Table 4 Factors related to use of a single or multimicronutrient periconceptional supplements

General points:

General points:

(a) Potential negative interactions between multiple nutrients [107] (b) Identification of the gestational timing of specific nutrient effects (c) Allows specific hypotheses to be tested as single nutrient effects can be identified, e.g., calcium supplementation and pre-eclampsia [108], or folic acid and neural tube defects (d) Preferred for assessment of dose–response associations (e) Facilitates safety and adverse outcome assessments, e.g., infection risk with iron supplementation (NIH), or folate use and cancer risk [109]

(a) Nutrient synergisms enhance potential benefits [110] (b) Theoretical need for multiple nutrients from early in gestation, and for normal placentation (c) Balanced supply of carbohydrates, lipids, proteins and vitamins is critical to meet fetal and maternal energy needs, and for substrates for metabolic pathways [104, 111] (d) Unlikely single nutrient intervention will improve placental function, as combined deficiencies are common in low resource settings, and combination of nutrients potentially ameliorates several underlying nutrient deficiencies (e) Requirement for ideal mixture of functional amino acids and micronutrients to regulate key metabolic pathways [82] (f) Optimal nutrition from early in pregnancy may help ameliorate need for advanced therapies of neonatal care in low resource settings (g) Greater increase in body stores of nutrients than with single nutrient supplementation

For iron:

Specific multimicronutrient effects:

(a) Targets pre-existing iron deficiency anaemia and addresses need to enter pregnancy with adequate iron stores [112] (b) Data from experimental animals that iron status early in gestation may effect auditory responsiveness [113] (c) Assessment of specific interactions related to safety, e.g., iron-infection interactions influencing susceptibility to infection [14]

(a) Vitamins B2, B6, B12, magnesium and iron combined with folic acid may have greater protective effect in reducing risk of neural tube defects [30, 35, 114] (b) Benefits in improving content of breast milk for several nutrients [115] (c) Nutrient-nutrient synergisms may enhance iron absorption [116] (d) Folate and other vitamins measured longitudinally in pregnancy have values mostly below recommended levels [64], and accelerated breakdown suggested in addition to haemodilution [117] (e) Observational studies for less growth restriction and reduced pre-term birth with regular periconceptional multivitamins [118] (f) Evidence for improved birth weight with later gestational supplementation [8]

For folate:

(a) Specific maternal and fetal metabolic enzyme polymorphisms can be targeted (e.g., methyl tetrahydrofolate reductase) [64] (b) Folate requirements increase steeply once the chorioallantoic placenta is formed and the fetal heart starts perfusion (about 22 days after fertilisation) (c) Folate and vitamin B12 linked to utero-placental vascular resistance [119]

For iodine:

(a) Mild to moderate iodine deficiency may influence cognitive development [102]

Placental and genetic

(a) Specific nutrients may be involved in expression of genes involved in placental function and cell cycle processes [120] (b) Identification of factors controlling trophoblast turnover from immature to mature villi