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![DATE 16 DOL 18DOL 21DOL 25DOL
S.Ca 4.3 5.2 8.7 9.5
iCa 0.48 0.61 11.14 1.28
S.Po4 10.8 9.1
S.Mg 1.5 1.4 2.0 1.9
ALP 394
iPTH 41.9 pg/dl 100 pg/dl
Vitamin D
25-OH D3
12.36 ng/dl
Additional
tests
UCa/Cr – 0.2
FeMg – 1.1
Rx •Inj CaGlu
60mkd
•Inj MgSO4
(50%)0.2ml/
kg
•2000IU Vit
D
•Calcitriol
was added.
•Inj CalGLu
MgSO4
contd.
•Oral Ca and
Mg at
150mkd
37.5md
•Inj CaGlu
and MgSO4
stopped.
•Calcitrol
stopped
• Oral Cal
Mg at
150mkd and
38mkd.
FeMg
{([Mg2+]urine ×
[creatinine]plasma)/ (0.7
[Mg2+]plasma ×
[creatinine]urine)} × 100
%.
A FEMg of >4 % in a
hypomagnesemic
patient is consistent
with renal
Mg2+ wasting, while a
patient with a FEMg
of <2 % will likely have
an extra-renal origin of
their hypomagnesemia](https://image.slidesharecdn.com/hypocalcemia-220912084151-0dcd34ad/85/Hypocalcemia-pptx-19-320.jpg)
Hypocalcemia.pptx
- 1. Hypocalcemia In Neonates:Case Based Approach Presenter- Dr. Snigdha Jagtap Department of Neonatology Bai Jerbai Wadia Hospital for Children , Mumbai
- 2. Overview • Case Scenarios •Calcium Phosphorous Homeostasis • Factors affecting Homeostasis • Hypocalcemia o Early Onset o Late Onset • Management
- 3. CASE 1 • 7day old full term /2600g/AGA/Male/ born by LSCS/ admitted with : – Delayed cry at birth, required DRR – Respiratory Distress since birth – Seizures on day 1 (multifocal)
- 4. Antenatal H/O • PrimiMother. • Uneventful. No maternal h/o of Diabetes Mellitus or Hyperparathyroidism. No H/o drug intake.
- 5. Course in OutsideHospital Day 1 Did not cry immediately. Apgar 5, 7. Required resuscitation at birth and mechanical ventilation. Had multiple episode of seizures on DOL 1 requiring AEDs(Inj Phenobarbitone and Levera). Sepsis Screen – normal. S. Electrolytes S. Calcium - normal Day 2 Developed Shock requiring Dopamine and Adrenaline 2D-ECHO : Mild PPHN Started on Milrinone. Day 7 Extubated to NIV Referred to our hospital on day 8 of life
- 6. Course in ourHospital On Examination at time of admission Baby was dull, lethargic CFT< 2seconds Pulse Volume – Normal SpO2 – 96% HR – 135/min RR – 48/min General Examination: Normal No Dysmorphism CNS – Cry – Normal Moros – Incomplete. Other Reflexes – Normal. Tone decreased in all four limbs
- 7. • Baby continuedon NIV. As distress settled then weaned to room air. Initial Septic Screen was normal. ABG and S. Electrolytes were normal. • No further episodes of seizures. • Started on EBM via RT on day of admission and reached full feeds by day 11 • EEG was normal. MRI Hyperintensities in whte matter of Rt central semiovale s/o sequlae to HIE.
- 8. DOL – 10 SepticScreen was normal. ABG - Normal CXR – NAD iCa – 0.88 meq/dl Serum Ca – 6.2 mg/dl S. Alb – 3.5 mg/dl S. Phosphorous – 3.5 mg/dl ALP – 343 U/L mg
- 9. S. Mg –2.0 mg/dl Renal Function Tests - Normal Vitamin D – 6.26 ng/dl iPTH – 99.64 pg/ml Mothers Vitamin D levels – 12.0 ng/dl
- 10. Diagnosis - Late onsetasymptomatic hypocalcemia secondary to Maternal Hypovitaminosis D.
- 11. Rx – Inj CalciumGluconate 60mg/kg/day Oral Vitamin D 2000IU after 48hours Serum Ca – 9mg/dl iCa – 1.12 meq/dl Discharged on Oral Calcium at 150mkd Drops Vitamin D 2000IU for 3months
- 12. • Vitamin Ddeficiency is the most common cause of hypocalcaemia after the first 3 days of life. • 6 High-dose vitamin D therapy with 1000-5000 IU/day for 3 months • Stoss therapy is effective for treating vitamin D deficiency in patients with poor compliance. It involves oral or intramuscular administration of vitamin D as 300 000 IU to 500 000 IU, as a single dose, or two to four divided doses for 3months.
- 13. • All pregnantwomen should have their serum 25- OHD concentration evaluated during the first trimester • If they are severely vitamin D deficient, they should be treated with 3000–5000 IU daily until the serum 25-OHD concentration is over 20 ng/ml.
- 14. CASE 2 13 days/male/term/2.5 kg admitted with Right focal since 2 days. Antenatal H/O • 29 year old Primi mother • No pre-existing medical or surgical illness / drug intake • Spontaneous conception • Antenatal period : uneventful
- 15. Birth H/O Gestation 38weeks Presentation Cephalic Liquor Clear Mode of delivery NVD Instrumentation No Cry Immediate Birth weight 2500 g APGAR (1,5 min) 8,9 Delivery room resuscitation No
- 16. • Baby dischargedon 2DOL. On exclusive breast feeds
- 17. Day 13 •Focal seizures involving RtUL and LL. Referred to Hospital. Loaded with AED Investigations S. Calcium – 3.6 iCa- 0.4 S.Mg – 1.1 Treated with Inj Calcium Gluconate 60mg/kg/day and Inj MgSO4 Investigations S. Ca – 6.5 iCa - 0.8 S. Mg 1.2 Day 15 • Referred to our Hospital
- 18. At Wadia • Vitals: – Temperature : 36.4 C – HR : 126/ min, RR : 50/ min – CRT <3 s, peripheral pulses : well palpable , BP : 76/41(53) mm Hg – SpO2 : 96 % on O2 prongs • General examination : normal • Systemic Examination : normal
- 19. DATE 16 DOL18DOL 21DOL 25DOL S.Ca 4.3 5.2 8.7 9.5 iCa 0.48 0.61 11.14 1.28 S.Po4 10.8 9.1 S.Mg 1.5 1.4 2.0 1.9 ALP 394 iPTH 41.9 pg/dl 100 pg/dl Vitamin D 25-OH D3 12.36 ng/dl Additional tests UCa/Cr – 0.2 FeMg – 1.1 Rx •Inj CaGlu 60mkd •Inj MgSO4 (50%)0.2ml/ kg •2000IU Vit D •Calcitriol was added. •Inj CalGLu MgSO4 contd. •Oral Ca and Mg at 150mkd 37.5md •Inj CaGlu and MgSO4 stopped. •Calcitrol stopped • Oral Cal Mg at 150mkd and 38mkd. FeMg {([Mg2+]urine × [creatinine]plasma)/ (0.7 [Mg2+]plasma × [creatinine]urine)} × 100 %. A FEMg of >4 % in a hypomagnesemic patient is consistent with renal Mg2+ wasting, while a patient with a FEMg of <2 % will likely have an extra-renal origin of their hypomagnesemia
- 20. • Diagnosis –Late onset Symptomatic Hypocalcemia with hypoparathyroidism secondary to hypomagnesemia. • Baby did not have any further episodes of seizures at our hospital. EEG was normal. AEDs stopped. • Discharged on Oral Calcium and Magnesium at 150mkd and 38mkd and Vitamin D 2000IU for three months.
- 21. • Hypomagnesemia causeshypocalcemia by interfering with the parathyroid cell CaSR-mediated release of PTH and by blunting end-organ PTH response
- 22. 1. Hypomagnesemia withsecondary hypocalcemia (HOMG1) present in the first weeks of life as persistent hypocalcemia, tetany, and seizures uncontrolled by anticonvulsants or calcium therapy. • AR. Results from defective intestinal magnesium absorption and renal magnesium leak. • Hypocalcemia is a secondary consequence of parathyroid failure and PTH resistance
- 23. 2. AR familialhypomagnesemia with hypercalciuria and nephrocalcinosis AD isolated renal magnesium wasting. • Recurrent urinary tract infections, polyuria and polydipsia, moderate metabolic acidosis with an inappropriately high urine pH, muscle weakness, persistent tetany, failure to thrive, SNHL and distal tubular acidosis. • Have hypercalciuria and nephrocalcinosis • S. Mg <0.8 mg/dL
- 24. 3. Transient Hypomagnesemia: • Decrease in serum magnesium level typically is less severe (0.8 to 1.4 mg/dL). • Magnesium salts are given, serum calcium and magnesium levels both rise.
- 25. 4. Secondary hypomagnesemia •Drug (e.g., loop diuretics, aminoglycosides, • amphotericin B) • Urinary tract obstruction. • Diuretic phase of acute renal failure
- 26. On follow up •Serum Magnesium levels were repeated when the baby was off Magnesium supplements. • They were found to be normal. • Dx - ?Transient Hypomagnesemia
- 27. Case 3 • 1day old/36 weeks/female/LSCS/2.7 kg/AGA admitted for o respiratory distress since birth.
- 28. Gestation 36 weeks PresentationCephalic Liquor Blood stained. No Meconium Mode of delivery LSCS (Abruptio Placenta) Instrumentation No Cry Immediate Birth weight 2700g APGAR (1,5 min) 7, 9 Delivery room resuscitation No
- 29. Antenatal H/O- • Firstand Second trimester was uneventful. • No maternal h/o of Diabetes Mellitus or Hyperparathyroidism. No H/o drug intake. • Born via LSCS (abruptio placenta).
- 30. Course • Intubated inv/o Respiratory distress and shifted to our hospital on 2DOL.
- 31. • Vitals :ET in situ – Temperature : 36.5 C – HR : 160/ min – CRT > 3 s, peripheral pulses : feeble – SPO2 : 94% with 30% Fio2 • General examination : Low set ears tented mouth and B/L CTEV • Systemic examination : Axial Hypotonia. Other systems normal.
- 32. Day 2 Atadmission baby in shock. Started on Dopamine f/b Adrenaline. Sepitc Screen normal. ABG - Metabolic Acidosis. 2D Echo – PPHN •Treated with Milrinone. Day 4 Extubated to NIV Day 6 Room Air. Haemodynmically stable On full feeds EBM 150/ml/kg/day.
- 33. DOL 11 1416 17 18 21 23 S. Ca 5.7 5.6 5.8 7.6 6 8.7 9.7 iCa 0.56 0.59 0.60 0.89 0.77 1.14 1.28 S. PO4 9.1 6.5 5.1 S.Mg 1.5 1.4 1.5 1.3 1.4 2.1 2.3 ALP 312 299 iPTH 39.7 Vit D 5 Others UCa/Creat – 0.3 FeMg – 1.8 Rx •Oral Vit D 2000IU •Oral Cal 100mg/kg/ d •Inj MgSO4 •Inj CaGlu at 60mg/kg/ day •Inj MgSO4 for 3d Oral calcitriol started. •Inc dose of Calcitriol. •Inj MgSO4 - BD Oral Calcium at 150mkd Inj MgSO4 stoppe d
- 34. • Genetic studiescould not be done due to non affordability.
- 35. Baby was dischargedon • Cap Calcitriol 0.25mg OD • Oral Calcium and magnesium 75mkd and 18mkd • Total Oral Vitamin D 2000 IU
- 36. Calcium • 99% oftotal body calcium - skeleton where, in combination with 89% of the total body phosphorous, it constitutes the major inorganic matrix of bone. • 1% - extracellular fluids and soft tissues.
- 37. Total serum calcium 50% Ionizedform at the normal serum protein concentration Biologically active component 40% Protein bound Albumin(80%) Globulins (20%) 8-10% Complexed to organic and inorganic acids (e.g., citrate, lactate, bicarbonate, sulfate, and phosphate Diffusible portion of circulating calcium Not biologically active Act as reserve
- 38. Factors affecting Calcium Concentration •Increases in ECF concentration of anions (phosphate, citrate, bicarbonate, edetic acid) will increase the proportion of bound calcium and decrease ionised calcium. • Alkalosis - increases the affinity of albumen for calcium and thereby decreases the concentration of ionised calcium. • Acidosis - inc iCa by decreasing the binding of calcium to albumen • While collecting, squeezed samples should be avoided.
- 39. • Hypoalbuminemia leadsto a decline in total serum calcium, but proportionate increases in the ionized fraction usually maintain serum Ca2+ concentration within the normal range. • correction formula in the setting of hypoalbuminemia • Corrected Ca Level = [0.8 ×(Normal Albumin Level − Patient’s Albumin Level Serum Ca Level
- 40. Perinatal calcium metabolism •In order to meet the high demand the fetus > maternal blood Ca and PO4 levels. • By active transport of calcium across the placenta by a calcium pump in the basal membrane that maintains a 1:1.4 maternal to fetal calcium gradient. • PTHrP produced by the parathyroids is largely responsible for regulating the calcium gradient and that the elevated fetal calcium level suppresses PTH release
- 41. • Fetal circulatingcalcium levels, as reflected in the cord blood total serum calcium concentration, increase with advancing gestational age, and at term the fetus is hypercalcaemic relative to maternal serum calcium concentrations.
- 42. • Close correlationbetween maternal and fetal serum 25(OH)D levels, consistent with transplacental transfer of this metabolite. • Hypocalcemia is commonly found in infants born to women with low circulating 25(OH)D levels resulting from poor dietary intake of vitamin D and lack of sunlight exposure.
- 43. • With birththe infant is abruptly disconnected from the placenta and the maternal supply of calcium and, thus, becomes entirely dependent on the intake of calcium from the gastrointestinal tract and skeletal calcium reserves to maintain serum calcium levels
- 44. After birth • Serumcalcium level falls over the first 24 h of life • PTH increases. But response deficient. Hence phsiological nadir in first two days. • 1, 25 (OH) D - Rise to adult levels within few days • Calcitonin - Rises 2-10 times of cord blood levels within 48 hrs. Highest levels in hypocalcemic premature and asphyxiated newborns
- 45. After birth, withthe abrupt termination of the maternal calcium supply, serum calcium in the newborn decreases, and serum PTH increases correspondingly VLBW have a decreased PTH surge compared with full-term infants
- 46. Factors affecting absorption LowGI pH Lactose Casein MCT oil Palmitic acid Precipitation Glucocorticoids Phenytoin Phenobarbital
- 47. Absorption : Humanmilk vs formula • Percentage of calcium absorption may be slightly less with formula milk (40% v/s 60%) but net calcium retention was similar 160-170 mg/d Fomon S.J., Nelson S.E. Calcium, phosphorus, magnesium, and sulfur. In: Fomon S.J., editor. Nutrition of Normal Infants. Mosby-Year Book, Inc.; St. Louis, MO, USA: 1993. pp. 192–218.
- 48. Phosphorous • The serumconcentrations of calcium and phosphate are reciprocally related under normal circumstances, and the calcium phosphate product approximates 30.
- 49. • The kidneyregulates phosphate homeostasis. • 85% - reabsorbed by active transport against an electrochemical gradient across the apical membrane of the cells lining the proximal renal tubule via the type II sodium/phosphate cotransporters encoded by SLC34A1 (NPT2a) and SLC34A3 (NPT2c)
- 50. Decreased expression ofSLC34A1 (NPT2a) and SLC34A3 (NPT2c) by • PTH, PTHrP, FGF23, and glucocorticoids • high phosphate intake
- 52. Parathyroid–Renal Hormonal Axis ParathyroidHormones • PTH is a 9500-Da, single-chain polypeptide. It is synthesized by the four parathyroid glands embedded within the thyroid gland poles • t1/2 - 4 minutes • The normal iPTH - 10 to 60 picogram (pg)/mL; • maximally stimulated (hypocalcemic)- 100 to 150 pg/mL • Minmally suppressed (hypercalcemic) - 2 to 5 pg/mL.
- 53. Role Of PTH •The parathyroid detects changes of blood Ca2+ concentration as small as 0.025 to 0.05 mmol/L and promptly adjusts PTH secretion. • These minute changes are detected by a member of G protein–coupled receptors, Ca2+- sensing receptor (CaSR) present in parathyroid cells, thyroidal C cells, renal tubular cells, osteoblasts.
- 54. • CaSR signalingin the parathyroid – Activates phosphatidylinositol 4,5 bisphosphate signal transduction pathway release of Ca2+ from intracellular storage sites and subsequent increase in synthesis and secretion of PTH.
- 55. PTH (+)osteoclastogenesis Inc bone resorption ProxRT - dec reabsorption of filtered phosphate directly and indirectly by inc fibroblast growth factor-23 Inc 1α hydroxylase Distal RT – inc reabsorption of filtered Ca2+ synthesis
- 58.
- 60. Other Hormones Calcitonin • Peptidehormone synthesized by thyroid parafollicular C cells (also known as clear cells) • Antihypercalcemic effect. • Inhibiting bone resorption • Increases calcium excretion in the kidneys
- 61. Glucocorticoids • lower serumcalcium concentration by inhibiting osteoclast formation and activity, but use for a long time causes osteoporosis by decreasing bone formation and increasing bone resorption. • They also decrease intestinal absorption and increase renal excretion of calcium and phosphorus.
- 62. Hypocalcemia • Total serumcalcium level of less than 2 mmol/L (8 mg/dL), less than 1.87 mmol/L, or less than 1.75 mmol/L Total Ionized >1500 g 8 mg/dL (2 mmol/L) 4.4 mg/dL (1.1 mmol/L) <1500g 7 mg/dL (1.75 mmol/L) 4 mg/dL (1 mmol/L) J. Oden and M. Bourgeois, “Neonatal endocrinology,” The Indian Journal of Pediatrics, vol. 67, no. 3, pp. 217–223, 2000.
- 63. Early-Onset Hypocalcemia (<48Hours of Age) • Prematurity • Perinatal distress/asphyxia • Infants of diabetic mothers • Intrauterine growth restriction
- 64. Early onset Preterm •Hypoalbuminemia •Reduced intake •Impairedresponse to PTH •Increased calcitonin levels •Increased urinary losses •High renal sodium excretion aggravates calciuric losses and •relative end-organ resistance to 1,25(OH)2D3 Asphyxia •Increased phosphate load caused by tissue catabolism •Decreased intake •Renal insufficiency •Increased calcitonin •Correction of acidosis with alkali
- 65. IDM • 10-50% cases •Exaggerated postnatal drop • The greater bone mass and relative undermineralization typical of macrosomic IDMs may increase the neonatal demand. • Urinary magnesium losses with diabetes and leads to fetal magnesium deficiency and secondary functional hypoparathyroidism in the fetus and newborn R. C. Tsang, R. Strub, D. R. Brown, J. Steichen, C.Hartman, and I.-W. Chen, “Hypomagnesemia in infants of diabetic mothers: perinatal studies,” Journal of Pediatrics, vol. 89, no. 1, pp. 115–119, 1976.
- 66. Late • 4-7 days •Usually symptomatic • More frequent in term than preterm infants
- 67. Root AW, DiamondFB. (2008) Disorders of Mineral Homeostasis in the Newborn, Infant, Child, and Adolescent
- 68.
- 70. Root AW, DiamondFB. (2008) Disorders ofMineralHomeostasis in theNewborn, Infant, Child, and Adolescent.
- 71. Clinical features • Jitteriness(increased neuromuscular irritability and activity) • Apnea • Generalized convulsions/ focal seizures • Lethargic, eat poorly, vomit, abdominal distention • Stridor
- 72. Treatment - SymptomaticHypocalcemia • Preparation : calcium gluconate (usual) or calcium chloride • Content : – 10% solution of calcium gluconate contains about 9.4 mg of elemental calcium / mL • Seizures : – 1 to 2 mL/kg of calcium gluconate (about 18 mg/kg of elemental calcium) IV over 10 minutes • Seizures resolved : – IV calcium solution @1.87 mmol/kg (75 mg/kg) of elemental calcium per day until the serum calcium in the normal range • Tapering : – Stepwise fashion (e.g., 50% for 4-12 hours, 25% for another 4-12 hours) and then discontinue
- 73. • Calcium chloride(20 mg/kg or 0.2 mL/kg) can be given; this preparation is metabolized more rapidly
- 74. Complications • Extravasation intosoft tissues • Cutaneous necrosis • Bradycardia
- 75. Precautions • PN solutionswith standard mineral (including calcium) content can be safely infused through appropriately positioned umbilical venous catheters or percutaneous centrally placed catheters • Direct administration of calcium preparations with bicarbonate results in precipitation • Continuous calcium gluconate infusion is preferred rather than 1 mL/kg/dose intravenous bolus doses every 6 h Vuralli D. Clinical approach to hypocalcemia in newborn period and infancy: who should be treated?. International Journal of Pediatrics. 2019;2019.
- 76. Oral therapy • Infantstolerating oral fluids • Not actively having seizures • IV calcium gluconate as oral at the same dose after the initial correction
- 77. Precautions • All calciumpreparations are hypertonic • May precipitate NEC • Absorption from calcium carbonate limited by higher pH of neonatal stomach • Calcium glubionate are commonly used in neonatal period • Duration of supplemental calcium therapy varies with course of hypocalcemia • Assess serum calcium frequently during the first few days and 1 or 2 days after discontinuation until the serum calcium and Ca2+ concentrations stabilized
- 78. Asymptomatic Hypocalcemia • Treator not to treat? • Resolves spontaneously with time • Hypocalcemia has potentially adverse effects on CVS and CNS • Treatment is recommended when the serum calcium level is <7 mg/dL (T), <6 mg/dL (PT) • 40 to 80 mg/kg/d elemental calcium Vuralli D. Clinical approach to hypocalcemia in newborn period and infancy: who should be treated?. International Journal of Pediatrics. 2019;2019.
- 79. Late Neonatal Hypocalcemia •Low-phosphorus infant formula similac 60/40 (or human milk) and oral calcium supplementation • Correct hypomagnesemia • Dose : – IV 50% solution of MgSO4 @25 mg/kg with continuous ECG monitoring – 25–50mg/kg or 0.2–0.4mEq/L per dose every 12 h, intravenously over 2 h or intramuscularly – Until serum magnesium concentration rises above 1.5mg/dL (0.62mmol/L). • True hypoparathyroidism : – Calcitriol . International Journal of PediatricsVolume 2019,
- 80.
Editor's Notes
- #6 CXR : b/l diffuse haziness
- #33 D/D : CCHD, severe pneumonia, PPHN, methemoglobinemia, pulmonary developmental disorder, CDH, ILD, spontaneous pneumothorax Sepsis screen : negative HCT : 57.1% CXR : b/l diffuse haziness
- #38 Ionized calcium is the only physiologically active fraction. The proteinbound calcium is not biologically active but provides a rapidly available reserve of calcium
- #48 ) or indirectly through interference with vitamin D metabolism
- #63 normal acid-base status and normal albumin levels, the serum total calcium level and Ca2+ are linearly correlated, so total serum calcium measurements remain useful as a screening test. However, because Ca2+ is the physiologically relevant fraction, in sick infants, it is preferable to directly determine Ca2+ in freshly obtained blood samples
- #65 IUGR : decreased transfer of Ca across the placenta.
- #66 Improved metabolic control for pregnant diabetic women has markedly diminished the occurrence and severity of early neonatal hypocalcemia in IDMs. The incidence of hypocalcemia is also increased in the infants of gestational diabetic mothers, and the role of hypomagnesemia has been demonstrated
- #67 The phosphate load increases calcium bone deposition, leading to hypocalcemia. In these infants, the renal tubular cells are unable to respond appropriately to PTH, leading to renal retention of phosphorus and hypocalcemia
- #68 stimulate PTH secretion, and increases suppress it. Acute decreases in magnesium concentrations also stimulate PTH secretion, and increases depress it. However, chronic magnesium deficiency paradoxically decreases PTH secretion, probably by altering the calcium-sensitive, magnesium-dependent adenylate cyclase involved in PTH secretion.
- #73 intravenous calcium solution can be reduced in a stepwise fashion (e.g., 50% for 4-12 hours, 25% for another 4-12 hours) and then discontinued. e changes in [Ca++] following calcium administration are short-lived (minutes); rapidity of ionization seems to exclude hepatic metabolism as an important factor in the dissociation of calcium gluconate; and equivalent rises in [Ca++] produced by calcium gluconate or calcium chloride resulted in equivalent cardiovascular effects
- #80 magnesium dose may be repeated every 12 hours, depending on the clinical response and the (monitored) serum magnesium levels.