Clinical perfusion endpoints in term neonates include a capillary refill time of <2 seconds, normal

pulses without differential between peripheral and central pulses, warm extremities, urine output

greater than 1 mL/kg/hr, low serum lactate, and mixed venous saturation of >70%.146 In premature

neonates, the mean arterial pressure (MAP) should be greater than or equal to 30 mm Hg.147 However,

a gestational age-based cutoff for “normal” blood pressure (goal MAP > GA) is used at many tertiary

centers, especially in the first 3 days after birth (Table 99-4).137

In term or older preterm infants, hypotension is generally managed with volume expansion (using 20

mL/kg of an isotonic solution with a repeat bolus as needed). In contrast, rapid volume expansion in

extremely premature infants has a significant risk of ICH in the first few days of life.108 Therefore, in

hypotensive premature neonates, after a single bolus of saline (10 mL/kg over 60 minutes), vasoactive

medications may be started.148,149 In cases of obvious acute volume loss in preterm infants, more

volume may be needed in addition.136

Dopamine (5 to 10 μg/kg/min) is generally the first vasoactive drug for neonates with shock.149

Patients with depressed myocardial function may benefit from infusion of dobutamine for both inotropy

and vasodilation. Dobutamine improves and maintains systemic blood flow better than dopamine but

can increase myocardial oxygen demand in high doses due to his chronotropic effect.150 With persistent

hypotension, glucocorticoids such as hydrocortisone,151 vasopressin,152 or other inotropes/vasoactive

agents may be needed. Epinephrine or norepinephrine infusions for refractory shock in neonates have

been studied to a very limited extent and should be considered for vasodilatory shock. Addition of these

agents (after fluids and dopamine/dobutamine) can improve blood pressure, reduce tissue lactate,

increase cerebral blood volume, and cerebral oxygen delivery in VLBW infants.153,154 Milrinone, a

phosphodiesterase inhibitor and potent pulmonary and systemic vasodilator, has not been well studied

in neonatal septic shock but is commonly used in pediatric patients with septic shock to increase cardiac

index, SV, and oxygen delivery while decreasing systemic vascular resistance without increasing HR or

blood pressure.150,155 Figure 99-5 demonstrates the management of neonatal and pediatric septic shock.

Congenital Heart Disease

Major neonatal cardiac abnormalities can be defined into two broad categories: acyanotic and cyanotic.

Acyanotic diseases do not present with hypoxia at birth and can be monitored over the next several

months. These conditions are grouped into those that increase pulmonary vascularity (from

overcirculation through the pulmonary vascular system) and those with ventricular tract outflow

obstruction.

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Figure 99-5. Management algorithms for septic shock in term and preterm neonates. (From Wynn JL, Wong HR. Pathophysiology

and treatment of septic shock in neonates. Clin Perinatol 2010;37(2):439–479, with permission.)

7 Ven tricular septal defect (VSD) is the most common heart defect occurring in nearly a third of

neonates with congenital heart disease, presenting at 2 to 6 weeks with a left-right shunt (depending on

size of the defect). Occasionally, neonates can present with Eisenmenger syndrome from a large VSD

and pulmonary vascular obstructive disease (either from an anatomic obstruction or persistent

pulmonary hypertension at birth), with resultant right-to-left shunt, cyanosis, and impending death.

These patients also have pulmonary hemorrhage, infections, and/or paradoxical emboli crossing over.

Surgical indications for VSD include uncontrolled congestive right heart failure, increased pulmonary

vascular resistance, failure to thrive despite maximal medical therapy with diuretics and fluid

restriction, recurrent pulmonary infections, endocarditis, or paradoxical emboli.

Atrial septal defect (ASD) is the third most common, occurring in approximately 8% to 10% of

patients with congenital heart disease. The symptoms depend on the size of defect and the relative

compliances of the right and left ventricles. Surgical indications include right ventricular overload,

arrhythmias, paradoxical emboli, and elevated pulmonary vascular resistance. AV septal defects,

occurring more commonly in patients with Down syndrome, can have symptoms of either VSD or ASD

and surgery is performed at 3 to 6 months to prevent consequences of pulmonary hypertension.

8 A PDA is when the connection between pulmonary artery to the descending aorta does not close

spontaneously in the first weeks of life. Symptoms (left-to-right shunt) depend on the size of PDA and

pressures in descending aorta and pulmonary artery. Fluid restriction is the first line of therapy when

appropriate with indomethacin reserved for persistent cases to help stimulate closure. In a few patients,

the duct will need to be ligated when symptomatic and not responsive to nonoperative measures.

Acyanotic cases with ventricular outflow tract obstruction can occur in aortic stenosis, coarctation of

the aorta, and pulmonic stenosis. In aortic stenosis, the commissures of the valve are fused and surgery

is indicated with the annulus is small and balloon valvuloplasty is unsuccessful. Coarctation can present

with shock in the first week after the DA spontaneously closes, and is managed with prostaglandin E1 to

keep the ductus open prior to surgical repair. Postoperatively, systemic hypertension is managed with

beta blockade. Pulmonic stenosis is the second most common cardiac disease and is secondary to the

fusion of commissures. It is treated with balloon valvuloplasty or surgery and valve replacement.

Cyanotic heart diseases with decreased pulmonary vascularity include tetralogy of Fallot and tricuspid

atresia. Tetralogy of Fallot accounts for 7% of all cardiac defects but is the most common cyanotic CHD.

The tetralogy is defined by (1) pulmonic stenosis, (2) VSD, (3) aorta overriding ventricular septum, and

(4) right ventricular hypertrophy. Classic “tetralogy spells” are due to elevated pulmonary pressures

and subsequent diversion of flow from pulmonary to systemic circulation, and resultant hypoxemia.

Infants further develop irritability, hypercapnia, and cyanosis. Treatment consists of knee-to-chest

position, oxygen, morphine, IV fluid, bicarbonate, and transfusion for anemia. Surgery is indicated for

increasing cyanosis or frequency of episodes.

Tricuspic atresia is a rare defect. The tricuspid valve lacks patency, and usually is associated with an

ASD or foramen ovale and a hypoplastic right ventricle or pulmonary outflow tract unless a VSD is also

present. The treatment consists of using a prostaglandin infusion to maintain DA patency, a modified

Blalock–Taussig shunt in the first week of life, modified bidirectional Glenn anastomosis (SVC to right

PA) at 6 to 9 months of age. A modified Fontan at 2 years of age is used to completely bypass right

heart with flow from SVC/IVC to PA.

Cyanotic heart diseases with increased pulmonary vascularity include transposition of the great

arteries, truncus arteriosus (TA), total anomalous pulmonary venous connection, and hypoplastic left

heart syndrome (HLHS). In transposition of great arteries, the aorta arises from right ventricle and

pulmonary artery from the left. The treatment is a stepwise approach with the use of a prostaglandin

infusion, followed by balloon septostomy and repair of the defect in the first week of life with an

arterial switch operation to reconnect each artery with the proper ventricle.

TA is a rare defect with a single vessel above both right and left ventricles with a large VSD. The

common vessel – TA – gives rise to the aorta, coronary arteries, and pulmonary arteries. TA is

associated with the DiGeorge sequence (thymic hypoplasia, third and fourth pharyngeal pouch

syndrome) and patients should be evaluated for hypocalcemia (hypoparathyroid) and T-cell

immunodeficiency (with only irradiated blood transfusions given to prevent graft-vs.-host disease). To

repair the defect, a conduit is created from right ventricle to pulmonary arteries with separation from

the TA which supplies the cardiac and systemic circulation. The VSD is also closed to allow for the left

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ventricle to empty into the TA.

Total anomalous pulmonary venous connection involves an abnormal connection of pulmonary

venous to systemic venous connections creating a cyanosis. Three subtypes exist: supracardiac to

innominate vein, intracardiac to coronary sinus, and infracardiac below diaphragm to hepatic, portal, or

umbilical venous systems. All subtypes require surgical repair upon presentation.

HLHS consists of stenosis of mitral and aortic valves, coarctation, and as the name suggests, a

hypoplastic left ventricle. HLHS presents with cyanosis and shock when the DA closes and the

management, similar to TA, is with a prostaglandin infusion to reopen the duct. Surgical correction

includes a Norwood procedure, which includes the Blalock–Taussig shunt, followed by a Glenn

procedure at 3 to 6 months and a modified Fontan at 2 years.

Renal Physiology

In utero, the fetus is nearly all water (94%) early in gestation and gradually decreases to 78% by term,

though most of the volume is still extracellular. Over the following week, another 3% to 5% reduction

occurs. Total body water continues to decline over the next year and a half (mostly in the extracellular

component) to approximately adult levels (60%). In premature infants, both fetal and neonatal excess

fluid is unloaded within the first week.

9 The glomerular filtration rate in neonates is lower than adults but quickly increases from 21 to 60

mL/min/1.73 m2 by 2 weeks and reaches adult levels by a year and a half. Furthermore, an infant

enduring water deprivation can only increase urine osmolality to 600 mOsm/kg, whereas adults can

concentrate to 1,200 mOsm/kg. Insensible water losses which decrease over time can be excessive in

preterm infants. Transepithelial water diffusion through the skin and through humidified inspired air

from the lungs can be greater than 120 mL/kg/d.

A neonate’s weight can be the best indicator of fluid status with the birth weight used to calculate

fluid/medication rates until a return to birth weight in 1 to 2 weeks. In premature infants insensible

losses from the respiratory tract account for 30%. From 1,500 to 2,500 g, fluid losses decrease from 30

to 60 mL/kg/d down to 10 to 15 mL/kg/d by about half with each 500 g increase in weight. In patients

with an ostomy, a nasogastric tube for drainage or increased stool output from malabsorption, there

may be substantial fluid and associated sodium losses that need to be accounted for in the administered

fluid.

Neonatal fluid requirements should be calculated using a combination of metabolic demands, preexisting fluid deficit, and continuing losses. Following a neonate’s urine output and concentration to

achieve an isotonic level of 280 mOsm/L, can help guide fluid administration. Augmenting this

information with frequent monitoring of serum sodium, BUN, creatinine, and osmolarity, and urine

sodium, creatinine and osmolarity allow titration of fluid to the infant’s response. In neonates with a

decreased urine output despite appropriate fluid administration, calculating a FeNa (fractional sodium

excretion) using the ratio of urine:serum sodium:creatinine values, helps differentiate prerenal causes

(FeNa <2) from acute tubular necrosis (FeNa >3).

Hypo- and hypernatremia are defined as values below 130 mmol/L or above 150 mmol/L,

respectively and reflect overall body fluid composition. With high urinary losses, hypoxic injury, or

diuretic use, there may be excessive sodium loss leading to hyponatremia. The replacement should be

done slowly over 24 to 48 hours by calculating the deficit ([desired level − actual level of sodium] ×

weight in kg × 0.6) and adding it to the maintenance fluid accounting for insensible losses. In low–

birth-weight infants, preemptively adding sodium enterally can be useful to prevent hyponatremia and

help with weight gain and growth.

Water retention can also lead to hyponatremia with excess dextrose solutions, renal failure or

congestive heart failure with fluid restriction usually the first-line treatment and rarely using hypertonic

saline if symptomatic to correct serum levels to 125 mmol/L. Occasionally, using diuretics can help with

excess fluid removal but at the cost of other electrolyte losses (potassium, calcium, magnesium).

With dehydration, and with renal or gastric losses, the sodium may actually rise with fluid deficits in

the 10% to 15% range. The correction should be done with caution over the next 24 to 48 hours by

calculating the water deficit ([1 − (serum sodium/140)] × weight in kg × 0.6). If the patient is

symptomatic (shock), resuscitation using 10 to 20 mL/kg saline from the total water deficit could be

helpful. Using hypotonic fluid can be deleterious if the cause is hypovolemia and replacement with

normal saline could correct the hypernatremia along with shock. In patients with hypervolemic

hypernatremia, the use of loop diuretics can help with removal of excess fluid and sodium.

Nutrition and Gastrointestinal Physiology

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10 A term newborn grows at 25 to 30 g/d over the first 6 months, doubling their birth weight by 5

months, tripling it by 12 months, four times the weight by 3 years, and a 20-fold increase over the first

decade.156 The body length increases by half in the first year and triples in the first decade. To sustain

this pace of growth, calorie supplementation in the neonate and premature infant is paramount.

The pace of growth for the preterm infant (less than 27 weeks) is substantially slower at 10 to 20 g/d

prior to the accelerated growth seen in the third trimester.157 Moreover, fat accounts for nearly 16% of

the birth weight in the term infant; whereas the premature infant has only 1% to 2% fat. Furthermore,

the premature infant loses nearly 15% of its birth weight in the initial 1 to 2 weeks of life. In contrast, a

term baby only loses about 7% to 10% of its weight. Therefore, though the caloric need remains high,

the growth rate and gestational age must be closely accounted for when providing said calories.

Assessment of caloric need in the surgical baby is further complicated by (1) a potentially

dysfunctional GI tract, (2) wound healing needs, and (3) any weight loss and malnutrition prior to

surgery. Anticipating postsurgical caloric needs begins with a subjective assessment of weight loss,

vomiting, fluid status, and muscle wasting, along with objective measures of weight on a standardized

growth curve, and differentiating chronic malnutrition using weight-to-height and head-circumference

measures. Biochemical measures such as albumin, prealbumin, and retinol-binding protein can be

inaccurate as do not have age-based norms, and can fluctuate with surgery and increased metabolic

demand.158 Bone age can be a useful measure for chronic malnutrition; however, can also be affected

with long-term TPN use in the surgical patient.159

As stated above, the energy needs of an infant vary by age and physiologic status. The recommended

daily calories and protein needs can fluctuate – therefore, the health care provider must carefully

monitor weight gain, fluid status, and changes in body morphomics to determine if the provided

calories match the needs of the baby. The most accurate method of measuring energy expenditure,

however, is indirect calorimetry.160

The primary enteral carbohydrate delivered to neonates is lactose.161 Lactase – the enzyme that

breakdown lactose – is commonly found in high levels in most children below the age of 3. Nonlactose

formulas are usually soy based and contain sucrose or corn syrup. Premature infants may not have

adequate lactase levels; therefore hydrolyzed mixtures with lactose and glucose polymers are commonly

provided.

Fats are an excellent source of energy (providing 9 kcal/g) and essential fatty acids. Withholding

lipids from a neonate can lead to fatty acid deficiency within 3 days.162 Manifestations of fatty acid

deficiency include scaly skin, hair loss, diarrhea, and impaired wound healing.163 Intralipid given with

parenteral nutrition, however, can also lead to liver disease and decreasing the amount given while

monitoring for fatty acid deficiency has been shown to decrease development of cholestasis.164

Of the 20 amino acids identified, 9 are considered essential in neonates. New tissue cannot be formed

unless all the essential amino acids are present in a diet simultaneously! Furthermore, these protein

requirements are higher in term neonates and infants (2 to 3 g/kg/d) than children, and even higher in

preterm infants (3 to 3.5 g/kg/d).165 The added protein needs, however, must be balanced with

development of uremia secondary to the immature kidney.

While the energy needs must be met using carbohydrates (50%), fat (35%), and protein (15%), the

fluid requirements, minerals and vitamin needs, and, trace elements must also be managed. Water

content of infants is 75% of the body weight compared to 60% in adults. In term neonates and preterm

infants, water makes up an even higher percentage. The daily consumption of fluid is nearly 10% to

15% of their body weight; compared to 2% to 4% in adults.

11 The enteral nutrition of choice is breast milk even in the premature or very low birth weight

(VLBW, less than 1,500 g) infant. The American Academy of Pediatrics recommends exclusive

breastfeeding for the first 6 months of life and continued breastfeeding for a year or more with the

introduction of solid foods.166 Benefits of human milk include “enhanced host defense, neurologic

development, and gastrointestinal function.”167 Human milk decreases the incidence and severity of

nosocomial infections and NEC, improves visual acuity and cognitive development,168 enhance gastric

motility and increases gastric emptying time allowing the infant to absorb nutrients more efficiently,

stimulates gastrointestinal growth and maturation, and provides protection of the gastrointestinal

mucosa, and decreases risk of feeding intolerance.169

The human-milk-fed premature infant might, however, still require nutrient supplementation, or

fortification, to maintain optimal nutritional status. Furthermore, despite hospital-grade double electric

breast pumps to initiate and maintain milk supply, pumping mothers struggle with low milk supply.170

Neonatal and infant formulas are commonly used as substitutes for human breast milk. Infants receiving

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formula, however, are 6.5 times more likely to develop NEC than those infants receiving human milk

diets alone. Use of donor human milk has been demonstrated “to decrease morbidity, nosocomial

infections, NEC, urinary tract infections, gastroesophageal reflux disease, diarrhea, and length of

hospital stay.”169 Pasteurization of donor milk does affect some nutritional and immunologic

components, but many immunoglobulins, enzymes, hormones, and growth factors are unchanged or

minimally decreased. Finally, symptoms of feeding intolerance, more commonly seen with formulafeeding, include vomiting, water-loss stools, increased abdominal girth, and increased gastric

residuals.169

Inadequate nutrient intake is common in premature infants for a variety of reasons including an

underdeveloped suck reflex, need for tube feeds, and, the variability in nutrient contents of the milk.

Feeding difficulties can occur twice as commonly in premature compared to term infants.171 Premature

infants less than 28 weeks have significant difficulties with initiation and progression to maximal

gavage and oral feedings. Typically, healthy premature infants achieve full oral feeding skills by 36 to

38 weeks.172 Nonnutritive sucking has been shown in premature infants to decrease in length of stay,

improved transition from tube to bottle feeds, and better bottle feeding performance and behavior.173

Continuous tube-feeding reduces fat delivery to the infant when compared with intermittent bolus

feeding.174 Differences in nutrient contents occur with milk and donor milk due to variable “milk

collection and storage, the feeding of ‘spot’ samples (individual samples of expressed milk from one or

both breasts, or milk partially expressed from one breast), and the use of feeding tubes.”167

Furthermore, the milk is often refrigerated and/or frozen. Finally, there is a significant decline in

protein from transitional to mature milk, and the concentrations of protein and sodium decline through

lactation; therefore, supplementation is often recommended in the premature infant.

Intolerance of feeds in neonates could be secondary to anatomic variations including obstruction (such

as congenital or acquired atresia) and dysmotility. Anatomic causes should be ruled out with imaging

studies (x-rays, followed by contrast studies). In neonates, ultrasound may be useful to identify external

obstructions such as enteric duplication cyst or mesenteric cyst. Bilious emesis in neonates requires an

immediate evaluation for malrotation and midgut volvulus. The use of ranitidine in neonates is

controversial and not recommended in premature infants due to its association with increasing incidence

of NEC.175

In neonates that cannot tolerate enteral feeds due to immaturity, congenital anomalies, or

hemodynamic instability, or enteral feeds do not meet caloric needs, the use of parental nutrition is

essential. As neonates and infants have limited reserves, the use of total parenteral nutrition (TPN)

should be fairly liberal. Premature infants may show signs of starvation in 1 to 2 days and young infants

require TPN if starvation extends 4 to 5 days, below the 7- to 10-day threshold used in adults.

Furthermore, the return of bowel function after surgery may be delayed in premature infants, and many

neonates on TPN have never been on full enteral feeds, encouraging the early use of TPN.

Neonates are usually maintained on a high dextrose solution for the first 2 days of life, unless a

prolonged starvation is anticipated. Dextrose concentrations in the TPN are generally started at 10% to

12.5%, as larger amounts are associated with hyperglycemia. The concentration is slowly increased to

20% to 25%, monitoring the levels along with electrolytes regularly. The risk of developing phlebitis in

peripheral veins increases when the osmolarity exceeds 600 to 900 mOsm/L,176 translating to

approximately 12.5% dextrose. Isotonic lipid infusions are also commonly coinfused with TPN

protecting the peripheral veins. Finally, cycling TPN under 24 hours usually requires the child to be

approximately 5 kg and to tolerate longer periods off TPN without development of hypoglycemia.

When ordering TPN, we start by calculating the total fluid and caloric needs of the child. We

generally order the lipids in quantities of g/kg/d, starting at 0.5 to 1, advancing to 3 by 0.5 to 1 each

day. Lipids will provide approximately 35% to 40% of the calories at goal. Protein is ordered next

starting at 0.5 to 1 g/kg/d, advancing by 0.5 to 1 each day, to a goal of 2.5 to 3 g/kg/d for a newborn

as stated above. Proteins should provide approximately 15% to 20% of the calories. Carbohydrates are

calculated to provide 45% to 50% of the calories, starting at 4 to 6 mg/kg/min and advancing by 1 to 2

to a goal of 12 mg/kg/min. The dextrose% multiplied by the total volume over a day (rate per hour

multiplied by 24 hours), times a constant 0.69, divided by the weight provides the mg/kg/min.

Additives to TPN are standard with vitamins, minerals, and trace elements. The electrolytes are ordered

based on laboratory values and the additives are adjusted for long term using laboratory values.

Generally, we monitor the chloride-acetate ratio based on the acid–base status and our goals for a given

patient, promoting the acetate to buffer a respiratory acidosis. Finally, the calcium-phosphate ratio is

adjusted to provide the maximum amounts without causing formation of a precipitate. As the

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calculations can quickly become complex, we recommend employing a dietician or pharmacist familiar

with neonatal TPN at institutions that commonly encounter the need to order long-term TPN in

neonates.

Complications of TPN are categorized into metabolic, hepatobiliary, mechanical, and infectious.

Metabolic complications include hyper- and hypoglycemia, metabolic derangements such as acid–base

disturbances, electrolyte abnormalities, and metabolic bone disease. Hyperglycemia is secondary to

excessive dextrose infused or rapid increase in the concentration. Hyperglycemia can result in osmotic

diuresis, dehydration, electrolyte abnormalities, impaired phagocytosis, and liver steatosis.177,178

Therapy for hyperglycemia includes lowering the rate of infusion, despite the loss in calories. If

hyperglycemia continues, an insulin drip, separated from the TPN due an unpredictable response to

insulin by neonates, can be started. Hypoglycemia occurs with a sudden drop in the rate of glucose

provided. As mentioned above, cycling is not safe in this age group, and discontinuation of TPN should

be done only after decreasing the rate over 1 to 2 hours. Metabolic acidosis from excess chloride or

cysteine hydrochloride can cause acidosis; whereas excess acetate can cause alkalosis. Electrolyte

abnormalities can occur with any of the following: sodium, potassium, magnesium, phosphate, and

calcium.

Metabolic bone disease, which occasionally presents as a pathologic fracture, includes osteopenia,

osteomalacia, and rickets. Calcium and phosphorus efficiency, excessive urinary losses of calcium

secondary to diuretics, and excessive vitamin D intake, and aluminum toxicity can all contribute to

metabolic bone disease. Maximizing calcium and phosphorus intake, and withdrawing vitamin D from

these patients actually improves bone demineralization, resolution of bone pain, positive calcium

balance, and normalizes active vitamin D and parathyroid hormone levels.

Hepatobiliary complications include cholestasis, steatosis, and cholelithiasis. Prematurity, prolonged

TPN use, and sepsis can contribute to these complications. Cholestasis is the most common and occurs 2

to 3 weeks after initiation. Prevention strategies for cholestasis include enteral feeding, weaning from

TPN, and prompt treatment of sepsis. Use of antibiotics to decrease bacterial overgrowth and

translocation has been successful but measures to promote bile flow have not shown to decrease

cholestasis. Use of omegaven and decreasing the lipid component of TPN has shown decreased rates of

cholestasis.

Mechanical complications of TPN arise from the need for venous access. Cardiac arrhythmias,

thrombosis, and infection can occur secondary to central line use. Proper positioning can avoid the rate

of cardiac irritation by the catheter tip. Thrombosis can be prevented and treated with the use of

prophylactic and therapeutic doses of anticoagulation. Prolonged thrombosis is a risk for line infection.

Furthermore, many patients on chronic TPN lose central access secondary to chronic thrombosis.

Finally, infectious complications can occur with and without a central line. Central lines require

meticulous care during insertion and maintenance.179 Fever, a sudden rise in bilirubin, and glucose

intolerance are indicators of sepsis. Sepsis can occur while on TPN from microorganisms that enter the

blood stream via the catheter, via infusion solutions, and from translocation from a disused, atrophic GI

tract. Finally, antibiotic-coated catheters and ethanol locks have been shown to decrease rates of line

infection.

Hypoglycemia

The fetal liver contains the enzymes needed for gluconeogenesis and glycogen synthesis but only

glycogen synthesis occurs in utero. Glycogen deposition increases from 3.4 mg/g of liver tissue at 8

weeks gestation to 50 mg/g by term.180 At birth, the glucose levels in the term neonate fall rapidly for

the first hour from 80% to 90% of maternal levels, then rises and stabilizes by hour 3 after birth,

independent of enteral intake.180 Within 12 hours, hepatic glycogen stores reach 10% of their initial

levels.180 In fact, hypoglycemia in breast-fed term neonates is uncommon, with glucose production

increasing to 4 to 6 mg/kg/min in the first few days, with glycogenolysis providing a third of the

glucose production.180 Preterm neonates, however, have increased rates of hypoglycemia because they

have lower hepatic glycogen reserves, decreased activity of gluconeogenic enzymes, and a reduced

ketogenic response.180

Following delivery and clamping of the umbilical cord, the newborn’s supply of glucose is abruptly

stopped. Over the next several hours, the neonate is susceptible to hypoglycemia, as defined as a serum

glucose level below 47 mg/dL (2.6 mmol/L).181 In order to prevent this hypoglycemia, the neonate

relies on a steady supply of substrate, such as breastmilk, with an inability to use the relatively small

amount of stored glycogen. The major energy source changes from glucose to fat during this adaptive

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phase. Infants born small for gestational age (<2 kg or below the 10th percentile), large for gestational

age (>4 kg or above 90th percentile), intrauterine growth restriction, those with insulin-dependent

mothers, or prematurely (<37 weeks) are at higher risk for hypoglycemia.182

Symptoms of hypoglycemia may include jitteriness, tachypnea, hypotonia, poor feeding, apnea,

temperature instability, seizures, and lethargy.183 Unfortunately, the infant may also remain asymptotic

with severe hypoglycemia, highlighting the importance of screening in high-risk infants in the first hour

of life. Treatment varies from observation, initiation of feeding, giving dextrose (D10 2 mg/kg bolus

followed by 80 mL/kg/d) via IV, starting TPN with a glucose infusion rate (GIR) of 4 to 6 mg/kg/min

at 80 mL/kg/d with steady increase in GIR based on glucose levels to target a level above 40 mg/dL.

Bilirubin Metabolism

One of the unique aspects of neonates is the extremely common, self-limited rise in bilirubin levels in

the first few weeks after birth. The liver metabolizes albumin-bound bilirubin, created in the breakdown

of hemoglobin, by conjugation using uridine diphosphate glucuronyl transferase (UDPGT). In term

neonates, hepatic UDPGT is only expressed at about 1% of the adult levels.180 Once hydrophilic

conjugated bilirubin is excreted into small intestines, however, increased reabsorption into the blood as

part of the enterohepatic circulation can also occur. The rise in bilirubin is at an earlier onset, for a

longer duration, at a greater frequency, and severity in preterm neonates due to higher production from

the larger proportion of senescent red blood cells, reduced ability to uptake bilirubin, and even more

reduced UDPGT activity.180

Hyperbilirubinemia (>5 mg/dL) occurs in 60% of term and 80% of preterm infants during the first

week of life.184 It is one of the most common reasons for hospital readmission for the newborn as the

peak level occurs after 3 to 5 days of life, commonly after discharge from the hospital. Etiology can be

dye to prematurity, increased production, genetic disorder such as Gilbert syndrome, or poorly feeding

or exclusively breast-fed late preterm infant.

Jaundice, seen initially in the mucous membranes of the inner mouth or eyes, must be categorized as

physiologic or pathologic (occurring in the first 24 hours secondary to hemolysis or elevated levels for

expected postnatal age and birth weight). Bilirubin toxicity starts with initial phase of sleepiness,

hypotonia, poor feeding, and progresses to lethargy and irritability, and finally seizures or a coma.185

Bilirubin-induced neurologic dysfunction (BIND) is tracked by following mental status, tone, and the

infant’s cry. Continued unrecognized bilirubin elevation can eventually lead to seizures, developmental

delay, hearing deficits, oculomotor disturbances, and kernicterus (permanent brain injury). There is no

cure for kernicterus.186

Management of elevated bilirubin is guided by established nomograms. Phototherapy promotes

photochemical reactions that change the shape and structure of the bilirubin: photo-isomerization

converts bilirubin to water-soluble isomers that are excreted in the bile; photo-oxidation converts

bilirubin to water-soluble products excreted in the urine. Fractionated bilirubin levels should be closely

followed as the direct component can increase with phototherapy leading to a “bronze baby.” Hydration

should also be carefully monitored as the therapy can increase insensible losses. Ensuring skin integrity,

thermoregulation, and monitoring stool patterns should also be part of the management. In patients

with Rh or ABO incompatibility, the use of intravenous immunoglobulin may reduce the need for the

next level of therapy, exchange transfusion.187

Exchange transfusion is similarly guided by levels on nomograms. The infant is made NPO, and

requires IV access (usually umbilical access), and correction of hypoglycemia, hypocalcemia,

hypotension, hypothermia, and acidosis. Thromboembolic complications, cardiac arrhythmias, sepsis,

and NEC can also occur. During exchange, phototherapy should still be continued and bilirubin levels

should continue to be monitored.

CONCLUSION

A thorough understanding of fetal, neonatal, and pediatric physiology is essential for understanding and

treating fetal and pediatric surgical problems. Pediatric patients are not “tiny adults” and the medical

and surgical approaches must be grounded in the understanding of their physiology and

pathophysiology. Finally, we believe that complex fetal and neonatal surgery should be performed in

centers with robust experience, which have pediatric subspecialists and facilities to care for these

patients. Already, establishment of levels of care is underway to categorize various pediatric surgical

institutions.188 This should globally improve outcomes on all pediatric patients by creating overall

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