The concentration of selected elements in the placenta according to selected sociodemographic factors and their effect on birth mass and birth length of newborns

Background and aimsThe placenta is a remarkable organ which provides critical transport functions between the maternal and fetal circulations during pregnancy. The demand for mineral components increases during the gestational period, therefore, an appropriate intake of minerals, such as calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese, determines the correct growth and development of a fetus. The aim of the study was to assess the concentration of selected elements in the placenta, and to assess the impact of their concentrations on the birth weight and birth length of newborns. The second aim of the study was to assess the influence of selected sociodemographic factors on the concentration of elements in the placenta.ResultsThe study demonstrated that the age of mothers affected the concentration of Ca and Mn in the placenta, and their habit of tobacco smoking during the gestational period was associated with higher concentrations of Ca, P, K, Mg, Fe, Cu, and Cd in the placental tissue. The results also showed that concentrations of K, Fe, Zn, and Mn in the placental tissue affected birth length. Furthermore, the association was demonstrated between a higher Cd concentration in the placenta (≥ 0.0503 μg/g) and the birth anthropometric parameters of neonates.ConclusionsSmoking during pregnancy and environment pollution are the factors that affects the concentration of elements in the placenta and contributes to their high accumulation in the placenta. Smoking during pregnancy causes an increased concentration of cadmium in the placenta which has negative health effects for the newborn. Women living in a big city or village had a higher concentration of cadmium in their placentas compared to women living in smaller cities. The significant influence of some elements (K, Fe, Zn, Cu and Cd) on the newborn’s birth parameters was also demonstrated. The results of our research indicate the importance of the mother’s lifestyle in providing the placenta with elements, which affects the growth of the fetus.

• •The placenta is an organ that is responsible for the proper course of pregnancy and fetal development.
• •The demand for mineral components increases during the gestational period, therefore, an appropriate intake of minerals determines the correct growth and development of a fetus
• •Increased exposure to arsenic, cadmium and lead during the gestational period can induce miscarriage, premature delivery, risk of fetal death, inhibition of intrauterine growth and development of the fetus, and low birth parameters.

     

Relationships among the concentrations of 25 inflammation-associated proteins during the first postnatal weeks in the blood of infants born before the 28th week of gestation

Background

Inflammation appears to be involved in processes leading to organ damage in preterm newborns, yet little is known about the relationships among elevated concentrations of inflammation-associated proteins in the blood of preterm newborns.

Methods

In this exploratory study, we used an electrochemiluminescence method to measure 25 proteins in blood obtained on postnatal day 1 (range 1-3), day 7 (range 5-8), and day 14 (range 12-15) from 939 children born before the 28th week of gestation and evaluated to what extent those whose concentration of each protein was elevated (defined as in the highest quartile for gestational age and day the specimen was obtained) also had an elevated concentration of every other protein the same day or on a day 1 or 2 weeks later (p < .0001).

Results

On each of the 3 days assessed, elevated concentrations of 17 proteins were associated with elevated concentrations of 15 or more of the other 24 proteins. VEGF, VEGF-R1, VEGF-R2 were among these proteins, while IGFBP-1 was associated with 13 other proteins on day 7. An elevated concentration of eight proteins on day 1 predicted an elevated concentration of 10 or more proteins on day 7, while an elevated concentration of only two proteins on day 7 were associated with elevated concentrations of 10 or more proteins on day-14. Few associations were seen between days 1 and 14.

Conclusions/inferences

Inflammation is a diffuse process in ELGANs, with elevated concentrations of cytokines, chemokines, adhesion molecules, matrix metalloproteinases, a growth factor and its receptors, as well as a growth factor binding protein associated with each other the same day, as well as on subsequent days.     

Evidence that cognitive deficit in children is associated not only with iron deficiency,but also with blood lead concentration: A preliminary study

ObjectiveTo investigate whether blood lead concentrations are elevated in iron-deficient children, and to examine the association between iron deficiency and/or elevated blood lead concentration and cognitive deficits in children.MethodThe present study is a component of the Mothers’ and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 194 children who underwent testing of blood lead and serum C-reactive proteins (CRPs) and ferritin concentrations, and the Korean version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R), at 60 months of age. In addition, the mothers’ blood lead concentrations during pregnancy were included in the analyses. Multivariate linear regression analysis was performed to analyze the correlation between high blood lead and low serum ferritin concentrations, after adjustment for covariates, in children, as well as to analyze the association of verbal IQ with serum ferritin and blood lead concentrations.ResultsLead and ferritin concentrations were inversely and significantly associated in children after adjustment for covariates. Moreover, both concentrations were associated with verbal IQ, after adjustment for covariates, and each was associated with cognitive deficits after adjustment for the other. Sobel test statistics showed that blood lead concentration was a significant partial mediator for the relationship between iron deficiency and verbal IQ.ConclusionDue to the results discussed in the present study, cognitive deficit in children seems to be associated not only with iron deficiency, but also with blood lead concentration.     

Elevated Endogenous Erythropoietin Concentrations Are Associated with Increased Risk of Brain Damage in Extremely Preterm Neonates

Background

We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO) concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI).

Methods

Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO) was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age.

Results

Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55) Mental (OR 2.3; 95% CI 1.5-3.5) and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7) Development Indices (MDI, PDI), and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8). Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3), but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI.

Conclusion

hyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly.     

Seasonal variation of circulating plasma carotenoids in Mediterranean Great Tit males Parus major

Capsule Mediterranean Great Tits showed a marked increase in levels of circulating carotenoids during moult and autumn.

Aims To study seasonal variation in plasma carotenoid content during a whole annual cycle for Great Tits Parus major inhabiting a Mediterranean woodland.

Methods We used a sample of 71 adult male Great Tits captured in NE Spain during a whole year. Data were organized into four seasons (winter, breeding, moult and autumn). We sampled blood to extract plasma. Carotenoid plasma concentrations were analysed by High-performance liquid chromatography (HPLC).

Results Lutein and zeaxanthin content varied seasonally, with a marked increase in levels during moult and autumn. Within the moulting period, levels increased gradually as the season progressed. This pattern differed significantly from that previously described in northern European populations, where high values appear mainly in the breeding season. Carotenoid concentrations (lutein: 1.2?±?0.25, zeaxanthin: 0.07?±?0.03?µg mL^?1) were also lower than in northern Europe.

Conclusion Mediterranean Great Tits show a very different pattern of circulating carotenoids and lower levels than northern European populations. The increasing pattern of carotenoid availability found within the moulting period raises the need to control for the effect of sampling date when analysing data on carotenoid concentrations at different times of year.     

Comparison of fresh to fixed weights of the vervet monkey (Chlorocebus sabaeus) placenta and its relation to gestational age

Background Focus on the placenta as an agent of fetal development and offspring health outcomes is growing. Primate research facilities or zoos may collect and fix placental tissue for long‐term storage, but little is known about the effects of formalin fixation on the non‐human primate placenta. Methods We obtained 48 vervet monkey placentas from the St. Kitts Biomedical Research Foundation. We investigated via correlation coefficients and ANOVAs the effects of gestational age and original fresh weight on weight change due to fixation. We also used linear regression models to determine whether fixed tissue weight was predictive of fresh weight and gestational age. Results Although the vervet monkey placenta is described as bidiscoid, 14.6% of the placentas in this sample were fused into a single mass. A decrease in weight was the most common response to formalin fixation, with the greatest degree of loss experienced by the heaviest placentas (ANOVA, F = 5.99, P = 0.005). Gestational age was unrelated to weight change. Those placentas that increased in weight had the lowest fresh weights. Fixed weights significantly predicted both fresh weight and gestational age (r² = 0.78, P < 0.00001; r² = 0.76, P < 0.00001, respectively). Conclusions This paper adds to a sparse literature on the vervet monkey placenta. That fixed placentas are excellent predictors of both fresh weight and gestational age suggests that banked tissue may be a valuable resource for reconstructing aspects of individual life history, although caution must be exercised given the variability of weight change as a function of original placental size.     

Adrenoceptor-mediated activation of liver glycogen phosphorylase: effects of thyroid state.

Fetal mouse tissues on gestational days 14, 16 and 19 were incubated with ¹⁴C-corticosterone (B) and ³H-11-dehydrocorticosterone (A), and the steroids were separated chromatograhically to determine the ratio reduction/dehydrogenation. In placenta the ratio remained high, >6, throughout this period, while it rose from 0.06 to 0.6 in brain and from 0.1 to 0.5 in gut. In liver, the ratio increased from 0.29 on day 14 to 3.54 on day 16; in lung it rose from 0.29 on day 16 to 6.7 on day 19. Injection of mothers 16 hr earlier with dexamethasone increased the ratio in lung and placenta on day 16 but not earlier. The unchanged ³H-corticosterone recovered from fetal tissues 15 min after injection into mothers was <3% on day 14 but increased manyfold in all tissues by day 19. It is concluded that corticosteroids are regulated in fetal mouse tissues by the interconversion of the hormone and its 11-dehydro metabolite, and that the pattern varies in different tissues and changes with gestational age.     

Association of organophosphate pesticide exposure and paraoxonase with birth outcome in Mexican-American women

BackgroundEpidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association.MethodsThe study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1₁₉₂ and PON1₋₁₀₈) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records.ResultsInfants'' PON1 genotype and activity were associated with birth outcome, but mothers'' were not. Infants with the susceptible PON1_−108TT genotype had shorter gestational age (β = −0.5 weeks, 95% Confidence Interval (CI): −0.9, 0.0) and smaller head circumference (β = −0.4 cm, 95% CI: −0.7, 0.0) than those with the PON1_−108CC genotype. Infants'' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1_−108TT genotype (p-value_interaction = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-value_interaction = 0.06) and head circumference (p-value_interaction<0.01) in infants with non-susceptible genotypes.ConclusionsInfants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing to preterm or low birth weight birth.     

Literature-Informed Analysis of a Genome-Wide Association Study of Gestational Age in Norwegian Women and Children Suggests Involvement of Inflammatory Pathways

BackgroundFive-to-eighteen percent of pregnancies worldwide end in preterm birth, which is the major cause of neonatal death and morbidity. Approximately 30% of the variation in gestational age at birth can be attributed to genetic factors. Genome-wide association studies (GWAS) have not shown robust evidence of association with genomic loci yet.MethodsWe separately investigated 1921 Norwegian mothers and 1199 children from pregnancies with spontaneous onset of delivery. Individuals were further divided based on the onset of delivery: initiated by labor or prelabor rupture of membranes. Genetic association with ultrasound-dated gestational age was evaluated using three genetic models and adaptive permutations. The top-ranked loci were tested for enrichment in 12 candidate gene-sets generated by text-mining PubMed abstracts containing pregnancy-related keywords.ResultsThe six GWAS did not reveal significant associations, with the most extreme empirical p = 5.1 × 10⁻⁷. The top loci from maternal GWAS with deliveries initiated by labor showed significant enrichment in 10 PubMed gene-sets, e.g., p = 0.001 and 0.005 for keywords "uterus" and "preterm" respectively. Enrichment signals were mainly caused by infection/inflammation-related genes TLR4, NFKB1, ABCA1, MMP9. Literature-informed analysis of top loci revealed further immunity genes: IL1A, IL1B, CAMP, TREM1, TFRC, NFKBIA, MEFV, IRF8, WNT5A.ConclusionOur analyses support the role of inflammatory pathways in determining pregnancy duration and provide a list of 32 candidate genes for a follow-up work. We observed that the top regions from GWAS in mothers with labor-initiated deliveries significantly more often overlap with pregnancy-related genes than would be expected by chance, suggesting that increased sample size would benefit similar studies.     

Cellular and molecular atlas of the placenta from a COVID‐19 pregnant woman infected at midgestation highlights the defective impacts on foetal health

ObjectivesThe impacts of the current COVID‐19 pandemic on maternal and foetal health are enormous and of serious concern. However, the influence of SARS‐CoV‐2 infection at early‐to‐mid gestation on maternal and foetal health remains unclear.Materials and methodsHere, we report the follow‐up study of a pregnant woman of her whole infective course of SARS‐CoV‐2, from asymptomatic infection at gestational week 20 to mild and then severe illness state, and finally cured at Week 24. Following caesarean section due to incomplete uterine rupture at Week 28, histological examinations on the placenta and foetal tissues as well as single‐cell RNA sequencing (scRNA‐seq) for the placenta were performed.ResultsCompared with the gestational age‐matched control placentas, the placenta from this COVID‐19 case exhibited more syncytial knots and lowered expression of syncytiotrophoblast‐related genes. The scRNA‐seq analysis demonstrated impaired trophoblast differentiation, activation of antiviral and inflammatory CD8 T cells, as well as the tight association of increased inflammatory responses in the placenta with complement over‐activation in macrophages. In addition, levels of several inflammatory factors increased in the placenta and foetal blood.ConclusionThese findings illustrate a systematic cellular and molecular signature of placental insufficiency and immune activation at the maternal–foetal interface that may be attributed to SARS‐CoV‐2 infection at the midgestation stage, which highly suggests the extensive care for maternal and foetal outcomes in pregnant women suffering from COVID‐19.     

Relatively Small Contribution of Methylation and Genomic Copy Number Aberration to the Aberrant Expression of Inflammation-Related Genes in HBV-Related Hepatocellular Carcinoma

BackgroundIt is well known that chronic inflammation plays a pivotal role in the development of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). However, the causes behind aberrant expression of inflammation-related genes occurred in HCC remain unclear.MethodsWe performed array-based analyses to comprehensively investigate the contributions of DNA methylation and somatic copy number aberration (SCNA) to the aberrant expression of 1,027 inflammation-related genes in 30 HCCs and paired non-tumor tissues. The results were validated in public datasets and an additional sample set of 47 paired HCCs and non-tumor tissues.ResultsWe identified 252 differentially expressed, 125 aberrantly methylated and 287 copy number changed inflammation-related genes. Despite reasonable statistical power, among them, only 11 genes and 56 genes whose aberrant expression was associated with DNA methylation or SCNA, respectively. DNA methylation and SCNA together contributed to less than 30% aberrant expression of inflammation-related genes.ConclusionThese results suggest that molecular mechanisms other than DNA methylation and SCNA might play major role in the regulation of aberrant expression of inflammation-related gene in HBV-related HCCs.     

High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth,and the source may be the damaged fetal membranes

BackgroundHigh Mobility Group Box-1 (HMGB1) is considered a prototype alarmin molecule. Upon its extracellular release, HMGB1 engages pattern recognition receptors and the Receptor for Advanced Glycation End-products (RAGE) followed by an outpouring of inflammatory cytokines, including interleukin (IL)-6.MethodsWe assayed the amniotic fluid (AF) levels of HMGB1 and IL-6 in 255 women that either had a normal pregnancy outcome or delivered preterm. Immunohistochemistry on fetal membranes was used for cellular localization and validation of immunoassay findings. HMGB1 also was analyzed in amniochorion tissue explants subjected to endotoxin.ResultsAF HMGB1 levels are not gestational age regulated but are increased in women with intra-amniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments.ConclusionsOur research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure to elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth.     

不同胎龄早产儿早期凝血指标的变化及其临床意义

目的:研究不同胎龄早产儿早期凝血指标的变化及其临床意义。方法:选取2012年1月至2017年7月期间我院出生的新生儿392例为研究对象。根据新生儿胎龄的不同分为早期早产儿组(胎龄27~31周)78例、中期早产儿组(胎龄32~33周)102例、晚期早产儿组(胎龄34~36周)116例以及足月新生儿组(胎龄37~42周)96例。四组新生儿出生后2h内抽取静脉血检测凝血指标,包括凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、纤维蛋白原(FIB),并应用Pearson相关性分析分析新生儿胎龄与上述各项凝血指标水平的相关性。结果:早期早产儿组、中期早产儿组、晚期早产儿组、足月新生儿组的出生体重以及胎龄呈逐渐上升趋势,不同组别新生儿的出生体重以及胎龄差异均有统计学意义(P0.05)。早期早产儿组、中期早产儿组、晚期早产儿组、足月新生儿组PT、APTT均呈逐渐下降趋势,FIB呈逐渐上升趋势,不同组别新生儿PT、APTT、FIB差异均有统计学意义(P0.05)。Pearson相关性分析显示,新生儿胎龄与PT、APTT呈负相关(r=-0.567、-0.691,P=0.000、0.000),而新生儿胎龄与FIB水平呈正相关(r=0.623,P=0.000)。结论:不同胎龄早产儿早期凝血功能存在异常变化,新生儿胎龄与PT、APTT均呈负相关关系,与FIB呈正相关关系,临床应予以重视,及时检测其凝血指标,必要时应予以干预治疗。     

Identification and characterization of the adenosine 3′,5′-cyclic monophosphate binding proteins appearing during the development of Dictyostelium discoideum

A photosensitive, radioactive analogue of cyclic adenosine monophosphate, 8-azido-adenosine 3′,5′-[³²P]monophosphate (8-N₃-cyclic AMP), was used to label the cyclic AMP binding proteins of Dictyostelium discoideum. During development cytosolic proteins appear which are specifically labeled by the photoaffinity agent. The proteins are developmentally regulated since they are only found in starved, developing cells. Unlabeled cyclic AMP competes specifically with the labeled analogue for protein binding sites in contrast to unlabeled 5′-AMP which does not compete. A mutant which develops spores but is deficient in stalk cell production produces a different set of cyclic AMP binding proteins from the parent strain.     

Sequelae of syndrome X in children born small for gestational age

OBJECTIVE: Low birth weight is associated with the presence of syndrome X in adults. We studied the components of this syndrome in prepubertal children born SGA (small for gestational age) and children born AGA (appropriate for gestational age). METHODS: Twenty-nine SGA children, age (mean +/- SD) 9.1 +/- 1.1 years and 24 AGA children, age 9.0 +/- 1.1 years were studied. Fasting serum lipid concentrations were determined. A hyperinsulinemic euglycemic clamp was performed to measure insulin sensitivity. Ambulatory monitoring was performed to obtain 24-hour recordings of blood pressure. RESULTS: Prepubertal SGA children are less insulin sensitive and have a higher nighttime systolic blood pressure (SBP) after correction for BMI than children born AGA. No differences were found in lipid concentrations between the 2 groups. CONCLUSIONS: Not all components of syndrome X can yet be found in 9-year-old children born SGA; follow-up of this cohort is required.     

Placental membrane-type metalloproteinases (MT-MMPs): Key players in pregnancy

abstract

Membrane-type matrix metalloproteinases (MT-MMPs) are a sub-family of zinc-dependent endopeptidases involved in the degradation of the extracellular matrix. Although MT-MMPs have been mainly characterized in tumor biology, they also play a relevant role during pregnancy. Placental MT-MMPs are required for cytotrophoblast migration and invasion of the uterine wall and in the remodeling of the spiral arteries. They are involved in the fusion of cytotrophoblasts to form the syncytiotrophoblast as well as in angiogenesis. All these processes are crucial for establishing and maintaining a successful pregnancy and, thus, MT-MMP activity has to be tightly regulated in time and space. Indeed, a de-regulation of MT-MMP expression has been linked with pregnancy complications such as preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM) and was also found in maternal obesity. Here we review what is currently known about MT-MMPs in the placenta, with a focus on their general features, their localization and their involvement in pregnancy disorders.     

Blood pressure in first 10 years of life: the Brompton study.

OBJECTIVES--To determine the normal range of blood pressure and its pattern of change in the first 10 years of life. To estimate at what age (if any) children consistently appear in one part of the blood pressure distribution and at what age familial correlations in blood pressure become significant. DESIGN--Longitudinal cohort study. SETTING--South east England. SUBJECTS--2088 children of both sexes born consecutively in Farnborough Hospital, Kent, and their parents. MAIN OUTCOME MEASURE--Blood pressure measured by Doppler ultrasonography and sphygmomanometry. RESULTS--Systolic blood pressure rose from a mean of 88.5 mm Hg at age 6 months to 96.2 mm Hg at 8 years measured with a 8 cm cuff and from 89.1 mm Hg at age 5 years to 94.3 mm Hg at age 10 years measured with a 12 cm cuff. The larger cuff gave blood pressure readings about 6 mm Hg lower. This effect was independent of body weight and arm circumference. Diastolic blood pressure rose from 57.8 mm Hg at 5 years to 61.8 mm Hg at 10 years (12 cm cuff). There was only about 1 mm Hg difference between sexes. Blood pressure was correlated with weight, weight adjusted for height, height, and arm circumference at all ages studied. The correlation coefficient of repeated yearly measurements increased steadily with age from 0.28 at 2 years to 0.59 at 10 years. The correlation coefficients between child''s blood pressure and mother''s average blood pressure increased from 0.1 at age 1 year to 0.23 at age 10. CONCLUSIONS--Blood pressure changes relatively little between the ages of 6 months and 10 years. Yet because of the increasing strength of between occasion and family correlations, children are more consistently occupying a specific part of the blood pressure distribution as they grow older. Studies in children should help determine why some adults have hypertension and others do not.