Maternal Stress During Pregnancy Predisposes for Iron Deficiency in Infant Monkeys Impacting Innate Immunity

Abstract

ABSTRACT:The influence of maternal stress during pregnancy on the postpartum iron status and immune maturation of infants was investigated in a nonhuman primate model. Forty infant rhesus monkeys were generated from two types of disturbed pregnancies, early or late gestation stress, and compared with 24 undisturbed controls. Prenatal stress increased the prevalence and magnitude of iron deficiency (ID) as the infants' growth-related demands for iron exceeded dietary intake from breast milk. At 4 -6 mo of age, the emergence of ID significantly accentuated an effect of prenatal stress on natural killer cell activity, an important component of innate immunity. These findings indicate that maternal stress, especially early in pregnancy, should be added to the list of risk factors that warrant closer scrutiny of hematological profiles in fast-growing babies. (Pediatr Res 61: 520-524, 2007) I D is a major nutritional problem affecting 1-2 billion people worldwide (1). The anemia caused by ID is very common in women due to the hematological demands of menstruation and pregnancy and is particularly prevalent in young infants, who also have high iron needs (2,3). To meet the iron requirements of a rapidly growing baby, many mammalian species, including humans, have evolved a two-stage transmission process, providing significant amounts of iron before birth via placental transfer, and the remainder postpartum through breast milk. As a consequence, if iron stores in the form of Hb and ferritin are low at birth, dietary iron intake from milk will often prove to be inadequate by 2-4 mo of age (4). These babies are then at greater risk for developing the "early anemia of childhood," which typically becomes evident at 4 -8 mo of age (5).Although the use of fortified formulas has reduced the prevalence of ID, it continues to impact 3-4% of 1 y olds in the United States and up to 8 -17% of infants in high-risk populations (6 -8). ID is also more likely to occur in babies provided only breast milk past the first year of age or in families that rely on bottle-feeding with cow's milk for economic or cultural reasons (9).Considerable evidence points to prenatal factors as predisposing and significant contributors to the development of ID (10). Because the bulk of maternal iron is transferred in the last month of pregnancy, babies born premature have low stores, and their iron needs are more likely to exceed the capacity of dietary intake (11). Similarly, small-forgestational age neonates and growth-restricted twins and triplets, who then undergo a compensatory growth spurt, are at higher risk (12,13). Recently, it was discovered that babies gestated by women who had developed pregnancy-induced diabetes or hypertension are also predisposed to ID (14,15). Rodent models suggest further that high alcohol consumption during pregnancy can compromise iron regulation in the offspring (16). Information about the importance of these prenatal factors has not been widely disseminated to pediatricians, and thus some high-risk babies may be ID fo...

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

“…An additional peripheral blood sample was collected at the same time point to determine total number of leukocytes, lymphocytes, as well as lymphocyte subpopulations [CD3 − /CD19 + (B cells), CD3 + /CD4 + (T-helper cells), CD3 + /CD8 + (T-cytotoxic cells), CD3 − /CD16, 56 + (NK cells); methods described in ref. 32)]. PSG and CG subjects did not differ significantly in any of these measures.…”

“…One important question that has yet to be addressed to our awareness is whether exposure to stress during intrauterine development can produce variations in telomere length, thereby potentially setting up a long-term trajectory at birth that defines or contributes to individual susceptibility for complex, common age-related diseases. Stress exposure during fetal development is an important factor shaping adult health and has been linked to adverse outcomes including, but not limited to, immune, endocrine, and metabolic dysregulation and related disorders (29)(30)(31)(32)(33)(34). However, we are aware of no studies to date that have examined the relationship between prenatal stress exposure and telomere length.…”

Risk of Cancer among the Offspring of Women Who Experienced Parental Death during Pregnancy

“…A major limitation was that the mechanisms of the possible oncogenic effects of psychosocial stress have not been established (1,3,4,11). Moreover, these are likely to be highly variable because individuals react and cope differentially with major stressors (12).…”

Influence of prenatal maternal stress on umbilical cord blood cytokine levels

“…Evidence from rats, swine, and macaques indicates that PNMS affects innate immunity as reflected by altered NK cell and macrophage function (Coe et al 2007;Kay et al 1998;Tuchscherer et al 2002). Also, several animal studies suggest a stress-induced immune imbalance: selectively skewing the system toward suppressed Th1-mediated cellular and/or enhanced Th2-mediated humoral, immune responses (Pincus- Knackstedt et al 2006;Veru et al 2014).…”