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In the newborn preterm infant a combination of inadequate reserves and increased loss of essential minerals is common and frequently compounded by difficulties in obtaining an intake sufficient to replace losses and restore reserves. Deficiencies in calcium and phosphate and disturbed balance between them are frequently encountered, and may lead to significant impairment of bone deposition. Osteopenia of prematurity – also known as neonatal rickets, rickets of prematurity or neonatal metabolic bone disease – is a common and important concern in neonatology, and effective management is hindered by difficulties in accurately assessing calcium and phosphate status and the ‘quality’ of bone deposition. It is well known that preterm infants are at risk of reduced bone mineral content (BMC) and subsequent bone disease and that many factors may contribute to this. The majority of calcium and phosphate accretion and bone mineralisation occur in the third trimester of pregnancy and from 24 weeks of gestation onwards, it has been estimated that the fetus in utero gains about 30 g in weight each day, and this daily requirement includes 310 mg of calcium and 170 mg phosphorus.1 It has been shown that BMC and bone mineral density (BMD) correlate positively with gestational age, birth weight, body area and length.2 Mineral deposition may be affected before an infant is born as a number of prenatal factors, particularly placental function, have been shown to play a part in the development of osteopenia. The placenta converts vitamin D to 1,25-dihydrocholecalciferol which enables phosphate to be transported across the placenta.3 A reduced ability to do so explains the higher incidence of postnatal rickets that may be seen in infants with intrauterine growth restriction suggesting that chronic injury to the placenta may limit the ability to transfer phosphate.4 Poor mineralisation may also occur in …

Measurement of newborn babies is widely regarded as being too inaccurate to justify its regular practice. It is common for infants to be weighed at birth and for no other measurements to be made. Although such assumptions are superficially correct, it is possible to train people to perform accurate measurements and for improved performance to be sustained. Accurate sequential measurements are possible and provide more information than single measurements. Detailed measurements show that postnatal growth may change rapidly and dramatically, particularly in preterm infants. Postnatal growth impairment is common in such infants and may be sustained. Limited evidence suggests that there may be a significant reduction in final stature. Preliminary data also suggest that many preterm infants may also show evidence of alterations in biochemical and physiological variables consistent with early programming and the potential for altered disease susceptibility in adult life.

Growth velocity is higher in late intra-uterine and early post-natal life than at any time thereafter, and accurate measurements are essential for appropriate monitoring. The accuracy with which such measurements are made and recorded is frequently questionable, however, and short- and medium-term changes in growth may be difficult to interpret in the light of normal variations in the pattern of growth. Infants who are small at birth must be accurately classified because intra-uterine growth retardation and small for gestational age have different implications for both causation and outcome. Prediction of expected growth on the basis of mid-parental height is essential but frequently omitted. Post-natal growth impairment is common in pre-term infants and is often rapid in onset. Poor growth may continue for many months, and catch-up may be incomplete. Early growth failure may have a significant influence on subsequent morbidity and mortality.

Concentrations of circulating antioxidants may be important in the aetiology of disease in premature infants. Blood samples were taken from 49 premature infants within two hours of birth. Plasma ascorbic acid, caeruloplasmin, and the ability of plasma to prevent lipid peroxidation in vitro were measured. Plasma ascorbic acid concentrations at birth ranged from 26.3 to 185.4 mumol/l. Plasma antioxidant activity at birth (microliter plasma required to inhibit lipid peroxidation) showed a strong negative correlation with plasma ascorbic acid and the plasma ascorbic acid to caeruloplasmin ratio. After correcting for gestational age and birth weight, plasma antioxidant activity at birth remained a significant predictor of mortality. Such plasma antioxidant activity is partly determined by the ferroxidase activity of caeruloplasmin. This may be modulated by high concentrations of ascorbic acid which may inhibit the antioxidant activity of plasma and thereby influence outcome.

Knemometry has been used to measure lower leg growth during 32 nine day courses of dexamethasone in 26 babies ranging from 24 to 32 weeks' gestation at birth. Mean leg length velocity was 0.37 mm/day in the 10 days before steroids. Administration of dexamethasone was associated with a decrease in velocity in all babies, and in 15 leg shortening was documented. Mean leg length velocity during steroid treatment was -0.003 mm/day. After the course of dexamethasone was completed there was an immediate increase in leg length velocity to a mean of 0.52 mm/day over the first 10 days then falling to a value similar to the growth velocity observed before treatment. Leg length had reached the value predicted by growth before steroids about 30 days after dexamethasone. The reduction in leg length velocity occurred despite a significant increase in energy intake and decrease in oxygen requirements.

We determined the contributions of IGF-I, IGFBP-3 and leptin to growth in extremely premature infants over the first two years. Weight (Wt), crown-to heel length (CHL), plasma IGF-I, IGFBP-3 and leptin were measured in infants (gestation 24-33 wk) at birth (n = 54), expected date of delivery (EDD) and 6, 12 and 24 mo post-EDD (n = 29). Area under the curve (AUC) for hormone levels was calculated over 4 periods: birth-EDD, EDD-200 d, EDD-350 d and EDD-700 d. IGFBP-3, but not IGF-I or leptin, on day 1 correlated with birth Wt SD scores (SDS) (r = 0.46, p = 0.002) and CHL SDS (r = 0.41, p = 0.01). Wt SDS at EDD correlated with AUC IGF-I, IGFBP-3 and leptin (birth-EDD), but leptin was the best predictor in multiple regression (r = 0.65, p < 0.0001). Wt at EDD + 700 d correlated with AUC leptin (EDD-700 d) (r = 0.62, p = 0.002). CHL SDS at EDD correlated with AUC IGFBP-3 and leptin (birth-EDD), but IGFBP-3 was the best predictor (r = 0.55, p < 0.0001). CHL at EDD + 700 d correlated with AUC IGF-I and IGFBP-3 (EDD-700 d), but IGFBP-3 was the best predictor (r = 0.47, p = 0.01). Wt and CHL at birth were associated with IGFBP-3 levels in these infants. Wt at EDD and EDD + 700 d was predicted by concurrent leptin output while linear growth at EDD and EDD + 700 d was predicted by IGFBP-3 output.

Accurate measurements of both healthy and premature neonates are possible but rarely performed. Routine anthropometry is often not performed at all or with large measurement errors due to inadequate training of personnel or inappropriate equipment. Sick neonates are often considered unsuitable for anthropometry and growth is wrongly equated with weight gain. Gain in length may be disturbed by poor health and permanent extrauterine growth retardation and changes in body proportions induced in some survivors of neonatal intensive care. Drug treatments may have profound effects on length gain and the relationship of length to weight.

High concentrations of total vitamin C have been measured in the plasma of premature infants. At these concentrations ascorbic acid inhibited the ferroxidase activity of caeruloplasmin measured directly in vitro. The degree of inhibition was dependent on the ratio of ascorbic acid: caeruloplasmin. Values for the ratio of vitamin C: caeruloplasmin measured in premature babies would be predicted to inhibit ferroxidase activity by up to at least 80%. Ferroxidase activity measured in the plasma of premature babies increased from birth but was significantly lower than in plasma collected from adults (

A study was conducted to investigate the relationship between vitamin C intake and the rate of tyrosine catabolism in premature babies. A 13C tyrosine breath test was developed for the measurement of tyrosine catabolism. Premature babies were randomly allocated to receive a daily intake of vitamin C which ranged from 8 to 100 mg/kg body weight, for 5 days. Tyrosine catabolism was measured at the beginning and the end of this period. Daily intakes of vitamin C of 20 mg/kg or more elicited a greater increase in tyrosine catabolism over 5 days than 8 mg/kg/day. The magnitude of the difference, in terms of percentage of tyrosine metabolised, was, however, small and of doubtful biological significance. Vitamin C intakes above 20 mg/kg/day had no further measurable effect on the catabolism of tyrosine.

To evaluate the effect of disturbance in early growth on subsequent stature we have made detailed measurements of weight, length and lower leg length in the early postnatal period and at 8 months corrected age in 33 babies who received intensive care. Mean leg length SD score decreased by 1.22 (p = 0.0001, paired t test) between birth and 36 weeks postconceptual age. Both length and weight at 8 months most closely correlated with length or mean leg length at 36 weeks (r = 0.762 & 0.703, p = 0.0001 for length; r = 0.556 & 0.511, p = 0.0017 & 0.003 for weight). Correlation with any measure of early weight was less strong. Using stepwise linear regression leg length velocity in the first eight weeks of life was most strongly associated with length at eight months (adjusted r squared = 0.3, F = 10.4, p =

In 1951 Silverman reported significant growth disturbance in premature infants who received ACTH for the treatment of retinopathy. Despite the dramatic response that was demonstrated the effects of steroids on growth in this age group remain poorly understood. We have used the neonatal knemometer to assess bone growth in 26 babies who received a total of 32 nine day courses of dexamethasone for the treatment of chronic lung disease. Growth of the lower leg and weight gain were assessed for 10 days before, during and 30 days after the course. There was a decrease in leg length velocity in all subjects during steroid administration and actual limb shrinkage occurred in 15. There was then catch-up growth to the estimated pre-steroid length by 30 days. Oxygen requirements fell and calorific intake rose during steroid treatment Dexamethasone has a profound effect on cartilage and bone growth even in the preterm neonate. The long term consequences of this effect are no clearer today than they were for Silverman more than 40 years ago.