Influence of low birth weight on bone and bodycomposition in early adulthood

Firstly, we studied skeletal parameters at the age of peak bone mass in two groups with LBW, namely adults born preterm with very low birth weight (VLBW) (Cohort 1) or small for gestational age (SGA) at term (Cohort 2) compared with term-born controls with normal birth weight (Cohort 2). We examined bone mineral content (BMC), bone mineral density (BMD) and trabecular bone score (TBS) by dual x-ray absorptiometry. Inferior BMC and BMD were observed in both LBW groups. This was most pronounced in the VLBW group, where the significant differences persisted after adjustment for height, weight, and potential confounders. Adjusted odds ratios for osteopenia/osteoporosis were 2.4 and 2.0 in VLBW and SGA adults, respectively. TBS, which is a measure of bone quality did not differ between groups, but it was lower in men than in women. Serum Dickkopf-1 was higher in VLBW subjects vs controls, indicating inhibition of bone formation. However, it was not significant after adjustment for multiple comparisons. In conclusion, we show that both LBW groups achieved a suboptimal peak bone mass and that they had a higher frequency of osteopenia/osteoporosis, this was most pronounced in the VLBW individuals. Our findings are of concern, as peak bone mass is an important determinant of future osteoporosis risk. Secondly, we examined the association between LBW and metabolic outcomes at adulthood (25-28 years) in the same population (including three more individuals) as in first study. We applied the International Diabetes Federation criteria for metabolic syndrome (MetS). Outcomes were indices of MetS: blood pressure (BP), waist circumference, fasting glucose, lipid profile. We used a calculated MetS score as a tool to assess the relationship between MetS and skeletal health (BMD and TBS). We observed a less favorable profile in VLBW individuals, and preferentially in females. This group displayed higher systolic and diastolic blood pressure (BP), higher glycated hemoglobin, higher C-peptide, increased insulin resistance, and lower HDL-cholesterol. Significant differences were mainly seen between VLBW females and control females. Females in the term-born SGA group had higher waist-hip ratio, and higher total and LDL-cholesterol compared with female controls, whereas the males in this group exhibited higher fasting blood glucose than did male controls. At least one feature of the MetS was present in a higher proportion of VLBW participants compared with controls. This is of significance, as the presence of one component implies enhanced risk of MetS in the future. MetS score correlated positively with BMD and inversely with TBS. When stratifying for sex, significant associations were found only in males. Finally, we included 41 mother-child pairs from Cohort 2. We assessed the associations between maternal serum vitamin A (retinol), 25-hydroxyvitamin D and 1,25-hydroxyvitamin D levels and offspring skeletal health at the age of 26 years. Blood samples were collected at three time-points in pregnancy (gestational week 17, 34 and 37) and in cord blood. After adjustment for relevant covariates, we observed a positive association between average maternal serum retinol level during pregnancy and offspring lumbar spine BMD and TBS. No association with maternal 25-hydroxyvitamin D and 1,25-hydroxyvitamin D could be revealed, and no correlations between vitamin levels in cord blood and offspring bone health were observed. Developmental origins of disease has gained increased attention during the past few decades. Low birth weight (LBW) is one of the factors shown to be associated with future disease. In infants born preterm, this has been attributed to deprivation of the benefits of the last trimester and to intrauterine growth restriction. Due to improved neonatal care, the survival rate of premature infants has increased dramatically and is estimated to be over 95% today. A substantial number of infants are also born small for gestational age (SGA) at term. The majority of these are considered to be constitutionally small, whereas some have experienced intrauterine growth restriction. Whether these infants have a similar risk for adverse health effects as those born preterm with LBW is not established. Our findings indicate that both those born with LBW preterm and at term are at increased risk of future osteoporosis and metabolic syndrome, although most pronounced in the VLBW group. Women in the VLBW group seemed to be at highest risk for metabolic syndrome. The inverse association observed between MetS score and TBS indicates increased susceptibility to fracture with worsening of the metabolic profile. Our data emphasize the importance of a thorough follow-up of those born with LBW to reduce the risk for these conditions in the future. We show for the first time that maternal vitamin A inadequacy in pregnancy may affect offspring peak bone mass and bone quality adversely. Given the high prevalence of hypovitaminosis A worldwide, this is of concern. There is a need for increased attention on vitamin A intake both during pregnancy and in the general population. If our findings hold true, supplementation of vitamin A to pregnant women could contribute to reduce the burden of osteoporotic fractures. Taken together, the findings of this doctoral thesis may result in novel strategies for follow-up of pregnant women and offspring born with LBW that could have a positive impact on public health.