Influence of low birth weight on bone and bodycomposition in early adulthood
The intrauterine environment may influence disease susceptibility in the offspring. We aimed to examine the association between prematurity, being born small for gestational age (SGA) and skeletal and metabolic health in the offspring at adulthood. We also wanted to study the association between maternal vitamin D status and peak bone mass. In the present study, we explore the assiociation between low birth weight (LBW) and peak bone mass and metabolic syndrome at 26-28 years. We also aimed to study the association between vitamin D status in the mother and bone mineral density (BMD) in the offspring. Two low birth weight groups and a control group, born between 1986 and 1988 were included: One group (n=56) born preterm with very low birth weight (VLBW, birth weight <1500g, ) and one group (n=59) born SGA (with birth weight <10th percentile) and a control group (n=75) born at term (with birth weight >10th percentile). Altogether 189 participants with equal gender distribution were included. A questionnaire addressing lifestyle, previous fractures, diseases, current medications and diet was answered. Height, weight, skinfold thickness in triceps and subscapular regions, waist-hip ratio and blood pressure (BP) were recorded, and fasting blood samples were collected. Bone mineral content (BMC) and BMD, body composition and bone microarchitecture via trabecular bone score (TBS) were analyzed by dual x-ray absorptiometry (DXA). Markers of bone metabolism, calcium, vitamin D, plasma insulin and glucose and lipid profile were analyzed. Analysis of maternal vitamin D in serum was performed. Preliminary results: The VLBW group showed significantly lower BMC and BMD at most sites measured, even after adjustment for known confounders. VLBW adults were physically less active. Previous fractures, smoking, calcium and vitamin D intake were similar between the groups.The SGA group displayed lower BMC at spine and lower whole body Z-score. No differences were observed in TBS or in bone markers, except for higher Dkk1 in the VLBW group. The VLBW and the SGA subjects were significantly shorter compared to controls. In the total population 31.3% had low bone mass and 47% had serum vitamin D levels lower than recommended (i.e. <50 nmol/L). The VLBW group had higher mean systolic BP (p=0.010) and mean diastolic BP (p=0.027), mean arterial pressure (p=0.014), mean heart rate (p=0.016) and waist-hip ratio (p=0.055) compared to controls. The VLBW group showed significantly higher levels of HbA1c, (p=0.021), borderline significant C-peptide (p=0.055) and significantly lower HDL-cholesterol levels (p=0.041). The main finding is that subjects born preterm with VLBW and those born SGA at term display significantly lower peak bone mass than their term-born peers. Adjusted odds ratio for osteopenia/osteoporosis were 2.0 and 2.4 in VLBW and SGA adults respectively. Furthemore, those born with VLBW had higher BP, unfavorable lipid profile and fat distribution, implying increased risk of metabolic syndrome compared with controls. Our study supports the hypothesis that the prematurity and LBW are risk factors for osteoporosis and development of metabolic syndrome. These results may give rise to increased awareness in prevention of these conditions in subjects with LBW. Maternal vitamin D status was not shown to be an influencial factor for offspring`s bone health in the study.
Growing evidence suggests that fetal environment plays an important role for development of certain chronic diseases in later life. In this study, we aimed to examine the influence of prematurity, low birth weight and maternal factors (vitamin A and D status) on skeletal health, and parameters for metabolic syndrome in young adults. This study is part of a larger study where the effect of low birth weight on mental and physical health will be studied. In the current study, we want to explore the effects of different etiologies of low birth weight on bone and body composition (lean and fat mass) in early adulthood. Furthermore, we aim to study indices of metabolic syndrome in the different groups. We also want to study the association between vitamin A and D status in the mother and BMD and body composition in the offspring. Two low birth weight groups and a control group, born between 1986 and 1988 are studied. One group (n=52) was born preterm with very low birth weight (VLBW, birth weight =1500g, ) and one group (n=59) was born small for gestational age at term (SGA, birth weight <10th percentile adjusted for gestational age, sex and parity ). The control group (n=75) was born at term with birth weight >10th percentile (adjusted for gestational age, sex and parity). Altogether 186 participants with equal gender distribution were included. A questionnaire addressing diseases, current medications, previous fractures, weight bearing physical activity, smoking and diet was completed. Height, weight, waist-hip ratio and blood pressure were recorded, and fasting blood samples were collected. Bone mineral content (BMC), bone mineral density (BMD), body composition and bone quality (trabecular bone score) were analyzed by dual x-ray absorptiometry (DXA). Markers of bone metabolism, calcium, vitamin D, plasma insulin and glucose and lipid profile were analyzed. Analyses of vitamin A and D in maternal serum from those born SGA will be performed. Preliminary results: The VLBW group was more physically inactive and reported higher calcium intake. Previous fractures, smoking habits and vitamin D were similar between the groups. The VLBW group showed significantly lower BMC and BMD at most sites measured, even after adjustment for known confounders like height, weight, calcium intake and physical activity. Each additional week of gestation resulted in 0.037 units increase in femoral neck Z- score. The SGA group displayed lower BMC at spine and lower whole body Z-score. No differences were observed in bone quality or bone markers, except for higher Dkk1 in the VLBW groups. The VLBW and the SGA groups were significantly shorter compared to controls. Another clinically important finding was that almost 31% of these young adults, independent of their birth weight, had low bone mass and 47% had serum vitamin D levels lower than recommended (i.e. <50 nmol/L). The VLBW group had higher mean systolic (p=0.007) and higher mean diastolic blood pressure (p=0.045), higher mean heart rate (p=0.016) compared to controls. The VLBW group showed significantly higher levels of HbA1c, (p=0.022) and an unfavorable lipid profile, implying increased risk for metabolic syndrome risk compared with term-born controls. The main finding is that both young adults born preterm with VLBW and those born SGA at term display significantly lower peak bone mass than their term-born peers.This may imply increased fracture risk in the future. Furthermore, those born with VLBW seem to be at risk for development of metabolic syndrome. The study may give new insight into the etiology of osteoporosis and development of metabolic syndrome and may give rise to increased awareness in prevention of these conditions in subjects with low birth weight.
Det er holdepunkter for at fostermiljøet kan påvirke fenotypen i voksen alder, blant annet pga av epigenetiske mekanismer. I denne studien vil vi undersøke hvordan lav fødselsvekt påvirker skjelett, kroppssammensetning og blodtrykk i ung voksen alder og vil også studere mulige epigenetiske mekansimer. I den aktuelle studien vil vi se på beintetthet, kroppsmasse, antropometriske parametere, blodtykk og en rekke serumparametere ved 26-28 årsalder hos to grupper født med lav fødselsvekt og en gruppe normalvektige født til termin. Studien er del av en større studie hvor effekten av lav fødselsvekt på mental og psykisk helse vil bli undersøkt. Det er et samarbeidsprosjekt med blant andre prof. Ann-Mari Brubakk og prof. Jon Skranes ved Avdeling for barnesykdommer, prof. Marit Indredavik ved Barne- og ungdomspsykiatrisk avdeling og prof. Arne Sandvik, ansvarlig for NTNU Genomic Core. Prof. Unni Syversen ved Avdeling for endokrinologi, St. Olavs hospital og IKM/NTNU er prosjektansvarlig for det aktuelle prosjekt. Vi vil blant annet se om det er forskjell i forekomst av osteopeni/osteoporose, fedme og metabolsk syndrom mellom gruppene. Beinomsetningen vil også bli vurdert ved analyse av spesifikke beinmarkører, kalsium, paratyroideahormon (PTH) og vitamin D mm. Videre er epigenetiske analyser med global metyleringsprofil planlagt. To grupper med lav fødselsvekt og en kontrollgruppe født mellom 1986 og 1988 vil bli studert. En gruppe ble født før termin med svært lav fødselsvekt (VLBW, <1500 g) og en gruppe ble født små for gestasjonell alder til termin (SGA, kroppsvekt <10. percentil). Deltakerne i kontrollgruppen ble født til termin med normal kroppsvekt (CTR, kroppsvekt >10. percentil). Inklusjon av deltakere i studien startet sommeren 2013 og ble avsluttet høsten 2014. Alle deltakere besvarte et spørreskjema angående fysisk aktivitet, røyking, alkoholinntak, kost og kosttilskudd, generell helse og tidligere beinbrudd. Vekt, høyde, midje, hudfold og blodtrykk ble målt. Beintetthet, muskelmasse og fettprosent ble analysert med dual-x-ray absorbsjonsmetri (DXA). Fastende blodprøver ble tatt og analysert ved sykehuslaboratoriet her. Blant annet er blodsukker, kolesterol, en rekke hormoner, vitamin D, PTH, kalsium og lever- og nyrefunksjon analysert. Serum er lagret i biobank for analyse av blant annet beinomsetningsmarkører og adipokiner. Buffycoat er også lagret med henblikk på epigenetiske analyser. Data er lagt inn i SPSS fortløpende. Foreløbige data: I alt ble 55 deltakere inkludert i VLBW-gruppen, 60 i SGA og 75 i kontrollgruppen, halvparten kvinner og menn. Gjennomsnittlig fødselsvekt for gruppene var: VLBW 1207.5 g, SGA 2924.2 g og kontroll 3730.4 g. Blodtrykket var høyere i VLBW-gruppen enn i kontrollgruppen (p=0.02). Det var signikant lavere beintetthet hos de med svært lav fødselsvekt (P=0,038) sammenlignet med de andre gruppene. Vi har foreløbig ikke analysert data på serumparametere. .
Balasuriya C, Evensen KAI, Mosti MP, Brubakk AM, Jarcobsen GW, Schei B, Indredavik MS, Stunes AK, Syversen U
Peak bone mass and bone microarchitecture in adults born with low birthweight at preterm or term: A cohort study
Sendt inn i desember 2016. Under review.