3960 eligible mother-and-offspring pairs were assessed in this study (). The mean age of offspring at the time of BMC assessment was 9·9 years. Maternal 25(OH)D concentrations were measured in the first trimester in 1035 (26%) women, in the second trimester in 879 (22%), and in the third trimester in 2046 (52%). The median 25(OH)D concentration was lowest in the first trimester (55·1 nmol/L, IQR 40·7–74·1), intermediate in the second trimester (60·1 nmol/L, 41·4–83·4), and highest in the third trimester (67·4 nmol/L, 46·8–93·0). For the predicted third-trimester 25(OH)D concentrations, we estimated that 2644 (67%) would be sufficient, 1096 (28%) insufficient, and 220 (6%) deficient.
Seasonally adjusted and unadjusted 25(OH)D levels correlated strongly. Estimated exposure to ultraviolet B in the third-trimester was marginally positively correlated with third-trimester 25(OH)D concentration, inversely correlated that in the second trimester, and not associated with that in the first trimester (). Maternal 25(OH)D concentration in pregnancy showed a weak association with offspring 25(OH)D concentration, whereas exposure to ultraviolet B showed no association ().
Correlations between maternal 25(OH)D concentrations in pregnancy, exposure to ultraviolet B in the third trimester, and offspring 25(OH)D concentrations
Compared with eligible participants, the mother-and-offspring pairs who were excluded because of missing maternal 25(OH)D or offspring BMC values had mothers who were younger, had lower educational attainment, were more likely to be of non-white ethnic origin, to have already had at least two previous pregnancies, and to have smoked during pregnancy (appendix p 6
). Maternal 25(OH)D in the third trimester and offspring gestational age, birthweight, spine BMD, age at outcome measure, and 25(OH)D concentration differed between eligible and excluded maternal-offspring pairs, but the median values were similar (appendix p 7
). These small p values have arisen because of the large sample size in this study. The differences are unlikely to be due to chance but are not clinically important.
A linear association was noted between maternal age and maternal 25(OH)D concentration, such that older age was associated with higher 25(OH)D concentrations in the second and third trimesters than was younger age, and greater parity was associated with higher 25(OH)D concentration in the third trimester (appendix p 8
). Non-white mothers had lower 25(OH)D levels, particularly from the second trimester onwards, than white mothers, and those who smoked during pregnancy had lower 25(OH)D across all trimesters than non-smokers. Maternal body-mass index before pregnancy and education were not associated with 25(OH)D concentrations in pregnancy.
Maternal 25(OH)D concentration, in any trimester of pregnancy, was not associated with offspring BMC. These null associations were similar in all multivariable models and when 25(OH)D was seasonally adjusted (, ). Mean offspring BMC was similar in the offspring of mothers with insufficient and deficient levels of 25(OH)D in the third trimester, compared with values for offspring of mothers with sufficient levels (). Sensitivity analyses in which the threshold for sufficient 25(OH)D concentration was changed to 75·0 nmol/L also showed no association. Tests of non-linear relationships across the maternal 25(OH)D sufficiency categories and higher-order polynomials were null ().
Mean differences in offspring bone-mineral content in relation to maternal 25(OH)D concentrations in pregnancy, by trimester
Multivariable associations between predicted maternal third-trimester 25(OH)D concentrations and offspring BMC
Multivariable associations between predicted third-trimester maternal 25(OH)D categories and offspring BMC
No maternal 25(OH)D measurement in any trimester, with or without seasonal adjustment, was associated with any offspring bone outcomes in any of the multivariable models (appendix pp 9–13
). Mean bone outcomes were similar in offspring of mothers with deficient or insufficient 25(OH)D concentrations to those in mothers with sufficient concentrations (appendix pp 10–11
). A measure of cumulative 25(OH)D in the last 10 weeks of the 3rd trimester similarly had null associations with all outcomes (results available from authors on request).
Data suggested that associations between maternal 25(OH)D concentrations in the second and third trimesters and offspring BMC differed for girls and boys. In the confounder-adjusted models, higher maternal 25(OH)D concentrations were associated with BMC in girls, but with higher BMC in boys (). This difference between the sexes, however, was completely explained by mediation by offspring characteristics. Specifically, this interaction was mediated by a difference in the relation between maternal 25(OH)D concentration in pregnancy and offspring height and lean mass for girls and boys. The difference in BMC between the sexes disappeared with adjustment for either of these features alone. Similar patterns of differences between boys and girls were also seen with TBLH adjusted bone area, but there were no other such interactions with maternal 25(OH)D concentrations for offspring bone outcomes in any models.
Mean differences in offspring bone-mineral content in relation to maternal 25(OH)D concentrations in pregnancy, by trimester and sex of offspring
Estimated exposure to ultraviolet B in the third trimester was positively associated with TBLH BMC (). When we adjusted for offspring age at the time of bone measurements, however, these associations became null. Associations between estimated exposure to ultraviolet B and all other bone outcomes were also null after age was taken into account (appendix p 14
). Reassessment of the previously reported sample16
showed that adjustment for offspring age completely attenuated all the associations to null. This removal of the association with adjustment for age occurred because estimated third-trimester exposure to ultraviolet B in the ALSPAC cohort is associated with offspring age at the time of BMC assessment (mean difference in age 1·2 months per 1 SD increase in estimated exposure to ultraviolet B (95% CI 1·1–1·3, p<0·0001).
Multivariable associations between maternal estimated exposure to ultraviolet B in the third trimester and offspring BMC