Hypocalcemia in the Newborn

Calcium (Ca) is the body's most abundant mineral, playing crucial roles in various physiological processes:

• Calcium in Bone: Approximately 99% of the body's calcium is stored within the bone, contributing to its structural integrity.
• Circulating Calcium: The remaining 1% is present in the serum, where it exists in distinct forms:

1. Bound to Albumin: About 40% of serum calcium is bound to albumin, a protein carrier.
2. Complexes with HCO3 and PO4: Roughly 10% forms complexes with bicarbonate (HCO3) and phosphate (PO4) ions.
3. Ionized Calcium: The remaining 50% exists in an ionized form, responsible for driving the essential physiological functions of calcium.

Definition

Hypocalcemia is defined by:

• Total Serum Calcium: Total serum calcium levels falling below 2.2 mmol/L.
• Ionized Serum Calcium: Alternatively, ionized serum calcium levels below 1.1 mmol/L can also indicate hypocalcemia.

Roles of Calcium in the Body

Calcium serves a multitude of critical roles within the body:

1. Cell Communication: Calcium functions as a signaling molecule that facilitates intercellular communication. This is paramount for processes like muscle contraction, nerve transmission, and the regulation of gene expression.
2. Skeletal Structure: Being a primary component of bones and teeth, calcium provides the structural integrity and rigidity required for the skeletal framework.
3. Coagulation Cascade: Calcium is indispensable for blood clotting. It participates in the activation of clotting factors, culminating in the formation of stable blood clots in response to injuries.
4. Cell Adhesion and Permeability: Calcium influences cell adhesion, fostering cellular cohesion. Additionally, it modulates membrane permeability, controlling the ingress and egress of substances.
5. Enzyme Activation: Numerous enzymes rely on calcium ions as cofactors to execute their functions effectively. Calcium-mediated enzyme activation underpins a plethora of biochemical reactions.
6. Hormone Regulation: Calcium stimulates the release of hormones, including insulin from pancreatic cells. These hormones play pivotal roles in metabolism and physiological regulation.
7. Cell Growth and Differentiation: Calcium signaling contributes to cell growth, differentiation, and programmed cell death (apoptosis). It ensures cells respond adequately to their surroundings.
8. Mitochondrial Function: Calcium is integral to regulating mitochondrial energy production and metabolism, influencing overall cellular energy balance.

The regulation of calcium levels within the body involves the interplay of several key hormones:

• Parathyroid Hormone (PTH): PTH is pivotal in maintaining calcium balance by orchestrating the following mechanisms:
• Mobilization from Bones: PTH stimulates the release of calcium from the bones, which serves to elevate serum calcium levels.

• Vitamin D: Vitamin D plays a significant role in calcium homeostasis through its impact on:
1. Increased Absorption: Vitamin D enhances calcium absorption from the gastrointestinal tract (GIT), thereby raising serum calcium levels.
2. Renal Reabsorption: It promotes the reabsorption of calcium by the kidneys, contributing to elevated calcium levels in the bloodstream.

• Calcitonin: Calcitonin influences calcium homeostasis by:
1. Inhibiting Bone Resorption: Calcitonin curtails the breakdown of bone tissue, effectively lowering serum calcium levels.
2. Enhancing Renal Excretion: It encourages the excretion of calcium through the kidneys, aiding in the reduction of calcium levels in the blood.

Hypocalcemia can be categorized based on the timing of its onset:

• Early-Onset Hypocalcemia: This form of hypocalcemia becomes apparent within the first 72 hours of an infant's life. It often arises as a result of factors related to the immediate postnatal period.
• Late-Onset Hypocalcemia: Late-onset hypocalcemia, on the other hand, becomes noticeable after the initial 72-hour period. It can be associated with various factors that develop or manifest later in the neonatal course.

This classification aids in understanding the potential underlying causes and timing of hypocalcemic episodes.

Causes of Early-Onset Hypocalcaemia

Early-onset hypocalcaemia can arise due to factors both maternal and fetal/newborn:

• Maternal Causes: The mother's condition can contribute to early-onset hypocalcaemia, with possible causes including:

1. Maternal Calcium or Vitamin D Deficiency
2. Maternal Hyperparathyroidism
3. Maternal Diabetes

• Fetal/Newborn Causes: Conditions related to the newborn can also lead to early-onset hypocalcaemia, which might include:

1. Perinatal Asphyxia
2. Prematurity
3. Hypoparathyroidism (e.g., DiGeorge Syndrome)
4. Respiratory Distress Syndrome (RDS)
5. Exposure to Narcotics

Causes of Late-Onset Hypocalcaemia (Rare)

Late-onset hypocalcaemia, although rare, can be attributed to specific factors:

• Hyperphosphataemia
• Magnesium Deficiency

Miscellaneous Causes

Several other factors have been associated with hypocalcaemia:

• Phototherapy (used in treating jaundice)
• Bicarbonate Treatment
• Frusemide (a diuretic)
• Exchange Blood Transfusion (EBT)- causes the most profound hypocalcemia. The anticoagilant of the blood stored in a bag chelates calcium, so calciium is usually administered to the neonate.
• Intravenous Lipid Administration
• Renal Disease

The clinical signs of hypocalcaemia can be nonspecific, often resembling those of other neonatal disorders:

• Jitteriness: Neonates with hypocalcaemia may exhibit tremors or jitteriness, indicative of neurological irritability.
• Apnoea: Breathing interruptions or apnoea can be observed, reflecting the effects of low calcium levels on respiratory muscles.
• Cyanosis: Cyanosis, a bluish discoloration of the skin, can occur due to compromised oxygenation.
• Seizures: Seizures are a potential manifestation of hypocalcaemia, arising from its impact on neuronal excitability.
• Lethargy: Hypocalcaemic neonates might appear lethargic, displaying reduced energy and responsiveness.
• Vomiting: Vomiting can be present, likely stemming from gastrointestinal disturbances.
• Uncommon Classical Signs: Classical signs of hypocalcaemia, such as carpopedal spasms and laryngeal spasms, are relatively uncommon in neonates.

Given the vagueness of these manifestations, a comprehensive assessment is essential for accurate diagnosis and intervention.

The evaluation of neonates suspected of having hypocalcaemia involves:

• History: A comprehensive history can provide valuable insights, including:

1. Maternal Illness: Information about the mother's health during pregnancy and any existing medical conditions.
2. Labour & Delivery: Details of the labor and delivery process, which could shed light on potential risk factors.
3. Dietary History: Knowledge of the infant's diet and nutritional intake, particularly in relation to calcium and vitamin D.

• Examination: A thorough physical examination is crucial, with emphasis on:

1. Identifying Dysmorphism: Looking for any signs of dysmorphic features, as they can be indicative of genetic conditions associated with hypocalcaemia. e.g. DiGeorge Syndrome (22q11.2 Deletion Syndrome) which can lead to underdevelopment of the parathyroid glands, causing hypoparathyroidism. As a result, the neonate may experience low levels of parathyroid hormone (PTH) and subsequently hypocalcemia.

Diagnosing and assessing hypocalcaemia often involves several investigations:

• Calcium, Phosphate, Magnesium Levels: provides insight into the mineral imbalances contributing to hypocalcaemia.
• Chest X-Ray: A chest X-ray might be performed to evaluate the presence of a thymic shadow, which can be associated with certain conditions causing hypocalcaemia.
• Electrocardiogram (ECG): An ECG helps assess cardiac function and may reveal any electrocardiographic changes associated with hypocalcaemia.

• Symptomatic Treatment: In cases of symptomatic hypocalcaemia, the following steps are taken:

1. Slow Calcium Infusion: Administer 40mg/kg of 10% calcium gluconate gradually over 20 minutes, while closely monitoring the heart's response.
2. Continuous Infusion: Follow up with an additional 160mg/kg over the course of 24 hours, delivered through intravenous fluids (IVF).

• Asymptomatic: Asymptomatic cases necessitate:
• Add 200mg/kg of calcium into the 24-hour IVF regimen.

• Address Underlying Cause: Effective management extends to identifying and managing the underlying factors contributing to hypocalcaemia.