormone known as estrogen. Progesterone is the hormone that supports pregnancy. The research shows different results and most were animal studies from which it is not always clear how the results translate to humans. Despite the limitations, the evidence increasingly supports that estradiol and progesterone play a key role in brain development and might be important modulators of brain vulnerability in the fetus with IUGR.

How does the insulin growth factor influence fetal development?

The regulation of fetal growth depends also on the regulation of Insulin-IGF/IGF binding protein 3 axis. The IGF factors I and II work together to control fetal growth through changes in size and function of the placenta:

• IGF-I acts as a nutrient sensor and regulates nutrient transfer across the placenta according to the maternal environment and fetal demand. The production of IGF-I is particularly sensitive to maternal undernutrition and parental imprinting. Disruption of this imprinting causes growth disorders, such as Beckwith-Wiedemann syndrome and Silver-Russell syndrome.
• IGF-II is important for placental growth and development. It allows more nutrients to reach the fetus.

How do thyroid hormones influence fetal development?

Thyroid hormones are essential for fetal brain development and maturation. Severe, mild, and subclinical neonatal hypothyroidism has been associated with neurodevelopmental impairment. Factors associated with neonatal hypothyroidism include prematurity and IUGR. The findings regarding the effect of IUGR on fetal serum concentration of thyroid hormones are conflicting.