Table 1.
Historical vitamin D pregnancy supplementation trials: health characteristics of mothers and their infants.
| Study (year) | Country and population | Intervention | Therapy duration (months) | Baseline 25(OH)D (nmol/l) | End point 25(OH)D (nmol/l) | Findings | Ref. |
|---|---|---|---|---|---|---|---|
| Brooke et al. (1980) | UK/Asian | 0 IU, n = 59 | 3 | 16.3 | – | More SGA and larger fontanelle area with higher incidence of profound hypocalcemia in placebo group | [102] |
| 1000 IU D2/day, n = 67 | 3 | 20.0 | 168† | ||||
| Cockburn et al. (1980) | Edinburgh, Scotland | 0 IU, n = 633; 25(OH)D available in n = 82 | 7 | 32.5 at 24 weeks | 32.5 | 0 IU group infants gained less wt and showed decreased linear growth Higher incidence of abnormal dental defects at 3 years. 400 IU D2/day group infants had improved calcium and phosphorous levels and a lower incidence of hypocalcemia | [45] |
| 400 IU D2/day, n = 506; 25(OH)D available in n = 82 | 7 | 39.0 at 24 weeks | 42.8 | ||||
| Brooke et al. (1981) | UK/Asian (follow-up of neonates from Brooke et al. study [102]) | 0 IU, n = 59 | 3 | 16.3 | – | Follow-up at 1 year: placebo group infants gained less wt and had a lower rate of linear growth compared with 1000 IU D2/day infant group | [104] |
| 1000 IU D2/day, n = 67 | 3 | 20.0 | 168† | ||||
| Maxwell et al. (1981) | Asian women living in the UK (follow-up of neonates from Brooke et al. study [102]) | 0 IU D2/day, n = 67 | 3 | 16.3 | – | Supplemented mothers with better wt gain, improved nutritional status and less SGA infants | [156] |
| 1000 IU D2/day, n = 59 | 3 | 20.0 | 168† | ||||
| Marya et al. (1981) | India | 0 IU, n = 75 | 3 | Not reported | Not reported | 1200 IU D2/day group showed significantly lower alkaline phosphatase levels and increased fetal birth wt. 600,000 IU D2/day proved more efficacious than placebo or 1200 IU D2/day in terms of significantly greater fetal birth wt. Dependence of fetal calcium on maternal levels: fetal calcium was significantly lower (p = 0.001) in mothers with calcium below 8.5 mg percent than those with higher levels (≥9.7) | [105] |
| 1200 IU D2/day, n = 25 | 3 | ||||||
| 600,000 IU D2 ×1 at 6 and again at 7 months, n = 20 | Months 6 and 7 | ||||||
| Delvin et al. (1986) | Lyon, France | 0 IU, n = 20 (25[OH]D available in n = 13) | 3 | Day 230: 11 | 13 (cord: 7) | Better calcium, alkaline phosphatase and vitamin D status in mothers and neonates of 1000 IU D3/day group. 25(OH)D and 1,25(OH)2D strongly correlated in control group only (r = 0.859, p < 0.005) | [157] |
| 1000 IU D3/day, n = 20 (25[OH]D available in n = 14) | 3 | 22 | 26 (cord: 18) | ||||
| Mallet et al. (1986) | Northwest France | 0 IU, n = 21 | 3 | – | 9.4 (cord 5.3) | 1000 IU/day during the last trimester of pregnancy resulted in only a 5-6 ng /ml increase in circulating 25(OH)D levels in maternal and cord serum | [158] |
| 1000 IU D2/day, n = 27 | 3 | – | 25.3 (cord 15.7) | ||||
| 200,000 IU D2 at month 7, n = 20 | ×1 at month 7 | – | 26.0 (cord 18.2) | ||||
| Datta et al. (2002) | UK/minority | 160 women screened. 80 had 25(OH)D <8 ng/ml and were treated with 800 IU D3/day starting at their initial booking. Women still deficient at 36 weeks gestation (number not given) had dose increased to 1600 IU D3/day | 3–? | 5.8 | 11.2 | 50% women were profoundly deficient at time of enrollment as defined by 25(OH)D <8 ng/ml | [159] |
| Sahu et al. (2009) | Uttar Pradesh, northern India | Group A: sunlight only; exposure limited to face, hands and feet, n = 14 | Sunlight only | 25.8 | 23.8 | A significant increase in 25(OH)D at delivery only in group C: 34.2% group C achieved 25(OH)D >80 nmol/l vs 7% group A and 5.75% group B at delivery | [160] |
| Group B: 60,000 IU D3 + sunlight, n = 35 | Month 5 | 33.4 | 30.9 | ||||
| Group C: 120,000 IU D3 + sunlight, n = 35 | Month 5 and 7 | 40.1 | 53.4 | ||||
| Hollis et al. (2011) | Charleston, SC, USA | 400 IU D3/day, n = 111 | 7 | 61.6 | 78.9 | No adverse events due to vitamin D supplementation; 2000 and 4000 IU D3/day groups with higher mean by second trimester than control group with higher percentage, meeting IOM definition of sufficiency; 4000 IU D3/day group achieved greater percentage sufficiency by second trimester than other two groups Infants of mothers in 4000 IU D3/day group with greater percentage sufficiency as per IOM definition | [4] |
| 2000 IU D3/day, n = 122 | 7 | 58.3 | 98.3 | ||||
| 4000 IU D3/day, n = 117 | 7 | 58.2 | 111.0 | ||||
†
Based on known pharmacokinetic data during the pregnant and nonpregnant states, it is most likely that the wrong dose of supplementation was given or the assay for 25(OH)D was invalid. The response observed is one that would be expected after supplementation with 10,000 IU/day vitamin D3 for 3 months.
–: Not given; 1,25(OH)2D: Dihydroxyvitamin D; 25(OH)D: 25-hydroxyvitamin D; D2: Ergocalciferol; D3 Cholecalciferol; IOM: Institute of Medicine; r: Correlation coefficient; SGA: Small for gestational age, defined as third percentile; wt: Weight.