CHAPTER I

INTRODUCTION

Calcium deficiency means a condition of low level of calcium in the blood

(hypocalcemia) which can make the nervous system highly irritable causing

tetany (spasms of the hands and feet, muscle cramps, abdominal cramps, and

overly active reflexes). Hypocalcemia is defined as a total serum calcium

concentration of less than 2.1 mmol/L (8.5 mg/dL) in children, less than 2 mmol/L

(8 mg/dL) in term neonates, and less than 1.75 mmol/L (7 mg/dL) in preterm

neonates (Singhal, 2010).

Hypocalcemia in children may be asymptomatic or there may be a wide range of

signs and symptoms. Because very young patients cannot accurately verbalize

symptoms, they are more likely to present with signs such as weakness, feeding

problems, facial spasm, jitteriness or seizures. In addition, features of conditions

known to be associated with hypocalcemia may be identified (Dawrant, 2007).

There are multiple causes of hypocalcemia in children, thus, diagnosis must

follow a systematic approach. Since pediatric hypocalcemia can represent the first

manifestation of a genetic disorder, a definitive diagnosis may eventually require

further testing at a specialized centre (Dawrant, 2007).

Once diagnosis of hypocalcemia has been made, a systematic workup that

includes a panel of blood tests can help sort out what may otherwise be a

confusing clinical picture. Hypocalcemia in children can be an early presentation

of a genetic syndrome, and a systematic approach can facilitate referral for

definitive diagnosis and treatment (Dawrant, 2007).

CHAPTER II

PEDIATRIC CALCIUM DEFICIENCY

2.1 Risk Factor

Risk factors for calcium deficiency are factors that do not seem to be a direct

cause of the disease, but seem to be associated in some way. Having a risk factor

for calcium deficiency makes the chances of getting a condition higher but does

not always lead to calcium deficiency. Also, the absence of any risk factors or

having a protective factor does not necessarily guard you against getting calcium

deficiency.

Obesity or overweight is a serious condition. There are various other conditions

for which obesity is a risk factor. Cholesterol as a risk factor for other medical

conditions. High cholesterol is a serious condition. There are various other

conditions for which cholesterol-related conditions are a risk factor.

Because bone stores of calcium can be used to maintain adequate blood calcium

levels, short-term dietary deficiency of calcium generally does not result in

significantly low blood calcium levels. But, over the long term, dietary deficiency

eventually depletes bone stores, rendering the bones weak and prone to fracture. A

low blood calcium level is more often the result of a disturbance in the body's

calcium regulating mechanisms, such as insufficient PTH or vitamin D, rather

than dietary deficiency. When calcium levels fall too low, nerve and muscle

impairments can result. Skeletal muscles can spasm and the heart can beat

abnormally—it can even cease functioning.

Toxicity from calcium is not common because the gastrointestinal tract normally

limits the amount of calcium absorbed. Therefore, short-term intake of large

amounts of calcium does not generally produce any ill effects aside from

constipation and an increased risk of kidney stones. However, more severe

toxicity can occur when excess calcium is ingested over long periods, or when

calcium is combined with increased amounts of vitamin D, which increases

calcium absorption. Calcium toxicity is also sometimes found after excessive

intravenous administration of calcium. Toxicity is manifested by abnormal

deposition of calcium in tissues and by elevated blood calcium levels

(hypercalcemia). However, hypercalcemia is often due to other causes, such as

abnormally high amounts of PTH. Usually, under these circumstances, bone

density is lost and the resulting hypercalcemia can cause kidney stones and

abdominal pain. Some cancers can also cause hypercalcemia, either by secreting

abnormal proteins that act like PTH or by invading and killing bone cells causing

them to release calcium. Very high levels of calcium can result in appetite loss,

nausea , vomiting, abdominal pain, confusion, seizures, and even coma.

2.2 Etiology

Overall, one of the most common causes of hypocalcemia is renal failure, which

results in hypocalcemia because of inadequate 1-hydroxylation of 25-

hydroxyvitamin D and hyperphosphatemia due to diminished glomerular filtration

(Singhal, 2010).

The causes of hypocalcemia can be classified by the child's age at presentation.

The first classification is early neonatal hypocalcemia (within 48-72 h of birth).

The possible causes are prematurity, birth asphyxia, diabetes mellitus in the

mother, intrauterine growth retardation (IUGR). In premature infants, the possible

mechanisms include poor intake, decreased responsiveness to vitamin D,

increased calcitonin, and hypoalbuminemia leading to decreased total but normal

ionized calcium (Singhal, 2010).

In infants with birth asphyxia, delayed introduction of feeds, increased calcitonin

production, increased endogenous phosphate load, and alkali therapy all may

contribute to hypocalcemia (Singhal, 2010).

The presence magnesium depletion in the mother with diabetes mellitus causes

hypomagnesemic state in the fetus. This hypomagnesemia induces functional

hypoparathyroidism and hypocalcemia in the infant. A high incidence of birth

asphyxia and prematurity in infants of diabetic mothers are also contributing

factors (Singhal, 2010).

Infants with IUGR may have hypocalcemia if they are also preterm or have had

perinatal asphyxia (Singhal, 2010).

The second classification is late neonatal hypocalcemia (3-7 d after birth, though

occasionally as late as age 6 week). The possible causes are exogenous phosphate

load, magnesium deficiency, transient hypoparathyroidism of newborn,

hypoparathyroidism due to other causes and gentamicin uses. Exogenous phospate

load-related hypocalcemia is most commonly seen in developing countries. The

identified cause is feeding with phosphate-rich formula or cow’s milk. Whole

cow’s milk has 7 times the phosphate load of breast milk (956 vs 140 mg/L in

breast milk) (Singhal, 2010).

The third classification is hypocalcemia in infants and children. The major causes

are hypoparathyroidism, abnormal vitamin D production or action, and

hyperphosphatemia (Singhal, 2010).

2.3 Epidemiology

The incidence of neonatal hypocalcemia varies in different studies. Hypocalcemia

occurs in as many as 30% of infants with very low birth weight (<1500 g) and in

as many as 89% of infants whose gestational age at birth was less than 32 weeks.

A high incidence is also reported in infants of mothers with diabetes mellitus and

in infants with birth asphyxia. No variation is reported across national boundaries.

However, late-onset hypocalcemia is more common in infants in developing

countries where babies are fed cow's milk or formulas containing high amounts of

phosphate than in countries where infants are fed human milk or formulas

containing low amounts of phosphate.

2.4 Pathophysiology

Calcium absorption is dependent upon the calcium needs of the body, the foods

eaten, and the amount of calcium in the foods eaten. Vitamin D from diet or

exposure to the ultraviolet light of the sun increases calcium absorption. Calcium

absorption tends to decrease with increased age for both men and women. More

than 99% of total body calcium is stored in the bones and teeth where it functions

to support their structure. The remaining 1% is found throughout the body in

blood, muscle, and the fluid between cells. Because of its biological importance,

calcium levels are carefully controlled in various compartments of the body. The

three major regulators of blood calcium are parathyroid hormone (PTH), vitamin

D, and calcitonin.

PTH is normally released by the four parathyroid glands in the neck in response to

low calcium levels in the bloodstream (hypocalcemia). PTH acts in three main

ways, it causes the gastrointestinal tract to increase calcium absorption from food,

it causes the bones to release some of their calcium stores, and it causes the

kidneys to excrete more phosphorous, which indirectly raises calcium levels.

Vitamin D works together with PTH on the bone and kidney and is necessary for

intestinal absorption of calcium. Vitamin D can either be obtained from the diet or

produced in the skin when it is exposed to sunlight. Insufficient vitamin D from

these sources can result in rickets in children and osteomalacia in adults,

conditions that result in bone deformities. Calcitonin, a hormone released by the

thyroid, parathyroid, and thymus glands, lowers blood levels by promoting the

deposition of calcium into bone.

Most dietary calcium is absorbed in the small intestine and transported in the

bloodstream bound to albumin, a simple protein . Because of this method of

transport, levels of albumin can also influence blood calcium measurements.

Calcium is deposited in bone with phosphorous in a crystalline form of calcium

phosphate.

2.5 Clinical Manifestation

The symptoms of hypocalcemia may vary depending on age. In newborns there

may be no specific symptoms found while later, there may be possibilities of

vomiting, abdominal distension, and poor feeding as early signs of hypocalcemia.

Earliest newborns may be premature, birth asphyxia may occur, and congenital

heart disease may be found.

Symptoms experienced in children are not as far as those experienced by the

adults. Often the earliest symptoms of hypocalcemia in children are paresthesias,

tingling sensation around the mouth and lips, and in the extremities of the hands

and feet. Additionally, petechias which appear as one-off spots become confluent

and appear as purpura in some parts of the body.

Tetany and signs of nerve irritability will be found it further calcium deficiency

happens. Usually carpopedal and generalized tetany all over the body shows an

unrelieved and strong contraction of the hands and muscles of the body. Further,

latent tetany showing signs of trousseau latent tetany shows carpal spasm by

inflating the blood pressure cuff and maintaining the cuff pressure above systolic.

Also Chvostek's sign odservable by tapping of the inferior portion of the zygoma

will produce facial spasms. Tendons of children are usually hyperactive during

reflexes.

There may be some serious life threatening clinical manifestation found in

calcium deficiency, although hypocalcemia is already an emergency condition.

Such condition such as laryngospasm, cardiac arrhythmias, and apnea is a

dangerous complication of calcium deficiency. Cardiac arrhythmias may develop

and ECG changes including intermittent QT prolongation on the echocardiogram

will be shown if further hypocalcemia occurs, it may lead to a ventricular

fibrillation that is a serious problem.

2.6 Diagnosis and Differential Diagnosis

There is a few methods must be used to diagnosis calcium deficiency

(hypocalcemia) in paediatrics. Adequate information is important for accurate

diagnosis. Firstly, a full history about the patients general health and diet should

be questioned such as is there any eating disorders, exposure to mercury,

including infantile acrodynia excessive dietary magnesium, as with

supplementation. Prolonged use of medications or laxatives containing

magnesium Chelation therapy for metal exposure, particularly EDTA, absent

parathyroid hormone (PTH). The degree of balance between nutrient intake and

nutrient requirement is referred to as nutritional status. As with all aspects of

assessment, several factors can affect the health status of a person.

For nutrition assessment, the physiologic, psychosocial, developmental, cultural,

and economic aspects of the individual’s life must be considered. The health

practitioner needs to determine whether the patient has optimal nutrition or

undernutrition. Besides this, physical examination or some clinical findings must

be done to confirm the diagnosis. For this case, clinical findings such as

weakness, fatigue, muscle cramping and spasm (difficulty speaking may indicate

laryngeal spasm), paresthesias (perioral or fingertip), abdominal pain, nausea or

vomiting, irritability, and depression delirium, psychosis, and seizures which is

caused by severe hypocalcemia. Skin exam may reveal patchy hair loss, dry

and/or scaly skin, hyperpigmentation, brittle nails, and mucocutaneous

candidiasis. Trousseau's sign-Carpal spasms upon inflation of a blood pressure

cuff for 2 to 3 minutes. Chvostek's sign-Tapping of cranial nerve VII (anterior to

ear) causes twitching of facial muscles, cardiac arrhythmias, decreased myocardial

contractility (may lead to CHF), hypotension, vitiligo, alopecia, nail fungal

infection, vital signs, growth parameters, facial dysmorphism (DiGeorge

syndrome, PHP IA), skeletal deformities (bowed legs, widened wrists/ankles,

rachitic rosary, frontal bossing) is also considered. Other than that, we must also

enquire about patients with post surgical hypoparathyroidism or chronic renal

insufficiency, or who have been given phosphate.

Laboratory evaluation should be guided by history and physical examination.

Renal failure, cell lysis syndromes, hypomagnesemia or hypermagnesemia, and

acute pancreatitis can be diagnosed or excluded using measurements of serum

creatinine, creatine kinase, magnesium, and amylase levels. A serum magnesium

concentration lower than 1.0 mg/dL should be considered significant and

corrected. In the absence of these conditions, disorders affecting the production or

action of PTH or vitamin D should be considered. The immunoreactive PTH

(iPTH), 25-hydroxyvitamin D, and 1,25-hydroxyvitaminvitamin D levels need to

be determined and the results are often delayed 2 to 7 days.

Futhermore, laboratory or biochemistry finding is important to contribute to the

diagnosis. Thus some laboratory testing, such as complete blood count (CBC) and

calcium levels. A serum calcium level less than 8.5 mg/dL or an ionized calcium

level less than 1.0 mmol/L is considered hypocalcemia. Analysis for ionized level

must be performed rapidly with whole blood to avoid changes in pH and anion

chelation. Blood should be drawn in an unheparinized syringe for best result.

Falsely depressed levels can be seen with heparin, oxalate, citrate, or

hyperbilirubinemia. Serum magnesium levels may be low in patients with

hypocalcemia. Severe hypomagnesemia (0.46 mmol/L) causes hypocalcemia by

impairing the secretion and action of parathormone (PTH). Serum electrolyte and

glucose levels, seizures and irritability in newborns and children can be associated

wih hypoglycemia and sodium abnormalities. Low bicarbonate levels and acidosis

may be associated with Fanconi syndrome and renal tubular acidosis. Phosphorus

levels estimating the phosphate level is essential to establish the etiology of

hypocalcemia. Phosphate levels are increased in cases of exogenous and

endogenous phosphate loading and renal failure. Levels are usually high in

patients with hypoparathyroidism. Levels are low in cases of vitamin D

abnormalities and rickets.

The imaging studies include, chest radiography to evaluate thymic shadow, which

may be absent in patients with DiGeorge syndrome. Ankle and wrist radiography,

evaluate for evidence of rickets. Changes appear at an early stage in the radius and

ulna, which is the distal ends are widened, concave, and frayed. Other tests,

electrocardiography, which show a prolonged QTc (>0.4 s), a prolonged ST

segment, and T-wave abnormalities and may be observed. Malabsorption workup,

total lymphocyte and T-cell subset analyses, findings are decreased in patients

with DiGeorge syndrome. Karyotyping to assess for 22q11 and 10p13 deletion.

Maternal and family screening, helpful in familial forms of hypocalcemia, such as

those caused by activating mutations of the calcium-sensing receptor. Accurate

identification of nutritional problems allows for earlier intervention.

Calcium deficiency is often misdiagnosed as other disease. This is due to the

similarities in the way the condition presents itself. Among those diseases are

hydrofluoric acid burns, hypernatremia, hypercalcemia, hyperosmolar

hyperglycemic nonketotic coma, hyperkalemia, hyperparathyroidism,

hypermagnesimia and hyperphosphatemia.

2.7 Treatment

Dietary calcium requirements depend in part upon whether the body is growing or

making new bone or milk. Requirements are therefore greatest during childhood,

adolescence, pregnancy, and breastfeeding. Recommended daily intake (of

elemental calcium) varies accordingly 400 mg for infants 0–6 months, 600 mg for

infants 6–12 months, 800 mg for children 1–10 years, 1,200 mg for ages 11–24

years, and 800 mg for individuals over 24 years of age. Pregnant women require

additional calcium (RDA 1,200 mg). Many experts believe that elderly persons

should take as much as 1,500 mg to help prevent osteoporosis , a common

condition in which bones become weak and fracture easily due to a loss of bone

density. Dairy products, meats, and some seafood (sardines, oysters) are excellent

sources of calcium. Spinach, beet greens, beans, and peanuts are among the best

plant-derived sources.

Calcium absorption is affected by many factors, including age, the amount needed, and

what foods are eaten at the same time.

CALCIUM

SUPPLEMENT

SUPPLEMENT

ELEMENTAL

CALCIUM BY

WEIGHT

COMMENT

Calcium carbonate 40% • Most commonly used

• Less well absorbed in

persons with decreased

stomach acid (e.g.,

elderly or those on anti-

acid medicines)

• Natural preparations

from oyster shell or bone

meal may contain

contaminants such as

lead

• Least expensive

Calcium citrate 21% • Better absorbed,

especially by those with

decreased stomach acid

• May protect against

kidney stones

• More expensive.

Calcium phosphate 38% or 31% • Tricalcium or dicalcium

phosphate

• Used more in Europe

• Absorption similar to

calcium carbonate

Calcium gluconate 9% • Used intravenously for

severe hypocalcemia

• Well absorbed orally,

but low content of

Calcium glubionate 6.5% • Available as syrup for

children

• Low content elemental

calcium.

Calcium lactate 13% • Well absorbed, but low

content elemental

calcium.

Source : Gregory, Philip J. (2000) "Calcium Salts." Prescriber's Letter.

In general, calcium from food sources is better absorbed than calcium taken as

supplements. Children absorb a higher percentage of their ingested calcium than

adults because their needs during growth spurts may be two or three times greater

per body weight than adults. Vitamin D is necessary for intestinal absorption,

making Vitamin D–fortified milk a very well-absorbed form of calcium. Older

persons may not consume or make as much vitamin D as is optimal, so their

calcium absorption may be decreased. Vitamin C and lactose (the sugar found in

milk) enhance calcium absorption, whereas meals high in fat or protein may

decrease absorption. Excess phosphorous consumption (as in carbonated sodas)

can decrease calcium absorption in the intestines. High dietary fiber and phytate (a

form of phytic acid found in dietary fiber and the husks of whole grains) may also

decrease dietary calcium absorption in some areas of the world. Intestinal pH also

affects calcium absorption—absorption is optimal with normal stomach acidity

generated at meal times. Thus, persons with reduced stomach acidity (e.g., elderly

persons, or persons on acid-reducing medicines) do not absorb calcium as well as

others do.

Calcium supplements are widely used in the treatment and prevention of

osteoporosis. Supplements are also recommended, or are being investigated, for a

number of conditions, including hypertension , colon cancer , cardiovascular

disease, premenstrual syndrome, obesity , stroke , and preeclampsia (a

complication of pregnancy). There are several forms of calcium salts used as

supplements. They vary in their content of elemental calcium, the amount

effectively absorbed by the body, and cost. Whatever the specific form, the

supplement should be taken with meals to maximize absorption.

Medical care

General medical care in patients with hypocalcemia involves stabilization with

management of the patient's airway and breathing if seizures occur.

Anticonvulsants are commonly administered before hypocalcemia is confirmed in

a new patient. Seizures usually do not respond to the usual antiseizure

medications until calcium is intravenously administered.

Treatment of an asymptomatic patient with hypocalcemia remains controversial,

especially in neonates. Some authorities suggest that treating such patients is

unnecessary. In contrast, most clinicians agree that hypocalcemia should be

treated promptly in any symptomatic neonate or older child because of its serious

implications for neuronal and cardiac function. Intravenous treatment is usually

indicated in patients having seizures, those who are critically ill, and those who

are planning to have surgery. Oral calcium therapy is used in asymptomatic

patients and as follow-up to intravenous calcium therapy.

In certain conditions like pancreatitis and rhabdomyolysis, full correction of

hypocalcemia should be avoided. After the primary condition is resolved, these

patients may develop hypercalcemia due to the release of complexed calcium.

In cases with concurrent acidemia, hypocalcemia should be corrected first.

Acidemia increases the ionized calcium levels by displacing calcium from

albumin. If acidemia is corrected first, it decreases ionized calcium levels.

Those patients should be given a diet high in calcium and low in phosphate is

required in most instances. Infants drinking regular cow's milk or evaporated milk

must be given humanized infant formula instead. Patients with renal failure should

be given a low-solute low-phosphate formula, such as Similac PM 60/40.

2.8 Complication

Children who do not consume sufficient quantities of calcium generally will

experience growth-related problems including bone deformation. Children also

can develop Rickets, a condition that leads to softening and weakening of the

bones. It cause by a lack of vitamin D, calcium, or phosphate that makes failure of

osteoid to calcify in adults is called osteomalacia.

Children that are faced with calcium deficiency are not going to grow properly

and they are not going to have strong and healthy bones.  This is very important

for small children as they learn to crawl and walk because you do not want your

child to injure themselves.  They may also suffer from a lack of an appetite and

they may get teeth later than other children.  When they do get teeth, they may be

decayed.  Your child may eventually have respiratory or intestinal complications

if these symptoms are not taken care of.

Young girls that are suffering from calcium deficiency symptoms are going to

have other complications such as developing into puberty at a late time or having

complications with their menstrual cycle.  They may also suffer from severe

cramping.   In addition, a child who refuses to eat foods, or drink beverages, that

are rich in calcium, including milk, may be experiencing a complication

associated with sensory input which will lead to mood disorders.

2.9 Prognosis

Prognosis is dependent on the etiology of hypocalcemia but is generally good.

The prognosis for correcting hypocalcemia is excellent. However, the eye damage

that may result from chronic hypocalcemia cannot be reversed.