Prenatal exposure to vitamin D from fortified margarine and risk of fractures in late childhood: period and cohort results from 222 000 subjects in the D-tect observational study

Abstract

Prenatal low vitamin D may have consequences for bone health. By means of a nationwide mandatory vitamin D fortification programme, we examined the risk of fractures among 10–18-year-old children from proximate birth cohorts born around the date of the termination of the programme. For all subjects born in Denmark during 1983–1988, civil registration numbers were linked to the Danish National Patient Registry for incident and recurrent fractures occurring at ages 10–18 years. Multiplicative Poisson models were used to examine the association between birth cohort and fracture rates. The variation in fracture rates across birth cohorts was analysed by fitting an age-cohort model to the data. We addressed the potential modification of the effect of vitamin D availability by season of birth. The risk of fractures was increased among both girls and boys who were born before the vitamin D fortification terminated in 1985 (rate ratio (RR) exposed v. non-exposed girls: 1·15 (95 % CI 1·11, 1·20); RR exposed v. non-exposed boys: 1·11 (95 % CI 1·07, 1·14). However, these associations no longer persisted after including the period effects. There was no interaction between season of birth and vitamin D availability in relation to fracture risk. The study did not provide evidence that prenatal exposure to extra vitamin D from a mandatory fortification programme of 1·25 µg vitamin D/100 g margarine was sufficient to influence the risk of fractures in late childhood, regardless of season of birth. Replication studies are needed.

Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project

“…In addition to the protocol paper [9], we have published 17 studies in the D-tect project on various outcomes. The primary outcomes were type 1 diabetes [10,11], birth weight and childhood obesity [12][13][14][15], and childhood fractures [16]. Secondary outcomes were gestational diabetes [17], pre-eclampsia [18,19], childhood asthma [20], adult celiac disease [21], inflammatory bowel disease [22], chance of live birth among women with fertility problems [23], and type 2 diabetes mellitus [24].…”

“…As already mentioned, the initial idea for the analyses in the D-tect fortification design studies was to compare the risk of selected chronic diseases in adjacent, as close as possible, exposed and unexposed birth cohorts, assuming that all other covariates or potential confounders would be equally distributed [9]. The discovery of the birth cohort effect documented for T1D cases for children born in Denmark around 1985 inspired us to look at different analytic approaches, and several of them were applied in subsequent studies: regression discontinuity [37] when analyzing T1D outcomes [10], age-period-cohort analyses [38] analyzing fracture outcomes [16], the approach similar to time series [39] analyzing birth weight seasonality [15]. For the latter outcome, the spectrum of the birth cohorts investigated was broad: slightly more than 50 years [15].…”

“…One study examined the effect of gestational exposure to vitamin D fortification on the risk of fractures among 10-18-year-old children born in Denmark during 1983-1988 [16]. The core date in the design was 1 June 1985, or cancelation of mandatory vitamin D fortification of margarine.…”

Nutrients, Diet, and Other Factors in Prenatal Life and Bone Health in Young Adults: A Systematic Review of Longitudinal Studies

“…Maternal diet and 25(OH)-vitamin D status during pregnancy might be associated with offspring bone development at birth and in childhood. However, the findings are inconsistent [4][5][6][7][8][9][10][11][12]. Maternal cigarette smoking might also have the ability to modulate bone mineral acquisition during intrauterine life [13].…”

Effect of birth season on anthropometrics and diseases of bone mineralization in the US population

“…It has been reported that bone mineral content (BMC) in neonates differs by season of birth (Namgung & Tsang, 2003), and the risk for osteoporotic fractures in 60 to 70 year‐olds seems to be influenced by month of birth (Alffram, 1964). Some studies have found that children born in summer have more forearm fractures (Petersen et al, 2015), and that adults and adolescents born in winter have less hip and bone fractures (Abrahamsen, Heitmann, & Eiken, 2012; Handel et al, 2017).…”