Hypocalcemia is a laboratory and clinical abnormality that is observed with relative frequency, especially

in neonatal pediatric patients. Laboratory hypocalcemia is often asymptomatic, and its treatment in
neonates is controversial. However, children with hypocalcemia in pediatric intensive care units (PICUs)
have mortality rates higher than those of children with normal calcium levels. (See Prognosis, Clinical,
Workup, and Treatment.)
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.
Calcium metabolism and function
Calcium is the most abundant mineral in the body. Of the body's total calcium, 99% is in bone, and serum
levels constitute less than 1%.[1] Various factors regulate the homeostasis of calcium and maintain serum
calcium within a narrow range. These include parathormone (PTH), vitamin D, hepatic and renal function
(for conversion of vitamin D to active metabolites), and serum phosphate and magnesium levels. (See
Etiology and Workup.)
Although total serum calcium levels are often measured and reported, ionized calcium is the active and
physiologically important component. Total calcium level includes the ionized fraction and the bound
fraction. The ionized calcium level is affected by the albumin level, blood pH, serum phosphate, serum
magnesium, and serum bicarbonate and may be reduced by exogenous factors that may bind calcium,
such as citrate from transfused blood or free fatty acids from total parenteral nutrition. At a physiologic pH
of 7.4, 40% of total calcium is bound to albumin; 10% is complexed with bicarbonate, phosphate, or
citrate; and the remaining 50% exists as free ionized calcium. The normal range for ionized calcium is 11.25 mmol/L (4-5 mg/dL).
The concentration of calcium in the serum is critical to many important biologic functions, including the
following:

Calcium messenger system by which extracellular messengers regulate cell function

Activation of several cellular enzyme cascades
Smooth muscle and myocardial contraction
Nerve impulse conduction
Secretory activity of exocrine glands
Hypoglycemia is the most common metabolic problem in neonates. In children, a blood glucose value of
less than 40 mg/dL (2.2 mmol/L) represents hypoglycemia. A plasma glucose level of less than 30 mg/dL
(1.65 mmol/L) in the first 24 hours of life and less than 45 mg/dL (2.5 mmol/L) thereafter
constitutes hypoglycemia in the newborn.
Patients with hypoglycemia may be asymptomatic or may present with severe central nervous system
(CNS) and cardiopulmonary disturbances. The most common clinical manifestations can include altered
level of consciousness, seizure, vomiting, unresponsiveness, and lethargy. Any acutely ill child should be
evaluated for hypoglycemia, especially when history reveals diminished oral intake. (See History and
Physical Examination.)
Sustained or repetitive hypoglycemia in infants and children has a major impact on normal brain
development and function. Evidence suggests that hypoxemia and ischemia potentiate hypoglycemia,
causing brain damage that may permanently impair neurologic development. (See Prognosis.)
Causes of hypoglycemia in neonates differ slightly from those in older infants and children. The causes in
neonates include the following (see Etiology):

Inappropriate changes in hormone secretion

Inadequate substrate reserve in the form of hepatic glycogen
Inadequate muscle stores as a source of amino acids for gluconeogenesis
Inadequate lipid stores for the release of fatty acids
Hyperinsulinism, or persistent hyperinsulinemic hypoglycemia of infancy (PHHI), is the most common
cause of hypoglycemia in the first 3 months of life. It is well recognized in infants of mothers with diabetes.
(See Etiology.)
Causes of hypoglycemia found in all ages include gram-negative sepsis, endotoxin shock, and ingestions,
including of salicylates, alcohol, hypoglycemic agents, or beta-adrenergic blocking agents.

Excluding insulin therapy, almost all hypoglycemia in childhood occurs during fasting. Postprandial
hypoglycemia is rare in children in the absence of prior gastrointestinal (GI) surgery. Management efforts
are directed toward the immediate normalization of glucose levels and the identification and treatment of
the various causes. (See Treatment and Medications.)
Patient education
Provide genetic counseling for families with affected children, including information about a possible 25%
risk of recurrence. Educate pregnant women with diabetes.
Glucose metabolism
Normal blood glucose is very narrowly regulated, usually from 80-90 mg/dL (4.4-5 mmol/L). Glucose levels
increase transiently after meals to 120-140 mg/dL (6.6-7.7 mmol/L). Feedback systems return the glucose
concentration rapidly back to the preprandial level, usually within 2 hours after the last absorption of
carbohydrates.
Insulin and glucagon are the important hormones in the immediate feedback control system of glucose.
When blood glucose increases after a meal, the rate of insulin secretion increases and stimulates the liver
to store glucose as glycogen. When cells (primarily liver and muscle) are saturated with glycogen,
additional glucose is stored as fat.
When blood glucose levels fall, glucagon secretion functions to increase blood glucose levels by
stimulating the liver to undergo glycogenolysis and release glucose back into the blood. (See the diagram
below.)
In starvation, the liver maintains the glucose level via gluconeogenesis. Gluconeogenesis is the formation
of glucose from amino acids and the glycerol portion of fat. Muscle provides a store of glycogen and
muscle protein breaks down to amino acids, which are substrates utilized in gluconeogenesis in the liver.
Circulating fatty acids are catabolized to ketones, acetoacetate, and B-hydroxybutyrate and can be used as
auxiliary fuel by most tissues, including the brain.
The hypothalamus stimulates the sympathetic nervous system, and epinephrine is secreted by the
adrenals, causing the further release of glucose from the liver. Over a period of hours to days of prolonged
hypoglycemia, growth hormone and cortisol are secreted and decrease the rate of glucose utilization by
most cells of the body.
In the newborn, serum glucose levels decline after birth until age 1-3 hours, then they spontaneously
increase. Liver glycogen stores become rapidly depleted within hours of birth, and gluconeogenesis,
primarily from alanine, can account for 10% of glucose turnover in the newborn infant by several hours of
age.
A new way to detect gestational diabetes mellitus
At first glance, screening pregnant women for gestational diabetes mellitus (GDM) seems like it should be
straightforward. After all, the tests are designed to identify pregnant woman with high concentrations of
glucose (sugar) in their blood and laboratory tests that measure glucose are accurate and precise. So
whats the problem?
For one, experts dont agree on how best to screen pregnant women for GDM. While nearly everyone
agrees that both mom and baby can have adverse outcomes if GDM goes undetected and untreated, there
is lack of consensus on the best way of identifying GDM.
Consider how it has been done for several years here in the United States using either a 1 or 2 step
process. In the 2-step approach, a screening test is done first followed by a diagnostic test if the screening
test is abnormal. To do the screening test, blood glucose is measured 1 hour after the non-fasting patient
drinks a 50-gram dose of glucose. A glucose result that is greater than 140 mg/dL is usually used as the
cutoff although a lower cutoff of 130 mg/dL is also used (again, no consensus). A woman that has an
abnormal screening test (i.e. glucose concentration greater than the cutoff) will go on to have the
diagnostic test. In the 1-step approach the screening test is skipped completely and only the diagnostic
test is performed.
The test used to diagnose GDM is the oral glucose tolerance test (OGTT). The OGTT requires women to be
fasting and then drink either a 75- or a 100-gram dose of glucose. Blood samples are collected every hour
for 2 or 3 hours if using the 75- or 100-gram dose, respectively. The test is considered positive, and GDM

confirmed, if 2 or more of the glucose results are above designated cutoffs (which differ depending upon
the glucose dose given).
Now, new criteria have recently been advocated.
The International Association of Diabetes in Pregnancy Study Groups (IADPSG) has
maderecommendations for glucose tolerance testing in pregnancy based on the results of
theHyperglycemia and Adverse Outcomes (HAPO) study. That study clearly demonstrated that the risks of
adverse maternal and fetal outcomes continually increase as maternal glucose concentrations increased.
Importantly, the relationship between glucose concentration and risks were continuous. That is, there
were no obvious glucose cutoffs above which risks increased. The new recommendations from the IADPSG
address this issue.
The IADPSG advocates for the use of the 75-gram OGTT in pregnant women between 24 and 28 weeks
gestation. The test is performed following an overnight fast of at least 8 hours and blood is collected at 1
and 2 hours after the glucose load. A diagnosis of GDM is made when any of the following glucose results
are met:

Fasting: greater or equal to 92 mg/dL

1 hour: greater or equal to 180 mg/dL

2 hour: greater or equal to 153 mg/dL

A couple of questions are called for here:

1.

Why were those cutoff selected? These are the glucose concentrations above which the
adverse risks of hyperglycemia were 1.75-fold higher than for women whose glucose results were
lower. Other thresholds were considered but higher cutoffs missed lots of women with adverse
pregnancy outcomes and lower cutoffs identified 25% of women as having GDM.

2.

What is the impact will this test have on the prevalence of GDM? It will definitely
increase. Currently, about 7% of pregnant women are diagnosed with GDM in the US each year. Using
the IADPSG approach that will more than double to about 18% of pregnant women.
Although the American Diabetes Association adopted the IAPDSG criteria and recommends that approach
to identifying women with GDM, it does recognize that there is the potential for harm. For example, more
interventions such as earlier delivery and increased C-section rates are likely to occur due to the increase
in the prevalence of GDM. Also, an increased number of women being diagnosed with GDM will be
accompanied by a rise in health care costs. Despite those considerations, the ADA supports the new
criteria in light of the increased rates of obesity and diabetes throughout the US and the world.
Birth weight is the body weight of a baby at its birth.[1]
There have been numerous studies that have attempted, with varying degrees of success, to show links
between birth weight and later-life conditions, including diabetes, obesity, tobacco
smoking and intelligence.
Determinants[edit]
There are basically two distinct determinants for birth weight:

The duration of gestation prior to birth, that is, the gestational age at which the child is born

The prenatal growth rate, generally measured in relation to what weight is expected for any
gestational age.
The incidence of birth weight being outside what is normal is influenced by the parents in numerous ways,
including:

Genetics

The health of the mother, particularly during the pregnancy

Environmental factors, including exposure of the mother to secondhand smoke[2]

Economic status of the parents gives inconsistent study findings according to a review on
2010, and remains speculative as a determinant.[3]

Other factors, like multiple births, where each baby is likely to be outside the AGA, one more
so than the other
Abnormalities[edit]

A low birth weight can be caused either by a preterm birth (low gestational age at birth) or
of the infant being small for gestational age (slow prenatal growth rate), or a combination of both.

A very large birth weight is usually caused by the infant having been large for gestational
age
Influence on adult life[edit]
Studies have been conducted to investigate how a person's birth weight can influence aspects of their
future life. This includes theorised links with obesity, diabetes and intelligence.
Obesity[edit]
A baby born small or large for gestational age (either of the two extremes) is thought to have an increased
risk of obesity in later life,[4][5] but it was also shown that this relationship is fully explained by maternal
weight.[6]
GH therapy at a certain dose induced catch-up of lean body mass (LBM). However percentage body fat
decreased in the GH-treated subjects. Bone mineral density SDS measured by DEXA increased significantly
in the GH-treated group compared to the untreated subjects, though there is much debate over whether or
not SGA (small for gestational age) is significantly adverse to children to warrant inducing catch-up. [7]
Diabetes[edit]
Babies that have a low birth weight are thought to have an increased risk of developing type 2 diabetes in
later life.[8][9][10]
Intelligence[edit]
Some studies have shown a direct link between an increased birth weight and an increased intelligence
quotient.[11][12][13] Increased birth weight is also linked to greater risk of developing autism.