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Title: Early life determinants of infant bone health
Author: McDevitt, Helen
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2010
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This thesis consists of a series of studies utilising quantitative ultrasound (Sunlight Omnisense 7000P) to assess bone health of infants. Preterm infants are at risk of osteopenia of prematurity (OP) which can result in fractures in the short term and may have an impact on growth in infancy and childhood. OP has a multifactorial aetiology including factors such as poor mineral intake and immobility. There is an increasing number of ex-preterm survivors therefore morbidity becomes more important. There is also increasing evidence from epidemiological studies that growth in infancy can have an effect on adult diseases such as osteoporosis. The first study was a cross-sectional study of bone quantitative ultrasound measurements in 110 term and preterm infants shortly after birth. Speed of sound (SOS) was measured at the tibial and the radius. This validated the technique showing reproducible measurements with low inter and intra-observer error, and also showed no benefit to measuring multiple sites. Preterm infants were found to have a significantly lower SOS than term infants. There was a positive correlation between tibial SOS and gestation, with birthweight being a less significant factor than gestation. The second study followed 18 preterm infants longitudinally from birth to hospital discharge or term corrected gestational age (CGA). SOS fell significantly with time in all infants. The most preterm infants had the greatest fall in SOS. SOS at the end of the study period was negatively associated with peak serum alkaline phosphatase and severity of illness score. SOS was significantly lower in the infants who required total parenteral nutrition for longer than 3 weeks. These results show that the neonatal course has a significant impact on SOS trajectory. When preterm infants were followed up in the out-patient clinic over the first two years of life the SOS measurements taken as the next part of this study showed a catch up phenomenon. In the majority of infants, but not all infants, SOS moved into the normal range by 6 months CGA. In the subgroup of infants followed longitudinally those with the lowest SOS at hospital discharge/term corrected age had the greatest increase in SOS over time. An interventional study of passive exercise was performed to explore its role in influencing the bone health of preterm infants. Thirty one infants born at less than 33 weeks gestation were randomised to receive range of motion flexion and extension exercises once daily for 5 days each week starting ‘early’(n=15) or ‘late’ (when on 100kcal/kg/day enteral feeds, n=16) and continuing until term corrected gestational age (CGA) or discharge from hospital. Tibial SOS declined significantly from birth to end of physical activity in both ‘early’ and ‘late’ groups, and this was similar to the decrease seen in a group of historical controls from the earlier longitudinal study. Weight gain and head growth did not show a significant difference between groups or between study infants and controls. No infant was reported to have sustained a fracture, and length of hospital stay was not significantly different between groups. There was no significant increase in sepsis rate, retinopathy of prematurity or chronic lung disease in study infants but numbers were small. On longer term follow-up the intervention was not associated with any adverse effects. To investigate the possibility that the maternal environment plays an important role in influencing infants’ bone health we also studied SOS changes in 188 pregnant women and their offspring. Most women had SOS in the normal range antenatally, and there was no significant change in SOS across pregnancy in the group as a whole. There was a significant negative correlation with SOS SDS and BMI in early pregnancy. Women who smoked cigarettes had lower SOS throughout pregnancy and so did their infants. Serum bone biochemistry was measured in the women antenatally and after delivery, and umbilical cord blood was also taken where possible. Vitamin D deficiency was found to be common at the end of pregnancy. Women of Asian origin had significantly lower vitamin D levels at all stages of pregnancy. There was no significant relationship between maternal and infant SOS, or between maternal vitamin D status and infant SOS. The work of this thesis establishes quantitative ultrasound as a useful technique in the assessment of infant bone health. It is a radiation free tool which provides precise and reproducible measurements in both term and preterm infants. In agreement with a small number of other studies we found that preterm infants have a lower speed of sound at birth compared to term infants; speed of sound increases with increasing gestation while in utero. By including infants who were both appropriately grown and small for gestational age we found maturity to be a more important factor in bone strength than birthweight. Despite the apparent self limiting nature of osteopenia of prematurity an intervention to improve neonatal bone health is still desirable, to prevent fractures. Our results do not substantiate conclusions from previous studies that physical activity alone can improve neonatal bone health. .Findings are however limited by the small sample size. Further studies are needed which investigate alternative exercise regimens, taking into account mineral and nutrient supply. Vitamin D deficiency, smoking and obesity may adversely affect bone health of women and their offspring. In the west of Scotland vitamin D deficiency is common in pregnancy: women of south asian origin are at particularly high risk, and should be supplemented with Vitamin D.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RJ Pediatrics ; RG Gynecology and obstetrics