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. 2023 May 17;21(5):e08006. doi: 10.2903/j.efsa.2023.8006

Reference Study name

Country

Duration

Funding

Design Subject characteristics at baseline Intervention Incident cases Results

Marathe et al. (1986)

NR

India

B6: Day 6–15 of gestation

Study: 0–20 weeks of gestation

NR

Animal (rat) study Parallel

N = 48

G1: 12 (control)

G2: 12

G3: 12

G4: 12

Sex (% female): 100

Wistar rats, weight range 200–220 g

Pyridoxine hydrochloride:

G1: 0 mg/kg per day

G2: 200 mg/kg per day

G3: 400 mg/kg per day

G4: 800 mg/kg per day

Background nutrient intake: All fed Hindustan Lever feed and water ad libitum

B6 intake: NR

Compliance: 100%

Pup weight

Pup weight (g, mean ± SD)

G1: 6.57 ± 0.16

G2: 6.37 ± 0.16

G3: 6.26 ± 0.15

G4: 6.21 ± 0.12

Difference NS

Schumacher et al. (1965)

NR

USA

2 weeks pre‐pregnancy + during pregnancy

NR

CT, parallel (rats)

Inclusion criteria: Long‐Evans rat strain

N = 55

G1 (control): n = 40

G2 (+pyridoxine): n = 15

Sex (% female): 100

Age: NR

Weight (g, mean):

G1 (control): 300 G2 (+pyridoxine): 300

Pyridoxine

Doses (g/100 g diet)

G1: 0.25

G2: 6.25

Background nutrient intake: NR

Compliance: NR

Birth weight

Birth weight (g/litter, mean) (average weight provided only)

G1: 6.2

G2: 6.1

Difference NS

Alton‐Mackey and Walker (1973)

NR

Canada

14 days pre‐pregnancy + during pregnancy

NR

CT, parallel (rats)

N = 48

Sex (% female):

100 Wistar rats, virgin

Weight (g): 200

Basal diet supplemented with 400% National Research Council (NRC) recommendations for pyridoxine for 2 weeks prior to mating (control)

During pregnancy, rats divided into six dietary groups. Basal diet supplemented with pyridoxine, % of NRC:

G1: 400

G2: 100

G3: 75

G4: 50

G5: 25

G6: 0

Group size: NR

Compliance: NR

Birth weight

Birth weight (g/four litters, mean ± SEM)

G1: 78.2 ± 3.8

G2: 74.3 ± 3.6

G3: 66.7 ± 3.1

G4: 60.9 ± 3.7

G5: 47.8 ± 3.6

G6: 44.8 ± 3.1

G4, G5, G6 lower than G1, G2, G3, p < 0.05

Alton‐Mackey and Walker (1978)

NR

Canada

14 days prepregnancy + pregnancy

NR

CT, parallel (rats)

N = 186

Sex (% female): 100

Wistar rats, virgin

Weight (g): 200

Basal diet supplemented with 400% National Research Council (NRC) recommendations for pyridoxine for 2 weeks prior to mating (control)

During pregnancy, basal diet supplemented with pyridoxine, % of NRC:

G1 (n = 31): 400

G2 (n = 31): 100

G3 (n = 31): 75

G4 (n = 31): 50

G5 (n = 31): 25

G6 (n = 31): 0

Group size: NR

Compliance: NR

Birth weight

Birth weight (g/litter, mean) (read from Figure 1)

G1: 50

G2: 41

G3: 39

G4: 38

G5: 30

G6: 7

G5 and G6 (0–25%) very low birth weight

Birth weight of G1, G2, G3, and G4 normal

Tests + p‐values NR

Ritchie et al. (1960)

NR

USA

~ 2nd month of pregnancy – delivery

Public

RCT, parallel (swine) Inclusion criteria: Basis for equal allotment to two treatments: Size, sex, breed, litter

N (randomised/completed) = 44/42

G1 (randomised/completed): n = 22/21

G2 (randomised/completed): n = 22/21

Sex (% female): 100

G1: Control

G2: Intervention Pregnant

Pyridoxine‐HCl

G1: Total pyridoxine (pyridoxine + pyridoxal + pyridoxamine)

G2: Pyridoxine‐HCl

Doses (mg/pound of diet)

G1: 0.45

G2: 5

Background nutrient intake: NR but controlled and similar in both groups

Birth weight

Birth weight (pounds/litter mean ± SEM)

G1: 29.1 ± 2.0

G2: 28.7 ± 2.0 Difference NS

Khera (1975)

NR

Canada

Gestation day 6–15

Public

RCT, parallel (rats)

Female Wistar rats

N = NR

n = 89

Sex (% women): 100

Weight range (g): 175–200

Pyridoxine hydrochloride

Doses (mg/kg day):

G1: 0

G2: 20

G3: 40

G4: 60

G5: 80

Birth weight + anomalies

Types of anomalies investigated: Wavy ribs; lumbar ribs; sternal defects; and runts. Less commonly: pericardial haemorrhage and subcutaneous oedema

Birth weight (g/animal, mean ± SD)

G1: 4.8 ± 0.4

G2: 4.8 ± 0.3

G3: 4.8 ± 0.3

G4: 4.9 ± 0.3

G5: 4.8 ± 0.4

Anomalies (no/total examine, frequency)

G1: 10/201

G2: 12/193

G3: 10/206

G4: 6/230

G5: 9/243

Dalto et al. (2016)

NR

Canada

30 days

Private

RCT, parallel (gilts)

Inclusion criteria: NR

N (randomised/completed/analysed) = 84/77/32

Sex (% female): 100

Age (d [range]): 135–170

Body weight (kg ± SD): 91.4 ± 1.0

Pyridoxine hydrochloride

Doses (mg/kg feed)

G1: 2.4

G2: 12.4

Compliance: NR

Embryo weight at 30 days of gestation

Embryo weight at 30 d of gestation (g, mean)

G1: 22.75

G2: 20.12

Tests and p‐values NR

Mean ± SD, unless specified otherwise.

CT: controlled trial; d: day; Gx: group; HCL: hydrochloride; NR: not reported; NS: not significant; RCT: randomised controlled trial; SEM: standard error of the mean; SD: standard deviation; USA: United States of America.