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. 2023 Jun 30;67:10.29219/fnr.v67.8626. doi: 10.29219/fnr.v67.8626

Table 4.

Summary of results and overall risk of bias for studies conducted during pregnancy, lactation or infancy

Author (year) Population Outcome, definition Vitamin B12 intake Results Effect estimates (final models) Overall risk of bias
Koebnick 2004
Pregnancy (20)		 Low B12 status (pmol/L):
s-B12:
First trimester <130
Second trimester <120
Third trimester <100
Elevated p-tHcy μmol/L:
First trimester: >9
Second to third trimester: >7.8		 Dietary intake median (IQR) μg/d:
Lacto-ovo vegetarians: 2.5 (1.3–3.8) (P < 0.001 vs. controls)
Low meat eaters (<405 g/week): 3.8 (3.0–4.9) (P < 0.001 vs. controls)
Western diet controls: 5.3 (4.3–6.3)
Supplement use:
Lacto-ovo vegetarians: 32.1% (P = 0.889 vs. controls)
Low meat eaters 27.9% (P = 0.559 vs. controls)
Western diet controls: 20.5%		 Lacto-ovo vegetarians:
↓ sB12
↓holo-TC
↑ tHcy
↑ odds of low B12 status
39% low s-B12
Low meat eaters:
↓ sB12
↑ tHcy (P = 0.061)
↑ odds of low B12 status
9% low s-B12
Optimal daily B12 intake during pregnancy should be >3 μg vitamin B12		 Risk of low B12 status:
OR (95% CI) = 3.9 (1.9–6.1) for lacto-ovo vegetarians compared to controls
OR (95% CI) = 1.8 (1.0–3.9) for low meat eaters compared to controls		 Serious
Visentin 2016
Pregnancy (21)		 B12 deficiency (pmol/L):
s-B12 <148
Marginal B12 deficiency (pmol/L):
s-B12: 148–220
Elevated p-tHcy (μmol/L): >13
Elevated p-MMA (nmol/L): <271		 Dietary intake mean (SD) μg/d:
Weeks 0–16: 4.7 (3.1)
Weeks 23–37: 4.6 (2.6)
Supplement intake median (IQR) μg/d:
Weeks 0–16: 2.6 (2.6–10.0)
Weeks 23–37: -		 Total vitamin B12 intake in early pregnancy:
↑ s-B12 (16.9% deficient, 35% marginal)
↓tHcy (0% elevated)
↓MMA (1.9% elevated)
Total vitamin B12 intake in mid-to late pregnancy:
↑s-B12 (38.2% deficient, 42.9% marginal)
↓tHcy (0% elevated)
↓ (5.3% elevated)
Supplement use:
↑s-B12		 s-B12 decreased by 23% during pregnancy (P = 0.005)
Per 10 μg increase in maternal total vitamin B12 intake:
In early pregnancy, β (95% CI):
s-B12 (pmol/L): 1.04 (1.02–1.06)
tHcy (μmol/L): -0.04 (-0.08–0.006)
MMA (nmol/L): 1.00 (0.99–1.02)
Mid-to-late pregnancy, β (95% CI):
s-B12 (pmol/L): 1.04 (1.02–1.06)
tHcy (μmol/L): 0.03 (-0.04–0.11)
MMA (nmol/L): 0.96 (0.93–0.98)		 Moderate
Denissen 2019
Pregnancy (22)		 Vitamin B-12 deficiency:
holoTC <35 pmol/L and MMA >0.45 μmol/L		 Dietary intake mean (95% CI) ug/day:
All: 5.0 (3.8. 6.5)
Omnivores: 5.1 (3.9. 6.6)
Vegetarians: 3.5 (2.4. 4.7)
Pescetarians: 4.3 (3.3. 6.1)
Lacto-ovo vegetarians: 2.3 (1.9. 2.9)		 Dose-response associations between of dietary vitamin B-12 intake and p-B12, holoTC and MMA.
B12 intake of ≥4.2 μg/d associated with ~90% reduced odds of deficiency compared to a lower intake.		 % Difference (95% CI), per 1 μg increment in B12 intake:
p- B12: 1.0 (0.9–2.0)
p-holoTC: 3.0 (2.0–3.0)
p-MMA: −2 (−3.0 to −1.0)
Deficiency, OR (95% CI):
Tertile 2 vs. 1 (5.0 vs. 3.2 ug): 0.07 (0.02–0.33)
Tertile 3 vs. 1 (9.1 vs. 3.2 ug): 0.1 (0.03–0.37)		 Study quality: moderate
Greibe 2013
Lactation and infancy (23)		 Continuous Mothers:
Supplement intake:
2 weeks: 79%
4 months: 67%
9 months: 50%
Infants:
Estimated intake from breastmilk:
2 weeks: 0.7 μg/d
4 months: 0.3 μg/d
9 months: -		 ↑ Maternal B12 status = ↑ breastmilk B12↑ Breastmilk B12 = ↑ infant B12 status at 4 months
B12 content of breastmilk decreased over time
Exclusive breastfeeding vs. not exclusive breastfeeding at 4 months:
↓ B12
↓ holoTC		 Maternal and infant p-B12 concentration:
2 weeks: r = 0.52 (P = 0.0001)
4 months: r = 0.47 (P = 0.0001)
9 months: r = 0.29 (P = 0.03)
Median (range) B12 content of hind milk, pmol/L:
2 weeks: 760 (210–1880)
4 months: 290 (140–690)
9 months: 440 (160–1940) (all significantly different)
Breastmilk B12 at 4 months postpartum: infant p-B12: r = 0.58 (P = 0.005)		 Low
Henjum 2020
Lactation (24)		 Continuous Mothers:
Vitamin B12 intake (μg/d):
Diet: 4.1
Diet + supplements: 5.0
Supplement use: 34%		 Breastmilk B12 content not associated with maternal B12 intake
Infant, B12 intake estimated from breastmilk (exclusive breastfeeding non-supplemented mothers), μg/d:1 months: 0.47
2 months: 0.33
3 months: 0.25
4 months: 0.28
5 months: 0.31
6 months: 0.29		 Breastmilk B12 concentration:
B12 supplement users vs. non-users mean (SD): 340 (179) vs. 320 (169) pmol/L, P = 0.46
Dietary B12 intake, β (95% CI): 3.8 (-7.0-14.6), P = 0.49
Content of breastmilk decreased over time content, β (95% CI):
Per week: −5.0 (−9.7 to −0.2), P = 0.04		 Study quality: low
Hay 2008
Lactation and infancy (25)		 Continuous B12 intake at 12 months, geometric mean (95% CI) μ/d:
Breastfed: 1.4 (1.3–1.6)
Non-breastfed: 2.4 (2.1–2.6) (P < 0.001)		 Exclusive breastfeeding infants at 6 months:
↓ sB12 (vs. non-breastfed)
↓holo-TC (vs. non-breastfed)
Breastfeeding infants at 12 months:
↓ sB12 (vs. non-breastfed)
↓holo-TC (vs. non-breastfed)
↑ tHcy (vs. non-breastfed)
↑MMA (vs. non-breastfed)
Introduction of formula and/or solids at 6 and 12 months:
↑ sB12
↑holo-TC
↓ tHcy
↓ MMA		 6 mo s-B12 (mean [95% CI]) pmol/L: Exclusive breastfed: 242 (202–289)
Non-breastfed: 365 (328–408)
Breastfed + solids:
244 (226–264)
Breastfed + solids and breastmilk substitutes: 249 (226–274)
Correlation between B12 intake from complementary foods and B12 status at 12 months:
sB12: r = 0.15 (P = 0.03)
holoTC: r = 0.25 (P = 0.001)
Correlation between no breastfeedings/d and B12 status at 12 months:
sB12: r = -0.25 (P < 0.001)
holoTC: r = -0.33 (P < 0.001)
12 months B12 (mean [95% CI]) pmol/L:
Breastfed + solids: 288 (242–342)
Non-breastfed: 397 (372–424)
Breastfed + solids and breastmilk substitutes: 343 (319–369)		 Low