Serum vitamin D metabolites in very low birth weight infants with and without rickets and fractures

Seventy-one very low birth weight (less than or equal to 1500 gm) infants were studied to determine the sequential changes in serum vitamin D metabolite concentrations between infants with and without radiographically documented rickets, fractures, or both (R/F). Usual intake of vitamin D included 20 IU/kg/day from parenteral nutrition or 400 IU/day supplementation with enteral feeding. Radiographs of both forearms and serum samples were obtained at 3, 6, 9, and 12 months. Twenty-two infants had R/F. At 3 months, significantly lower mean (+/- SEM) serum phosphorus levels (4.5 +/- 0.4 vs 6.1 +/- 0.2 mg/dl), higher 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations (96 +/- 5 vs 77 +/- 4 pg/ml), and higher free 1,25-(OH)2D index (1,25-[OH]2D:vitamin D binding protein ratio; 5.2 +/- 0.3 x 10(5) vs 4.0 +/- 0.2 x 10(5] were found in the R/F group. These values returned to normal and were similar between groups on subsequent measurements. Serum calcium, magnesium, and 25-hydroxyvitamin D (25-OHD) concentrations were normal and similar between groups. In both groups, serum vitamin D binding concentrations increased initially but remained stable and normal beyond 6 months. We conclude that in very low birth weight infants with R/F, the vitamin D status (as indicated by serum 25-OHD concentrations) is normal, and that lowered serum phosphorus levels, higher serum 1,25-(OH)2D levels, and a higher free 1,25-(OH)2D index support the thesis that mineral deficiency (especially of phosphorus) may be important in the pathogenesis of R/F in small preterm infants.     

Absorption, dosage, and effect on mineral homeostasis of 25-hydroxycholecalciferol in premature infants: comparison with 400 and 800 IU vitamin D2 supplementation

Because the efficiency of vitamin D absorption or hepatic uptake and 25-hydroxylation appears decreased in very premature infants, the routine use of 25-hydroxycholecalciferol (25-OHD3) supplementation has been suggested. Absorption studies of a 3 micrograms/kg orally administered dose of 25-OHD3 showed peak serum 25-hydroxyvitamin D2 and -vitamin D3 (25-OHD) concentrations at 4 to 8 hours similar in timing but of lesser magnitude to those seen in adults. Administration of 1 microgram/kg birth weight/day of 25-OHD3 corrected moderately low, but not very low serum (25-OHD) concentrations, and 2 micrograms/kg BW/day resulted in rapid and sustained increase in serum 25-OHD. Administration of 800 IU ergocalciferol (D2) also produced significantly higher serum 25-OHD concentrations than those in infants given 400 IU vitamin D2, but increases in serum 25-OHD were more gradual than in infants given 25-OHD3. In treatment trials with infants weighing less than 1500 gm, those given 800 IU D2, compared with those given 400 IU D2, had higher serum calcium concentrations and less frequent moderate or severe hypomineralization. Infants given 2 micrograms/kg BW 25-OHD3 had a significant increase in serum phosphorus values, but a decrease in serum calcium and magnesium concentrations, and parathyroid hormone also was suppressed to low normal values. The frequency of moderate to severe hypomineralization remained the same as in infants given 400 IU D2. In a subgroup of infants, serum 1,25-dihydroxyvitamin D was elevated over adult values, both in infants given 25-OHD3 (68.5 +/- 8.4 pg/ml) and in infants given vitamin D2 (60 +/- 6.7 pg/ml). Serum vitamin D concentrations were undetectable in four of six infants receiving 25-OHD3, but were elevated (5 to 31 ng/ml) in four infants receiving vitamin D2. Although 800 to 1000 IU D2 can be recommended as routine vitamin D supplementation in very premature infants fed standard formula, the use of 25-OHD3 requires further study.     

Increased serum concentrations of 1,25(OH)2 vitamin D in children with fasting hypercalciuria

Inappropriately elevated concentrations of 1,25(OH)2 vitamin D in serum appear to be responsible for excessive gastrointestinal absorption of dietary calcium in patients with absorptive hypercalciuria. We have examined serum 1,25(OH)2 vitamin D concentrations in another group of children with hypercalciuria in whom urinary calcium excretion was excessive after an overnight fast. Eleven children with idiopathic fasting hypercalciuria (IH) (urinary calcium excretion greater than 4 mg/kg/24 hr and fasting urinary calcium/urinary creatinine ratio greater than 0.21) and seven healthy children were observed while they were eating a diet containing 1 gm calcium per day. Fasting serum 1,25(OH)2 vitamin D concentrations were elevated in children with IH compared with control values (35.3 +/- 3.2 vs 21 +/- 2 pg/ml, P = 0.003), whereas fasting serum parathyroid hormone, 25-OH vitamin D, phosphorus, and ionized calcium concentrations were similar in the two groups. These data suggest that disordered 1,25(OH)2 vitamin D metabolism occurs in children with fasting IH. Absorptive and fasting IH may represent a spectrum of a single disorder characterized by excessive urinary calcium excretion and inappropriately elevated serum concentrations of 1,25(OH)2 vitamin D.     

Serum concentrations of vitamin D metabolites in exclusively breast-fed infants at 70 degrees north

The effect of prolonged breast-feeding on the serum concentrations of vitamin D metabolites, calcium, phosphate, and alkaline phosphatase was studied longitudinally in 7 infants from Northern Norway. They were exclusively breast-fed for a median of 7 1/2 months. Three of the mothers were supplemented with vitamin D throughout lactation. All but one of the infants had 25-hydroxyvitamin D (25-OHD) levels in the rachitic range (less than 20 nmol/l) on at least one occasion. Vitamin D supplementation of the mother had no apparent effect on the infants' 25-OHD levels, but the values increased during summer. The infant who had the lowest 25-OHD levels also had decreased 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations, while the others maintained 1,25-(OH)2D levels within normal limits. 24,25-(OH)2D concentrations were undetectable when the 25-OHD levels were below 35 nmol/l, but the two metabolites were closely correlated for higher values of 25-OHD. Low 25-OHD levels were associated with decreased phosphate concentrations at 6 months. The calcium levels were normal throughout the study period of one year, as were all but two of the alkaline phosphatase values. Although none of the infants had clinical or biochemical evidence of rickets, the results suggest that the vitamin D supply from human milk is inadequate, and that routine vitamin D supplementation is advisable for breast-fed infants who are deprived of sunlight exposure.     

Mineral homeostasis in very premature infants: serial evaluation of serum 25-hydroxyvitamin D, serum minerals, and bone mineralization

This study was designed to evaluate the role of vitamin D sufficiency, as reflected in serum 25-hydroxyvitamin D (25-OHD) concentrations, on serum minerals and bone mineralization in very premature infants. Seventy-two infants (mean +/- SD gestation 30.1 +/- 2.5 weeks, mean +/- SD birth weight 1178 +/- 278 gm) were observed serially for the first 3 months of life. Mean serum calcium and phosphorus values, but not magnesium, remained low prior to 12 weeks. The percentage of infants with moderate to severe hypomineralization was 75% at 3 weeks, 55% at 6 weeks, 54% at 9 weeks, and 15% at twelve weeks. Low serum calcium and phosphorus values, high alkaline phosphatase activity, and moderate-severe hypomineralization were more frequent in infants weighing less than 1000 gm and in those with lower mineral intake. With a 400 IU vitamin D supplement, 45% of infants could maintain an initially normal serum 25-OHD concentration or increase low concentrations, whereas 55% had falling or persistently low (less than or equal to 15 ng/ml) 25-OHD concentrations. Birth weight and mineral intakes were comparable in these two groups, yet the group with the lower serum 25-OHD concentration had lower serum calcium and higher alkaline phosphatase values, and a higher percentage of moderate to severe hypomineralization. Regardless of birth weight, mineral intake, or 25-OHD concentration, increases in serum calcium and phosphorus values and in mineralization were seen at postconception term (12 weeks in most infants, nine weeks in those weighing 1250 to 1600 gm). At 12 weeks of age, but not before, serum 25-OHD concentration was directly correlated with serum calcium (r = 0.47, P less than 0.01) and serum phosphorus (r = 0.47, P less than 0.01) and inversely correlated with alkaline phosphatase values (r = -0.71, P less than 0.01). Mineral availability and 25-OHD sufficiency both appear to be important and to act synergistically, with neither totally compensating for the other.     

Serum Concentrations of Vitamin D Metabolites in Exclusively Breast-Fed Infants at 70° North

ABSTRACT. The effect of prolonged breast-feeding on the serum concentrations of vitamin D metabolites, calcium, phosphate, and alkaline phosphatase was studied longitudinally in 7 infants from Northern Norway. They were exclusively breast-fed for a median of 71/2 months. Three of the mothers were supplemented with vitamin D throughout lactation. All but one of the infants had 25-hydroxyvitamin D (25-OHD) levels in the rachitic range (< 20 nmol/l) on at least one occasion. Vitamin D supplementation of the mother had no apparent effect on the infants' 25-OHD levels, but the values increased during summer. The infant who had the lowest 25-OHD levels also had decreased 1,25-dihydroxyvitamin D (1,25-(OH)₂D) concentrations, while the others maintained l,25-(OH)₂D levels within normal limits. 24,25-(OH)₂D concentrations were undetectable when the 25-OHD levels were below 35 nmol/l, but the two metabolites were closely correlated for higher values of 25-OHD. Low 25-OHD levels were associated with decreased phosphate concentrations at 6 months. The calcium levels were normal throughout the study period of one year, as were all but two of the alkaline phospatase values. Although none of the infants had clinical or biochemical evidence of rickets, the results suggest that the vitamin D supply from human milk is inadequate, and that routine vitamin D supplementation is advisable for breast-fed infants who are deprived of sunlight exposure.     

Serum concentrations of 25-hydroxyvitamin D in rickets of extremely premature infants.

Nine premature infants developed radiographic and biochemical rickets at a mean +/- SD of 12.6 +/- 2.8 weeks of age. Serum 25-hydroxyvitamin D concentrations were all low, with a mean of less than 3.6 +/- 2.1 ng/ml. The mean average daily intake of vitamin D since birth had been 300 +/- 181 IU, and the mean average daily intake during the week of diagnosis was 587 +/- 313 IU. All of the infants were extremely premature (mean weight 948 +/- 153 gm, mean gestation 27.7 +/- 1.1 weeks), and were being fed either a low-calcium "human milk-like" formula or a soy formula. It is postulated that low-calcium intake may have increased 25-OHD utilization in the face of a decreased ability of the extremely premature infant to produce 25-OHD. Because of multiple factors leading to both decreased production and possible increased utilization of 25-OHD, such infants have an increased requirement for vitamin D to maintain normal serum 25-OHD concentrations, and daily intakes of at least 400 IU vitamin D orally must be assured. Serum 25-OHD measurements and radiographs may be important in following infants at risk.     

Vitamin D metabolism in biliary atresia: intestinal absorptions of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3

In children with biliary atresia, defective intestinal absorption of vitamin D and impaired hepatic uptake and 25-hydroxylation of vitamin D lead to a deficiency of vitamin D and rickets. We recently observed severe rickets in a 3-year-old boy with corrected biliary atresia resulting in jaundice, despite oral treatment with 1 alpha-hydroxyvitamin D3 (1 alpha-OHD3) or 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. He had low 25-hydroxyvitamin D (25-OHD) and high 1,25-(OH)2D serum levels. Intramuscular vitamin D2 administration produced radiological and biochemical evidence of recovery. Oral 1,25-(OH)2D3 (0.1 microgram/kg) and 25-OHD3 (10 micrograms/kg) tolerance tests were done to assess the ability to absorb vitamin D and the effectiveness of using these drugs orally. Eleven children with corrected biliary atresia, aged 9 months to 7 years, were studied. In oral 1,25-(OH)2D3 tolerance tests, the increments above the baseline serum levels of 1,25-(OH)2D were 140.7 +/- 27.4 pg/ml in nonjaundiced patients (n = 5). In jaundiced patients (n = 3), 1,25-(OH)2D3 absorption in two patients with high basal 1,25-(OH)2D values was lower than that of nonjaundiced patients; however, the absorption in the third patient with a low basal value was similar to that of nonjaundiced patients. In oral 25-OHD3 tolerance tests, the mean increase of serum 25-OHD was 48.9 +/- 30.6 ng/ml in nonjaundiced patients (n = 5) and 23.7 +/- 9.5 ng/ml in jaundiced patients (n = 4), the peak serum 25-OHD levels being reached 6-12 h after 25-OHD3 loading.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma Concentrations of Vitamin D Metabolites before and during Treatment of Vitamin D Deficiency Rickets in Children

ABSTRACT. Plasma concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)₂D), and 24,25-dihydroxyvitamin D (24,25-(OH)₂D) were determined in 17 children with vitamin D deficiency rickets before therapy was started. Thirteen of them also had these tests repeated during treatment. The median 25-OHD concentration was at the lower limit of the reference range before, but increased distinctly within one week of treatment with 1700–4000 IU vitamin D per day (17 vs. 37 nmol/l, p < 0.01). 24,25-(OH)₂D was undetectable in twelve of the patients before therapy. Detectable concentrations were in the range of 1.7 to 3.5 % of the corresponding 25-OHD levels throughout the study, and the two metabolites were closely correlated ( r = 0.84, p < 0.0005). The median l,25-(OH)₂D concentration was near the average of the reference range before, but increased to well above the upper limit of normal within one week of treatment (121 vs. 368 pmol/l, p < 0.01). The levels were largely normal after 10 weeks of therapy, as were the plasma concentrations of calcium, phosphate, and alkaline phosphatase. Parathyroid activity, as judged by serum parathyroid hormone or urinary cyclic AMP concentrations, was stimulated in 11 of 12 children studied prior to treatment. It is concluded that there may be no clear-cut differences between normal nad rachitic values of the different vitamin D metabolites under practical clinical conditions. A low 25-OHD level combined with evidence of a stimulated parathyroid activity, and a rise of l,25-(OH)₂D levels to supernormal values following a few days of vitamin D therapy may be diagnostic clues.     

Vitamin D metabolism in pre-operative extrahepatic biliary atresia

In order to clarify the pathogenesis of rickets in preoperative patients with extrahepatic biliary atresia, we evaluated baseline serum 25-OHD and 1,25(OH)2D levels and correlated serum 25-OHD levels with increase in age and season of birth in 16 preoperative patients. Further, parenteral vitamin D2 tolerance tests were performed in 5 cases. Serum 25-OHD and 1,25(OH)2D levels were significantly lower than those in 15 normal controls. There was a negative correlation between the serum 25-OHD levels and increase in age. The patients born during the winter had lower serum 25-OHD concentrations than those born in summer. The mean value of increased 25-OHD levels after the parenteral vitamin D2 tolerance tests did not differ from that of 6 controls. Since there was no impairment of vitamin D 25-hydroxylation, the reduction in serum 25-OHD may therefore be mainly due to disturbed intestinal vitamin D absorption. It was also concluded that season of birth and increase in age are pathogenic factors in the etiology of rickets in preoperative patients with extrahepatic biliary atresia.     

Vitamin D metabolism in osteogenesis imperfecta during calcitonin therapy

The effect of calcitonin on plasma concentrations of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] was studied in six patients with osteogenesis imperfecta. The mean pretreatment value of plasma 1,25-(OH)2D was significantly higher than the mean value of age-matched control subjects (P less than .05). High or normal plasma levels of 1,25-(OH)2D before calcitonin therapy were decreased after 1 month of therapy and remained normal thereafter in all six patients. Plasma 25-hydroxyvitamin D concentrations, which were normal before calcitonin injection, remained normal during calcitonin administration. These results indicate that there may be acute and chronic effects of calcitonin on vitamin D metabolism.     

Risk of hypervitaminosis D from prolonged feeding of high vitamin D premature infant formula

BACKGROUND: Most premature infant formulas marketed in Japan have high vitamin D content. Potential for vitamin D intoxication was assessed in premature infants with prolonged feeding of such a premature formula vitamin D content, 2700 IU/L. METHODS: Serum vitamin D, calcium and phosphorus, and urinary calcium, were measured in 12 very premature infants fed premature infant formula, regular formula (vitamin D content; 460 IU/L), and/or mother's milk. RESULTS: Concentrations of 25(OH)D in sera associated with sole feeding of premature infant formula (n = 40) were significantly higher than sera corresponding to regular formula or breast milk (n = 25; 175 versus 115 nmol/L, P <0.0001). No sample showed a serum 25(OH)D concentration below 25 nmol/L. Of 65 samples, 49 (75.4%) showed 25(OH)D concentrations exceeding 100 nmol/L, but serum calcium and phosphorus concentrations were normal. Unexpectedly, urinary calcium correlated negatively with serum 25(OH)D. CONCLUSION: In prolonged feeding of premature infant formula with high vitamin D, it was concluded that it could cause a high blood concentration of vitamin D in premature infants, and also that in these infants urine calcium is not a reliable indicator of excessive vitamin D intake.     

Minimal vitamin D and high calcium and phosphorus needs of preterm infants receiving parenteral nutrition

Preterm infants (birth weight, 1,089 +/- 91 g; gestational age, 28.9 +/- 0.7 weeks; mean +/- SEM) with mixed medical and surgical indications for parenteral nutrition (PN) were observed to determine the adequacy of infusates with fixed, low-dose vitamin D (25 IU/dl) and two combinations of calcium and phosphorus. The duration of low-dose vitamin D PN ranged from 5 to 52 days, with a median of 27 days. Twelve infants were randomly assigned to low (standard) Ca and P doses (5 mM each; 20 mg/dl of Ca and 15.5 mg/dl of P) and 13 high Ca and P doses (15 mM each; 60 mg/dl of Ca and 46.5 mg/dl of P). The maximum daily vitamin D intake was similar for both groups (31 +/- 1.3 versus 33 +/- 1.2 IU/kg). Vitamin D status in either group, as indicated by serum 25-hydroxyvitamin D (25-OHD) concentrations, was normal. There was no significant difference in observed changes of serial measurements of serum calcium, magnesium, phosphorus, alkaline phosphatase, creatinine (Cr), 25-OHD, and vitamin D-binding protein concentrations or urinary Ca:Cr and Mg:Cr ratios. In the low-dose Ca and P group, the serum P level was consistently less than 4 mg/dl in five infants, serum 1,25-dihydroxyvitamin D concentrations were higher, and tubular reabsorption of phosphorus was consistently greater than 95% and significantly higher than in the high-dose Ca and P groups. Severe bone demineralization apparent on X-ray occurred in two infants, with a fractured distal left ulna in one of the two infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin D Metabolism in Pre-Operative Extrahepatic Biliary Atresia

ABSTRACT. In order to clarify the pathogenesis of rickets in preoperative patients with extrahepatic biliary atresia, we evaluated baseline serum 25-OHD and 1,25(OH)₂D levels and correlated serum 25-OHD levels with increase in age and season of birth in 16 preoperative patients. Further, parenteral vitamin D₂ tolerance tests were performed in 5 cases. Serum 25-OHD and 1,25(OH)₂D levels were significantly lower than those in 15 normal controls. There was a negative correlation between the serum 25-OHD levels and increase in age. The patients born during the winter had lower serum 25-OHD concentrations than those born in summer. The mean value of increased 25-OHD levels after the parenteral vitamin D₂ tolerance tests did not differ from that of 6 controls. Since there was no impairment of vitamin D 25-hydroxylation, the reduction in serum 25-OHD may therefore be mainly due to disturbed intestinal vitamin D absorption. It was also concluded that season of birth and increase in age are pathogenic factors in the etiology of rickets in preoperative patients with extrahepatic biliary atresia.     

Parity and vitamin D metabolites

Twenty-five hydroxycalciferol (25-OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), calcium (Ca), phosphorus (P), alkaline phosphatase, and total protein were estimated in 86 Saudi pregnant women. They were divided into two groups, group I, parity 5 or more, and group II, parity 4 or less. The mean level of 25-OHD was 10.4 (S.D. 6.5) ng/ml in group I, and for group II 8.2 (6.1) ng/ml with no significant statistical difference between the groups. 1,25(OH)2D mean levels, in group I 45.5 (S.D. 30.2) ng/ml and in group II 36.9 (S.D. 27.1) pg/ml, also showed no significant difference. Levels of vitamin D metabolites were comparable with non-pregnant levels in Saudi Arabia but lower than others reported in Western populations. We found no effect of increasing parity on levels of vitamin D metabolites in our study.     

25-hydroxyvitamin D and calcium levels in maternal, cord and infant serum in relation to maternal vitamin D intake

The plasma levels of 25-hydroxyvitamin D (25-OHD), total calcium, phosphorus and proteins were measured in 40 healthy mothers and their infants at the time of delivery during the months of December and January. Calcium, phosphorus and proteins were again measured in the plasma of the infants on the fourth day of life. Vitamin D intake of the mothers during their last 3 months of pregnancy were estimated by interviews. The mean (+/-SE) plasma levels of 25-OHD was 9.0 +/- 0.9 ng/ml in the mothers and 5.05 +/- 0.4 ng/ml in cords. There was a significant correlation between mother and cord plasma levels (r = 0.75, p less than or equal to 0.001). The concentration gradient of 25-OHD plasma levels between mother and cord is higher at high 25-OHD maternal concentrations. This suggests that the placenta plays a regulating role in the 25-OHD transfer between mother and foetus. The 4-day-old infants from mothers having a suboptimal vitamin D intake (less than 150 IU/day) have a lower mean serum plasma level than infants born from mothers with a vitamin D intake of more than 500 IU/day.     

Serum 25-hydroxyvitamin D concentrations in sudden infant death syndrome

Among the many theories put forth to explain sudden infant death syndrome (SIDS) is a theory of vitamin D deficiency. 25-Hydroxyvitamin D (25-OHD) serum concentrations were measured in 31 SIDS and 24 postmortem control infants. 25-OHD was 19.0 +/- 7.9 mg/ml in SIDS, 16.9 +/- 5.2 ng/ml in acute death control infants, and 11.9 +/- 4.4 ng/ml in in-hospital deaths. For four "near miss" infants the mean serum 25-OHD concentration was 21.1 +/- 4.1 ng/ml. The mean serum 25-OHD concentration of 39 living premature or small-for-gestational-age infants at 3 months of age was 26 +/- 9.9. Serum calcium and serum copper concentrations were also the same in SIDS and control infants. Parathyroid hormone was measured in ten and was detectable in five SIDS infants. These data eliminate a simple vitamin D deficiency or a 25-OHD deficiency as a significant contribution to the pathophysiology of SIDS.     

Early response to vitamin D2 in children with calcium deficiency rickets

OBJECTIVE: To assess the effect of vitamin D(2) administration on serum vitamin D metabolite concentrations in calcium deficiency rickets. STUDY DESIGN: We administered vitamin D(2), 50,000 IU orally to 16 Nigerian children 15 to 48 months of age with radiographically active rickets. We measured calcium and vitamin D metabolites at baseline and at 1, 3, 7, and 14 days. RESULTS: At baseline, ranges of serum 25-hydroxyvitamin D (25(OH)D) concentrations were 18 to 40 nmol/L (7-16 ng/mL), and 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentrations were 290 to 790 pmol/L (120-330 pg/mL). After vitamin D administration, serum 25(OH)D and 1,25(OH)(2)D concentrations rapidly rose and peaked at 2.8 and 1.9 times the baseline values (P < .001), respectively, at 3 days. Positive correlations between 1,25(OH)(2)D and 25(OH)D were strongest at day 3 (r = 0.84, P < .001) and weakest at day 14 (r = 0.41, P = .11). The relationship of 1,25(OH)(2)D with 25(OH)D at baseline and the increase in 1,25(OH)(2)D in response to vitamin D were similar to those described in children with vitamin D deficiency. However, unlike the pattern in vitamin D deficiency, 1,25(OH)(2)D remained positively correlated with 25(OH)D after administration of vitamin D. CONCLUSION: Dietary calcium deficiency increases the demand for 25(OH)D above that required in vitamin D deficiency to optimize 1,25(OH)(2)D concentrations. Assessment of vitamin D sufficiency in persons or communities may need to be adjusted for habitual dietary calcium intake.     

Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin-10

The cytokine interleukin-10 (IL-10) plays a pivotal regulatory role in tolerizing exogenous antigens. Experimental data indicate that low cellular availability of the vitamin D hormone 1,25-dihydroxyvitamin D [1,25(OH)2D] results in a down-regulation of IL-10 concentrations. The tissue production of an adequate amount of 1,25(OH)2D depends on a high circulating 25-hydroxyvitamin D (25-OHD) level. The present study was thus aimed at evaluating the associations between season of birth, vitamin D status, and the allergy risk markers IL-10 and total immunoglobulin (IgE) in newborns. Cord blood was obtained from 49 infants born during the summer half year (mid-April to mid-October, geographic latitude 51 degrees N) and from 47 infants born during the winter half year (mid-October to mid-April, geographic latitude of 51 degrees N). Serum levels of 25-OHD were 99% higher, and IL-10 levels were 43% higher in the summer half year compared with the winter half year (p < 0.001 and p = 0.018). Moreover, the ratio of IL-10 to total IgE was 124% higher in the summer half year compared with the winter half year (p = 0.039). Serum levels of 25-OHD were correlated with IL-10 levels (r = +0.22; p < 0.05). Mothers' age, gestational ages, birth weights and serum 1,25(OH)2D levels did not differ between study groups. We conclude that the low vitamin D status of infants born in winter may at least in part adversely affect biomarkers of allergy risk.     

Vitamin D supplementation during pregnancy: effect on neonatal calcium homeostasis

We assessed whether modification of vitamin D nutritional status during the last trimester of pregnancy affects maternal and neonatal calcium homeostasis. At the end of the first trimester, 40 pregnant women were randomly assigned to either of two groups, and blood taken to assess the basal values of Ca, Pi, Mg, iPTH, 25-OHD, and 1,25(OH)2D. From the sixth month on, group 1 (+D) received 1000 IU vitamin D3 daily; group 2 (-D) served as control. At the time of delivery, maternal serum 25-OHD was higher in the +D group (P less than 0.0005). Ca, Pi, iPTH, and 1,25(OH)2D were not affected. At term, venous cord 25-OHD levels were also higher in the +D group (P less than 0.0005), and 1,25(OH)2D levels slightly lower (P less than 0.05), but neither Ca, Pi, nor iPTH differed between the two groups. Serum CaT dropped significantly (P less than 0.002) at 4 days of age in the infants from both groups, although to a lesser extent in these from the +D group (P less than 0.05). Circulating iPTH increased in both groups. Serum 25-OHD remained low in the -D group, and dropped slightly in the +D group; 1,25(OH)2D remained stable during the first 4 days of life in the -D group, and increased in the +D group (P less than 0.001). Our data demonstrate the importance of providing adequate maternal vitamin D stores to ensure better perinatal handling of calcium. This is of particular importance for populations at risk for hypovitaminosis D.