Maternal Zinc Intakes and Homeostatic Adjustments during Pregnancy and Lactation

Zinc plays critical roles during embryogenesis, fetal growth, and milk secretion, which increase the zinc need for pregnancy and lactation. Increased needs can be met by increasing the dietary zinc intake, along with making homeostatic adjustments in zinc utilization. Potential homeostatic adjustments include changes in circulating zinc, increased zinc absorption, decreased zinc losses, and changes in whole body zinc kinetics. Although severe zinc deficiency during pregnancy has devastating effects, systematic reviews and meta-analysis of the effect of maternal zinc supplementation on pregnancy outcomes have consistently shown a limited benefit. We hypothesize, therefore, that zinc homeostatic adjustments during pregnancy and lactation improve zinc utilization sufficiently to provide the increased zinc needs in these stages and, therefore, mitigate immediate detrimental effects due to a low zinc intake. The specific questions addressed are the following: How is zinc utilization altered during pregnancy and lactation? Are those homeostatic adjustments influenced by maternal zinc status, dietary zinc, or zinc supplementation? These questions are addressed by critically reviewing results from published human studies on zinc homeostasis during pregnancy and lactation carried out in different populations worldwide.     

孕期/哺乳期砷暴露对子鼠心、肝、脾、肾发育的影响

[目的]探讨孕期/哺乳期砷暴露对子鼠心、肝、脾、肾发育影响。[方法]昆明种孕小鼠48只,随机分成4组,每组12只。全孕期和哺乳期以自由饮水方式连续染毒。按饮水砷浓度分别设空白对照组,1、4、16 mg/L染砷组。子鼠生后追踪体重和身长发育情况。哺乳喂养,3周断乳。测量断乳子鼠心、肝、脾、肾脏器系数,观察子鼠心、肝、脾和肾组织形态。[结果]体格发育:出生第3、10、15和21天,各组子鼠平均体重和身长均随母鼠饮水砷浓度升高而降低(P<0.05)。脏器系数:生后3周,各组子鼠心、肝、脾、肾脏器系数均随母鼠饮水砷浓度升高而升高(P<0.05)。病理形态:染砷组断乳子鼠心肌纤维厚薄不均,排列紊乱,心肌细胞核密集;肝细胞以及肾皮质区近曲小管内皮细胞出现水变性,高剂量染砷组子鼠肾远曲小管出现蛋白管型;脾脏出现特征性结构边界不清,白髓面积逐渐变小,红髓面积逐渐增大等表现;上述病理损伤随染砷浓度增加而逐渐加重。[结论]孕期/哺乳期砷暴露导致断乳期子鼠多器官组织形态异常,此可能是砷致生后远期慢性疾病发生的解剖学基础和发育源性病因。     

Impact of Maternal Nutritional Supplementation during Pregnancy and Lactation on the Infant Gut or Breastmilk Microbiota: A Systematic Review

Recent evidence indicates that maternal dietary intake, including dietary supplements, during pregnancy and lactation may alter the infant gut or breastmilk microbiota, with implications for health outcomes in both the mother and infant. To review the effects of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota a systematic literature search was conducted. A total of 967 studies published until February 2020 were found, 31 were eligible and 29 randomized control trials were included in the qualitative synthesis. There were 23 studies that investigated the effects of probiotic supplementation, with the remaining studies investigating vitamin D, prebiotics or lipid-based nutrient supplements (LNS). The effects of maternal nutritional supplementation on the infant gut microbiota or breastmilk microbiota were examined in 21 and 12 studies, respectively. Maternal probiotic supplementation during pregnancy and lactation generally resulted in the probiotic colonization of the infant gut microbiota, and although most studies also reported alterations in the infant gut bacterial loads, there was limited evidence of effects on bacterial diversity. The data available show that maternal probiotic supplementation during pregnancy or lactation results in probiotic colonization of the breastmilk microbiota. There were no observed effects between probiotic supplementation and breastmilk bacterial counts of healthy women, however, administration of Lactobacillus probiotic to nursing women affected by mastitis was associated with significant reductions in breastmilk Staphylococcal loads. Maternal LNS supplementation during pregnancy and lactation increased bacterial diversity in the infant gut, whilst vitamin D and prebiotic supplementation did not alter either infant gut bacterial diversity or counts. Heterogeneity in study design precludes any firm conclusions on the effects of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota, warranting further research.     

Nutrient Intake Values for Folate during Pregnancy and Lactation Vary Widely around the World

Folate is a B-vitamin with particular importance during reproduction due to its role in the synthesis and maintenance of DNA. Folate is well known for its role in preventing neural tube defects (NTDs) during the periconceptional period. There is also an increased need for folate throughout pregnancy to support optimal growth and development of the fetus and blood volume expansion and tissue growth of the mother. During lactation, women are at risk of folate deficiency due to increased demands to accommodate milk folate levels. Nutrient Intake Values (NIVs) for folate have been calculated to take into account additional needs during pregnancy and lactation. However, these values vary widely between countries. For example, the folate requirement that is set to meet the needs of almost all healthy women during pregnancy varies from 300 µg/day in the United Kingdom to 750 µg/day in Mexico. Currently, there is no accepted standardized terminology or framework for establishing NIVs. This article reviews country-specific NIVs for folate during pregnancy and lactation and the basis for setting these reference values.     

Differential Effects of Maternal High Fat Diet During Pregnancy and Lactation on Taste Preferences in Rats

Maternal intake of high fat diet (HFD) increases risk for obesity and metabolic disorders in offspring. Developmental programming of taste preference is a potential mechanism by which this occurs. Whether maternal HFD during pregnancy, lactation, or both, imposes greater risks for altered taste preferences in adult offspring remains a question, and in turn, was investigated in the present study. Four groups of offspring were generated based on maternal HFD access: (1) HFD during pregnancy and lactation (HFD); (2) HFD during pregnancy (HFD-pregnancy); (3) HFD during lactation (HFD-lactation); and (4) normal diet (ND) during pregnancy and lactation (ND). Adult offspring 70 days of age underwent sensory and motivational taste preference testing with various concentrations of sucrose and Intralipid solutions using brief-access automated gustometers (Davis-rigs) and 24 h two-bottle choice tests, respectively. To control for post-gestational diet effects, offspring in all experimental groups were weaned on ND, and did not differ in body weight or glucose tolerance at the time of testing. Offspring exposed to maternal HFD showed increased sensory taste responses for 0.3, 0.6, 1.2 M sucrose solutions in HFD and 0.6 M in HFD-pregnancy groups, compared to animals exposed to ND. Similar effects were noted for lower concentrations of Intralipid in HFD (0.05, 0.10%) and HFD-pregnancy (0.05, 0.10, 0.5%) groups. The HFD-lactation group showed an opposite, diminished responsiveness for sucrose at the highest concentrations (0.9, 1.2, 1.5 M), but not for Intralipid, compared to ND animals. Extended-access two-bottle tests did not reveal major difference across the groups. Our study shows that maternal HFD during pregnancy and lactation has markedly different effects on preferences for palatable sweet and fatty solutions in adult offspring and suggests that such developmental programing may primarily affect gustatory mechanisms. Future studies are warranted for determining the impact of taste changes on development of obesity and metabolic disorders in a “real” food environment with food choices available, as well as to identify specific underlying mechanisms.     

Poor Knowledge and Practices Related to Iodine Nutrition during Pregnancy and Lactation in Australian Women: Pre- and Post-Iodine Fortification

A before-after review was undertaken to assess whether knowledge and practices related to iodine nutrition, supplementation and fortification has improved in Australian women since the introduction of mandatory iodine fortification in 2009. Surveys of pregnant (n = 139) and non-pregnant (n = 75) women in 2007–2008 are compared with surveys of pregnant (n = 147) and lactating women (n = 60) one to two years post-fortification in a regional area of New South Wales, Australia. A self-administered questionnaire was completed and dietary intake of iodine was assessed using a validated food frequency questionnaire. A generally poor knowledge about the role and sources of iodine in the diet remained after fortification. Post-fortification, iodine-containing supplements were being taken by 60% (up from 20% pre-fortification) and 45% of pregnant and lactating women, respectively. Dairy foods were the highest contributors to dietary iodine intake (57%–62%). A low intake of fish and seafood resulted in this food group contributing only 3%–8% of total intake. A low level of public awareness regarding the role of iodine in health supports the need for public health strategies in addition to fortification, such as an accompanying consumer education campaign, increased uptake of supplementation, and on-going monitoring.     

Pasteurized Akkermansia muciniphila Ameliorate the LPS-Induced Intestinal Barrier Dysfunction via Modulating AMPK and NF-κB through TLR2 in Caco-2 Cells

Akkermansia muciniphila is well known for the amelioration of inflammatory responses and restoration of intestinal barrier function. The beneficial effect of A. muciniphila occurred through contacting Toll-like receptor 2 (TLR2) on intestinal epithelial cells by wall components. In this case, the downstream mechanism of pasteurized A. muciniphila stimulating TLR2 for ameliorated intestinal barrier function is worth investigating. In this study, we evaluated the effect of live and pasteurized A. muciniphila on protecting the barrier dysfunction of Caco-2 intestinal epithelial cells induced by lipopolysaccharide (LPS). We discovered that both live and pasteurized A. muciniphila could attenuate an inflammatory response and improve intestinal barrier integrity in Caco-2 monolayers. We demonstrated that A. muciniphila enhances AMP-activated protein kinase (AMPK) activation and inhibits Nuclear Factor-Kappa B (NF-κB) activation through the stimulation of TLR2. Overall, we provided a specific mechanism for the probiotic effect of A. muciniphila on the intestinal barrier function of Caco-2 cells.     

Maternal DHA Supplementation during Pregnancy and Lactation in the Rat Protects the Offspring against High-Calorie Diet-Induced Hepatic Steatosis

Maternal supplementation during pregnancy with docosahexaenoic acid (DHA) is internationally recommended to avoid postpartum maternal depression in the mother and improve cognitive and neurological outcomes in the offspring. This study was aimed at determining whether this nutritional intervention, in the rat, protects the offspring against the development of obesity and its associated metabolic disorders. Pregnant Wistar rats received an extract of fish oil enriched in DHA or saline (SAL) as placebo by mouth from the beginning of gestation to the end of lactation. At weaning, pups were fed standard chow or a free-choice, high-fat, high-sugar (fc-HFHS) diet. Compared to animals fed standard chow, rats exposed to the fc-HFHS diet exhibited increased body weight, liver weight, body fat and leptin in serum independently of saline or DHA maternal supplementation. Nevertheless, maternal DHA supplementation prevented both the glucose intolerance and the rise in serum insulin resulting from consumption of the fc-HFHS diet. In addition, animals from the DHA-fc-HFHS diet group showed decreased hepatic triglyceride accumulation compared to SAL-fc-HFHS rats. The beneficial effects on glucose homeostasis declined with age in male rats. Yet, the preventive action against hepatic steatosis was still present in 6-month-old animals of both sexes and was associated with decreased hepatic expression of lipogenic genes. The results of the present work show that maternal DHA supplementation during pregnancy programs a healthy phenotype into the offspring that was protective against the deleterious effects of an obesogenic diet.     

Multiple Micronutrients,Lutein, and Docosahexaenoic Acid Supplementation during Lactation: A Randomized Controlled Trial

Breastfed infants require an adequate supply of critical nutrients for growth, tissue functions, and health. Recommended intakes for several nutrients are considerably higher in lactating than non-lactating women but are not always met with habitual diets. We report a randomized, double-blind clinical trial in 70 healthy lactating women in Germany evaluating the effects of supplementation with multiple micronutrients, lutein, and docosahexaenoic acid (DHA) compared to placebo on maternal nutrient status and milk composition. The primary endpoint was the effect on the change of human milk DHA content (as a proportion of total milk fatty acids) during 12 weeks of supplementation. Maternal blood and milk biomarkers were measured as secondary endpoints. Supplementation increased maternal milk DHA by 30% compared to a decline in the placebo group. Supplementation also increased maternal blood DHA (17%), eicosapentaenoic acid (4%), 25-OH-vitamin D (24%), vitamin B12 (12%), lutein (4%), and beta carotene (49%), while homocysteine decreased. No significant difference in the number of adverse events was observed between supplementation and placebo groups. In conclusion, multi-micronutrient supplementation was safe and increased maternal blood and milk concentrations of selected nutrients in healthy women.     

Probiotics Improve Gastrointestinal Function and Life Quality in Pregnancy

We studied whether probiotics were beneficial for hormonal change-associated dysbiosis, which may influence the enteric nervous system and GI function during early pregnancy. The study was 16 days consisting of two cycles of six daily probiotics mainly Lactobacillus and 2 days without probiotics. Daily surveys were conducted to monitor GI function and life quality. A subset of the participants who contributed fecal specimens was used for microbiota metagenomic sequencing, metabolomics, and quantification of bacterial genes to understand potential underlying mechanisms. Statistical analyses were done by generalized linear mixed-effects models. Thirty-two obstetric patients and 535 daily observations were included. The data revealed that probiotic supplementation significantly reduced the severity of nausea, vomiting, constipation, and improved life quality. Moreover, a low copy number of fecal bsh (bile salt hydrolase), which generates free bile acids, was associated with high vomiting scores and probiotic intake increased fecal bsh. In exploratory analysis without adjusting for multiplicity, a low fecal α-tocopherol, as well as a high abundance of Akkemansia muciniphila, was associated with high vomiting scores and times, respectively. The potential implications of these biomarkers in pregnancy and GI function are discussed. Probiotics likely produce free bile acids to facilitate intestinal mobility and metabolism.     

Glutamine Supplementation Decreases Intestinal Permeability and Preserves Gut Mucosa Integrity in an Experimental Mouse Model

Background: Glutamine (GLN) is the preferred fuel for enterocytes, and GLN supplementation is critical during stressful conditions. The aim of this study was to evaluate the effect of GLN on intestinal barrier permeability and bacterial translocation in a murine experimental model. Methods: Swiss male mice (25–30 g) were randomized into 3 groups: (1) sham group; (2) intestinal obstruction (IO) group; (3) IO and GLN (500 mg/kg/d) group. Two different experiments were carried out to assess intestinal permeability and bacterial translocation. In the first experiment, the animals were divided into the 3 groups described above and received diethylenetriamine pentaacetate radiolabeled with technetium (^99mTc) on the eighth day. At different time points after intestinal obstruction, blood was collected to determine radioactivity. The animals were killed, and the small intestine was removed for histological analyses. In the bacterial translocation study, on the eighth day all groups received Escherichia coli labeled with ^99mTc. After 90 minutes, the animals underwent intestinal obstruction and were killed 18 hours later. Blood, mesenteric lymph nodes, liver, spleen, and lungs were removed to determine radioactivity. Statistical significance was considered when P ≤ .05. Results: The levels of intestinal permeability and bacterial translocation were higher in the IO group than in the sham and GLN groups (P < .05). GLN decreased intestinal permeability and bacterial translocation to physiologic levels in the treated animals and preserved intestinal barrier integrity. Conclusions: GLN had a positive impact on the intestinal barrier by reducing permeability and bacterial translocation to physiologic levels and preserving mucosal integrity.     

Maternal Fish Oil Supplementation in Pregnancy: A 12 Year Follow-Up of a Randomised Controlled Trial

A number of trials have been undertaken to assess whether the intake of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy can influence the neurological development of the offspring, yet no consensus from these trials has been reached. We aimed to investigate the long-term effects (12 years) of fish oil supplementation in pregnancy on neurodevelopment, including cognition, language and fine motor skills. In a follow up of a previously published randomised controlled trial of 98 pregnant women, their children were assessed at 12 years of age using a battery of neurodevelopmental assessments. Fifty participants were assessed at 12 years, with 25 participant’s mothers receiving fish oil supplementation, and 25 receiving control capsules. There were no significant differences for any of the assessment measures completed. Our data indicate that fish oil supplementation during pregnancy does not influence the cognition, language or fine motor skills of children in late primary school (12 years of age).     

Fermented Rice Bran Supplementation Prevents the Development of Intestinal Fibrosis Due to DSS-Induced Inflammation in Mice

Fermented rice bran (FRB) is known to protect mice intestines against dextran sodium sulfate (DSS)-induced inflammation; however, the restoration of post-colitis intestinal homeostasis using FRB supplementation is currently undocumented. In this study, we observed the effects of dietary FRB supplementation on intestinal restoration and the development of fibrosis after DSS-induced colitis. DSS (1.5%) was introduced in the drinking water of mice for 5 days. Eight mice were sacrificed immediately after the DSS treatment ended. The remaining mice were divided into three groups, comprising the following diets: control, 10% rice bran (RB), and 10% FRB-supplemented. Diet treatment was continued for 2 weeks, after which half the population of mice from each group was sacrificed. The experiment was continued for another 3 weeks before the remaining mice were sacrificed. FRB supplementation could reduce the general observation of colitis and production of intestinal pro-inflammatory cytokines. FRB also increased intestinal mRNA levels of anti-inflammatory cytokine, tight junction, and anti-microbial proteins. Furthermore, FRB supplementation suppressed markers of intestinal fibrosis. This effect might have been achieved via the canonical Smad2/3 activation and the non-canonical pathway of Tgf-β activity. These results suggest that FRB may be an alternative therapeutic agent against inflammation-induced intestinal fibrosis.     

母鼠孕期及哺乳期骨骼铅水平及其与甲状旁腺激素的关系

[目的]研究母体孕期和哺乳期骨骼铅动员的规律及机制。[方法]36只雌性昆明小鼠通过饮水暴露于醋酸铅（含铅元素10.0mol/L）4周后怀孕,分别在孕期的第1、7和14天,哺乳期的第1、10和21天取股骨、全血和血清,用石墨炉原子吸收法测定铅含量,用放射免疫法测定总血清甲状旁腺激素（parathyroid hormone,PTH）含量,分别与同日龄非染铅母鼠比较。[结果]自孕中期开始,铅暴露组母鼠的血铅（blood lead）及血清总PTH水平开始明显上升,血钙、骨钙及骨铅水平开始明显下降;血铅水平在哺乳期末上升至（0.38±0.02）μmol/L,较孕初期上升65.22%（P〈0.05）;骨铅水平（femur lead）在哺乳期末下降至（269.14±9.78）nmol/g,较孕初期下降28.45%（P〈0.05）;血钙、骨钙水平在哺乳期末分别下降至（1.85±0.07）mmol/L、（12.74±0.38）mmol/g,较孕初期分别下降18.50%、17.75%（P〈0.05）;在孕中期,血清总PTH水平上升至（6.04±0.50）μg/L,较孕初期上升103.37%（P〈0.05）,直至哺乳期末仍维持在较高水平;两组的血铅、骨铅、血钙、骨钙及血清总PTH水平在观察期内各个阶段均有明显差异（P〈0.05）;铅暴露组血铅水平与血清总PTH水平之间有正相关关系（r=0.790,P〈0.0001）。[结论]母鼠孕期及哺乳期骨骼铅动员可能与血清PTH水平的变化有关。     

Effect of Dietary Fat Supplementation during Late Pregnancy and First Six Months of Lactation on Maternal and Infant Vitamin A Status in Rural Bangladesh

Dietary fat intake is extremely low in most communities with vitamin A deficiency. However, its role in vitamin A status of pregnant and lactating women is poorly understood. The aim of the study was to examine the effect of supplementing women with fat from mid-/late pregnancy until six months postpartum on their vitamin A status and that of their infants. Women recruited at 5-7 months of gestation were supplemented daily with 20 mL of soybean-oil (n=248) until six months postpartum or received no supplement (n=251). Dietary fat intake was assessed by 24-hour dietary recall at enrollment and at 1, 3 and 6 months postpartum. Concentrations of maternal plasma retinol, β-carotene, and lutein were measured at enrollment and at 1, 3 and 6 months postpartum, and those of infants at six months postpartum. Concentration of breastmilk retinol was measured at 1, 3 and 6 months postpartum. The change in concentration of plasma retinol at three months postpartum compared to pregnancy was significantly higher in the supplemented compared to the control women (+0.04 vs -0.07 μmol/L respectively; p<0.05). Concentrations of plasma β-carotene and lutein declined in both the groups during the postpartum period but the decline was significantly less in the supplemented than in the control women at one month (β-carotene -0.07 vs -0.13 μmol/L, p<0.05); lutein -0.26 vs -0.49 μmol/L, p<0.05) and three months (β-carotene -0.04 vs -0.08 μmol/L, p<0.05; lutein -0.31 vs -0.47 μmol/L, p<0.05). Concentration of breastmilk retinol was also significantly greater in the supplemented group at three months postpartum than in the controls (0.68±0.35 vs 0.55±0.34 μmol/L respectively, p<0.03). Concentrations of infants’ plasma retinol, β-carotene, and lutein, measured at six months of age, did not differ between the groups. Fat supplementation during pregnancy and lactation in women with a very low intake of dietary fat has beneficial effects on maternal postpartum vitamin A status.Key words: Community-based studies, Fat supplementation, Infant, Postpartum;Pregnancy, Vitamin A, Vitamin A deficiency, Bangladesh     

Towards an Optimized Fetal DHA Accretion: Differences on Maternal DHA Supplementation Using Phospholipids vs. Triglycerides during Pregnancy in Different Models

Docosahexaenoic acid (DHA) supplementation during pregnancy has been recommended by several health organizations due to its role in neural, visual, and cognitive development. There are several fat sources available on the market for the manufacture of these dietary supplements with DHA. These fat sources differ in the lipid structure in which DHA is esterified, mainly phospholipids (PL) and triglycerides (TG) molecules. The supplementation of DHA in the form of PL or TG during pregnancy can lead to controversial results depending on the animal model, physiological status and the fat sources utilized. The intestinal digestion, placental uptake, and fetal accretion of DHA may vary depending on the lipid source of DHA ingested by the mother. The form of DHA used in maternal supplementation that would provide an optimal DHA accretion for fetal brain development, based on the available data obtained most of them from different animal models, indicates no consistent differences in fetal accretion when DHA is provided as TG or PL. Other related lipid species are under evaluation, e.g., lyso-phospholipids, with promising results to improve DHA bioavailability although more studies are needed. In this review, the evidence on DHA bioavailability and accumulation in both maternal and fetal tissues after the administration of DHA supplementation during pregnancy in the form of PL or TG in different models is summarized.     

The Influence of Smoking on Vitamin C Status During the Third Trimester of Pregnancy and on Vitamin C Levels in Maternal Milk

Objective: The aim of the present investigation was to determine the differences in vitamin C status of 57 Spanish women smokers (S) and nonsmokers (N) in their third trimester of pregnancy, and the concentrations of vitamin C in their milk.

Methods: Vitamin C intake during the third trimester was determined by recording the consumption of foods over a 5-day period (including a Sunday) and by registering vitamin C provided by dietary supplements. Vitamin C levels in maternal serum during this stage of pregnancy and in transition (days 13 to 14 of lactation) and mature milk (day 40 of lactation) were determined colorimetrically. Subjects also answered a questionnaire on their smoking habits during pregnancy.

Results: S subjects (n=16) showed a lower intake of fruits, vegetables and vitamin C than did N subjects (n=41), though these differences were not significant (17.1% of N subjects and 31.2% of S subjects took less than 80 mg of vitamin C per day). Neither were any differences found between the two groups in serum vitamin C levels. However, N subjects showed significantly greater vitamin C levels in both transition and mature milk (431.6±296.5 μmol/L and 496.1±325.6 μmol/L, respectively for N subjects, and 233.7±202.9 μmol/L and 241.3±293.1 μmol/L for S subjects). Further investigations are necessary to determine the clinical consequences of these observations, though it is already known that maternal smoking favors peroxidation events in newborn infants.

Conclusions: If the concentration of antioxidants (vitamin C) in smokers’ breast milk is also lower, this might aggravate the peroxidation problems of their newborn.