Pregnant Control Subjects Research Articles

Associations between AGT, MTHFR, and VEGF gene polymorphisms and preeclampsia in the Chinese population.

Preeclampsia (PE) is a pregnancy-specific multisystemic syndrome. This study aimed to investigate the associations between angiotensinogen (AGT), methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF) polymorphisms, and PE in the Han Chinese population. We genotyped 26 single-nucleotide polymorphisms (SNP) in three genes by using QuantStudio™ 12K Flex Real-Time PCR technology in 168 patients with PE and 204 healthy pregnant control subjects. The associations of tested polymorphisms with PE were analyzed at allele, genotype, and haplotype levels. A common coding variant in MTHFR, rs2274976, was significantly associated with increased risk of PE in both allelic and genotype models (P<0.05). The heterozygous genotypes of rs699 (G/A vs G/G) in AGT gene and rs3025035 (C/T vs C/C) in VEGF gene showed weak associations with increased PE risk, whereas the mutant homozygous genotype of rs3024987 (TT vs C/C) and the heterozygous genotype of rs3025039 (C/T vs C/C) in VEGF gene displayed weak associations with decreased PE risk (P<0.05). However, these weak associations lost significance after multiple testing correction. The results indicated that rs2274976 in MTHFR gene may contribute to the increased risk of PE in pregnant women. AGT and VEGF gene polymorphisms may not play a significant role in PE development.

Expression and clinical significance of lncRNA TCL6 in serum of patients with preeclampsia.

Preeclampsia is a common syndrome in pregnancy and a leading cause of mortality of pregnant females and their infants. To investigate the diagnostic and prognostic utility of lncRNA T-cell leukemia/lymphoma 6 (TCL6) in patients with preeclampsia, 120 singleton pregnant females with preeclampsia and another 100 healthy pregnant control subjects were analyzed in the present study. The expression of lncRNA TCL6 in the serum of the included patients was detected. Receiver operating characteristic curve analysis was applied to evaluate the efficiency of lncRNA TCL6 in terms of preeclampsia diagnosis and grading. Kaplan-Meier analysis was adopted to assess the effect of lncRNA TCL6 expression on the rate of adverse pregnancy. Multivariate logistic regression was used to determine high-risk factors of adverse pregnancy. The results indicated that lncRNA TCL6 was significantly increased in the serum of patients with preeclampsia. Furthermore, TCL6 was elevated in subgroups of patients with early-onset or severe preeclampsia and with Haemolysis, Elevated Liver enzymes and Low Platelet count syndrome in comparison with other patients with preeclampsia. High expression of TCL6 in pregnant females corresponded to a higher rate of adverse pregnancy outcomes. Severe preeclampsia, early-onset preeclampsia and high TCL6 expression were identified as independent risk factors for adverse pregnancy outcomes. For each unit increase in TCL6 expression, a 9.5-fold increase of the risk of adverse maternal and fetal outcomes was determined. Collectively, high expression of lncRNA TCL6 may assist the diagnosis and grading of preeclampsia and may be adopted as an independent risk factor for adverse pregnancy outcomes.

A study of serum growth differentiation factor 15 in Indian women with and without gestational diabetes mellitus in the third trimester of pregnancy and its association with pro-inflammatory markers and glucose metabolism

The pathogenesis of gestational diabetes mellitus (GDM) is multifactorial and it shares many features with type 2 diabetes mellitus. Growth differentiation factor 15 (GDF-15), a member of transforming growth factor-β superfamily, is expressed in a high amount in the placenta in addition to other organs. This cross-sectional study was performed to assess the difference of GDF-15 and pro-inflammatory cytokines between pregnant women with or without GDM, and to explore the possible association of GDF-15 with the parameters of dysglycemia (Serum insulin, HOMA-IR, fasting, 60min, and 120min post-75 gm oral glucose plasma glucose levels) and inflammation (IL-6 and TNF-α) in women with GDM at 24-28weeks of gestation. Thirty-five women with GDM and 30 age-matched non-diabetic pregnant control (NDPC) subjects were recruited for the study. Mean serum GDF-15, IL-6, and TNF-α levels were significantly higher in GDM in comparison to the NDPC population. These differences persisted even after adjusting for the possible confounders like maternal age and BMI. GDF-15 level showed a positive correlation with parameters of dysglycemia (Serum insulin, HOMA-IR, fasting, 60min, and 120min post-75 gm oral glucose plasma glucose levels) but a variable correlation with the markers of inflammation. In conclusion, our study provides evidence that, in Indian women, serum GDF-15 level is higher in GDM in comparison to age-matched pregnant subjects without GDM in the early third trimester pregnancy. Moreover, in third trimester, GDF-15 level increases with increase in plasma glucose and insulin resistance.

Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia.

Preeclampsia (PE) is regarded as a pregnancy-associated hypertension disorder that is related to excessive inflammatory responses. Although the gut microbiota (GM) and short-chain fatty acids (SCFAs) have been related to hypertension, their effects on PE remain unknown. We determined the GM abundance and faecal SCFA levels by 16S ribosomal RNA (rRNA) sequencing and gas chromatography, respectively, using faecal samples from 27 patients with severe PE and 36 healthy, pregnant control subjects. We found that patients with PE had significantly decreased GM diversity and altered GM abundance. At the phylum level, patients with PE exhibited decreased abundance of Firmicutes albeit increased abundance of Proteobacteria; at the genus level, patients with PE had lower abundance of Blautia, Eubacterium_rectale, Eubacterium_hallii, Streptococcus, Bifidobacterium, Collinsella, Alistipes, and Subdoligranulum, albeit higher abundance of Enterobacter and Escherichia_Shigella. The faecal levels of butyric and valeric acids were significantly decreased in patients with PE and significantly correlated with the above-mentioned differential GM abundance. We predicted significantly increased abundance of the lipopolysaccharide (LPS)-synthesis pathway and significantly decreased abundance of the G protein-coupled receptor (GPCR) pathway in patients with PE, based on phylogenetic reconstruction of unobserved states (PICRUSt). Finally, we evaluated the effects of oral butyrate on LPS-induced hypertension in pregnant rats. We found that butyrate significantly reduced the blood pressure (BP) in these rats. In summary, we provide the first evidence linking GM dysbiosis and reduced faecal SCFA to PE and demonstrate that butyrate can directly regulate BP in vivo, suggesting its potential as a therapeutic agent for PE.

Serum amphiregulin and cerebellin-1 levels in severe preeclampsia

Purpose Preeclampsia is a form of hypertensive disorders of pregnancy and defined as the presence of new-onset hypertension and proteinuria or other end organ damage occurring after 20-week gestation. Preeclampsia can be a destructive process that can cause maternal and infant mortality. The exact etiopathogenesis of preeclampsia is still undefined. We aimed to compare serum amphiregulin and cerebellin-1 levels of severe preeclampsia patients with healthy pregnant women and healthy control subjects. Materials and methods A total of 88 women were enrolled in this study. Patients diagnosed with severe preeclampsia were group 1 (n = 28), healthy non-pregnant normotensive women group 2 (n = 30), and healthy pregnant women group 3 (n = 30). The participants in each group were matched for age. Pregnant women in groups 1 and 3 were also matched for gestational age. Serum amphiregulin and cerebellin-1 levels were measured using ELISA. Results Serum amphiregulin levels were 3413 ± 1.38 ng/ml (1748–7739), 8510 ± 7213 ng/ml (2019–24,000), and 6580 ± 5360 ng/ml (2484–24,000) in preeclampsia patients, controls and healthy pregnant women, respectively. Amphiregulin levels were significantly lower in preeclampsia patients than healthy pregnant women (p=.008) and controls (p = .015). Amphiregulin levels were similar between healthy controls and healthy pregnant women (p = 1.00). Cerebellin-1 levels were 222.039 ± 92.681 pg/ml (138,580–557,757) in preeclamptic patients, 537.043 ± 525.117 pg/ml (150,432–1,600,000) in controls and 415.091 ± 436.580 pg/ml (137,284–1,600,000) in healthy pregnant women. Cerebellin-1 levels were similar among groups (p = .272). Serum amphiregulin and cerebellin-1 levels were significantly and positively correlated with each other in preeclampsia patients (r = 0.693, p < .001), controls (r = 0.882, p < .001), and healthy pregnant women (r = 0.591, p = .001). Serum level of amphiregulin ≤3590 pg/ml had a sensitivity of 67.9% and specificity of 63.3% in the diagnosis of preeclampsia (AUC: 0.751; p = .001). Conclusions Serum amphiregulin decreases in severe preeclampsia patients.

Analysis of amino acid and acyl carnitine profiles in maternal and fetal serum from preeclampsia patients

Objectives: To analyze and compare concentrations of amino acids (AAs) and acylcarnitine (AC) profiles in maternal–fetal serum from women with preeclampsia (PE) and to assess their use as possible predictors of PE.Methods: This is a retrospective study in which we enrolled a total of 38 pregnant women and their offspring. Pregnant women with PE (n = 14) and healthy pregnant control subjects (n = 24) participated voluntarily in the study. Maternal blood and cord blood were tested using dry blood spot (DBS) specimens, and we detected concentrations of 18 types of AAs and 31 types of AC by using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS), and compared metabolites between the groups. We used logistic regression modeling to estimate the association of each metabolite with development of PE.Results: Concentrations of most AAs and AC in PE mothers were significantly higher than those in the group of control mothers. Cord plasma concentrations of AC in most PE mothers were significantly higher than those in controls; however, in PE, levels of cord plasma concentrations of most AAs were significantly lower, except for Gly, compared with controls. Levels of most AAs and AC were lower in the control and PE groups, with a tendency for lower levels in maternal blood compared to cord blood. Receiver operating characteristics (ROC) and areas under the curves (AUC) analyses using these metabolites did not predict PE individually.Conclusions: Maternal–fetal levels of AAs and AC were associated with PE. But the use of metabolites did not constitute a reliable method for use as a biomarker in the diagnosis of PE. Further prospective studies are needed to clarify the roles of different metabolites involved in the mechanism underlying the development of PE.

Prevalence of hepatitis E virus infection among pregnant women in Zhenjiang, China

BackgroundMost hepatitis E virus (HEV) infections are mild or subclinical, however, the infections are characteristically associated with a high incidence of symptomatic presentation among pregnant women. ObjectivesThe aim of this study was to assess the HEV prevalence among pregnant women in Zhenjiang, China. Materials and methods225 and 208 of serum samples collected from pregnant and healthy nonpregnant women, respectively, were used to detect anti-HEV IgG and IgM levels. IgM positive samples were further tested for HEV RNA by using RT-nested PCR (nPCR) method. Positive PCR products were sequenced and subjected to phylogenetic analysis. Results21.8% (49/225) of samples were anti-HEV IgG positive in pregnant women, whereas 7.7% (16/208) of samples were anti-HEV IgG positive in control subjects (P < 0.001). With respect to anti-HEV IgM testing, 3.6% (8/225) and 0.0% (0/208) were positive in pregnant women and control subjects, respectively (P = 0.006 < 0.01). 4 out of 8 IgM positive samples were positive for HEV RNA. Phylogenetic analysis indicated that four HEV strains had distinct nucleotide sequences and clustered into two different sub-genotypes in genotype 4. ConclusionsIn the current study, the prevalence of HEV infection with respect to IgG and IgM levels among pregnant women was significantly higher than that in the healthy nonpregnant group. Additionally, all four HEV strains belonged to genotype 4 implying that genotype 4 is the predominant genotype in the area.

Urinary congophilia in women with hypertensive disorders of pregnancy and preexisting proteinuria or hypertension

Congophilia indicates the presence of amyloid protein, which is an aggregate of misfolded proteins, that is implicated in the pathophysiologic condition of preeclampsia. Recently, urinary congophilia has been proposed as a test for the diagnosis and prediction of preeclampsia. The purpose of this study was to determine whether urine congophilia is present in a cohort of women with preeclampsia and in pregnant and nonpregnant women with renal disease. With the use of a preeclampsia, chronic hypertension, renal disease, and systemic lupus erythematosus cohort, we analyzed urine samples from healthy pregnant control subjects (n= 31) and pregnant women with preeclampsia (n= 23), gestational hypertension (n= 10), chronic hypertension (n= 14), chronic kidney disease; n= 28), chronic kidney disease with superimposed preeclampsia (n= 5), and chronic hypertension and superimposed preeclampsia (n= 12). Samples from nonpregnant control subjects (n= 10) and nonpregnant women with either systemic lupus erythematosus with (n= 25) and without (n= 14) lupus nephritis were analyzed. For each sample, protein concentration was standardized before it was mixed with Congo Red, spotted to nitrocellulose membrane, and rinsed with methanol. The optical density of the residual Congo Red stain was determined; Congo red stain retention was calculated, and groups were compared with the use of the Mann-Whitney test or Kruskal-Wallis analysis of Variance test, as appropriate. Congophilia was increased in urine from women with preeclampsia (median Congo red stain retention, 47%; interquartile range, 22-68%) compared with healthy pregnant control subjects (Congo red stain retention: 16%; interquartile range, 13-21%; P= .002), women with gestational hypertension (Congo red stain retention, 20%; interquartile range, 13-27%; P= .008), or women with chronic hypertension (Congo red stain retention, 17%; interquartile range, 12-28%; P= .01). There were no differences in Congo red retention between pregnant women with chronic hypertension and normal pregnant control subjects (Congo red stain retention, 17% [interquartile range, 12-28%] vs 16% [interquartile range, 13-21%], respectively; P= .72). Congophilia was present in pregnant women with chronic kidney disease (Congo red stain retention, 32%; interquartile range, 14-57%), being similar to values found in women with preeclampsia (P= .22) and for women with chronic kidney disease and superimposed preeclampsia (Congo red stain retention, 57%; [interquartile range, 29-71%; P= .18). Nonpregnant women with lupus nephritis had higher congophilia levels compared with nonpregnant female control subjects (Congo red stain retention, 38% [interquartile range, 17-73%] vs 9% [7-11%], respectively; P < .001) and nonpregnant women with systemic lupus erythematosus without nephritis (Congo red stain retention, 38% [interquartile range, 17-73%] vs 13% [interquartile range, 11-17%], respectively; P= .001). A significant positive correlation was observed between congophilia and protein:creatinine ratio (Spearman rank correlations, 0.702; 95% confidence interval, 0.618-0.770; P < .001). This study confirms that women with preeclampsia and chronic kidney disease without preeclampsia have elevated urine congophilia levels compared with healthy pregnant women. Nonpregnant women with lupus nephritis also have elevated urine congophilia levels compared with healthy control subjects. An elevated Congo Red stain retention may not be able to differentiate between these conditions; further research is required to explore the use of congophilia in clinical practice.

Impact of maternal obesity on the fetal electrocardiogram during labor

Objective: Maternal obesity affects one in every five women giving birth worldwide. This condition is associated with adverse perinatal outcomes, as well as increased morbidity and mortality for mother and offspring.Methods: We carried out a prospective study at the University of Pecs Medical Center, Pecs, Hungary, between 1 January 2013 and 1 January 2014. We enrolled 60 obese (body mass index >30 kg/m2) low-risk pregnant women and 108 age-, ethnicity-, and parity-matched nonobese pregnant control subjects. The ST segment of the fetal electrocardiogram was assessed by STAN® monitoring. Neonatal outcomes and cord gas analysis of the umbilical vessels were evaluated after birth.Results: No infant with definitive metabolic acidosis was delivered in either group. We observed 32 and 106 ST events in the obese and control group, respectively, but this difference was not statistically significant. To date, none of the infants delivered as part of this study have demonstrated developmental insufficiency.Conclusions: Obesity might not influence the fetal electrocardiogram during labor as an independent risk factor for adverse pregnancy outcomes. Studies with larger cohort sizes are needed to confirm our findings.

Genetic association study of phosphodiesterase 8B gene with subclinical hypothyroidism in pregnant women

Objective: To explore whether phosphodiesterase 8B (PDE8B) gene is involved in the etiology of subclinical hypothyroidism (SCH) in pregnant women. Methods: A total of 180 pregnant patients with SCH and 311 healthy, pregnant control subjects were recruited in this study to detect 4 (rs4704397, rs6885099, rs2046045, and rs12514694 in PDE8B) single nucleotide polymorphisms (SNPs). Univariate associations were studied using Pearson’s χ2 test for categorical variables and Student t/ANOVA tests for continuous ones. Nonparametric Kruskal–Wallis test were used to study the associations of TSH level in different genotypes. Genotyping of SNPs was performed by the MassARRAY® iPLEX® Gold SNP genotyping analysis technique. The SHEsis program was used to analyze the genotyping data. Results: There was a significant difference in the rate of high TSH in three genotypes of rs4704397 in all pregnant women. After adjusting for multiple testing by the program SNPSpD, allelic frequencies of rs4704397 (p = 0.016, OR = 1.692), rs6885099 (p = 0.031, OR = 0.621), and rs2046045 (p = 0.023, OR = 0.602) in PDE8B gene showed significant differences between patients with SCH and control subjects. There were no significant differences of genotype frequencies between patients and controls at any of the analyzed SNPs (p > 0.05).The haplotypes ‘‘A G C G’’ (p = 0.002; OR, 1.533; 95% CI, 1.172–2.006) and “G A A G” (p = 0.014; OR, 0.576; 95% CI, 0.369–0.899) in PDE8B were observed to be significantly associated with SCH in pregnant women. Conclusion: Genetic variation of the PDE8B gene may be involved in the etiology of SCH in pregnant women.

Comparison of the Thickness of Lateral Abdominal Muscles Between Pregnant Women With and Without Low Back Pain

ObjectivesTo compare the thickness of the external oblique, internal oblique, and transversus abdominis muscles in pregnant subjects with and without low back pain (LBP) by the use of ultrasound to measure thickness. DesignA case-control study. SettingAn academic and tertiary care referral spine and sports medicine center. ParticipantsFifty pregnant women with LBP during pregnancy and 54 pregnant control subjects. MethodsCase and control subjects were matched for body mass index, gestational age, and number of previous pregnancies. A multiple linear regression model with adjustment for the gestational age of the subjects, as the potential confounder of the primary outcomes, was used to evaluate the association between LBP appearance and abdominal muscles thickness of the subjects. Main Outcome MeasuresThe thickness of lateral abdominal muscles was measured by ultrasound with the subject in a hook-lying position on the examination table. ResultsWe found that there was no significant difference between pregnant subjects with and without LBP in terms of the thickness of external oblique, internal oblique, and transversus abdominis muscles. ConclusionThese findings suggest that other factors rather than the thickness of core stabilizing muscles are influential in the etiology of LBP during pregnancy. We hypothesize that enlargement of uterus during pregnancy might influence the thickness of the lateral abdominal muscles.

Seroprevalence of hepatitis E virus among pregnant women and control subjects in China

Hepatitis E infection, caused by the hepatitis E virus (HEV), is an important global public health concern, with particularly high mortality in pregnant women. China is generally judged to be an HEV-endemic area, but epidemiological data for HEV among pregnant women are limited. Between June 2011 and July 2013, a case-control study was conducted to estimate the seroprevalence and potential risk factors associated with the acquisition of HEV infection by pregnant women in China. Nine-hundred and ninety pregnant women who visited hospitals for antenatal follow-up or medication in Qingdao and Weihai and 965 control subjects matched by age, gender and residence were examined for the presence of anti-HEV IgG and IgM antibodies by enzyme immunoassays. Socio-demographic and behavioral characteristics from the study subjects were obtained. The overall prevalence of anti-HEV IgG in all 1,955 samples was 20.7%. In pregnant women, 16.2% of samples were anti-HEV IgG positive whereas, in control subjects 25.3% of samples were anti-HEV IgG positive, (P < 0.01). For anti-HEV IgM detection, 62 (3.2%) of the 1,955 serum samples were positive and the seroprevalence in pregnant women and control subjects was 2.6% and 3.6%, respectively. Age, contact with cats, contact with pigs and exposure to soil were found to be associated with HEV infection. These findings demonstrated the high prevalence of HEV and the considerable potential for the transmission of HEV infection in pregnant women in China.

Serum levels of fractalkine are associated with markers of insulin resistance in gestational diabetes

Fractalkine has recently been introduced as an adipokine that improves glucose tolerance. Regulation of fractalkine in gestational diabetes, as well as its association with markers of obesity, glucose and lipid metabolism, inflammation and renal function, has not been elucidated. Circulating fractalkine was quantified by enzyme-linked immunosorbent assay in 74 women with gestational diabetes and 74 healthy, pregnant control subjects matched for age, BMI, and gestational age. Median (interquartile range) levels of fractalkine were not significantly different between the two groups [gestational diabetes: 2.24 (2.16) μg/l; control: 2.45 (1.38) μg/l] (P=0.461). In multivariate linear regression analysis, fractalkine remained independently associated with homeostasis model assessment of insulin resistance (β=-0.253, P=0.002) and the proinflammatory adipokine progranulin (β=0.218, P=0.007). Circulating fractalkine is not different between women with gestational diabetes and control subjects, but the adipokine is independently associated with markers of insulin resistance and proinflammatory progranulin in pregnancy.

Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects

BACKGROUNDS100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.METHODSA cross-sectional case–control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.RESULTSLevels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).CONCLUSIONSS100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.

Inflammation and impaired endothelium-dependant vasodilatation in non obese women with gestational diabetes mellitus: preliminary results.

BackgroundTo evaluate whether abnormal endothelial function, a common finding in gestational diabetes mellitus (GDM) pregnancies, can be explained by inflammatory cytokines.MethodsForearm skin blood flow (FSBF), into response to acetylcholine (Ach) (endothelium-dependent vasodilatation), were measured in 24 pregnant control subjects and 28 gestational diabetes mellitus (GDM) women, in the third trimester of gestation. A fasting glycemic and lipidic panel was obtained, and inflammatory cytokines (TNF-α and IL-6) and adiponectin were also determined.ResultsFSBF is significantly reduced in GDM group compared with control subjects (344.59 ± 57.791 vs.176.38 ± 108.52, P < 0.05). Among all subjects, FSBF showed a strong negative correlation with TNF-α and IL-6 (r = −0.426, P < 0.0001 and r = −0.564, P < 0.0001, respectively) and positive correlation with adiponectin (r = 0.468, P < 0.0001).ConclusionsEndothelial function, an early marker of macrovascular disease, is present in non-obese pregnancies complicated by GDM. This alteration seems to be directly related to inflammatory status, which may represent a patho-physiological link between GDM and type 2 diabetes and, later on, metabolic syndrome.

English

&nbsp; Preeclampsia (PE) is the most serious complication of pregnancy that causes maternal and fetal morbidity and mortality. Although the exact pathophysiology of PE is unknown, a large number of studies have shown that abnormalities in nitric oxide (NO) synthesis may contribute to the development of this disorder. There are some evidences that polymorphisms of the endothelial nitric oxide synthase (eNOS) gene affect NO production and have been associated with hypertension and PE in some populations. Therefore the aim of this study was to assess the relation of the Glu298Asp eNOS polymorphism and PE in an Iranian population. We compared the frequency of the Glu298Asp polymorphism in 147 women with PE and 137 healthy pregnant control subjects by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of Glu298Asp genotypes were significantly different between PE women and controls (p &lt; 0.001). The frequency of Asp allele was 0.32 in PE patients and 0.20 in controls and was significantly different (p &lt; 0.001). The risk of PE was 2.4 fold in pregnant women with Asp allele. In conclusion, the Asp allele could be a risk factor for PE in South East of Iran. &nbsp; Key words:&nbsp;Nitric oxide synthase, polymorphism, preeclampsia, pregnancy.

The Evaluation of the Oxidative State of Low-Density Lipoproteins in Intrauterine Growth Restriction and Preeclampsia

Objective. To evaluate the oxidative state of lipoproteins in pregnancies complicated by intrauterine growth restriction (IUGR) in comparison to preeclampsia (PE) and healthy pregnant control subjects (CN). Methods. Maternal serum of 20 PE, 29 IUGR, and 29 gestational age-matched CN were analyzed. Total cholesterol (TC), low-density lipoprotein (LDL)-bound cholesterol (LDL-C), and oxidized LDL (oxLDL) concentration were measured once between 25 and 34 weeks of gestation. Statistical estimates were performed by Student's t-test. Results. Serum concentrations of LDL-C and TC were significantly reduced in IUGR [LDL-C: CN – mean = 146 mg/dL, SD = ± 40.1; IUGR – mean = 102 mg/dL, SD = ± 27.3 (p < 0.0001); PE – mean = 130 mg/dL, SD = 38.8 mg/dL; TC: CN – mean = 259/dL, SD = ± 46.8; IUGR – mean = 218 mg/dL, SD = ± 35.0 (p < 0.001); PE – mean = 244 mg/dL, SD = 48.2]. There was no significant difference in oxLDL/LDL-C ratio within the three groups (CN: mean = 0.76, SD = 0.24; IUGR: mean = 0.74, SD = 0.12; PE: mean = 0.77, SD = 0.22). Conclusion. Our results show a lower maternal LDL-C and TC concentration in IUGR pregnancies. These data contribute to the hypothesis of a decreased cholesterol supply to the fetus in IUGR. However, we could not confirm the hypothesis of an altered oxidative state in neither IUGR nor PE.

Serum Anti-Carbonic Anhydrase II Antibodies and Oxidant-Antioxidant Balance in Pre-eclampsia

PROBLEM The aim of this study was to investigate the presence of anti-carbonic anhydrase II antibodies (anti-CA II) antibodies in pre-eclampsia and the relationships between the autoantibodies, total antioxidant capacity (TAC) and total oxidant capacity (TOC), malondialdehyde (MDA) and oxidative stres index (OSI) parameters. METHOD OF STUDY We studied 40 early and late onset pre-eclamptic patients and 40 healthy pregnant control and 39 healthy non-pregnant control subjects. Serum CA II antibodies, TAC and TOC, and MDA parameters were studied by ELISA. RESULTS The mean values for TAC, TOC, OSI, MDA, and anti-CA II were significantly increased in patients with pre-eclampsia compared to the other groups. The anti-CA II antibody levels for the pregnant control subjects were 0.129 ± 0.04 and that for the pre-eclamptic patients were 0.282 ± 0.18. In this study, any absorbance value higher than 0.136, the mean absorbance + 2 S.D. of pregnant control subjects, was defined as positive. Positive results were obtained in 29 of 40 pre-eclamptic patients (72.5%). There were significant positive correlations between serum anti-CA II antibodies and TOC, MDA levels, and OSI levels. CONCLUSION The results suggest that anti-CA II antibodies and impairment in oxidant-antioxidant balance may be involved in multifactorial etiology of pre-eclampsia.

Expression of Adiponectin Receptors in Human Placenta and Its Possible Implication in Gestational Diabetes

Problem statement: Similar to obese patients and type 2 diabetic patients, adiponectin levels are reduced in former Gestational Diabetes Mellitus (GDM) patients and are lower in GDM women during late pregnancy compared with pregnant control subjects matched for BMI. Diabetic insult at later stages in gestation, such as may occur in gestational diabetes, will foremost lead to short-term changes in a variety of molecules for key functions including gene expression in the placenta. Approach: In this study we assessed the expression of adiponectin receptors in human placenta to identify the site (s) of expression and to clarify the effect of gestational diabetes in this expression. This study was carried on 10 normoglycemic pregnant women and 20 GDM women. The placental tissue was collected immediately after delivery and tissue biopsies were taken from both fetal and maternal sides of each placenta. One step-RT-PCR for ADIPOR1 and ADIPOR2 was done by Real Time PCR using Syber Green technique. Relative quantification of mRNA of the ADIPOR1 and ADIPOR2 genes was measured using ABI7900 Real Time machine. Results: Both types of Adiponectin Receptors (ADIPOR1 and ADIPOR2) are expressed in human placenta. ADIPOR1 is more highly expressed than ADIPOR2 in both fetal and maternal sides of GDM cases and normal pregnant women. ADIPOR1 mRNA expression was significantly up regulated in GDM women compared to normal pregnant women, whereas no significant difference in the expression of ADIPOR2 was detected between the two groups. There was no evidence of maternal-fetal side difference in the expression of adiponectin receptors in GDM cases but in normal pregnant women there is a statistically significant difference between both sides in the expression of both ADIPOR1 and ADIPOR2. Conclusion: We concluded that adiponectin plays an important role in mediation the glucose metabolism in fetal tissues through its receptors, mainly Adiponectin Receptor 1 (ADIPOR1).

Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G2Subclass Deficiency

. Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G(2) (IgG(2)) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection. Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random sample of healthy pregnant women. Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant; 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P < .001), anemia (P < .001), and low levels of total IgG (P= .01), IgG(1) (P= .022), and IgG(2) (15 of 19 vs 5 of 20; P= .001; mean value +/- standard deviation [SD], 1.8 +/- 1.7 g/L vs 3.4 +/- 1.4 g/L; P= .003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P= .02) and low mean IgG(2) levels (P= .043) remained significant after multivariate analysis. Follow-up of 15 (79%) surviving IgG(2)-deficient patients at a mean (+/- SD) of 90 +/- 23 days (R, 38-126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG(2) deficient. Among 17 healthy pregnant control subjects, mildly low IgG(1) and/or IgG(2) levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG(2) (P= .001). Severe H1N1 infection is associated with IgG(2) deficiency, which appears to persist in a majority of patients. Pregnancy-related reductions in IgG(2) level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG(2) deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.