Pregnancy support- Vitamin Treatment

Vitamin B12 (vegetarians only) -

Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development

Food Nutr Bull. 2008 Jun;29(2 Suppl):S101-11;

Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL.

The importance of folate in reproduction can be appreciated by considering that the existence of the vitamin was first suspected from efforts to explain a potentially fatal megaloblastic anemia in young pregnant women in India. Today, low maternal folate status during pregnancy and lactation remains a significant cause of maternal morbidity in some communities. The folate status of the neonate tends to be protected at the expense of maternal stores; nevertheless, there is mounting evidence that inadequate maternal folate status during pregnancy may lead to low infant birthweight, thereby conferring risk of developmental and long-term adverse health outcomes. Moreover, folate-related anemia during childhood and adolescence might predispose children to further infections and disease. The role of folic acid in prevention of neural tube defects (NTD) is now established, and several studies suggest that this protection may extend to some other birth defects. In terms of maternal health, clinical vitamin B12 deficiency may be a cause of infertility or recurrent spontaneous abortion. Starting pregnancy with an inadequate vitamin B12 status may increase risk of birth defects such as NTD, and may contribute to preterm delivery, although this needs further evaluation. Furthermore, inadequate vitamin B12 status in the mother may lead to frank deficiency in the infant if sufficient fetal stores of vitamin B12 are not laid down during pregnancy or are not available in breastmilk. However, the implications of starting pregnancy and lactation with low vitamin B12 status have not been sufficiently researched.

Publication Types:

• Review

Metabolic complications and neurologic manifestations of vitamin B12 deficiency in children of vegetarian mothers

Cas Lek Cesk. 2001 Nov 22;140(23):732-5

Smolka V, Bekárek V, Hlídková E, Bucil J, Mayerová D, Skopková Z, Adam T, Hrubá E, Kozich V, Buriánková L, Saligová J, Buncová M, Zeman J.

BACKGROUND: Serious hematological, metabolic and neurological complications owing to the nutritional deficiency of vitamin B12 may occur in infants of mothers on a strict vegetarian diet. METHODS AND RESULTS: The mother of the first child was a strict vegetarian. She had an elevated urinary methylmalonic acid level and a low concentration of serum vitamin B12. Her 13-month-old daughter was exclusively breast-fed until the age of 9 month and then she was fed only vegetables. Physical examination revealed psychomotoric retardation, apathy, muscular hypotonia, abnormal movements and failure to thrive. Laboratory analysis showed a megaloblastic anaemia, a low level of vitamin B12 and methylmalonic aciduria. MRI of the brain revealed diffuse frontotemporoparietal atrophy and retardation of myelination. After treatment with vitamin B12 supplements, abnormal movements disappeared and development improved, but a mild generalised hypotonia continued. A cranial MRI 9 months after treatment still showed signs of retardation of myelination. The second patient, an 8 month-old male, son of a strict vegetarian mother too, was referred for investigation of psychomotoric retardation, hypotonia, dyskinesia, failure to thrive and microcephaly. He was breast-fed and from 6 month of age he had also received fruit juices. Laboratory analysis revealed megaloblastic anaemia, high methylmalonic aciduria and homocystinuria. The patient's and his mother's serum level of vitamin B12 were low. After treatment with vitamin B12 supplements, biochemical and metabolic markers of disease were normal but there continued a generalised hypotonia, microcephaly and language delay. CONCLUSION: Our observations emphasize the health complications of nutritional cobalamine deficiency and a requirement of clinical, biochemical and metabolic monitoring in infants within strict vegetarian families.

Publication Types:

• Study

Blood folic acid and vitamin B12 in relation to neural tube defects

Br J Obstet Gynaecol. 1996 Apr;103(4):319-24

Wald NJ, Hackshaw AD, Stone R, Sourial NA.

OBJECTIVE: To determine the relation between blood folic acid and serum vitamin B12 in neural tube defect pregnancies using data from the MRC Vitamin Study and a literature review of all studies. DESIGN: Stored blood samples collected as part of a randomised trial of vitamin supplementation in the prevention of neural tube defects were retrieved from affected pregnancies (cases) and unaffected pregnancies (controls). Four controls were matched with each case by centre, maternal age and duration of storage of the blood sample. The samples had been collected from women at entry to the trial, immediately before the women became pregnant, and at around 12 weeks of pregnancy. Our results were combined with those already published from other studies to obtain an overall assessment of blood folic acid and vitamin B12 in relation to neural tube defects. SETTING: Blood samples were collected as part of the MRC Vitamin Study. The collaborating centres were in the United Kingdom, Hungary, Israel, Australia, Canada and Russia. PARTICIPANTS: Twenty-seven women with neural tube defect pregnancies and 108 matched controls with unaffected pregnancies. RESULTS: Serum and red cell folic acid and serum vitamin B12 levels were lower in the cases than in controls at each of the three occasions when blood samples were collected, but no comparison was significant (P > 0.05). A systematic review of all studies from the literature showed that on average, during the 1st trimester of pregnancy, serum folic acid was 0.6 ng/ml lower in neural tube defect pregnancies (P < 0.01), red cell folic acid was 77 ng/ml lower (P < 0.001) and serum vitamin B12 was 38 ng/l lower (P < 0.001). A logistic regression showed no association between serum B12 and neural tube defects after allowing for serum folic acid. CONCLUSION: our results are consistent with other evidence that folic acid and vitamin B12 levels are lower in women with neural tube defect pregnancies and consistent with evidence from randomised trials which showed that folic acid is protective.

Publication Types:

• Review

Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms

Nutr Rev. 2008 May;66(5):250-5

Dror DK, Allen LH.

Severe vitamin B(12) deficiency produces a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression, which respond remarkably rapidly to supplementation. The underlying mechanisms may involve delayed myelination or demyelination of nerves; alteration in the S-adenosylmethionine:S-adenosylhomocysteine ratio; imbalance of neurotrophic and neurotoxic cytokines; and/or accumulation of lactate in brain cells. This review summarizes the current knowledge concerning infantile vitamin B(12) deficiency, including a pooled analysis of case studies of infants born to mothers with untreated pernicious anemia or a strict vegetarian lifestyle and a discussion of the mechanisms that may underlie the manifestations of deficiency.

Publication Types:

• Review

Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population

Epidemiology. 2007 May;18(3):362-6

Ray JG, Wyatt PR, Thompson MD, Vermeulen MJ, Meier C, Wong PY, Farrell SA, Cole DE.

BACKGROUND: Low maternal vitamin B(12) status may be a risk factor for neural tube defects (NTDs). Prior studies used relatively insensitive measures of B(12), did not adjust for folate levels, and were conducted in countries without folic acid food fortification. In Canada, flour has been fortified with folic acid since mid-1997. METHODS: We completed a population-based case-control study in Ontario. We measured serum holotranscobalamin (holoTC), a sensitive indicator of B(12) status, at 15 to 20 weeks' gestation. There were 89 women with an NTD and 422 unaffected pregnant controls. A low serum holoTC was defined as less than 55.3 pmol/L, the bottom quartile value in the controls. RESULTS: The geometric mean serum holoTC levels were 67.8 pmol/L in cases and 81.2 pmol/L in controls. There was a trend of increasing risk with lower levels of holoTC, reaching an adjusted odds ratio of 2.9 (95% confidence interval = 1.2-6.9) when comparing the lowest versus highest quartile. CONCLUSIONS: There was almost a tripling in the risk for NTD in the presence of low maternal B(12) status, measured by holoTC. The benefits of adding synthetic B(12) to current recommendations for periconceptional folic acid tablet supplements or folic-acid-fortified foods need to be considered. It remains to be determined what fraction of NTD cases in a universally folate-fortified environment might be prevented by higher periconceptional intake of B(12).

Publication Types:

• population-based case-control study

Maternal Western dietary patterns and the risk of developing a cleft lip with or without a cleft palate

Obstet Gynecol. 2007 Aug;110(2 Pt 1):378-84

Vujkovic M, Ocke MC, van der Spek PJ, Yazdanpanah N, Steegers EA, Steegers-Theunissen RP.

OBJECTIVE: To identify maternal dietary patterns in association with a cleft lip or cleft palate or both in the offspring. METHODS: In a case-control study of 203 mothers of a child with a cleft lip or cleft palate and 178 mothers with non-malformed offspring, maternal nutritional intakes were assessed 14 months after the birth of the index child to estimate the preconception intake. We measured serum and red blood cell folate, serum vitamin B12, whole blood vitamin B6, and total plasma homocysteine as biomarkers. Dietary patterns were analyzed by factor analysis. Univariate and multivariate analyses were performed and odds ratios with 95% confidence intervals calculated. RESULTS: Two major dietary patterns were identified. The Western dietary pattern, eg, high in meat, pizza, legumes, and potatoes, and low in fruits, was associated with a higher risk of a cleft lip or cleft palate (odds ratio 1.9; 95% confidence interval 1.2-3.1). This risk remained significant after adjustment for potential confounders of maternal education and smoking at the time of the study, and periconception use of folic acid or multivitamins. This dietary pattern was associated with lower red blood cell folate (P=.02), vitamin B6 (P=.001), vitamin B12 (P=.02), and higher homocysteine (P=.05) concentrations. The use of the Prudent pattern, eg, high intakes of fish, garlic, nuts, vegetables, increased vitamin B12 (P<.001) and serum folate (P=.05) levels, was not associated with cleft lip or cleft palate risk compared with the Western diet. CONCLUSION: The use of the maternal Western diet increases the risk of offspring with a cleft lip or cleft palate approximately two fold. Therefore, dietary and lifestyle profiles should be included in preconception screening programs.

Publication Types:

• case-control study

Case for folic acid and vitamin B12 fortification in Europe

Semin Vasc Med. 2005 May;5(2):156-62

Czernichow S, Noisette N, Blacher J, Galan P, Mennen L, Hercberg S, Ducimetičre P.

The number of pregnancies affected by neural tube defects has been estimated to be 4000/year in Europe, with a higher prevalence in Celtic populations and in women of low socioeconomic status. Since the 1980s, it has been shown that supplementation with folic acid during the periconceptual period reduces the risk of neural tube defects in the fetus. However, in view of the period during which supplementation should be taken (< 4 weeks before conception until 8-10 weeks after) and the fact that in some countries 30-50% of pregnancies are unplanned, a public health initiative based solely on increasing dietary folate intake or recommendations on use of folic acid supplements is likely to be insufficient. Mandatory fortification has been started in 38 countries throughout the world. Several European countries have advocated mandatory flour folic acid fortification over the last 6 years, but none has introduced it. A recent public health decision in Hungary stimulated flour fortification on a voluntary basis, but it remains the only European country to take this action. Many European countries have deferred a decision to introduce fortification because of concerns about possible masking of vitamin B (12) deficiency. This review advocates a proposal for combined fortification of folic acid and vitamin B (12) to address possible hazards of fortification with folic acid alone.

Publication Types:

• Review

Vitamin B12 metabolism and status during pregnancy, lactation and infancy

Adv Exp Med Biol. 1994;352:173-86

Allen LH.

This overview of vitamin B12 metabolism and requirements during the continuum of pregnancy and lactation has identified several gaps in our knowledge. More information is needed concerning the roles of the different transcobalamins during pregnancy and lactation, including their impact on placental and mammary transfer of cobalamin and their effect on intestinal absorption in the infant. Knowledge is needed about the relative importance of maternal stores and current dietary intake on fetal storage of the vitamin, and on its concentration in breast milk. Because there is some evidence that infant's urinary methylmalonic acid excretion is reduced by intakes slightly higher than the current RDA, the adequacy of the current RDA for vitamin B12 during infancy should be verified. Finally, it is possible that vitamin B12 deficiency is more common in pregnant and lactating women and their young children in developing countries than has been recognized previously, due primarily to malabsorption. It is important to confirm whether or not this is the case, in view of its potential impact on infant neurobehavioral development and the relative ease with which supplements of the vitamin could be provided.

PIP: Vitamin B12 metabolism and requirements during pregnancy and lactation are reviewed. Pregnant women who have been strict vegetarians for only a few years, and even those who consume low amounts of animal products, are more likely to become vitamin B12 deficient during pregnancy and lactation, to give birth to an infant who develops clinical or biochemical signs of B12 deficiency, and/or to have low levels of this vitamin in their breast milk. Populations that consume large amounts of animal products ingest 3-32 mcg/day, compared to 0-0.25 mcg/day for strict vegetarians. Changes in B12 metabolism during pregnancy affect intestinal absorption, changes in plasma concentrations, and placental transport. The recommended dietary allowance (RDA) during pregnancy is an increase from 2.0 mcg/day to 2.2 mcg/day to cover fetal storage. The World Health Organization (WHO) advises an increase of 0.4 mcg/day to a total of 1.4 mcg/day. Vitamin B12 metabolism during lactation involves the mechanism of secretion and forms in milk. For lactating women the WHO recommends that intake be increased by 0.3 mcg/day to a total of 1.3 mcg/day, while the RDA is increased from 2.0 to 2.6 mcg/day. There is some evidence that the infant's urinary methylmalonic acid excretion is reduced by intakes slightly higher than the current RDA, therefore the adequacy of the current RDA for vitamin B12 during infancy should be verified. More information is needed concerning the roles of the different transcobalamins during pregnancy and lactation, including their impact on placental and mammary transfer of cobalamin and their effect on intestinal absorption in the infant. Knowledge is also needed about the relative importance of maternal stores and current dietary intake on fetal storage of the vitamin, and on its concentration in breast milk. It is possible that vitamin B12 deficiency is more common in pregnant and lactating women and their young children in developing countries than has been recognized previously, primarily because of malabsorption.

Publication Types:

• Review

Publication Types:

• Review