| Study population | Diet characteristics | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Biblio graphy |
Nb | Health status | Full term | Vit D source ‐trials | Vit D form | D_ wks |
Method for serum 25(OH)D |
VitD dose analytically checked | Compliance check | Ca‐ supp | Comments on study characteristics |
|
(Country) Hemisphere: Latitude |
TofFeed | Vit D dose μg/day | L‐ wks | > | |||||||
|
DESIGN: RCT AGE CLASS: ALL INFANTS | |||||||||||
| Gallo et al. (2013a) | 132 | Healthy | Full term | Drop | D3 | 12 | LC‐MS,MS | Yes | Yes | No | Authors mentioned that infants grew in an age‐appropriate way over time, with no differences over groups. Vitamin D from other foods than breast milk assessed using 3‐d dietary records. |
|
(CA) N:>= 40 & <= 50 |
Mixed |
G1:10 G2:20 G3:30 G4:40 |
11 | ||||||||
| Grant et al. (2014) | 200 | Healthy | Mixed | Drop | D3 | 7 | LC‐MS,MS | No | Yes | No | All mean weight at birth above 3.4 kg. Preterm received vitamin D through parenteral and oral nutrition. Mothers of infants in groups 2 and 3 supplemented during pregnancy. |
|
(NZ) S:< 40 |
Mixed |
G1:0 G2:10 G3:20 |
6 | ||||||||
| Holmlund‐Suila et al. (2012) | 113 | Healthy | Full term | Drop | D3 | 3 | Other | Yes | Yes | No | Analytical method for 25(OH)D: automated chemiluminiscence immunoassay (CLIA). |
|
(FI) N:>= 50 |
Mixed |
G1:10 G2:30 G3:40 |
3 | ||||||||
| Kunz et al. (1982) | 29 | Healthy | Mixed | Pill | NA | 2 | CPBA | No | No | No | Infants received formula containing 10 μg/L vitamin D. |
|
(DE) N:>= 50 |
Formula |
G1:25 G2:12.5 |
1.4 | ||||||||
| Nguema‐Asseko et al. (2005) | 79 | Healthy | Mixed | S‐NA | NA | 7 | NA | No | No | No |
Vitamin D provided via Uvestero®. Unclear if exclusively breastfed (but assumed to). All infants born in August. |
|
(GA) N:< 40 |
Breast |
G1:25 G2:0 |
6 | ||||||||
| Pittard et al. (1991) | 25 | Healthy | Full term | S‐NA | NA | 4 | NA | No | No | No | Throughout the study, each neonate was given an 84J/30 mL formula, that contained 12.8 mmol/L of calcium, and no added vitamin D. |
|
(US) N:< 40 |
Unclear |
G1:1 0G2:20 |
3.7 | ||||||||
| Siafarikas et al. (2011) | 40 | Healthy | Full term | Pill | D3 | 2 | RIA | No | No | No | In each group, an even number of infants born in summer and in winter |
|
(DE) N:>= 50 |
Breast |
G1:6.25 G2:12.5 |
1.4 | ||||||||
| Vervel et al. (1997)(Study 1 and Study 2) | 80 | Healthy | Full term | Drop | D2 | 4 | CPBA | No | Yes | No |
Results reported i) according to whether the mothers were supplemented (n = 22) or not (n = 48) and ii) according to the dose given to infants. Content of vitamin D in formula reported. Intake of formula measured but not reported Study 1: infants from unsupplemented mothers Study 2: infants from supplemented mothers |
|
(FR) N:>= 40 & <= 50 |
Formula |
G1:12.5 G2:25 |
3 | ||||||||
| Zeghoud et al. (1997) |
14 (Study 1); 36 (Study 2); 29 (Study 3) |
Healthy | Full term | S‐NA | D2 | 4 | CPBA | No | No | No |
Vitamin D provided via Uvesterol®. Vitamin D content in formula 11 +/− 1 μg/L D3. Study nr 1: neonates with vitamin D deficiency (25(OH)D < 30 nmol/L) and with high PTH (> 60 ng/L). Study nr 2: neonates with 25(OH)D < 30 nmol/L. Study nr 3: neonates with 25(OH)D strictly > 30 nmol/L |
|
(FR) N:>= 40 & = 50 |
Formula |
G1:25 G2:12.5 |
3 | ||||||||
| Ziegler et al. (2014) | 213 | Healthy | Full term | Drop | D3 | 9 | RIA | Yes | Yes | No |
Complementary feeding possible but not formula until 9 mo. Mean vitamin D supplement really consumed, according to time points: Group 1: 5.5–6 μg/day Group 2: 10–11 μg/day Group 3: 14–15 μg/day Group 4: 19–20.5 μg/day |
|
(US) N:< 40 |
Breast |
G1:5 G2:10 G3:15 G4:20 |
11 | ||||||||
|
DESIGN: RCT AGE CLASS: MIXED POPULATION | |||||||||||
| Gordon et al. (2008) | 26 | HypovitD | Mixed | Drop | D2,D3 | 2 | Other | Yes | Yes | Yes |
25(OH)D measured by chemiluminescence. Data on arm on weekly dose (n = 14) not extracted |
| (US) N:>= 40 & <= 50 | Mixed |
G1:50 G2:50 |
1.4 | ||||||||
|
DESIGN: RNCT, NRCT,NRNCT AGE CLASS: ALL INFANTS | |||||||||||
| Ala‐Houhala (1985) |
47 (Study 1) 45 (Study 2) |
Healthy | Full term | S‐NA | NA | 5 | CPBA | No | No | No |
From the main study (n = 100, including 8 in a pilot study, results not extracted), 9 infants excluded as mothers interrupted exclusive breastfeeding, but unclear if they belong to the pilot or the main study. Half of the mothers were supplemented during pregnancy. Mothers of group 1 are supplemented after delivery, while those of group 2 and 3 are not. Study 1: infants followed in winter Study 2: infants followed in summer |
|
(FI) N:>= 50 |
Breast |
G1:0 G2:10 G3:25 |
4.6 | ||||||||
| Fomon et al. (1966) | NA | Healthy | Full term | FORT | NA | 6 | NA | No | No | No | Commercial complementary feeding free of vitamin D was permitted. Mean birth weight of 3.4–3.6 kg in each group. Group 1: received formula with 10 μg/405 mL, median vitamin D intake is 11.25 μg/day (range 9–14 μg/day). 13 subjects at inclusion (11 completed 112 days and 2 were lost to follow up before). Group 2: received 40 μg/405 mL. Median intake of vitamin D 45 μg/day (range 34.5–54 μg/day). Group 3: Control group of 31 breastfed infants (not exclusively breastfed, as they receive 1 μg/100 mL of formula). Vitamin D content in breast milk not measured. Average vitamin D intake of 2 μg/day from formula and supplements consumed (5 μg/day). Authors say total vitamin D intake in this group was about 7.5 μg/day |
|
(US) N:>= 40 & <= 50 |
Mixed |
G1:11.25 G2:45 G3:7.5 |
5.6 | ||||||||
| Holst‐Gemeiner et al. (1978) | 10 | Healthy | Mixed | Drop | D3 | 2 | RIA | No | No | No | Infants received breastmilk or formula but no other vitamin D supplementation. Data for the group receiving a bolus dose not extracted |
| (AT) N:>= 40 & <= 50 | Mixed | G1:30 | 1.2 | ||||||||
| Pehlivan et al. (2003) | 40 | Healthy | Mixed | S‐NA | NA | 4 | Other | No | No | No | The paper mentions 65 infants and 40 breastfed infants. Not clear if the 40 are included in the 65 or not. Only data for 40 breastfed infants extracted. Supplementation started at the start of the second week in both groups. Baseline values not reported |
|
(TR) N:>= 40 & <= 50 |
Breast |
G1:10 G2:20 |
4 | ||||||||
| Pincus et al. (1954) | NA | Healthy | Mixed | FORT/S‐NA | NA | 1 | NA | No | No | No |
All infants were breastfed but unclear if exclusively. Group 1: no supplement. Group 2: supplement was an aqueous preparation. Group 3: fed with a formula not containing vitamin D. Group 4: fed with formula containing 10 μg/L vitamin D. Unclear how much formula was consumed, so real vitamin D intake is unknown. Group 5: fed with a formula not containing vitamin D. Infants received vitamin D supplement in an aqueous preparation |
|
(US) N:>= 40 & <= 50 |
Mixed |
G1:0 G2:15 G3:0 G4:10 G5:15 |
1 | ||||||||
| Ribot (1981) | 35 | Healthy | Mixed | S‐NA | NA | 1 | CPBA | No | No | No |
Vitamin D provided via Uvesterol®. Group1: newborns, group 2: aged 2–6 mo. Data for the group of premature infants not extracted |
|
(FR) N:>= 40 & <= 50 |
NA |
G1:25 G2:25 |
1 | ||||||||
|
DESIGN: PROSP AGE CLASS: ALL INFANTS | |||||||||||
|
Czech‐Kowalska et al. (2012) (PL) N:>= 50 |
19 (Study 1), 11 (Study 2) |
Hypovit D | Full term | Drop | D3 | 3 | Other | No | Yes | No |
No signs of rickets. Median birth weight of 3570 g (3405;3890). Seventeen infants (56.7%) born in summer and 13 infants (43.3%) in winter. Twenty‐five infants (83.3%) were regularly supplemented (1 drop daily), while in 5 cases (4 deficient and 1 insufficient at T1) the supplementation scheme was different, i.e. 2 drops of vitamin D ingested occasionally in a time period of 2–10 weeks. Most of the infants were exclusively breastfed. |
| Mixed | 2.3 |
Median intake at time point 1 for the full study 14 μg/day (P25–P75 12.5–17). Analytical method for 25OHD: immunochemiluminescence. Study 1 : newborn infants with 25OHD less than 27.5 nmol/L (‘deficient’ group). All infants were supplemented, but they did not receive vitamin D supplementation at baseline. Time point 0, median (IQR): vitamin D supplements (μg/day) 0 (0;0); total vitamin D intake (μg/day) 0.5 (0.5;0.5) Time point 1, median (IQR): vitamin D supplements (μg/day) 17 (12.5;19); total vitamin D intake (μg/day) 18 (13.5;20). Study 2: newborn infants with 25OHD between 27.5 and 50 nmol/L (‘insufficient’ group). Time point 0, median (IQR): vitamin D supplements (μg/day) 0 (0;0); total vitamin D intake (μg/day) 0.5 (0.5;0.5) Time point 1, median (IQR): vitamin D supplements (μg/day) 12.5 (12.5;15); total vitamin D intake (μg/day) 19 (13.5;20). Both groups did not differ by maternal vitamin D supplementation, infants’ age, gender, birth weight, season of birth, type of feeding and vitamin D intake. 86% of mothers reported vitamin D supplementation during pregnancy. |
|||||||||
| Hoppe et al. (1997) | 37 | Healthy | Full term | S‐NA | D3 | 3 | NA | No | No | No |
Birth weight in term infants, mean (SD): formula‐fed 3,316 (562), breastfed 3,047 (710) g. Calcium content of infant feedings (mg/100 mL)‐Human milk 30‐ formula A 57 – Formula B 45. Authors indicate that serum ca and creatinine were in the normal age‐related range (range not given). Group 1: only formula‐fed term infants. Group 2: only breastfed term infants. |
| (CH, DE) N:>= 40 & <= 50 | Mixed |
G1:12.5 G2:12.5 |
2 | ||||||||
| Pludowski et al. (2011) | 75 | Healthy | Full term | Drop | D3 | 7 | Other | No | Yes | No |
Analytical method for 25OHD: radioreceptor method. A subgroup from the full study group (n = 132) of 82 infants with a complete data set was selected, divided into 3 subgroups according to vitamin D supplementation scheme reported by caregivers: 1. Regular supplementation at both 6 and 12 months (n = 43) (Group 1). 2. Supplementation scheme changed between the 6th and the 12th month (n = 32) i.e. regular supplementation, then occasional, or the other way round, or discontinued supplementation. Group 2) 3. Occasional supplementation at both 6 and 12 months (n = 7). Questionnaire used to collect dietary data and data on vitamin D supplements. Vitamin D intake from breast milk not taken into account. Group 1: Infants regularly supplemented with vitamin D). T0: Total intake (food + supplements): 29 +/− 18 μg/day. T1: Total intake (food+supplements): 29 +/− 14 μg/day. Group 2: Infants with reported changes in the supplementation scheme. T0: Total intake (food+supplements): 28.5 +/− 15.5 μg/day. T1: Total intake (food+supplements): 19 +/− 14 μg/day. |
|
(PL) N:>= 50 |
Mixed |
G1:NA G2:NA |
6 | ||||||||
|
DESIGN: PROSP AGE CLASS: MIXED POPULATION | |||||||||||
| Gallo et al. (2016) | 132 | Healthy | Full term | Drop | D3 | 12 | LC‐MS, MS | Yes | Yes | No |
Same cohort as Hazell et al., 2017. Dietary intake from other foods assessed using three 24h recalls and validated FFQ for preschool children used to assess calcium and vitamin D (from food and supplements) intake over the past month. Background intake (food only) at 36 months not significantly different among groups, in particular for calcium and vitamin D: calcium: 931–970 mg/day; vitamin D: 6–7.5 μg/day Vitamin D, total diet and supplements (group 1,2,3,4) Tertile 1: % ≤ 9 μg/day 40.0, 25.0, 19.0, 36.0Tertile 2: % 9–13 μg/day 16.0, 42.0, 46.0, 9.0Tertile 3: % ≥ 13 μg/day 44.0, 33.0, 35.0, 55.0. No information given on intake between the end of the trial and one month before the follow‐up. |
|
(CA) N:>= 40 & <= 50 |
Mixed |
G1:10 G2:20 G3:30 G4:40 |
0.1 | ||||||||
| Hazell et al. (2017) | 132 | Healthy | Full term | Drop | D3 | 12 | LC‐MS,MS | Yes | Yes | No | Same cohort as Gallo et al., 2016; follow‐up of the trial Gallo et al., 2013a; From the original 132 participants in the trial, 66% (49 boys and 38 girls) returned for the 3‐year follow‐up. |
| (CA) N:>= 40 & <= 50 | Mixed |
G1:10 G2:20 G3:30 G4:40 |
0.1 | ||||||||
| Hyppönen et al. (2011) | 12058 | Mixed | Mixed | Drop | NA | 13 | NA | No | Yes | No |
200 infants identified as having rickets. Daily dose of vitamin D calculated on the basis of the concentration of vitamin D in the product used and the reported dosage (as number of droplets) of the product. 84 children who had received cod liver oil were classified as having received the recommended dose (50 μg/day). No information on vitamin D supplementation after the first year. According to contemporary recommendations, vitamin D supplementation of 50 μg/day was recommended to all children up to 2 y, which may suggest that systematic supplementation in many cases was restricted to the first 2 y of life. Subjects grouped according to frequency of supplementation: none, irregularly, regularly. Analysis according to daily doses done only in those that received supplementation regularly |
| NA |
G1:0 G2:< 50 G3:50 G4:> 50 |
0.6 | |||||||||
AT: Austria; Breast: exclusively breastfed at inclusion; CA: Canada; Ca‐supp: calcium supplementation (yes/no); CBPA: competitive protein‐binding assay; CH: Switzerland; CLIA: automated chemiluminiscence immunoassay; D: Duration of vitamin D additional intake (converted into weeks and rounded); DE: Germany; FI: Finland; Formula : exclusively formula‐fed at inclusion; FORT: fortified food (formula); FR: France; GA: Gabon; L: Length of follow‐up (converted into weeks and rounded); LCMS‐MS: liquid chromatography‐tandem mass spectrometry; N: North; Nb: number of subjects at randomisation/inclusion; NA: type of feeding at inclusion not specified; NRCT: non‐randomised controlled trial; NRNCT: non‐randomised non‐controlled trial; NZ: New Zealand; PL: Poland; PROSP: prospective cohort study; RCT: randomised controlled trial; RNCT: randomised non‐controlled trial; RIA: radioimmunoassay; S: South; S‐NA: supplements in an unspecified form; TofFeed: type of feeding at inclusion; TR: Turkey; US: United States; wks: weeks.