Plasma Ceramides and Triglycerides Are Elevated during Pregnancy in Association with Markers of Insulin Resistance in Hutterite Women.

Changes in maternal insulin sensitivity and circulating lipids typically occur during the metabolic transitions of pregnancy and lactation. Although ceramides can cause insulin resistance in mammals, their potential roles during pregnancy and lactation are unknown. We hypothesized that changes in lipids like ceramide and triglycerides could occur across different reproductive states and relate to insulin resistance. Our objectives were to comprehensively characterize lipids in the plasma of pregnant, lactating, and nonpregnant and nonlactating (NPNL) women, and to evaluate the relationship between ceramides and the triglyceride index, a proxy of insulin resistance. Middle-aged Hutterite women from the South Dakota Rural Bone Health Study were classified by reproductive status as nonpregnant and nonlactating (NPNL; 19 observations), pregnant (14 observations), or lactating (31 observations). Several plasma lipids were elevated in pregnancy such as ceramides, triglycerides, and total- and high-density lipoprotein cholesterol. The triglyceride index was highest during pregnancy and was positively associated with long- and very long-chain ceramides. Lipidomics revealed lipid signatures specific to reproductive state, including triglycerides, phosphatidylcholines, sphingomyelins, and cholesteryl esters, which were also related to the triglyceride index. Our data support the possibility that ceramides contribute to the development of insulin resistance during pregnancy, and reveal distinct lipid signatures associated with pregnancy and lactation

ajcn037523 789..800

ABSTRACT Background: Folate dose-response studies in women of childbearing age who consumed a folic acid (FA)-containing multivitamin in the era of FA fortification are lacking. Objective: We sought to investigate folate-status response to a known folate dose comprising an FA-containing prenatal supplement (750 mg/d) plus natural food folate (400 mg/d) in third-trimester pregnant women, lactating women 5-15 wk postpartum, and nonpregnant women. Design: Pregnant (n = 26), lactating (n = 28), and nonpregnant (n = 21) women consumed the study folate dose under controlled intake conditions for 10-12 wk. Blood, urine, and breast milk were collected at baseline, study midpoint, and study end. Results: Study-end serum total folate concentrations averaged w30 ng/mL and did not differ by physiologic group (P = 0.876). Studyend urinary folate excretion represented w9-43% of total folate intake and ranged from 100 to 500 mg/d. Third-trimester pregnant women excreted less urinary folate than did lactating (P = 0.075) and nonpregnant (P , 0.001) women. Lactating women excreted less (P , 0.001) urinary FA than did nonpregnant women. Breastmilk total folate concentrations remained constant (P = 0.244; 61.8 ng/mL at study end), whereas breast-milk FA concentrations increased (P = 0.003) to 24.1 ng/mL at study end. Conclusions: The consumption of the study folate dose yielded a supranutritional folate status regardless of the physiologic state. Based on urinary folate excretion, folate use was greatest to least: pregnant . lactating . nonpregnant women. Breast-milk folate species were responsive to maternal folate intake, and FA made up w40% of breast-milk total folate at study end. These findings warrant revisiting prenatal supplement FA formulation in populations exposed to FA-fortification programs. This trial was registered at clinicaltrials.gov as NCT01127022. Am J Clin Nutr 2012;96:789-800

Human Milk for Vulnerable Infants: Breastfeeding and Milk Sharing Practice among Ghanaian Women

Human milk has the best impact on childhood survival. In Ghana, it is estimated that 43% of women exclusively breastfeed for 0–5 months and only 42% of breastfeeding mothers continue through 20–23 months. Although the Ghanaian government has implemented policies to facilitate exclusive breastfeeding, substantial gaps to achieve optimal newborn health and wellbeing remain. The purpose of this study was to evaluate breastfeeding prevalence and human milk sharing practices among Ghanaian women. Qualitative responses were received from Ghanaian females (n = 1050). In our sample, 81% indicated they breastfed their children and 8% reported ever sharing breastmilk with another mother. Reasons for sharing milk included (i) insufficient breastmilk production of the recipient mother, and (ii) mother’s unavailability prompting women to offer their milk to a crying baby. About 60% of our sample reported that they were not concerned about sharing their milk. Findings present a strong indicator for milk donation towards the establishment of a human milk bank in Ghana. Health promotion efforts should aim at increasing education about the risks involved in milk sharing as well as the benefits of human milk donation through formal and safer channels such as a Human Milk Bank

Pregnancy Induces Transcriptional Activation of the Peripheral Innate Immune System and Increases Oxidative DNA Damage among Healthy Third Trimester Pregnant Women

<div><h3>Background</h3><p>Pregnancy induces physiological adaptations that may involve, or contribute to, alterations in the genomic landscape. Pregnancy also increases the nutritional demand for choline, an essential nutrient that can modulate epigenomic and transcriptomic readouts secondary to its role as a methyl donor. Nevertheless, the interplay between human pregnancy, choline and the human genome is largely unexplored.</p> <h3>Methodology/Principal Findings</h3><p>As part of a controlled feeding study, we assessed the influence of pregnancy and choline intake on maternal genomic markers. Healthy third trimester pregnant (n = 26, wk 26–29 gestation) and nonpregnant (n = 21) women were randomized to choline intakes of 480 mg/day, approximating the Adequate Intake level, or 930 mg/day for 12-weeks. Blood leukocytes were acquired at study week 0 and study week 12 for microarray, DNA damage and global DNA/histone methylation measurements. A main effect of pregnancy that was independent of choline intake was detected on several of the maternal leukocyte genomic markers. Compared to nonpregnant women, third trimester pregnant women exhibited higher (<em>P<0.05</em>) transcript abundance of defense response genes associated with the innate immune system including pattern recognition molecules, neutrophil granule proteins and oxidases, complement proteins, cytokines and chemokines. Pregnant women also exhibited higher (<em>P</em><0.001) levels of DNA damage in blood leukocytes, a genomic marker of oxidative stress. No effect of choline intake was detected on the maternal leukocyte genomic markers with the exception of histone 3 lysine 4 di-methylation which was lower among pregnant women in the 930 versus 480 mg/d choline intake group.</p> <h3>Conclusions</h3><p>Pregnancy induces transcriptional activation of the peripheral innate immune system and increases oxidative DNA damage among healthy third trimester pregnant women.</p> </div

Select list of genes involved in defense response that were upregulated in third trimester pregnant women at the end of the controlled feeding study.

<p><i>P</i> values<0.05 with or without adjusting for leukocyte sub-populations as analyzed with general linear models or the LEMMA statistical package, respectively. Fold change was calculated as the average transcript abundance in pregnant women/the average transcript abundance in nonpregnant women.</p

Hierarchical clustering of differentially expressed immune defense genes (GO: 0006952) in pregnant versus nonpregnant women.

<p>This figure presents the hierarchical clustering of 112 differentially expressed immune defense genes in third trimester women versus nonpregnant women (reference group) at the beginning and end of the controlled feeding study. Color scheme: blue represents low expression and yellow represents high expression. n = 12 for pregnant women; n = 10 for nonpregnant women. Analyzed with Euclidean distances using MultiExperiment Viewer.</p

Genes involved in adaptive immune response that were downregulated in third trimester pregnant women at the end of the controlled feeding study.

<p><i>P</i> values<0.05 with or without adjusting for leukocyte sub-populations as analyzed with general linear models or the LEMMA statistical package, respectively. Fold change was calculated as the average transcript abundance in pregnant women/the average transcript abundance in nonpregnant women.</p

Peripheral blood leukocyte counts in third trimester pregnant women and nonpregnant women at the beginning and end of the controlled feeding study.

<p>Data were analyzed using general linear models.</p

Venn diagram of differentially expressed genes by pregnancy.

<p>This figure presents the number of genes differentially expressed in third trimester pregnant versus nonpregnant women at study-baseline (circle on the left) and study-end (circle on the right). The number of genes altered both at study-baseline and study-end are presented in the intersecting area of the two circles. Color scheme: blue represents low expression and yellow represents high expression. n = 12 for pregnant women; n = 10 for nonpregnant women. Analyzed with the LEMMA statistical package.</p