Bone Mineralization and Turnover in Preterm Infants at 8–12 Years of Age: The Effect of Early Diet

Abstract

Our previous studies raised two hypotheses: first that suboptimal early nutrition and second that human milk have enhancing effects on long-term bone mineralization. To test these hypotheses experimentally, we measured whole body and regional bone mineral content (BMC) and bone mineral density (BMD), using dual-energy X-ray absorptiometry and single-photon absorptiometry, and bone turnover at 8-12 years in 244 preterm children (128 boys) who participated in a prospective randomized study of diet during the neonatal period. Dietary randomizations studied were: banked human milk (BBM, n = 87) versus preterm formula (PTF, n = 96) as the sole diet or as a supplement to mother's expressed breast milk (EBM); PTF (n = 25) versus term formula (TF, n = 36) as sole diet. Ninety-five term children of the same age were also studied. First, preterm children were shorter and lighter than term children (height SD scores −0.49 (1.1) vs. +0.22 (0.9), weight SD scores −0.41 (1.2) vs. +0.38 (1.0)) and had significantly lower whole-body BMC than their peers; decrements were also evident at some regional sites. These differences disappeared after adjusting for bone area, body size, and pubertal status. Second, children previously randomized to BBM versus PTF or TF versus PTF showed no significant differences in anthropometry, BMC, BMD, or osteocalcin (OC). Third, there was no independent effect of the proportion of EBM on BMC, BMD, or OC and no interaction between randomized diet and the amount of EBM received. Fourth, plasma OC was significantly higher in preterm children than in term children (12.4 vs. 11.0 ng/ml, p < 0.005) and in preterm children who had received a low-nutrient (BBM/TF) as opposed to a high-nutrient diet (PTF) during the neonatal period (12.9 vs. 11.9 ng/ml, p = 0.03). In conclusion, preterm children are shorter, lighter, and have lower bone mass than their peers at age 8-12 years. The lower BMC is, however, appropriate for the bone and body size achieved. Despite large differences in early mineral intake, early diet does not affect bone mass in preterm children, and fresh human milk has no specific effect. However, poor nutrition during the neonatal period may result in higher bone formation rates during childhood. (J Bone Miner Res 1999;14:810-820)

Maternal diet during pregnancy is associated with bone mineral density in children: a longitudinal study

“…In humans, this appears to be the case for ischaemic heart disease, diabetes mellitus and hypertension (Barker, 1993). It appears likely to apply to bone also as we, and others, have previously reported early life associations with smoking in utero and breast-feeding in early life (Jones et al, 2000a,b;Backstrom et al, 1999) as well as breast milk supplementation, although the bene®t reported at age 5 y did not persist at age 11 y (Bishop et al, 1996;Fewtrell et al, 1999). The dietary associations we report in this paper are independent of these factors and, unlike both breast-feeding and smoking, are present in both term and preterm infants, suggesting that they are not dependent on a possible physiology of maturity.…”

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age

“…Our preterm infants seemed to have normal BMD and BMC compared with the age-and height-matched control group at 4 y of age, which contradicted our initial hypothesis. Ex-preterm infants and adults have lower bone mass (2-5) than full-term controls, although other studies have found that the bone mass in ex-preterm infants either is appropriate for their body size or does not differ from normal-weight full-term infants (7,8,11). These findings might reflect different treatment strategies in modern neonatal intensive care units.…”

“…Many studies have found that ex-preterm infants are shorter, lighter, and have lower bone mass (2-5) than their full-term peers, and ex-preterm infants who are small for gestational age at birth seem to have the most risk (6). However, several studies have found that the bone mass in ex-preterm infants is appropriate for their body size (7,8) and one study proposed that bone mineral density (BMD) in very-low-birth-weight infants is normalized at 2 y of age (9). During adolescence, children who were born prematurely do not have different bone mineral content (BMC ) (10) or BMD (11) (adjusted for height and weight) in comparison with normal-weight children born at full term.…”

Postdischarge nutritional therapy

“…Long-term data show that the neonatal period is critical in terms of the effects of nutrition on later health and developmental outcomes. [9][10][11][12] The first year of life may provide an important opportunity for human somatic and brain growth to compensate for earlier deprivation. A key question is whether VLBW infants have special nutritional requirements in the postdischarge period and, in more biologic terms, whether this period of nutrition is also critical for later health and development, particularly since it is common for human milk fortifiers to be stopped and/or term infant formulae to be substituted at an arbitrary time point, at hospital discharge.…”