Tactile and Kinesthetic Stimulation (TKS) intervention improves outcomes in weanling rat bone in a neonatal stress model.

OBJECTIVES: Preterm infants are born with low bone mineral. Neonatal stress further impedes bone mineralization. Clinical evidence suggests that tactile and kinesthetic stimulation (TKS) improves bone phenotype and decreases stress response. Clinical and translational studies indicate the IGF-1 axis, responsible for postnatal growth and bone mineralization, is a key player. We hypothesized that TKS would attenuate the negative impact of neonatal stress on bone phenotype and the IGF-1 axis in weanling rats. METHODS: Neonatal stress (STRESS) or TKS (STRESS + 10min TKS) was administered from D6 to D10. Control animals received standard care. Tissue was harvested on D21. Dual energy x-ray absorptiometry (DXA) and bone morphometry were performed and serum osteocalcin, type I procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase (TRAP), and bone and liver mRNA levels of IGF-1, IGF-1 receptor (IGF-1R), and growth hormone receptor (GHR) were measured. RESULTS: Neonatal stress increased bone mineral content (BMC), area (BA), growth plate width, liver IGF-1 mRNA, and serum IGF-1. TKS maintained areal bone mineral density (aBMD) and bone specific IGF-1 and IGF-1R mRNA while STRESS decreased compared to controls. CONCLUSIONS: Neonatal stress results in apparent accelerated growth response. TKS differed from STRESS with improved tibia aBMD and increased bone specific IGF-1 mRNA.

The effect of massage on heart rate variability in preterm infants.

OBJECTIVE: To test the hypothesis that massage would improve autonomic nervous system (ANS) function as measured by heart rate variability (HRV) in preterm infants. STUDY DESIGN: Medically stable, 29- to 32-week preterm infants (17 massage, 20 control) were enrolled in a masked, randomized longitudinal study. Licensed massage therapists provided the massage or control condition twice a day for 4 weeks. Weekly HRV, a measure of ANS development and function, was analyzed using SPSS generalized estimating equations. RESULTS: Infant characteristics were similar between groups. HRV improved in massaged infants but not in the control infants (P<0.05). Massaged males had a greater improvement in HRV than females (P<0.05). HRV in massaged infants was on a trajectory comparable to term-born infants by study completion. CONCLUSION: Massage-improved HRV in a homogeneous sample of hospitalized, medically stable, preterm male infants and may improve infant response to exogenous stressors. We speculate that massage improves ANS function in these infants.

Tactile/kinesthetic stimulation (TKS) increases tibial speed of sound and urinary osteocalcin (U-MidOC and unOC) in premature infants (29-32weeks PMA).

Preterm delivery (<37 weeks post-menstrual age) is associated with suboptimal bone mass. We hypothesized that tactile/kinesthetic stimulation (TKS), a form of infant massage that incorporates kinesthetic movement, would increase bone strength and markers of bone accretion in preterm infants. Preterm, AGA infants (29-32 weeks) were randomly assigned to TKS (N=20) or Control (N=20). Twice daily TKS was provided 6 days per week for 2 weeks. Control infants received the same care without TKS treatment. Treatment was masked to parents, health care providers, and study personnel. Baseline and week two measures were collected for tibial speed of sound (tSOS, m/sec), a surrogate for bone strength, by quantitative ultrasound (Sunlight8000) and urine markers of bone metabolism, pyridinium crosslinks and osteocalcin (U-MidOC and unOC). Infant characteristics at birth and study entry as well as energy/nutrient intake were similar between TKS and Control. TKS intervention attenuated the decrease in tSOS observed in Control infants (p<0.05). Urinary pyridinium crosslinks decreased over time in both TKS and CTL (p<0.005). TKS infants experienced greater increases in urinary osteocalcin (U-MidOC, p<0.001 and unOC, p<0.05). We conclude that TKS improves bone strength in premature infants by attenuating the decrease that normally follows preterm birth. Further, biomarkers of bone metabolism suggest a modification in bone turnover in TKS infants in favor of bone accretion. Taken together, we speculate that TKS improves bone mineralization.

Mechanical-tactile stimulation (MTS) intervention in a neonatal stress model improves long-term outcomes on bone.

OBJECTIVES: Neonatal stress impairs postnatal bone mineralization. Evidence suggests that mechanical tactile stimulation (MTS) in early life decreases stress hormones and improves bone mineralization. Insulin-like growth factor (IGF1) is impacted by stress and essential to bone development. We hypothesized that MTS administered during neonatal stress would improve bone phenotype in later life. We also predicted an increase in bone specific mRNA expression of IGF1 related pathways. METHODS: Neonatal stress (STRESS) and MTS (STRESS+10 min of MTS) were given from D6 to D10 of rat life and tissue was harvested on D60 of life. Dual energy x-ray absorptiometry (DXA), bone morphometry, serum osteocalcin, type I procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase (TRAP), and bone and liver mRNA levels of IGF1, IGF1 receptor (IGF1R), and growth hormone receptor (GHR) were measured. RESULTS: Stress resulted in reduced bone area and bone mineral content (BMC) compared to naive control (CTL). MTS intervention increased BMC and tibial growth plate width compared to STRESS. MTS also resulted in higher osteocalcin, and, in males, lower TRAP (p<0.05). MTS resulted in three-fold, two-fold, and six-fold higher bone specific IGF1, IGF1R, and GHR, respectively (p ≤ 0.001) compared to STRESS. CONCLUSIONS: MTS in early postnatal life improves long-term bone mineralization. IGF1 and related pathways may explain improved BMC.

Maternal-administered physical activity enhances bone mineral acquisition in premature very low birth weight infants.

OBJECTIVE: To determine if physical activity delivered by an infant's mother would be as effective in promoting bone mineral acquisition in preterm very low birth weight (VLBW) infants as the same intervention administered by a trained therapist. PATIENTS AND METHODS: Preterm VLBW infants were randomized to receive daily physical activity administered by the infant's mother (MOM, n=11) or a trained therapist (OT, n=11), or control (n=11). Physical activity consisted of range of motion movements against passive resistance to all extremities for 5 to 10 min daily. All infants were fed mother's milk with fortification to 24 kcal oz(-1). Dual energy x-ray of the forearm bone area (BA, cm(2)), mineral content (BMC, g), and density (BMD, g/cm(2)) and measurement of bone formation (bone-specific alkaline phosphatase, BAP) and resorption (urine pyridinium crosslinks of collagen, Pyd) were obtained at study entry and at 2.0 kg of body weight. RESULT: Forearm BA and BMC gains were greater in MOM and OT infants compared to the control infants despite similar postnatal growth rate and nutrient intake. Serum BAP levels decreased in controls but remained unchanged in MOM and OT infants. Urine Pyd levels were similar at baseline to 2.0 kg for all groups. These findings suggest greater bone growth and mineral acquisition in MOM and OT infants than control infants. CONCLUSION: This study demonstrates that a physical activity program administered by the infant's own mother is as equally effective as therapist-administered physical activity in promoting greater bone growth and mineral acquisition in preterm VLBW infants.

Case-control study of the muscular compartments and osseous strength in neurofibromatosis type 1 using peripheral quantitative computed tomography.

Skeletal anomalies are observed in neurofibromatosis type 1 (NF1), but the pathogenesis is unknown. Given that muscle mass is important in the development of the strength of bone, peripheral quantitative computed tomography (pQCT) was utilized to compare measurements of muscle compartments between NF1 individuals and controls. Forty individuals with NF1 (age 5-18 years) were evaluated. Cross-sectional measurements, at the 66% tibial site, were obtained using pQCT (XCT-2000, Stratec) and variables were compared to controls without NF1 ((age 5-18 years, N=380) using analysis-of-covariance controlling for age, height, Tanner stage, and gender. The NF1 cohort showed decreased total cross-sectional area [p<0.001], decreased muscle plus bone cross-sectional area [p<0.001], decreased muscle cross-sectional area [p<0.001], and decreased Stress Strain Index [p=0.010]. These data indicate that NF1 individuals have decreased muscle cross-sectional area and decreased bone strength than individuals without NF1.

Bone mass and density response to a 12-month trial of calcium and vitamin D supplement in preadolescent girls.

BACKGROUND: Maximal bone acquisition in adolescent girls through dietary and lifestyle practices is advocated to prevent or minimize the development of osteoporosis and its associated complications in later life. Longitudinal investigations of bone acquisition in children and adolescents have utilized areal bone mineral density (BMD, mg/cm(2)) as a measure of bone mass and strength. Peripheral quantitative computed tomography (pQCT), which provides a three-dimensional display of data, separate analyses of bone compartments, and bone mass in terms of volumetric BMD (vBMD, mg/cm(3)), has recently been introduced for clinical use. OBJECTIVE: To assess the impact of a 12-month daily calcium supplement on total and trabecular bone acquisition as measured by pQCT in preadolescent girls. DESIGN: Early adolescent Caucasian girls (aged 12 years, Tanner Stage 2) were enrolled in a randomized trial of daily calcium supplement (TX, 800 mg calcium carbonate and 400 IU vitamin D) or placebo (C). Body weight, height, and distal tibia measurements by pQCT were obtained at enrollment, 6 and 12 months. Pubertal status and physical activity records were assessed at baseline and 12 months. Three-day food intake records were completed every three months. RESULTS: Seventy-one girls completed the 12-month trial (TX=35, C=36). No differences were found for age, weight, height, body mass index, pubertal maturation, or reported physical activity at enrollment or during the study. Average intakes during the study were 1524 mg calcium and 496 IU vitamin D (TX) versus 865 mg calcium and 160 IU vitamin D (C) per day. Baseline total bone values were similar, however, trabecular values were greater in TX girls despite randomization. Percent changes were calculated to adjust for baseline differences. Because of the small cortical thickness at the 10% site (mean values < 1.6 mm), cortical mass and density were not analyzed. The percent changes for trabecular bone mineral content (BMC, mg) and vBMD were significantly greater in TX girls (+4.1% BMC and +1.0% vBMD TX versus -1.6% BMC and -2.0% vBMD C, p<0.006; ANCOVA) after 12 months of supplement. Trabecular bone area (BA, cm(2)) and total bone change, however, did not differ between groups. CONCLUSIONS: Daily calcium and vitamin D supplementation promotes greater trabecular BMC and vBMD acquisition in preadolescent girls. The single site selected for pQCT evaluation in this study did not allow evaluation of the cortical bone compartment. Future studies that utilize the pQCT technique need to incorporate multiple measurement sites to better assess total, cortical, and trabecular bone.

Daily physical activity program increases bone mineralization and growth in preterm very low birth weight infants.

OBJECTIVE: A study of daily physical activity was performed with 32 preterm infants to evaluate changes in body weight and bone mineralization. STUDY DESIGN: Subjects were matched by birth weight and gestational age and randomly assigned to the physical activity (PA; n = 16) or to the control (C; n = 16) program. PA consisted of range of motion against passive resistance to all extremities for 5 to 10 minutes daily. Peripheral dual-energy x-ray of the right forearm (ulna and radius); biomarkers of bone formation (serum type I collagen C-terminal propeptide [PICP]) and resorption (urine pyridinoline cross-links of collagen [Pyd]); serum calcium, phosphate, alkaline phosphatase, parathyroid hormone (PTH), and 1, 25-(OH)(2) vitamin D; and urine levels of calcium, phosphate, and creatinine were obtained. All measurements were made at study entry and at 2.0 kg of body weight. RESULTS: Despite a similar nutrient intake at advised levels for preterm infants, gains in body weight (g) and forearm bone length (cm), bone area (BA; cm(2)), bone mineral content (BMC; mg), and fat-free mass (g) were greater in PA infants. Forearm bone mineral density and fat mass gains did not differ between groups. Serum PICP levels remained constant in PA infants but decreased in C infants suggesting a slower rate of bone formation. Urine Pyd or bone resorption activity was similar between groups. A higher level of serum PTH was observed in PA infants at 2. 0 kg of body weight; however, the change from study entry to completion did not differ between groups. All other serum and urine values were similar and within normal limits. CONCLUSION: A daily PA program promotes greater gains in body weight, forearm length, BA, BMC, and fat-free mass in premature infants.

Eliminating sleep-associated hypoxemia improves growth in infants with bronchopulmonary dysplasia.

OBJECTIVE: Infants with bronchopulmonary dysplasia (BPD) have been previously reported to have a decrease in growth velocity after stopping supplemental oxygen (SO). SO was stopped after a short-term recording (20-30 minutes) of pulse oxygen saturation (Sao2) of 92% or greater in room air. Other studies have documented that Sao2 decreases further during feedings and sleep in infants with BPD. Two questions were asked: (1) whether short-term, awake Sao2 studies would reliably predict prolonged sleep Sao2; and (2) how Sao2 sustained at 88% to 91% vs 92% or greater in room air would impact growth velocity in infants with BPD. METHODOLOGY: Short-term Sao2 studies were prospectively compared with prolonged sleep Sao2 (n = 63) and the growth velocity of infants who had SO discontinued after a prolonged sleep Sao2 recording of 88% to 91% (group 1; n = 14) versus 92% or greater (group 2; n = 34) in room air. RESULTS: Failure to maintain Sao2 at predetermined levels occurred in 18 (29%) of 63 infants during their first prolonged sleep study. There was no correlation between short-term awake Sao2 and prolonged sleep Sao2 recordings (r = .02). Body weight, height, weight for height, and rate of weight gain were similar for all study infants before SO was stopped and remained constant for group 2 infants after SO was stopped. However, group 1 infants had a significant decrease in the rate of weight gain (17.3 +/- 13.1 vs 3.7 +/- 6.1 g/kg per day), and the mean z scores for weight gain and weight for height also decreased significantly for group 1 infants. Energy intake, incidence of acute infection, hematocrit values, and medication use did not differ before or after stopping SO in either group. CONCLUSIONS: This study indicated that short-term, awake Sao2 measurements do not predict prolonged sleep Sao2, and overall, infants with BPD continued a positive growth trend when Sao2, remained greater than 92% during prolonged sleep.

Selenium status of term infants fed human milk or selenite-supplemented soy formula.

Infants fed a soy formula supplemented with selenite had plasma and erythrocyte selenium values lower than those of infants fed human milk. However, plasma and erythrocyte glutathione peroxidase activities were normal, indicating that the physiologic requirement for selenium was being met.

Selenium status of preterm infants fed human milk, preterm formula, or selenium-supplemented preterm formula.

The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.