During pregnancy, micronutrient requirements increase more than those of macronutrients, and inadequate intakes (and, thus, a low nutritional quality of the diet) can have significant consequences for both the mother and the developing fetus. In particular, there is evidence to support the physiologic role played by selected minerals and vitamins [12
Involved in numerous enzymatic processes, iron (the foremost constituent of hemoglobin, myoglobin and various enzymes) plays essential roles in the transfer of oxygen to tissues. Iron deficiency causes anemia, a very common condition worldwide, affecting 22% of women of childbearing age in Europe and as much as 50% in developing countries [33
]. In addition, iron deficiency is frequent in children between 6 and 36 months of age [34
Meat and fish, but also legumes and green leafy vegetables are the main dietary sources of iron. In Italy, most dietary iron is found in a non-heme form, the absorption of which is closely linked to the overall composition of the diet and the individual nutritional status. For example, phytates and polyphenols are able to inhibit the absorption of non-heme iron, which is favored by ascorbic acid or by the consumption of meat and fish. In general, the human body is able to absorb 2%–13% of non-heme versus about 25% of heme iron [7
During pregnancy, iron requirement progressively increases until the third month, in parallel with the accumulation in fetal tissues. The transfer from the maternal compartment to the fetus is regulated by a complex mechanism of transport that include: release from maternal liver—in which it is stored as ferritin—into circulation as Fe2+
, uptake by the placenta, transfer to the fetus (by a specific protein), oxidation to Fe3+
, storage (as ferritin) or transport into the fetal circulation (still bound to transferrin) [35
Inadequate intakes during pregnancy associated with the increase of iron demand makes pregnant mothers at even greater risk of iron deficiency, that may affect growth and development of the fetus and increase the risk of preterm delivery, low birth weight and post-partum hemorrhages [36
]. Moreover, according to some recent studies, inadequate iron intakes during pregnancy are associated with increased cardiovascular risk for the offspring in adulthood [38
In fact, iron supplementation in pregnancy is often recommended to improve pregnancy and birth outcomes [35
]. On the other hand, an excessively high iron intake may expose women to oxidative stress, lipid peroxidation, impaired glucose metabolism, and gestational hypertension [40
]. International recommendations in terms of intake levels range from the 27 mg per day for all pregnant women as advised by the Center for Disease Control and Prevention and the WHO to the 30–60 mg as advised by the Italian RDA (Table 2
The immediate postpartum period is characterized by maternal susceptibility to anemia because of blood loss at delivery even in industrialized countries, where almost 50% of women require iron supplementation. However, the amount of iron secreted in milk is quite small and the WHO and FAO indications support a reduced supply of iron during breastfeeding to compensate for amenorrhea. Eleven mg per day should therefore be recommended and increased to 18 mg/day after the resumption of menstruation.
Iodine is a major component of thyroid hormones and is essential for their functions, namely growth, formation and development of organs and tissues, in addition to the metabolism of glucose, proteins, lipids, calcium and phosphorus, and thermogenesis. Iodine is mostly found in organic form in the body, bound to thyroglobulin. The inadequate availability of iodine causes deficiency of circulating thyroid hormones, increase of pituitary thyroid stimulating hormone (TSH) and the consequent hypertrophy of the thyroid gland (goiter) [42
Fish and shellfish are the main food sources of iodine, receiving it from the algae they eat, that absorb the mineral from marine water. However, due to water evaporation and rain, iodine is also absorbed by the soil and, consequently, enters into water, fruits, vegetables, and—in relevant concentrations—in milk, eggs and then meat (to a variable extent).
The average daily intake of iodine in the general population is less than that indicated by WHO, at the European level, where iodine deficiency affects mainly the child population [43
], and all over the Italian territory (85–88 µg/day vs. 150 µg/day) [44
In pregnancy, iodine deficiency can increase the risk of spontaneous abortion, perinatal mortality, birth defects and neurological disorders [45
], and is considered by the WHO as the most important preventable cause of brain damage.
In the general population, iodine deficiency can be prevented by supplementing the diet with adequate amounts of this mineral, for example by using iodized salt.
During pregnancy, when iodine is necessary also for the production of fetal thyroid hormones (as the fetal thyroid begins to function only around the twelfth week of gestation), women need to increase iodine intake by about 50% [46
Moreover, even in conditions of only mild or moderate iodine nutritional deficiency, the fetus and the newborn (especially preterm born) have a much higher risk of developing hypothyroidism compared to all other age groups (National Observatory for the Monitoring of Iodoprophylaxis in Italy). The most critical period goes from the second trimester of pregnancy to the third year of extrauterine life. Adequate supplementation with iodine, from pre-conception and until the end of the first trimester of pregnancy, reduces—up to 73%—the incidence of cretinism in the areas of highest deficiency risk [48
]. The estimated amount that would avoid deficiency is 200 µg/day (compared to 150 µg/day for adults) according to the EFSA, or 250 µg/day according to the WHO/UNICEF joint document [49
]. Two hundred µg/day are recommended also during lactation, to ensure a milk content of about 100–150 µg/100 mL.
As the most abundant mineral in the human body, 99% located in the skeleton and in the teeth, calcium is critical to reach the peak bone mass in the first decades of life, to maintain bone mass in adulthood, and to slow the physiological age related reduction of bone mineral density.
Calcium deficiency may be worsened by genetic and hormonal factors along with insufficient physical activity. Calcium metabolism also requires vitamin D, the lack of which can also be due to calcium deficiency: in both cases, the result is a reduced mineralization of the bone matrix. Inadequate levels of calcium in children can result in rickets [50
The main sources of calcium are milk and derivatives (about 50%), followed by cereals and vegetables (11% each) [51
]. The bioavailability of calcium from these foods is different, being highest for milk and derivatives and for mineral water. Conversely, bioavailability from fiber- and phytate-rich vegetables is quite low. The efficiency of calcium absorption from food affects calcium concentrations in the body, which remains constant from adolescence to adulthood and decreases in post-menopausal women, by 2% every 10 years [50
The EPIC (European Prospective Investigation into Cancer and Nutrition) study has shown a wide variability in calcium levels among the different European populations, with the lowest values in Italian women [52
]. According to the results of the Italian survey INRAN-SCAI 2005-06, calcium intake in the Italian population corresponds to 76% of the recommendations [53
Calcium is essential for fetal development. The requirement increases during pregnancy (from 50 mg/day at the halfway point, up to 330 mg/day at the end) and lactation, due to the mobilization from the maternal skeleton, the greater efficiency of intestinal absorption and the increased renal retention [54
]. High birth weight, reduced risk of preterm delivery, and better blood pressure control are also associated with an adequate calcium intake during pregnancy. The transport of calcium from the maternal compartment to the fetus takes place through active transporters in the epithelial layer of the placenta. From the 20th week of pregnancy, calcium levels in the fetal circulation are higher than those detectable in the maternal plasma.
The recommendations for calcium intake are different in different countries, also for pregnant and breastfeeding women. The Italian RDA indicate PRI values of 1.2 g/day in the gestational period, while the WHO recommends 1.5–2.0 g/day from the 20th week until the end of pregnancy, especially for women at risk of gestational hypertension.
It has been proposed that a low-dose supplementation with calcium during pregnancy reduces the risk of developing both gestational hypertension and pre-eclampsia [55
]. However, excessively high levels correlate with increased risk of developing HELLP (Haemolysis, Elevated Liver enzymes and Low Platelets) syndrome.
The daily amount of calcium secreted in breastmilk is quite variable (150 to 300 mg/day), mainly depending on the mobilization from bones and the reduced urinary secretion. Calcium stores in maternal bones are restored after weaning and the recovery of ovarian function [56
Some studies have shown that calcium secretion in milk is substantially independent of its dietary intake and of supplementation. Therefore, the recommended intake during lactation is not different from that of the healthy adult female population (1.0 g/day). However, women with dietary calcium intakes lower than 300 mg/day and adolescents, with high basal requirements (1.2 g/day according to the RDA) are at risk of deficiency also during lactation.
3.4. Vitamin D
The term vitamin D comprises the two main molecular species that share vitamin activity: cholecalciferol (vitamin D3, derived from cholesterol and synthesized by the animal organisms) and ergocalciferol (vitamin D2, derived from ergosterol, found in vegetables).
The circulating levels of vitamin D are only partly affected by the dietary intakes. In fact, only the first of the two hydroxylation processes occurring in vitamin D metabolism (e.g., that responsible for the production of 25-hydroxy-vitamin D) is modulated by the dietary contribution to some extent (the increase of circulating levels is not proportional to the amount ingested). The hydroxylation into 1,25-hydroxy-vitamin D in the proximal renal tubules is closely regulated by feedback mechanisms and primarily depends on the requirement for calcium and phosphorus [57
The endogenous synthesis of vitamin D requires exposure to ultraviolet radiation with a wavelength between 290 and 315 nm, and is influenced by several factors, related to both the individual’s characteristics (such as sex and phenotype, weight), and environmental factors (the degree of physical activity, latitude, season, time of exposure to sunlight, pollution, use of sunscreens and supplements). With aging, the synthesis of vitamin D in the epidermis layer becomes less efficient; also, diseases associated with intestinal malabsorption, such as celiac disease, Crohn’s disease, cystic fibrosis, ulcerative colitis, liver and kidney disorders and some pharmacological treatments, may contribute to the development of vitamin D deficiency [57
Vitamin D deficiency is common in Italy too [52
], in the geriatric population and during winter. Higher intakes may be required for obese subjects, due to the high depots of the vitamin in adipose tissue [58
High amounts of vitamin D are contained in cod liver oil. Fish (especially fatty fish such as herring and salmon) are also major food sources, while pork liver, eggs, butter, high fat cheeses provide smaller amounts, but relevant to the total intake.
In the first stage of pregnancy, vitamin D (mainly Vitamin D3, the predominant form in the maternal blood) is involved in the regulation of cytokine metabolism and in the modulation of the immune system, thereby contributing to the embryo implantation and regulating the secretion of several hormones.
Vitamin D deficiency in mothers and breastfed infants was observed several decades ago in some Nordic countries, especially in winter, because of the lack of natural light [59
]. However, vitamin D deficiency is very common during pregnancy even in countries with sunny climates and is associated with an increased risk of developing pre-eclampsia and gestational diabetes mellitus. The season of birth, ethnicity, and maternal prophylaxis during pregnancy affect the vitamin D status of infants. Low birth weight, impaired skeletal development, and respiratory infections and allergic diseases in the early years of life are often associated with inadequate contribution of vitamin D from the mother’s diet.
According to a recent systematic review, maternal supplementation during pregnancy reduces the risk of pre-eclampsia as well as preterm delivery and low birth weight [60
Despite the lack of consensus on adequate intakes among different countries (Table 3
), supplementation with vitamin D is recommended for all pregnant women at a dose of 600 IU/day (15 µg/day) [57
In women at risk for vitamin D deficiency, the recommendations should be reach 1000–2000 IU/day. Prophylaxis with vitamin D should be planned from the beginning and throughout the pregnancy, as underlined also in the recent consensus document from the Italian pediatric societies [61
Given the influence of sunlight exposure on vitamin D metabolism, attention to ethnic groups with hyper-pigmented skin or with little exposure to sunlight should be paid also during lactation. Moreover, the habitual dietary intake of vitamin D may be limited in specific conditions of higher requirements and in areas and/or countries with little availability of food sources [62
]. Breastmilk, in fact, contains amounts of vitamin D (<80 IU/L) that are insufficient for deficit prevention in the first year of life [63
]. An intake of 15 µg/day (600 IU/day), e.g., in women of childbearing age, is therefore needed to meet the requirement for vitamin D during breastfeeding, as highlighted in the aforementioned consensus document. These levels can be increased up to 1000–2000 IU/day for the whole breastfeeding period in presence of risk factors for deficiency.
3.5. Folic Acid
Folates play a crucial role in many metabolic reactions such as the biosynthesis of DNA and RNA, methylation of homocysteine to methionine, and amino acid metabolism. In fact, metabolically active forms of folates act as transport co-enzymes facilitating the transfer of carbon units from one compound to another. They are therefore essential for health: inadequate dietary levels can give rise to anemia, leucopenia, and thrombocytopenia [64
Folates are mostly found in green leafy vegetables, fruits (such as oranges), cereals and offal. Their bioavailability from foods depends on the presence of anti-nutrients, which can reduce their absorption.
The requirement for folates undergoes a progressive increase throughout the periconceptional period, in association with the use for the development of cells and fetal tissues [65
]. Maternal supplementation with folic acid is widely recommended to all women of childbearing age, especially to reduce the risk of neural tube defects [66
]. According to recent studies, folic acid supplementation during pregnancy should also reduce the risk of congenital heart disease and support proper development of the placenta [68
The RDA during pregnancy increases by 50% for pregnant as compared with non-pregnant women of childbearing age (600 µg/day vs. 400 µg/day). Ideally, supplementation should begin two months before conceiving and even reach 800 µg/day [69
]. The use of folic acid-based supplements is considered as safe [65
]. The benefits of higher amounts are unclear.
The folate concentrations in breastmilk increase progressively from colostrum to mature milk, reaching much higher levels than those measured in maternal plasma. The absence of a correlation between maternal status and breastmilk content suggests an active role of the mammary glands in the transport and regulation of folate secretion, only marginally influenced by dietary intakes [70
Intakes of folates by the breastfeeding mother should be increased by 25%, up to 500 µg/day [71