Table 25. The effect of Vitamin D supplementation in gestation on offspring serum calcium (Ca) concentration – Intervention studies.
| First Author, year |
Risk of bias |
Setting | Randomisation | Adjustments/ confounders accounted for |
Number of weeks gestation when 25(OH)D was measured | Mean (SD)/ Mean (SE)* or median (IQR) 25(OH)D concentration (nmol/l) | Mean (SD) or Mean (SE)* offspring serum calcium conc (mmol/l) in un-supplemented group | Mean (SD) or *Mean (SE) serum calcium conc (mmol/l) in supplemented group | Conclusion | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Brooke, 1980 4 | −2 (high) | London, UK, n=126 women (all Asian) |
Double-blinded Randomised to either placebo (n=67) or 1000 IU/day of vitamin D2 in last trimester (n=59) | Nil, but groups of similar age, height, parity, offspring sex, length of gestation 27% of control group and 22% of treatment group bottle fed their infants |
28-32 weeks (allocation) and at birth | At allocation 25(OH)D = 20.1 (1.9)* At term, placebo group= 25(OH)D= 16.2 (2.7*) At term, supplemented group 25(OH)D = 168.0 (12.5)* |
cord | 2.65 (0.02)* | Cord | 2.71 (0.02)* | No significant difference in cord Ca between groups at birth , but significantly higher levels in the treatment group at day 3 and 6, but higher rates of breast feeding in the treatment group, which in itself was positively associated with offspring calcium conc. Compared to bottle feeding) When groups considered separately, a weak correlation see between maternal 25(OH)D and cord Ca in the treatment group. r= 0.31, p<0.05 5 cases of symptomatic hypocalcaemia in control group, 0 in treatment group (X2 = 4.6, p<0.01) | ||
| Day 3 | 2.18 (0.04)* | Day 3 | 2.30 (0.04)* | ||||||||||
| Day 6 | 2.29 (0.02* | Day 6 | 2.49 (0.04) | ||||||||||
| Cockburn, 1980 21 | −1 (high) | Edinburgh, UK n=1139 women |
Either given placebo (n=633) or 400 IU vitamin D2 (n=506) from week 12 of gestation Deliveries on one ward given placebo, deliveries on another ward given supplement. |
Nil, but groups similar in terms of social class, parity, and maternal age. All deliveries between September to May. Maternal age, parity, type of delivery, offspring Apgar score at birth, social class, maternal preeclampsia, birth weight and gestational age were not associated with offspring 6 day Ca concentration |
24, 34 weeks and delivery | 25(OH)D in placebo |
25(OH)D in supp |
Cord | 2.69 (0.26) (n=452) | Cord | 2.66 (0.27) (n=262) | No significant difference in cord blood serum Ca at delivery. Significantly higher serum Ca in infants at day 6 in the supplemented group, independent of infant sex and effects of type of feeding (breast vs. formula) 6% of infants in thesupplemented group were hypocalcaemic at day 6 (Ca<1.85 mmol/l) compared with 13% in the placebo group. |
|
| 24 wks | 32.5 (n=82) | 39.0 (n=82) | |||||||||||
| 34 wks | 38.5 (n=80) | 44.5 (n=80) | Day 6 | 2.25 (0.3) (n=394) | Day 6 | 2.34 (0.2) (n=233) | |||||||
| delivery | 32.5 (n=84) | 42.8 (n=80) | |||||||||||
| Marya, 1981 5 | −6 (high) | Rohtak, India n= 120 women | 3 arms: Randomised to either no supplement (n=75) or 1,200 IU vitamin D + 375mg calcium/ day△ throughout the 3rd trimester (n=25); or oral 600,000i IU vitamin D2; 2 doses in 7th and 8th months gestation (n=20) | Nil | Not measured | Not measured | 2.52 (0.23) (value represents cord blood at delivery) |
1200IU/+ ca= 2.55 (0.17) 600,000 IU = 2.67 (0.12) (values represents cord blood at delivery) | No difference in cord calcium between un-supplemented and 1200 IU+ 375 mg Ca/ day supplementation Cord Ca significantly higher in those taking 600,000iu supplement compared to un-supplemented (p=0.001) | ||||
| Congdon, 1983 22 | −9 (high) | Leeds, UK n=64, all Asian women | Either 1000 IU vitamin D plus calcium (calcium dose not given) daily in the 3rd trimester (n=19) or no supplement (n=45) | Nil, but groups similar in terms of maternal age, infant sex, gestation length, birth weight | Not measured | Not measured | 2.50 (0.03) | 2.64 (0.05) | Cord Ca significantly higher in the supplemented group P<0.025 | ||||
| Mallet, 1986 8 | −3 (high) | Rouen, France n=77 women | 3 arms: Randomised to either no supplement (n=29) or 1,000 IU vitamin D/day△ in last 3 months of pregnancy (n=21), or single oral dose of vitamin D△ 200,000iu in 7th month (n=27) | Nil, but groups of similar maternal age, parity, calcium intake and frequency of outdoors outings | During labour (February and March) | Overall mean not given According to group: Un-supplemented = 9.4 (4.9) 1000IU/day = 25.3 (7.7) 200,000 IU= 26.0 (6.4) | 2.37 (0.11) (value represents cord blood at delivery) | 1000 IU/day =2.44 (0.14) 200,000 IU = 2.41 (0.21) (values represents cord blood at delivery) | No significant difference in serum Ca between the 3 groups 1 case of neonatal hypocalcaemia observed in the un-supplemented group (serum Ca 1.69 mmol/l) | ||||
| Delvin, 1986 7 | −2 (high) | Lyon, France n=40 women |
Randomised to either no supplement (n=20) or 1000 IU vitamin D3/day during 3rd trimester (n=20) | Nil Groups similar in terms of maternal age and parity. All deliveries occurred in the same month (June) All infants of similar gestational age and breast fed from the 6th hour of life |
At recruitment (n=50) and at delivery | 25(OH)D in suppl. group |
25(OH)D in unsuppl group |
When measured | Mean infant serum Ca (SE) (mmol/l) | When measured | Mean infant serum Ca (SE) (mmol/l) | Significant correlation between maternal 25(H)D and cord blood total Ca concentration (p<0.005) No significant difference in cord blood total Ca concentration at delivery between groups. At day 4, infant Ca levels were significantly higher in those in the supplemented group (p<0.025) Infant Ca fell significantly more from delivery to day 4 in the un-supplemented group compared to the supplemented group (p<0.05) |
|
| At recruitment (185 days gest) | 54.9 (10.0)* | 27.5 (10.0)* | Cord at delivery n=15 | 2.63 (0.025)* | Cord at delivery n=15 | 2.55 (0.5)* | |||||||
| Delivery | 64.9 (17.5)* | 32.4 (20.0)* | Infant day 6 n=12 | 2.1 (0.05)* | Infant day 6 n=13 | 2.28 (0.5)* | |||||||
| Marya, 1988 6 | −2 (high) | Rohtak, India n=200 women | Randomised to either no supplement (n=100) or oral 600,000 IU vitamin D3; 2 doses in 7th and 8th months gestation (n=100) | Nil, but groups had similar maternal age, maternal height, maternal height, parity, haemoglobin, calcium intake and vitamin D intake | Not measured | Not measured directly, but mean daily vitamin D intake given as follows Un-supplemented = 35.71 (6.17) IU/day Supplemented group = 35.01 (7.13) IU/day |
2.57 (0.26) (value represents cord blood at delivery) | 2.77 (0.18) (value represents cord blood at delivery) | Cord serum Ca concentration significantly higher in the supplemented group (P<0.001) | ||||
Table includes any studies that measured maternal vitamin D status in pregnancy and either cord calcium concentration of offspring serum calcium concentration.