Metabolic Adaptation to Birth and Lactation

Transition from Fetus to Infant

Five BIG changes

(1) Fuel metabolism: prior to birth, the fetus receives all of its energy from the mother’s blood glucose. After birth the infant must maintain its own blood glucose.
(2) Change from fetal to adult circulation: the closing of embryonic shunts
(3) Respiration: air is in the lungs
(4) Excretion: through the kidneys, no longer through the placenta
(5) Homeostasis: endogenous regulation of pH, H₂O balance, temp, etc, instead of the maternal environment.

While in utero, the fetus has lots of Insulin around to deal with mom’s blood glucose. After birth Insulin levels plummet, glucagon levels rise, and glucocorticoid levels drop, all three resulting in what is essentially a catabolic state. (Ý cAMP)

Thyroid Stimulating Hormone has a surge at birth and subsides within 24 hrs. Function is uncertain.

Metabolic Changes in the Perinatal Period

During the late fetal period, the fetus makes the enzymes necessary for glycogen synthesis (glycogen synthase, phosphoglucomutase, glycogen phosphorylase) and starts to store glycogen.

At the end of the third trimester the fetus makes the enzymes necessary for gluconeogensis except for PEPCK. After birth, PEPCK is synthesized once its promoter C/EBPa is turned on by Ý cAMP. (the Ý cAMP is due Ý epinephrine from the stress of birth). The Ý cAMP also causes the breakdown of glycogen (remember Ý cAMP activates phosphorylase kinase which activates glycogen phosphorylase) Within hours the infant is able to make glucose.

The infant’s blood glucose drops to ~40g/dL one hr after birth. It comes back up, along with an increase in Free Fatty Acids (FFA’s), because of Ý Epi and ß Insulin levels immediately after birth.

Very premature infants may not have these enzymes turned on and may lack glycogen. Without IV Glucose, these preemies will be unable to maintain their blood glucose at a level that is compatible with a seizure free life.

At birth the infant has only 4grams/kg (16kcal/kg) of glycogen stored. This equals ~4 hr supply. Infants typically need 100grams/kg in their first day. The 160g/kg of fat that the fetus stored in the last month of pregnancy is what helps the fetus maintain it energy.

Babies born to uncontrolled diabetic mothers are bigger and fatter than normal due to the effects of their own overactive pancreas hypersecreting Insulin to compensate for mom’s high serum glucose. After birth, these infants can suffer hypoglycemia because they can not stop hypersecreting Insulin rapidly enough to allow the transition from a maternal to an endogenous glucose source.

Considerations in Nutrition of Premature Infants

Difficulties in delivery of nutrients

Incomplete intestinal development

Potential for more rapid growth (remember the most rapid growth occurs between weeks 32-36, at a 3% increase/day)

Narrow range between too little and too much

Lactation – "provides everything the infant needs" (nutrition and mother/child bonding)

Human milk is used as the reference standard. In formula, cow’s milk is "cut" with oil and lactose to resemble human milk. (cow’s milk has too much protein, especially casein, and too much Ca²⁺ and PO₄^-)

Premature infants require milk with a higher energy content, higher protein content (more lactalbumin = more essential amino acids) and more medium chain fatty acids (absorbed directly). Preemies also need extra Ca²⁺ and PO₄^- to allow for normal bone development.

Premature infants have only recently been able to survive and therefore are not reflected in the evolution of human milk.

Recipe for mature human milk

40% of energy is CHO (lactose) – 20 kcal/oz (1/2 is from fat / long chain fatty acids)
6% protein (lactalbumin and casein) – Ca²⁺ and PO₄^-(less than cow’s milk but good for baby)

How milk is made

Pregnancy induces secretory cells in the mammary gland to produce milk in response to the Lactogenic Complex (Insulin, Estrogen, glucocorticoids, and Prolactin) and Placental Lactagens. If any one of these is missing – No milk.

Ý Progesterone, from the placenta inhibits this process until after birth when the placenta is gone.

Suckling causes Ý oxytocin. This stimulates the myoepithelial cells that surround the milk acini to contract forcing the milk into the ducts. The milk travels through ducts to reach the nipple. This process can be negatively influenced by stress, embarrassment, fear, etc.

The gene for a - lactalbumin is turned on selectively in the mammary gland. The binding of a -lactalbumin to the ER enzyme galactosyl transferase (which normally takes UDP-Galactose + Glucose Þ D-Galactosyl-N-acetyl-glucosamine) causes galactosyl transferase to take UDP Galactose + Glucose Þ Lactose.