Of the approximate 1000 mg ofiron required for normal pregnancy, about 300 mg is actively transferred to the fetus and placenta, and another 200 mg is lost through various normal excretion routes, primarily the gastrointestinal tract. These are obligatory losses and accrue even when the mother is iron deficient. The average increase in the total circulating erythrocyte volume-about 450 mL-requires another 500 mg. Recall that each 1 mL oferythrocytes contains 1.1 mg of iron.
As shown in Figure 4-6, because most iron is used during the latter halfofpregnancy, the iron requirement becomes large after midpregnancy and averages 6 to 7 mg/d (Pritchard, 1970). In most women, this amount is usually not available from iron stores or diet. Thus, without supplemental iron, the optimal rise in maternal erythrocyte volume will not develop, and the hemoglobin concentration and hematocrit will fall appreciably as plasma volume rises. At the same time, fetal red cell production is not impaired because the placenta transfers iron even if the mother has severe iron-deficiency anemia. In severe cases, we have documented maternal hemoglobin values of 3 gldL, and at the same time, fetuses had hemoglobin concentrations of 16 gldL. The mechanisms of placental iron transport and regulation are complex (Koenig, 2014; McArdle, 2014).
Ifthe nonanemic pregnant woman is not given supplemental iron, then serum iron andferritin concentrations decline atermidpregnancy. Importantly, hepcidin levels drop early in pregnancy (Hedengran, 2016; Koenig, 2014). s noted, lower hepcidin levels aid iron transfer into the maternal circulation via ferroportin in enterocytes. Lower hepcidin levels also augment iron transport into the fetus via ferroportin in syncytiotrophoblast.
With normal vaginal delivery, 500 to 600 mL of blood is typically lost, and thus not all the maternal iron added in the form of hemoglobin is spent (Pritchard, 1965). he excess hemoglobin iron becomes stored iron.
Pregnancy is associated with suppression of various humoral and cell-mediated immunological functions (Chap. 5, p. 95). his permits accommodation of the "foreign" semiallogeneic fetal graft that contains antigens of both maternal and paternal origin (Redman, 2014). he tolerance that exists at the maternal-fetal interface remains a great unsolved medical mystery. This tolerance is complex and involves certain immune system adaptations and crosstalk among the maternal microbiome, uterine decidua, and trophoblast. In particular, areas of the uterus that were previously considered sterile are colonized with bacteria. In most cases, these microbes are believed to be commensal and play a tolerizing and protective role. Indeed, commensal organisms may inhibit the proliferation of certain pathogens. Several reviewers have described these relationships (Mor, 2015; Racicot, 2014; Sisti, 2016).
tection at the maternal-fetal interface involves the expression of the trophoblast. Recall that all cells of the body express a "badge" immune responses. For most cells of the body, this "badge" is known as MHC Class Ia. However, it is uncommon for two unrelated individuals to share compatible MHC class Ia. This creates a potential problem for reproduction because half of the fetus is composed of paternally derived antigens. To circumvent this problem, trophoblast cells express a form of MHC that does not vary between individuals. This "nonclassic" MHC is known as human leukocyte antigen class Ib and includes HLA-E, HLA