Maternal smoking during pregnancy and cord blood DNA methylation: new insight on sex differences and effect modification by maternal folate levels

Maternal smoking during pregnancy may affect newborn DNA methylation (DNAm). However, little is known about how these associations vary by a newborn’s sex and/or maternal nutrition. To fill in this research gap, we investigated epigenome-wide DNAm associations with maternal smoking during pregnancy in African American mother-newborn pairs. DNAm profiling in cord (n = 379) and maternal blood (n = 300) were performed using the Illumina HumanMethylation450 BeadChip array. We identified 12 CpG sites whose DNAm levels in cord blood were associated with maternal smoking, at a false discovery rate <5%. The identified associations in the GFI1 gene were more pronounced in male newborns than in females (P = 0.002 for maternal smoking × sex interaction at cg18146737). We further observed that maternal smoking and folate level may interactively affect cord blood DNAm level at cg05575921 in the AHRR gene (P = 5.0 × 10^?4 for interaction): compared to newborns unexposed to maternal smoking and with a high maternal folate level (>19.2 nmol/L), the DNAm level was about 0.03 lower (P = 3.6 × 10^?4) in exposed newborns with a high maternal folate level, but was 0.08 lower (P = 1.2 × 10^?8) in exposed newborns with a low maternal folate level. Our data suggest that adequate maternal folate levels may partly counteract the impact of maternal smoking on DNAm. These findings may open new avenues of inquiry regarding sex differences in response to environmental insults and novel strategies to mitigate their intergenerational health effects through optimization of maternal nutrition.     

Maternal lipid metabolism and placental lipid transfer

During early pregnancy, long-chain polyunsaturated fatty acids (LC-PUFA) may accumulate in maternal fat depots and become available for placental transfer during late pregnancy, when the fetal growth rate is maximal and fetal requirements for LC-PUFAs are greatly enhanced. During this late part of gestation, enhanced lipolytic activity in adipose tissue contributes to the development of maternal hyperlipidaemia; there is an increase in plasma triacylglycerol concentrations, with smaller rises in phospholipid and cholesterol concentrations. Besides the increase in plasma very-low-density lipoprotein, there is a proportional enrichment of triacylglycerols in both low-density lipoproteins and high-density lipoproteins. These lipoproteins transport LC-PUFA in the maternal circulation. The presence of lipoprotein receptors in the placenta allows their placental uptake, where they are hydrolysed by lipoprotein lipase, phospholipase A(2) and intracellular lipase. The fatty acids that are released can be metabolized and diffuse into the fetal plasma. Although present in smaller proportions, maternal plasma non-esterified fatty acids are also a source of LC-PUFA for the fetus, their placental transfer being facilitated by the presence of a membrane fatty acid-binding protein. There is very little placental transfer of glycerol, whereas the transfer of ketone bodies may become quantitatively important under conditions of maternal hyperketonaemia, such as during fasting, a high-fat diet or diabetes. The demands for cholesterol in the fetus are high, but whereas maternal cholesterol substantially contributes to fetal cholesterol during early pregnancy, fetal cholesterol biosynthesis rather than cholesterol transfer from maternal lipoproteins seems to be the main mechanism for satisfying fetal requirements during late pregnancy.     

Evaluation of cord blood immunoglobulin E and its association with maternal factors in a group of Iranian newborns

Allergic disorders are among the most common diseases around the world especially in children. Many factors contribute to the pathogenesis of atopic disorders, but early events during the pregnancy are very important. The aim of this study was to evaluate the level of cord blood immunoglobulin E (CB-IgE) and its association with maternal in a group of Iranian newborns. In a cross-sectional study, 163 pregnant women randomly selected and information about pregnancy and atopy were taken by questionnaire. Blood samples of mothers and matched cord blood were collected and total serum IgE levels were measured by enzyme-linked immunosorbent assay (ELISA) method. To rolling out the possibility of contamination with maternal blood, total IgA was checked for all the cord blood samples. Sixteen percent of mothers had the history of atopic diseases and the mean IgE level was significantly higher in an atopic than nonatopic mothers (241 vs 102, P < 0.001). About 73.9% of cord blood samples, had high IgE level (>0.9 IU/mL). The level of cord blood IgE (CB-IgE) was not significantly different in male and female newborns (2.14 vs 2.15 IU/mL). There was no significant correlation between maternal factors such as age, pregnancy variables, allergens exposure, smoking, and maternal IgE with cord blood IgE. The results of this study showed that CB-IgE is high in a remarkable number of samples; independent of maternal or fetal factors. Further studies need to evaluate the reasons for the high level of IgE in cord blood in our area.     

Cord blood ASP is predicted by maternal lipids and correlates with fetal birth weight

Background: The acylation stimulating protein (ASP) is a potent lipogenic adipokine that correlates with postprandial triglyceride (TG) clearance and is linked to the pathophysiology of obesity and related disorders. Objective: To investigate ASP levels in cord blood and its relation to maternal and cord blood lipid parameters and fetal birth weight. Methods and Procedures: Thirty nondiabetic pregnant women, their newborns, and thirty‐three nonpregnant controls were included in this study. Fasting maternal and cord blood ASP, TGs, nonesterified fatty acids (NEFAs), cholesterol, glucose levels, in addition to maternal BMI and fetal birth weight were measured. Results: No significant difference was found between cord blood ASP (16.3 ± 0.96 nmol/l) and ASP levels in the adult controls (15.7 ± 1.0 nmol/l). Cord blood ASP, however, was lower than maternal plasma ASP levels (25.4 ± 1.6 nmol/l, P < 0.001). Yet, lipid levels in cord blood, particularly TGs were markedly decreased compared to control and maternal TG levels (threefold and 7.4‐fold, P < 0.001 respectively). Maternal TGs significantly correlated with fetal birth weight (r = 0.54, P = 0.002). Multiple regression analysis showed that maternal TGs (β = 0.57, P = 0.01) and NEFAs (β = 0.43, P = 0.024) predicted 45% variation in cord blood ASP levels, independent of all measured maternal and cord blood parameters. Cord blood ASP showed a positive correlation with fetal birth weight (r = 0.524, P = 0.037) in neonates above average fetal birth weight of the studied population. Discussion: This is the first study investigating ASP in cord blood. We suggest that maternal hypertriglyceridemia is associated with increased fetal ASP production, thus enhancing fetal fat storage independent of maternal glucose variations in nondiabetic women.     

Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placenta

Maternal hypercholesterolemia (HC) during pregnancy and gestational diabetes mellitus (GDM) are associated with disturbance of fetal development which may also modify key features of placental functions. In this study, we evaluated the impact of maternal hypercholesterolemia on placental cholesterol and lipid metabolism in 59 women classified in two groups according to the median concentration of plasma total cholesterol (6.42 mM). The impact of GDM was also evaluated on the metabolism of placentas obtained from 7 insulin-treated GDM and 7 non-GDM women. We showed that high maternal circulating cholesterol is associated with a significant increase in the LDL-cholesterol, ApoB-100 and triglyceride concentrations in the maternal blood. However the level of cholesterol in the venous cord blood and placenta remains unchanged in response to modification in maternal cholesterol profile. The levels of Fatty acid synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in the HC group while expression of both sterol regulatory element-binding proteins-1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified. GDM is not associated with modification in the maternal lipid profile but it increases the concentration of inflammatory cytokines (IL-1beta and TNF-alpha) in placenta which correlates with a dramatic induction of FAS expression without affecting the expression of mature SREBPs proteins. In conclusion, our study suggests that in placenta, expressions of key proteins involved in de novo lipid synthesis are affected by changes in maternal metabolism (HC and GDM) that may subsequently affect fetal development.     

Importance of apolipoproteins in lipid metabolism

Lipids, which serve as a source of energy and are an important constituent of cell membrane structure, are readily stored in the body. By definition they are insoluble in water. Specific proteins called apolipoproteins interact with lipids to form soluble lipid-protein complexes called lipoproteins. It is in this form that the major lipids — cholesterol, triglyceride and phospholipid — circulate in plasma. Unesterified fatty acids, another major lipid group, are bound to albumin in the circulation. The plasma lipoproteins are complex macromolecules composed of lipids, apolipoproteins and carbohydrates. The relative proportions of these components differ markedly between lipoprotein classes.

Hyperlipidemia is a term used for increased concentrations of plasma cholesterol and/or triglycerides. Any one plasma lipid is present in several types of lipoproteins. Thus, hyperlipidemia implies the presence of hyperlipoproteinemia. The latter has important therapeutic implications. Most of the recent attempts at classification have been directed at the lipoprotein level of plasma lipid organization.

Decreased concentrations of lipids in plasma can be achieved by altering the rates of metabolism of lipoproteins. Decrease in lipoprotein synthesis, increased catabolism or impaired release from cells into the blood stream may all result in a decrease of plasma lipids. Drugs which affect one or more of these factors are used to treat hyperlipoproteinemia. In order to elucidate the mechanism of action of hypolipidemic drugs it is necessary to understand the lipoprotein defect at the molecular level. This requires a more detailed knowledge of lipoprotein metabolism than is presently available for most of the hyperlipoproteinemias.

This paper will review some of the generally accepted properties of the plasma lipoproteins, describe some difficulties which hamper the understanding of lipoprotein metabolism, and identify possible mechanisms by which drugs may affect lipoprotein metabolism.     

Selenium levels in related biological samples: human placenta, maternal and umbilical cord blood, hair and nails.

A study on selenium levels has been carried out in human placenta, maternal and umbilical cord blood, hair and nails of a group of 50 mothers and in the hair of the newborns. The determinations were perfomed by electrothermal atomic absorption spectrometry. The selenium concentration obtained for each sample type was as follows: For the human placenta the values obtained were between 0.56 and 1.06 microg/g (mean +/- standard deviation: 0.81 +/- 0.02 microg/g). The levels for the umbilical cord blood were 51.1-104.2 microg/l (76.3 +/- 6.5 microg/l). For the maternal blood the values measured were between 57.3 and 117.9 microg/l (90.0 +/- 15.2 microg/l), and for hair and nails were 0.22-1.5 microg/g (0.60 +/- 0.37 microg/g) and 0.46-1.57 microg/g (0.90 +/- 0.27 microg/g), respectively. For the hair of the newborns the values obtained were between 0.40 and 2.53 microg/g (1.04 +/- 0.48 microg/g). The effect of different variables as age, habitat, nutritional index or gestation age of the mothers on the selenium concentration in the samples was studied. The influence of the habitat is significant with a confidence level of 95% for the selenium concentration in maternal blood and umbilical cord blood samples. The influence of the mothers' age is significant with a confidence level of 95% for the selenium concentration in the umbilical cord blood samples. For the placenta samples, the effect of the nutritional index is significant with a confidence level of 95%. There is a positive correlation between samples of umbilical cord blood and the newborns' hair, between placenta and umbilical cord, and between cord blood and maternal blood.     

1H-NMR-based metabolic profiling of maternal and umbilical cord blood indicates altered materno-foetal nutrient exchange in preterm infants

Background

Adequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used ¹H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth.

Methodology

The metabolic profile in ¹H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates.

Principal Findings

Clear distinctions between maternal and cord plasma of all samples were observed by principal component analysis (PCA). Levels of amino acids, glucose, and albumin-lysyl in cord plasma exceeded those in maternal plasma, whereas lipoproteins (notably low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and lipid levels were lower in cord plasma from both VLBW and FT neonates. The metabolic signature of mothers delivering VLBW infants included decreased levels of acetate and increased levels of lipids, pyruvate, glutamine, valine and threonine. Decreased levels of lipoproteins glucose, pyruvate and albumin-lysyl and increased levels of glutamine were characteristic of cord blood (both arterial and venous) from VLBW infants, along with a decrease in levels of several amino acids in arterial cord blood.

Conclusion

These results show that, because of its characteristics and simple non-invasive mode of collection, cord plasma is particularly suited for metabolomic analysis even in VLBW infants and provides new insights into the materno-foetal nutrient exchange in preterm infants.     

Cord blood plasma lipoproteins inhibit mitogen-stimulated lymphocyte proliferation

Lipoproteins were isolated from adult plasma and the umbilical cord blood plasma of newborn infants and were compared for their capacity to inhibit mitogen-stimulated [3H]thymidine uptake of adult peripheral blood mononuclear cells in vitro. Relative to the comparable adult lipoproteins, cord blood low density lipoproteins and high density lipoproteins inhibited mitogen stimulation at twofold to fourfold lower total protein concentrations. Apoproteins AI, B, and E were quantitated by radioimmunoassay of each of the adult and cord blood lipoprotein fractions. A strong correlation was observed between inhibitory activity and the amount of apoprotein E in the cord blood low and high density lipoproteins. Further evidence that lipoproteins containing apoprotein E accounted for the difference in suppressive activity of cord blood low and high density lipoproteins relative to the adult lipoproteins was obtained by selective removal of the apoprotein E-containing lipoproteins by using immunoaffinity chromatography or heparin-agarose adsorption. The results indicated that cord blood lipoproteins containing apoprotein E in association with apoproteins AI or B are capable of suppressing lymphocyte proliferation in vitro.     

Prevention of coronary heart disease by raising high-density lipoprotein cholesterol?

Consistent with several potentially anti-atherogenic activities of high-density lipoproteins in vitro, low plasma levels of high-density lipoprotein cholesterol are associated with an increased risk of coronary heart disease. In addition to genes, lifestyle factors (e.g. smoking, being overweight and physical inactivity) strongly affect plasma high-density lipoprotein cholesterol levels. Moreover, a low level of high-density lipoprotein cholesterol interacts with other risk factors. Raising of high-density lipoprotein cholesterol by either adjustments of lifestyle or drug intervention as well as elimination of additional risk factors are thus thought to affect coronary risk. Here, we summarize the outcomes of observational and interventional studies as well as genetic and experimental research which have recently much advanced our understanding of the function and regulation of high-density lipoprotein metabolism. We conclude from the data that changes in the kinetics and functionality of high-density lipoprotein rather than changes in plasma high-density lipoprotein cholesterol levels per se will affect the anti-atherogenicity of therapeutic interference with high-density lipoprotein metabolism.     

Role of plasma lecithin:cholesterol acyltransferase in the metabolism of high density lipoproteins

The role of the plasma lecithin:cholesterol acyltransferase reaction in the esterification of the cholesterol of human and baboon plasma high density lipoproteins has been studied. Human plasma was incubated in vitro, and the initial rate of cholesterol esterification in lipoprotein fractions obtained by chromatography on hydroxylapatite was determined. The rate of esterification was greater in the high density lipoprotein fraction than in the low density lipoprotein fraction. High density lipoproteins from human and baboon plasma were filtered through columns of Sephadex G 200, and the relative concentrations in the effluent of key lipids involved in the acyltransferase reaction were determined. The ratio of esterified to unesterified cholesterol varied across the lipoprotein peak obtained from either type of plasma. The relative concentration of lecithin compared to sphingomyelin also varied across the peaks obtained with human high density lipoproteins. When human or baboon plasma was incubated with cholesterol-(14)C and the high density lipoproteins were filtered through Sephadex, the specific activity of the esterified cholesterol varied across the lipoprotein peak. Similar results were obtained when plasma esterified cholesterol was labeled in vivo by the injection of labeled mevalonate into baboons. The data suggest that the acyltransferase reaction is the major source of the esterified cholesterol of the high density lipoproteins.     

Effects of alcohol on the major steps of reverse cholesterol transport

The effects of moderate alcohol consumption on the capacity of blood sera to promote acceptance of cholesterol (C) from Fu5AH hepatoma cells, esterification of delivered free C, and transfer of produced cholesteryl esters to apolipoprotein (apo) B-containing lipoproteins have been studied. Twenty male subjects with relatively high (>50 mg/dl, n = 10) and low (<50 mg/dl, n = 10) high density lipoprotein (HDL) C levels consumed for eight weeks red grape wine (0.3 g ethanol/kg body mass per day). Alcohol consumption reduced total C and low density lipoprotein C levels in both groups of subjects. Low HDL C subjects showed an increase in HDL C, apo AI, apo AII, and lipoprotein (Lp) AI particle levels after alcohol consumption. Alcohol did not affect free C efflux from the cells. However, after the following period of substitution of alcohol with an isocaloric amount of red grape juice, cellular C efflux markedly reduced. While lecithin:cholesterol acyltransferase (LCAT) activity increased during alcohol consumption only in subjects with low HDL C, high HDL C subjects showed a significant decrease in cholesteryl ester transfer protein (CETP) activity. At the same time, alcohol consumption reduced the endogenous C esterification rate and increased the transfer of endogenous cholesteryl esters to apo B-containing lipoproteins in both groups. Thus, alcohol consumption in moderate doses enhanced the anti-atherogenicity of the serum lipoprotein spectrum, supporting more effective C efflux from peripheral cells and transport of accepted C to apo B-containing lipoproteins. The effects of alcohol on the reverse cholesterol transport depend on the initial HDL C level.     

Psychosocial and reproductive influences on plasma lipids, lipoproteins, and atherosclerosis in nonhuman primates

Until recently, research in experimental atherosclerosis focused primarily on nutritional influences on plasma lipids, lipoproteins, and atherosclerosis. We review here the results of recent studies of independent and interactive influences of psychosocial and reproductive influences on atherosclerosis in nonhuman primates. These studies have produced evidence that, as in human beings, individuals with certain personality characteristics who are frequently faced with stressful or challenging situations are at increased risk of coronary artery disease. Preliminary evidence suggests that this relationship may be mediated, in part, by heightened sympathetic arousal, i.e., cardiovascular hyperresponsiveness, to the environmental challenge. Also, as in human beings, evidence has been produced that certain negative behavioral and psychosocial variables can have a significant independent influence on plasma lipids. As regards reproductive influences, the cynomolgus macaque seems to share with premenopausal white women a relative protection against coronary artery atherosclerosis. This "female protection" against diet-induced atherosclerosis is abolished by ovariectomy, which also results in increased total plasma and low density lipoprotein (LDL) cholesterol concentrations. Subordinate social status also seems to abolish female protection in some individuals. Preliminary evidence suggests that subordinate females most liable to this loss of protection are those with apparent stress-induced chronic ovarian endocrine dysfunction, which, in turn, is associated with increased plasma LDL cholesterol and decreased plasma high density lipoprotein (HDL) cholesterol concentrations.     

Serum lipoproteins in cholesterol-fed pigs after partial ileal bypass

Partial ileal bypass (PIB) surgery was performed in hypercholesterolaemic mini-pigs and Yorkshire pigs fed a semipurified diet containing 1% (W/W) of cholesterol. PIB drastically reduced serum total cholesterol and phospholipid concentrations and the cholesterol: phospholipid ratio in spite of continuation of cholesterol feeding. The relative distribution of cholesterol between serum lipoproteins was affected by PIB; the surgical treatment caused an increase in the ratio of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) cholesterol. Serum apo B and apo A levels were rapidly decreased by PIB. The operation induced a decrease in the cholesterol: apo B and cholesterol: apo A ratios. It is suggested that the pig is a suitable animal model to study PIB-induced changes in lipoprotein metabolism.     

Transfer of excess cholesterol from human red blood cells to plasma in vitro

This study examined the ability of plasma and plasma fractions from normolipidaemic subjects and plasma from a patient with homozygous familial high density lipoprotein deficiency (Tangier disease) to promote loss of excess cholesterol from red blood cells in vitro. Isolated high density lipoproteins were the most potent plasma fraction for removing excess cellular cholesterol. Lipoprotein-deficient plasma and human serum albumin, but not very low density lipoproteins and low density lipoproteins, also removed excess cholesterol from the red blood cells. The near absence of high density lipoproteins in plasma from the patient with Tangier disease did not result in an abnormally low rate of cholesterol loss from the enriched red blood cells. These results suggest that normal levels of high density lipoproteins are not vital for the removal of excess cholesterol from red blood cells by plasma.     

Relationship between Irisin Concentration and Serum Cytokines in Mother and Newborn

IntroductionIrisin is considered to be a myokine and adipokine that may also participate in reproductive functions, as it increases significantly throughout pregnancy. However, the regulation of circulating irisin and its relationship with other cytokines has not been assessed thus far in pregnant women and their offspring.ObjectiveThe aim of this study was to evaluate differences in irisin and cytokine concentrations between women at the end of pregnancy and their offspring, as well as the relationship between maternal and newborn irisin and maternal and newborn biomarkers.MethodsTwenty-eight mother/newborn pairs were included in this study. The following biomarkers were evaluated in maternal venous and arterial umbilical cord blood samples: irisin, 27 cytokine panel, total antioxidant capacity (TAC), total plasma protein, and free fatty acid concentration.ResultsThe newborns had significantly lower irisin concentrations compared to their mothers (p = 0.03), but this difference was present only in babies born from mothers without labor prior to cesarean section delivery (p = 0.01). No significant differences in maternal and newborn irisin concentrations were found between diabetic and non-diabetic mothers or between overweight/obese and normal weight mothers. A significant positive correlation was found between TAC level and irisin concentration in newborns. Maternal and newborn interleukin (IL)-1β, IL-1RA, IL-5, IL-7, and interferon gamma-induced protein (IP)-10 levels were significantly positively correlated with irisin concentrations in both study groups. In addition, maternal IL1β, IL-5, IL-7, and IP-10 levels positively predicted maternal irisin concentrations. Furthermore, arterial cord blood TAC and IL-1β and IL1-RA levels positively predicted newborn irisin concentrations. Multiple regression analyses showed that maternal IL-13 negatively predicted offspring irisin levels (p = 0.03) and that maternal IL-1β positively predicted newborn irisin concentrations (p = 0.046).ConclusionNo evidence was found that serum irisin concentrations in mothers at pregnancy termination or those of their newborns correlated with maternal body mass index, the presence of diabetes mellitus, or free fatty acid levels. However, the results of this study indicated that cytokines might predict irisin concentration in mothers and their offspring, although interactions between irisin levels during pregnancy and the newborn have not yet been fully elucidated.     

孕期增重过多对孕妇肠道菌群及妊娠结局的影响

目的 探讨孕期增重过多对孕妇肠道菌群及妊娠结局的影响。方法 选取2016年10月至2017年7月中国人民解放军联勤保障部队第九六七医院行产前检查并住院分娩的孕妇及其新生儿配对,共69对,根据孕期体质量增长情况,分为孕期体质量增长正常组和孕期体质量增长过多组,收集孕妇孕晚期粪便样本,分析孕妇粪便菌群的变化;比较两组孕妇妊娠期并发症、空腹血糖水平、血脂指标［总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）］、新生儿出生体质量和新生儿并发症等数据。结果 （1）与孕期增重正常组相比,增重过多组孕妇肠道内肠杆菌、酵母高于增重正常组,而双歧杆菌、乳杆菌、拟杆菌低于增重正常组（Ps<0.05）;（2）增重过多组血清TC、TG和LDL-C水平明显增高,HDL-C水平降低（Ps<0.05）;（3）增重过多组妊娠期并发症发生率增加（P<0.05）;（4）增重过多组新生儿体质量明显增加,导致巨大儿发生率明显升高,高胆红素血症的发生率也增加（P<0.05）。结论 孕期增重过多孕妇肠道内菌群出现异常改变,导致母亲及子代并发症发生率增加,尽早进行干预治疗可能为降低发病率提供契机。     

原发性肾病综合征高脂血症发生机制的研究进展*

摘要：原发性肾病综合征高脂血症主要表现为血浆总胆固醇（Ch）和低密度脂蛋白胆固醇（LDL-Ch）明显升高,甘油三酯（TG）和极 低密度脂蛋白胆固醇（VLDL-Ch）升高。高密度脂蛋白胆固醇（HDL-Ch）浓度可降低或不变,但HDL的亚型分布异常,即HDL3 增 加而HDL2 减少。这提示我们HDL3 转变为富含CH的HDL2 成熟障碍。不过,关于高脂血症在肾病综合征的发生机制较为复杂, 还不十分清楚。但是目前有关该机制的观点主要集中在（1）低白蛋白血症刺激肝脏合成胆固醇、甘油三酯、脂蛋白增加,（2）外周 脂蛋白的清除障碍,（3）高密度脂蛋白（HDL）的成熟障碍,本文就此做一综述。     

Maternal and fetal leptin,adiponectin levels and associations with fetal insulin sensitivity

Objective:

It remains uncertain whether leptin and adiponectin levels are correlated in maternal vs. fetal circulations. Little is known about whether leptin and adiponectin affect insulin sensitivity during fetal life.

Design and Methods:

In a prospective singleton pregnancy cohort (n = 248), we investigated leptin and adiponectin concentrations in maternal (at 24‐28 and 32‐35 weeks of gestation) and fetal circulations, and their associations with fetal insulin sensitivity (glucose/insulin ratio, proinsulin level).

Results:

Comparing concentrations in cord vs. maternal blood, leptin levels were 50% lower, but adiponectin levels more than doubled. Adjusting for gestational age at blood sampling, consistent and similar positive correlations (correlation coefficients: 0.31‐0.34, all P < 0.0001) were observed in leptin or adiponectin levels in maternal (at 24‐28 or 32‐25 weeks of gestation) vs. fetal circulations. For each SD increase in maternal plasma concentration at 24‐28 weeks, cord plasma concentration increased by 12.7 (95% confidence interval 6.8‐18.5) ng/ml for leptin, and 2.9 (1.8‐4.0) µg/ml for adiponectin, respectively (adjusted P < 0.0001). Fetal insulin sensitivity was negatively associated with cord blood leptin (each SD increase was associated with a 5.4 (2.1‐8.7) mg/dl/µU/ml reduction in cord plasma glucose/insulin ratio, and a 5.6 (3.9, 7.4) pmol/l increase in proinsulin level, all adjusted P < 0.01) but not adiponectin (P > 0.4) levels). Similar associations were observed in nondiabetic full‐term pregnancies (n = 211).

Conclusions:

The results consistently suggest a maternal impact on fetal leptin and adiponectin levels, which may be an early life pathway in maternal‐fetal transmission of the propensity to obesity and insulin resistance.     

Association between the Lipid Levels and Single Nucleotide Polymorphisms of ABCA1, APOE and HMGCR Genes in Subjects with Spontaneous Preterm Delivery

Spontaneous preterm delivery (SPTD) with gestational age between 28 and 37 complete weeks was reported to have a genetic predisposition in lipids metabolism. This study aimed to investigate the association between the lipid levels and gene polymorphisms of ABCA1 (rs2422493), APOE (rs7412) and HMGCR (rs12916) in Chinese pregnant women with SPTD. A case-control study was conducted at the baseline randomization in 200 SPTD and 178 healthy full term delivery (FTD) women. Maternal blood lipids were detected close to delivery of fetus in SPTD group and in FTD group with gestational age-matched. Cord blood lipids were detected after delivery in two groups. Three genotypes both in maternal and cord blood were determined by real time PCR. The results showed that the levels of total cholesterol (TCHO), triglyceride (TG), high density lipoprotein (HDL), and low-density lipoprotein cholesterol (LDL) in the maternal blood in the SPTD group were significantly lower than those in the FTD group, while the levels of TCHO, HDL, and LDL in the cord blood in the SPTD group were significantly higher than those in the FTD group. In the SPTD subjects, the levels of TG and LDL in the maternal blood were associated with different genotypes of HMGCR gene rs12916 loci. These results indicate that abnormal lipid metabolism may exist in SPTD women and the premature fetus and the HMGCR gene may be a susceptible gene for SPTD.