Chapter Forty-Nine. Adaptation to extrauterine life 2
gastrointestinal, metabolic, neural and immunological considerations
Introduction
The human placenta is a discoid haemochorial organ that usually connects to a small part of the internal aspects of the uterus (see Ch. 12). It has many functions including serving as a metabolic unit capable of exchanging nutrients and metabolic waste products between mother and embryo/fetus. At term, in a single pregnancy, a normal placenta and its membranes weigh 450–500 g averaging 12% of the neonate’s body weight. After birth, these physiological processes are supported by the neonate’s own systems.
The gastrointestinal tract
Neonatal characteristics
The embryological development of the gut is described in Chapter 11 and it may be necessary to revise this before reading on. Significant anatomical and physiological limitations exist in the neonatal gastrointestinal (GI) tract, many of which may be partly attributed to the requirement of the fetus to swallow amniotic fluid (Polin & Fox 2004). The swallowing of small boluses of amniotic fluid may be fundamental to the patency of the GI tract. Although the fetal GI tract seems not to serve any nutritional purposes, it must process nutrients after birth.
The oral cavity
The walls of the oral cavity should be well formed with a central, short, broad but freely moveable tongue accommodated comfortably within it. The hard palate is slightly arched and gently corrugated by 5 or 6 irregular transverse folds which assist with suckling. Neonates have a high epiglottis that makes direct contact with the soft palate. As milk passes from the mouth to the pharynx, the larynx is elevated so that its opening is above the level of the oral cavity. The high position of the larynx, further elevated during suckling, directs its opening into the nasopharynx enabling neonates to breath when they suckle. Although neonates are thought to be obligate nose breathers, oral breathing occurs in the presence of nasal occlusion (Rodenstein 1985).
The stomach at birth
The neonate’s stomach has a small capacity, holding only 15–30 ml at birth, but increasing rapidly within the first few weeks. Neonatal swallowing may distend/enlarge the stomach capacity by 4 or 5 times and shift its position relative to other viscera. Gastric emptying time is initially slow, averaging 2–3 h. This is influenced by nutrient digestibility: for example, carbohydrates increase emptying time while fats decrease it. The presence of mucus in the stomach during the first 24–48 h can delay gastric emptying, whereas weakness of the cardiac sphincter contributes to milk regurgitation.
Gastric acidity at birth equals that of an adult, but the pH rises gradually to alkaline values because of a fall in hydrochloric acid production. This rise in pH allows commensals essential to the production of vitamin K and vitamin B complex to colonise the large bowel but also allows pathogens to survive, making the baby vulnerable to infection (Michie 1999). Furthermore during the first 6 months the intestinal mucosal barrier remains immature, allowing the transport of antigens and other macromolecules across the epithelium into the systemic circulation. However, maternal colostrum is rich in antibodies and helps the passage of meconium so that the risk of systemic infection is reduced. Postnatal maturation of the gut is stimulated by increases in peptide hormones such as gastrin and motilin (see Ch. 21), which are secreted following the commencement of feeding.
At term the neonate’s small intestine averages 300 cm in length and the large intestine averages 66 cm in length (Collins 2004); both intestines share a diameter of about 1 cm. Both forms of intestine have many secretory glands and villi but the muscular structures are weak and poorly developed. The villi increase the intestine’s absorptive surface area. As the haustra are not present for 6 months, the external surface of the large intestine appears smooth. Term neonates have a relatively long rectum that should connect to a patent anus. Digestive enzymes are synthesised and released as required. However, the relative deficiency of amylase and lipase causes difficulties in digesting carbohydrates and fats. The entry of food into the stomach induces a gastrocolic reflex, resulting in ileocaecal valve opening. As the ileal contents enter the colon they stimulate forceful peristalsis accompanied by a reflex emptying of the rectum (Michie 1999).
Meconium
Meconium is a dark, rather sticky substance that collects in the intestines of the fetus from the 16th week and forms the first stools of the neonate. Its presence may ensure the patency of the intestine. Its characteristic viscid consistency and greenish-black colour is attributed to the accumulation of digestive enzymes, intestinal gland secretions, bile salts and components of amniotic fluid such as vernix, lanugo, fatty acids, epithelial cells, mucus and blood cells (Blackburn 2003). Initially, meconium is sterile but within 24 h of birth it begins to be colonised with bacteria, largely in response to enteral feeding. Most neonates pass meconium within 24 h of birth and failure to do so could be an early indication of intestinal malformation, malfunction, obstruction such as imperforate anus or cystic fibrosis.
Milk feeding induces a change in the neonate’s stools. As digested milk enters the colon, a gradual transition results in stools that are fairly liquid and yellow-brownish in appearance. Following this, the consistency and frequency of the stools depends on the type of feeding. Breastfed babies pass loose, bright yellow, inoffensive stools on average 6–10 times in 24 h in the earlier days to once a day when feeding is established. By contrast, bottle-fed babies pass paler, more formed stools with a recognisable smell and generally less frequently with a tendency towards constipation.
The liver
The fetal liver is a proportionally large organ and the liver in mature neonates accounts for 4–5% of total body weight. Although immature, it is considered to be the central organ of homeostasis. The neonatal liver has less than 20% of the hepatocytes found in an adult liver and ongoing mitosis is critical to the development of a functionally mature organ.
At birth, although physiologically immature, the liver produces small quantities of enzymes which metabolise substances by utilising oxidative and conjugation processes. One of the major functions that the liver must be capable of is the synthesis of glucuronyl transferase, which is essential for bilirubin conjugation. Shortfalls in this enzyme lead to a rise in plasma values of unconjugated bilirubin. This situation is often exacerbated by the breakdown of superfluous erythrocytes during the first 6 weeks of postnatal life. Binding of unconjugated bilirubin to fatty tissue contributes to a transient neonatal jaundice on the 3rd–5th days. Feeding stimulates liver function and bacterial colonisation of the gut which in turn stimulates vitamin K production crucial to normal coagulation.
Metabolism
Fetal metabolic processes are mainly anabolic, required to support rapid growth. After birth neonates must support their own metabolic needs by utilising essential nutrients and gases as fuels. These adaptive changes are energy demanding. The fetus prepares for independence by laying down a store of glycogen and lipids during the last few weeks of gestation; fetal blood glucose during the last trimester averages 80% of maternal blood glucose concentration (Carlton 2003). However, nutrient reserves are fairly limited and most neonates require an intake of glucose, protein, fat and water within the first few hours of birth. The risk of a neonate developing hypoglycaemia is considerable. The relative excess water in neonates confers no protection against dehydration since the daily turnover of water equals 15–20%. Evaporative water loss is also costly in energy terms as the loss of 1 g of water causes the loss of 0.6 kcal of heat.
After birth, body heat production is attributed to brown adipose tissue and hepatic tri-iodothyronine synthesis which facilitates the transition from a net anabolic state to a catabolic state as glycogen and lipid reserves are mobilised to meet the metabolic increase (Blackburn 2003). These adaptations are influenced by factors such as maternal nutrition in late pregnancy, neonatal maturity, respiratory function and the ambient humidity and temperature.
Glucose metabolism
Glucose is the major substrate for carbohydrate metabolism in newborn babies (Garrow & James 2006). At birth, neonatal plasma glucose concentration depends upon such factors as the timing of the last maternal meal, the duration and nature of labour and delivery and the type and quantity of intravenous fluid administered to the labouring mother. After birth, as the neonate loses the maternal glucose source, falling plasma insulin levels and slow production of insulin prevent cellular uptake of glucose. This is coupled with an increase in serum glucagon levels which mobilise glucose from the intracellular glycogen stores.
Hepatic glycogen stores decrease rapidly as 90% is utilised by the neonate within the first 24 h after birth. Muscle glycogen is also reduced by 50–80%. After birth, gluconeogenesis is regulated by changes in the serum insulin:glucose ratio, catecholamine release, fatty acid oxidation and activation of liver gluconeogenic enzymes. The concentration of hepatic enzymes increases for the next 1–4 days. Lactose is the principal carbohydrate in human milk and many milk formulae, and term neonates consume 10–12 g/100 kcal/day.
Neonatal blood glucose falls to the lowest values between 2 and 6 h after birth, stabilises, then rises and equilibrates at about 3.6 mmol/L as he adapts to the extrauterine environment (Dodds 1996). Most paediatricians believe that the lowest safe level for neonatal blood glucose is not less than 2 mmol/L (Koh & Vong 1996). The method of feeding can influence neonatal blood glucose levels. The average neonatal blood glucose level in 132 breastfed term babies was found to be 3.6 mmol/L with a range of 1.5–5.3 mmol/L (Hawdon et al 1992). These values are significantly lower than blood glucose values found in bottle-fed neonates.
Fat metabolism
Lipolysis increases rapidly after birth, reaching a maximum within a few hours of birth and adult levels by 24 h, resulting in a rise in plasma free fatty acids. During this time about two-thirds of neonatal energy is produced from fat oxidation, the major form of neonatal stored calories.
The major differences between human milk and formula milk are the absence of long-chain unsaturated fatty acids in formulae compared with high concentrations of long-chain unsaturated fatty acids and cholesterol in mature human milk (see Ch. 56). The fat content in colostrum averages 2%, but phospholipids and cholesterol are found in higher concentrations. Mature human milk has a fat content of 3.5–4.5% contained within membrane-enclosed fat globules, whose core consists of triglycerides which permits dispersion of the lipids in the milk and protects them from hydrolysis by milk lipase.
Alternative fat stores and ketone body release are stimulated by the release of catecholamines associated with the body cooling following birth. Ketone bodies are produced during fatty acid metabolism and these form important metabolites. Similarly, acetate is metabolised by the mitochondria and contributes to further energy release. Ketone bodies may be a major energy source for the developing brain and the myocardium (Polin & Fox 2004).
Protein metabolism
Whereas the basic fetal cellular building blocks are supplied by the placenta, the neonate has to digest milk proteins into amino acids and oligopeptides which requires proteolytic enzymes. The relatively high concentration of free amino acids and peptides in human milk probably enhances the release of gastrin and cholecystokinin, which promotes the release of the proteolytic enzymes. The neonate’s ability to synthesise protein is limited, due to hepatic immaturity. As a consequence, serum amino acid levels are higher in the first few weeks and there is significant urinary amino acid excretion. Protein synthesis in mature fetuses and neonates is greater than later in life and this excessive protein turnover could be attributed to the significant remodelling during a period of rapid cell differentiation and tissue growth (Philipps & Sherman 2003).
Calcium, phosphorus and magnesium balance
Compared with maternal blood values, most neonates manifest hypercalcaemia and hyperphosphataemia.
Calcium
Calcium is the most abundant mineral in the body and at term most newborn babies have accumulated between 20 and 30 g of it, 80% of which is accrued in the last trimester of pregnancy (Polin & Fox 2004). Of this, 99% is located in the neonate’s developing skeleton. Serum calcium exists in three separate fractions:
1. Protein-bound calcium represents approximately 40% of the total serum concentration, with albumin serving as the primary binding protein.
2. Calcium is also bound to other anions such as citrate, phosphate, bicarbonate and sulphate.
3. Free, ionised calcium, which is the physiologically active form of calcium.
The ultimate balance in plasma calcium is partly determined by an ongoing exchange between the skeletal system, muscles, the intestine and the kidneys (Garrow & James 2006). This movement of calcium is controlled by parathyroid hormone, 1,25-dihydroxycholecalciferol and calcitonin. Calcium metabolism is also influenced by growth hormones, corticosteroids and some locally acting hormones and co-factors including cytokines.
The normal range for blood calcium in a neonate is 1.8–2.2 mmol/L. During the first 2 days of life serum calcium levels fall and there is a physiological hypocalcaemia, increasing back to normal between 5 and 10 mmol/L once intestinal absorption of calcium matures. Renal excretion of calcium is efficient and continues to increase in conjunction with glomerular filtration rate.
Neonatal aspects of calcium metabolism
• As serum calcium levels decrease parathyroid hormone (PTH) levels increase. By 3–4 days the parathyroid glands are responding adequately to calcium levels.
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