Table 14. The effect of maternal vitamin D status in gestation on offspring bone mass – Observational studies.
| First Author and year |
Bias score |
Study Type |
Study Details, age at which children were assessed and technique used | Offspring bone outcomes assessed (units) | Confounders/ adjustments |
Number of weeks gestation when maternal 25(OH)D 3 was measured | Mean (SD) or median (IQR) maternal 25(OH)D concentration (nmol/l) | Mean (SD) bone outcome according to maternal 25(OH)D category/Unadjusted correlation co-efficient (r) or regression co-efficient (β) (95% CI) | Adjusted correlation co-efficient (r) or regression co-efficient (B) (95% CI) | conclusion | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Weiler, 2005 86 |
3 (med) | Cross- sectional |
Winnipeg, Canada Overall cohort= 342 women Sample size for analysis=50 Neonates delivered at term and assessed within 15 days of birth by DXA |
Lumbar spine (LS) BMC (g) LS BMC/bod y weight (wt) (g/kg) Femur BMC Femur BMC/wt Whole Body (WB) BMC WB BMC/wt |
Infant weight, gestational age at birth, infant weight, gestational age at scan, infant vitamin D status, lean mass Infant sex, infant length and maternal ethnicity not included in the final model since they did not significantly predict infant BMC |
Within 48 hours of delivery | Overall mean not given Mean in adequate 25(OH)D group (≥37.5 nmol/l, n=32)= 61.6 (24.7) Mean in the deficient group (≤37.5 nmol/l, n=18)= 28.6 (7.8) |
25(OH) D nmol/l | <35 | >35 | P value | Not given | No significant difference in lumbar spine BMC or lumbar spine BMC/body weight, femur BMC or whole body BMC was observed between those with adequate and deficient maternal 25(OH)D Significantly higher femur BMC/body weight and WB BMC/ body weight in those with adequate maternal 25(OH)D |
|||
| LS BMC(g) | 2.3 (0.5) | 2.3 (0.5) | ≥0.99 | |||||||||||||
| LS BMC/wt (g/kg) | 0.59 (.14) | 0.66 (.125) | 0.08 | |||||||||||||
| Femur BMC (g) | 2.8 (0.7) | 2.9 (0.6) | 0.60 | |||||||||||||
| Femur BMC/wt (g/kg) | 0.71 (.17) | 0.81 (.15) | 0.027 | |||||||||||||
| WB BMC (g) | 76.4 (12.9 ) | 75.7 (13.7) | 0.86 | |||||||||||||
| WB BMC/wt (g/kg) | 19.49 (3.05 ) | 21.33 (2.03) | 0.017 | |||||||||||||
|
Javaid, 2006 2 |
5 (low) | Cohort | Princess Anne Cohort, Southampton, UK n=198 women Children assessed at mean 8.9 years by DXA |
WB BMC (g) BA (cm2) BMD (g/cm2) Lumbar spine (LS) BMC(g) BA (cm2) BMD(g/cm2) |
Gestational age , offspring age at DXA | 34 weeks | 25(OH) D conc (nmol/l) | n (%) | Not given | Outcome | r for each 2.5 nmol/l increase in maternal 25(OH) D | P value | Positive association found between maternal 25(OH)D in late pregnancy and offspring WB and LS BMC, WB BA, WB and LS BMD at aged 9 years | |||
| <27.5 | 28 (18) | WB BMC | 0.21 | 0.0088 | ||||||||||||
| 27.5-50 | 49 (31) | WB BA | 0.17 | 0.0269 | ||||||||||||
| WB BMD | 0.21 | 0.0063 | ||||||||||||||
| >50 | 83 (52) | LS BMC | 0.17 | 0.03 | ||||||||||||
| LS BA | 0.07 | 0.3788 | ||||||||||||||
| LS BMD | 0.21 | 0.0094 | ||||||||||||||
|
Prentice, 2009 95 |
5 (low) | Cohort | Gambia, Africa Subset of pregnant Gambian women participating in a calcium supplementatio n trial n=125 women Children assessed at 2, 13 and 52 weeks by SPA for radial measurements and DXA for whole body measurements |
Radial midshaft BMC (g) and bone width WB BMC (g/cm) WB BA (cm2) |
Season, mat height, weight, weight gain, infant sex and whether received calcium supplement | 20 weeks and 36 weeks | 20 weeks = 103 (25) 36 weeks = 111 (27) |
Not given | Not given | No association between maternal 25(OH)D and infant radial midshaft BMC and bone width, or WB BMC and WB BA at either time point | ||||||
|
Sayers, 2009 42 |
3 (med) | Cohort | ALSPAC, cohort, UK n=6955 women Children assessed at mean age 9.9 years by DXA |
WB less head BMC, (g), BA (cm2) BMD (g/cm2), aBMC (g) | BMC adjusted for area BA adjusted for height | Not directly measured Ambient UVB measured during 98 days preceding birth |
Not measured | Outcome | β (change in outcome per 1 SD increase in UVB) (95% CI) | p value | Not given | Maternal UVB exposure in pregnancy was positively associated with offspring BMC, BA and BMD. This remained with BA even after adjusting for height. No relationship was observed with maternal UV exposure and aBMC |
||||
| BMC (g) | 9.6 (5.3, 13.8) | <0.0001 | ||||||||||||||
| BA (cm2) | 8.1 (4.3, 11.9) | <0.0001 | ||||||||||||||
| BMD (g/cm2) | 0.003 (0.001, 0.004 | <0.0001 | ||||||||||||||
| aBMC (g) | 0.69 (0.22, 1.60) | 0.14 | ||||||||||||||
|
Akcakus 2009 100 |
4 (med) | Cross- sectional |
Turkey Cohort=100 women 3 groups, 30 SGA, 40 AGA, 30 LGA infants Most women veiled Children assessed within 24hour of birth by DXA |
WB BMC(g) WB BMD (g/cm2) |
Nil | Delivery | Overall not given SGA= 21.8 (7.5) AGA= 21.5 (7.5) LGA=19.3 (7.0) >90% had 25(OH)D <25 nmol/l |
WB BMC; r= −0.055 WB BMD; r=0.042 |
Not given | No relationship observed between maternal 25(OH)D at delivery and neonatal BMC and BMD | ||||||
|
Viljakainen, 2010 94 |
3 (med) | Cohort | Helsinki, Finland n=125 women recruited during last trimester (Oct-Dec). All Caucasian, non-smokers, primiparous Children assessed when newborn by pQCT of tibia |
Tibial BMC (g/cm), tibial CSA (mm2) and tibial BMD (mg/cm3) | 3 models:
|
First trimester (8-10 weeks) and 2 days post-partum. Mean of 2 values used to calculate ,vitamin D status- | At 8-10 weeks = 41.0 (13.6) Postpartum = 45.1 (11.9) Overall median ,vitamin D status=- 42.6 | Bone outcome | r for log 25(OH) D p value |
r after adjust 1 | r after adjust 2 | r after adjust 3 | A positive significant association seen between maternal 25(OH)D status and offspring tibial BMC and tibial CSA. Tibial BMC and CSA significantly higher in those with maternal 25(OH)D above median than those below even after adjustments No association seen with tibial BMD |
|||
| Tibial BMC | 0.149, p=0.163 | 0.232 P=0.034 | 0.230 p=0.036 | 0.192 P=0.085 | ||||||||||||
| Log (tibial CSA) | 0.197, p=0.05 | 0.214 p=0.05 | 0.218 P=0.048 | 0.226 P=0.042 | ||||||||||||
|
Viljakainen 2011 99 |
4 (med ) | Cohort | Helsinki, Finland n=68 women Children assessed at 14 months by pQCT of tibia This was a follow-up study of same cohort as Viljakainen, 2010). 55 children had bone data at both time-points |
Tibial BMC (g/cm), tibial CSA (mm2) and tibial BMD (mg/cm3) | Sex, birth weight z score, walking age, exclusive breast feeding and offspring 25(OH)D at 14 months. | First trimester (8-10 weeks) and 2 days post-partum. Mean of 2 values used to calculate ,vitamin D status- | Not given Overall median “vitamin D status” = 42.6 |
Not given | Not given | No difference in tibial BMC or BMD in offspring with maternal 25(OH)D above median than those below CSA higher at 14 months in offspring with maternal 25(OH)D above median than those below. This suggest that postnatal vitamin D supplementatio n only partly improved the differences in bone variables induced by maternal vitamin D status during pregnancy |
||||||
|
Dror, 2012 93 |
7 (low) | Cross- sectional |
Oakland California, USA n=120 women Children assessed between 8-21 days old by DXA |
WB BMC WB aBMC |
Maternal height, GDM, infant age at DXA, feeding practice (breast, formula, mixed), infant weight-for-height z score, infant height-for age z score, bone area and size for gestational age | Per-natal | 75.5 (32.3) | WB BMC β= −0.02 (p=0.52) | WB aBMC: β= 0.0007 (−0.031, 0.032) P=0.97 |
No association seen between maternal 25(OH)D and offspring WB BMC or WB aBMC either analysed continuously or categorically | ||||||
SGA = small for gestational age, AGA = appropriate for gestational age, LGA = large for gestational age
WB BMC= whole body bone mineral content, WB BMD = whole body bone mineral density, WB BA= whole body bone area, aBMC= bone mineral content adjusted for bone area)
DXA= Dual energy X-ray absorptiometry
SPA= Single photon absorptiometry
pQCT= peripheral quantitative computed tomography