Vitamin B12 and Folate Status in Pregnant Females and Their Infants in Norway: Secondary Analysis from the Mommy's Food Study.
Sol Maja G Bjørkevoll,
Carolien Konijnenberg,
Ingrid Kvestad,
Adrian McCann,
Per M Ueland
et al.
Other
The Journal of nutrition
2023
4 Zitierungen
PubMed
DOI
CC-BY
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Study Design
- Studientyp
- Cohort
- Stichprobengröße
- 136
- Dauer
- 36 weeks
- Intervention
- Vitamin B12 and Folate Status in Pregnant Females and Their Infants in Norway: Secondary Analysis from the Mommy's Food Study. None
- Vergleichsgruppe
- Placebo
- Wirkungsrichtung
- Positive
- Verzerrungsrisiko
- Moderate
Abstract
BACKGROUND: Vitamin B12 and folate are essential micronutrients important for normal infant growth and development. OBJECTIVES: The aims were to describe vitamin B12 and folate status in pregnant females and their infants according to commonly used status cutoffs and examine the associations between maternal status, maternal supplement use, and breastfeeding and infant status. METHODS: Pregnant females were recruited at 18 wk gestation in Bergen, Norway. Maternal vitamin B12 and folate status were measured at gestational weeks 18 (n = 136) and 36 (n = 116), and infant status was measured at ages 3 (n = 73) and 6 (n = 74) mo. RESULTS: At gestational weeks 18 and 36, respectively, 4.4% and 2.6% of the mothers had plasma cobalamin concentrations <148 pmol/L, 0.7% and 6.9% had methylmalonic acid (MMA) concentrations >0.26 μmol/L, and 3.7% and 30% had folate concentrations <10 nmol/L. None of the females had total homocysteine (t-Hcy) concentrations >13 μmol/L or 3 combined indicator of vitamin B12 (cB12) < -0.5. At 3 and 6 mo, respectively, 4.1% and 5.4% of the infants had cobalamin concentrations <148 pmol/L, 63% and 74% had t-Hcy concentrations >6.5 μmol/L, 59% and 66% had MMA concentrations >0.26 μmol/L, and 47% and 60% had cB12 > -0.5. None of the infants had folate concentrations <10 nmol/L. Several of the vitamin B12 biomarkers in infants were associated with maternal vitamin B12 status during pregnancy. Breastfed infants had lower vitamin B12 status (as indicated by plasma cobalamin, t-Hcy, and cB12) than nonbreastfed infants at both 3 and 6 mo. Use of supplements during pregnancy was associated with better vitamin B12 status among infants at 3 and 6 mo, as indicated by infants' cobalamin and t-Hcy concentrations. CONCLUSIONS: Subclinical vitamin B12 deficiency among infants was common and associated with maternal vitamin B12 status during pregnancy and breastfeeding. Among the mothers, an increase in biochemical folate deficiency was discovered toward the end of gestation. Further studies are needed to investigate clinical consequences. This trial was registered at clinicaltrials.gov as NCT02610959.
Full Text
Figures
FIGURE 1
Study flow or recruitment diagram for the secondary analysis of vitamin B12 and folate status in pregnant females and their infants from Norway's Mommy's Food Study.
flowchart
FIGURE 2
Vitamin B12 and folate serum concentrations across pregnancy trimesters and in cord blood, revealing the prevalence of deficiency among Norwegian mothers and infants.
chart
FIGURE 3
Associations between maternal dietary intake or supplement use and vitamin B12 and folate biomarker levels during pregnancy and at delivery.
chartTables
TABLE 1
| Indicator | Cutoff | Definition |
|---|---|---|
| Vitamin B12 status | ||
| Cobalamin | <148 pmol/L | Low B12-status [ |
| t-Hcy | >13 μmol/L (mothers) | Elevated t-Hcy [ |
| >6.5 μmol/L (infants) | Subclinical B12 deficiency [ | |
| MMA | >0.26 | |
| cB12 | < −0.5 | Low B12 status [ |
| Folate status | ||
| Folate | <10 nmol/L | Folate deficiency [ |
| t-Hcy | >13 μmol/L (mothers) | Elevated t-Hcy [ |
TABLE 2
| Characteristics | mean (SD) or % | |
|---|---|---|
| Mothers | ||
| Age, y | 135 | 29.3 (3.8) |
| BMI before pregnancy | 132 | 23.1 (4.0) |
| BMI during pregnancy | 118 | 24.5 (4.0) |
| Education, y | ||
| | 19 | 14.3 |
| 14–17 | 33 | 24.8 |
| >17 | 81 | 60.9 |
| Household income, NOK | ||
| Low (<549,999) | 39 | 29.3 |
| Medium (550,000–1,249,999) | 77 | 57.9 |
| High (>1,250,000) | 17 | 12.8 |
| Marital status | ||
| Single or divorced | 2 | 1.5 |
| Cohabitant | 85 | 63.9 |
| Married | 43 | 32.3 |
| Other | 3 | 2.3 |
| Supplement users | ||
| GW18 | ||
| Users | 79 | 72.5 |
| Nonusers | 30 | 27.5 |
| GW36 | ||
| Users | 53 | 43.6 |
| Nonusers | 41 | 56.4 |
| 3 mo postpartum | ||
| Users | 39 | 48.2 |
| Nonusers | 42 | 51.9 |
| 6 mo postpartum | ||
| Users | 29 | 40.9 |
| Nonusers | 42 | 59.2 |
| Infants | ||
| Sex (female) | 58 | 50.4 |
| Birth weight, g | 93 | 3491 (536) |
| GA at time of delivery, wk | 122 | 40.2 (2.1) |
| Preterm delivery | 6 | 4.9 |
| Breastfeeding status, 3 mo | ||
| Not breastfed | 5 | 4.4 |
| Partially breastfed | 19 | 16.5 |
| Exclusively breastfed | 91 | 79.1 |
| Breastfeeding status, 6 mo | ||
| Not breastfed | 8 | 7.3 |
| Partially breastfed | 98 | 89.9 |
| Exclusively breastfed | 3 | 2.8 |
TABLE 3
| Mothers | Infants | |||||||
|---|---|---|---|---|---|---|---|---|
| GW18 ( | GW36 ( | 3 mo ( | 6 mo ( | |||||
| Median (IQR) | Def, | Median (IQR) | Def, | Median (IQR) | Def, | Median (IQR) | Def, | |
| Cob | 220.0 (184.5, 301.9) | 6 (4.4) | 224.4 (187.9, 291.1) | 3 (2.6) | 244.9 (199.0, 321.8) | 3 (4.1) | 221.6, (194.2, 324.8) | 4 (5.4) |
| t-Hcy | 4.7 (4.3, 5.3) | 0 (0.0) | 5.7 (4.9, 6.5) | 0 (0.0) | 7.3 (6.2, 8.8) | 46 (63.0) | 7.5 (6.5, 8.8) | 55 (74.3) |
| MMA | 0.1 (0.1, 0.2) | 1 (0.7) | 0.2 (0.1, 0.2) | 8 (6.9) | 0.4 (0.2, 0.9) | 43 (58.9) | 0.5 (0.2, 1.0) | 49 (66.2) |
| Folate | 26.4 (16.4, 34.9) | 5 (3.7) | 14.2 (9.4, 27.3) | 35 (30.2) | 42.0 (34.7, 58.7) | 0 (0.0) | 45.7 (34.2, 63.4) | 0 (0.0) |
| cB12 | 0.7 (0.5, 0.9) | 0 (0.0) | 0.4 (0.2, 0.7) | 0 (0.0) | −0.4 (−1.0, 0.2) | 34 (46.6) | −0.7 (−1.0, 0.0) | 44(59.5) |
TABLE 4
| Mothers GW18 ( | Mothers GW36 ( | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cobalamin | t-Hcy | MMA | Folate | cB12 | Cobalamin | t-Hcy | MMA | Folate | cB12 | ||
| Infants 3 mo ( | Cobalamin | 0.36 (0.002) | −0.29 (0.013) | −0.15 (0.218) | 0.21 (0.075) | 0.37 (0.001) | 0.39 (0.001) | −0.25 (0.037) | −0.27 (0.022) | 0.25 (0.036) | 0.44 (<0.001) |
| t-Hcy | −0.28 (0.017) | 0.18 (0.124) | 0.21 (0.081) | −0.27 (0.023) | −0.33 (0.004) | −0.39 (0.001) | 0.40 (<0.001) | 0.34 (0.004) | −0.32 (0.006) | −0.54 (<0.001) | |
| MMA | −0.15 (0.196) | 0.06 (0.598) | 0.32 (0.006) | 0.04 (0.730) | −0.29 (0.013) | −0.22 (0.077) | −0.02 (0.884) | 0.31 (0.010) | 0.08 (0.521) | −0.26 (0.031) | |
| Folate | 0.14 (0.265) | 0.01 (0.909) | −0.01 (0.965) | −0.06 (0.627) | 0.03 (0.831) | 0.06 (0.655) | −0.10 (0.405) | −0.05 (0.685) | 0.01 (0.904) | 0.08 (0.534) | |
| cB12 | 0.26 (0.026) | −0.19 (0.113) | −0.34 (0.004) | 0.04 (0.735) | 0.41 (<0.001) | 0.33 (0.006) | −0.14 (0.243) | −0.38 (0.001) | 0.04 (0.732) | 0.43 (<0.001) | |
| Infants 6 mo ( | Cobalamin | 0.22 (0.060) | −0.15 (0.217) | −0.07 (0.578) | 0.24 (0.043) | 0.22 (0.059) | 0.29 (0.014) | −0.19 (0.119) | −0.17 (0.142) | 0.29 (0.016) | 0.31 (0.009) |
| t-Hcy | −0.13 (0.287) | 0.16 (0.184) | 0.25 (0.031) | −0.18 (0.126) | −0.24 (0.036) | −0.21 (0.076) | 0.27 (0.021) | 0.36 (0.002) | −0.13 (0.287) | −0.42 (<0.001) | |
| MMA | −0.17 (0.146) | 0.07 (0.528) | 0.43 (<0.001) | 0.05 (0.700) | −0.40 (<0.001) | −0.27 (0.025) | 0.19 (0.106) | 0.48 (<0.001) | 0.01 (0.923) | −0.49 (<0.001) | |
| Folate | 0.18 (0.130) | −0.04 (0.726) | −0.04 (0.737) | −0.06 (0.612) | 0.10 (0.397) | 0.07 (0.580) | 0.06 (0.618) | −0.09 (0.469) | −0.07 (0.575) | 0.04 (0.767) | |
| cB12 | 0.23 (0.053) | −0.09 (0.442) | −0.42 (<0.001) | 0.06 (0.612) | 0.43 (<0.001) | 0.36 (0.002) | −0.26 (0.031) | −0.52 (<0.001) | 0.11 (0.357) | 0.59 (<0.001) | |
TABLE 5
| Log cob | Log t-Hcy | Log MMA | Log folate | cB12 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Exp (95%CI) | Exp (95%CI) | Exp (95%CI) | Exp (95%CI) | Coef. (95%CI) | ||||||
| Infant status 3 mo | ||||||||||
| BF status 3 mo | 0.041 | |||||||||
| Non-BF ( | Ref | Ref | Ref | Ref | Ref | |||||
| BF ( | 0.64 (0.43, 0.94) | 0.023 | 1.44(1.04, 2.00) | 0.030 | 2.04(0.60, 6.94) | 0.251 | 0.63(0.38, 1.06) | 0.080 | −0.94(−1.83, −0.04) | 0.041 |
| Infant status 6 mo | ||||||||||
| BF status 6 mo | ||||||||||
| Non-BF ( | Ref | Ref | Ref | Ref | Ref | |||||
| BF ( | 0.50 (0.40, 0.64) | <0.001 | 1.55 (1.30, 1.85) | <0.001 | 3.15 (1.58, 6.29) | 0.001 | 0.70 (0.52, 0.93) | 0.015 | −1.40 (−1.89, −0.90) | <0.001 |
TABLE 6
| 3 mo | 6 mo | |||||||
|---|---|---|---|---|---|---|---|---|
| BF( | Non-BF ( | BF ( | Non-BF ( | |||||
| Median (IQR) | Def, | Median (IQR) | Def, | Median (IQR) | Def, | Median (IQR) | Def, | |
| Cob | 239.1 (194.9, 313.0) | 3 (4.3) | 390.8 (364,0, 446.8) | 0 (0.0) | 212.8 (188.2, 277.1) | 4 (6.1) | 461.0, 374,5, 562,4) | 0 (0.0) |
| t-Hcy | 7.5 (6.3, 9.0) | 46 (65.7) | 4.7 (4.7, 6.1) | 0 (0.0) | 7.8 (6.7, 9.0) | 54 (81.8) | 5.6 (4.3, 5.6) | 0 (0.0) |
| MMA | 0.4 (0.2, 1.0) | 42 (60.0) | 0.2 (0.2, 0.3) | 1 (33.3) | 0.6 (0.3, 1.1) | 49 (74.2) | 0.2 (0.2, 0.3) | 0 (0.0) |
| cB12 | −0.5 (−1.0, 1.4) | 34 (48.6) | 0.5 (0.3, 0.5) | 0 (0.0) | −0.8 (−1.1, −0.2) | 44 (66.7) | 0.6 (0.6, 1.1) | 0 (0.0) |
TABLE 7
| Log cob | Log t-Hcy | Log MMA | Log folate | cB12 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Exp (95%CI) | Exp (95%CI) | Exp (95%CI) | Exp (95%CI) | Coef. (95%CI) | ||||||
| Infants’ status 3 mo | ||||||||||
| Supplement use GW18, ( | ||||||||||
| No | Ref | Ref | Ref | Ref | Ref | |||||
| Yes | 1.33 (1.09, 1.63) | 0.005 | 0.89 (0.76, 1.05) | 0.165 | 0.95 (0.50, 1.79) | 0.863 | 1.07 (0.81, 1.41) | 0.641 | 0.28 (−0.20, 0.77) | 0.249 |
| Supplement use GW36 ( | ||||||||||
| No | ||||||||||
| Yes | 1.10 (0.91, 1.32) | 0.323 | 0.98 (0.84, 1.14) | 0.777 | 1.11 (0.64, 1.91) | 0.717 | 1.00 (0.80, 1.26) | 0.985 | 0.01 (−0.39, 0.42) | 0.954 |
| Supplement use 3 mo PP ( | ||||||||||
| No | Ref | Ref | Ref | Ref | Ref | |||||
| Yes | 1.09 (0.91, 1.32) | 0.351 | 0.86 (0.74, 1.00) | 0.056 | 1.00 (0.55, 1.81) | 0.995 | 1.08 (0.84, 1.38) | 0.553 | 0.15 (−0.30, 0.60) | 0.512 |
| Infants’ status 6 mo | ||||||||||
| Supplement use GW18 ( | ||||||||||
| No | Ref | Ref | Ref | Ref | Ref | |||||
| Yes | 1.21 (0.95, 1.52) | 0.118 | 0.85 (0.73, 0.99) | 0.042 | 0.74 (0.42, 1.28) | 0.276 | 0.88 (0.69, 1.12) | 0.295 | 0.41 (−0.05, 0.86) | 0.084 |
| Supplement use GW36 ( | ||||||||||
| No | Ref | Ref | Ref | Ref | Ref | |||||
| Yes | 1.20 (1.01, 1.44) | 0.043 | 0.89 (0.78, 1.02) | 0.104 | 0.91 (0.56, 1.49) | 0.707 | 0.87 (0.71, 1.06) | 0.161 | 0.24 (−0.15, 0.63) | 0.223 |
| Supplement use 3 mo PP ( | ||||||||||
| No | Ref | Ref | Ref | Ref | Ref | |||||
| Yes | 1.10 (0.91, 1.33) | 0.334 | 0.92 (0.81, 1.05) | 0.212 | 1.39 (0.85, 2.25) | 0.188 | 1.01 (0.83, 1.24) | 0.900 | −0.09 (−0.48, 0.29) | 0.641 |
| Supplement use 6 mo PP ( | ||||||||||
| No | Ref | Ref | Ref | Ref | Ref | |||||
| Yes | 1.02 (0.82, 1.27) | 0.875 | 0.88 (0.77, 1.02) | 0.089 | 1.26 (0.73, 2.18) | 0.398 | 0.95 (0.77, 1.18) | 0.670 | −0.06 (−0.48, 0.36) | 0.785 |
References
- Vitamin B-12 and cognition in children Adv. Nutr., 2016
- B vitamins and n-3 fatty acids for brain development and function: review of human studies Ann. Nutr. Metab., 2012
- Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease Eur. J. Clin. Nutr., 2014
- Acquired vitamin B12 deficiency in newborns: positive impact on newborn health through early detection Nutrients, 2022
- Common metabolic profile in infants indicating impaired cobalamin status responds to cobalamin supplementation Pediatrics, 2008
- The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants Eur. J. Paediatr. Neurol., 2021
- Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial BMC Pediatr, 2015
- Cobalamin and folate status among breastfed infants in Bhaktapur, Nepal Nutrients, 2018
- Maternal and infant vitamin B12 status during infancy predict linear growth at 5 years Pediatr. Res., 2018
- Vitamin B12 and folic acid improve gross motor and problem-solving skills in young North Indian children: a randomized placebo-controlled trial PLOS ONE, 2015
- Prevalence of vitamin B-12 insufficiency during pregnancy and its effect on offspring birth weight: a systematic review and meta-analysis Am. J. Clin. Nutr., 2016
- Folic acid food fortification-its history, effect, concerns, and future directions Nutrients, 2011
- Maternal folic acid and multivitamin supplementation: international clinical evidence with considerations for the prevention of folate-sensitive birth defects Prev. Med. Rep., 2021
- Untitled
- Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms Nutr. Rev., 2008
- Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency Front. Mol. Biosci., 2016
- Studies of biomarker responses to intervention with vitamin B-12: a systematic review of randomized controlled trials Am. J. Clin. Nutr., 2009
- Vitamin B12 status in health and disease: a critical review. Diagnosis of deficiency and insufficiency - clinical and laboratory pitfalls Crit. Rev. Clin. Lab. Sci., 2021
- Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points Clin. Chem. Lab. Med., 2015
- Laboratory assessment of vitamin B12 status J. Clin. Pathol., 2017
- Laboratory assessment of folate (vitamin B9) status J. Clin. Pathol., 2018
- Effects of cod intake in pregnancy on iodine nutrition and infant development: study protocol for Mommy’s Food - a randomized controlled trial BMC Nutr, 2018
- Effects of two weekly servings of cod for 16 weeks in pregnancy on maternal iodine status and infant neurodevelopment: Mommy’s Food, a randomized-controlled trial Thyroid, 2021
- Microbiological assay for vitamin B12 performed in 96-well microtitre plates J. Clin. Pathol., 1991
- Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method Methods Enzymol, 1997
- Combined measurement of 6 fat-soluble vitamins and 26 water-soluble functional vitamin markers and amino acids in 50 μL of serum or plasma by high-throughput mass spectrometry Anal. Chem., 2016
- A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population Clin. Chem. Lab. Med., 2015
- Untitled
- Untitled
- Validation and reproducibility of a new iodine specific food frequency questionnaire for assessing iodine intake in Norwegian pregnant women Nutr. J., 2019
- Correlation coefficients: appropriate use and interpretation Anesth. Analg., 2018
- Maternal serum cobalamin at 18 weeks of pregnancy predicts infant cobalamin status at 6 months-a prospective, observational study J. Nutr., 2018
- Maternal folate and cobalamin status predicts vitamin status in newborns and 6-month-old infants J. Nutr., 2010
- Maternal vitamin B12 deficiency and perinatal outcomes in southern India PLOS ONE, 2021
- Determinants of cobalamin status in newborns Pediatrics, 2001
- Vitamin B12 among parturients and their newborns and its relationship with birthweight Eur. J. Obstet. Gynecol. Reprod. Biol., 1992
- The relationship of neonatal serum vitamin B12 status with birth weight, Asia Pac J. Clin. Nutr., 2006
- Child’s homocysteine concentration at 2 years is influenced by pregnancy vitamin B12 and folate status J. Dev. Orig. Health Dis., 2012
- B vitamins in breast milk: relative importance of maternal status and intake, and effects on infant status and function Adv. Nutr., 2012
- B vitamins: proposed fortification levels for complementary foods for young children J. Nutr., 2003
- Folate and cobalamin status in relation to breastfeeding and weaning in healthy infants Am. J. Clin. Nutr., 2008
- Micronutrient status and nutritional intake in 0- to 2-year-old children consuming a cows’ milk exclusion diet J. Pediatr. Gastroenterol. Nutr., 2018
- Biomarkers of Nutrition for Development (BOND): vitamin B-12 review J. Nutr., 2018
- A longitudinal study of serum cobalamins and its binding proteins in lactating women Eur J Clin Nutr, 2007
- Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh Eur. J. Nutr., 2016
- Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status J. Nutr., 2014
- Cobalamin supplementation improves motor development and regurgitations in infants: results from a randomized intervention study Am. J. Clin. Nutr., 2013
- Effects of vitamin B12 supplementation on neurodevelopment and growth in Nepalese infants: a randomized controlled trial PLOS Med, 2020
- The effect of infant vitamin B12 supplementation on neurodevelopment: a follow-up of a randomized placebo-controlled trial in Nepal Br. J. Nutr., 2023
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