Cobalamin Status from Pregnancy to Early Childhood: Lessons from Global Experience

Abstract

Low cobalamin intake and status during pregnancy or lactation have been linked to adverse maternal and perinatal health outcomes, whereas low cobalamin status during early childhood is associated with impaired development in children. Women who begin pregnancy with depleted stores (low or very low plasma cobalamin) will give birth to depleted infants who are likely to develop deficiency symptoms during the first few weeks or months postpartum. Newly ingested cobalamin during pregnancy and lactation (from diet or supplements) is transferred to the child and is not likely to correct cobalamin status in depleted women. The prevalence of low cobalamin status is high especially in low-income settings or in populations with a low intake of animal products. Folate and cobalamin play interdependent roles in one-carbon metabolism. Although folic acid supplementation during early pregnancy is widely recommended and practiced, cobalamin supplementation during pregnancy and lactation has received little attention. Furthermore, the intake recommendations for pregnant and lactating women and in early life need reevaluation in the light of newly available evidence in the field.

Laboratory assessment of folate (vitamin B9) status

“…The pregnancy-related cut-offs may be further categorised by trimesters. Lower tHcy concentrations in the first trimester reflect the intake of folic acid and haemodilution, while higher tHcy concentrations in the third trimester are reflective of lowering of B 12 status 94. tHcy 3.7–6.9 (first), 2.7–7.2 (second) and 2.4–9.6 (third trimester) µmol/L are examples of pregnancy-specific reference ranges recently established by the authors 95…”

Time course of serum cobalamin, folate, and total iron binding capacity concentrations in pregnant bitches and association with hematological variables and survival

“…1 Cobalamin and folate tissue demand greatly increase during pregnancy in women, as reflected by elevated serum methylmalonic acid and homocysteine concentrations, even in face of normal cobalamin and folate concentrations. 16,17 Therefore, the reference intervals for cobalamin in nonpregnant women might not apply to pregnant ones, and cobalamin supplementation might help ameliorate PRA, even in normocobalaminemic pregnant women. 26 Additionally, maternal cobalamin reserves are highly diet-dependent, 16 as the diet serves as the main cobalamin intake source, and preexisting vitamin deficiencies reduce maternal-fetal cobalamin transport, thereby increasing the risk of fetal complications.…”

“…In women, the frequencies of hypocobalaminemia, hypofolatemia and ID progressively increase during pregnancy. 1,11,12,[15][16][17][18][19] Deficiencies thereof bear direct deleterious ramifications on various tissues, including fetal central nervous system, irrespective of PRA. 16,19 Consequently, daily oral iron and folic acid supplementation is routinely recommended to pregnant women by the World Health Organization as part of the antenatal care, notwithstanding the lack of robust evidence to support this practice.…”

Maternal and infant vitamin B12 status and development

“…Maternal B12 status is an important determinant of the B12 status of the infant during gestation and also later: infants that are breastfed have markedly lower B12 status than nonbreastfed infants (reviewed in refs. 5,12,13 ). A low B12 status even occurs in infants that are only intermittently breastfed compared with those not breastfed.…”

“…Low B12 status in the mother has been associated with several adverse outcomes in the child. 5,13,16,17 It is not often recognized that low-normal periconceptual B12 status leads to an increased risk of neural tube defects. [18][19][20] In countries that have fortified flour with folic acid, low B12 status is a likely cause of some of the residual neural tube defects.…”