|Year : 2013 | Volume
| Issue : 4 | Page : 697-703
Clinical, biochemical, and radiological manifestations of vitamin D deficiency in newborns presented with hypocalcemia
Ashraf Soliman1, Husam Salama2, Sufwan Alomar2, Emad Shatla2, Khaled Ellithy3, Elsaid Bedair4
1 Department of Pediatrics, Women’s Hospital, Hamad Medical Center, Doha, Qatar
2 Newborn and Infant Intensive Care Unit, Women's Hospital, Hamad Medical Center, Doha, Qatar
3 Pediatric Intensive Care Unit, Hamad General Hospital, Hamad Medical Center, Doha, Qatar
4 Department of Radiology, Al Khor Hospital, Hamad Medical Center, Hamad Medical Center, Doha, Qatar
|Date of Web Publication||20-Jun-2013|
Department of Pediatrics, Hamad Medical Center, P.O. Box 3050, Doha
Source of Support: Hamad Medical Center, Conflict of Interest: None
| Abstract|| |
Introduction: The Clinical and radiological manifestations of newborns with severe VDD have not been studied well. Materials and Methods: We studied the clinical, biochemical, and radiological manifestations of 10 full-term (FT) newborns (6: M, 4: F) infant presented to with symptomatic hypocalcemia (seizure) secondary to vitamin D deficiency (VDD) during the first 10 days of life are described. All were exclusively breastfed since birth. All their mothers have low 25 hydroxy vitamin D (25OHD) level <10 ng/mL and were not taking vitamin supplements during pregnancy. Results: FT newborns with hypocalcemia secondary to VDD presented with generalized convulsions (10/10) and craniotabes (8/10), but none had rachitic chest rosaries or joint broadening. Cranial ultrasonographic evaluation was normal. Serum 25OHD concentrations were low in these newborns (13.2 ± 3.8 ng/mL) and their mothers (8.1 ± 1.5 ng/mL). A total of 60% of them had increased parathormone (PTH) concentrations (>60 ng/mL) and 60% had decreased magnesium (Mg) concentrations (<0.7 mmol/L). Their alkaline phosphatase (ALP) concentrations were significantly higher than normal newborns. All other laboratory results (liver function tests, urea and electrolytes, C reactive protein, lumbar puncture, blood culture, and lactate) were normal. In all patients, seizures ceased within 2 days of starting treatment with alphacalcidol and calcium. Radiological manifestations included metaphyseal band of relative lucency (osteopenia), just under the line of provisional calcification, within distal radius (7/10), femur (4/10), and tibia (3/10), mild cupping and haziness of distal radius (2/10). Discussion: Newborns with VDD had significantly lower serum calcium, ALP and PTH and higher phosphate concentrations, compared to older infants with VDD rickets. In newborns with VDD, serum calcium levels were correlated significantly with 25OHD (r = 0.597, P < 0.001), Mg concentrations (r = 0.436, P < 0.001) and negatively with ALP concentrations (r = −0.451, P < 0.001). Serum PTH concentrations were correlated significantly with serum Mg (r = 0.78, P < 0.0001) but not with serum calcium (r = −0.103, P = 0.3) or 25OHD (r = −0.03, P = 0.7) concentrations. Conclusion: The clinical, biochemical, and radiological manifestations of VDD in newborns indicate that they are less adapted to VDD compared to older infants. VD supplementation for mothers and newborns should be considered to avoid short-term complications of VDD in the neonatal period and on the growing infants especially in countries with high prevalence of VDD.
Keywords: Adaptation, calcium, infants, maternal, newborns, 25OH vitamin D, parathormone, phosphate, radiology, rickets, vitamin D deficiency
|How to cite this article:|
Soliman A, Salama H, Alomar S, Shatla E, Ellithy K, Bedair E. Clinical, biochemical, and radiological manifestations of vitamin D deficiency in newborns presented with hypocalcemia. Indian J Endocr Metab 2013;17:697-703
|How to cite this URL:|
Soliman A, Salama H, Alomar S, Shatla E, Ellithy K, Bedair E. Clinical, biochemical, and radiological manifestations of vitamin D deficiency in newborns presented with hypocalcemia. Indian J Endocr Metab [serial online] 2013 [cited 2019 Nov 13];17:697-703. Available from: http://www.ijem.in/text.asp?2013/17/4/697/113764
| Introduction|| |
Recent reports showed high incidence of vitamin D deficiency (VDD) in pregnant women. Placental transfer of 25OHD is the major source of vitamin D to the developing human fetus. There is growing concern about adverse health impacts that VDD during pregnancy may have on the mother, fetus, infant, and later in life. ,,,,,,
Classically, VDD presents with skeletal manifestations of rickets in childhood and osteomalacia in adults. ,, However, the clinical and radiological manifestations of severe VDD in newborns are scantily described. Craniotabes in breastfed newborns, with normal serum calcium and phosphorus levels, has been shown to be associated with VDD in utero, and the deficiency persists at 1 month but becomes undetectable after 3-4 week of treatment with vitamin D. , Deficient maternal vitamin D status has been shown to be associated with lower birth weight, higher small for gestational age risk and altered neonatal growth, both in weight and in length.  Severe VDD deficiency in newborns can also present with hypocalcemia and hypocalcemic symptoms including seizures. ,, Rarely, hypocalcemia secondary to VDD deficiency presents as reversible cause of dilated cardiomyopathy in newborns. 
The aim of this study was to describe the clinical, biochemical, and radiological manifestations of full-term (FT) newborns with VDD, born to mothers with VDD, who presented with hypocalcemia during the neonatal period.
| Materials and Methods|| |
All singleton term infants (gestational age = or >37 weeks, and birth weight >2.5 kg) with VDD and symptomatic hypocalcemia born to VDD mothers. VDD were studied between January 2011 and January 2012. 10 FT infants were identified as candidates for this study who presented with symptomatic neonatal hypocalcemia during the first 10 days of their life (5.9 ± 2.2 days). One hundred FT normal infants, born at the same period, and 18 infants aged >6 months with clinically florid rickets due to VDD served as controls.
Gestational age, measured in weeks completed, was based on maternal dates and early ultrasounds or the modified Ballard score assessment. 
All patients were subjected to the following:
Hypocalcemia was diagnosed when serum calcium <2 mmol/L, hypomagnesemia was diagnosed when serum magnesium <0.7 mmol/L, hypophosphatemia was diagnosed when serum PO4 was <0.9 mmol/L, and high parathormone was diagnosed when PTH (intact molecule) >60 ng/L. 
- Detailed history taken from the mother including nutritional intake
- Physical examination including clinical manifestations of rickets
- Anthropometric measurements including weight, length, and head circumference. Length was measured with an infant length measuring board: This board has a 100-cm capacity (collapses to 30 cm) and has 0.1 cm increments, with the sliding head-foot piece. The weight was measured using an electronic baby scale with digital display
- Venous blood sample were collected at presentation (5.9 ± 2.2 days of age) for measurement of serum calcium (Ca), phosphate (PO4), albumin, alkaline phosphatase (ALP), parathormone (intact molecule) (PTH), and 25OHD concentrations. The serum was stored at −30°C prior to testing. Serum Ca was corrected for individual variations in serum albumin using the following formula: Corrected serum Ca (in millimoles per liter) = Measured serum Ca (in millimoles per liter) +0.02 × [40 - measured albumin (in grams per liter)]. Newborns and mothers with plasma 25OHD levels less than 10 ng/mL were considered to have VDD. PTH and 25-OH-D were measured by radioimmunometric assay using reagents purchased from Mediagnost (Reutlingen, Germany). Intraassay coefficients of variation were 6.9% and 5.8%, respectively; and interassay coefficient of variations was 8.9% and 8.2%, respectively.
Ethical committee of Hamad Medical Center (HMC) approved the study and informed consent was obtained from all parents of the newborns. For ethical reasons, hormonal concentrations for normal controls were not measured. The presence or absence of radiological evidence of rickets was determined from routine radiographic report of the hand and knee in patients. Informed consents were obtained from the parents.
Results were expressed as the mean ± standard deviation. A nonpaired Student's t test was used to compare growth parameters and analyte concentrations between hypocalcemic and control groups. Correlation and linear regression analyses were used to investigate the relation between growth parameters and the other variables. Significance was accepted at P < 0.05.
| Results|| |
Ten FT newborns with hypocalcemia secondary to VDD were recruited in this study. They had gestational age = 37 ± 1.2 weeks compared to normal controls (39.7 ± 1.1 weeks) (P < 0.05). Their birth weight, length, head circumference, and the size of anterior fontanel did not differ compared to normal newborns [Table 1].
|Table 1: Anthropometric and lab data of newborns with VDD and hypocalcemia|
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These newborns with VDD developed neonatal seizure between the 5 th and 10 th days of their life. Eight out of 10 had craniotabes, but none had rachitic chest rosaries or joint broadening. One newborn had dilated cardiomyopathy diagnosed by chest x ray (CXR) and echocardiography that responded to vitamin D therapy for 4 months. Neurological examination was within normal limits. Cranial ultrasonography was normal in all patients.
Hypocalcemic newborns had serum 25OHD concentrations = 13.2 ± 3.8 ng/mL and their mothers had 25OHD concentrations =8.1 ± 1.5 ng/mL. Serum magnesium was low (0.65 ± 0.08 nmol/L) in all. Their serum ALP concentrations were significantly higher than normal newborns. A total of 6/10 patients had increased PTH concentrations (>60 ng/mL). Serum PO4 concentration did not differ between patients and normal newborns [Table 2].
|Table 2: Anthropometric and biochemical data of newborns with Vitamin D defi ciency versus controls|
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Newborns with VDD had significantly lower serum calcium, ALP and PTH and higher PO4 concentrations compared to older infants with VDD [Table 3].
In newborns with VDD, plain x-ray studies performed between the 5 th and 10 th days after birth showed a metaphyseal band of relative lucency (osteopenia) (8/10), just under the line of provisional calcification, within distal radius (7/10), femur (4/10) and tibia (3/10) [Figure 1]. Mild cupping and haziness of distal radius and ulna occurred in two patients [Figure 2]. No significant change was seen in the cortical thickness or trabeculations of the other long bones.
|Figure 1: Metaphyseal band of relative lucency (just under the line of professional ossifi cation) within distal radius, femur, and tibia|
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|Table 3: Anthropometric and lab data of newborns versus infants with Vitamin D deficiency|
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In newborns with VDD, serum calcium levels were correlated significantly with 25OHD concentrations (r = 0.597, P < 0.001), magnesium concentrations (r = 0.436, P < 0.001), and negatively with ALP concentrations (r = −0.451, P < 0.001). PTH concentrations were correlated significantly with serum magnesium (r = 0.78, P < 0.0001) [Figure 3] but not with serum calcium (r = −0.103, P = 0.3) or 25OHD (r = −0.03, P = 0.7) concentrations.
|Figure 3: Correlation between parathormone and Mg concentrations in newborns with vitamin D deficiency|
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All newborn patient with VDD were started on alphacalcidol (100 ng/kg once a day, which was reduced to 50 ng/kg/day after 1 week), and calcium supplements (0.25 mmol/kg/day). In all patients, seizures ceased within 2 days of starting treatment.
| Discussion|| |
VDD during pregnancy has been associated with neonatal hypocalcemia, osteopenia, hypoplasia of the enamel of primary teeth, slow statural growth during the 1 st year of life and uncommonly with neonatal rickets. [17-24]
Rickets is a bone disease caused by a deficiency of vitamin D that causes decreased calcium absorption from the intestine and abnormalities in formation and mineralization of skeletal bone and results in weak bones, along with slowed growth and skeletal development. ,, Although there have been sporadic case reports of congenital rickets, the characteristics of early-onset rickets are not well-described. Here, we report our experience with 10 newborns presenting with hypocalcemia due to VDD in the first 2 weeks of life and characterize their clinical, biochemical, and radiological features in comparison with older infants (>6 months) with VDD rickets.
Observational studies and clinical trials found a relationship between maternal vitamin D status and neonatal calcium metabolism, with a greater risk of hypocalcemia among infants born to vitamin D deficient mothers.  Our newborns with VDD, born to VVD mothers, who presented with symptomatic hypocalcemia had normal serum phosphate, mild or no elevation (60%) of PTH level levels in response to hypocalcemia and mild increase of ALP level. Clinically, 80% of them had craniotabes and 80% had radiological changes. Hatun et al.,  reported symptomatic hypocalcemia (79%), normal or high serum phosphate concentrations (71%) and subtle radiological changes in their young infants with VDD during the first 3 months of life.
These biochemical, hormonal, and radiological manifestations of neonatal rickets differed significantly from those for older infants with VDD. Older infants with VDD rickets had normal serum calcium, low serum phosphorus, markedly elevated serum alkaline phosphatase, low 25OHD levels, and secondary hyperparathyroidism that enabled them of better adaptation compared to newborns with VDD. ,
Vitamin D and 25OHD cross the placenta during the last months of gestation and establish vitamin D stores for the newborn. Cord concentrations of the major vitamin D metabolites are consistently lower than those measured in the mother's serum. Placental vein 25OHD correlates significantly with those found in the maternal circulation, implying that it diffuses easily across the placental barrier and that the vitamin D pool of the fetus depends entirely on that of the mother. After birth, vitamin D requirements of infants are influenced by the body stores at birth, which in turn are related to the length of gestation and maternal stores. [30-32] Breastfed infants rely primarily on cutaneous synthesis to maintain a normal vitamin D status because the amount of vitamin D obtained through human milk is usually insufficient (12-60 U/L). ,
Abruptly severed from the placental supply of nutrients after birth, newborns must adapt rapidly to ensure positive calcium balance for normal skeletal growth and development. In healthy, FT newborns, total and ionized calcium concentrations progressively decrease after birth, so that by the 2 nd or 3 rd day of life calcium concentrations are often lower than that those found in older infants and children. Serum PTH concentrations tend to be low in cord blood but increase within the first 48 h of life in response to the decrease in serum calcium. The latter also induces increased synthesis of 1,25-dihydroxyvitamin D to the 5 th day of life in a normal fashion. The mainly passive absorption of intestinal calcium during the first 4-5 days after birth changes to the active 1-25 dihydroxyvitamin D dependent mechanism and therefore calcium concentrations usually return to normal by 5-10 day of age.  This explains the occurrence of hypocalcemia in our newborns with low 25OH D because of lack/or attenuation of these changes (adaptation). ,,, The significant correlation between serum calcium and 25OHD concentrations in our newborns with VDD supports this view.
In addition, in our VDD newborns, the low calcium and 25OHD levels were not associated with adequate increase PTH level (as occurred in older infants with VDD), denoting relative deficiency of PTH secretion in response to hypocalcemia. PTH concentrations were not correlated with serum calcium or 25OHD levels. The significant correlation between serum magnesium and PTH concentrations in our VDD newborns supported this explanation. In accordance with our findings, most patients with Mg deficiency and hypocalcemia have low or inappropriate normal (for the hypocalcemia) serum concentrations of PTH. Serum concentration of 1,25(OH)2-vitamin D is usually low in hypocalcemic Mg deficient patients. Hypomagnesemia can impair PTH secretion and induce resistance to PTH. Both lead to decreased renal synthesis of 1,25(OH)2-vitamin D. Magnesium deficiency induces skeletal resistance to the action of PTH. ,,,,
Similarly, Thomas et al.,  studied 78 infants moderate-to-severe transient neonatal hypocalcemia at median age of 8.0 days. Their neonates were severely hypocalcemic and hyperphosphatemic. Seventy-five of 78 were hypomagnesemic, and the majority had low or inappropriately normal parathyroid hormone responses. Levels of 25-hydroxyvitamin D were ≤25 ng/mL. All infants responded to therapy of limited duration with 1 or more of the following: Calcium supplements, calcitriol, low phosphorus formula, and magnesium supplementation. They suggested that severe late-onset neonatal hypocalcemia is often a sign of coexistent vitamin D insufficiency or deficiency and hypomagnesemia, and is readily managed with therapy of limited duration.
Other possible explanation is that maternal VDD leads to secondary hyperparathyroidism, which results in a transitory hypoparathyroidism and hypocalcemia in the neonate.  A controlled study showed that maternal vitamin D supplementation dampens the decrease in serum calcium observed in newborns at 4 day of age. 
Maternal vitamin D supplementation may allow ready transfer of a large pool of 25-hydroxyvitamin D to the newborn followed by rapid renal synthesis of 1,25-dihydroxyvitamin D to meet the needs of the newborn: This view is supported by the higher values of circulating 1,25-dihydroxyvitamin D observed at 4 day of age in infants born to supplemented mothers. 
Ahmed et al.,  reported 65 infants with neonatal hypocalcaemic seizures, who were totally breast fed and did not receive vitamin D supplementation, and subsequently found to have rickets. In a subgroup of 15 mothers and their infants, had very low plasma levels of 25(OH) vitamin D.
The normal serum phosphate concentration in our newborns may be explained also by the relative renal immaturity of phosphate handling and/or resistance to the phosphaturic effect of PTH levels in these newborns compared to those in older infants. Low serum calcium concentrations, even in the presence of normal PO4 concentrations, (low calcium × phosphate solubility product) may explain in part the defective mineralization of the metaphysis that appeared in 8/10 of these patients.
Data relating to vitamin D and fetal bone growth are limited. A study of 198 children born in the United Kingdom indicated that the maternal use of vitamin D supplements was significantly associated with greater childhood bone mineral mass and vitamin D supplementation of pregnant women can decrease bone resorption in vitamin D inadequate newborns. ,,
In this study, 8/10 of our hypocalcemic newborns with VDD had craniotabes and radiological evidence of bone disease in the metaphysis (metaphyseal band of osteopenia) of long bones. It is known that osteoporosis of any etiology developing in utero, or during infancy, is most pronounced in the metaphyses and may assume a striped appearance that we found in our newborns with VDD.  Craniotabes in FT newborn is a further evidence of bone affection by VDD in utero.  Other studies showed that maternal vitamin D status can affect bone mineral accrual during the intrauterine period and influence bone size at birth. ,,, Collectively, these data provide evidence that in utero VDD is important for bone development and growth. It appears that newborns, especially those with VDD due to maternal VDD, are less adapted than older infants and toddlers to VDD because they have lower PTH secretion in response to hypocalcemia, decreased skeletal response to PTH, and decreased bone mass. ,
In conclusion, hypocalcaemia in newborns with VDD is exaggerated by the relatively immature PTH response to hypocalcemia. In countries with high prevalence of VDD, maternal vitamin D supplementation during pregnancy and early supplementation of vitamin D to newborns should be considered to avoid hypocalcemia and skeletal abnormalities in the newborns and growing infants.
| References|| |
|1.||Hollis BW, Wagner CL. Vitamin D deficiency during pregnancy: An ongoing epidemic. Am J Clin Nutr 2006;84:273. |
|2.||Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr 2007;137:447-52. |
|3.||van der Meer IM, Karamali NS, Boeke AJ, Lips P, Middelkoop BJ, Verhoeven I, et al. High prevalence of vitamin D deficiency in pregnant non-Western women in The Hague, Netherlands. Am J Clin Nutr 2006;84:350-3. |
|4.||Judkins A, Eagleton C. Vitamin D deficiency in pregnant New Zealand women. N Z Med J 2006;119:U2144. |
|5.||Lee JM, Smith JR, Philipp BL, Chen TC, Mathieu J, Holick MF. Vitamin D deficiency in a healthy group of mothers and newborn infants. Clin Pediatr (Phila) 2007;46:42-4. |
|6.||Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, et al. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: A longitudinal study. Lancet 2006;367:36-43. |
|7.||Dror DK, Allen LH. Vitamin D inadequacy in pregnancy: Biology, outcomes, and interventions. Nutr Rev 2010;68:465-77. |
|8.||Thomas TC, Smith JM, White PC, Adhikari S. Transient neonatal hypocalcemia: Presentation and outcomes. Pediatrics 2012;129:e1461-7. |
|9.||Yorifuji J, Yorifuji T, Tachibana K, Nagai S, Kawai M, Momoi T, et al. Craniotabes in normal newborns: The earliest sign of subclinical vitamin D deficiency. J Clin Endocrinol Metab 2008;93:1784-8. |
|10.||Leffelaar ER, Vrijkotte TG, van Eijsden M. Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: Results of the multi-ethnic Amsterdam Born Children and their Development cohort. Br J Nutr 2010;104:108-17. |
|11.||Camadoo L, Tibbott R, Isaza F. Maternal vitamin D deficiency associated with neonatal hypocalcaemic convulsions. Nutr J 2007;6:23. |
|12.||Teaema FH, Al Ansari K. Nineteen cases of symptomatic neonatal hypocalcemia secondary to vitamin D deficiency: A 2-year study. J Trop Pediatr 2010;56:108-10. |
|13.||Salama MM, El-Sakka AS. Hypocalcemic seizures in breastfed infants with rickets secondary to severe maternal vitamin D deficiency. Pak J Biol Sci 2010;13:437-42. |
|14.||Al Azkawi H, Al Mutair A. Newborn with dilated cardiomyopathy secondary to vitamin d deficiency. Case Rep Pediatr 2012;2012:945437. |
|15.||Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R. New Ballard Score, expanded to include extremely premature infants. J Pediatr 1991;119:417-23. |
|16.||Fenton TR, Lyon AW, Rose MS. Cord blood calcium, phosphate, magnesium, and alkaline phosphatase gestational age-specific reference intervals for preterm infants. BMC Pediatr 2011;11:76. |
|17.||Ford JA, Davidson DC, McIntosh WB, Fyfe WM, Dunnigan MG. Neonatal rickets in Asian immigrant population. Br Med J 1973;3:211-2. |
|18.||Moncrieff M, Fadahunsi TO. Congenital rickets due to maternal vitamin D deficiency. Arch Dis Child 1974;49:810-1. |
|19.||Hoff N, Tyrala E, Haddad I, Hillman L. 25-hydroxyvitamin D deficiency in osteopenia of the extreme premature. Pediatr Res 1976;10:4-10. |
|20.||Brooke OG, Brown IR, Bone CD, Carter ND, Cleeve HJ, Maxwell JD, et al. Vitamin D supplements in pregnant Asian women: Effects on calcium status and fetal growth. Br Med J 1980;280:751-4. |
|21.||Brooke OG, Butters F, Wood C. Intrauterine vitamin D nutrition and post natal growth in Asian infants. Br Med J (Clin Res Ed) 1981;283:1024. |
|22.||Purvis RJ, Barrie WJ, MacKay GS, Wilkinson EM, Cockburn F, Belton NR. Enamel hypoplasia of the teeth associated with neonatal tetany: A manifestation of maternal vitamin D deficiency. Lancet l973;2:811-4. |
|23.||Cockburn F, Belton NR, Purvis RI, Giles MM, Brown JK, Turner TL, et al. Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants. Br Med J 1980;28l:11-4. |
|24.||Pettifor JM, Isdale JM, Sahakian J, Hansen JD. Diagnosis of subclinical rickets. Arch Dis Child 1980;55:l55-7. |
|25.||Hatun S, Ozkan B, Orbak Z, Doneray H, Cizmecioglu F, Toprak D, et al. Vitamin D deficiency in early infancy. J Nutr 2005;135:279-82. |
|26.||Soliman AT, Al Khalaf F, Alhemaidi N, Al Ali M, Al Zyoud M, Yakoot K. Linear growth in relation to the circulating concentrations of insulin-like growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: Endocrine adaptation to vitamin D deficiency. Metabolism 2008;57:95-102. |
|27.||Specker B. Nutrition influences bone development from infancy through toddler years. J Nutr 2004;134:691-5S. |
|28.||Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81:353-73. |
|29.||Delvin EE, Glorieux FH, Salle BL, David L, Varenne JP. Control of vitamin D metabolism in preterm infants: Feto-maternal relationships. Arch Dis Child 1982;57:754-7. |
|30.||Gertner JM, Glassman MS, Coustan DR, Goodman DB. Feto-maternal vitamin D relationship at term. J Pediatr 1980;97:637-40. |
|31.||David L. Common vitamin D3 deficiency rickets. In: Glorieux FH, editor. Rickets. Nestle nutrition workshop series. New York, USA: Raven Press; 1991. p. 107-12. |
|32.||Specker BL, Valanis B, Hertzberg V, Edwards N, Tsang RC. Sunshine exposure and serum 25-hydroxyvitamin D concentrations in exclusively breast-fed infants. J Pediatr 1985;107:372-6. |
|33.||Hollis BW, Roos BA, Draper HH, Lambert PW. Vitamin D and its metabolites in human and bovine milk. J Nutr 1981;111:1240-8. |
|34.||Christopher SK, Fuleihan GE. Calcium and bone disorders during pregnancy and lactation. In endocrine disorders during pregnancy. Endocrinol Metab Clin N Am 2006;35:21-52. |
|35.||Davis OK, Hawkins DS, Rubin LP, Posillico JT, Brown EM, Schiff I. Serum parathyroid hormone (PTH) in pregnant women determined by an immunoradiometric assay for intact PTH. J Clin Endocrinol Metab 1988;67:850-2. |
|36.||David L, Anast CS. Calcium metabolism in newborn infants. The interrelationship of parathyroid function and calcium, magnesium, and phosphorus metabolism in normal, "sick," and hypocalcemic newborns. J Clin Invest 1974;54:287-96. |
|37.||Steichen JJ, Tsang RC, Gratton TL, Hamstra A, DeLuca HF. Vitamin D homeostasis in the perinatal period: 1,25-dihydroxyvitamin D in maternal, cord, and neonatal blood. N Engl J Med 1980;302:315-9. |
|38.||Paunier L, Lacourt G, Pilloud P, Schlaeppi P, Sizonenko PC. 25-hydroxyvitamin D and calcium levels in maternal, cord and infant serum in relation to maternal vitamin D intake. Helv Paediatr Acta 1978;33:95-103. |
|39.||Rude RK, Oldham SB, Sharp CF Jr, Singer FR. Parathyroid hormone secretion in magnesium deficiency. J Clin Endocrinol Metab 1978;47:800-6. |
|40.||Litosch I. G protein regulation of phospholipase C activity in a membrane-solubilized system occurs through a Mg2(+)- and time-dependent mechanism. J Biol Chem 1991;266:4764-71. |
|41.||Volpe P, Alderson-Lang BH, Nickols GA. Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release. I. Effect of Mg2+. Am J Physiol 1990;258:C1077-85. |
|42.||Northup JK, Smigel MD, Gilman AG. The guanine nucleotide activating site of the regulatory component of adenylate cyclase. Identification by ligand binding. J Biol Chem 1982;257:11416-23. |
|43.||Rude RK, Oldham SB, Singer FR. Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency. Clin Endocrinol (Oxf) 1976;5:209-24. |
|44.||Rude RK, Adams JS, Ryzen E, Endres DB, Niimi H, Horst RL, et al. Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency. J Clin Endocrinol Metab 1985;61:933-40. |
|45.||Delvin EE, Salle BL, Glorieux FH, Adeleine P, David LS. Vitamin D supplementation during pregnancy: Effect on neonatal calcium homeostasis. J Pediatr 1986;109:328-34. |
|46.||Namgung R, Tsang RC. Bone in the pregnant mother and newborn at birth. Clin Chim Acta 2003;333:1-11. |
|47.||Ahmed I, Atiq M, Iqbal J, Khurshid M, Whittaker P. Vitamin D deficiency rickets in breast-fed infants presenting with hypocalcaemic seizures. Acta Paediatr 1995;84:941-2. |
|48.||Francis AB, Martti K, Tomi P, editors. Differential Diagnosis in Conventional Radiology. 3 rd ed. New York: Thieme; 2008. p. 32-5. |
|49.||Specker BL. Does vitamin D during pregnancy impact offspring growth and bone? Proc Nutr Soc 2012;71:38-45. |
|50.||Viljakainen HT, Saarnio E, Hytinantti T, Miettinen M, Surcel H, Mäkitie O, et al. Maternal Vitamin D status determines bone variables in the newborn. J Clin Endocrinol Metab 2010;95:1749-57. |
|51.||Kalkwarf HJ, Zemel BS, Yolton K, Heubi JE. Bone mineral content and density of the lumbar spine of infants and toddlers: Influence of age, sex, race, growth, and human milk feeding. J Bone Miner Res 2013;28:206-12. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]
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|[Pubmed] | [DOI]|
||The Frequency of Early and Late Hypocalcemia Among Hospitalized Newborns in An Iranian Hospital
| ||Nasrin Khalesi,Parva Namiranian,Sara Samavati,Zahra Farahani |
| ||Shiraz E-Medical Journal. 2015; 16(6) |
|[Pubmed] | [DOI]|
||Hypocalcemic Cardiomyopathy—Different Mechanisms in Adult and Pediatric Cases
| ||Beena Bansal,Manish Bansal,Pankaj Bajpai,Hardeep Kaur Garewal |
| ||The Journal of Clinical Endocrinology & Metabolism. 2014; 99(8): 2627 |
|[Pubmed] | [DOI]|