Reginald C. Tsang

Sunshine exposure and serum 25-hydroxyvitamin D concentrations in exclusively breast-fed infants.

The relationship between serum 25-hydroxyvitamin D (25-OHD) concentrations and sunshine exposure in 61 term, exclusively breast-fed infants younger than 6 months of age was investigated. Sunshine exposure was quantitated using a sunshine and clothing diary, which was verified by infant-adapted ultraviolet dosimetry. By multiple regression techniques, infant serum 25-OHD concentrations were significantly related to UV exposure and maternal serum 25-OHD concentrations. Infant 25-OHD concentrations correlated with sunshine exposure in infants whose mothers had low (less than 35 ng/ml) or high (greater than 35 ng/ml) serum concentrations of 25-OHD (r = 0.70, P less than 0.001 and r = 0.53, P = 0.004, respectively). Estimates were made to determine sunshine exposure conditions necessary to maintain serum 25-OHD concentrations above the lower limit of the normal range (11 ng/ml). A conservative estimate would be 30 minutes per week wearing only a diaper or 2 hours a week fully clothed without a hat.

Vitamin D homeostasis in the perinatal period. 1,25-Dihydroxyvitamin D in maternal, cord, and neonatal blood.

To investigate vitamin D homeostasis in term pregnancy, we measured 1,25-dihydroxyvitamin D (1,25(OH)2D) in serum samples from 19 term pregnant women and in samples from the placental veins of their infants. Samples were obtained from 14 neonates at 24 hours of age. At delivery, maternal concentrations of 1,25(OH)2D were elevated above normal adult values; placental-vein concentrations in the infants were significantly lower than adult normal or maternal values and bore no relation to maternal values. By the time the infants reached 24 hours of age, their serum concentrations had reached normal adult values, concomitant with a decrease in serum concentration of ionized calcium. We speculate that low 1,25(OH)2D concentrations in utero suggest that there is no need for intestinal calcium absorption in the fetus. Postnatal increase of 1,25(OH)2D may result from its production as a prerequisite to extrauterine requirements for intestinal absorption of calcium and phosphorus.

Effects of infant nutrition on cholesterol synthesis rates.

ABSTRACT: Nutrient effects on cholesterol fractional synthesis rates (FSR) in infancy by stable isotope determination have not been studied. We hypothesized that FSR is significantly reduced with high dietary cholesterol and phytoestrogen intake and increased with low dietary cholesterol and phytoestrogen intake. We prospectively studied 33 term male infants exclusively fed human milk (high cholesterol, low phytoestrogen, n = 12), cow milk-based formula (low cholesterol, low phytoestrogen, n = 8), soy milk-based formula (zero cholesterol, high phytoestrogen, n = 7), or soy milk-based formula modified to contain cholesterol (low cholesterol, high phytoestrogen, n = 6) during the first 4 mo of life. Cholesterol FSR was determined from rate of incorporation of deuterium into erythrocyte membrane cholesterol, and urinary isoflavone excretion (an index of dietary phytoestrogen exposure) was measured by gas chromatography-mass spectrometry. Significant differences in cholesterol FSR were found. FSR (%/d) was lowest in human milk (2.62 ± 0.38), highest in soy milk-based formula (9.40 ± 0.51), and intermediate in cow milk-based and modified soy milk-based formula (6.90 ± 0.48 and 8.03 ± 0.28, respectively), p < 0.0001. Cholesterol FSR was significantly lower in modified soy milk-based compared with soy milk-based formula, p < 0.05. We also show for the first time that dietary phytoestrogens are absorbed and excreted by the infant fed soy protein-based formula. Urinary isoflavone excretion was inversely related to cholesterol FSR, but it was not significantly related to serum cholesterol concentration. We conclude that the type of infant nutrition and dietary cholesterol are major factors influencing cholesterol fractional synthesis rates in infancy.

Cardiac septal hypertrophy in hyperinsulinemic infants

One infant with nesidioblastosis, and five of 18 infants of diabetic mothers had echocardiographically determined septal hypertrophy (greater than or equal to 6 mm). No correlation was found between the septal hypertrophy and the presence of hypocalcemia, polycythemia, birth asphyxia, or other observed clinical findings. All of the infants with septal hypertrophy, however, had profound hypoglycemia shortly after birth in contrast to those infants without septal hypertrophy. Macrosomic IDM have intrauterine hyperglycemia and hyperinsulinemia. The presence of profound neonatal hypoglycemia is consistent with the metabolic effects of significant neonatal hyperinsulinemia which is also present in the fetus. Infants with nesidioblastosis also have fetal hyperinsulinemia. Recent investigations have suggested an important role for insulin in the developing heart since it is rich in insulin receptors and contains marked insulin degrading capacity. Although fetal hyperglycemia has been suggested as the cause of septal hypertrophy in IDM, we hypothesize that fetal hyperinsulinemia contributes directly to the spinal hypertrophy.

Hypocalcemia in infants of diabetic mothers: Studies in calcium, phosphorus, and magnesium metabolism and parathormone responsiveness

Since infants of diabetic mothers are often delivered prematurely, it has been uncertain whether the hypocalcemia reported in them is related to maternal diabetes or to prematurity. In this study of 28 infants of diabetic mothers and 28 prospectively matched infants born to nondiabetic mothers, the incidence of hypocalcemia was significantly increased in the infants of diabetic mothers, even when gestational age and perinatal complications were taken into consideration. Renal studies demonstrated no differences in excretion of calcium, magnesium, and phosphorus between infants of diabetic mothers and control infants. Serum calcium levels were higher in diabetic mothers than in nondiabetic control subjects. Lower serum calcium levels and higher serum phosphate levels were present in infants of diabetic mothers postnatally. End organ responsiveness was shown by a calcemic and phosphaturic response to exogenous parathormone. It is speculated that relative maternal hyperparathyroidism leading to fetal hypoparathyroidism may be a factor in the pathogenesis of neonatal hypocalcemia in infants of diabetic mothers.

Bone mineral content and serum 25-hydroxyvitamin D concentrations in breast-fed infants with and without supplemental vitamin D: One-year follow-up

in association with hypothyroidism. We did not obtain parietal cell or intrinsic factor antibodies. There was no evidence of other au to immune diseases or deficiencies in the mother (or int2ant) on the basis of routine clinical and laboratory tests. Breast-fed infants are at risk for nutr i t ional deficiencies if the mother is malnourished, a vegan, or if she has an abnormali ty in nut r ien t metabolism. Physicians should be aware tha t even with a well-balanced mate rna l diet, an occasional breast-fed infant can develop a serious nutritional deficiency.

Fractures and rickets in very low birth weight infants: conservative management and outcome.

Fractures and rickets (F/R) often occur in very low birth weight (VLBW < 1500 g) infants who are acutely ill. However, there are no prospective longitudinal studies of the clinical course of F/R in these infants. In a prospective study of 78 VLBW infants during the first year after birth, radiographic evidence of healing and remodeling of F/R was noted in affected infants (n = 25) concurrent with increased enteral intake and physical growth, and regardless of whether specific orthopedic treatment was initiated. Skeletal maturation as indicated by the development of ossification centers at the wrists was directly related to weight gain, and was similar to term infants by 1 year. No infant had skeletal deformities on follow-up examination. We suggest that VLBW infants with F/R can be managed “conservatively,” with emphasis on nutritional intake to achieve weight gain.

Bone mineral content in term and preterm appropriate-for-gestational-age infants

Photon absorptiometry adapted for use in small infants was utilized to measure bone mineral content in 42 term and 30 perterm appropriate-for-gestational-age infants. BMC at birth correlated significantly with gestational age and birth weight. Sequential measurements of BMC in premature infants during the first three months showed that the postnatal increase in BMC was significantly less than the BMC expected in utero. We speculate that decreased intake of calcium and phosphate effects postnatal bone mineralization in premature infants.

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.

Major malformations in Infants of IDDM Women: Vasculopathy and Early First-Trimester Poor Glycemic Control

From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of <100 mg/dl and a 90-min postprandial blood glucose of <140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%). By both univariate and multivariate analyses, the following two factors were significantly associated with major CMs: preexisting vasculopathy (retinopathy and/or nephropathy; 54 vs. 25% in the CM and non-CM groups, respectively; P < .05) and increased maternal HbA, at 9 wk gestation (P < .001). CMs were not associated with White class, insulin requirements, and frequency of maternal hypoglycemia as assessed clinically. There was no significant interaction between maternal HbA, and the presence of vasculopathy. We conclude that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal clinical hypoglycemia or insulin therapy per se are independent factors associated with major CMs in IDMs. We suggest, based on these data, that in addition to establishment of meticulous glycemic control, IDDM women be assessed for vasculopathy before pregnancy and given appropriate counseling regarding risk of CMs.