Maternal Se Research Articles

Cross-species apical microinjected selenomethionine toxicity in embryo-larval fishes

Selenium (Se) is an essential micronutrient that becomes toxic when exposures minimally exceed those that are physiologically required. Studies on Se contaminated aquatic environments have identified that embryo-larval fishes are at particular risk of Se toxicity, primarily due to maternal Se transfer to developing eggs during oogenesis. This study emulated these exposures in embryo-larval fathead minnow (FHM), rainbow trout (RBT), white sucker (WSu), and white sturgeon (WSt) using embryonic selenomethionine (SeMet) microinjections. Adverse Se-outcomes observed across these species included spinal and edematous deformities, total individuals deformed, and reduced survival. Spinal deformity was the most sensitive sublethal endpoint and developed at the lowest concentrations in WSt (10 % effects concentration (EC10) = 12.42 μg (total) Se/g dry weight (d.w.)) followed by WSu (EC10 = 14.49 μg Se/g d.w.) and FHM (EC10 = 18.10 μg Se/g d.w.). High mortality was observed in RBT, but SeMet influences were confounded by the species' innate sensitivity to the microinjections themselves. 5 % hazardous concentrations derived across exposure type data subsets were ∼49 % higher when derived from within-species maternal transfer exclusive data as opposed to all, or within-species microinjection exclusive, data. These results support the current exclusion of SeMet microinjections during regulatory guideline derivation and their inclusion when studying mechanistic Se toxicity across phylogenetically distant fishes.

Maternal suboptimal selenium intake and low-level lead exposure affect offspring’s microglial immune profile and its reactivity to a subsequent inflammatory hit

Micronutrients such as selenium (Se) are essentials since prenatal life to support brain and cognitive development. Se deficiency, which affects up to 1 billion people worldwide, can interact with common adverse environmental challenges including (Pb), exacerbating their toxic effects. Exploiting our recently validated rat model of maternal Se restriction and developmental low Pb exposure, our aims were to investigate: (i) the early consequences of suboptimal Se intake and low-Pb exposure on neuroinflammation in neonates’ whole brains; (ii) the potential priming effect of suboptimal Se and low-Pb exposure on offspring’s glial reactivity to a further inflammatory hit. To these aims female rats were fed with suboptimal (0.04 mg/kg; Subopt) and optimal (0.15 mg/kg; Opt) Se dietary levels throughout pregnancy and lactation and exposed or not to environmentally relevant Pb dose in drinking water (12.5 µg/mL) since 4 weeks pre-mating. We found an overall higher basal expression of inflammatory markers in neonatal brains, as well as in purified microglia and organotypic hippocampal slice cultures, from the Subopt Se offspring. Subopt/Pb cultures were highly activated than Subopt cultures and showed a higher susceptibility to the inflammatory challenge lipopolysaccharide than cultures from the Opt groups. We demonstrate that even a mild Se deficiency and low-Pb exposure during brain development can influence the neuroinflammatory tone of microglia, exacerbate the toxic effects of Pb and prime microglial reactivity to subsequent inflammatory stimuli. These neuroinflammatory changes may be responsible, at least in part, for adverse neurodevelopmental outcomes.

Assessment of the oxidative status in mother-child couples from Seville (Spain): A prospective cohort study

Pregnancy requires a high demand of energy, which leads to an increase of oxidative stress. The aim of this study was to assess the oxidative status in 200 couples of pregnant women-newborns at the time of delivery, for the first time, who gave birth in two University Hospitals from the province of Seville. Recruited women filled an epidemiological questionnaire with their demographic characteristics and dietary habits during pregnancy. At the time of delivery, both maternal and cord blood samples were collected. Protein oxidation, superoxide dismutase, and catalase levels were measured to assess the oxidative status of these women, together with the levels of vitamins D, B12, Zn, Se, and Cu. Our results showed a tendency for all biomarkers measured to be higher in cord blood than in maternal blood. For the correlations established between the OS markers and sociodemographic characteristics, only significant differences for carbonyl groups values were found on both maternal and cord blood, relating these higher values to the use of insecticides in the women’s homes. For newborns, only a significant correlation was detected between antioxidant enzymes and the newborn’s weight, specifically for superoxide dismutase activity. Additionally, the higher values obtained in cord blood might suggest metabolization, while a higher production of ROS and antioxidant enzymes might be required to maintain the balance. Measured levels for Se were similar in both maternal and cord blood, unlike Cu and Zn, where higher levels were found for maternal blood than cord blood, indicating a correlation between maternal Se values and SOD as OS biomarker. Furthermore, vitamin D levels were around the optimum values established, finding a relationship between vitamin D and new-born’s height, unlike for vitamin B12 values, where a correlation with maternal food consumption characteristics was established. Overall values were inside normal ranges and consistent for our population.

Evaluation of Selenium Status among Iranian Pregnant Women: A Systematic Review and Met-Analysis

Background: Selenium (Se) plays an important role in numerous immunological functions of human health. It has been shown that maternal Se deficiency contributes to many pregnancy complications such as pre-eclampsia, gestational diabetes mellitus (GDM), miscarriage, and even fetal growth restriction. Due to the evidence of importance of Se in pregnancy outcomes and the inconsistency of current shreds of evidence on Se adequacy in Iranian pregnant women, this study aimed to provide a comprehensive evaluation of published studies. This systematic review explored studies reporting dietary Se intake, serum or plasma Se, and Umbilical cord Se in Iranian pregnant women.
 Methods: PubMed, Scopus, Web of Science, Embase, Google scholar (in English and Persian), and Persian databases, including Scientific Information Database, IranDoc, Iranian National Library, Magiran, and Regional Information Center for Science and Technology, were reviewed.
 
 Results: A total of 30 studies were included in the meta-analysis. Pooled effect sizes show an overall value of 90.09 µg/l (95% CI: 81.89, 98.29) and 75.08 µg/d (95% CI: 63.01, 87.16) for serum and dietary Se. Geographically, the lowest serum Se was in Fars and East-Azerbaijan with values of 61.97 µg/l (51.38, 72.55) and 55.12 µg/l (48.5, 61.74), respectively. Dietary intake pooled estimate showed that the lowest Se intake was in West-Azerbaijan with a value of 42.80 µg/d (95% CI: 38.95, 46.65).
 Conclusion: The current study shows that the overall serum and dietary intake of Se in Iranian pregnant women is acceptable. Some parts of the country need monitoring to prevent Se inadequacy and related-adverse complications in pregnant women.

Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development.

Decreased selenium (Se) levels during childhood and infancy are associated with worse respiratory health. Se is biologically active after incorporation into Se-containing antioxidant enzymes (AOE) and proteins. It is unknown how decreased maternal Se during pregnancy and lactation impacts neonatal pulmonary selenoproteins, growth, and lung development. Using a model of neonatal Se deficiency that limits Se intake to the dam during pregnancy and lactation, we evaluated which neonatal pulmonary selenoproteins are decreased in both the saccular (postnatal day 0, P0) and early alveolar (postnatal day 7, P7) stages of lung development. We found that Se deficient (SeD) pups weigh less and exhibit impaired alveolar development compared to Se sufficient (SeS) pups at P7. The activity levels of glutathione peroxidase (GPx) and thioredoxin reductase (Txnrd) were decreased at P0 and P7 in SeD lungs compared to SeS lungs. Protein content of GPx1, GPx3 and Txnrd1 were decreased in SeD lungs at P0 and P7, whereas Txnrd2 content was unaltered compared to SeS controls. The expression of NRF-2 dependent genes and several non-Se containing AOE were similar between SeS and SeD lungs. SeD lungs exhibited a decrease in selenoprotein N, an endoplasmic reticulum protein implicated in alveolar development, at both time points. We conclude that exposure to Se deficiency during pregnancy and lactation impairs weight gain and lung growth in offspring. Our data identify multiple selenoproteins in the neonatal lung that are vulnerable to decreased Se intake, which may impact oxidative stress and cell signaling under physiologic conditions as well as after oxidative stressors.

Association between Maternal Selenium Exposure and Congenital Heart Defects in Offspring: A Systematic Review and Meta-Analysis.

The association between congenital heart defects (CHDs) and selenium (Se) is still unclear. We aimed to systematically review and quantitative analyze the potential relationship between maternal Se exposure and CHDs in the offspring. PubMed, Embase, Web of Science and Scopus databases were searched from inception up to August 2021 for relevant studies. Methodological quality of the studies was assessed through Newcastle-Ottawa scale. The Standard mean difference (SMD) and corresponding 95% confidence interval (CI) were calculated to compare maternal Se levels between CHDs groups and control groups using a random-effects model. Four articles covering five studies were included in the systematic review, and three articles covering four studies were included in the meta-analysis. One study measured Se concentrations in maternal hair and found a positive correlation between high concentrations and increased risk of CHDs in offspring. However, one study on cord blood, and one on whole blood illustrated that Se exposure was associated with decreased risk of CHDs. There was no significant association found between serum Se levels and CHDs in two studies. Pooled results showed decreased Se levels in the circulation of mothers with CHDs offspring (SMD = -108.27, 95% CI: -192.72, -23.82), with statistically significant heterogeneity (I2 = 99.8%, P < 0.001) but not in hair, as compared with controls. Low maternal Se status may be associated with increased risk of CHDs in offspring. However, further larger-scale studies with strict and consistent design methods are still required to investigate this issue.

PSIII-7 Evaluation of Maternal Selenium Supplementation and Plane of Nutrition During Gestation on the Neonatal Fc Receptor (Fcrn) in Lamb Intestinal Tissue

Abstract Maternal selenium (Se) supply and plane of nutrition alter morbidity and mortality in lambs as well as 24-h serum IgG. The neonatal Fc receptor (FcRn) transports IgG across mucosal surfaces; however, its role in intestinal protection in the lamb is unknown. Additionally, the effects of maternal nutrition on offspring FcRn abundance has not been reported. The objective of this study was to evaluate intestinal FcRn abundance in lambs born from ewes fed differing levels of nutrition and Se. Intestinal tissues from two experiments (EXP1 n=71; EXP2 n=80) were used. Both experiments utilized a 2x3 factorial design. Main effects included Se supplementation [adequate (9.5 or 11.5 μg/kg of BW in EXP1 or EXP2; respectively) or high, (81.1 or 77.0 μg/kg of BW in EXP1 or EXP2; respectively)] and plane of nutrition [60% (RES), 100% (CON), or 140% (HIGH) of requirements for both experiments]. Lambs were raised to 57 d or 21 d (EXP1 and EXP2; respectively). Intestinal tissues were collected and fixed in 10% NBF prior to paraffin embedding. Cross-sections were stained for FcRn and counterstained with DAPI. Areas of tissue cross-sections were captured with Plan-Apochromat 20x/0.8 NA lens using the tiling module of Zeiss. Images were analyzed using ImagePro Premiere software. Relative fluorescence within areas of interest was used as an indicator of FcRn receptor abundance. Data were analyzed using the general linear model procedure of SAS. Maternal nutrition tended (P≤0.07) to affect lamb intestinal FcRn abundance with CON having higher abundance compared to HIGH or RES (EXP1). There was no effect of maternal nutrition in EXP2 or maternal Se supplementation on intestinal FcRn abundance in lambs from either experiment (P≥0.56). These data show that maternal nutrition may influence offspring FcRn abundance and that further studies examining the contribution of lamb age are needed.

Selenium Status and Supplementation Effects in Pregnancy-A Study on Mother-Child Pairs from a Single-Center Cohort.

The demand for selenium (Se) increases during pregnancy since this element supports child growth, proper neuronal development and maternal thyroid function. The issue is particularly relevant for populations living in areas with a limited selenium supply, where many pregnant women opt for Se supplementation. The efficiency of this measure is unknown, although it seems vital in the prevention of severe Se deficiency. In order to evaluate this hypothesis, an observational study was conducted in Poland, where Se deficiency is prevalent. Pregnant women were invited to participate in the study and provided serum samples at the end of pregnancy (n = 115). Information on the supplemental intake of micronutrients was recorded in a face-to-face interview. In addition, serum samples were isolated from the cord blood of newborns at delivery (n = 112) and included in the analyses. Thyroid hormone status was evaluated by routine laboratory tests, and Se status was determined by total Se and selenoprotein P (SELENOP) concentrations and extracellular glutathione peroxidase (GPX3) activity. The three parameters of Se status correlated strongly within the group of mothers and within the group of newborns, with an additional significant correlation found among mother–child pairs. One-third of mothers reported additional Se intake, mainly as a component of multi-micronutrient supplements, at a mean (±SD) dosage of 42 ± 14 µg Se/day. Despite this regime, most of the women presented an insufficient Se status, with 79% of mothers displaying serum Se concentrations below 70 µg/L (indicating Se deficiency) and 22% showing levels below 45.9 µg/L (severe Se deficiency). The inadequate Se supply was also reflected in relatively low SELENOP concentrations and GPX3 activity. Neither total Se nor SELENOP or GPX3 levels were significantly higher in the group of mothers reporting the intake of supplements than in the non-supplementing group. Nevertheless, elevated SELENOP concentrations were observed in the subgroup receiving supplements with more than 55 µg/day. We conclude that the self-administered supplementation of small Se dosages was not sufficient to achieve replete Se status in the micronutrient scant area. However, the maternal Se deficit measured by either Se, SELENOP or GPX3 was transferred from mothers to the newborns, as the parameters correlated strongly in the mother–newborn pairs of samples. It is vital to re-evaluate the guidelines concerning pregnancy care and monitoring of micronutrient status during pregnancy, in particular in areas where deficiencies are present.

A Multi-country Association Analysis of Maternal Selenium (Se) Levels and Infant Birth Outcomes: Findings From the Women First Study

ObjectivesSelenium (Se) soil content varies worldwide impacting population levels. Maternal Se deficiency may be related to preterm birth, small for gestational age (SGA), and low birth weight (LBW, < 2,500g) possibly through its roles in antioxidant and thyroid hormone function particularly during the first trimester. We examined associations of Se levels and birth outcomes in a multi-country nutritional intervention trial of pregnant women.MethodsThis is a secondary analysis of the Women First trial (NCT01883193), a randomized controlled study investigating timing of maternal multiple micronutrient (with 130 mcg Se) and protein-energy supplementation (MNS) on fetal growth. MNS was started 3 months prior to conception (Arm 1), at ∼12 wk of gestation (Arm 2), or not at all (Arm 3) in women in India, Guatemala, and Pakistan. Gestational age was determined by first trimester ultrasound. At 12 and 34 wk gestation, maternal serum Se was measured by ICP-MS (n = 143–325 per timepoint per site). TSH was measured by 1-step sandwich (Guatemala and Pakistan) or chemiluminescence immunoassay (India). We used t-test or ANOVA to test group differences and linear models to test association of Se with infant outcomes and TSH, adjusting for treatment arm and study site.ResultsSe levels were highest in Guatemalan women (mean ± SD, 12 wk: 102.1 ug/L ± 12.6; 34 wk: 103.9 ± 14.2) and lowest in Pakistani women (12 wk: 85.7 ± 14.5; 34 wk: 77.9 ± 14.8) at both timepoints (P < 0.0001). MNS supplementation before or during gestation increased serum Se levels at 34 wk in Guatemalan women only (p = 0.038). In Pakistan a negative association between maternal Se at 34 wk and LBW was seen in female (n = 153; p = 0.041) but not male (n = 143; p = 0.97) infants. Se levels were not associated with preterm birth or SGA status at any site. TSH levels did not differ by study arm but were lower in Pakistan at 12 and 34 wk compared to other sites. There was no association between TSH and Se levels at any timepoint at any site.ConclusionsMaternal Se levels may impact fetal birth weight in vulnerable populations in a sexually dimorphic manner. Preconception Se supplementation as part of a comprehensive MNS did not increase Se levels in Pakistan where soil Se content is low. Although Se did not correlate with TSH levels in this study, future work will incorporate co-influence of iodine.Funding SourcesBill & Melinda Gates Foundation, NIH NICHD/ODS.

Critical Role of Maternal Selenium Nutrition in Neurodevelopment: Effects on Offspring Behavior and Neuroinflammatory Profile

Research in both animals and humans shows that some nutrients are important in pregnancy and during the first years of life to support brain and cognitive development. Our aim was to evaluate the role of selenium (Se) in supporting brain and behavioral plasticity and maturation. Pregnant and lactating female rats and their offspring up to postnatal day 40 were fed isocaloric diets differing in Se content—i.e., optimal, sub-optimal, and deficient—and neurodevelopmental, neuroinflammatory, and anti-oxidant markers were analyzed. We observed early adverse behavioral changes in juvenile rats only in sub-optimal offspring. In addition, sub-optimal, more than deficient supply, reduced basal glial reactivity in sex dimorphic and brain-area specific fashion. In female offspring, deficient and sub-optimal diets reduced the antioxidant Glutathione peroxidase (GPx) activity in the cortex and in the liver, the latter being the key organ regulating Se metabolism and homeostasis. The finding that the Se sub-optimal was more detrimental than Se deficient diet may suggest that maternal Se deficient diet, leading to a lower Se supply at earlier stages of fetal development, stimulated homeostatic mechanisms in the offspring that were not initiated by sub-optimal Se. Our observations demonstrate that even moderate Se deficiency during early life negatively may affect, in a sex-specific manner, optimal brain development.

Associations between Maternal Selenium Status and Cord Serum Vitamin D Levels: A Birth Cohort Study in Wuhan, China.

Serum selenium (Se) has been reported to be associated with serum 25-hydroxyvitamin D [25(OH)D], but epidemiological findings are limited in pregnant women. We aimed to assess the associations between maternal urinary Se concentrations and cord serum 25(OH)D levels. We measured urinary concentrations of Se in the first, second, and third trimesters and cord serum 25(OH)D of 1695 mother-infant pairs from a prospective cohort study in Wuhan, China. The results showed that each doubling of urinary Se concentrations in the first, second, third trimester, and whole pregnancy (average SG-adjusted concentrations across three trimesters) were associated with 8.76% (95% confidence interval (CI): 4.30%, 13.41%), 15.44% (95% CI: 9.18%, 22.06%), 11.84% (95% CI: 6.09%, 17.89%), and 21.14% (95% CI: 8.69%, 35.02%) increases in 25(OH)D levels. Newborns whose mothers with low (<10 μg/L) or medium (10.92–14.34 μg/L) tertiles of urinary Se concentrations in whole pregnancy were more likely to be vitamin D deficient (<20 ng/mL) compared with those with the highest tertile (>14.34 μg/L). Our study provides evidence that maternal Se levels were positively associated with cord serum vitamin D status.

The Role of Selenoprotein Tissue Homeostasis in MetS Programming: Energy Balance and Cardiometabolic Implications.

Selenium (Se) is an essential trace element mainly known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, as it is part of the catalytic center of 25 different selenoproteins. Some of them are related to insulin resistance (IR) and metabolic syndrome (MetS) generation, modulating reactive oxygen species (ROS), and the energetic sensor AMP-activated protein kinase (AMPK); they can also regulate the nuclear transcription factor kappa-B (NF-kB), leading to changes in inflammation production. Selenoproteins are also necessary for the correct synthesis of insulin and thyroid hormones. They are also involved in endocrine central regulation of appetite and energy homeostasis, affecting growth and development. MetS, a complex metabolic disorder, can appear during gestation and lactation in mothers, leading to energetic and metabolic changes in their offspring that, according to the metabolic programming theory, will produce cardiovascular and metabolic diseases later in life. However, there is a gap concerning Se tissue levels and selenoproteins’ implications in MetS generation, which is even greater during MetS programming. This narrative review also provides an overview of the existing evidence, based on experimental research from our laboratory, which strengthens the fact that maternal MetS leads to changes in Se tissue deposits and antioxidant selenoproteins’ expression in their offspring. These changes contribute to alterations in tissues’ oxidative damage, inflammation, energy balance, and tissue function, mainly in the heart. Se imbalance also could modulate appetite and endocrine energy balance, affecting pups’ growth and development. MetS pups present a profile similar to that of diabetes type 1, which also appeared when dams were exposed to low-Se dietary supply. Maternal Se supplementation should be taken into account if, during gestation and/or lactation periods, there are suspicions of endocrine energy imbalance in the offspring, such as MetS. It could be an interesting therapy to induce heart reprogramming. However, more studies are necessary.

Effects of maternal and progeny dietary selenium supplementation on growth performance and antioxidant capacity in ducklings

This study evaluated the effects of selenium (Se) supplementation in maternal and offspring diets on performance and antioxidant capacity of ducklings aged from 0 to 2 wk. A total of 144 female Longyan duck breeders aged 22-wk were allotted into 2 treatments and fed a control diet or a 0.16 mg Se/kg supplemented diet. At 40-wk, 120 offspring from each treatment were divided into 2 groups, with 6 replicates of 10 birds. Using a 2 × 2 factorial design, ducklings from each maternal dietary treatment were assigned to a control diet or a 0.16 mg Se/kg supplemented diet from hatch to 2-wk. Compared with Se-deficient diet, maternal diet supplemented with 0.16 mg Se/kg increased the BW of hatchlings (P < 0.01). There were interactions between maternal and progeny diet with 0.16 mg Se/kg in BW of ducklings aged 2 wk and BW gain (BWG) as ducklings from maternal Se/progeny none treatment had the lightest BW and BWG (P < 0.01). Maternal diet with 0.16 mg Se/kg decreased plasma concentration of uric acid and insulin-like growth factor 1 (P < 0.01), and progeny diet supplemented with 0.16 mg Se/kg increased the activities of glutathione peroxidase 3 (GPx3) in plasma and glutathione peroxidase 1 in erythrocyte (P < 0.01). Maternal diet with 0.16 mg Se/kg increased (P < 0.05) the hepatic activity of total superoxide dismutase (T-SOD). Progeny diet supplemented with 0.16 mg Se/kg increased (P < 0.01) hepatic activity of GPx3 and decreased (P < 0.01) the hepatic concentration of malondialdehyde. Interactions were detected between maternal and progeny diet with 0.16 mg Se/kg in hepatic activity of T-SOD and maternal and progeny diet supplemented with Se displayed the highest hepatic activity of T-SOD (P < 0.05). Overall, Se supplementation in the diet of duck breeders and offspring increased the antioxidant capacity of ducklings. Maternal Se supplementation increased the BW of hatchlings, whereas maternal and progeny dietary Se supplementation did not affect the BWG of ducklings aged from 0 to 2 wk. Se supplementation with additional 0.16 mg/kg in the diet of duck breeders and offspring displayed beneficial effects particularly on the antioxidant capacity in ducklings.

Maternal prenatal selenium levels and child risk of neurodevelopmental disorders: A prospective birth cohort study.

Selenium (Se) is an essential trace element involved in various biological processes, including neurodevelopment. Available literature indicates that both Se deficiency and excess may be detrimental to health. It is also known that Se can cross the placenta from maternal to fetal circulation. To date, the role of maternal Se status in child long-term neurodevelopment is largely unexplored. This study investigated the temporal and dose-response associations between maternal Se status and child risk of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). It consisted of 1550 mother-infant dyads from the Boston Birth Cohort. Maternal red blood cell (RBC) Se levels were measured in samples collected within 72 h of delivery (biomarker of third trimester Se status). Pediatric neurodevelopmental diagnoses were obtained from electronic medical records. Data analyses showed that maternal RBC Se levels were positively associated with child risk of developing ASD, with an adjusted odds ratio of 1.49 for ASD (95% CI: 1.09, 2.02) per IQR increase in Se. There was also a positive association between maternal Se and ADHD (OR: 1.29; 95% CI: 1.04, 1.56, per IQR increase in Se). These associations remained robust even after adjusting for pertinent covariables; and there was no significant interaction between Se and these covariables. Our findings suggest that prenatal exposure to high maternal Se levels may adversely affect child neurodevelopment. Our findings warrant further investigation; if confirmed, optimizing maternal prenatal Se levels may be necessary to maximize its health benefits while preventing undue risk. LAY SUMMARY: Selenium (Se) is an essential nutrient for the health of the pregnant mother and her baby. While Se can readily cross the placenta from maternal to fetal circulation, little is known about maternal Se status on her child's neurodevelopmental outcomes. We studied over 1500 mother-child dyads from birth to school age of the child. We found that babies born from mothers with high blood Se levels may be at increased risk of developing autism spectrum disorder or attention deficit hyperactivity disorder. Given this is the first study of the kind, more study is needed to confirm our findings.

Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis

BackgroundSelenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational...

Maternal selenium levels and whole genome screen in recurrent spontaneous preterm birth population: A nested case control study

ObjectiveTo establish if low maternal selenium (Se) was associated with sPTB in women with recurrent sPTB and identify genetic link with maternal Se levels. DesignNested case-control study. SettingTertiary Maternity Hospital. PopulationPlasma and whole blood from pregnant women with history of early sPTB/PPROM < 34+0 and European ancestry were obtained at 20 weeks (range 15–24 weeks). ‘Cases’ were recurrent PTB/PPROM < 34+0 weeks and term (≥37+0) deliveries were classified as ‘high-risk controls.’ Women with previous term births and index birth ≥ 39 weeks were ‘low-risk controls’. MethodsMaternal plasma Se measured by ICP-MS was used as a continuous phenotype in a GWAS analysis. Se was added to a logistic regression model using PTB predictor variables. Main outcome measuresMaternal Se concentration, recurrent early sPTB/PPROM. Results53/177 high-risk women had a recurrent sPTB/PPROM < 34+0weeks and were 2.7 times more likely to have a Se level < 83.3 ppm at 20weeks of pregnancy compared with low-risk term controls (n = 179), (RR 2.7, 95%CI 1.5–4.8; p = .001). One SNP from a non-coding region (FOXN3 intron variant, rs55793422) reached genome-wide significance level (p = 3.73E−08). Targeted analysis of Se gene variant did not show difference between preterm and term births. (χ2 test, OR = 0.95; 95%CI = 0.59–1.56; p = 0.82). When Se levels were added to a clinical prediction model, only an additional 5% of cases (n = 3) and 0.6% (n = 1) of controls were correctly identified. ConclusionsLow plasma Se is associated with sPTB risk but is not sufficiently predictive at individual patient level. We did not find a genetic association between maternal Se levels and Se-related genes.

Fetal Programming Is Deeply Related to Maternal Selenium Status and Oxidative Balance; Experimental Offspring Health Repercussions.

Nutrients consumed by mothers during pregnancy and lactation can exert permanent effects upon infant developing tissues, which could represent an important risk factor for diseases during adulthood. One of the important nutrients that contributes to regulating the cell cycle and tissue development and functionality is the trace element selenium (Se). Maternal Se requirements increase during gestation and lactation. Se performs its biological action by forming part of 25 selenoproteins, most of which have antioxidant properties, such as glutathione peroxidases (GPxs) and selenoprotein P (SELENOP). These are also related to endocrine regulation, appetite, growth and energy homeostasis. In experimental studies, it has been found that low dietary maternal Se supply leads to an important oxidative disruption in dams and in their progeny. This oxidative stress deeply affects gestational parameters, and leads to intrauterine growth retardation and abnormal development of tissues, which is related to endocrine metabolic imbalance. Childhood pathologies related to oxidative stress during pregnancy and/or lactation, leading to metabolic programing disorders like fetal alcohol spectrum disorders (FASD), have been associated with a low maternal Se status and intrauterine growth retardation. In this context, Se supplementation therapy to alcoholic dams avoids growth retardation, hepatic oxidation and improves gestational and breastfeeding parameters in FASD pups. This review is focused on the important role that Se plays during intrauterine and breastfeeding development, in order to highlight it as a marker and/or a nutritional strategy to avoid diverse fetal programming disorders related to oxidative stress.

Interaction of prenatal bisphenols, maternal nutrients, and toxic metal exposures on neurodevelopment of 2-year-olds in the APrON cohort

BackgroundEpidemiological studies suggest that Bisphenol-A (BPA) is a developmental neurotoxicant, but the modifying effects of maternal nutrient status or neurotoxicant metal co-exposures have not been reported. Bisphenol-S (BPS) is being used as a BPA-alternative, but few epidemiological studies have evaluated its effects. ObjectivesTo examine if prenatal maternal BPA or BPS exposure are associated with children’s neurodevelopment at two years of age while adjusting for effect-measure modification by sex, maternal nutrients, and co-exposure to neurotoxic metals. MethodsTotal BPA and BPS concentrations were analyzed in spot maternal urine from the second trimester; metals and maternal nutrient status were analyzed in blood. Child neurodevelopment was evaluated with the Bayley Scales of Infant Development-III (Bayley-III) at age 2 (394 maternal-child pairs) and linear regression was used to investigate associations. ResultsAmong nutrients and neurotoxic metals, selenium (Se) and cadmium (Cd) were the most significant predictors of Bayley-III scale scores. Higher maternal Cd was significantly correlated with poorer motor performance (p < 0.01), and higher levels of maternal Se were significantly associated with poorer performance on the cognitive, motor, and adaptive behavior scales (p < 0.05). While maternal Cd did not modify relationships between bisphenol exposures and Bayley-III scores, both maternal Se and child sex were significant effect-measure modifiers. Associations between BPA exposure and social emotional scores were negative for boys (p = 0.056) but positive for girls (p = 0.046). Higher exposure to bisphenols was associated with lower motor scores among children with lower levels of maternal Se. ConclusionHigher maternal Cd was associated with poorer motor development, but it was not an effect-measure modifier of bisphenols’ effects on motor development. Maternal Se may be protective against adverse effects of bisphenols, and additional nutrient-bisphenol interaction studies examining sex-specific effects of BPA and BPS on child development are warranted.

The mediation effect of placental weight change in the association between prenatal exposure to selenium and birth weight: Evidence from a prospective birth cohort study in China.

All participants were selected from the Prenatal Environment and Offspring Health cohort conducted in 2016 in Guangzhou, China. Se in each participant was measured by inductively coupled plasma mass spectrometry in their urine samples. The urinary Se concentrations were corrected by creatinine and transformed by natural logarithm (ln-Se). Multiple-linear regression models were applied to estimate the associations among Se exposure levels, placenta weight, and birth weight. A total of 2758 mother-newborn pairs were included in this study. Each interquartile range (0.53 μg/g creatinine) increment in urine ln-Se concentration during the first trimester was associated with a mean 21.7 g (95% CI = -41.3g to -2.1g) decrease in birth weight and 3.6g (95% CI = -6.3g to -0.9g) decrease in placental weight. Compared with the lowest quartile (Q1) of ln-Se concentrations during the first trimester, significantly lower birth weight was found in the highest quartile (Q4) (β = -45.7g; 95% CI = -90.7g to -0.7g). Similar dose-response associations with birthweight and placental weight were found for Se exposure during the third trimester. Mediation analyses showed that 44.2% and 18.2% of the effects of Se exposure in first and third trimester on birth weight were mediated by decreased placental weight, respectively. Maternal Se exposure during pregnancy was negatively associated with birth weight, the reduction of placental weight may partially mediate the association of prenatal Se exposure with birth weight.

Maternal High Fat Diet Consumption Exaggerates Metabolic Disorders in Mice With Cigarette-Smoking Induced Intrauterine Undernutrition.

Objectives: Maternal smoking causes fetal underdevelopment and results in births which are small for gestation age due to intrauterine undernutrition, leading to various metabolic disorders in adulthood. Furthermore, postnatal high fat diet (HFD) consumption is also a potent obesogenic factor, which can interact with maternal smoking. In this study, we aimed to determine whether maternal HFD consumption during pregnancy can reverse the adverse impact of maternal smoking and change the response to postnatal HFD consumption.Methods: Female mice were exposed to cigarette smoke (SE, 2 cigarettes/day) or sham exposed for 5 weeks before mating, with half of the SE dams fed HFD (43% fat, SE+HFD). The same treatment continued throughout gestation and lactation. Male offspring from each maternal group were fed the same HFD or chow after weaning and sacrificed at 13 weeks.Results: Maternal SE alone increased body weight and fat mass in HFD-fed offspring, while SE+HFD offspring showed the highest energy intake and glucose metabolic disorder in adulthood. In addition, postnatal HFD increased the body weight and aggravated the metabolic disorder caused by maternal SE and SE+HFD.Conclusions: Maternal HFD consumption could not ameliorate the adverse effect of maternal SE but exaggerate metabolic disorders in adult offspring. Smoking cessation and a healthy diet are needed during pregnancy to optimize the health outcome in the offspring.