Mona L. Ho

Prospective study of vitamin D supplementation and rickets in China

To determine whether amounts of vitamin D lower than recommended doses are effective in preventing rickets, 256 term infants from two northern and two southern cities in China were studied in a randomized trial of vitamin D supplementation (100, 200, or 400 IU/day) during the first 6 months of life. Cord blood and 6-month blood samples were collected and radiographs were obtained at 3 to 5 days and at 6 months of age. Cord serum 25-hydroxyvitamin D concentrations were lower in the north than in the south (5 vs 14 ng/ml (12.5 vs 35.0 nmol/L); p less than 0.01). Wrist ossification centers were less likely to be present at birth in the northern children than in the southern children (p = 0.009) and were more likely to be present in infants born in the fall who had higher cord serum concentrations of 25-hydroxyvitamin D (p = 0.04). Serum 25-hydroxyvitamin D concentrations were lower in northern children 6 months of age than in southern children (p = 0.005) and were higher with an increasing supplemental dosage of vitamin D (p less than 0.001), particularly in infants in the north. None of the infants had rickets at 6 months of age. Because of the low serum 25-hydroxyvitamin D concentrations, especially among infants in the north, it may be prudent to supplement the diet with vitamin D at a dose of 400 IU/day.

Low total body bone mineral content and high bone resorption in Korean winter-born versus summer-born newborn infants☆☆☆★★★

Seasonal differences in newborn total body bone mineral content (TBBMC) have not been studied, particularly in relation to alterations in vitamin D status in winter. In vitamin D deficiency bone resorption may be high and bone mineralization low. Bone resorption may be assessed by serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP) measures. Because vitamin D supplements throughout pregnancy are uncommon in Korea, we hypothesized that in Korean winter newborns, TBBMC is low and serum ICTP high from high bone resorption and low 25-hydroxyvitamin D (25-OHD) compared with those in summer newborns. Seventy-one Korean term infants were studied prospectively in summer (July through September, n = 37) versus winter (January through March, n = 34); TBBMC was measured before 3 days of age by dual-energy x-ray absorptiometry. Significant seasonal differences were found: winter newborns had 6% lower TBBMC (least squares means +/- SD; 86.7 +/- 7.7 gm vs 93.9 +/- 7.8 gm, p = 0.0002), lower cord serum 25-OHD (10.7 +/- 8 nm vs 30 +/- 15 nm, p = 0.0001) and 1,25-dihydroxyvitamin D, and higher ICTP (96.4 +/- 20.3 microg/L vs 74.8 +/- 24 microg/L, p = 0.0002) and calcium than summer newborns. TBBMC correlated with serum 25-OHD (r = 0.243, p = 0.047) and inversely with ICTP (r = -0.333, p = 0.008). We suggest that in Korea low maternal vitamin D status in winter results in marked reduction in newborn TBBMC.

Reduced serum osteocalcin and1,25-dihydroxyvitamin D concentrations and low bone mineral content in small for gestational age infants: Evidence of decreased bone formation rates

In small for gestational age (SGA) infants, bone mineral content (BMC) is low but the reasons are unclear and the possible relationships between calcium-regulating hormones and BMC have not been studied. We hypothesized that BMC would be lower and concentrations of serum parathyroid hormone and 1,25-dihydroxyvitamin D would be higher at birth in SGA infants than in appropriate for gestational age (AGA) infants. Forty-two term SGA infants and 126 term AGA infants, matched 1:3 specifically by gestation (+/- 1 week) and birth month, were studied prospectively. The BMC of the distal one third of the radius was measured before 3 days of age by photon absorptiometry. The BMC was lower in SGA than in AGA infants. Both SGA and AGA infants had lower BMC in summer or spring than in winter; BMC differences between groups remained significant after adjustment for season (p = 0.0001). Cord serum osteocalcin and 1,25-dihydroxyvitamin D values were lower in SGA than in AGA infants. There were no differences between groups in cord serum levels of intact parathyroid hormone, 25-hydroxyvitamin D, calcium, phosphorus, and magnesium. Relationships were positive between BMC and birth weight and were inverse between BMC and intact parathyroid hormone values. We suggest that reduced uteroplacental blood flow in SGA infants may result in reduced fetal-placental production of 1,25-dihydroxyvitamin D, which results in low BMC and low serum osteocalcin values; fetal serum parathyroid hormone values may be relatively elevated because of reduced placental mineral supply.

Low Bone Mineral Content and High Serum Osteocalcin and 1,25-dihydroxyvitamin D in Summer- Versus Winter-born Newborn Infants: An Early Fetal Effect?

Seasonal differences in bone mineral indices have not been studied in newborn infants. In adults, indicators of bone metabolism may show seasonal variations. In postneonatal infants and possibly in adults, vitamin D metabolism shows seasonal variations. We hypothesized that in winter-born infants, the bone mineral content is low and serum osteocalcin is high, related to increased bone turnover and high serum 1,25-dihydroxyvitamin D [l,25(OH)2D]. We studied 246 healthy, term appropriate-for-gestation infants in winter (January through March; 140 children) and summer (July through September; 106 children). The bone mineral content (BMC) of the one-third distal radius was measured before 3 days of age by photon absorptiometry. Significant seasonal differences were found: summer-born infants had significantly lower BMC, higher serum osteocalcin and l,25(OH)2D, and lower serum total calcium than winter-born infants. Seasonal differences in BMC remained significant after adjusting for race and sex. BMC was not correlated with serum biochemical measures. Thus, summer-born newborn infants have low BMC and high serum osteocalcin and l,25(OH)2D than winter-born infants; these findings are the opposite of adult findings. We suggest that seasonal effects on fetal bone operate especially in early pregnancy (-6 months before birth) resulting in a “phase effect” and opposite findings from later life.

Randomized study of sunshine exposure and serum 25-OHD in breast-fed infants in Beijing, China

The hypothesis that breastfed infants in Beijing, China, have low vitamin D status and that sunshine exposure increases serum 25-hydroxyvitamin D (25-OHD) concentrations was tested in a randomized prospective study involving 42 healthy infants 1-8 months of age. 24 controls were exposed to the usual amount of sunshine, while the 18 cases were provided with 2 hours of sunshine/day. All infants were being breastfed without vitamin D supplementation. Serum 25-OHD concentrations at entry into the study ranged from 3-61 ng/ml and increased with age. 3 infants in each group were diagnosed as having rickets. Serum 25-OHD concentrations did not change significantly during the 2-month study period among controls, while serum 25-OHD values increased significantly in the experimental group. Final infant serum 25-OHD concentrations correlated with ultraviolet exposure scores (p.001). The estimate of ultraviolet score needed to maintain a serum 25-OHD of 11 ng/ml was 2.4 (24 minutes/day with only the face uncovered). Rickets has been reported in as many as 18% of Chinese infants and seems to especially affect those 2-4 months of age. The fact that not all infants with rickets in this study had low 25-OHD concentrations suggests 2 possibilities: 1) not all rickets is necessarily related to a vitamin D deficiency, or 2) serum 25-OHD concentrations are not the best indicator of vitamin D status. The low serum 25-OHD concentrations in many Chinese infants may be related to low maternal milk vitamin D content resulting from the lack of vitamin D food fortification. Overall, these results suggest that the diet of breastfed Chinese infants should be supplemented with orally administered vitamin D.

Low bone mineral content in summer-born compared with winter-born infants

Summary Possible seasonal differences in newborn bone mineral content (BMC) have not been studied. Adult studies show seasonal variations with lower BMC in winter versus summer. Assuming that BMC variations may relate in part to vitamin D status, we hypothesized that newborn BMC would be lower in winter than summer. BMC of one third distal radius was measured in 55 healthy term newborns using a single beam photon absorptiometer [coefficient of variation (CV) for phantom standard 2.1%]. Infants were enrolled during summer (July-September, 1988) and winter (January-March, 1989) for a longitudinal nutrition study. Contrary to our hypothesis, there was a 12% lower BMC in summer versus winter (mean ± SD 75.94 ± 17.42 vs. 86.55 ± 17.54 mg/cm, respectively; p = 0.035). The difference remained significant after controlling for possible race and gender effects (p = 0.02). We conclude that BMC is lower in summer- compared with winter-born infants. Since any seasonal effects on fetal bone are presumably related to effects through the mother, we speculate that if maternal vitamin D status influences fetal bone mineralization, the effect (possible sunshine deprivation in winter) may operate especially in early pregnancy, thus resulting in lower BMC, evident at birth in summer.

Normal serum indices of bone collagen biosynthesis and degradation in small for gestational age infants.

Serum carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), new markers of bone collagen type I biosynthesis and degradation, have not been studied in small for gestational age (SGA) infants. In an earlier study, we found a lower bone mineral content (BMC) and decreased serum osteocalcin in SGA than in appropriate for gestational age (AGA) infants, supporting the thesis that decreased fetal bone formation is a cause of lower BMC in SGA. In view of the role of insulin-like growth factor-I (IGF-I) in the regulation of collagen type I synthesis and degradation, and low serum IGF-I concentrations in SGA infants, we hypothesized that serum PICP would be lower and serum ICTP would be higher in SGA than in AGA infants, reflecting decreased bone collagen type I biosynthesis or enhancement of bone collagen type I degradation in SGA. We studied 19 term SGA and 38 term AGA infants that were matched specifically 1:2 by gestation and birth month. There were no differences between SGA and AGA infants in serum PICP nor ICTP concentrations. Serum ICTP was correlated with osteocalcin and with PICP in SGA infants but not in AGA infants. Thus, serum biochemical indices of bone collagen type I biosynthesis and degradation in term SGA infants are similar to those in term AGA infants. These findings are not consistent with the thesis of altered fetal bone collagen type I biosynthesis or degradation in SGA. We suggest that the reduced bone mineral content in SGA infants is predominantly related to a lower supply of minerals rather than defective regulation of bone collagen type I metabolism.

Seasonal and Geographical Variations in the Growth Rate of Infants in China Receiving Increasing Dosages of Vitamin D Supplements

In theory, sunshine exposure is sufficient to maintain normal vitamin D concentrations for the optimal growth of newborn infants. To determine whether season of birth, latitude (north v. south) and increasing dosages of vitamin D supplements would influence the growth rate for the first 6 months of life, 255 healthy fall-and spring-born infants from two northern and two southern cities in China were randomly assigned to receive either 100, 200, or 400 IU of vitamin D a day. The study showed that season of birth and dose of vitamin D did not affect the growth rate of infants born in the same latitude, but a significant difference was found in the gain in length over the 6-month period between infants from the north and infants from the south (P = 0.0001). Regional differences among the Chinese people, other than sunshine exposure, may have influenced the difference in length gain.

Randomized trial of early vs. late introduction and commercially-prepared vs. parent's choice of solid foods on growth and body composition • 495

Objective: The optimal time and choice of solid foods to introduce to an infants diet is unknown. The aim of this randomized trial was to determine whether early vs. late introduction and commercially-prepared vs. parents choice of solid foods affects growth or body composition.