THE PLASMA LEVELS OF 25-HYDROXYVITAMIN D IN PATIENTS WITH VARIOUS LIVER DISEASES AND THE RESPONSE OF 25-HYDROXYVITAMIN D TO VITAMIN D TREATMENT

ABSTRACT. The mean plasma levels of 25-hydroxyvitamin D (25-OH-D) were measured before and after the administration of 2000 units of daily oral vitamin D₂ for a period of 2 weeks in 9 normal infants and children, 7 infants with neonatal hepatitis and persistent neonatal hepatitis, and 4 infants with congenital biliary atresia. The mean plasma level of 25-OH-D increased significantly from 19.5±3.7 (S.E.) ng/ml to 34.0±6.8 (S.E.) ng/ml after administration of vitamin D₂ in controls ( p <0.05). The mean plasma level of 25-OH-D also increased from 8.0±2.1 (S.E.) ng/ml to 22.1±2.6 (S.E.) ng/ml after vitamin D treatment in hepatitis group ( p <0.05). In patients with congenital biliary atresia, vitamin D treatment did not affect the plasma levels of 25-OH-D.     

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)     

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.     

25-hydroxy-vitamin-D in serum of newborns and infants during continuous oral vitamin D treatment (author's transl)

Using the Haddad modified method, 25-OH-D were measured in the blood of the umbilical cord of 29 infants and in peripheral serum after 6 weeks. 16 infants were given a daily dosage of 1000 I. E., 13 infants 500 I. E. vitamin D against rickets. Further they were fed with an adapted milk containing 400 I. E. vitamin D/1. The mean cord serum values were 13 and 15 ng/ml. After treatment with 1000 I. E., 25-OH-D values around 54 ng/ml were measured after 6 weeks and under 500 I. E. daily, values of 37 ng/ml, respectively. Treatment using a dosage of 500 I. E. vitamin D combined with feeding with vitamin D fortified milk seems adequate, to prevent vitamin D depletion.     

Serum 25-hydroxyvitamin D in infantile rickets.

In small children with nutritional vitamin D deficiency, the serum concentration of 25-hydroxyvitamin D (25-OH-D), the major circulating metabolite of vitamin D, was correlated with the stage of clinical disease. It was low (16 to 20 ng/ml) but within the normal range in the earliest (hypocalcemic) stage of the deficiency syndrome and decreased (less than 15 ng/ml) in the more advanced stages. In patients with familial hypophosphatemia (X-linked dominant), mean serum 25-OH-D concentration was the same as in age-matched normal controls. Evidence is presented that endogenous parathyroid hormone may have a role in the depletion of serum 25-OH0D in deficiency states.     

Serum 25-hydroxy-vitamin D in hepatobiliary disease in infancy.

Serum 25-hydroxy-vitamin D (25-OHD) concentrations were measured in 49 patients with hepatobiliary disease in infancy. Low mean values were found in groups of patients with biliary atresia, neonatal hepatitis, choledochal cyst, and chronic intrahepatic cholestatic syndrome. In the group of patients with surgically repaired biliary atresia, the mean value did not differ from normal. Parenteral vitamin D increased 25-OHD in serum in patients with biliary atresia, but did not do so in one patient with neonatal hepatitis. In contrast, oral vitamin D did not increase serum 25-OHD concentrations in patients with biliary atresia. It is concluded that the reduction of serum 25-OHD seen in biliary atresia was largely due to the malabsorption of vitamin D, while in neonatal hepatitis it was due to impairment of 25-hydroxylation of the vitamin.     

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 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.     

Hepatobiliary scintigraphy and the string test in the evaluation of neonatal cholestasis

We evaluated [99mTc]diisopropylphenyl-carbamoylmethylimidodiacetic acid ([99mTc]DISIDA) cholescintigraphy with measurement of duodenal fluid radioactivity collected by the string test in patients with neonatal cholestasis. Twenty-six infants with prolonged jaundice and acholic stools were studied prospectively. Twelve patients had neonatal hepatitis, 12 biliary atresia, and one each Alagille syndrome and alpha 1-antitrypsin deficiency liver disease. All infants except the biliary atresia patients and four of the neonatal hepatitis patients revealed bowel activity on scan 6 h after tracer administration. At 24 h, three of these latter patients with neonatal hepatitis and two of the patients with biliary atresia revealed bowel activity. String radioactive counts for neonatal hepatitis ranged from 99,574 to 967,205 cpm (374,504 +/- 232,210 cpm; mean +/- SD) and for biliary atresia from 8,342 to 370,346 cpm (117,149 +/- 98,698 cpm; mean +/- SD). While neither test alone was capable of correctly differentiating among all patients, those patients with biliary atresia had either a negative hepatobiliary scan at 24 h or string radioactive count below 197,007 cpm. Disparity between the hepatobiliary scan and the string radioactive counts mandates further diagnostic investigation. These data suggest that simultaneous administration of the string test with hepatobiliary scintigraphy is advantageous in the evaluation of infants with cholestatic jaundice.     

CONGENITAL HYPERPARATHYROIDISM AND VITAMIN D DEFICIENCY SECONDARY TO MATERNAL HYPOPARATHYROIDISM

Abstract. A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 μlEq/ml (Normal: <50 μlEq/ml). A very low plasma 25-OH-D concentration (<4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remainded high 3 weeks before (210 μlEq/ml) were found to be normal one week after this vitamin D load (37 μlEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.     

Congenital hyperparathyroidism and vitamin D deficiency secondary to maternal hypoparathyroidism.

A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 mulEq/ml (Normal: less than 50 mulEq/ml). A very low plasma 25-OH-D concentration (less than 4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remained high 3 weeks before (210 mulEq/ml) were found to be normal one week after this vitamin D load (37 mulEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.     

Effect of season and vitamin D supplementation on plasma concentrations of 25-hydroxyvitamin D in Norwegian infants

Plasma concentrations of 25-hydroxyvitamin D (25OHD) were determined in 81 vitamin D supplemented or unsupplemented infants at the end of winter. The values were compared with maternal levels and with concentrations found in 22 unsupplemented infants at the end of summer. The 25OHD levels of the neonates were lower, but closely related to maternal values (r = 0.95, p less than 0.0005). Unsupplemented breast-fed infants had lower 25OHD levels at 6 weeks than at 4 days (16 +/- 7 vs. 32 +/- 15 nmol/l, mean +/- 1 SD, p less than 0.0005). The mean 25OHD level of vitamin D supplemented 6-12 months old infants was intermediate between those of the unsupplemented nursed groups and the unsupplemented children studied during summer (53 +/- 28 vs. 85 +/- 28 nmol/l, p less than 0.0005). Six weeks old infants who had received a milk formula containing 400 IU vitamin D3 per liter had levels similar to the latter group (92 +/- 21 nmol/l). The data suggest that the vitamin D stores acquired during fetal life, or from ultraviolet light exposure during the summer, may be inadequate to maintain safe levels of 25OHD throughout the winter, but that a daily supplement of 400 IU is adequate to establish concentrations in the summer range.     

25-Hydroxyvitamin D levels during breast-feeding with or without maternal or infantile supplementation of vitamin D

Serum 25-hydroxyvitamin D (25-OHD), calcium, phosphorus, magnesium, and alkaline phosphatase levels of breast-fed infants and their mothers were studied by following 100 healthy term mother-infant pairs with different supplementation protocols of vitamin D. A pilot study in winter revealed that six of eight breast-fed infants without vitamin D supplementation had serum 25-OHD levels below the risk limit for rickets (5 ng/ml) at the age of 8 weeks. In the main study in winter groups, it was found that the 25-OHD levels were low (5.6 +/- 3.7 ng/ml) at the age of 8 weeks in the unsupplemented breast-fed infants, whose mothers were given vitamin D supplementation of 1,000 IU/day during lactation (group I), compared with the levels of those infants receiving either 400 (18.0 +/- 8.4 ng/ml, group II) or 1,000 IU (22.8 +/- 11.2 ng/ml, group III) vitamin D (group I vs. group II or III, p less than 0.001; group II vs. group III, NS). In group I 10 of 18 infants had serum 25-OHD levels less than 5 ng/ml compared with none of the infants in groups II and III. Yet the infants with 25-OHD levels less than 5 ng/ml showed no signs of clinical or biochemical rickets at the age of 8 or 20 weeks. In summer at delivery the maternal 25-OHD levels were good, but decreased thereafter. Also in summer groups, the infantile 25-OHD concentrations decreased; however, because the levels at delivery were high, they stayed in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Seasonal differences in serum vitamin D binding protein in exclusively breast-fed infants: negative relationship to sunshine exposure and 25-hydroxyvitamin D

Vitamin D binding protein (DBP) is the major carrier for vitamin D and its metabolites in serum. DBP increases in pregnancy and decreases in cirrhosis; no seasonal variation has been reported in adults. We observed significant seasonal differences in 41 exclusively breast-fed infants who were less than 6 months of age. Winter DBP concentrations exceeded summer DBP concentrations: 398 +/- 22 versus 297 +/- 20 micrograms/ml (mean +/- SEM). The mean concentration for spring and fall was 329 +/- 25 micrograms/ml. Maternal DBP concentrations did not differ by season. A sunshine exposure score, previously verified, was used to document time and body surface exposed to the sun. DBP was inversely related to sun exposure (r = -0.46, p = 0.005). Infant DBP was significantly and negatively correlated with 25-hydroxyvitamin D concentrations (r = - 0.38, p = 0.02). We speculate that serum DBP fluctuations are a response to varying vitamin D needs: increased serum DBP occurs in low vitamin D status to maximize uptake of vitamin D from skin.     

Plasma 25-hydroxyvitamin D and rickets in infants of extremely low birthweight.

Rickets is now a well-known entity in infants of very low birthweight. In a 1-year period (1981) 8 of 15 neonatal survivors whose birthweight was less than 1000 g (extremely low birthweight) developed rickets despite high supplementation with ergo-calciferol, 2000 units a day. At the time of radiological diagnosis their postnatal age was 8 (range 5-14) weeks, and they all had normal or high plasma concentrations of 25-hydroxyvitamin D (mean 80 nmol/l, range 40-160 nmol/l). Although 4 infants received alfacalcidol which healed the rickets, in 4 infants the rickets healed spontaneously without change in treatment. The results suggest that inadequate vitamin D supplementation is not the cause of rickets in such infants.     

Comparison of vitamin E and 25-hydroxyvitamin D absorption during childhood cholestasis

To characterize differences in intestinal absorption of fat-soluble vitamins during cholestasis, intestinal absorption of vitamin E was compared with that of 25-hydroxyvitamin D in eight infants and young children with prolonged neonatal cholestasis. Oral tolerance tests were performed using 100 IU/kg/dose dl-alpha-tocopherol and 10 micrograms/kg/dose 25-hydroxyvitamin D. Mean vitamin E absorption was only 1.0% to 1.9% of that of control children, whereas 25-hydroxyvitamin D absorption was 22.5% to 25.1% of that of controls. Although intestinal absorption of both vitamins is impaired during cholestasis, the severity of vitamin E malabsorption far exceeds that of 25-hydroxyvitamin D.     

Bone disease in chronic childhood cholestasis. II. Better absorption of 25-OH vitamin D than vitamin D in extrahepatic biliary atresia

Infants with extrahepatic biliary atresia (EHBA) commonly develop rickets in infancy, whereas long-term survivors with EHBA commonly develop osteopenia with increasing age. We evaluated baseline vitamin D (D2 and D3), 25-OH vitamin D2 and D3, 1,25(OH)2 vitamin D, bone mineral content, and vitamin D2 and 25-OH vitamin D3 absorption in six infants and children (age 4-22 mo) with EHBA whose portoenterostomy failed to produce bile flow (group 1) and five infants and children (age 10/12 to 8-4/12 y) with EHBA whose portoenterostomy repair led to good postoperative bile flow (group 2). Baseline serum vitamin D2 and D3 were undetectable in all subjects in group 1 despite supplements of 2500-5000 IU/day, whereas all group 2 subjects given supplements (doses 400-5000 IU/d) had measurable levels. Baseline serum 25-OH vitamin D was less than 15 ng/mL in five of six (three with rickets) in group 1, whereas only one in group 2 had concentrations less than 15 ng/mL. A significantly blunted rise of vitamin D2 above baseline and reduced area under the absorption curve after 1000 IU/kg vitamin D2 were found in group 1 patients compared to group 2 (both p less than 0.01), and five pediatric controls (both p less than 0.01). The peak change and area under the absorption curve for serum 25-OH vitamin D3 from baseline after 10 micrograms/kg 25-OH vitamin D3 were significantly reduced for group 1 (both at least p less than 0.05) and group 2 compared to controls (both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Alpha1-fetoprotein in neonatal hepatobiliary disease.

It has been suggested that the quantitative estimation of serum alpha-1-fetoprotein may help in distinguishing the neonatal hepatitis syndrome from biliary atresia. We measured the serum AFP concentration in 52 neonates and infants with various hepatobiliary disorders, including neonatal hepatitis syndrome (group I), biliary atresia (group II), and other hepatopathies such as choledochal cyst (group III). The mean serum AFP concentration in patients with neonatal hepatitis was significantly greater than the mean concentration in the other two groups. There was no significant difference between the mean serum AFP concentrations in patients with biliary atresia and in group III patients. Patient age was noted to be an important factor: Serum AFP levels greater than 35 microgram/ml in infants one to four months of age suggpst the diagnosis of neonatal hepatitis syndrome. Serum AFP levels below 10 microgram/ml in infants less than four months of age suggest the diagnosis of biliary atresia or hepatopathies other than neonatal hepatitis. However, the variable and significant overlapping of serum AFP values between 10 and 35 microgram/ml limit the diagnostic value of this test.     

胆道闭锁Kasai术后自体肝生存良好患儿的营养状况调查

目的回顾性调查胆道闭锁行肝门空肠吻合术(Kasai术)后自体肝生存良好患儿的营养状况,为制定个体化营养方案提供依据。方法收集46例胆道闭锁Kasai手术后1年且自体肝生存良好患儿的临床资料,包括年龄、身高/身长、体重、血清脂溶性维生素(A、D、E、K)水平。以WHO生长曲线软件分别计算患儿年龄别身高Z评分(height-for-age,HAZ)、年龄别体重Z评分(weight-for-age,WAZ)、身高别体重Z评分(weight-for-height,WHZ);以正常参考值为标准,计算营养不良和维生素缺乏的比例。结果46例患儿中男童26例,女童20例,平均年龄(14.5±0.8)个月。患儿HAZ评分为(-0.14±0.86),WAZ评分为(0.21±0.81),WHZ评分为(0.62±1.80),其中生长迟缓2例(4.3%),无低体重及消瘦患儿。25例行脂溶性维生素检查的患儿,其临床和实验室指标与46例自体肝生存良好的患儿均无明显差异(P>0.05)。25例患儿维生素A、D、E、K的水平分别为(290.61±80.26)ng/mL、(30.88±16.15)ng/mL、(7.69±2.77)μg/mL和(1.34±0.98)ng/mL。其中维生素A缺乏4例(16%),维生素D缺乏5例(20%),维生素E缺乏1例(4%),无一例维生素K缺乏者;至少有一种维生素缺乏者有7例(28%)。结论胆道闭锁行Kasai术后1年,自体肝生存良好的患儿营养状况良好;脂溶性维生素A、D缺乏较为常见,应在术后注意监测并补充。     

Vitamin D metabolism in children with malabsorption syndrome

In 16 children with malabsorption syndrome, out of which 5 had impaired lipid absorption or diarrhoea, and in 14 children in the control group the concentrations of vitamin D and 25 OH D3 were determined after oral administration of vitamin D in dose of 1200 U/kg.b.wt. or 12000 U/kg.b.wt. No decrease in initial 25 OH D3 concentrations was noted in children with malabsorption syndrome (40,5 +/- 0,7 ng/ml) in comparison with the control group (40,0 +/- 0,4 ng/ml). In children with impaired lipid absorption and diarrhoea the 25 OH D3 concentration was 33,6 +/- 2,4 ng/ml. After oral administration of vitamin D in small doses no differences were noted in the increase in vitamin D and 25 OH D3 concentrations in children with malabsorption syndrome or the control group. After administration of vitamin D in the dose 10 times higher no difference in the increase in vitamin D concentration was noted in children with malabsorption syndrome and the control group. However the increase in 25 OH D3 concentration in children with malabsorption syndrome was 49,8 +/- 1,2 ng/ml and 145,0 +/- 3,5 ng/ml in the control group. In the children with impaired lipid absorption and diarrhoea decreased vitamin D and 25 OH D3 concentrations were noted. This means that physiological doses of vitamin D in children with malabsorption syndrome are sufficient to supply vitamin D. Diarrhoea and impaired lipid absorption however, are indications for stimulation of skin synthesis of vitamin D.